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Effects of naloxone on opioid-induced hyperalgesia and tolerance to remifentanil under sevoflurane anesthesia in rats

Background: Opioid antagonists at ultra-low doses have been used with opioid agonists to prevent or limit opioid tolerance. The aim of this study was to evaluate whether an ultra-low dose of naloxone combined with remifentanil could block opioid-induced hyperalgesia and tolerance under sevoflurane anesthesia in rats. Methods: Male adult Wistar rats were allocated into one of four treatment groups (n = 7), receiving remifentanil (4 μg·kg· min) combined with naloxone (0.17 ng·kg·min), remifentanil alone, naloxone alone, or saline. Animals were evaluated for mechanical nociceptive thresholds (von Frey) and subsequently anesthetized with sevoflurane to determine the baseline minimum alveolar concentration (MAC). Next, treatments were administered, and the MAC was redetermined twice during the infusion. The experiment was performed three times on nonconsecutive days (0, 2, and 4). Hyperalgesia was considered to be a decrease in mechanical thresholds, whereas opioid tolerance was considered to be a decrease in sevoflurane MAC reduction by remifentanil. Results: Remifentanil produced a significant decrease in mechanical thresholds compared with baseline values at days 2 and 4 (mean ± SD, 30.7 ± 5.5, 22.1 ± 6.4, and 20.7 ± 3.7g at days 0, 2, and 4, respectively) and an increase in MAC baseline values (2.5 ± 0.3, 3.0 ± 0.3, and 3.1 ± 0.3 vol% at days 0, 2, and 4, respectively). Both effects were blocked by naloxone coadministration. However, both remifentanil-treated groups (with or without naloxone) developed opioid tolerance determined by their decrease in MAC reduction. Conclusions: An ultra-low dose of naloxone blocked remifentanil-induced hyperalgesia but did not change opioid tolerance under inhalant anesthesia. Moreover, the MAC increase associated with hyperalgesia was also blocked by naloxone. © 2013 the American Society of Anesthesiologists, Inc. Lippincott Williams & Wilkins. Anesthesiology.

Remifentanil preconditioning reduces hepatic ischemia-reperfusion injury in rats via inducible nitric oxide synthase expression

Background: Opioid preconditioning against ischemia reperfusion injury has been well studied in myocardial and neuronal tissues. The objective of this study was to determine whether remifentanil could attenuate hepatic injury and to investigate the mechanisms. Methods: A rat model of hepatic ischemia reperfusion injury and a hepatocyte hypoxia reoxygenation (HR) injury model were used, respectively, in two series of experiments. Remifentanil was administered before ischemia or hypoxia and the experiments were repeated with previous administration of naloxone, l-arginine and N-ω-nitro-l-arginine methyl ester, a nonselective opioid receptor antagonist, a nitric oxide donor, and nitric oxide synthase (NOS) inhibitor, respectively. Serum aminotransferase, cytokines, and hepatic lipid peroxidation were measured. Histopathology examination and apoptotic cell detection were assessed. For the in vitro study, cell viability, intracellular nitric oxide, apoptosis, and NOS expression were evaluated. Results: Remifentanil and l-arginine pretreatment reduced concentrations of serum aminotransferases and cytokines, decreased the concentrations of hepatic malondialdehyde and myeloperoxidase activity, and increased superoxide dismutase, nitric oxide, and inducible NOS expression in vivo. Decreased histologic damage and apoptosis were also seen in these two groups. These changes were prevented by previous administration of N-ω-nitro-l-arginine methyl ester but not naloxone. There was an increase in inducible NOS protein expression but not endogenous NOS in remifentanil and l-arginine pretreated groups compared with control, naloxone, and N-ω-nitro-l-arginine methyl ester groups. Conclusion: Pretreatment with remifentanil can attenuate liver injury both in vivo and in vitro. Inducible NOS but not opioid receptors partly mediate this effect by exhausting reactive oxygen species and attenuating the inflammatory response. Copyright © 2011, the American Society of Anesthesiologists, Inc. Lippincott Williams & Wilkins. Anesthesiology.

5-hydroxytryptamine type 3 receptor modulates opioid-induced hyperalgesia and tolerance in mice

Background: Opioid-induced hyperalgesia (OIH) and tolerance are challenging maladaptations associated with opioids in managing pain. Recent genetic studies and the existing literature suggest the 5-hydroxytryptamine type 3 (5-HT3) receptor participates in these phenomena. The location of the relevant receptor populations and the interactions between the 5-HT3 system and other systems controlling OIH and tolerance have not been explored, however. We hypothesized that 5-HT3 receptors modulate OIH and tolerance, and that this modulation involves the control of expression of multiple neurotransmitter and receptor systems. Methods: C57BL/6 mice were exposed to a standardized 4-day morphine administration protocol. The 5-HT3 antagonist ondansetron was administered either during or after the conclusion of morphine administration. Mechanical testing was used to quantify OIH, and thermal tail-flick responses were used to measure morphine tolerance. In other experiments spinal cord and dorsal root ganglion tissues were harvested for analysis of messenger RNA concentrations by real-time polymerase chain reaction or immunochemistry analysis. Results: The results showed that (1) systemic or intrathecal injection of ondansetron significantly prevented and reversed OIH, but not local intraplantar injection; (2) systemic or intrathecal injection of ondansetron prevented and reversed tolerance; and (3) ondansetron blocked morphine-induced increases of multiple genes relevant to OIH and tolerance in dorsal root ganglion and spinal cord. Conclusions: Morphine acts via a 5-HT3-dependent mechanism to support multiple maladaptations to the chronic administration of morphine. Furthermore, the use of 5-HT3 receptor antagonists may provide a new avenue to prevent or reverse OIH and tolerance associated with chronic opioid use. Copyright © 2011, the American Society of Anesthesiologists, Inc. Lippincott Williams & Wilkins. Anesthesiology.

Countering Opioid-induced Respiratory Depression in Male Rats with Nicotinic Acetylcholine Receptor Partial Agonists Varenicline and ABT 594

Background: Opioids can induce significant respiratory depression when administered as analgesics for the treatment of acute, postoperative, and chronic pain. There are currently no pharmacologic means of reversing opioid-induced respiratory depression without interfering with analgesia. Further, there is a growing epidemic of opioid overdose that could benefit from therapeutic advancements. The aim of this study was to test the ability of two partial agonists of α4β2 nicotinic acetylcholine receptors, varenicline (used clinically for smoking cessation) and ABT 594 (tebanicline, developed as an analgesic), to reduce respiratory depression induced by fentanyl, remifentanil, morphine, and a combination of fentanyl and diazepam. Methods: Whole body plethysmographic recordings, nociception testing, and righting reflex testing were used to examine ventilation, analgesia, and sedation in adult male Sprague-Dawley rats. Results: Pre-, co-, or postadministration of varenicline or ABT 594 did not alter baseline breathing but markedly reduced opioid-induced respiratory depression. Varenicline had no effect on fentanyl-induced analgesia and ABT 594 potentiated fentanyl-induced analgesia. Specifically, 10-min administration of fentanyl induced a decrease in respiratory rate to 43 ± 32% of control in vehicle group, which was alleviated by preadministration of varenicline (85 ± 14% of control, n = 8, P < 0.001) or ABT 594 (81 ± 36% of control, n = 8, P = 0.001). ABT 594 or varenicline with a low dose of naloxone (1 μg/kg), but not varenicline alone, partially reversed fentanyl-induced lethal apnea, but neither compound provided the very rapid and complete reversal of apnea achieved with high doses of naloxone (0.03 to 1 mg/kg). Administration of varenicline (n = 4, P = 0.034) or ABT 594 (n = 4, P = 0.034) prevented lethal apneas induced by the combination of fentanyl and diazepam. Conclusions: Activation of α4β2 nicotinic acetylcholine receptors by varenicline and ABT 594 counters opioid-induced respiratory depression without interfering with analgesia. (ANESTHESIOLOGY 2020; 132:1197-211). © 2020, the American Society of Anesthesiologists, Inc. All Rights Reserved.

Local anesthetic-like inhibition of voltage-gated Na + channels by the partial μ-opioid receptor agonist buprenorphine

Background: Opioids induce analgesia mainly by inhibiting synaptic transmission via G protein-coupled opioid receptors. In addition to analgesia, buprenorphine induces a pronounced antihyperalgesia and is an effective adjuvant to local anesthetics. These properties only partially apply to other opioids, and thus targets other than opioid receptors are likely to be employed. Here we asked if buprenorphine inhibits voltage-gated Na channels. Methods: Na + currents were examined by whole cell patch clamp recordings on different recombinant Na + channel α-subunits. The effect of buprenorphine on unmyelinated mouse C-fibers was examined with the skin-nerve preparation. Data are presented as mean ± SEM. Results: Buprenorphine induced a concentration-dependent tonic (IC50 33 ± 2 μM) and use-dependent block of endogenous Na channels in ND7/23 cells. This block was state-dependent and displayed slow on and off characteristics. The effect of buprenorphine was reduced on local anesthetic insensitive Nav1.4-mutant constructs and was more pronounced on the inactivation-deficient Nav1.4-WCW mutant. Neuronal (Nav1.3, Nav1.7, and Nav1.8), cardiac (Nav1.5), and skeletal muscle (Nav1.4) α-subunits displayed small differences in tonic block, but similar degrees of use-dependent block. According to our patch clamp data, buprenorphine blocked electrically evoked action potentials in C-fiber nerve terminals. Buprenorphine was more potent than other opioids, including morphine (IC50 378 ± 20 μM), fentanyl (IC50 95 ± 5 μM), sufentanil (IC50 111 ± 6 μM), remifenatil (IC50 612 ± 17 μM), and tramadol (IC50 194 ± 9 μM). Conclusions: Buprenorphine is a potent local anesthetic and blocks voltage-gated Na channels via the local anesthetic binding site. This property is likely to be relevant when buprenorphine is used for pain treatment and for local anesthesia. © 2012 the American Society of Anesthesiologists, Inc. Lippincott Williams &amp; Wilkins. Anesthesiology.

Consent for anesthesia clinical trials on the day of surgery: Patient attitudes and perceptions

Background: Opportunities for anesthesia research investigators to obtain consent for clinical trials are often restricted to the day of surgery, which may limit the ability of subjects to freely decide about research participation. The aim of this study was to determine whether subjects providing same-day informed consent for anesthesia research are comfortable doing so. Methods: A 25-question survey was distributed to 200 subjects providing informed consent for one of two low-risk clinical trials. While consent on the day of surgery was permitted for both studies, a preadmission telephone call was required for one. The questionnaire was provided to each subject at the time of discharge from the hospital. The questions were structured to assess six domains relating to the consent process, and each question was graded on a 5-point Likert scale (1 = strongly disagree to 5 = strongly agree). Overall satisfaction with same-day consent was assessed using an 11-point scale with 0 = extremely dissatisfied and 10 = extremely satisfied. Results: Completed questionnaires were received from 129 subjects. Median scores for satisfaction with the consent process were 9.5 to 10. Most respondents reported that the protocol was well explained and comprehended and that the setting in which consent was obtained was appropriate (median score of 5). Most patients strongly disagreed that they were anxious at the time of consent, felt obligated to participate, or had regrets about participation (median score of 1). Ten percent or less of subjects reported negative responses to any of the questions, and no differences were observed between the study groups. Conclusion: More than 96% of subjects who provided same-day informed consent for low-risk research were satisfied with the consent process. © 2016, the American Society of Anesthesiologists, Inc. Wolters Kluwer Health, Inc.

Consistency, inter-rater reliability, and validity of 441 consecutive mock oral examinations in anesthesiology: Implications for use as a tool for assessment of residents

Background: Oral practice examinations (OPEs) are used extensively in many anesthesiology programs for various reasons, including assessment of clinical judgment. Yet oral examinations have been criticized for their subjectivity. The authors studied the reliability, consistency, and validity of their OPE program to determine if it was a useful assessment tool. Methods: From 1989 through 1993, we prospectively studied 441 OPEs given to 190 residents. The examination format closely approximated that used by the American Board of Anesthesiology. Pass-fail grade and an overall numerical score: were the OPE results of interest. Internal consistency and inter rater reliability were determined using agreement measures. To assess their validity in describing competence, OPE results were correlated with in- training examination results and faculty evaluations. Furthermore, we analyzed the relationship of OPE with implicit indicators of resident preparation such as length of training. Results: The internal consistency coefficient for the overall numerical score was 0.82, indicating good correlation among component scores. The interexaminer agreement was 0.68, indicating moderate or good agreement beyond that expected by chance. The actual agreement among examiners on pass-fail was 84%. Correlation of overall numerical score with in-training examination scores and faculty evaluations was moderate (r = 0.47 and 0.41, respectively; P < 0.01). OPE results were significantly (P < 0.01) associated with training duration, previous OPE experience, trainee preparedness, and trainee anxiety. Conclusion: Our results show the substantial internal consistency and reliability of OPE results at a single institution. The positive correlation of OPE scores with in-training examination scores, faculty evaluations, and other indicators of preparation suggest that OPEs are a reasonably valid tool for assessment of resident performance.

Short-term, mild hypothermia can increase the beneficial effect of permissive hypotension on uncontrolled hemorrhagic shock in rats

Background: Our previous and other studies have shown that hypotensive or hypothermic resuscitation have beneficial effects on uncontrolled hemorrhagic shock. Whether hypothermia can increase the beneficial effect of hypotensive resuscitation on hemorrhagic shock is not known. Methods: Two-hundred and twenty Sprague-Dawley rats were used to make uncontrolled hemorrhagic shock. Before bleeding was controlled, rats received normotensive or hypotensive resuscitation (target mean arterial pressure at 80 or 50 mmHg) in combination with normal (37°C) or mild hypothermia (34°C) (phase II). After bleeding was controlled, rats received whole blood and lactated Ringer's solution resuscitation for 2 h (phase III). The animal survival, blood loss, fluid requirement, cardiac output, and coagulation functions, as well as vital organ function, mitochondrial function, and energy metabolism of liver, kidney and intestines, were noted. Results: Short-term, mild hypothermia before bleeding was controlled increased the beneficial effect of hypotensive resuscitation. Hypothermia further decreased blood loss, oxygen consumption, and functional damage to the liver, kidney, and intestines during hypotensive resuscitation, protected mitochondrial function and energy metabolism (activity of Na +-K +-ATPase), and further improved survival time and survival rate (hypothermic/hypotensive combined group: survival rate, 9/10; survival time, 616 min; normothermic/normotensive group: 1/10, 256 min; hypothermic/normotensive group: 4/10, 293 min). Hypothermia slightly inhibited coagulation function. Conclusion: Mild hypothermia before bleeding is controlled can increase the beneficial effect of hypotensive resuscitation on uncontrolled hemorrhagic shock. The mechanism underlying the benefits of short-term hypothermia may be related to the decrease in oxygen consumption and metabolism, and protection of mitochondrial and organ functions. © 2012 the American Society of Anesthesiologists, Inc. Lippincott Williams &amp; Wilkins. Anesthesiology.

Dantrolene Ameliorates Impaired Neurogenesis and Synaptogenesis in Induced Pluripotent Stem Cell Lines Derived from Patients with Alzheimer's Disease

Background: Overactivation of ryanodine receptors and the resulting impaired calcium homeostasis contribute to Alzheimer's disease-related pathophysiology. This study hypothesized that exposing neuronal progenitors derived from induced pluripotent stems cells of patients with Alzheimer's disease to dantrolene will increase survival, proliferation, neurogenesis, and synaptogenesis. Methods: Induced pluripotent stem cells obtained from skin fibroblast of healthy subjects and patients with familial and sporadic Alzheimer's disease were used. Biochemical and immunohistochemical methods were applied to determine the effects of dantrolene on the viability, proliferation, differentiation, and calcium dynamics of these cells. Results: Dantrolene promoted cell viability and proliferation in these two cell lines. Compared with the control, differentiation into basal forebrain cholinergic neurons significantly decreased by 10.7% (32.9 ± 3.6% vs. 22.2 ± 2.6%, N = 5, P = 0.004) and 9.2% (32.9 ± 3.6% vs. 23.7 ± 3.1%, N = 5, P = 0.017) in cell lines from sporadic and familial Alzheimer's patients, respectively, which were abolished by dantrolene. Synapse density was significantly decreased in cortical neurons generated from stem cells of sporadic Alzheimer's disease by 58.2% (237.0 ± 28.4 vs. 99.0 ± 16.6 arbitrary units, N = 4, P = 0.001) or familial Alzheimer's disease by 52.3% (237.0 ± 28.4 vs.113.0 ± 34.9 vs. arbitrary units, N = 5, P = 0.001), which was inhibited by dantrolene in the familial cell line. Compared with the control, adenosine triphosphate (30 μM) significantly increased higher peak elevation of cytosolic calcium concentrations in the cell line from sporadic Alzheimer's patients (84.1 ± 27.0% vs. 140.4 ± 40.2%, N = 5, P = 0.049), which was abolished by the pretreatment of dantrolene. Dantrolene inhibited the decrease of lysosomal vacuolar-type H+-ATPase and the impairment of autophagy activity in these two cell lines from Alzheimer's disease patients. Conclusions: Dantrolene ameliorated the impairment of neurogenesis and synaptogenesis, in association with restoring intracellular Ca2+ homeostasis and physiologic autophagy, cell survival, and proliferation in induced pluripotent stem cells and their derived neurons from sporadic and familial Alzheimer's disease patients. (ANESTHESIOLOGY 2020; 132:1062-79). © 2020, the American Society of Anesthesiologists, Inc. All Rights Reserved.

Part task and variable priority training in first-year anesthesia resident education: A combined didactic and simulation-based approach to improve management of adverse airway and respiratory events

BACKGROUND: Part task training (PTT) focuses on dividing complex tasks into components followed by intensive concentrated training on individual components. Variable priority training (VPT) focuses on optimal distribution of attention when performing multiple tasks simultaneously with the goal of flexible allocation of attention. This study explored how principles of PTT and VPT adapted to anesthesia training would improve first-year anesthesiology residents' management of simulated adverse airway and respiratory events. The authors hypothesized that participants with PTT and VPT would perform better than those with standard training. METHODS: Twenty-two first-year anesthesia residents were randomly divided into two groups and trained over 12 months. The control group received standard didactic and simulation-based training. The experimental group received similar training but with emphasis on PTT and VPT techniques. Participant ability to manage seven adverse airway and respiratory events were assessed before and after the training period. Performance was measured by the number of correct tasks, making a correct diagnosis, assessment of perceived workload, and an assessment of scenario comprehension. RESULTS: Participants in both groups exhibited significant improvement in all metrics after a year of training. Participants in the experimental group were able to complete more tasks and answered more comprehension questions correctly. There was no difference in perceived workload or the number of correct diagnoses between groups. CONCLUSION: This study in part confirmed the study hypotheses. The results suggest that VPT and PTT are promising adjuncts to didactic and simulation-based training for management of adverse airway and respiratory events. © 2008 American Society of Anesthesiologists, Inc.

Do they understand? (Part II): Assent of children participating in clinical anesthesia and surgery research

Background: Participation of children in clinical research requires not only parental permission but also the assent of the child. Although there is no fixed age at which assent should be sought, investigators should obtain assent from children considered able to provide it. This study was designed to determine children's understanding of the elements of disclosure for studies in which they had assented to participate. Methods: The study population included 102 children aged 7-18 yr who had given their assent to participate in a clinical anesthesia or surgical study. Children were interviewed using a semistructured format to determine their understanding of eight core elements of disclosure for the study to which they had agreed to participate. Two independent assessors scored the children's levels of understanding of these elements. Results: The children's perceived level of understanding of the elements of disclosure was significantly greater than their measured understanding (7.0 > 2.4vs. 5.3 ± 2.7, 0-10 scale; P < 0.0001). Complete understanding of the elements of disclosure for all children ranged from 30.4 to 89.4%. Children aged more than 11 yr had significantly greater understanding compared with younger children, particularly with respect to understanding of the study protocol, the benefits, and the freedom to withdraw. Conclusions: Children approached for their assent to participate in a clinical anesthesia or surgery study have limited understanding of the elements of disclosure and their role as a research participant, particularly if they are aged less than 11 yr.

Appropriateness of Language Used in Patient Educational Materials from 24 National Anesthesiology Associations

Background: Patient education materials produced by national anesthesiology associations could be used to facilitate patient informed consent and promote the discipline of anesthesiology. To achieve these goals, materials must use language that most adults can understand. Health organizations recommend that materials be written at the grade 8 level or less to ensure that they are understood by laypersons. The authors, therefore, investigated the language of educational materials produced by anesthesiology associations. Methods: Educational materials were downloaded from the Web sites of 24 national anesthesiology associations, as available. Materials were divided into eight topics, resulting in 112 separate passages. Linguistic measures were calculated using Coh-Metrix (version 3.0; Memphis, USA) linguistic software. The authors compared the measures to a grade 8 standard and examined the influence of both passage topic and country of origin using multivariate ANOVA. Results: The authors found that 67% of associations provided online educational materials. None of the passages had all linguistic measures at or below the grade 8 level. Linguistic measures were influenced by both passage topic (F = 3.64; P < 0.0001) and country of origin (F = 7.26; P < 0.0001). Contrast showed that passages describing the role of anesthesiologists in perioperative care used language that was especially inappropriate. Conclusions: Those associations that provided materials used words that were long and abstract. The language used was especially inappropriate for topics that are critical to facilitating patient informed consent and promoting the discipline of anesthesiology. Anesthesiology associations should simplify their materials and should consider screening their materials with linguistic software before making them public. Copyright © 2016, the American Society of Anesthesiologists, Inc. Wolters Kluwer Health, Inc. All Rights Reserved.

Evaluation of patient simulator performance as an adjunct to the oral examination for senior anesthesia residents

Background: Patient simulators possess features for performance assessment. However, the concurrent validity and the "added value" of simulator-based examinations over traditional examinations have not been adequately addressed. The current study compared a simulator-based examination with an oral examination for assessing the management skills of senior anesthesia residents. Methods: Twenty senior anesthesia residents were assessed sequentially in resuscitation and trauma scenarios using two assessment modalities: an oral examination, followed by a simulator-based examination. Two independent examiners scored the performances with a previously validated global rating scale developed by the Anesthesia Oral Examination Board of the Royal College of Physicians and Surgeons of Canada. Different examiners were used to rate the oral and simulation performances. Results: Interrater reliability was good to excellent across scenarios and modalities: intraclass correlation coefficients ranged from 0.77 to 0.87. The within-scenario between-modality score correlations (concurrent validity) were moderate: r = 0.52 (resuscitation) and r = 0.53 (trauma) (P < 0.05). Forty percent of the average score variance was accounted for by the participants, and 30% was accounted for by the participant-by-modality interaction. Conclusions: Variance in participant scores suggests that the examination is able to perform as expected in terms of discriminating among test takers. The rather large participant-by-modality interaction, along with the pattern of correlations, suggests that an examinee's performance varies based on the testing modality and a trainee who "knows how" in an oral examination may not necessarily be able to "show how" in a simulation laboratory. Simulation may therefore be considered a useful adjunct to the oral examination. © 2006 American Society of Anesthesiologists, Inc. Lippincott Williams & Wilkins, Inc.

Assessing and Comparing Anesthesiologists' Performance on Mandated Metrics Using a Bayesian Approach

Background: Periodic assessment of performance by anesthesiologists is required by The Joint Commission Ongoing Professional Performance Evaluation program. Methods: The metrics used in this study were the (1) measurement of blood pressure and (2) oxygen saturation (Spo2) either before or less than 5 min after anesthesia induction. Noncompliance was defined as no measurement within this time interval. The authors assessed the frequency of noncompliance using information from 63,913 cases drawn from the anesthesia information management system. To adjust for differences in patient and procedural characteristics, 135 preoperative variables were analyzed with decision trees. The retained covariate for the blood pressure metric was patient's age and, for Spo2 metric, was American Society of Anesthesiologist's physical status, whether the patient was coming from an intensive care unit, and whether induction occurred within 5 min of the start of the scheduled workday. A Bayesian hierarchical model, designed to identify anesthesiologists as "performance outliers," after adjustment for covariates, was developed and was compared with frequentist methods. Results: The global incidences of noncompliance (with frequentist 95% CI) were 5.35% (5.17 to 5.53%) for blood pressure and 1.22% (1.14 to 1.30%) for Spo2 metrics. By using unadjusted rates and frequentist statistics, it was found that up to 43% of anesthesiologists would be deemed noncompliant for the blood pressure metric and 70% of anesthesiologists for the Spo2 metric. By using Bayesian analyses with covariate adjustment, only 2.44% (1.28 to 3.60%) and 0.00% of the anesthesiologists would be deemed "noncompliant" for blood pressure and Spo2, respectively. Conclusion: Bayesian hierarchical multivariate methodology with covariate adjustment is better suited to faculty monitoring than the nonhierarchical frequentist approach.

Mild Acute Kidney Injury after Noncardiac Surgery Is Associated with Longterm Renal Dysfunction A Retrospective Cohort Study

Background: Perioperative acute kidney injury is common. However, it is unclear whether this merely represents a transient increase in creatinine or has prognostic value. Therefore, the long-term clinical importance of mild postoperative acute kidney injury remains unclear. This study assessed whether adults who do and do not experience mild kidney injury after noncardiac surgery are at similar risk for long-term renal injury. Methods: This study is a retrospective cohort analysis of adults having noncardiac surgery at the Cleveland Clinic who had preoperative, postoperative, and long-term (1 to 2 yr after surgery) plasma creatinine measurements. The exposure (postoperative kidney injury) and outcome (long-term renal injury) were defined and staged according to the Kidney Disease: Improving Global Outcomes (KDIGO) initiative criteria. The primary analysis was for lack of association between postoperative kidney injury (stage I vs. no injury) and long-term renal injury. Results: Among 15,621 patients analyzed, 3% had postoperative stage I kidney injury. Long-term renal outcomes were not similar in patients with and without postoperative stage I injury. Specifically, about 26% of patients with stage I postoperative kidney injury still had mild injury 1 to 2 yr later, and 11% had even more severe injury. A full third (37%) of patients with stage I kidney injury therefore had renal injury 1 to 2 yr after surgery. Patients with postoperative stage I injury had an estimated 2.4 times higher odds of having long-term renal dysfunction (KDIGO stage I, II, or III) compared with patients without postoperative kidney injury (odds ratio [95% CI] of 2.4 [2.0 to 3.0]) after adjustment for potential confounding factors. Conclusions: In adults recovering from noncardiac surgery, even small postoperative increases in plasma creatinine, corresponding to stage I kidney injury, are associated with renal dysfunction 1 to 2 yr after surgery. Even mild postoperative renal injury should therefore be considered a clinically important perioperative outcome. (ANESTHESIOLOGY 2020; 132:1053-61). © 2020, the American Society of Anesthesiologists, Inc. All Rights Reserved.

An Automated Software Application Reduces Controlled Substance Discrepancies in Perioperative Areas

Background: Perioperative controlled substance diversion and tracking have received increased regulatory focus throughout the United States. The authors' institution developed and implemented an automated web-based software application for perioperative controlled substance management. The authors hypothesized that implementation of such a system reduces errors as measured by missing controlled substance medications, missing controlled substance kits (a package of multiple controlled substance medications), and missing witness signatures during kit return. Methods: From December 1, 2014 to March 31, 2017, the authors obtained missing controlled substance medication, controlled substance kit, and witness return signature data during the preimplementation, implementation, and study period of the controlled substance management application at a single university hospital. This before and after study was based on a QI project at the authors' institution. The authors included all cases requiring anesthesia services. The primary outcome of this study was the rate of missing controlled substance medications. Secondary outcomes included rates for kits not returned to pharmacy and missing kit return witness signatures. Results: There were 54,302 cases during the preimplementation period, 57,670 cases during the implementation period, and 65,911 cases during the study period. The number of missing controlled substance medication (difference 0.7 per 1,000 cases; 95% CI, 0.38-1.02; P < 0.001) and kit return errors (difference 0.45 per 1,000 cases; 95% CI, 0.24-0.66, P < 0.001) declined after implementation of the application. There was no difference in the number of missing witness return signatures (difference 0.09 per 1,000 cases; 95% CI,-0.08 to 0.26, P = 0.350). A user survey with 206 of 485 (42%) response rate demonstrated that providers believed the new application managed controlled substances better than the previous system. Conclusions: A software application that tracks perioperative controlled substance kits with deep integration into the electronic health record and pharmacy systems is associated with a decrease in management errors. Copyright © 2019, the American Society of Anesthesiologists, Inc. All Rights Reserved.

Perioperative nerve injury after total knee arthroplasty: Regional anesthesia risk during a 20-year cohort study

Background: Perioperative nerve injury (PNI) is one of the most debilitating complications after total knee arthroplasty (TKA). Although regional anesthesia (RA) techniques reduce pain and improve functional outcomes after TKA, they may also contribute to PNI. The objective of this study was to test the hypothesis that PNI risk differs among patients according to RA use during TKA. Methods: All patients aged at least 18 yr who underwent elective TKA from January 1988 to July 2007 were retrospectively identified. The primary outcome variable was the presence of a new PNI documented within 3 months of the procedural date. Age, sex, body mass index, type of procedure, tourniquet time, type of anesthesia, and use of peripheral nerve blockade were evaluated as potential risk factors for PNI using multivariable logistic regression. Results: Ninety-seven cases of PNI were identified among 12,329 patients. Overall incidence of PNI was 0.79% (95% CI, 0.64-0.96%). PNI was not associated with peripheral nerve blockade (odds ratio [OR], 0.97) or type of anesthesia (OR, 1.10 [neuraxial vs. general]; OR, 1.82 [combined vs. general]). Risk for PNI decreased with age (OR, 0.68 [per decade]; P < 0.001) but increased with tourniquet time (OR, 1.28 [per 30-min increase]; P = 0.003) and bilateral procedures (OR, 2.51; P < 0.001). Patients with PNI who underwent peripheral nerve blockade were less likely to have complete neurologic recovery (OR, 0.37; P = 0.03). Conclusions: Risk for PNI after TKA was unchanged by the use of RA techniques. This finding supports the notion that the known benefits of RA for patients undergoing TKA can be achieved without increasing risk of neurologic injury. However, in rare situations when PNI occurs, complete recovery may be less likely if it develops after peripheral nerve blockade. © 2011, the American Society of Anesthesiologists, Inc. Lippincott Williams & Wilkins. Anesthesiology.

Pulmonary Aspiration of Gastric Contents: A Closed Claims Analysis

Background: Perioperative pulmonary aspiration of gastric contents has been associated with severe morbidity and death. The primary aim of this study was to identify outcomes and patient and process of care risk factors associated with gastric aspiration claims in the Anesthesia Closed Claims Project. The secondary aim was to assess these claims for appropriateness of care. The hypothesis was that these data could suggest opportunities to reduce either the risk or severity of perioperative pulmonary aspiration. Methods: Inclusion criteria were anesthesia malpractice claims in the American Society of Anesthesiologists Closed Claims Project that were associated with surgical, procedural, or obstetric anesthesia care with the year of the aspiration event 2000 to 2014. Claims involving pulmonary aspiration were identified and assessed for patient and process factors that may have contributed to the aspiration event and outcome. The standard of care was assessed for each claim. Results: Aspiration of gastric contents accounted for 115 of the 2,496 (5%) claims in the American Society of Anesthesiologists Closed Claims Project that met inclusion criteria. Death directly related to pulmonary aspiration occurred in 66 of the 115 (57%) aspiration claims. Another 16 of the 115 (14%) claims documented permanent severe injury. Seventy of the 115 (61%) patients who aspirated had either gastrointestinal obstruction or another acute intraabdominal process. Anesthetic management was judged to be substandard in 62 of the 115 (59%) claims. Conclusions: Death and permanent severe injury were common outcomes of perioperative pulmonary aspiration of gastric contents in this series of closed anesthesia malpractice claims. The majority of the patients who aspirated had either gastrointestinal obstruction or acute intraabdominal processes. Anesthesia care was frequently judged to be substandard. These findings suggest that clinical practice modifications to preoperative assessment and anesthetic management of patients at risk for pulmonary aspiration may lead to improvement of their perioperative outcomes. © 2021 Lippincott Williams and Wilkins. All rights reserved.

Modulation of tight junction proteins in the perineurium to facilitate peripheral opioid analgesia

Background: Peripheral application of opioids reduces inflammatory pain but is less effective in noninflamed tissue of rats and human patients. Hypertonic solutions can facilitate the antinociceptive activity of hydrophilic opioids in noninflamed tissue in vivo. However, the underlying mechanisms are not well understood. We hypothesized that the enhanced efficacy of opioids may be because of opening of the perineurial barrier formed by tight junction-proteins like claudin-1. Methods: Male Wistar rats were treated intraplantarly with 10% NaCl. Pain behavior (n = 6) and electrophysiological recordings (n = 9 or more) from skin-nerve preparations after local application of the opioid [d-Ala2,N-Me-Phe4,Gly5-ol]enkephalin (DAMGO) were explored. Tight junction-proteins as well as permeability of the barrier were examined by immunohistochemistry and Western blot (n = 3 or more). Results: Local administration of 10% NaCl facilitated increased mechanical nociceptive thresholds in response to DAMGO, penetration of horseradish peroxidase into the nerve, as well as a reduced response of C-but not Aδ-nociceptors to mechanical stimulation after application of DAMGO in the skin-nerve preparation. In noninflamed paw tissue, claudin-1 was expressed in the epidermis, blood vessels, and the perineurium, surrounding neurons immunoreactive for calcitonin gene-related peptide or protein gene product 9.5. Claudin-1 but not claudin-5 or occludin was significantly reduced after pretreatment with 10% NaCl. Intraplantar application of a metalloproteinase inhibitor (GM6001) completely reversed these effects. Conclusion: Hypertonic saline opens the perineurial barrier via metalloproteinase activation and claudin-1 regulation, thereby allowing access of hydrophilic drugs to peripheral opioid receptors. This principle may be used to specifically target hydrophilic drugs to peripheral neurons. © 2012 the American Society of Anesthesiologists, Inc. Lippincott Williams & Wilkins. Anesthesiology.

Artifact processing methods influence on intraoperative hypotension quantification and outcome effect estimates

Background: Physiologic data that is automatically collected during anesthesia is widely used for medical record keeping and clinical research. These data contain artifacts, which are not relevant in clinical care, but may influence research results. The aim of this study was to explore the effect of different methods of filtering and processing artifacts in anesthesiology data on study findings in order to demonstrate the importance of proper artifact filtering. Methods: The authors performed a systematic literature search to identify artifact filtering methods. Subsequently, these methods were applied to the data of anesthesia procedures with invasive blood pressure monitoring. Different hypotension measures were calculated (i.e., presence, duration, maximum deviation below threshold, and area under threshold) across different definitions (i.e., thresholds for mean arterial pressure of 50, 60, 65, 70 mmHg). These were then used to estimate the association with postoperative myocardial injury. results: After screening 3,585 papers, the authors included 38 papers that reported artifact filtering methods. The authors applied eight of these methods to the data of 2,988 anesthesia procedures. The occurrence of hypotension (defined with a threshold of 50 mmHg) varied from 24% with a median filter of seven measurements to 55% without an artifact filtering method, and between 76 and 90% with a threshold of 65 mmHg. Standardized odds ratios for presence of hypotension ranged from 1.16 (95% CI, 1.07 to 1.26) to 1.24 (1.14 to 1.34) when hypotension was defined with a threshold of 50 mmHg. Similar variations in standardized odds ratios were found when applying methods to other hypotension measures and definitions. conclusions: The method of artifact filtering can have substantial effects on estimates of hypotension prevalence. The effect on the association between intraoperative hypotension and postoperative myocardial injury was relatively small. Nevertheless, the authors recommend that researchers carefully consider artifacts handling and report the methodology used. Copyright © 2020, the American Society of Anesthesiologists, Inc. All Rights Reserved.

Spontaneous breathing during general anesthesia prevents the ventral redistribution of ventilation as detected by electrical impedance tomography: A randomized trial

Background: Positive-pressure ventilation causes a ventral redistribution of ventilation. Spontaneous breathing during general anesthesia with a laryngeal mask airway could prevent this redistribution of ventilation. We hypothesize that, compared with pressure-controlled ventilation, spontaneous breathing and pressure support ventilation reduce the extent of the redistribution of ventilation as detected by electrical impedance tomography. Methods: The study was a randomized, three-armed, observational, clinical trial without blinding. With approval from the local ethics committee, we enrolled 30 nonobese patients without severe cardiac or pulmonary comorbidities who were scheduled for elective orthopedic surgery. All of the procedures were performed under general anesthesia with a laryngeal mask airway and a standardized anesthetic regimen. The center of ventilation (primary outcome) was calculated before the induction of anesthesia (AWAKE), after the placement of the laryngeal mask airway (BEGIN), before the end of anesthesia (END), and after arrival in the postanesthesia care unit (PACU). Results: The center of ventilation during anesthesia (BEGIN) was higher than baseline (AWAKE) in both the pressure-controlled and pressure support ventilation groups (pressure control: 55.0 vs. 48.3, pressure support: 54.7 vs. 48.8, respectively; multivariate analysis of covariance, P < 0.01), whereas the values in the spontaneous breathing group remained at baseline levels (47.9 vs. 48.5). In the postanesthesia care unit, the center of ventilation had returned to the baseline values in all groups. No adverse events were recorded. Conclusions: Both pressure-controlled ventilation and pressure support ventilation induce a redistribution of ventilation toward the ventral region, as detected by electrical impedance tomography. Spontaneous breathing prevents this redistribution. © 2012 the American Society of Anesthesiologists, Inc. Lippincott Williams & Wilkins. Anesthesiology.

Surgery results in exaggerated and persistent cognitive decline in a rat model of the metabolic syndrome

Background: Postoperative cognitive decline can be reproduced in animal models. In a well-validated rat model of the Metabolic Syndrome, we sought to investigate whether surgery induced a more severe and persistent form of cognitive decline similar to that noted in preliminary clinical studies. Methods: In rats that had been selectively bred for low and high exercise endurance, the low capacity runners (LCR) exhibited features of Metabolic Syndrome (obesity, dyslipidemia, insulin resistance, and hypertension). Tibial fracture surgery was performed under isoflurane anesthesia in LCR and high capacity runner (HCR) rats and cognitive function was assessed postoperatively in a trace-fear conditioning paradigm and Morris Water Maze; non-operated rats were exposed to anesthesia and analgesia (sham). Group sizes were n = 6. Results: On postoperative D7, LCR rats had shorter freezing times than postoperative HCR rats. Five months postoperatively, LCR rats had a flatter learning trajectory and took longer to locate the submerged platform than postoperative HCR rats; dwell-time in the target quadrant in a probe trial was shorter in the postoperative LCR compared to HCR rats. LCR and HCR sham rats did not differ in any test. Conclusion: Postoperatively, LCR rats diverged from HCR rats exhibiting a greater decline in memory, acutely, with persistent learning and memory decline, remotely; this could not be attributed to changes in locomotor or swimming performance. This Metabolic Syndrome animal model of surgery-induced cognitive decline corroborates, with high fidelity, preliminary findings of postoperative cognitive dysfunction in Metabolic Syndrome patients. © 2013 the American Society of Anesthesiologists, Inc. Lippincott Williams & Wilkins. Anesthesiology.

Global health implications of preanesthesia medical examination for ophthalmic surgery

Background: Preanesthesia medical examination is a common procedure performed before ophthalmic surgery. The frequency and characteristics of new medical issues and unstable medical conditions revealed by ophthalmic preanesthesia medical examination are unknown. We conducted a prospective observational study to estimate the proportion of patients with new medical issues and unstable medical conditions discovered during ophthalmic preanesthesia medical examination. Secondary aims were to characterize abnormal findings and assess surgical delay and adverse perioperative events, in relation to findings. Methods: Patients having preanesthesia medical examination, before ophthalmic surgery, were enrolled over a period of 2 years. A review was conducted of historical, physical examination, and test findings from the preanesthesia medical examination. Results: From review of medical records of 530 patients, 100 patients (19%; 95% CI, 16-23%) were reported by providers to have abnormal conditions requiring further medical evaluation. Of these, 12 (12%) had surgery delayed. Retrospective review of examination results identified an additional 114 patients with abnormal findings for a total of 214 (40%; 95% CI, 36-45%) patients. Among the 214 patients, primary findings were cardiovascular (139, 26%), endocrine (26, 5%), and renal (24, 5%). Complications occurred in 49 (9%; 95% CI, 7-12%) patients within 1 month of surgery. Conclusions: Ophthalmic preanesthesia medical examination frequently detects new medical issues or unstable existing conditions, which do not typically alter conduct of perioperative procedures or outcomes. However, these conditions are relevant to long-term patient health and should be conveyed to primary care physicians for further evaluation. © 2013 the American Society of Anesthesiologists, Inc. Lippincott Williams & Wilkins. Anesthesiology.

Interactions between nitrous oxide and tissue plasminogen activator in a rat model of thromboembolic stroke

Background: Preclinical evidence in rodents has suggested that inert gases, such as xenon or nitrous oxide, may be promising neuroprotective agents for treating acute ischemic stroke. This has led to many thinking that clinical trials could be initiated in the near future. However, a recent study has shown that xenon interacts with tissue-type plasminogen activator (tPA), a well-recognized approved therapy of acute ischemic stroke. Although intraischemic xenon inhibits tPA-induced thrombolysis and subsequent reduction of brain damage, postischemic xenon virtually suppresses both ischemic brain damage and tPA-induced brain hemorrhages and disruption of the blood-brain barrier. The authors investigated whether nitrous oxide could also interact with tPA. Methods: The authors performed molecular modeling of nitrous oxide binding on tPA, characterized the concentration-dependent effects of nitrous oxide on tPA enzymatic and thrombolytic activity in vitro, and investigated the effects of intraischemic and postischemic nitrous oxide in a rat model of thromboembolic acute ischemic stroke. RESULTS:: The authors demonstrate nitrous oxide is a tPA inhibitor, intraischemic nitrous oxide dose-dependently inhibits tPA-induced thrombolysis and subsequent reduction of ischemic brain damage, and postischemic nitrous oxide reduces ischemic brain damage, but in contrast with xenon, it increases brain hemorrhages and disruption of the blood-brain barrier. Conclusions: In contrast with previous studies using mechanical acute stroke models, these data obtained in a clinically relevant rat model of thromboembolic stroke indicate that nitrous oxide should not be considered a good candidate agent for treating acute ischemic stroke compared with xenon. © 2011 the American Society of Anesthesiologists, Inc. Lippincott Williams & Wilkins. Anesthesiology.

Spectral and Entropic Features Are Altered by Age in the Electroencephalogram in Patients under Sevoflurane Anesthesia

Background: Preexisting factors such as age and cognitive performance can influence the electroencephalogram (EEG) during general anesthesia. Specifically, spectral EEG power is lower in elderly, compared to younger, subjects. Here, the authors investigate age-related changes in EEG architecture in patients undergoing general anesthesia through a detailed examination of spectral and entropic measures. Methods: The authors retrospectively studied 180 frontal EEG recordings from patients undergoing general anesthesia, induced with propofol/fentanyl and maintained by sevoflurane at the Waikato Hospital in Hamilton, New Zealand. The authors calculated power spectral density and normalized power spectral density, the entropic measures approximate and permutation entropy, as well as the beta ratio and spectral entropy as exemplary parameters used in current monitoring systems from segments of EEG obtained before the onset of surgery (i.e., with no noxious stimulation). Results: The oldest quartile of patients had significantly lower 1/f characteristics (P < 0.001; area under the receiver operating characteristics curve, 0.84 [0.76 0.92]), indicative of a more uniform distribution of spectral power. Analysis of the normalized power spectral density revealed no significant impact of age on relative alpha (P = 0.693; area under the receiver operating characteristics curve, 0.52 [0.41 0.63]) and a significant but weak effect on relative beta power (P = 0.041; area under the receiver operating characteristics curve, 0.62 [0.52 0.73]). Using entropic parameters, the authors found a significant age-related change toward a more irregular and unpredictable EEG (permutation entropy: P < 0.001, area under the receiver operating characteristics curve, 0.81 [0.71 0.90]; approximate entropy: P < 0.001; area under the receiver operating characteristics curve, 0.76 [0.66 0.85]). With approximate entropy, the authors could also detect an age-induced change in alpha-band activity (P = 0.002; area under the receiver operating characteristics curve, 0.69 [0.60 78]). Conclusions: Like the sleep literature, spectral and entropic EEG features under general anesthesia change with age revealing a shift toward a faster, more irregular, oscillatory composition of the EEG in older patients. Agerelated changes in neurophysiological activity may underlie these findings however the contribution of age-related changes in filtering properties or the signal to noise ratio must also be considered. Regardless, most current EEG technology used to guide anesthetic management focus on spectral features, and improvements to these devices might involve integration of entropic features of the raw EEG. (ANESTHESIOLOGY 2020; 132:1003-16). © 2020, the American Society of Anesthesiologists, Inc. All Rights Reserved.

A Human factors engineering study of the medication delivery process during an anesthetic self-filled syringes versus prefilled syringes

Background: Prefilled syringes (PFS) have been recommended by the Anesthesia Patient Safety Foundation. However, aspects in PFS systems compared with self-filled syringes (SFS) systems have never been explored. The aim of this study is to compare system vulnerabilities (SVs) in the two systems and understand the impact of PFS on medication safety and efficiency in the context of anesthesiology medication delivery in operating rooms. Methods: This study is primarily qualitative research, with a quantitative portion. A work system analysis was conducted to analyze the complicated anesthesia work system using human factors principles and identify SVs. Anesthesia providers were shadowed: (1) during general surgery cases (n = 8) exclusively using SFS and (2) during general surgery cases (n = 9) using all commercially available PFS. A proactive risk assessment focus group was followed to understand the risk of each identified SV. Results: PFS are superior to SFS in terms of the simplified work processes and the reduced number and associated risk of SVs. Eight SVs were found in the PFS system versus 21 in the SFS system. An SV example with high risk in the SFS system was a medication might need to be "drawn-up during surgery while completing other requests simultaneously." This SV added cognitive complexity during anesthesiology medication delivery. However, it did not exist in the PFS system. Conclusions: The inclusion of PFS into anesthesiology medication delivery has the potential to improve system safety and work efficiency. However, there were still opportunities for further improvement by addressing the remaining SVs and newly introduced complexity. © 2016, the American Society of Anesthesiologists, Inc. Wolters Kluwer Health, Inc. All Rights Reserved.

Preparation of the siemens KION anesthetic machine for patients susceptible to malignant hyperthermia

Background: Preparation of anesthetic machines for use with malignant hyperthermia-susceptible (MHS) patients requires that the machines be flushed with clean fresh gas. We investigated the washout of inhalational anesthetics from the KION anesthetic machine. Methods: In part 1, halothane was circulated through KION anesthetic machines for either 2 or 12 h using a test lung. The times to washout halothane (to 10 parts per million [ppm]) first, from the internal circuitry and second, from the ventilator-patient cassette (without the carbon dioxide absorber) were determined at 5 and 10 1/min fresh gas flow (FGF). In part 2, the rates of washout of halothane or isoflurane from either the KION or Ohmeda Excel 210 machines were compared. The effluent gases were analyzed using calibrated Datex Capnomac Ultima (Helsinki, Finland) and a Miran LB2 Portable Ambient Air Analyzer (Foxboro, Norwalk, CT). Results: Halothane was washed out of the internal circuitry of the KION within 5 min at 10 1/min FGF. Halothane was eliminated from the ventilator-patient cassette in 22 min at the same FGF. The times to reach 10 ppm concentration of halothane and isoflurane in the KION at 10 1/min FGF, 23 to 25 min, was four-fold greater than those in the Ohmeda Excel 210, 6 min. Conclusions: To prepare the KION anesthetic machine for MHS patients, the machine without the carbon dioxide absorber must be flushed with 10 1/min FGF for at least 25 min to achieve 10 ppm anesthetic concentration. This FGF should be maintained throughout the anesthetic to avoid increases in anesthetic concentration in the FGF.

Production pressure in the work environment: California anesthesiologists' attitudes and experiences

Background: Pressure to put efficiency, output, or continued production ahead of safety has caused catastrophic accidents in various industries. The authors assessed the attitudes and experiences of anesthesiologists concerning production pressure. Methods: A random, repeated-mailing survey was conducted among 647 members of the American Society of Anesthesiologists residing in California. Questions were asked about attitudes toward production pressure and other patient safety issues, frequency of occurrence of various operating room events, encounters with situations involving unsafe actions, and ratings of sources of production pressure. Results: Forty-seven percent of those sampled returned surveys. The demographics of the respondent population were largely similar to those of the population of anesthesiologists in California. There was no systematic difference between the respondents to the first versus the second mailing, reducing (but not eliminating) the possibility of self-selection bias. Nearly half (49%) of respondents had witnessed production pressure result in what they believed to be unsafe actions by an anesthesiologist. Such events included elective surgery in patients without adequate evaluation or with significant contraindications to surgery. Anesthesiologists felt pressures within themselves to work agreeably with surgeons, avoid delaying cases, and avoid litigation. They also reported overt pressure by surgeons to proceed with cases instead of canceling them, and to hasten anesthetic procedures. Some aspects of production pressure were perceived differently by those reimbursed by fee-for-service versus those paid by salary. Conclusions: Production pressure from internal and external sources is a reality for many anesthesiologists and is perceived in some cases to have resulted in unsafe actions being performed.

Disruption of the transient receptor potential vanilloid 1 can affect survival, bacterial clearance, and cytokine gene expression during murine sepsis

Background: Previous studies suggest that the transient receptor potential vanilloid 1 (TRPV1) channel has a role in sepsis, but it is unclear whether its effect on survival and immune response is beneficial or harmful. Methods: We studied the effects of genetic (Trpv1-knockout vs. wild-type [WT] mice) and pharmacologic disruption of TRPV1 with resiniferatoxin (an agonist) or capsazepine (an antagonist) on mortality, bacterial clearance, and cytokine expression during lipopolysaccharide or cecal ligation and puncture-induced sepsis. Results: After cecal ligation and puncture, genetic disruption of TRPV1 in Trpv1-knockout versus WT mice was associated with increased mortality risk (hazard ratio, 2.17; 95% CI, 1.23-3.81; P = 0.01). Furthermore, pharmacologic disruption of TRPV1 with intrathecal resiniferatoxin, compared with vehicle, increased mortality risk (hazard ratio, 1.80; 95% CI, 1.05-3.2; P = 0.03) in WT, but not in Trpv1-knockout, mice. After lipopolysaccharide, neither genetic (Trpv1 knockout) nor pharmacologic disruption of TRPV1 with resiniferatoxin had significant effect on survival compared with respective controls. In contrast, after lipopolysaccharide, pharmacologic disruption of TRPV1 with capsazepine, compared with vehicle, increased mortality risk (hazard ratio, 1.92; 95% CI, 1.02-3.61; P = 0.04) in WT animals. Furthermore, after cecal ligation and puncture, increased mortality in resiniferatoxin-treated WT animals was associated with higher blood bacterial count (P = 0.0004) and higher nitrate/nitrite concentrations and down-regulation of tumor necrosis factor α expression (P = 0.004) compared with controls. Conclusions: Genetic or pharmacologic disruption of TRPV1 can affect mortality, blood bacteria clearance, and cytokine response in sepsis in patterns that may vary according to the sepsis-inducing event and the method of TRPV1 disruption. Copyright © 2011, the American Society of Anesthesiologists, Inc. Lippincott Williams & Wilkins. Anesthesiology.

Application of the continual reassessment method to dose-finding studies in regional anesthesia: An estimate of the ED95 dose for 0.5% bupivacaine for ultrasound-guided supraclavicular block

Background: Previously reported estimates of the ED95 doses for local anesthetics used in brachial plexus blocks vary. The authors used the continual reassessment method, already established in oncology trials, to determine the ED95 dose for 0.5% bupivacaine for the ultrasound-guided supraclavicular block. Methods: A double-blind, prospective trial was scheduled for 40 patients of American Society of Anesthesiologists class I-III presenting for upper limb surgery and supraclavicular block. The study dose to be administered was arbitrarily divided into six dose levels (12, 15, 18, 21, 24, and 27 ml) with a priori probabilities of success of 0.5, 0.75, 0.90, 0.95, 0.98, and 0.99 respectively. A continual reassessment method statistical program created a dose-response curve, which would shift direction depending on the success or failure of the block. Our starting dose was 21 ml and the next allocated dose was reestimated by the program to be the dose level with the updated posterior response probability closest to 0.95. Results: After recruitment of eight patients, our initial dose levels and associated probabilities were deemed too low to determine the ED95. Updated a prioris were calculated from the statistical program, and the study recommenced with a new starting dose of 30 ml. On completion, the ED95 dose was estimated to be 27 ml (95% CI, 24-28 ml). Conclusions: The continual reassessment method trial design provided a credible estimate for the ED95 dose for 0.5% bupivacaine for our technique of supraclavicular block and may be of value as a statistically robust method for dosefinding studies in anesthesiology. Copyright © 2013, the American Society of Anesthesiologists, Inc. Lippincott Williams & Wilkins.

Estimation of the bispectral index by anesthesiologists: An inverse turing test

Background: Processed electroencephalographic indices, such as the bispectral index (BIS), are potential adjuncts for assessing anesthetic depth. While BIS® monitors might aid anesthetic management, unprocessed or nonproprietary electroencephalographic data may be a rich source of information for clinicians. We hypothesized that anesthesiologists, after training in electroencephalography interpretation, could estimate the index of a reference BIS as accurately as a second BIS® monitor (twin BIS®) (Covidien Medical, Boulder, CO) when provided with clinical and electroencephalographic data. Methods: Two sets of electrodes connected to two separate BIS® monitors were placed on the foreheads of 10 surgical patients undergoing general anesthesia. Electroencephalographic parameters, vital signs, and end-tidal anesthetic gas concentrations were recorded at prespecified time points, and were provided to two sets of anesthesiologists. Ten anesthesiologists received brief structured training in electroencephalograph interpretation and 10 were untrained. Although electroencephalographic waveforms and open-source processed electroencephalograph metrics were provided from the reference BIS®, both groups were blinded to BIS values and were asked to estimate BIS. Results: The trained anesthesiologists averaged as close to or closer to the reference BIS® compared with the twin BIS® monitor for 34% of their BIS estimates versus 26% for the untrained anesthesiologists. Using linear mixed effects model analysis, there was a statistically significant difference between the trained and untrained anesthesiologists (P = 0.02), but no difference between the twin BIS® monitor and trained anesthesiologists (P = 0.9). Conclusion: With limited electroencephalography training and access to clinical data, anesthesiologists can estimate the BIS almost as well as a second BIS® monitor. These results reinforce the potential utility of training anesthesia practitioners in unprocessed electroencephalogram interpretation. Copyright © 2011, the American Society of Anesthesiologists, Inc. Lippincott Williams & Wilkins. Anesthesiology.

State-specific effects of sevoflurane anesthesia on sleep homeostasis: Selective recovery of slow wave but not rapid eye movement sleep

Background: Prolonged propofol administration does not result in signs of sleep deprivation, and propofol anesthesia appears to satisfy the homeostatic need for both rapid eye movement (REM) and non-REM (NREM) sleep. In the current study, the effects of sevoflurane on recovery from total sleep deprivation were investigated. Methods: Ten male rats were instrumented for electrophysiologic recordings under three conditions: (1) 36-h ad libitum sleep; (2) 12-h sleep deprivation followed by 24-h ad libitum sleep; and (3) 12-h sleep deprivation, followed by 6-h sevoflurane exposure, followed by 18-h ad libitum sleep. The percentage of waking, NREM sleep, and REM sleep, as well as NREM sleep δ power, were calculated and compared for all three conditions. Results: Total sleep deprivation resulted in significantly increased NREM and REM sleep for 12-h postdeprivation. Sevoflurane exposure after deprivation eliminated the homeostatic increase in NREM sleep and produced a significant decrease in the NREM sleep δ power during the postanesthetic period, indicating a complete recovery from the effects of deprivation. However, sevoflurane did not affect the time course of REM sleep recovery, which required 12 h after deprivation and anesthetic exposure. CONCLUSION:: Unlike propofol, sevoflurane anesthesia has differential effects on NREM and REM sleep homeostasis. These data confirm the previous hypothesis that inhalational agents do not satisfy the homeostatic need for REM sleep, and that the relationship between sleep and anesthesia is likely to be agent and state specific. © 2011, the American Society of Anesthesiologists, Inc. Lippincott Williams & Wilkins. Anesthesiology.

Lack of Association between Blood Pressure Management by Anesthesia Residents and Competence Committee Evaluations or In-training Exam Performance: A Cohort Analysis

Background: Prompt treatment of severe blood pressure instability requires both cognitive and technical skill. The ability to anticipate and respond to episodes of hemodynamic instability should improve with training. The authors tested the hypothesis that the duration of severe hypotension during anesthesia administered by residents correlates with concurrent adjusted overall performance evaluations by the Clinical Competence Committee and subsequent in-training exam scores. Methods: The authors obtained data on 70 first-and second-year anesthesia residents at the Cleveland Clinic. Analysis was restricted to adults having noncardiac surgery with general anesthesia. Outcome variables were in-training exam scores and subjective evaluations of resident performance ranked in quintiles. The primary predictor was cumulative systolic arterial pressure less than 70 mmHg. Secondary predictors were administration of vasopressors, frequency of hypotension, average duration of hypotensive episodes, and blood pressure variability. Results: The primary statistical approach was mixed-effects modeling, adjusted for potential confounders. The authors considered 15,216 anesthesia care episodes. A total of 1,807 hypotensive episodes were observed, lasting an average of 32 ± 20 min (SD) per 100 h of anesthesia, with 68% being followed by vasopressor administration. The duration of severe hypotension (systolic pressure less than 70 mmHg) was associated with neither Competence Committee evaluations nor in-training exam scores. There was also no association between secondary blood pressure predictors and either Competence Committee evaluations or in-training exam results. Conclusions: There was no association between any of the five blood pressure management characteristics and either in-training exam scores or clinical competence evaluations. However, it remains possible that the measures of physiologic control, as assessed from electronic anesthesia records, evaluate useful but different aspects of anesthesiologist performance. © 2015 the American Society of Anesthesiologists, Inc.

Prophylactic Intrathecal Morphine and Prevention of Post-Dural Puncture Headache A Randomized Double-blind Trial

Background: Prophylactic epidural morphine administration after unintentional dural puncture with a large-bore needle has been shown to decrease the incidence of post-dural puncture headache. The authors hypothesized that prophylactic administration of intrathecal morphine would decrease the incidence of post-dural puncture headache and/or need for epidural blood patch after unintentional dural puncture. Methods: Parturients with an intrathecal catheter in situ after unintentional dural puncture with a 17-g Tuohy needle during intended epidural catheter placement for labor analgesia were enrolled in this randomized, double-blind trial. After delivery, subjects were randomized to receive intrathecal morphine 150 μg or normal saline. The primary outcome was the incidence of post-dural puncture headache. Secondary outcomes included onset, duration, and severity of post-dural puncture headache, the presence of cranial nerve symptoms and the type of treatment the patient received. Results: Sixty-one women were included in the study. The incidence of post-dural puncture headache was 21 of 27 (78%) in the intrathecal morphine group and 27 of 34 (79%) in the intrathecal saline group (difference,-1%; 95% CI,-25% to 24%). There were no differences between groups in the onset, duration, or severity of headache, or presence of cranial nerve symptoms. Epidural blood patch was administered to 10 of 27 (37%) of subjects in the intrathecal morphine and 11 of 21 (52%) of the intrathecal saline group (difference 15%; 95% CI,-18% to 48%). Conclusions: The present findings suggest that a single prophylactic intrathecal morphine dose of 150 μg administered shortly after delivery does not decrease the incidence or severity of post-dural puncture headache after unintentional dural puncture. This study does not support the clinical usefulness of prophylactic intrathecal morphine after an unintentional dural puncture. (ANESTHESIOLOGY 2020; 132:1045-52). © 2020, the American Society of Anesthesiologists, Inc. All Rights Reserved.

AZD-3043: A novel, metabolically labile sedative-hypnotic agent with rapid and predictable emergence from hypnosis

Background: Propofol can be associated with delayed awakening after prolonged infusion. The aim of this study was to characterize the preclinical pharmacology of AZD-3043, a positive allosteric modulator of the γ-aminobutyric acid type A (GABAA) receptor containing a metabolically labile ester moiety. The authors postulated that its metabolic pathway would result in a short-acting clinical profile. Methods: The effects of AZD-3043, propofol, and propanidid were studied on GABAA receptor-mediated chloride currents in embryonic rat cortical neurons. Radioligand binding studies were also performed. The in vitro stability of AZD-3043 in whole blood and liver microsomes was evaluated. The duration of the loss of righting reflex and effects on the electroencephalograph evoked by bolus or infusion intravenous administration were assessed in rats. A mixed-effects kinetic-dynamic model using minipigs permitted exploration of the clinical pharmacology of AZD-3043. Results: AZD-3043 potentiated GABAA receptor-mediated chloride currents and inhibited [S]tert-butylbicyclophosphorothionate binding to GABAA receptors. AZD-3043 was rapidly hydrolyzed in liver microsomes from humans and animals. AZD-3043 produced hypnosis and electroencephalograph depression in rats. Compared with propofol, AZD-3043 was shorter acting in rats and pigs. Computer simulation using the porcine kinetic-dynamic model demonstrated that AZD-3043 has very short 50 and 80% decrement times independent of infusion duration. Conclusions: AZD-3043 is a positive allosteric modulator of the GABAA receptor in vitro and a sedative-hypnotic agent in vivo. The esterase dependent metabolic pathway results in rapid clearance and short duration of action even for long infusions. AZD-3043 may have clinical potential as a sedative-hypnotic agent with rapid and predictable recovery. © 2012 the American Society of Anesthesiologists, Inc. Lippincott Williams & Wilkins. Anesthesiology.

In vitro kinetic evaluation of the free radical scavenging ability of propofol

Background: Propofol is a widely used, short-acting, and intravenously administered hypnotic agent with notable antioxidant and free radical scavenging activities. However, there are relatively few kinetic studies on the free radical scavenging ability of propofol. The goal of this study is to evaluate the kinetics of propofol scavenging 2,2′-azino-bis (3- ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical (ABTS +). Methods: The stock solution of ABTS was prepared by incubating 7 mM ABTS with 2.8 mM potassium persulfate in deionized water, and then diluted with 5 mM phosphate-buffered saline (pH 7.2) to get a working solution (36 μM ABTS and 18 μM ABTS). The reaction was monitored by measuring specific absorbance changes of ABTS and ABTS after adding 4 μM propofol (final concentration) to the working solution. The propofol-ABTS reaction products were analyzed by high-performance liquid chromatography and liquid chromatography mass spectrometry/mass spectrometry. Results: Wave scanning and kinetic evaluation demonstrated that the ABTS scavenging process of propofol is relatively fast. The ABTS consumption rate by propofol is greater than the rate of ABTS formation. The degradation products of reaction between propofol and ABTS were mainly ABTS-propofol, a part of the ABTS molecule, and a combination of propofol with a part of the ABTS molecule. Conclusions: Propofol scavenges ABTS with a fast and stable kinetic feature in vitro, which is useful and important for understanding propofol's antioxidant properties. The kinetic process of the free radical scavenging activity of propofol may also play a role in dynamic protection in the body. © 2012 the American Society of Anesthesiologists, Inc. Lippincott Williams &amp; Wilkins. Anesthesiology.

Comparison of Neonatal and Adult Fibrin Clot Properties between Porcine and Human Plasma

Background: Recent studies suggest that adult-specific treatment options for fibrinogen replacement during bleeding may be less effective in neonates. This is likely due to structural and functional differences found in the fibrin network between adults and neonates. In this investigation, the authors performed a comparative laboratory-based study between immature and adult human and porcine plasma samples in order to determine if piglets are an appropriate animal model of neonatal coagulopathy. Methods: Adult and neonatal human and porcine plasma samples were collected from the Children's Hospital of Atlanta and North Carolina State University College of Veterinary Medicine, respectively. Clots were formed for analysis and fibrinogen concentration was quantified. Structure was examined through confocal microscopy and cryogenic scanning electron microscopy. Function was assessed through atomic force microscopy nanoindentation and clotting and fibrinolysis assays. Lastly, novel hemostatic therapies were applied to neonatal porcine samples to simulate treatment. Results: All sample groups had similar plasma fibrinogen concentrations. Neonatal porcine and human plasma clots were less branched with lower fiber densities than the dense and highly branched networks seen in adult human and porcine clots. Neonatal porcine and human clots had faster degradation rates and lower clot stiffness values than adult clots (stiffness [mmHg] mean ± SD: Neonatal human, 12.15 ± 1.35 mmHg vs. adult human, 32.25 ± 7.13 mmHg; P = 0.016; neonatal pig, 10.5 ± 8.25 mmHg vs. adult pigs, 32.55 ± 7.20 mmHg; P = 0.015). The addition of hemostatic therapies to neonatal porcine samples enhanced clot formation. Conclusions: The authors identified similar age-related patterns in structure, mechanical, and degradation properties between adults and neonates in porcine and human samples. These findings suggest that piglets are an appropriate preclinical model of neonatal coagulopathy. The authors also show the feasibility of in vitro model application through analysis of novel hemostatic therapies as applied to dilute neonatal porcine plasma. (ANESTHESIOLOGY 2020; 132:1091-101). © 2020, the American Society of Anesthesiologists, Inc. All Rights Reserved.

Neuroprotective effect of orexin-A is mediated by an increase of hypoxia-inducible factor-1 activity in rat

Background: Recent studies suggest that the novel neuropeptide orexin-A may play an essential role during neuronal damage. However, the function of orexin-A during brain ischemia remains unclear. Recently, hypoxia-inducible factor-1α (HIF-1α) was shown to be activated by orexin-A. The aim of the current study is to test the hypothesis that administration of exogenous orexin-A can attenuate ischemia-reperfusion injury through the facilitation of HIF-1α expression. Methods: Sprague-Dawley rats were subjected to transient middle cerebral artery occlusion for 120 min. Rats were treated with different doses of orexin-A or vehicle before the ischemia and at the onset of reperfusion. To investigate the action of HIF-1α in the neuroprotective effects of orexin-A, the HIF-1α inhibitor YC-1 was used alone or combined with orexin-A. Neurologic deficit scores and infarct volume were assessed. Brains were harvested for immunohistochemical staining and western blot analysis. Results: Orexin-A significantly ameliorated neurologic deficit scores and reduced infarct volume after cerebral ischemia reperfusion. Administration of 30 μg/kg orexin-A showed optimal neuroprotective effects. This effect was still present 7 days after reperfusion. Furthermore, orexin-A decreased the number of apoptotic cells and significantly enhanced HIF-1α expression after cerebral ischemia reperfusion. Moreover, the facilitation of HIF-1α expression was accompanied with inhibition of von Hippel-Lindau expression. Administration of HIF-1α inhibitor suppressed the increase of HIF-1α and reversed the neuroprotective effects of orexin-A. Conclusions: Orexin-A has a neuroprotective effect against cerebral ischemia-reperfusion injury. These effects may be mediated through the HIF-1α pathway. © 2011, the American Society of Anesthesiologists, Inc. Lippincott Williams & Wilkins. Anesthesiology.

Combination of EuroSCORE and cardiac troponin i improves the prediction of adverse outcome after cardiac surgery

Background: Reclassification tables have never been used to compare concentrations of cardiac troponin I (cTnI) with predictive models of risk in the perioperative setting. The current study aimed to evaluate the prognostic value of pre- and/or postoperative serum cTnI when combined with The European System for Cardiac Operative Risk Evaluation (EuroSCORE) in predicting adverse outcome after cardiac surgery. Methods: Nine hundred five consecutive patients were included. Standard EuroSCORE as well as preoperative and 24-h postoperative cTnI were measured in all patients. Major adverse cardiac events and in-hospital mortality were chosen as study endpoints. The performance of EuroSCORE with and without pre- and/or postoperative cTnI were assessed by means of receiver operating characteristic curves, net reclassification index, and integrated discrimination improvement analyses. Data are expressed as ±SD. Results: Death occurred in 28 of 905 (3%) patients and major adverse cardiac events in 202/905 (22%) patients. Models including EuroSCORE alone were characterized by a low discriminative power (c-index = 0.60 ± 0.05) in predicting major adverse cardiac events. The c-index increased to 0.61 ± 0.05 (P = 0.46), 0.70 ± 0.04 (P < 0.001), and 0.71 ± 0.04 (P < 0.001) when preoperative, postoperative, and pre/postoperative cTnI were included, respectively. The better predictive ability was confirmed by net reclassification index (0.41 ± 0.08, P < 0.001; 0.67 ± 0.08, P < 0.001; and 0.68 ± 0.08, P < 0.001, respectively) and integrated discrimination improvement (0.003 ± 0.002, P = 0.12; 0.099 ± 0.015, P < 0.001; and 0.094 ± 0.016, P < 0.001, respectively). Similar results were observed for in-hospital mortality. Conclusions: The combination of EuroSCORE and postoperative cTnI provides the best discriminative power and performance in predicting adverse outcome after cardiac surgery and is suggested as being an effective model that improves early identification of high-risk patients. © 2011, the American Society of Anesthesiologists, Inc. Lippincott Williams & Wilkins. Anesthesiology.

The pharmacokinetics of the new short-acting opioid remifentanil (GI87084B) in healthy adult male volunteers

Background: Remifentanil (GI87084B) is a new short-acting opioid with a unique ester structure. Metabolism of remifentanil by ester hydrolysis results in very rapid elimination. The aim of this study was to characterize in detail the pharmacokinetic profile of remifentanil in healthy male volunteers. Methods: Ten healthy adult male volunteers received a zero-order infusion of remifentanil at doses ranging from 1 to 8 μg · kg-1 · min- 1 for 20 min. Frequent arterial blood samples were drawn and analyzed by gas chromatographic mass spectroscopy to determine the remifentanil blood concentrations. The raw pharmacokinetic data were analyzed using three different parametric compartmental modeling methods (traditional two-stage, naive pooled data, and NONMEM). The raw pharmacokinetic data also were analyzed using numeric deconvolution and a nonparametric moment technique. A computer simulation using the pharmacokinetic parameters of the NONMEM compartmental model was performed to provide a more intuitively meaningful and clinically relevant description of the pharmacokinetics. The simulation estimated the time necessary to achieve a 50% decrease in remifentanil concentration after a variable-length infusion. Results: For each parametric method, a three-compartment mammillary model that accurately describes remifentanil's concentration decay curve was constructed. The NONMEM analysis-population pharmacokinetic parameters included a central clearance of 2.8 l/min, a volume of distribution at steady state of 32.8 l, and a terminal half-life of 48 min. The mean results of the nonparametric moment analysis included a clearance of 2.9 l/min, a volume of distribution at steady state of 31.8 l, and a mean residence time of 10.9 min. The computer simulation revealed the strikingly unique pharmacokinetic profile of remifentanil compared to that of the currently available fentanyl family of opioids. Conclusions: Remifentanil is a new, short-acting opioid with promising clinical potential in anesthesiology.

Isoflurane activates intestinal sphingosine kinase to protect against renal ischemia-reperfusion-induced liver and intestine injury

Background: Renal ischemia-reperfusion injury (IRI) is a major cause of acute kidney injury and often leads to multiorgan dysfunction and systemic inflammation. Volatile anesthetics have potent antiinflammatory effects. We aimed to determine whether the representative volatile anesthetic isoflurane protects against acute kidney injury-induced liver and intestinal injury and to determine the mechanisms involved in this protection. Methods: Mice were anesthetized with pentobarbital and subjected to 30 min of left renal ischemia after right nephrectomy, followed by exposure to 4 h of equianesthetic doses of pentobarbital or isoflurane. Five hours after renal IRI, plasma creatinine and alanine aminotransferase concentrations were measured. Liver and intestine tissues were analyzed for proinflammatory messenger RNA (mRNA) concentrations, histologic features, sphingosine kinase-1 (SK1) immunoblotting, SK1 activity, and sphingosine-1-phosphate concentrations. Results: Renal IRI with pentobarbital led to severe renal, hepatic, and intestinal injury with focused periportal hepatocyte vacuolization; small-intestinal apoptosis; and proinflammatory mRNA up-regulation. Isoflurane protected against renal IRI and reduced hepatic and intestinal injury via induction of small-intestinal crypt SK1 mRNA, protein and enzyme activity, and increased sphingosine-1-phosphate. We confirmed the importance of SK1 because mice treated with a selective SK inhibitor or mice deficient in the SK1 enzyme were not protected against hepatic and intestinal dysfunction with isoflurane. Conclusions: Isoflurane protects against multiorgan injury after renal IRI via induction of the SK1/sphingosine-1-phosphate pathway. Our findings may help to unravel the cellular signaling pathways of volatile anesthetic-mediated hepatic and intestinal protection and may lead to new therapeutic applications of volatile anesthetics during the perioperative period. © 2011, the American Society of Anesthesiologists, Inc. Lippincott Williams & Wilkins. Anesthesiology.

Anesthesiology Resident Night Float Duty Alters Sleep Patterns: An Observational Study

BACKGROUND: Residency programs utilize night float systems to adhere to duty hour restrictions; however, the influence of night float on resident sleep has not been described. The study aim was to determine the influence of night float on resident sleep patterns and quality of sleep. We hypothesized that total sleep time decreases during night float, increases as residents acclimate to night shift work, and returns to baseline during recovery. METHODS: This was a single-center observational study of 30 anesthesia residents scheduled to complete six consecutive night float shifts. Electroencephalography sleep patterns were recorded during baseline (three nights), night float (six nights), and recovery (three nights) using the ZMachine Insight monitor (General Sleep Corporation, USA). Total sleep time; light, deep, and rapid eye movement sleep; sleep efficiency; latency to persistent sleep; and wake after sleep onset were observed. RESULTS: Mean total sleep time ± SD was 5.9 ± 1.9 h (3.0 ± 1.2.1 h light; 1.4 ± 0.6 h deep; 1.6 ± 0.7 h rapid eye movement) at baseline. During night float, mean total sleep time was 4.5 ± 1.8 h (1.4-h decrease, 95% CI: 0.9 to 1.9, Cohen's d = -1.1, P < 0.001) with decreases in light (2.2 ± 1.1 h, 0.7-h decrease, 95% CI: 0.4 to 1.1, d = -1.0, P < 0.001), deep (1.1 ± 0.7 h, 0.3-h decrease, 95% CI: 0.1 to 0.4, d = -0.5, P = 0.005), and rapid eye movement sleep (1.2 ± 0.6 h, 0.4-h decrease, 95% CI: 0.3 to 0.6, d = -0.9, P < 0.001). Mean total sleep time during recovery was 5.4 ± 2.2 h, which did not differ significantly from baseline; however, deep (1.0 ± 0.6 h, 0.4-h decrease, 95% CI: 0.2 to 0.6, d = -0.6, P = 0.001 *, P = 0.001) and rapid eye movement sleep (1.2 ± 0.8 h, 0.4-h decrease, 95% CI: 0.2 to 0.6, d = -0.9, P < 0.001 P < 0.001) were significantly decreased. CONCLUSIONS: Electroencephalography monitoring demonstrates that sleep quantity is decreased during six consecutive night float shifts. A 3-day period of recovery is insufficient for restorative sleep (rapid eye movement and deep sleep) levels to return to baseline.

Driving performance of residents after six consecutive overnight work shifts

Background: Residency training requires work in clinical settings for extended periods of time, resulting in altered sleep patterns, sleep deprivation, and potentially deleterious effects on safe performance of daily activities, including driving a motor vehicle. Methods: Twenty-nine anesthesiology resident physicians in postgraduate year 2 to 4 drove for 55 min in the Virginia Driving Safety Laboratory using the Driver Guidance System (MBFARR, LLC, USA). Two driving simulator sessions were conducted, one experimental session immediately after the final shift of six consecutive night shifts and one control session at the beginning of a normal day shift (not after call). Both sessions were conducted at 8:00 am. Psychomotor vigilance task testing was employed to evaluate reaction time and lapses in attention. Results: After six consecutive night shifts, residents experienced significantly impaired control of all the driving variables including speed, lane position, throttle, and steering. They were also more likely to be involved in collisions. After six consecutive night shifts, residents had a significant increase in reaction times (281.1 vs. 298.5 ms; P = 0.001) and had a significant increase in the number of both minor (0.85 vs. 1.88; P = 0.01) and major lapses (0.00 vs. 0.31; P = 0.008) in attention. Conclusions: Resident physicians have greater difficulty controlling speed and driving performance in the driving simulator after six consecutive night shifts. Reaction times are also increased with emphasis on increases in minor and major lapses in attention after six consecutive night shifts. © 2016, the American Society of Anesthesiologists, Inc. Wolters Kluwer Health, Inc.

Inappropriate Citation of Retracted Articles in Anesthesiology and Intensive Care Medicine Publications

Background: Retracted articles represent research withdrawn from the existing body of literature after publication. Research articles may be retracted for several reasons ranging from honest errors to intentional misconduct. They should not be used as reliable sources, and it is unclear why they are cited occasionally by other articles. This study hypothesized that several mechanisms may contribute to citing retracted literature and aimed to analyze the characteristics of articles citing retracted literature in anesthesiology and critical care. Methods: Using the Retraction Watch database, we retrieved retracted articles on anesthesiology and intensive care medicine up to August 16, 2021, and identified the papers citing these retracted articles. A survey designed to investigate the reasons for citing these articles was sent to the corresponding authors of the citing papers. Results: We identified 478 retracted articles, 220 (46%) of which were cited at least once. We contacted 1297 corresponding authors of the papers that cited these articles, 417 (30%) of whom responded to our survey and were included in the final analysis. The median number of authors in the analyzed articles was five, and the median elapsed time from retraction to citation was 3 yr. Most of the corresponding authors (372, 89%) were unaware of the retracted status of the cited article, mainly because of inadequate notification of the retraction status in journals and/or databases and the use of stored copies. Conclusions: The corresponding authors were generally unaware of the retraction of the cited article, usually because of inadequate identification of the retracted status in journals and/or web databases and the use of stored copies. Awareness of this phenomenon and rigorous control of the cited references before submitting a paper are of fundamental importance in research. © 2022 Lippincott Williams and Wilkins. All rights reserved.

Salvinorin a produces cerebrovasodilation through activation of nitric oxide synthase, κ receptor, and adenosine triphosphate-sensitive potassium channel

Background: Salvinorin A is a nonopioid, selective κ opioid-receptor agonist. Despite its high potential for clinical application, its pharmacologic profile is not well known. In the current study, we hypothesized that salvinorin A dilates pial arteries via activation of nitric oxide synthase, adenosine triphosphate-sensitive potassium channels, and opioid receptors. Methods: Cerebral artery diameters and cyclic guanosine monophosphate in cortical periarachnoid cerebrospinal fluid were monitored in piglets equipped with closed cranial windows. Observation took place before and after salvinorin A administration in the presence or absence of an opioid antagonist (naloxone), a κ opioid receptor-selective antagonist (norbinaltorphimine), nitric oxide synthase inhibitors (N(G)-nitro-L-arginine and 7-nitroindazole), a dopamine receptor D2 antagonist (sulpiride), and adenosine triphosphate-sensitive potassium and Ca-activated K channel antagonists (glibenclamide and iberiotoxin). The effects of salvinorin A on the constricted cerebral artery induced by hypocarbia and endothelin were investigated. Data were analyzed by repeated measures ANOVA (n = 5) with statistical significance set at a P value of less than 0.05. Results: Salvinorin A induced immediate but brief vasodilatation that was sustained for 30 min via continual administration every 2 min. Vasodilatation and the associated cyclic guanosine monophosphate elevation in cerebrospinal fluid were abolished by preadministration N(G)-nitro-L-arginine, but not 7-nitroindazole. Although naloxone, norbinaltorphimine, and glibenclamide abolished salvinorin A-induced cerebrovasodilation, this response was unchanged by iberiotoxin and sulpiride. Hypocarbia and endothelin-constricted pial arteries responded similarly to salvinorin A, to the extent observed under resting tone. Conclusions: Salvinorin A dilates cerebral arteries via activation of nitric oxide synthase, adenosine triphosphate-sensitive potassium channel, and the κ opioid receptor. © 2011, the American Society of Anesthesiologists, Inc. Lippincott Williams & Wilkins. Anesthesiology.

Cysteinyl leukotrienes impair hypoxic pulmonary vasoconstriction in endotoxemic mice

Background: Sepsis impairs hypoxic pulmonary vasoconstriction (HPV) in patients and animal models, contributing to systemic hypoxemia. Concentrations of cysteinyl leukotrienes are increased in the bronchoalveolar lavage fluid of patients with sepsis, but the contribution of cysteinyl leukotrienes to the impairment of HPV is unknown. Methods: Wild-type mice, mice deficient in leukotriene C4 synthase, the enzyme responsible for cysteinyl leukotriene synthesis, and mice deficient in cysteinyl leukotriene receptor 1 were studied 18 h after challenge with either saline or endotoxin. HPV was measured by the increase in left pulmonary vascular resistance induced by left mainstem bronchus occlusion. Concentrations of cysteinyl leukotrienes were determined in the bronchoalveolar lavage fluid. Results: In the bronchoalveolar lavage fluid of all three strains, cysteinyl leukotrienes were not detectable after saline challenge; whereas endotoxin challenge increased cysteinyl leukotriene concentrations in wild-type mice and mice deficient in cysteinyl leukotriene receptor 1, but not in mice deficient in leukotriene C4 synthase. HPV did not differ among the three mouse strains after saline challenge (120 ± 26, 114 ± 16, and 115 ± 24%, respectively; mean ± SD). Endotoxin challenge markedly impaired HPV in wild-type mice (41 ± 20%) but only marginally in mice deficient in leukotriene C 4 synthase (96 ± 16%, P &lt; 0.05 vs. wild-type mice), thereby preserving systemic oxygenation. Although endotoxin modestly decreased HPV in mice deficient in cysteinyl leukotriene receptor 1 (80 ± 29%, P &lt; 0.05 vs. saline challenge), the magnitude of impairment was markedly less than in endotoxin-challenged wild-type mice. Conclusion: Cysteinyl leukotrienes importantly contribute to endotoxin-induced impairment of HPV in part via a cysteinyl leukotriene receptor 1-dependent mechanism. © 2011, the American Society of Anesthesiologists, Inc. Lippincott Williams &amp; Wilkins. Anesthesiology.

Optimized perioperative analgesia reduces chronic phantom limb pain intensity, prevalence, and frequency: A prospective, randomized, clinical trial

Background: Severe preamputation pain is associated with phantom limb pain (PLP) development in limb amputees. We investigated whether optimized perioperative analgesia reduces PLP at 6-month follow-up. Methods: A total of 65 patients underwent lower-limb amputation and were assigned to five analgesic regimens: (1) Epi/Epi/Epi patients received perioperative epidural analgesia and epidural anesthesia; (2) PCA/Epi/Epi patients received preoperative intravenous patient-controlled analgesia (PCA), postoperative epidural analgesia, and epidural anesthesia; (3) PCA/Epi/PCA patients received perioperative intravenous PCA and epidural anesthesia; (4) PCA/GA/PCA patients received perioperative intravenous PCA and general anesthesia (GA); (5) controls received conventional analgesia and GA. Epidural analgesia or intravenous PCA started 48 h preoperatively and continued 48 h postoperatively. The results of the visual analog scale and the McGill Pain Questionnaire were recorded perioperatively and at 1 and 6 months. Results: At 6 months, median (minimum-maximum) PLP and P values (intervention groups vs. control group) for the visual analog scale were as follows: 0 (0-20) for Epi/Epi/Epi (P = 0.001), 0 (0-42) for PCA/Epi/Epi (P = 0.014), 20 (0-40) for PCA/Epi/PCA (P = 0.532), 0 (0-30) for PCA/GA/PCA (P = 0.008), and 20 (0-58) for controls. The values for the McGill Pain Questionnaire were as follows: 0 (0-7) for Epi/Epi/Epi (P < 0.001), 0 (0-9) for PCA/Epi/Epi (P = 0.003), 6 (0-11) for PCA/Epi/PCA (P = 0.208), 0 (0-9) for PCA/GA/PCA (P = 0.003), and 7 (0-15) for controls. At 6 months, PLP was present in 1 of 13 Epi/Epi/Epi, 4 of 13 PCA/Epi/Epi, and 3 of 13 PCA/GA/PCA patients versus 9 of 12 control patients (P = 0.001, P = 0.027, and P = 0.009, respectively). Residual limb pain at 6 months was insignificant. Conclusions: Optimized epidural analgesia or intravenous PCA, starting 48 h preoperatively and continuing for 48 h postoperatively, decreases PLP at 6 months. Copyright © 2011, the American Society of Anesthesiologists, Inc. Lippincott Williams & Wilkins. Anesthesiology.

Simulation-based training improves physicians performance in patient care in high-stakes clinical setting of cardiac surgery

Background: Simulation-based training is useful in improving physicians skills. However, no randomized controlled trials have been able to demonstrate the effects of simulation teaching in real-life patient care. This study aimed to determine whether simulation-based training or an interactive seminar resulted in better patient care during weaning from cardiopulmonary bypass (CPB)-a high stakes clinical setting. METHODS:: This study was conducted as a prospective, single-blinded, randomized controlled trial. After institutional research board approval, 20 anesthesiology trainees, postgraduate year 4 or higher, inexperienced in CPB weaning, and 60 patients scheduled for elective coronary artery bypass grafting were recruited. Each trainee received a teaching syllabus for CPB weaning 1 week before attempting to wean a patient from CPB (pretest). One week later, each trainee received a 2-h training session with either high-fidelity simulation-based training or a 2-h interactive seminar. Each trainee then weaned patients from CPB within 2 weeks (posttest) and 5 weeks (retention test) from the intervention. Clinical performance was measured using the validated Anesthesiologists Nontechnical Skills Global Rating Scale and a checklist of expected clinical actions. Results:Pretest Global Rating Scale and checklist performances were similar. The simulation group scored significantly higher than the seminar group at both posttest (Global Rating Scale [mean ± standard error]: 14.3 ± 0.41 vs. 11.8 ± 0.41, P < 0.001; checklist: 89.9 ± 3.0% vs. 75.4 ± 3.0%, P = 0.003) and retention test (Global Rating Scale: 14.1 ± 0.41 vs. 11.7 ± 0.41, P < 0.001; checklist: 93.2 ± 2.4% vs. 77.0 ± 2.4%, P < 0.001). CONCLUSION:: Skills required to wean a patient from CPB can be acquired through simulation-based training. Compared with traditional interactive seminars, simulation-based training leads to improved performance in patient care by senior trainees in anesthesiology.

Disrupted sleep and delayed recovery from chronic peripheral neuropathy are distinct phenotypes in a rat model of metabolic syndrome

Background: Sleep apnea, hypertension, atherosclerosis, and obesity are features of metabolic syndrome associated with decreased restorative sleep and increased pain. These traits are relevant for anesthesiology because they confer increased risks of a negative anesthetic outcome. This study tested the one-tailed hypothesis that rats bred for low intrinsic aerobic capacity have enhanced nociception and disordered sleep. Methods: Rats were developed from a breeding strategy that selected for low aerobic capacity runners (LCR) and high aerobic capacity runners (HCR). Four phenotypes were quantified. Rats underwent von Frey sensory testing (n = 12), thermal nociceptive testing (n = 12), electrographic recordings of sleep and wakefulness (n = 16), and thermal nociceptive testing (n = 14) before and for 6 weeks after a unilateral chronic neuropathy of the sciatic nerve. Results: Paw withdrawal latency to a thermal nociceptive stimulus was significantly (P < 0.01) lower in LCR than HCR rats. There were also significant differences in sleep, with LCR rats spending significantly (P < 0.01) more time awake (18%) and less time in nonrapid eye movement sleep (-19%) than HCR rats. Nonrapid eye movement sleep episodes were of shorter duration (-34%) in LCR than HCR rats. Rapid eye movement sleep of LCR rats was significantly more fragmented than rapid eye movement sleep of HCR rats. LCR rats required 2 weeks longer than HCR rats to recover from peripheral neuropathy. Conclusions: Rodents with low aerobic capacity exhibit features homologous to human metabolic syndrome. This rodent model offers a novel tool for characterizing the mechanisms through which low aerobic function and obesity might confer increased risks for anesthesia. © 2010, the American Society of Anesthesiologists, Inc. Lippincott Williams & Wilkins.

Gender differences in anesthesiologists' annual incomes

BACKGROUND: Specialty, work effort, and gender have been shown to be associated with physicians' annual incomes; however, careful examination of the association between provider gender and annual income after correcting for other factors likely to influence income has not been conducted for anesthesiologists. METHODS: Survey responses collected throughout the 1990s from 819 actively practicing anesthesiologists and linear regression analysis were used to determine the association between provider gender and annual incomes after controlling for work effort, provider characteristics, and practice characteristics. RESULTS: White female anesthesiologists reported working 12% fewer annual hours than their white male counterparts. White female anesthesiologists had practiced medicine for fewer years than white males and were more likely to be employees, as opposed to having an ownership interest in the practice, but less likely to be board certified. After adjustment for work effort, provider characteristics, and practice characteristics, white females' mean annual income was $236,628, or $60,337 (20%) lower than that for white males (95% confidence interval, $81,674 lower to $39,001 lower; P < 0.001). CONCLUSIONS: During the 1990s, female gender was associated with lower annual incomes among anesthesiologists. These findings warrant further exploration to determine what factors might cause these gender-based income differences. © 2007 American Society of Anesthesiologists, Inc.

Reversal of the sedative and sympatholytic effects of dexmedetomidine with a specific α2-adrenoceptor antagonist atipamezole. A pharmacodynamic and kinetic study in healthy volunteers

Background: Specific and selective α2-adrenergic drugs are widely exploited in veterinary anesthesiology. Because α2-agonists are also being introduced to human practice, the authors studied reversal of a clinically relevant dexmedetomidine dose with atipamezole, an α2-antagonist, in healthy persons. Methods: The study consisted of two parts. In an open dose- finding study (part 1), the intravenous dose of atipamezole to reverse the sedative effects of 2.5 μg/kg of dexmedetomidine given intramuscularly was determined (n = 6). Part 2 was a placebo-controlled, double-blinded, randomized cross-over study in which three doses of atipamezole (15, 50, and 150 μg/kg given intravenously in 2 min) or saline were administered 1 h after dexmedetomidine at 1-week intervals (n=8). Subjective vigilance and anxiety, psychomotor performance, hemodynamics, and saliva secretion were determined, and plasma catecholamines and serum drug concentrations were measured for 7 h. Results: The mean ± SD atipamezole dose needed in part 1 was 104 ± 44 μg/kg. In part 2, dexmedetomidine induced clear impairments of vigilance and psychomotor performance that were dose dependently reversed by atipamezole (P &lt; 0.001). Complete resolution of sedation was evident after the highest (150 μg/kg) dose, and the degree of vigilance remained high for 7 h. Atipamezole dose dependently reversed the reductions in blood pressure (P &lt; 0.001) and heart rate (P = 0.009). Changes in saliva secretion and plasma catecholamines were similarly biphasic (i.e., they decreased after dexmedetomidine followed by dose-dependent restoration after atipamezole). Plasma norepinephrine levels were, however, increased considerably after the 150 μg/kg dose of atipamezole. The pharmacokinetics of atipamezole were linear, and elimination half-lives for both drugs were approximately 2 h. Atipamezole did not affect the disposition of dexmedetomidine. One person had symptomatic sinus arrest, and another had transient bradycardia approximately 3 h after receiving dexmedetomidine. Conclusions: The sedative and sympatholytic effects of intramuscular dexmedetomidine were dose dependently antagonized by intravenous atipamezole. The applied infusion rate (75 μg·kg-1·min-1) for the highest atipamezole dose was, however, too fast, as evident by transient sympathoactivation. Similar elimination half- lives of these two drugs are a clear advantage considering the possible clinical applications.

Effect of inhibition of spinal cord glutamate transporters on inflammatory pain induced by formalin and complete freund's adjuvant

Background: Spinal cord glutamate transporters clear synaptically released glutamate and maintain normal sensory transmission. However, their ultrastructural localization is unknown. Moreover, whether and how they participate in inflammatory pain has not been carefully studied. Methods: Immunogold labeling with electron microscopy was carried out to characterize synaptic and nonsynaptic localization of glutamate transporters in the superficial dorsal horn. Their expression and uptake activity after formalin- and complete Freund's adjuvant (CFA)-induced inflammation were evaluated by Western blot analysis and glutamate uptake assay. Effects of intrathecal glutamate transporter activator (R)-(-)-5-methyl-1-nicotinoyl-2-pyrazoline and inhibitors (DL-threo-β-benzyloxyaspartate [TBOA], dihydrokainate, and DL-threo-β-hydroxyaspartate), or TBOA plus group III metabotropic glutamate receptor antagonist (RS)-α-methylserine-O-phosphate, on formalin- and CFA-induced inflammatory pain were examined. Results: In the superficial dorsal horn, excitatory amino acid carrier 1 is localized in presynaptic membrane, postsynaptic membrane, and axonal and dendritic membranes at nonsynaptic sites, whereas glutamate transporter-1 and glutamate/aspartate transporter are prominent in glial membranes. Although expression of these three spinal glutamate transporters was not altered 1 h after formalin injection or 6 h after CFA injection, glutamate uptake activity was decreased at these time points. Intrathecal (R)-(-)-5-methyl-1-nicotinoyl-2-pyrazoline had no effect on formalin-induced pain behaviors. In contrast, intrathecal TBOA, dihydrokainate, and DL-threo-β-hydroxyaspartate reduced formalin-evoked pain behaviors in the second phase. Intrathecal TBOA also attenuated CFA-induced thermal hyperalgesia at 6 h after CFA injection. The antinociceptive effects of TBOA were blocked by coadministration of (RS)-α-methylserine-O-phosphate. Conclusion: Our findings suggest that spinal glutamate transporter inhibition relieves inflammatory pain through activation of inhibitory presynaptic group III metabotropic glutamate receptors. © 2011, the American Society of Anesthesiologists, Inc. Lippincott Williams & Wilkins. Anesthesiology.

Simulator training enhances resident performance in transesophageal echocardiography

Background: Standardized training via simulation as an educational adjunct may lead to a more rapid and complete skill achievement. The authors hypothesized that simulation training will also enhance performance in transesophageal echocardiography image acquisition among anesthesia residents. © 2013, the American Society of Anesthesiologists, Inc. Lippincott Williams & Wilkins.

Positioning in anesthesiology

Background: Stretch-induced neuropathy of the brachial plexus and median nerve in conventional perioperative care remains a relatively frequent and poorly understood complication. Guidelines for positioning have been formulated, although the protective effect of most recommendations remains unexamined. The similarity between the stipulated potentially dangerous positions and the components of the brachial plexus tension test (BPTT) justified the analysis of the BPTT to quantify the impact of various arm and neck positions on the peripheral nervous system. Methods: Four variations of the BPTT in three different shoulder positions were performed in 25 asymptomatic male participants. The impact of arm and neck positions on the peripheral nervous system was evaluated by analyzing the maximal available range of motion, pain intensity, and type of elicited symptoms during the BPTT. Results: Cervical contralateral lateral flexion, lateral rotation of the shoulder and fixation of the shoulder girdle in a neutral position in combination with shoulder abduction, and wrist extension all significantly reduced the available range of motion. Elbow extension also challenged the nervous system substantially. A cumulative impact could be observed when different components were simultaneously added, and a neutralizing effect was noted when an adjacent region allowed for unloading of the nervous system. Conclusions: The experimental findings support the experientially based guidelines for positioning. Especially when simultaneously applied, submaximal joint positions easily load the nervous system, which may substantially compromise vital physiologic processes in and around the nerve. Therefore, even when the positioning of all upper limb joints is carefully considered, complete prevention of perioperative neuropathy seems almost inconceivable.

Autologous transplantation of peripheral blood-derived circulating endothelial progenitor cells attenuates endotoxin-induced acute lung injury in rabbits by direct endothelial repair and indirect immunomodulation

Background: Studies have demonstrated the role of circulating endothelial progenitor cells (EPCs) in maintaining normal endothelial function and in endothelial repairing. This study was aimed to observe the protective effects of autologous transplantation of circulating EPCs against endotoxin-induced acute lung injury in rabbits and to investigate the underlying mechanisms. Methods: One-hundred-and-fifty rabbits were enrolled. After acute lung injury was induced by endotoxin, autologous circulating EPCs, endothelial cell, or normal saline were transfused intravenously, respectively. PaO 2/FiO 2 ratios, concentrations of plasma nitric oxide, malonyldialdehyde, and activity of superoxide dismutase were examined. The lung wet-to-dry weight ratios were counted; polymorphonuclear cell ratios and areas of hyaline membrane formation and hemorrhage were measured. The levels of interleukin-1β, E-selectin, intercellular adhesion molecule-1, interleukin-10, vascular endothelial growth factor protein, and inducible nitric oxide synthase protein were analyzed. Results: PaO 2/FiO 2 ratios were significantly increased with EPC transfusion. Infiltration of polymorphonuclear cells, lung wet-to-dry weight ratios, and area of hyaline membrane and hemorrhage in lung tissue were significantly decreased after EPC transplantation. Plasma level of nitric oxide and malondialdehyde were significantly inhibited, and the activity of superoxide dismutase was enhanced in the EPC-treated animals. EPC transplantation significantly increased level of interleukin-10 and vascular endothelial growth factor protein and reduced levels of interleukin-1β, E-selectin, intercellular adhesion molecule-1, and inducible nitric oxide synthase in injury lung tissues. Conclusions: Autologous transplantation of circulating EPCs can partly restore the pulmonary endothelial function and effectively attenuate endotoxin-induced acute lung injury by direct endothelial repair and indirect immunomodulation of antioxidation and antiinflammation. © 2012 the American Society of Anesthesiologists, Inc. Lippincott Williams &amp; Wilkins. Anesthesiology.

Substance use disorder in physicians after completion of training in anesthesiology in the United States from 1977 to 2013

Background: Substance use disorder among physicians can expose both physicians and their patients to significant risk. Data regarding the epidemiology and outcomes of physician substance use disorder are scarce but could guide policy formulation and individual treatment decisions. This article describes the incidence and outcomes of substance use disorder that resulted in either a report to a certifying body or death in physicians after the completion of anesthesiology training. Methods: Physicians who completed training in U.S. anesthesiology residency programs from 1977 to 2013 and maintained at least one active medical license were included in this retrospective cohort study (n = 44,736). Substance use disorder cases were ascertained through records of the American Board of Anesthesiology and the National Death Index. Results: Six hundred and one physicians had evidence of substance use disorder after completion of training, with an overall incidence of 0.75 per 1,000 physician-years (95% CI, 0.71 to 0.80; 0.84 [0.78 to 0.90] in men, 0.43 [0.35 to 0.52] in women). The highest incidence rate occurred in 1992 (1.79 per 1,000 physician-years [95% CI, 1.12 to 2.59]). The cumulative percentage expected to develop substance use disorder within 30 yr estimated by Kaplan-Meier analysis equaled 1.6% (95% CI, 1.4 to 1.7%). The most common substances used by 353 individuals for whom information was available were opioids (193 [55%]), alcohol (141 [40%]), and anesthetics/hypnotics (69 [20%]). Based on a median of 11.1 (interquartile range, 4.4 to 19.8) yr of follow-up, the cumulative proportion of survivors estimated to experience at least one relapse within 30 yr was 38% (95% CI, 31 to 43%). Of the 601 physicians with substance use disorder, 114 (19%) were dead from a substance use disorder-related cause at last follow-up. Conclusions: A substantial proportion of anesthesiologists who develop substance use disorder after the completion of training die of this condition, and the risk of relapse is high in those who survive. © 2020 Lippincott Williams and Wilkins. All rights reserved.

Blind intubation through self-pressurized, disposable supraglottic airway laryngeal intubation masks: An international, multicenter, prospective cohort study

Background: Supraglottic airway devices commonly are used for securing the airway during general anesthesia. Occasionally, intubation with an endotracheal tube through a supraglottic airway is indicated. Reported success rates for blind intubation range from 15 to 97%. The authors thus investigated as their primary outcome the fraction of patients who could be intubated blindly with an Air-Qsp supraglottic airway device (Mercury Medical, USA). Second, the authors investigated the influence of muscle relaxation on air leakage pressure, predictors for failed blind intubation, and associated complications of using the supraglottic airway device. Methods: The authors enrolled 1,000 adults having elective surgery with endotracheal intubation. After routine induction of general anesthesia, a supraglottic airway device was inserted and patients were ventilated intermittently. Air leak pressure was measured before and after full muscle relaxation. Up to two blind intubation attempts were performed. Results: The supraglottic airway provided adequate ventilation and oxygenation in 99% of cases. Blind intubation succeeded in 78% of all patients (95% CI, 75 to 81%). However, the success rate was inconsistent among the three centers (P < 0.001): 80% (95% CI, 75 to 85%) at the Institute of Anesthesia and Pain Therapy, Kantonsspital Winterthur, Winterthur, Switzerland; 41% (95% CI, 29 to 53%) at the Department of Anesthesiology and Intensive Therapy, Medical University of Lodz, Lodz, Poland; and 84% (95% CI, 80 to 88%) at the Institute of Anesthesiology, University Hospital Zurich, Zurich, Switzerland. Leak pressure before relaxation correlated reasonably well with air leak pressure after relaxation. Conclusions: The supraglottic airway device reliably provided a good airway and allowed blind intubation in nearly 80% of patients. It is thus a reasonable initial approach to airway control. Muscle relaxation can be used safely when unparalyzed leak pressure is adequate. © 2017, the American Society of Anesthesiologists, Inc. Wolters Kluwer Health, Inc.

Effect of perioperative systemic α2 agonists on postoperative morphine consumption and pain intensity: Systematic review and meta-analysis of randomized controlled trials

Background: Systemic α2 agonists are believed to reduce pain and opioid requirements after surgery, thus decreasing the incidence of opioid-related adverse effects, including hyperalgesia. Methods: The authors searched for randomized placebo-controlled trials testing systemic α2 agonists administrated in surgical patients and reporting on postoperative cumulative opioid consumption and/or pain intensity. Meta-analyses were performed when data from 5 or more trials and/or 100 or more patients could be combined. Results: Thirty studies (1,792 patients, 933 received clonidine or dexmedetomidine) were included. There was evidence of postoperative morphine-sparing at 24 h; the weighted mean difference was-4.1 mg (95% confidence interval,-6.0 to-2.2) with clonidine and-14.5 mg (-22.1 to-6.8) with dexmedetomidine. There was also evidence of a decrease in pain intensity at 24 h; the weighted mean difference was-0.7 cm (-1.2 to-0.1) on a 10-cm visual analog scale with clonidine and-0.6 cm (-0.9 to-0.2) with dexmedetomidine. The incidence of early nausea was decreased with both (number needed to treat, approximately nine). Clonidine increased the risk of intraoperative (number needed to harm, approximately nine) and postoperative hypotension (number needed to harm, 20). Dexmedetomidine increased the risk of postoperative bradycardia (number needed to harm, three). Recovery times were not prolonged. No trial reported on chronic pain or hyperalgesia. Conclusions: Perioperative systemic α2 agonists decrease postoperative opioid consumption, pain intensity, and nausea. Recovery times are not prolonged. Common adverse effects are bradycardia and arterial hypotension. The impact of α2 agonists on chronic pain or hyperalgesia remains unclear because valid data are lacking. © 2012 the American Society of Anesthesiologists, Inc. Lippincott Williams & Wilkins. Anesthesiology.

Assessment of the intrarater and interrater reliability of an established clinical task analysis methodology

Background: Task analysis may be useful for assessing how anesthesiologists alter their behavior in response to different clinical situations. In this study, the authors examined the intraobserver and interobserver reliability of an established task analysis methodology. Methods: During 20 routine anesthetic procedures, a trained observer sat in the operating room and categorized in real-time the anesthetist's activities into 38 task categories. Two weeks later, the same observer performed task analysis from videotapes obtained intraoperatively. A different observer performed task analysis from the videotapes on two separate occasions. Data were analyzed for percent of time spent on each task category, average task duration, and number of task occurrences. Rater reliability and agreement were assessed using intraclass correlation coefficients. Results: Intrarater reliability was generally good for categorization of percent time on task and task occurrence (mean intraclass correlation coefficients of 0.84-0.97). There was a comparably high concordance between real-time and video analyses. Interrater reliability was generally good for percent time and task occurrence measurements. However, the interrater reliability of the task duration metric was unsatisfactory, primarily because of the technique used to capture multitasking. Conclusions: A task analysis technique used in anesthesia research for several decades showed good intrarater reliability. Off-line analysis of videotapes is a viable alternative to real-time data collection. Acceptable interrater reliability requires the use of strict task definitions, sophisticated software, and rigorous observer training. New techniques must be developed to more accurately capture multitasking. Substantial effort is required to conduct task analyses that will have sufficient reliability for purposes of research or clinical evaluation.

Effectiveness of written and oral specialty certifcation examinations to predict actions against the medical licenses of anesthesiologists

Background: Te American Board of Anesthesiology administers written and oral examinations for its primary certifcation. Tis retrospective cohort study tested the hypothesis that the risk of a disciplinary action against a physician's medical license is lower in those who pass both examinations than those who pass only the written examination. Methods: Physicians who entered anesthesiology training from 1971 to 2011 were followed up to 2014. License actions were ascertained via the Disciplinary Action Notifcation Service of the Federation of State Medical Boards. Results: Te incidence rate of license actions was relatively stable over the study period, with approximately 2 to 3 new cases per 1,000 person-years. In multivariable models, the risk of license actions was higher in men (hazard ratio = 1.88 [95% CI, 1.66 to 2.13]) and lower in international medical graduates (hazard ratio = 0.73 [95% CI, 0.66 to 0.81]). Compared with those passing both examinations on the frst attempt, those passing neither examination (hazard ratio = 3.60 [95% CI, 3.14 to 4.13]) and those passing only the written examination (hazard ratio = 3.51 [95% CI, 2.87 to 4.29]) had an increased risk of receiving an action from a state medical board. Te risk was no different between the latter two groups (P = 0.81), showing that passing the oral but not the written primary certifcation examination is associated with a decreased risk of subsequent license actions. For those with residency performance information available, having at least one unsatisfactory training record independently increased the risk of license actions. Conclusions: Tese fndings support the concept that an oral examination assesses domains important to physician performance that are not fully captured in a written examination. © 2017, the American Society of Anesthesiologists, Inc. Wolters Kluwer Health, Inc. All Rights Reserved.

Assessment of clinical performance during simulated crises using both technical and behavioral ratings

Background: Techniques are needed to assess anesthesiologists' performance when responding to critical events. Patient simulators allow presentation of similar crisis situations to different clinicians. This study evaluated ratings of performance, and the interrater variability of the ratings, made by multiple independent observers viewing videotapes of simulated crises. Methods: Raters scored the videotapes of 14 different teams that were managing two scenarios: malignant hyperthermia (MH) and cardiac arrest. Technical performance and crisis management behaviors were rated. Technical ratings could range from 0.0 to 1.0 based on scenario-specific checklists of appropriate actions. Ratings of 12 crisis management behaviors were made using a five-point ordinal scale. Several statistical assessments of interrater variability were applied. Results: Technical ratings were high for most teams in both scenarios (0.78 ± 0.08 for MH, 0.83 ± 0.06 for cardiac arrest). Ratings of crisis management behavior varied, with some teams rated as minimally acceptable or poor (28% for MH, 14% for cardiac arrest). The agreement between raters was fair to excellent, depending on the item rated and the statistical test used. Conclusions: Both technical and behavioral performance can be assessed from videotapes of simulations. The behavioral rating system can be improved; one particular difficulty was aggregating a single rating for a behavior that fluctuated over time. These performance assessment tools might be nseful for educational research or for tracking a resident's progress. The rating system needs more refinement before it can be used to assess clinical competence for residency graduation or board certification.

Study of the "sniffing position" by magnetic resonance imaging

Background: The "sniffing position" is widely considered essential to the performance of orotracheal intubation and has become the cornerstone of training in anesthesiology. However, the anatomic superiority of this patient head position has not been established. Methods: Eight healthy young adult volunteers underwent magnetic resonance imaging scanning in three anatomic positions: head in neutral position, in simple extension, and in the "sniffing position" (neck flexed and head extended by means of a pillow). The following measurements were made on each scan: (1) the axis of the mouth (MA); (2) the pharyngeal axis (PA); (3) the laryngeal axis (LA); and (4) the line of vision. The various angles between these axes were defined: α angle between the MA and PA, β angle between PA and LA, and δ angle between line of vision and LA. Results: Both simple extension and sniffing positions significantly improved (P < 0.05) the δ angle associated with best laryngoscopic view. Our results show that the β value increases significantly (P < 0.05) when the head position is shifted from the neutral position (β = 7 ± 6°) to the sniffing position (β = 13 ± 6°), and the α value slightly (but significantly) decreases (from 87 ± 10° to 63 ± 11°;P < 0.05). Anatomic alignment of the LA, PA, and MA axes is impossible to achieve in any of the three positions tested. There were no significant differences between angles observed in simple extension and sniffing positions. Conclusions: The sniffing position does not achieve alignment of the three important axes (MA, PA, and LA) in awake patients with normal airway anatomy.

Spinal anesthesia: Functional balance is impaired after clinical recovery

Background: The ability of patients to walk without assistance after spinal anesthesia is a determining factor in the time to discharge following ambulatory surgery. The authors compared clinical markers of gross motor recovery with objective data of functional balance after spinal anesthesia. Methods: Twenty-two male patients with American Society of Anesthesiology physical status I or II who were scheduled for perineal surgery were studied during recovery from spinal anesthesia to compare the predictive accuracy of clinical markers of ambulatory readiness (e.g., full knee flexion and extension) with that of an objective method of measurement focused on functional balance. Lumbar puncture was performed at the L2-L3 or L3-L4 interspace using a 25-gauge Whitacre needle, with patients in the sitting position. A 3-ml mixture of 5 mg bupivacaine (heavy) and 10 μg fentanyl was injected. Block regression and restoration of motor function were assessed and recorded. Functional balance was measured using a computerized force platform method. Results: The majority of patients maintained motor function and proprioception sensation at the onset of surgical anesthesia, as indicated by performance on clinical tests of function: 96% were able to perform the straight leg increase; 82, 77, and 91%, respectively, were able to perform full knee flexion and extension, perform heel-to-shin maneuvers, and identify joint position in the supine position. Postoperatively, clinical return of motor function occurred much earlier than recovery of functional balance. At 60 min after onset of spinal anesthesia, 22 patients (100%) had recovered sensory and gross motor function, but only 36% could stand, and 8% could walk without assistance (P < 0.01). At 150-180 min after onset, 96-100% of patients achieved the levels of functional balance that permitted adequate ambulation. Conclusions: The results suggest that the recovery time to unassisted ambulation is longer than has been assumed, and that the standard clinical markers of gross motor function are poor predictors of functional balance following ambulatory surgery.

Measurement of individual clinical productivity in an academic anesthesiology department

Background: The ability to measure productivity, work performed, or contributions toward the clinical mission has become an important issue facing anesthesiology departments in private practice and academic settings. Unfortunately, the practice and billing of anesthesia services makes it difficult to quantify individual productivity. This study examines the following methods of measuring individual productivity: normalized clinical days per year (nCD/yr); time units per operating-room day worked (TU/OR day); normalized time units per year (nTU/yr); total American Society of Anesthesiologists (ASA) units per OR day (tASA/OR day); and normalized total ASA units per year (ntASA/yr). Methods: Billing and scheduling data for clinical activities of faculty members of an anesthesiology department at a university medical center were collected and analyzed for the 1998 fiscal year. All clinical sites and all clinical faculty anesthesiologists were included unless they spent less than 20% of their time during the fiscal year providing clinical care, i.e., less than 0.2 clinical full-time equivalent. Outliers, defined as faculty who had productivity greater or less than 1 SD from the mean, were examined in detail. Results: Mean and median values were reported for each measurement, and different groups of outliers were identified. nCD/yr identified faculty who worked more than their clinical full-time equivalent would have predicted. TU/OR day and tASA/OR day identified apparently low-productivity faculty as those who worked a large portion of their time in obstetric anesthesia or an ambulatory surgicenter. tASA/OR day identified specialty anesthesiologists as apparently high-productivity faculty. nTU/yr and ntASA/yr were products of the per-OR day measurement and nCD/yr. Conclusion: Each of the measurements studied values certain types of productivity more than others. By defining what type of service is most important to reward, the most appropriate measure or combination of measures of productivity can be chosen. In the authors' department, nCD/yr is the most useful measure of individual productivity because it measures an individual anesthesiologist's contribution to daily staffing, includes all clinical sites, is independent of nonanesthesia factors, and is easy to collect and determine.

Thoracic epidural anesthesia for cardiac surgery: A randomized trial

Background: The addition of thoracic epidural anesthesia (TEA) to general anesthesia (GA) during cardiac surgery may have a beneficial effect on clinical outcomes. TEA in cardiac surgery, however, is controversial because the insertion of an epidural catheter in patients requiring full heparinization for cardiopulmonary bypass may lead to an epidural hematoma. The clinical effects of fast-track GA plus TEA were compared with those of with fast-track GA alone. Methods: A randomized controlled trial was conducted in 654 elective cardiac surgical patients who were randomly assigned to combined GA and TEA versus GA alone. Follow-up was at 30 days and 1 yr after surgery. The primary endpoint was 30-day survival free from myocardial infarction, pulmonary complications, renal failure, and stroke. Results: Thirty-day survival free from myocardial infarction, pulmonary complications, renal failure, and stroke was 85.2% in the TEA group and 89.7% in the GA group (P = 0.23). At 1 yr follow-up, survival free from myocardial infarction, pulmonary complications, renal failure, and stroke was 84.6% in the TEA group and 87.2% in the GA group (P = 0.42). Postoperative pain scores were low in both groups. Conclusions: This study was unable to demonstrate a clinically relevant benefit of TEA on the frequency of major complications after elective cardiac surgery, compared with fast-track cardiac anesthesia without epidural anesthesia. Given the potentially devastating complications of an epidural hematoma after insertion of an epidural catheter, it is questionable whether this procedure should be applied routinely in cardiac surgical patients who require full heparinization. © 2011, the American Society of Anesthesiologists, Inc. Lippincott Williams & Wilkins. Anesthesiology.

Treatment with carbon monoxide-releasing molecules and an HO-1 inducer enhances the effects and expression of μ-opioid receptors during neuropathic pain

Background: The administration of μ-opioid receptors (MOR) and δ-opioid receptors (DOR) as well as cannabinoid-2 receptor (CB2R) agonists attenuates neuropathic pain. We investigated if treatment with two carbon monoxide-releasing molecules (CORM-2 and CORM-3) or an inducible heme oxygenase inducer (cobalt protoporphyrin IX, CoPP) could modulate the local and systemic effects and expression of MOR, DOR, and CB2R during neuropathic pain. Methods: In C57BL/6 mice, at 10 days after the chronic constriction of sciatic nerve, we evaluated the effects of the intraperitoneal administration of 10 mg/kg of CORM-2, CORM-3, or CoPP on the antiallodynic and antihyperalgesic actions of a locally or systemically administered MOR (morphine), DOR ([d-Pen(2),d-Pen(5)]- enkephalin) or CB2R ((2-methyl-1-propyl-1H-indol-3-yl)-1-naphthalenylmethanone ) agonist. The effects of CORM-2 and CoPP treatments on the expression of MOR, DOR, CB2R, inducible and constitutive heme oxygenases, microglia activation marker (CD11b/c), and neuronal and inducible nitric oxide synthases were also assessed. Results: Treatments with CO-RMs and CoPP reduced the mechanical and thermal hypersensitivity induced by sciatic nerve injury, increased the local, but not systemic, antinociceptive effects of morphine, and decreased those produced by DPDPE and JWH-015. Both CORM-2 and CoPP treatments enhanced MOR and inducible heme oxygenase expression, unaltered DOR and constitutive heme oxygenase expression, and decreased the overexpression of CB2R, CD11b/c, and neuronal and inducible nitric oxide synthases induced by sciatic nerve injury. Conclusions: This study shows that CO-RMs and CoPP treatments increase the local antinociceptive effects of morphine through enhancing MOR peripheral expression and inhibiting spinal microglial activation and overexpression of neuronal/inducible nitric oxide synthases. © 2013 the American Society of Anesthesiologists, Inc. Lippincott Williams & Wilkins. Anesthesiology.

Patient-controlled regional analgesia (PCRA) at home: Controlled comparison between bupivacaine and ropivacaine brachial plexus analgesia

Background: The aim of this randomized, double-blinded study was to compare the analgesic efficacy of bupivacaine versus ropivacaine brachial plexus analgesia after ambulatory hand surgery. An additional aim was to study the feasibility and safety of patient-controlled regional analgesia (PCRA) outside the hospital. Methods: Sixty patients scheduled for ambulatory hand surgery underwent surgery with axillary plexus blockade. After surgery, the plexus catheter was connected to an elastomeric, disposable "homepump," containing 100 ml of either 0.125% bupivacaine or 0.125% ropivacaine. When patients experienced pain, they self-administered 10 ml of the study drug. Analgesic efficacy of PCRA was evaluated by self-assessment of pain intensity by visual analog scale (VAS) and verbal scale. Patients recorded adverse effects, technical problems, use of rescue analgesic tablets, and overall satisfaction. A follow-up telephone call was made the day after surgery. Results: Visual analog scale scores decreased after each treatment in both groups, but there were no significant differences between the two drugs. One patient in each group took rescue dextropropoxyphene tablets. In both groups, 87% patients expressed their desire to have the same treatment again. On the day of surgery, significantly more patients were satisfied with ropivacaine PCRA. None of the patients had any signs or symptoms of local anesthetic toxicity or catheter infection. Conclusions: This double-blinded study has demonstrated the feasibility of self-administration of local anesthetic to manage postoperative pain outside the hospital. Ropivacaine and bupivacaine provided effective analgesia, and patient satisfaction with PCRA was high. Patient selection, follow-up telephone call, and 24-h access to anesthesiology services are prerequisites for PCRA at home.

Thoracic epidural anesthesia improves early outcomes in patients undergoing off-pump coronary artery bypass surgery: A prospective, randomized, controlled trial

Background: The aim of this two-center, open, randomized, controlled trial was to evaluate the impact of thoracic epidural anesthesia on early clinical outcomes in patients undergoing off-pump coronary artery bypass surgery. Methods: Two hundred and twenty-six patients were randomized to either general anesthesia plus epidural (GAE) (n = 109) or general anesthesia only (GA) (n = 117). The primary outcome was length of postoperative hospital stay. Secondary outcomes were: arrhythmia, inotropic support, intubation time, perioperative myocardial infarction, neurologic events, intensive care stay, pain scores, and analgesia requirement. Results: Baseline characteristics were similar in the two groups. One patient died in the GAE group. Median postoperative stay was significantly reduced in the GAE, compared with the GA, group (5 days, interquartile range [5-6] vs. 6 days, interquartile range [5-7], hazard ratio = 1.39, 95% CI [1.06-1.82]; P = 0.017). The incidence of arrhythmias and the median intubation time were both significantly lower in the GAE, compared with the GA, group (odds ratio = 0.41, 95% CI [0.22-0.78], P = 0.006 and hazard ratio = 1.73, 95% CI [1.31-2.27], P < 0.001, respectively). Patients in the GAE group were more likely to need vasoconstrictors intraoperatively than in the GA group (odds ratio = 2.50, 95% CI [1.22-5.12]; P = 0.012). The GAE, compared with GA, group reported significantly lower levels of impairment for all pain domains and reduced morphine usage (odds ratio = 0.07, 95% CI [0.03-0.17]; P < 0.001). Conclusion: In patients undergoing off-pump coronary artery bypass surgery, the addition of thoracic epidural to general anesthesia significantly reduces the incidence of postoperative arrhythmias and improves pain control and overall quality of recovery, allowing earlier extubation and hospital discharge. © 2011, the American Society of Anesthesiologists, Inc. Lippincott Williams & Wilkins. Anesthesiology.

Effect of the BASIC Examination on Knowledge Acquisition during Anesthesiology Residency

Background: The American Board of Anesthesiology recently introduced the BASIC Examination, a component of its new staged examinations for primary certification, typically offered to residents at the end of their first year of clinical anesthesiology training. This analysis tested the hypothesis that the introduction of the BASIC Examination was associated with an acceleration of knowledge acquisition during the residency training period, as measured by increments in annual In-Training Examination scores. Methods: In-Training Examination performance was compared longitudinally among four resident cohorts (n = 6,488) before and after the introduction of the staged system using mixed-effects models that accounted for possible covariates. Results: Compared with previous cohorts in the traditional examination system, the first resident cohort in the staged system had a greater improvement in In-Training Examination scores between the first and second years of clinical anesthesiology training (by an estimated 2.0 points in scaled score on a scale of 1 to 50 [95% CI, 1.7 to 2.3]). By their second year, they had achieved a score similar to that of third-year clinical anesthesiology residents in previous cohorts. The second cohort to enter the staged system had a greater improvement of the scores between the clinical base year and the first clinical anesthesiology year, compared with the previous cohorts. Conclusions: These results support the hypothesis that the introduction of the BASIC Examination is associated with accelerated knowledge acquisition in residency training and provides evidence for the value of the new staged system in promoting desired educational outcomes of anesthesiology training. © 2018, the American Society of Anesthesiologists, Inc. Wolters Kluwer Health, Inc. All Rights Reserved.

A Smartphone-based decision support tool improves test performance concerning application of the guidelines for managing regional anesthesia in the patient receiving antithrombotic or thrombolytic therapy

Background: The American Society of Regional Anesthesia and Pain Medicine (ASRA) consensus statement on regional anesthesia in the patient receiving antithrombotic or thrombolytic therapy is the standard for evaluation and management of these patients. The authors hypothesized that an electronic decision support tool (eDST) would improve test performance compared with native physician behavior concerning the application of this guideline. Methods: Anesthesiology trainees and faculty at 8 institutions participated in a prospective, randomized trial in which they completed a 20-question test involving clinical scenarios related to the ASRA guidelines. The eDST group completed the test using an iOS app programmed to contain decision logic and content of the ASRA guidelines. The control group completed the test by using any resource in addition to the app. A generalized linear mixed-effects model was used to examine the effect of the intervention. Results: After obtaining institutional review board's approval and informed consent, 259 participants were enrolled and randomized (eDST = 122; control = 137). The mean score was 92.4 ± 6.6% in the eDST group and 68.0 ± 15.8% in the control group (P < 0.001). eDST use increased the odds of selecting correct answers (7.8; 95% CI, 5.7 to 10.7). Most control group participants (63%) used some cognitive aid during the test, and they scored higher than those who tested from memory alone (76 ± 15% vs. 57 ± 18%, P < 0.001). There was no difference in time to completion of the test (P = 0.15) and no effect of training level (P = 0.56). Conclusions: eDST use improved application of the ASRA guidelines compared with the native clinician behavior in a testing environment. © 2015, the American Society of Anesthesiologists, Inc. Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.

Protective and detrimental effects of sodium sulfide and hydrogen sulfide in murine ventilator-induced lung injury

Background: The antiinflammatory effects of hydrogen sulfide (H 2S) and sodium sulfide (Na2S) treatment may prevent acute lung injury induced by high tidal volume (HVT) ventilation. However, lung protection may be limited by direct pulmonary toxicity associated with H 2S inhalation. Therefore, the authors tested whether the inhalation of H2S or intravascular Na2S treatment can protect against ventilator-induced lung injury in mice. Methods: Anesthetized mice continuously inhaled 0, 1, 5, or 60 ppm H2S or received a single bolus infusion of Na2S (0.55 mg/kg) or vehicle and were then subjected to HVT (40 ml/kg) ventilation lasting 4 h (n = 4-8 per group). RESULTS:: HVT ventilation increased the concentrations of protein and interleukin-6 in bronchoalveolar lavage fluid, contributing to reduced respiratory compliance and impaired arterial oxygenation, and caused death from lung injury and pulmonary edema. Inhalation of 1 or 5 ppm H2S during HVT ventilation did not alter lung injury, but inhalation of 60 ppm H2S accelerated the development of ventilator-induced lung injury and enhanced the pulmonary expression of the chemoattractant CXCL-2 and the leukocyte adhesion molecules CD11b and L-selectin. In contrast, pretreatment with Na2S attenuated the expression of CXCL-2 and CD11b during HVT ventilation and reduced pulmonary edema. Moreover, Na2S enhanced the pulmonary expression of Nrf2-dependent antioxidant genes (NQO1, GPX2, and GST-A4) and prevented oxidative stress-induced depletion of glutathione in lung tissue. Conclusions: The data suggest that systemic intravascular treatment with Na2S represents a novel therapeutic strategy to prevent both ventilator-induced lung injury and pulmonary glutathione depletion by activating Nrf2-dependent antioxidant gene transcription. © 2011 the American Society of Anesthesiologists, Inc. Lippincott Williams &amp; Wilkins. Anesthesiology.

Usefulness of Parasternal Intercostal Muscle Ultrasound during Weaning from Mechanical Ventilation

Background: The assessment of diaphragm function with diaphragm ultrasound seems to bring important clinical information to describe diaphragm work and weakness. When the diaphragm is weak, extradiaphragmatic muscles may play an important role, but whether ultrasound can also assess their activity and function is unknown. This study aimed to (1) evaluate the feasibility of measuring the thickening of the parasternal intercostal and investigate the responsiveness of this muscle to assisted ventilation; and (2) evaluate whether a combined evaluation of the parasternal and the diaphragm could predict failure of a spontaneous breathing trial. Methods: First, an exploratory evaluation of the parasternal in 23 healthy subjects. Second, the responsiveness of parasternal to several pressure support levels were studied in 16 patients. Last, parasternal activity was compared in presence or absence of diaphragm dysfunction (assessed by magnetic stimulation of the phrenic nerves and ultrasound) and in case of success/failure of a spontaneous breathing trial in 54 patients. Results: The parasternal was easily accessible in all patients. The interobserver reproducibility was good (intraclass correlation coefficient, 0.77 (95% CI, 0.53 to 0.89). There was a progressive decrease in parasternal muscle thickening fraction with increasing levels of pressure support (Spearman ρ =-0.61 [95% CI,-0.74 to-0.44]; P < 0.0001) and an inverse correlation between parasternal muscle thickening fraction and the pressure generating capacity of the diaphragm (Spearman ρ =-0.79 [95% CI,-0.87 to-0.66]; P < 0.0001). The parasternal muscle thickening fraction was higher in patients with diaphragm dysfunction: 17% (10 to 25) versus 5% (3 to 8), P < 0.0001. The pressure generating capacity of the diaphragm, the diaphragm thickening fraction and the parasternal thickening fraction similarly predicted failure or the spontaneous breathing trial. Conclusions: Ultrasound assessment of the parasternal intercostal muscle is feasible in the intensive care unit and provides novel information regarding the respiratory capacity load balance. (ANESTHESIOLOGY 2020; 132:1114-25). © 2020, the American Society of Anesthesiologists, Inc. All Rights Reserved.

Motivation and maternal presence during induction of anesthesia

Background: The authors developed a measure to determine whether maternal motivation to be present during induction (Motivation for Parental Presence during Induction of Anesthesia [MPPIA]) is related to children's anxiety during the induction process. Methods: Mothers and children (aged 2-12 yr) undergoing outpatient, elective surgery and general anesthesia were enrolled in this study (n = 289 dyads). Items to assess motivation for parental presence during induction were selected by experts in anesthesiology, psychology, and child development; mothers completed the resulting 14-item measure as well as assessments of anxiety and coping style. Children's anxiety and compliance was assessed during induction of anesthesia. Factor analysis was performed, and maternal motivation was then examined against children's anxiety during induction of anesthesia. Results: Factor analysis resulted in four scales with a total variance of 72.3%: MPPIA-Desire, MPPIA-Hesitancy, MPPIA-Anxiety, and MPPIA-Preparatlon. Analysis supported the reliability (0.89-0.94) and validity of the MPPIA. The authors found that mothers with high MPPIA-Desire and low MPPIA-Hesitancy had children with significantly higher anxiety (P < 0.0001) during induction of anesthesia, as compared with mothers with low MPPIA-Desire and MPPIA-Hesitancy. The authors also found that highly motivated mothers reported significantly higher levels of anxiety (P = 0.007). Conclusion: Clinicians should be aware that many mothers who have a high desire to be present in the operating room are very anxious and that their children are likely to exhibit high anxiety levels during induction of anesthesia. © 2005 American Society of Anesthesiologists, Inc. Lippincott Williams & Wilkins, Inc.

Effect of single recombinant human erythropoietin injection on transfusion requirements in preoperatively anemic patients undergoing valvular heart surgery

Background: The authors investigated the effect of a single preoperative bolus of erythropoietin on perioperative transfusion requirement and erythropoiesis in patients with preoperative anemia undergoing valvular heart surgery. Methods: In this prospective, single-site, single-blinded, randomized, and parallel-arm controlled trial, 74 patients with preoperative anemia were randomly allocated to either the erythropoietin or the control group. The erythropoietin group received 500 IU/kg erythropoietin and 200 mg iron sucrose intravenously 1 day before the surgery. The control group received an equivalent volume of normal saline. The primary endpoint was transfusion requirement assessed during the surgery and for 4 days postoperatively. Reticulocyte count and iron profiles were measured serially and compared preoperatively and on postoperative days 1, 2, 4, and 7. RESULTS:: Transfusion occurred in 32 patients (86%) of the control group versus 22 patients (59%) of the erythropoietin group (P = 0.009). The mean number of units of packed erythrocytes transfused per patient during the surgery and for 4 postoperative days (mean ± SD) was also significantly decreased in the erythropoietin group compared with the control group (3.3 ± 2.2 vs. 1.0 ± 1.1 units/patient, P = 0.001). The reticulocyte count was significantly greater in the erythropoietin group at postoperative days 4 (P = 0.001) and 7 (P = 0.001). Conclusions: A single intravenous administration of erythropoietin and an iron supplement 1 day before surgery significantly reduced the perioperative transfusion requirement in anemic patients undergoing valvular heart surgery, implicating its potential role as a blood conservation strategy. © 2011 the American Society of Anesthesiologists, Inc. Lippincott Williams & Wilkins. Anesthesiology.

Trends in quality of anesthesia care associated with changing staffing patterns, productivity, and concurrency of case supervision in a teaching hospital

Background: The authors used continuous quality improvement (CQI) program data to investigate trends in quality of anesthesia care associated with changing staffing patterns in a university hospital. Methods: The monthly proportion of cases performed by solo attending anesthesiologists versus attending-resident teams or attending-certified registered nurse anesthetist (CRNA) teams was used to measure staffing patterns. Anesthesia team productivity was measured as mean monthly surgical anesthesia hours billed per attending anesthesiologist per clinical day. Supervisory ratios (concurrency) were measured as mean monthly number of cases supervised concurrently by attending anesthesiologists. Quality of anesthesia care was measured as monthly rates of critical incidents, patient injury, escalation of care, operational inefficiencies, and human errors per 10,000 cases. Trends in quality at increasing productivity and concurrency levels from 1992 to 1997 were analyzed by the one-sided Jonckheere-Terpstra test. Results: Productivity was positively correlated with concurrency (r = 0.838; P < 0.001). Productivity levels ranged from 10 to 17 h per anesthesiologist per clinical day. Concurrency ranged from 1.6 to 2.2 cases per attending anesthesiologist. At higher productivity and concurrency levels, solo anesthesiologists conducted a smaller percentage of cases, and the proportion of cases with CRNA team members increased. The patient injury rate decreased with increased productivity levels (P = 0.002), whereas the critical incident rate increased (P = 0.001). Changes in operational inefficiency, escalation of care, and human error rates were not statistically significant (P = 0.072, 0.345, 0.320, respectively). Conclusions: Most aspects of quality of anesthesia care were apparently not effected by changing anesthesia team composition or increased productivity and concurrency. Only team performance was measured; the role of individuals (attending anesthesiologist, resident, or CRNA) in quality of care was not directly measured. Further research is needed to explain lower patient injury rates and increases in critical incident reporting at higher concurrency and productivity levels.

Trends in anesthesia-related death and brain damage: A closed claims analysis

BACKGROUND: The authors used the American Society of Anesthesiologists Closed Claims Project database to determine changes in the proportion of claims for death or permanent brain damage over a 26-yr period and to identify factors associated with the observed changes. METHODS: The Closed Claims Project is a structured evaluation of adverse outcomes from 6,894 closed anesthesia malpractice claims. Trends in the proportion of claims for death or permanent brain damage between 1975 and 2000 were analyzed. RESULTS: Claims for death or brain damage decreased between 1975 and 2000 (odds ratio, 0.95 per year; 95% confidence interval, 0.94-0.96; P < 0.01). The overall downward trend did not seem to be affected by the use of pulse oximetry and end-tidal carbon dioxide monitoring, which began in 1986. The use of these monitors increased from 6% in 1985 to 70% in 1989, and thereafter varied from 63% to 83% through the year 2000. During 1986-2000, respiratory damaging events decreased while cardiovascular damaging events increased, so that by 1992, respiratory and cardiovascular damaging events occurred in approximately the same proportion (28%), a trend that continued through 2000. CONCLUSION: The significant decrease in the proportion of claims for death or permanent brain damage from 1975 through 2000 seems to be unrelated to a marked increase in the proportion of claims where pulse oximetry and end-tidal carbon dioxide monitoring were used. After the introduction and use of these monitors, there was a significant reduction in the proportion of respiratory and an increase in the proportion of cardiovascular damaging events responsible for death or permanent brain damage. © 2006 American Society of Anesthesiologists, Inc.

The validity of performance assessments using simulation

Background: The authors wished to determine whether a simulator-based evaluation technique assessing clinical performance could demonstrate construct validity and determine the subjects' perception of realism of the evaluation process. Methods: Research ethics board approval and informed consent were obtained. Subjects were 33 university-based anesthesiologists, 46 community-based anesthesiologists, 23 final-year anesthesiology residents, and 37 final-year medical students. The simulation involved patient evaluation, induction, and maintenance of anesthesia. Each problem was scored as follows: no response to the problem, score = 0; compensating intervention, score = 1; and corrective treatment, score = 2. Examples of problems included atelectasis, coronary ischemia, and hypothermia. After the simulation, participants rated the realism of their experience on a 10-point visual analog scale (VAS). Results: After testing for internal consistency, a seven-item scenario remained. The mean proportion scoring correct answers (out of 7) for each group was as follows: university-based anesthesiologists = 0.53, community-based anesthesiologists = 0.38, residents = 0.54, and medical students = 0.15. The overall group differences were significant (P < 0.0001). The overall realism VAS score was 7.8. There was no relation between the simulator score and the realism VAS (R = -0.07, P = 0.41). Conclusions: The simulation-based evaluation method was able to discriminate between practice categories, demonstrating construct validity. Subjects rated the realism of the test scenario highly, suggesting that familiarity or comfort with the simulation environment had little or no effect on performance.

Simulation technology: A comparison of experiential and visual learning for undergraduate medical students

Background: The availability of simulator technology at the University of Toronto (Toronto, Ontario, Canada) provided the opportunity to compare the efficacy of video-assisted and simulator-assisted learning. Methods: After ethics approval from the University of Toronto, all final-year medical students were invited to participate in the current randomized trial comparing video-based to simulator-based education using three scenarios. After an introduction to the simulator environment, a 5-min performance-based pretest was administered in the simulator operating room requiring management of a critical event. A posttest was administered after students had participated in either a faculty-facilitated video or simulator teaching session. Standardized 12-point checklist performance protocols were used for assessment purposes. As well, students answered focused questions related to the educational sessions on a final examination. Student opinions regarding the value of the teaching sessions were obtained. Results: One hundred forty-four medical students participated in the study (scenario 1, n = 43; scenario 2, n = 48; scenario 3, n = 53). There was a significant improvement in posttest scores over pretest scores in all scenarios. There was no statistically significant difference in scores between simulator or video teaching methods. There were no differences in final examination marks when the two educational methods were compared. Student opinions indicated that the experiential simulator sessions were more enjoyable and valuable than the video teaching sessions. Conclusions: Both simulator and video types of faculty-facilitated education offer a valuable learning experience. Future work is needed that addresses the long-term effects of experiential learning in the retention of knowledge and acquired skills.

Teaching with a video system improves the training period but not subsequent success of tracheal intubation with the Bullard laryngoscope

Background: The Bullard laryngoscope is useful for the management of a variety of airway management scenarios. Without the aid of a video system, teaching laryngoscopy skills occurs with indirect feedback to the instructor. The purpose of this study was to determine if use of a video system would quicken the process of learning the Bullard laryngoscope or improve the performance (speed or success) of its use. Methods: Thirty-six anesthesia providers with no previous Bullard laryngoscope experience were randomly divided into two groups: initial training (first 15 intubations) with looking directly through the eyepiece (n = 20), or with the display of the scope on a video monitor (n = 16). The subjects each then performed 15 Bullard intubations by looking directly through the eyepiece. Results: There was not an overall significant difference in laryngoscopy or intubation times between the groups. When only the first 15 intubations were considered, the laryngoscopy time was shorter in the video group (26 ± 24) than in the nonvideo group (32 ± 34; P < 0.04). In the first 15 patients, there were fewer single attempts at intubation (67.9% vs. 80.3%; P < 0.002) and more failed intubations (17.2% vs. 6.0%; P < 0.0001) in the nonvideo group. Conclusions: In conclusion, the authors have shown that use of a video camera decreases time for laryngoscopic view and improves success rate when the Bullard laryngoscope is first being taught to experienced clinicians. However, these benefits are not evident as more experience with the Bullard laryngoscope is achieved, such that no difference in skill with the Bullard laryngoscope is discernible after 15 intubations whether a video system was used to teach this technique.

Postoperative modulation of central nervous system prostaglandin E2 by cyclooxygenase inhibitors after vascular surgery (Retraction in: Anesthesiology (2009) 110:3 (689))

Background: The clinical availability of injectable cyclooxygenase inhibitors allows examination of the importance of cyclooxygenase 1 and 2 after surgery. The authors hypothesize that spinal prostaglandin E2 increases with lower extremity vascular surgery and that spinal prostaglandin E2 decreases with intravenous postsurgical administration of either a mixed cyclooxygenase 1/2 inhibitor (ketorolac) or a cyclooxygenase 2 selective inhibitor (parecoxib). Methods: Thirty patients undergoing elective lower extremity revascularization under continuous spinal anesthesia had cerebrospinal fluid obtained at baseline and then up to 6 h after the start of surgery. Four hours after surgical incision, patients were randomized to receive intravenous parecoxib 40 mg, ketorolac 30 mg, or preservative-free normal saline. Patients were administered intravenous fentanyl in the postanesthesia care unit and acetaminophen/oxycodone on the surgical ward to control pain. Results: Cerebrospinal fluid prostaglandin E2 concentrations were increased during and after surgery. After surgery, intravenous parecoxib 40 mg rapidly decreased cerebrospinal fluid prostaglandin E2, and intravenous ketorolac 30 mg also reduced cerebrospinal fluid prostaglandin E2 compared with placebo, but not as much as parecoxib. Postanesthesia care unit pain scores were reduced in the two drug groups compared with placebo, and surgical ward pain scores were also decreased for both drug groups, especially with parecoxib. No patient receiving parecoxib required postoperative intravenous fentanyl. Acetaminophen/oxycodone consumption was reduced in both drug groups compared with placebo, more so with parecoxib. Conclusions: Cerebrospinal fluid prostaglandin E2 is elevated in patients after lower extremity vascular surgery. Postsurgical intravenous administration of the cyclooxygenase 1/2 inhibitor ketorolac, and especially the cyclooxygenase 2 inhibitor parecoxib, reduces cerebrospinal fluid prostaglandin E2 concentration and postoperative pain. © 2006 American Society of Anesthesiologists, Inc. Lippincott Williams &amp; Wilkins, Inc.

Perineural dexmedetomidine added to ropivacaine for sciatic nerve block in rats prolongs the duration of analgesia by blocking the hyperpolarization- activated cation current

Background: The current study was designed to test the hypothesis that the increased duration of analgesia caused by adding dexmedetomidine to local anesthetic results from blockade of the hyperpolarization-activated cation (Ih) current. Methods: In this randomized, blinded, controlled study, the analgesic effects of peripheral nerve blocks using 0.5% ropivacaine alone or 0.5% ropivacaine plus dexmedetomidine (34 μM or 6 μg/kg) were assessed with or without the pretreatment of α1-and α2- adrenoceptor antagonists (prazosin and idazoxan, respectively) and antagonists and agonists of the Ih current (ZD 7288 and forskolin, respectively). Sciatic nerve blocks were performed, and analgesia was measured by paw withdrawal latency to a thermal stimulus every 30 min for 300 min postblock. Results: The analgesic effect of dexmedetomidine added to ropivacaine was not reversed by either prazosin or idazoxan. There were no additive or attenuated effects from the pretreatment with ZD 7288 (Ih current blocker) compared with dexmedetomidine added to ropivacaine. When forskolin was administered as a pretreatment to ropivacaine plus dexmedetomidine, there were statistically significant reductions in duration of analgesia at time points 90-180 min (P &lt; 0.0001 for each individual comparison). The duration of blockade for the forskolin (768 μM) followed by ropivacaine plus dexmedetomidine group mirrored the pattern of the ropivacaine alone group, thereby implying a reversal effect. Conclusion: Dexmedetomidine added to ropivacaine caused approximately a 75% increase in the duration of analgesia, which was reversed by pretreatment with an Ih current enhancer. The analgesic effect of dexmedetomidine was not reversed by an α2- adrenoceptor antagonist. © 2011, the American Society of Anesthesiologists, Inc. Lippincott Williams &amp; Wilkins. Anesthesiology.

Accuracy of pharmacokinetic models for predicting plasma fentanyl concentrations in lean and obese surgical patients: Derivation of dosing weight ("pharmacokinetic mass")

Background: The currently available pharmacokinetic models for fentanyl were derived from normal weight patients and were not scaled to body weight. Their application to obese patients may cause overprediction of the plasma concentration of fentanyl. This study examined the influence of body weight on the predictive accuracy of two models (ANESTHESIOLOGY 1990; 73:1091-102 and J Pharmacol Exp Ther 1987; 240:159-66). Further, we attempted to derive suggested dosing mass weights for fentanyl that improved predicted accuracy. Method: Seventy patients undergoing major elective surgery with total body weight (TBW) <85 kg and body mass index <30 (Group L) and 39 patients with TBW ≥85 kg and body mass index >30 (Group O) were studied. In Group L and Group O, the mean TBW was 69 kg, and 125 kg, respectively and the mean body mass index in Group L and Group O was 24 and 44, respectively. Fentanyl infusion was used during surgery and postoperatively for analgesia. Plasma fentanyl concentrations were measured and predicted concentrations were obtained by computer simulation; 465 pairs of measured and predicted values were obtained. Results: The influence of TBW on the performance errors of the original two models was examined with nonlinear regression analysis. Shafer error versus TBW showed a highly significant negative relationship (R squared = 0.689, P < 0.001); i.e., the Shafer model systematically overestimated fentanyl concentration as weight increased. The Scott and Stanski model showed greater variation (R squared = 0.303). We used the exponential equation for Shafer performance error versus TBW to derive suggested dosing weights ("pharmacokinetic mass") for obese patients. The pharmacokinetic mass versus TBW curve was essentially linear below 100 kg (with slope of 0.65) and approached a plateau above 140 kg. For patients weighing 140 to 200 kg, dosing weights of 100-108 kg are projected. Total body clearance (ml/min) showed a strong linear correlation with pharmacokinetic mass (r = 0.793; P < 0.001), whereas the relationship with TBW was nonlinear. Conclusion: Actual body weight overestimates fentanyl dose requirements in obese patients. Dosing weight (pharmacokinetic mass) derived from the nonlinear relationship between prediction error and TBW proved to have a linear relationship with clearance.

Value of debriefing during simulated crisis management: Oral versus video-assisted oral feedback

BACKGROUND: The debriefing process during simulation-based education has been poorly studied despite its educational importance. Videotape feedback is an adjunct that may enhance the impact of the debriefing and in turn maximize learning. The purpose of this study was to investigate the value of the debriefing process during simulation and to compare the educational efficacy of two types of feedback, oral feedback and videotape-assisted oral feedback, against control (no debriefing). METHODS: Forty-two anesthesia residents were enrolled in the study. After completing a pretest scenario, participants were randomly assigned to receive no debriefing, oral feedback, or videotape-assisted oral feedback. The debriefing focused on nontechnical skills performance guided by crisis resource management principles. Participants were then required to manage a posttest scenario. The videotapes of all performances were later reviewed by two blinded independent assessors who rated participants' nontechnical skills using a validated scoring system. RESULTS: Participants' nontechnical skills did not improve in the control group, whereas the provision of oral feedback, either assisted or not assisted with videotape review, resulted in significant improvement (P < 0.005). There was no difference in improvement between oral and video-assisted oral feedback groups. CONCLUSIONS: Exposure to a simulated crisis without constructive debriefing by instructors offers little benefit to trainees. The addition of video review did not offer any advantage over oral feedback alone. Valuable simulation training can therefore be achieved even when video technology is not available. © 2006 American Society of Anesthesiologists, Inc. Lippincott Williams & Wilkins, Inc.

Development of an objective scoring system for measurement of resident performance on the human patient simulator

BACKGROUND: The decrease in the percentage of patients having cesarean delivery during general anesthesia has led some educators to advocate the increased use of simulation-based training for this anesthetic. The authors developed a scoring system to measure resident performance of this anesthetic on the human patient simulator and subjected the system to tests of validity and reliability. METHODS: A modified Delphi technique was used to achieve a consensus among several experts regarding a standardized scoring system for evaluating resident performance of general anesthesia for emergency cesarean delivery on the human patient simulator. Eight third-year and eight first-year anesthesiology residents performed the scenario and were videotaped and scored by four attending obstetric anesthesiologists. RESULTS: Third-year residents scored an average of 150.5 points, whereas first-year residents scored an average of 128 points (P = 0.004). The scoring instrument demonstrated high interrater reliability with an intraclass correlation coefficient of 0.97 (95% confidence interval, 0.94-0.99) compared with the average score. CONCLUSIONS: The developed scoring tool to measure resident performance of general anesthesia for emergency cesarean delivery on the patient simulator seems both valid and reliable in the context in which it was tested. This scoring system may prove useful for future studies such as those investigating the effect of simulator training on objective assessment of resident performance. © 2006 American Society of Anesthesiologists, Inc. Lippincott Williams & Wilkins, Inc.

Effect of simulation training on compliance with difficult airway management algorithms, technical ability, and skills retention for emergency cricothyrotomy

Background: The effectiveness of simulation is rarely evaluated. The aim of this study was to assess the impact of a short training course on the ability of anesthesiology residents to comply with current difficult airway management guidelines. Methods: Twenty-seven third-year anesthesiology residents were assessed on a simulator in a "can't intubate, can't ventilate" scenario before the training (the pretest) and then randomly 3, 6, or 12 months after training (the posttest). The scenario was built so that the resident was prompted to perform a cricothyrotomy. Compliance with airway management guidelines and the cricothyrotomy's duration and technical quality were assessed as a checklist score [0 to 10] and a global rating scale [7 to 35]. Results: After training, all 27 residents (100%) complied with the airway management guidelines, compared with 17 (63%) in the pretest (P < 0.005). In the pretest and the 3-, 6-, and 12-month posttests, the median [range] duration of cricothyrotomy was respectively 117 s [70 to 184], 69 s [43 to 97], 52 s [43 to 76], and 62 s [43 to 74] (P < 0.0001 vs. in the pretest), the median [range] checklist score was 3 [0 to 7], 10 [8 to 10], 9 [6 to 10], and 9 [4 to 10] (P < 0.0001 vs. in the pretest) and the median [range] global rating scale was 12 [7 to 22], 30 [20 to 35], 33 [23 to 35], and 31 [18 to 33] (P < 0.0001 vs. in the pretest). There were no significant differences between performance levels achieved in the 3-, 6-, and 12-month posttests. Conclusion: The training session significantly improved the residents' compliance with guidelines and their performance of cricothyrotomy. Copyright © 2014, the American Society of Anesthesiologists, Inc. Lippincott Williams & Wilkins.

Scholarly productivity and National Institutes of Health funding of Foundation for Anesthesia Education and Research grant recipients: Insights from a bibliometric analysis

Background: The Foundation for Anesthesia Education and Research (FAER) grant program provides fellows and junior faculty members with grant support to stimulate their careers. The authors conducted a bibliometric analysis of recipients of FAER grants since 1987. Methods: Recipients were identified in the FAER alumni database. Each recipient's affiliation was identified using an Internet search (keyword "anesthesiology"). The duration of activity, publications, publication rate, citations, citation rate, h-index, and National Institutes of Health (NIH) funding for each recipient were obtained using the Scopus® (Elsevier, USA) and NIH Research Portfolio Online Reporting Tools® (National Institutes of Health, USA) databases. Results: Three hundred ninety-seven individuals who received 430 FAER grants were analyzed, 79.1% of whom currently hold full-time academic appointments. Recipients published 19,647 papers with 548,563 citations and received 391 NIH grants totaling $448.44 million. Publications, citations, h-index, the number of NIH grants, and amount of support were dependent on academic rank and years of activity (P < 0.0001). Recipients who acquired NIH grants (40.3%) had greater scholarly output than those who did not. Recipients with more publications were also more likely to secure NIH grants. Women had fewer publications and lower h-index than men, but there were no gender-based differences in NIH funding. Scholarly output was similar in recipients with MD and PhD degrees versus those with MD degrees alone, but recipients with MD and PhD degrees were more likely to receive NIH funding than those with MDs alone. Conclusion: Most FAER alumni remain in academic anesthesiology and have established a consistent record of scholarly output that appears to exceed reported productivity for average faculty members identified in previous studies. Copyright © 2015, the American Society of Anesthesiologists, Inc. Wolters Kluwer Health, Inc. All Rights Reserved.

Evaluation of the foundation for anesthesia education and research medical student anesthesia research fellowship program participants' scholarly activity and career choices

Background: The Foundation for Anesthesia Education and Research Medical Student Anesthesia Research Fellowship (MSARF) program is an 8-week program that pairs medical students with anesthesiologists performing anesthesia-related research. This study evaluated the proportion of students who published an article from their work, as well as the percentage of students who entered anesthesiology residency programs. Methods: A list of previous MSARF participants (2005 to 2012), site, and project information was obtained. Searches for publications were performed using PubMed. The primary outcome was the publication rate for MSARF projects. The MSARF abstract-to-publication ratio was compared with the percentage of abstracts presented at biomedical meetings that resulted in publication as estimated by a Cochrane review (44%). For students who had graduated from medical school, match lists from the students' medical schools were reviewed for specialty choice. Results: Forty-two percent of the 346 MSARF projects were subsequently published. There was no difference between the MSARF abstract-to-publication ratio and the publication rate of articles from abstracts presented at scientific meetings (P = 0.57). Thirty percent (n = 105; 95% CI, 25 to 35%) of all the MSARF students were authors on a publication. Fifty-eight percent of the students for whom residency match data (n = 255) were available matched into anesthesiology residencies (95% CI, 52 to 64%). Conclusions: The MSARF program resulted in many students being included as a co-author on a published article; the majority of these students entered anesthesiology residency programs. Future research should determine whether the program has a long-term impact on the development of academic anesthesiologists. © 2016, the American Society of Anesthesiologists, Inc. Wolters Kluwer Health, Inc.

Lipid emulsion reverses levobupivacaine-induced responses in isolated rat aortic vessels

Background: The goal of this in vitro study was to investigate the effects of lipid emulsion (LE) on local anesthetic levobupivacaine-induced responses in isolated rat aorta and to determine whether the effect of LE is related to the lipid solubility of local anesthetics. Methods: Isolated rat aortic rings were suspended for isometric tension recording. The effects of LE were determined during levobupivacaine-, ropivacaine-, and mepivacaine-induced responses. Endothelial nitric oxide synthase and caveolin-1 phosphorylation was measured in human umbilical vein endothelial cells treated with levobupivacaine alone and with the addition of LE. Results: Levobupivacaine produced vasoconstriction at lower, and vasodilation at higher, concentrations, and both were significantly reversed by treatment with LE. Levobupivacaine and ropivacaine inhibited the high potassium chloride-mediated contraction, which was restored by LE. The magnitude of LE-mediated reversal was greater with levobupivacaine treatment than with ropivacaine, whereas this reversal was not observed in mepivacaine-induced responses. In LE-pretreated rings, low-dose levobupivacaine- and ropivacaine-induced contraction was attenuated, whereas low-dose mepivacaine-induced contraction was not significantly altered. Treatment with LE also inhibited the phosphorylation of endothelial nitric oxide synthase induced by levobupivacaine in human umbilical vein endothelial cells. Conclusions: These results indicate that reversal of levobupivacaine-induced vasodilation by LE is mediated mainly through the attenuation of levobupivacaine-mediated inhibition of L-type calcium channel-dependent contraction and, in part, by inhibition of levobupivacaine-induced nitric oxide release. LE-mediated reversal of responses induced by local anesthetics may be related to their lipid solubility. © 2011, the American Society of Anesthesiologists, Inc. Lippincott Williams & Wilkins. Anesthesiology.

Risk and outcomes of substance use disorder among anesthesiology residents: A matched cohort analysis

Background: The goal of this work is to evaluate selected risk factors and outcomes for substance use disorder (SUD) in physicians enrolled in anesthesiology residencies approved by the Accreditation Council for Graduate Medical Education. Methods: For each of 384 individuals with evidence of SUD while in primary residency training in anesthesiology from 1975 to 2009, two controls (n = 768) who did not develop SUD were identified and matched for sex, age, primary residency program, and program start date. Risk factors evaluated included location of medical school training (United States vs. other) and anesthesia knowledge as assessed by In-Training Examination performance. Outcomes (assessed to December 31, 2013, with a median follow-up time of 12.2 and 15.1 yr for cases and controls, respectively) included mortality and profession-related outcomes. Results: Receiving medical education within the United States, but not performance on the first in-Training examination, was associated with an increased risk of developing SUD as a resident. Cases demonstrated a marked increase in the risk of death after training (hazard ratio, 7.9; 95% CI, 3.1 to 20.5), adverse training outcomes including failure to complete residency (odds ratio, 14.9; 95% CI, 9.0 to 24.6) or become board certified (odds ratio, 10.4; 95% CI, 7.0 to 15.5), and adverse medical licensure actions subsequent to residency (hazard ratio, 6.8; 95% CI, 3.8 to 12.2). As of the end of follow-up, 54 cases (14.1%) were deceased compared with 10 controls (1.3%); 28 cases and no controls died during residency. Conclusion: The attributable risk of SUD to several adverse outcomes during and after residency training, including death and adverse medical license actions, is substantial. Copyright © 2015, the American Society of Anesthesiologists, Inc.

The effect of anesthetic technique on postoperative outcomes in hip fracture repair

Background: The impact of anesthetic choice on postoperative mortality and morbidity has not been determined with certainty. Methods: The authors evaluated the effect of type of anesthesia on postoperative mortality and morbidity in a retrospective cohort study of consecutive hip fracture patients, aged 60 yr or older, who underwent surgical repair at 20 US hospitals between 1983 and 1993. The primary outcome was defined as death within 30 days of the operative procedure. The secondary outcomes were postoperative 7-day mortality, postoperative myocardial infarction, postoperative pneumonia, postoperative congestive heart failure, and postoperative change in mental status. Numerous comorbid conditions were controlled for individually and by several comorbidity indices using logistic regression. Results: General anesthesia was used in 6,206 patients (65.8%) and regional anesthesia in 3,219 patients (3,078 spinal anesthesia and 141 epidural anesthesia). The 30-day mortality rate in the general anesthesia group was 4.4%, compared with 5.4% in the regional anesthesia group (unadjusted odds ratio = 0.80; 95% confidence interval = 0.66-0.97). However, the adjusted odds ratio for general anesthesia increased to 1.08 (0.84-1.38). The adjusted odds ratios for general anesthesia versus regional anesthesia for the 7-day mortality was 0.90 (0.59-1.39) and for postoperative morbidity outcomes were as follows: myocardial infarction: adjusted odds ratio = 1.17 (0.80-1.70); congestive heart failure: adjusted odds ratio = 1.04 (0.80- 1.36); pneumonia: adjusted odds ratio = 1.21 (0.87-1.68); postoperative change in mental status: adjusted odds ratio = 1.08 (0.95-1.22). Conclusions: The authors were unable to demonstrate that regional anesthesia was associated with better outcome than was general anesthesia in this large observational study of elderly patients with hip fracture. These results suggest that the type of anesthesia used should depend on factors other than any associated risks of mortality or morbidity.

Perioperative comparative effectiveness of anesthetic technique in orthopedic patients

Background: The impact of anesthetic technique on perioperative outcomes remains controversial. We studied a large national sample of primary joint arthroplasty recipients and hypothesized that neuraxial anesthesia favorably influences perioperative outcomes. Methods: Data from approximately 400 hospitals between 2006 and 2010 were accessed. Patients who underwent primary hip or knee arthroplasty were identified and subgrouped by anesthesia technique: general, neuraxial, and combined neuraxial-general. Demographics, postoperative complications, 30-day mortality, length of stay, and patient cost were analyzed and compared. Multivariable analyses were conducted to identify the independent impact of choice of anesthetic on outcomes. Results: Of 528,495 entries of patients undergoing primary hip or knee arthroplasty, information on anesthesia type was available for 382,236 (71.4%) records. Eleven percent were performed under neuraxial, 14.2% under combined neuraxial-general, and 74.8% under general anesthesia. Average age and comorbidity burden differed modestly between groups. When neuraxial anesthesia was used, 30-day mortality was significantly lower (0.10, 0.10, and 0.18%; P < 0.001), as was the incidence of prolonged (>75th percentile) length of stay, increased cost, and in-hospital complications. In the multivariable regression, neuraxial anesthesia was associated with the most favorable complication risk profile. Thirty-day mortality remained significantly higher in the general compared with the neuraxial or neuraxial-general group for total knee arthroplasty (adjusted odds ratio [OR] of 1.83, 95% CI 1.08-3.1, P = 0.02; OR of 1.70, 95% CI 1.06-2.74, P = 0.02, respectively). Conclusions: The utilization of neuraxial versus general anesthesia for primary joint arthroplasty is associated with superior perioperative outcomes. More research is needed to study potential mechanisms for these findings. © 2013 the American Society of Anesthesiologists, Inc. Lippincott Williams & Wilkins. Anesthesiology.

Association between intraoperative blood transfusion and mortality and morbidity in patients undergoing noncardiac surgery

Background: The impact of intraoperative erythrocyte transfusion on outcomes of anemic patients undergoing noncardiac surgery has not been well characterized. The objective of this study was to examine the association between blood transfusion and mortality and morbidity in patients with severe anemia (hematocrit less than 30%) who are exposed to one or two units of erythrocytes intraoperatively. Methods: This was a retrospective analysis of the association of blood transfusion and 30-day mortality and 30-day morbidity in 10,100 patients undergoing general, vascular, or orthopedic surgery. We estimated separate multivariate logistic regression models for 30-day mortality and for 30-day complications. Results: Intraoperative blood transfusion was associated with an increased risk of death (odds ratio [OR], 1.29; 95% CI, 1.03-1.62). Patients receiving an intraoperative transfusion were more likely to have pulmonary, septic, wound, or thromboembolic complications, compared with patients not receiving an intraoperative transfusion. Compared with patients who were not transfused, patients receiving one or two units of erythrocytes were more likely to have pulmonary complications (OR, 1.76; 95% CI, 1.48-2.09), sepsis (OR, 1.43; 95% CI, 1.21-1.68), thromboembolic complications (OR, 1.77; 95% CI, 1.32-2.38), and wound complications (OR, 1.87; 95% CI, 1.47-2.37). Conclusions: Intraoperative blood transfusion is associated with a higher risk of mortality and morbidity in surgical patients with severe anemia. It is unknown whether this association is due to the adverse effects of blood transfusion or is, instead, the result of increased blood loss in the patients receiving blood. © 2011, the American Society of Anesthesiologists, Inc. Lippincott Williams & Wilkins. Anesthesiology.

Reducing the incidence of substance use disorders in anesthesiology residents 13 years of comprehensive urine drug screening

Background: The incidence of substance use disorders in the United States among residents in anesthesiology is between 1% and 2%. A recent study reported that the incidence of substance use disorders in U.S. anesthesiology residents has been increasing. There are no reports of effective methods to prevent substance use disorder in residents. A comprehensive drug testing program including a random component may reduce the incidence of substance use disorders. Methods: The authors initiated a comprehensive urine drug screening program of residents, fellows, faculty physicians, and certified nurse anesthetists. The authors performed 3,190 tests over 13 yr. The authors determined the incidence of substance use disorders among residents in our large anesthesiology residency program during the decade before (January 1, 1994, to December 31, 2003) and for the 13 yr after (January 1, 2004 to December 31, 2016) instituting a random urine drug testing program. A total of 628 residents trained in the program over these 23 yr; they contributed a total of 1,721 resident years for analysis. Fewer faculty and certified nurse anesthetists were studied, so we do not include them in our analysis. Results: The incidence of substance use disorders among trainees in our department during the 10 yr before initiation of urine drug screening was four incidents in 719 resident years or 0.0056 incidents per resident-year. In the 13 yr after the introduction of urine drug screening, there have been zero incidents in 1,002 resident years in our residency program (P = 0.0305). Conclusions: This single-center, comprehensive program including preplacement and random drug testing was associated with a reduction of the incidence of substance use disorders among our residents in anesthesiology. There were no instances of substance use disorders in our residents over the recent 13 yr. A large, multicenter trial of a more diverse sample of academic, government, and community institutions is needed to determine if such a program can predictably reduce the incidence of substance use disorders in a larger group of anesthesiology residents. Copyright © 2018, the American Society of Anesthesiologists, Inc. Wolters Kluwer Health, Inc. All Rights Reserved.

Ventilatory protective strategies during thoracic surgery: Effects of alveolar recruitment maneuver and low-tidal volume ventilation on lung density distribution

Background: The increased tidal volume (VT) applied to the ventilated lung during one-lung ventilation (OLV) enhances cyclic alveolar recruitment and mechanical stress. It is unknown whether alveolar recruitment maneuvers (ARMs) and reduced VT may influence tidal recruitment and lung density. Therefore, the effects of ARM and OLV with different VT on pulmonary gas/tissue distribution are examined. Methods: Eight anesthetized piglets were mechanically ventilated (VT = 10 ml/kg). A defined ARM was applied to the whole lung (40 cm H2O for 10 s). Spiral computed tomographic lung scans were acquired before and after ARM. Thereafter, the lungs were separated with an endobronchial blocker. The pigs were randomized to receive OLV in the dependent lung with a VT of either 5 or 10 ml/kg. Computed tomography was repeated during and after OLV. The voxels were categorized by density intervals (i.e., atelectasis, poorly aerated, normally aerated, or overaerated). Tidal recruitment was defined as the addition of gas to collapsed lung regions. Results: The dependent lung contained atelectatic (56 ± 10 ml), poorly aerated (183 ± 10 ml), and normally aerated (187 ± 29 ml) regions before ARM. After ARM, lung volume and aeration increased (426 ± 35 vs. 526 ± 69 ml). Respiratory compliance enhanced, and tidal recruitment decreased (95% vs. 79% of the whole end-expiratory lung volume). OLV with 10 ml/kg further increased aeration (atelectasis, 15 ± 2 ml; poorly aerated, 94 ± 24 ml; normally aerated, 580 ± 98 ml) and tidal recruitment (81% of the dependent lung). OLV with 5 ml/kg did not affect tidal recruitment or lung density distribution. (Data are given as mean ± SD.) Conclusions: The ARM improves aeration and respiratory mechanics. In contrast to OLV with high VT, OLV with reduced VT does not reinforce tidal recruitment, indicating decreased mechanical stress. Copyright © 2011, the American Society of Anesthesiologists, Inc. Lippincott Williams & Wilkins. Anesthesiology.

Exhaled breath condensate in mechanically ventilated brain-injured patients with no lung injury or sepsis

Background: The inflammatory influence of prolonged mechanical ventilation in uninjured lungs remains a matter of controversy and largely unexplored in humans. The authors investigated pulmonary inflammation by using exhaled breath condensate (EBC) in mechanically ventilated, brain-injured patients in the absence of acute lung injury or sepsis and explored the potential influence of positive end-expiratory pressure (PEEP). Methods: Inflammatory EBC markers were assessed in 27 mechanically ventilated, brain-injured patients with neither acute lung injury nor sepsis and in 12 healthy and 8 brain-injured control subjects. Patients were ventilated with 8 ml/kg during zero end-expiratory pressure (ZEEP group, n = 12) or 8 cm H2O PEEP (PEEP group, n = 15). EBC was collected on days 1, 3, and 5 of mechanical ventilation to measure pH; interleukins (IL)-10, 1β, 6, 8, and 12p70; and tumor necrosis factor-α. Results: EBC pH was lower, whereas IL-1β and tumor necrosis factor-α were greater in both patient groups compared with either control group; IL-6 was higher, whereas IL-10 and IL-12p70 were sporadically higher than in healthy control subjects; no differences were noted between the two patient groups, except for IL-10, which decreased by day 5 during PEEP. Leukocytes, soluble IL-6, and soluble triggering receptor expressed on myeloid cells-1 in blood were constantly higher during zero end-expiratory pressure; EBC cytokines appeared mostly related to soluble IL-8 and inversely related to soluble triggering receptor expressed on myeloid cells-1. Conclusions: In brain-injured, mechanically ventilated patients with neither acute lung injury nor sepsis, EBC markers appear to indicate the presence of subtle pulmonary inflammation that is mostly unaffected by PEEP. There is evidence for a systemic inflammatory response, especially in patients during zero end-expiratory pressure. Copyright © 2011, the American Society of Anesthesiologists, Inc. Lippincott Williams & Wilkins. Anesthesiology.

Polymorphism in the interleukin-1 receptor antagonist gene is associated with serum interleukin-1 receptor antagonist concentrations and postoperative opioid consumption

Background: The interleukin-1 receptor antagonist (IL-1Ra) is the principal determinant of IL-1β bioactivity within the IL-1 gene cluster, regulating IL-1α and IL-1β release. This study was designed to determine whether polymorphisms of the IL-1Ra gene (IL1RN) produce clinically measurable differences in serum IL-1Ra concentrations and opioid consumption in the postoperative period. Methods: Opioid consumption and pain scores were evaluated in 96 patients undergoing a nephrectomy. DNA was extracted from all patients, and the genotypes of IL1RN were determined by polymerase chain reaction amplification of the variable number of tandem repeats of 86 base pairs in intron 2 of IL1RN. The concentrations of serum IL-1Ra concentrations at baseline and at 24 h postoperatively in 58 subjects were measured. Results: Differences in opioid consumption among the three genotype groups (IL1RN*1 homozygotes and *2 and *3 carriers) were statistically significant in the first and second 12-h postoperative periods (P = 0.010). The IL1RN*2 carrier group consumed 43% (95% CI, 38-48%) less opioids in the first 24 h after surgery than the IL1RN*1 homozygote group (P = 0.003). Differences in the serum IL-1Ra concentration among the three genotype groups were statistically significant at 24 h postoperatively (P = 0.003), with IL1RN*2 carriers having the highest serum IL-1Ra concentrations. Conclusions: The variable number of tandem repeats in intron 2 of IL1RN may contribute to interindividual variations in opioid consumption in the first 24 h after surgery. Patients homozygous for the IL1RN*1 allele have lower concentrations of IL-1Ra and require higher doses of opioids postoperatively than patients carrying at least one IL1RN*2 allele. Copyright © 2011, the American Society of Anesthesiologists, Inc. Lippincott Williams & Wilkins. Anesthesiology.

Teamwork in the operating room: Frontline perspectives among hospitals and operating room personnel

BACKGROUND: The Joint Commission on Accreditation of Healthcare Organizations is proposing that hospitals measure culture beginning in 2007. However, a reliable and widely used measurement tool for the operating room (OR) setting does not currently exist. METHODS: OR personnel in 60 US hospitals were surveyed using the Safety Attitudes Questionnaire. The teamwork climate domain of the survey uses six items about difficulty speaking up, conflict resolution, physician-nurse collaboration, feeling supported by others, asking questions, and heeding nurse input. To justify grouping individual-level responses to a single score at each hospital OR level, the authors used a multilevel confirmatory factor analysis, intraclass correlations, within-group interrater reliability, and Cronbach's α. To detect differences at the hospital OR level and by caregiver type, the authors used multivariate analysis of variance (items) and analysis of variance (scale). RESULTS: The response rate was 77.1%. There was robust evidence for grouping individual-level respondents to the hospital OR level using the diverse set of statistical tests, e.g., Comparative Fit Index = 0.99, root mean squared error of approximation = 0.05, and acceptable intraclasss correlations, within-group interrater reliability values, and Cronbach's α = 0.79. Teamwork climate differed significantly by hospital (F59, 1,911 = 4.06, P < 0.001) and OR caregiver type (F4, 1,911 = 9.96, P < 0.001). CONCLUSIONS: Rigorous assessment of teamwork climate is possible using this psychometrically sound teamwork climate scale. This tool and initial benchmarks allow others to compare their teamwork climate to national means, in an effort to focus more on what excellent surgical teams do well. © 2006 American Society of Anesthesiologists, Inc.

Current Transfusion Practices of Members of the American Society of Anesthesiologists: A Survey

Background: The last published survey of transfusion practices among members of the American Society of Anesthesiologists (ASA) was conducted in 1981. The ASA Committee on Transfusion Medicine conducted a new transfusion survey in 2002. Methods: The survey was mailed to 2,500 randomly selected active ASA members. The previous survey was modified to incorporate questions based on the ASA Practice Guidelines for Blood Component Therapy. The chi-square test was used for comparisons. Two-tailed P values of 0.05 or less were considered as nonchance differences. Results: A total of 862 survey responses were completed by anesthesiologists who provided or directly supervised anesthesia for patients who may have required transfusion. In a given week, 62% rarely or never transfused 3 or more units of blood to the same patient. The percentage of anesthesiologists who responded that it is never or rarely (1% or less of the time) necessary to cancel elective surgery because of unavailability of blood products was 96% in 2002. In 1981, 92% responded that it was rarely necessary, and 8% said that it was occasionally necessary. The percentage of anesthesiologists who required patients undergoing elective surgery to have a hemoglobin concentration of at least 10 g/dl decreased from 65% to 9% (P < 0.001). Before intraoperative erythrocyte transfusion, 89% of respondents performed hemoglobin or hematocrit determinations routinely or sometimes. Intraoperative autologous transfusion equipment availability increased from 39% to 95% (P < 0.001). Awareness of the ASA Guidelines was 72%. Conclusions: Transfusion practices have changed considerably since 1981. Current transfusion practices are, in general, consistent with the ASA Guidelines.

Efficacy, safety, and pharmacokinetics of sugammadex for the reversal of rocuronium-induced neuromuscular blockade in elderly patients

Background: The management of elderly patients can be challenging for anesthesiologists for many reasons, including altered pharmacokinetics and dynamics. This study compared the efficacy, safety, and pharmacokinetics of sugammadex for moderate rocuronium-induced neuromuscular blockade reversal in adult (aged 18-64 yr) versus elderly adult (aged 65 yr or older) patients. Methods: This phase 3a, multicenter, parallel-group, comparative, open-label study enrolled 162 patients aged 18 yr and older, American Society of Anesthesiologists class 1-3, scheduled for surgery with general anesthesia and requiring neuromuscular blockade. After anesthesia induction, patients received rocuronium, 0.6 mg/kg, before tracheal intubation, with maintenance doses of 0.15 mg/kg as required. At the end of surgery, patients received sugammadex, 2.0 mg/kg, at reappearance of the second twitch of the train-of-four (TOF) for reversal. The primary efficacy variable was time from sugammadex administration to recovery of the TOF ratio to 0.9 or greater. Pharmacokinetics and safety were also evaluated. Results: Overall, 150 patients were treated and had at least one postbaseline efficacy assessment; 48 were aged 18-64 yr (adult), 62 were aged 65-74 yr (elderly), and 40 were aged 75 yr or older (old-elderly). The geometric mean time (95% confidence interval) from sugammadex administration to recovery of the TOF ratio to 0.9 increased with age, from 2.3 (2.0-2.6) min (adults) to 2.9 (2.7-3.2) min (elderly/old-elderly groups combined). Recovery of the TOF ratio to 0.9 was estimated to be 0.7 min faster in adults compared with patients aged 65 yr or older (P = 0.022). Sugammadex was well tolerated by all patients. Conclusion: Sugammadex facilitates rapid reversal from moderate rocuronium-induced neuromuscular blockade in adults of all ages. © 2011, the American Society of Anesthesiologists, Inc. Lippincott Williams & Wilkins. Anesthesiology.

Lidocaine blocks the hyperpolarization-activated mixed cation current, ih, in rat thalamocortical neurons

Background: The mechanisms that underlie the supraspinal central nervous system effects of systemic lidocaine are poorly understood and not solely explained by Na+ channel blockade. Among other potential targets is the hyperpolarization-activated cation current, Ih, which is blocked by lidocaine in peripheral neurons. Ih is highly expressed in the thalamus, a brain area previously implicated in lidocaine's systemic effects. The authors tested the hypothesis that lidocaine blocks Ih in rat thalamocortical neurons. Methods: The authors conducted whole cell voltage-and current-clamp recordings in ventrobasal thalamocortical neurons in rat brain slices in vitro. Drugs were bath-applied. Data were analyzed with Student t tests and ANOVA as appropriate; α = 0.05. Results: Lidocaine voltage-independently blocked Ih, with high efficacy and a half-maximal inhibitory concentration (IC50) of 72 μM. Lidocaine did not affect Ih activation kinetics but delayed deactivation. The Ih inhibition was accompanied by an increase in input resistance and membrane hyperpolarization (maximum, 8 mV). Lidocaine increased the latency of rebound low-threshold Ca2+ spike bursts and reduced the number of action potentials in bursts. At depolarized potentials associated with the relay firing mode (&gt;-60 mV), lidocaine at 600 μM concurrently inhibited a K conductance, resulting in depolarization (7-10 mV) and an increase in excitability mediated by Na+-independent, high-threshold spikes. Conclusions: Lidocaine concentration-dependently inhibited Ih in thalamocortical neurons in vitro, with high efficacy and a potency similar to Na+ channel blockade. This effect would reduce the neurons' ability to produce intrinsic burst firing and δ rhythms and thereby contribute to the alterations in oscillatory cerebral activity produced by systemic lidocaine in vivo. © 2011, the American Society of Anesthesiologists, Inc. Lippincott Williams &amp; Wilkins. Anesthesiology.