bluuebunny/crossref_metadata_2025 huggingface dataset:
The Validity of Performance Assessments Using Simulation
Authors: Devitt J. Hugh , Kurrek Matt M. , Cohen Marsha M. , Cleave-Hogg Doreen
Published: November 2003

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.
A Randomized, Controlled Trial of Advance Care Planning Discussions during Preoperative Evaluations
Authors: Grimaldo Denise A. , Wiener-Kronish Jeanine P. , Jurson Tamara , Shaughnessy Thomas E. , Curtis J. Randall , Liu Linda L.
Published: November 2003

Background

Although many patients and physicians support the concept of advance care planning, only a small percentage of patients actually have the necessary discussion with health care providers. Hospital-based physicians other than primary care providers often are needed to increase physician, patient, and proxy communication about advanced directives. This study evaluated the effectiveness of a 5-10-min discussion designed to foster dialogue between patients and their proxies in a preoperative evaluation clinic. The discussions were lead by anesthesiologists.

Methods

A randomized controlled trial was conducted from September 1998 through May 1999 in a preoperative evaluation clinic at University of California, San Francisco, a tertiary care center. English-speaking patients aged 65 yr or older who were scheduled for elective surgery were randomized to receive a short information session stressing the importance of communication about end-of-life care between the patients and their proxies. Patients randomized to the control group received the standard preoperative anesthesia screening. An admitting counselor questioned all patients (control and intervention) about whether they have an advanced directive as part of the registration process before their arrival in clinic.

Results

The intervention significantly increased discussions about end-of-life care between patients and their proxies. Eighty seven percent of patients reported having discussions with their proxies as compared with only 66% of control patients (P = 0.001). The intervention also increased durable power of attorney completion rate to 27% as compared with 10% completion rate by controls.

Conclusions

The preoperative evaluation period can be an opportunity to encourage patient and proxy communication about end-of-life care.
Distribution of the Probability of Survival Is a Strategic Issue for Randomized Trials in Critically Ill Patients
Authors: Riou Bruno , Landais Paul , Vivien Benoît , Stell Philippe , Labbene Iheb , Carli Pierre
Published: November 2003

Background

Many randomized clinical trials in trauma have failed to demonstrate a significant improvement in survival rate. Using a trauma patient database, we simulated what could happen in a trial designed to improve survival rate in this setting.

Methods

The predicted probability of survival was assessed using the TRISS methodology in 350 severely injured trauma patients. Using this probability of survival, the authors simulated the effects of a drug that may increase the probability of survival by 10-50% and calculated the number of patients to be included in a triad, assuming alpha = 0.05 and beta = 0.10 by using the percentage of survivors or the individual probability of survival. Other distributions (Gaussian, J shape, uniform) of the probability of survival were also simulated and tested.

Results

The distribution of the probability of survival was bimodal with two peaks (< 0.10 and > 0.90). There were major discrepancies between the number of patients to be included when considering the percentage of survivors or the individual value of the probability of survival: 63,202 versus 2,848 if the drug increases the probability of survival by 20%. This discrepancy also occurred in other types of distribution (uniform, J shape) but to a lesser degree, whereas it was very limited in a Gaussian distribution.

Conclusions

The bimodal distribution of the probability of survival in trauma patients has major consequences on hypothesis testing, leading to overestimation of the power. This statistical pitfall may also occur in other critically ill patients.
Anaphylactic Reactions to Aprotinin Reexposure in Cardiac Surgery
Authors: Dietrich Wulf , Späth Paul , Zühlsdorf Michael , Dalichau Harald , Kirchhoff Paul G. , Kuppe Hermann , Preiss Dieter U. , Mayer Gabriele
Published: November 2003

Background

Aprotinin, a serine proteinase inhibitor, reduces bleeding during cardiac surgery. As aprotinin is derived from bovine lung, it has antigenic properties. This investigation examined the incidence of anaphylactic reactions in patients reexposed to aprotinin and the relation to preformed antiaprotinin immunoglobulin (Ig)G and IgE antibodies.

Methods

This prospective observational study conducted at five centers in Germany evaluated patients undergoing repeat cardiac surgery reexposed to aprotinin between 1995 and 1996. Antiaprotinin IgG and IgE antibody measurements, using a noncommercial enzyme-linked immunosorbent assay and an immunofluorescence assay, respectively, were performed preoperatively and postoperatively. An anaphylactic reaction was defined as major changes from baseline within 10 min of aprotinin administration of systolic pressure 20% or greater, heart rate 20% or greater, inspiratory pressure greater than 5 cm H2O, or a skin reaction.

Results

In 121 cases (71 adults, 46 children), a mean aprotinin reexposure interval of 1,654 days (range, 16-7,136 days) was observed. Preoperative antiaprotinin IgG (optical density ratio > 3) and IgE antibodies (radioallergosorbent test [RAST] score < 3) were detected in 18 and 9 patients, respectively. High concentrations of each (IgG, optical density ratio > 10; IgE, RAST score > or = 3) were detected in five patients. Three patients (2.5%; 95% confidence interval, 0.51-7.1%) experienced an anaphylactic reaction after aprotinin exposure, followed by full recovery; these patients had reexposure intervals less than 6 months (22, 25, and 25 days) and the highest preoperative IgG concentrations of all patients (P < 0.05). Assay sensitivity was 100%, as no anaphylactic reactions occurred in IgG-negative patients (95% confidence interval, 0.0-3.1%); assay specificity was 98%. Preoperative IgE measurements were quantifiable in two of three reactive patients and in three nonreacting patients.

Conclusions

Quantitative detection of antiaprotinin IgE and IgG lacks specificity for predictive purposes; however, quantitation of antiaprotinin IgG may identify patients at risk for developing an anaphylactic reaction to aprotinin reexposure.
Local Anesthetic Effects on Priming and Activation of Human Neutrophils
Authors: Hollmann Markus W. , Gross Ariane , Jelacin Niko , Durieux Marcel E.
Published: November 2003

Background

Local anesthetics (LAs) have been shown to inhibit human polymorphonuclear neutrophil (hPMN) functions in vitro, but mechanisms are poorly understood. In this study the authors determined how LAs affect superoxide anion production of hPMNs primed with platelet-activating factor (PAF). The authors studied which pharmacologic properties of LAs are important for this action and assessed the LA site of action within the PAF signaling pathway.

Methods

Metabolic activity of primed and/or activated hPMNs were measured using the cytochrome-c assay. hPMNs were incubated with several LAs for 1 h to assess interference with PAF signaling. Using protein kinase C (PKC) inhibitors, the PKC activator phorbol myristate acetate (PMA), and the phospholipase C (PLC) antagonist U-73122, we studied involvement of PKC and PLC in the priming process. Pertussis toxin (PTX) was used to characterize the G proteins mediating this pathway. Combined administration of lidocaine with PMA or PTX was used to determine the LA site of action within the priming pathway.

Results

Platelet-activating factor effectively primed hPMNs. Ester LAs (tetracaine and benzocaine) exerted the most profound inhibitory effect on PAF-primed hPMNs, whereas inhibitory potency of amide LAs increased with decreased charged fraction. The major PAF-induced priming pathway is PLC- and PKC-dependent and mainly Gq-mediated. The main target site for LA in this pathway is located upstream of PKC.

Conclusions

Local anesthetics in clinically relevant concentrations inhibit superoxide anion production of PAF-primed hPMNs. Effects on priming by these compounds might explain, at least in part, the previously unexplained difference between concentrations of LAs required for their antiinflammatory action in vitro and in vivo. This study suggests a target site for LAs within a Gq-coupled signaling pathway.
Intravenous Anesthetics Inhibit Nonadrenergic Noncholinergic Lower Esophageal Sphincter Relaxation via Nitric Oxide–Cyclic Guanosine Monophosphate Pathway Modulation in Rabbits
Authors: Kohjitani Atsushi , Miyawaki Takuya , Funahashi Makoto , Mitoh Yoshihiro , Matsuo Ryuji , Shimada Masahiko
Published: November 2003

Background

Nonadrenergic noncholinergic (NANC) nerves have important roles in the regulation of the lower esophageal sphincter (LES) motility and function. The effects of thiopental, ketamine, and midazolam on NANC LES relaxation were investigated.

Methods

The isometric tension of circular muscle strips from Japanese White rabbits was examined. The NANC relaxation was induced by KCl (30 mM) in the presence of atropine (3 x 10(-6) M) and guanethidine (3 x 10(-6) M). The modifications of the NANC and sodium nitroprusside (SNP; 10(-5) M)-induced relaxation by the anesthetics were examined. The content of 3',5'-cyclic guanosine monophosphate (cGMP) was measured by radioimmunoassay.

Results

The KCl-induced relaxation was abolished by pretreating with tetrodotoxin (10(-6) M). The NANC relaxation was inhibited in the presence of N(G)-nitro-L-arginine (L-NNA; 3 x 10(-5) M), methylene blue (10(-6) M), apamin (10(-7) M), and glibenclamide (10(-5) M). The SNP-induced relaxation was inhibited by methylene blue but was not affected by tetrodotoxin, L-NNA, apamin, or glibenclamide. Ketamine (EC50 = 8.8 x 10(-5) M) and midazolam (EC50 = 4.8 x 10(-6) M) suppressed the NANC response in a concentration-dependent manner, leaving SNP-induced response unchanged. Thiopental altered neither of the relaxations. cGMP content was decreased in the presence of ketamine and midazolam.

Conclusion

The NANC relaxation was mediated by nitric oxide and by low-conductance calcium- and adenosine triphosphate-sensitive potassium channels of smooth muscle. The modulation of the nitric oxide-cGMP pathway was related, at least in part, to the inhibitory actions of ketamine and midazolam on the NANC LES relaxation.
Sedative but Not Analgesic α2Agonist Tolerance Is Blocked by NMDA Receptor and Nitric Oxide Synthase Inhibitors
Authors: Davies M. Frances , Reid Kristina , Guo Tian-Zhi , Agashe Geeta S. , Amin Yogen K. , Maze Mervyn
Published: November 2003

Background

Studies show that the sedative and analgesic effects of alpha2 adrenergic agonists decrease over time, which is a form of synaptic plasticity referred to as tolerance. Because both the N-methyl-D-aspartate (NMDA) receptor complex and nitric oxide synthase are pivotal for some forms of synaptic plasticity, their role in tolerance to the hypnotic and analgesic effects of alpha2 agonists was investigated.

Methods

After institutional approval, rats were made tolerant to the hypnotic or analgesic action of an alpha2 agonist, dexmedetomidine. The hypnotic response to dexmedetomidine was assessed by the duration of loss of righting reflex, and the analgesic response to dexmedetomidine was assessed by the tail-flick assay. In separate cohorts, either the NMDA receptors or nitric oxide synthase was antagonized by coadministration of MK-801, ketamine, or NO2-arginine, respectively, during induction of tolerance. In a separate series of experiments, after tolerance was induced, the hypnotic and analgesic responses to dexmedetomidine were assessed in the presence of acutely administered MK-801 or NO2-arginine.

Results

Induction of tolerance to the hypnotic effect of dexmedetomidine is blocked by coadministration of MK-801, ketamine, and NO2-arginine. However, after tolerance developed, acute administration of MK-801, ketamine, or NO2-arginine did not prevent the expression of tolerance. Coadministration of MK-801 or NO2-arginine neither prevents the development nor reverses the expression of tolerance to the analgesic action of dexmedetomidine.

Conclusion

The underlying processes responsible for the development of tolerance to the hypnotic and analgesic actions of systemically administered alpha2 agonists were different, with only the sedative tolerance involving the NMDA receptor and nitric oxide synthase system.
Venous Air Embolism during Endoscopic Strip Craniectomy for Repair of Craniosynostosis in Infants
Authors: Tobias Joseph D. , Johnson Joel O. , Jimenez David F. , Barone Constance M. , McBride D. Scott
Published: November 2003

Background

Various studies have reported an incidence of venous air embolism (VAE) as high as 82.6% during surgical procedures for craniosynostosis. There has been an increase in the use of minimally invasive, endoseopie surgical procedures, including applications for endoscopic strip craniectomy. The current study prospectively evaluated the incidence of VAF during endoscopic strip craniectomy.

Methods

Continuous, intraoperative monitoring for VAE was performed using precordial Doppler monitoring. A recording was made of the Doppler tones and later reviewed to verify its accuracy.

Results

The cohort for the study included 50 consecutive neonates and infants ranging in age from 3.5 to 36 weeks and ranging in weight from 3 to 9 kg. Surgical time varied from 31 to 95 min for a total of 2,701 mm of operating time, during which precordial Doppler tones were auscultated. In 46 patients, there was no evidence of VAE. In four patients, there was a single episode of VAE. Two of the episodes of VAE were grade I (change in Doppler tones), and two were grade H (change in Doppler tones and decrease in end-tidal carbon dioxide). No grade III (decrease in systolic blood pressure by 20% from baseline) VAF was noted.

Conclusion

In addition to previously reported benefits of decreased blood loss, decreased surgical time, and improved postoperative recovery time, the authors noted a low incidence of VAF during endoscopic strip craniectomy in neonates and infants.
Preoperative Intradermal Acupuncture Reduces Postoperative Pain, Nausea and Vomiting, Analgesic Requirement, and Sympathoadrenal Responses
Authors: Kotani Naoki , Hashimoto Hiroshi , Sato Yutaka , Sessler Daniel I. , Yoshioka Hideki , Kitayama Masatou , Yasuda Tadanobu , Matsuki Akitomo
Published: November 2003

Background

In a controlled and double-blind study, the authors tested the hypothesis that preoperative insertion of intradermal needles at acupoints 2.5 cm from the spinal vertebrae (bladder meridian) provide satisfactory postoperative analgesia.

Methods

The authors enrolled patients scheduled for elective upper and lower abdominal surgery. Before anesthesia, patients undergoing each type of surgery were randomly assigned to one of two groups: acupuncture (n = 50 and n = 39 for upper and lower abdominal surgery, respectively) or control (n = 48 and n = 38 for upper and lower abdominal surgery, respectively). In the acupuncture group, intradermal needles were inserted to the left and right of bladder meridian 18-24 and 20-26 in upper and lower abdominal surgery before induction of anesthesia, respectively. Postoperative analgesia was maintained with epidural morphine and bolus doses of intravenous morphine. Consumption of intravenous morphine was recorded. Incisional pain at rest and during coughing and deep visceral pain were recorded during recovery and for 4 days thereafter on a four-point verbal rating scale. We also evaluated time-dependent changes in plasma concentrations of cortisol and catecholamines.

Results

Starting from the recovery room, intradermal acupuncture increased the fraction of patients with good pain relief as compared with the control (P < 0.05). Consumption of supplemental intravenous morphine was reduced 50%, and the incidence of postoperative nausea was reduced 20-30% in the acupuncture patients who had undergone either upper or lower abdominal surgery (P < 0.01). Plasma cortisol and epinephrine concentrations were reduced 30-50% in the acupuncture group during recovery and on the first postoperative day (P < 0.01).

Conclusion

Preoperative insertion of intradermal needles reduces postoperative pain, the analgesic requirement, and opioid-related side effects after both upper and lower abdominal surgery. Acupuncture analgesia also reduces the activation of the sympathoadrenal system that normally accompanies surgery.
Role of the Atrial Natriuretic Factor in Obstetric Spinal Hypotension
Authors: Frölich Michael A.
Published: November 2003

Background

In recent years, the concept of prophylactic volume expansion to prevent hypotension caused by spinal anesthesia has been challenged. Investigators have reevaluated the concept of prehydration in the obstetric patient and the physiologic mechanisms involved. This article addresses whether the hypotensive effects attributed to the atrial natriuretic factor are the reason for the apparent failure of prehydration.

Methods

Atrial natriuretic factor was measured before (baseline) and 10 min after spinal anesthetic drug injection (control) in 48 healthy pregnant patients scheduled for elective cesarean section. Sixteen patients received hydration with 15 ml/kg crystalloid immediately before spinal anesthesia, 16 patients received the same volume starting with the spinal anesthetic injection, and the remaining 16 patients received no prehydration (control). Blood pressure, heart rate, ephedrine requirements, infused fluids, and urine output were measured.

Results

Atrial natriuretic factor concentrations increased significantly in prehydrated patients but not in the control group. There was a significant correlation in the change in atrial natriuretic factor concentrations and urine output but no correlation in the control atrial natriuretic factor concentrations and blood pressure or ephedrine requirements. Ephedrine requirements and blood pressure did not differ significantly among study groups.

Conclusions

Atrial natriuretic factor is a potent endogenous diuretic in the pregnant patient but does not appear to be involved in short-term cardiovascular homeostasis after spinal anesthesia. Prehydration appears to be an ineffective measure to prevent post spinal hypotension in the obstetric patient [corrected].
Allosteric Adenosine Modulation to Reduce Allodynia
Authors: Pan Hui-Lin , Xu Zemin , Leung Edward , Eisenach James C.
Published: November 2003

Background

Adenosine and adenosine agonists reduce hypersensitivity following inflammation and peripheral nerve injury models of chronic pain. Because inhibitors of adenosine reuptake or metabolism are also effective at reducing hypersensitivity, it is likely that there is a tonic release of spinal adenosine in these models. One approach to avoid adverse effects from direct agonists is to enhance the effect of the endogenous ligand by administering a positive allosteric modulator of its receptor.

Methods

Rats with mechanical hypersensitivity after spinal nerve ligation received intrathecal injections of adenosine, the allosteric adenosine receptor modulator T62, or their combination, or received systemic T62 alone or with intrathecal injection of a specific A1 adenosine antagonist.

Results

Both adenosine and T62 reduced hypersensitivity alone, with 50% maximal doses (ED50) of 14+/-5.9 and 3.7+/-0.8 microg, respectively. They interacted in an additive manner as determined by isobolography. T62 also reduced mechanical hypersensitivity after systemic administration (15 mg/kg), and this effect was blocked by intrathecal injection of 9 microg of the A1-specific adenosine receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine.

Conclusions

These results add to previous studies that suggest ongoing spinal release of adenosine, which is antiallodynic, in this animal model of neuropathic pain. Positive allosteric modulation of the adenosine receptor reduces hypersensitivity by a spinal mechanism involving A1 adenosine receptor stimulation. Although obvious adverse effects were not observed in this investigation, further study is required to determine the feasibility of the use of such modulators in the treatment of chronic pain associated with hyperalgesia and allodynia.
Neuroprotective Effect of Low-dose Lidocaine in a Rat Model of Transient Focal Cerebral Ischemia
Authors: Lei Baiping , Cottrell James E. , Kass Ira S.
Published: November 2003

Background

A low concentration of lidocaine (10 microM) has been shown to reduce anoxic damage in vitro. The current study examined the effect of low-dose lidocaine on infarct size in rats when administered before transient focal cerebral isehemia.

Methods

Male Wistar rats (weight, 280-340 g) were anesthetized with isoflurane, intubated, and mechanically ventilated. After surgical preparation, animals were assigned to lidocaine 2-day (n = 10), vehicle 2-day (n 12), lidocaine 7-day (n = 13), and vehicle 7-day (n = 14) groups. A 1.5-mg/kg bolus dose of ildocaine was injected intravenously 30 mm before isehemia in the lidocaine 2-day and 7-day groups. Thereafter, an infusion was initiated at a rate of 2 mg x kg(-1) x h(-1) until 60 min of reperfusion after isehemia. Rats were subjected to 90 min of focal cerebral isehemia using the intraluminal suture method. Infarct size was determined by image analysis of 2,3,5-triphenyltetrazolium chloride-stained sections at 48 h or hematoxylin and eosin-stained sections 7 days after reperfusion. Neurologic outcome and body weight loss were also evaluated.

Results

The infarct size was significantly smaller in the lidocaine 2-day group (185.0+/-43.7 mm3) than in the vehicle 2-day group (261.3+/-45.8 mm3, P < 0.01). The reduction in the size of the infarct in the lidocaine 7-day group (130.4+/-62.9 mm3) was also significant compared with the vehicle 7-day group (216.6+/-73.6 mm3, P < 0.01). After 7 days of reperfusion, the rats in the lidocaine group demonstrated better neurologic outcomes and less weight loss.

Conclusions

The current study demonstrated that a clinical anriarrhythmic dose of lidocaine, when given before and during transient focal cerebral isehemia, significantly reduced infaret size, improved neurologic outcome, and inhibited postisehemic weight loss.
Mechanisms of Direct Inhibitory Action of Ketamine on Vascular Smooth Muscle in Mesenteric Resistance Arteries
Authors: Akata Takashi , Izumi Kaoru , Nakashima Mikio
Published: November 2003

Background

Ketamine was previously suggested to relax vascular smooth muscle by reducing the intracellular Ca2+ concentration ([Ca2+]i). However, no direct evidence is available to indicate that ketamine reduces the [Ca2+]i in vascular smooth muscle of systemic resistance arteries.

Methods

Endothelium-intact or -denuded smooth muscle strips were prepared from rat small mesenteric arteries. Isometric force and [Ca2+]i were measured simultaneously in the fura-2-loaded, endothelium-denuded strips. In some experiments, only isometric force was measured in either the endothelium-intact or beta-escin-treated, endothelium-denuded strips.

Results

In the endothelium-intact strips, lower concentrations (< or = 30 microm) of ketamine slightly enhanced norepinephrine-induced contraction, whereas higher concentrations (> or = 100 microM) of ketamine inhibited both norepinephrine- and KCl-induced contractions. In the fura-2-loaded strips, ketamine (> or = 100 microM) inhibited the increases in both [Ca2+]i and force induced by either norepinephrine or KCl. Ketamine also inhibited the norepinephrine-induced increase in [Ca2+]i after treatment with ryanodine. In the absence of extracellular Ca2+, ketamine notably inhibited the norepinephrine-induced increase in [Ca2+]i, whereas it only minimally inhibited caffeine-induced increase in [Ca2+]i. Ketamine had little influence on the [Ca2+]i-force relation during force development to stepwise increment of extracellular Ca2+ concentration during either KCl depolarization or norepinephrine stimulation. Ketamine did not affect Ca2+-activated contractions in the beta-escin membrane-permeabilized strips.

Conclusions

The action of ketamine on contractile response to norepinephrine consists of endothelium-dependent vasoconstricting and endothelium-independent vasodilating components. The direct vasorelaxation is largely a result of reduction of[Ca2+]i in vascular smooth muscle cells. The [Ca2+]i-reducing effects are caused by inhibitions of both voltage-gated Ca2+ influx and norepinephrine-induced Ca2+ release from the intracellular stores.
Acute Pain Induces Insulin Resistance in Humans
Authors: Greisen Jacob , Juhl Claus B. , Grøfte Thorbjørn , Vilstrup Hendrik , Jensen Troels S. , Schmitz Ole
Published: November 2003

Background

Painful trauma results in a disturbed metabolic state with impaired insulin sensitivity, which is related to the magnitude of the trauma. The authors explored whether pain per se influences hepatic and extrahepatic actions of insulin.

Methods

Ten healthy male volunteers underwent two randomly sequenced hyperinsulinemic-euglycemic (insulin infusion rate, 0.6 mU x kg(-1) x min(-1) for 180 min) clamp studies 4 weeks apart. Self-controlled painful electrical stimulation was applied to the abdominal skin for 30 min, to a pain intensity of 8 on a visual analog scale of 0-10, just before the clamp procedure (study P). In the other study, no pain was inflicted (study C).

Results

Pain reduced whole-body insulin-stimulated glucose uptake from 6.37+/-1.87 mg x kg(-1) x min(-1) (mean +/- SD) in study C to 4.97+/-1.38 mg x kg(-1) x min(-1) in study P (P < 0.01) because of a decrease in nonoxidative glucose disposal, as determined by indirect calorimetry (2.47+/-0.88 mg x kg(-1) x min(-1) in study P vs. 3.41+/-1.03 mg x kg(-1) x min(-1) in study C; P < 0.05). Differences in glucose oxidation rates were not statistically significant. The suppression of isotopically determined endogenous glucose output during hyperinsulinemia tended to be decreased after pain (1.67+/-0.48 mg x kg(-1) x min(-1) in study P vs. 2.04+/-0.45 mg x kg(-1) x min(-1) in study C; P = 0.06). Pain elicited a twofold to threefold increase in serum cortisol (P < 0.01), plasma epinephrine (P < 0.05), and serum free fatty acids (P < 0.05). Similarly, circulating concentrations of glucagon and growth hormone tended to increase during pain.

Conclusions

Acute severe pain decreases insulin sensitivity, primarily by affecting nonoxidative glucose metabolism. It is conceivable that the counterregulatory hormonal response plays an important role. This may indicate that pain relief in stress states is important for maintenance of normal glucose metabolism.
North American Malignant Hyperthermia Population
Authors: Sambuughin Nyamkhishig , Sei Yoshitatsu , Gallagher Kathleen L. , Wyre Hadley W. , Madsen Daniel , Nelson Thomas E. , Fletcher Jeffrey E. , Rosenberg Henry , Muldoon Sheila M.
Published: November 2003

Background

Malignant hyperthermia (MH) is a disorder of skeletal muscle manifested as a life-threatening hypermetabolic crisis in susceptible individuals after exposure to inhalational anesthetics and depolarizing muscle relaxants. Mutations in the gene encoding the skeletal muscle ryanodine receptor (RYR1) are considered a common cause of the disorder, and, to date, more than 20 RYR1 mutations have been reported in European and Canadian families. Some studies suggest that differences may exist in the frequencies and distribution of mutations in the RYR1 gene between European and North American MH families the frequency and distribution of mutations in the RYR1 gene.

Methods

Skeletal muscle samples from 73 unrelated individuals diagnosed as MH susceptible according to the North American MH caffeine-halothane contracture test were studied. Genomic DNA of MH-susceptible patients was investigated by polymerase chain reaction-based restriction fragment length polymorphism, single-strand conformation polymorphism, and sequencing analysis. The majority of known RYR1 mutations were analyzed using the restriction fragment length polymorphism method, whereas new mutations were searched by single-strand conformation polymorphism in exons 12, 15, 39, 40, 44, 45, and 46 of the gene.

Results

Seven known RYR1 mutations (Arg163Cys, Gly248Arg, Arg614Cys, Val2168Met, Thr2206Met, Gly2434Arg, and Arg2454His) were detected at frequencies of 2.7, 1.4, 1.4, 1.4, 1.4, 5.5, and 4.1%, respectively. In addition, three novel amino acid substitutions (Val2214Ile, Ala2367Thr, and Asp2431Asn) were detected at frequency of 1.4% each. These 10 mutations account for 21.9% of the North American MH-susceptible population.

Conclusion

Three novel candidate mutations in the RYR1 gene were identified in these MH patients. The frequency and distribution of RYR1 mutations observed in this North American MH population was markedly different from that previously identified in Europe. Larger-scale studies are necessary to clarify the type and frequency of mutations in RYR1 associated with MH in North American families.
Response to Mivacurium in a Patient Compound Heterozygous for a Novel and a Known Silent Mutation in the Butyrylcholinesterase Gene
Authors: Gätke Mona R. , Østergaard Doris , Bundgaard Jens R. , Varin France , Viby-Mogensen Jørgen
Published: November 2003

Background

Patients who are homozygous for the atypical mutation, compound heterozygous for atypical and silent mutations, or homozygous for silent mutations (SS) respond to mivacurium with extensively prolonged neuromuscular block. Although important, exact phenotyping of these patients is difficult. This article presents the pharmacodynamics and pharmacokinetics of a normal dose of mivacurium in a patient with phenotype SS, including a pedigree analysis and delineation of the molecular genetic method used to identify the genotype.

Methods

The neuromuscular block following administration of mivacurium, at a dose of 0.14 mg/kg, was monitored in a 30-yr-old healthy man with use of a mechanosensor and mechanomyography, and times to different levels of recovery were measured. Venous samples for determination of the mivacurium isomers were collected during the interval 134-494 min after administration of mivacurium, and the terminal half-lives were calculated. Butyrylcholinesterase activity, phenotype, and genotype were determined for both the patient and the family. Complete nucleotide sequencing was used to identify the genotype.

Results

A train-of-four ratio of 0.75 was reached 469 min after the injection of mivacurium. The terminal elimination half-lives of the mivacurium isomers, cis-trans and trans-trans, were 90 min. Complete nucleotide sequencing revealed two point mutations, the known silent variant S7 and a previously undescribed mutation of amino acid residue 170 introducing a stop codon.

Conclusions

The patient was compound heterozygous for silent mutations in the butyrylcholinesterase gene. The response to mivacurium was an extensively prolonged duration of action. Identification of the rare silent mutations presupposes access to modern molecular genetic methods such as complete nucleotide sequencing.
Clinical Experience of Percutaneous Femoral Venous Catheterization in Critically Ill Preterm Infants Less Than 1,000 Grams
Authors: Chen Kuen-Bao
Published: November 2003

Background

Venous access is relatively difficult in preterm infants. Central venous catheterization is indicated for pressure monitoring, drug therapy, and nutrition supplementation, which are often critical in the anesthetic management of infants undergoing major surgery.

Methods

In 49 critically ill preterm infants weighing less than 1,000 g, the femoral vein was cannulated using a 22-gauge Angiocath (25 mm; Beckton Dickinson, Sandy, UT). A 2.5-ml syringe was attached to the Angiocath, and the Angiocath was advanced with constant negative pressure over the syringe. When blood return was observed, the cannula was advanced. When free blood reflux was achieved, a J wire was inserted, followed by a 24-gauge central venous catheter.

Results

The overall catheterization success rate was 79.6% (39 of 49 attempts). The time required for successful catheterization was less than 10 min in 18 cases (46.2%), 10-20 min in 17 cases (43.6%), and 20-30 min in 4 cases (10.3%). In the successful group, 1 catheter tip was positioned in the vein of the liver (2.6%), 2 were in the common iliac vein (5.1%), 6 were in the right atrium (15.4%), and 30 were in the infracardiac inferior vena cava (76.9%). Complications included hematoma in six cases (12.2%), arterial puncture in five cases (10.2%), bleeding in two cases (4.1%), and transient bradycardia in two cases (4.1%).

Conclusions

The results indicate that percutaneous femoral venous catheterization is a reliable and valuable technique for critically ill preterm infants weighing less than 1,000 g.
Hemodynamic and Catecholamine Responses to Laryngoscopy and Tracheal Intubation in Patients with Complete Spinal Cord Injuries
Authors: Yoo Kyung Y. , Lee JongUn , Kim Hak S. , Im Woong M.
Published: November 2003

Background

Endotracheal intubation in patients undergoing general anesthesia often causes hypertension and tachycardia, which may be altered when the efferent sympathetic fiber to the cardiovascular system is interrupted. The aim of the current study was to investigate the effects of different levels of spinal cord injury on the cardiovascular responses to intubation.

Methods

Fifty-four patients with traumatic complete cord injuries requiring tracheal intubation were grouped into quadriplegics (above C7; n = 22), high paraplegics (T1-T4, n = 8), and low paraplegics (below T5, n = 24) according to the level of injury. Twenty patients without spinal injury served as controls. Arterial pressure, heart rate, and rhythm were recorded at intervals for up to 5 min after intubation. Plasma concentrations of catecholamines were also measured.

Results

The intubation increased the systolic blood pressure similarly in control, high-paraplegic, and low-paraplegic groups (P < 0.05), whereas it did not alter the blood pressure in the quadriplegic group. Heart rate was significantly increased in all groups; however, the magnitude was more pronounced in the high-paraplegic group (67%) than in the control (38%) and quadriplegic (33%) groups. Plasma concentrations of norepinephrine were significantly increased after intubation in all groups; however, values were lower in the quadriplegic group and higher in the low-paraplegic group compared with those in the control group. Incidence of arrhythmias did not differ among groups.

Conclusions

The cardiovascular and plasma catecholamine changes associated with endotracheal intubation may differ according to the affected level in patients with complete spinal cord injuries.
Direct Neurotoxicity of Tetracaine on Growth Cones and Neurites of Growing Neurons In Vitro
Authors: Saito Shigeru , Radwan Inas , Obata Hideaki , Takahashi Kenichiro , Goto Fumio
Published: November 2003

Background

Local anesthetics have direct neurotoxicity on neurons. However, precise morphologic changes induced by the direct application of local anesthetics to neurons have not yet been fully understood. Also, despite the fact that local anesthetics are sometimes applied to the sites where peripheral nerves may be regenerating after injury, the effects of local anesthetics on growing or regenerating neurons have never been studied.

Methods

Three different neuronal tissues (dorsal root ganglion, retinal ganglion cell layer, and sympathetic ganglion chain) were isolated from an age-matched chick embryo and cultured for 20 h. Effects of tetracaine were examined microscopically and by a quantitative morphologic assay, growth cone collapse assay.

Results

Tetracaine induced growth cone collapse and neurite destruction. Three neuronal tissues showed significantly different dose-response, both at 60 min and at 24 h after the application of tetracaine (P < 0.01). The ED50 values (mean +/- SD) at 60 min were 1.53+/-1.05 mM in dorsal root ganglion, 0.15+/-0.05 mM in retinal, and 0.06+/-0.02 mM in sympathetic ganglion chain cultures. The ED50 values at 24 h were 0.43+/-0.15 mM in dorsal root ganglion, 0.07+/-0.03 mM in retinal, and 0.02+/-0.01 mM in sympathetic ganglion chain cultures. Concentration of nerve growth factor in the culture media did not influence the ED50 values. The growth cone collapsing effect was partially reversible in dorsal root ganglion and retinal neurons. However, in the sympathetic ganglion culture, no reversibility was observed after exposure to 1 mM tetracaine for 10 or for 60 min. Bupivacaine had similar neurotoxicity to the three types of growing neurons. (The ED50 values at 60 min were 2.32+/-0.50 mM in dorsal root ganglion, 0.96+/-0.16 mM in retinal, and 0.18+/-0.05 mM in sympathetic ganglion chain cultures. The ED50 values at 24 h were 0.34+/-0.09 mM in dorsal root ganglion, 0.21+/-0.06 mM in retinal, and 0.45+/-0.10 mM in sympathetic ganglion chain cultures.)

Conclusions

Short-term exposure to tetracaine produced irreversible changes in growing neurons. Growth cones were quickly affected, and neurites degenerated subsequently. Sensitivity varied with neuronal type and was not influenced by the concentration of nerve growth factor. Because a similar phenomenon was observed after exposure to bupivacaine, the toxicity to growing neurons may not be unique to tetracaine.
Only Carbon Dioxide Absorbents Free of Both NaOH and KOH Do Not Generate Compound A during In Vitro Closed-system Sevoflurane
Authors: Versichelen Linda F. M. , Bouche Marie-Paule L. A. , Rolly Georges , Van Bocxlaer Jan F. P. , Struys Michel M. R. F. , De Leenheer André P. , Mortier Eric P.
Published: November 2003

Background

Insufficient data exist on the production of compound A during closed-system sevoflurane administration with newer carbon dioxide absorbents.

Methods

A modified PhysioFlex apparatus (Dräger, Lübeck, Germany) was connected to an artificial test lung (inflow at the top of the bellow approximately/= 160 ml/min CO2; outflow at the Y piece of the lung model approximately/= 200 ml/min, simulating oxygen consumption). Ventilation was set to obtain an end-tidal carbon dioxide partial pressure of approximately 40 mmHg. Various fresh carbon dioxide absorbents were used: Sodasorb (n = 6), Sofnolime (n = 6), and potassium hydroxide (KOH)-free Sodasorb (n = 7), Amsorb (n = 7), and lithium hydroxide (n = 7). After baseline analysis, liquid sevoflurane was injected into the circuit by syringe pump to obtain 2.1% end-tidal concentration for 240 min. At baseline and at regular intervals thereafter, end-tidal carbon dioxide partial pressure, end-tidal sevoflurane concentration, and canister inflow (T degrees(in)) and canister outflow (T degrees(out)) temperatures were measured. To measure compound Ainsp concentration in the inspired gas of the breathing circuit, 2-ml gas samples were taken and analyzed by capillary gas chromatography plus mass spectrometry.

Results

The median (minimum-maximum) highest compound Ainsp concentrations over the entire period were, in decreasing order: 38.3 (28.4-44.2)* (Sofnolime), 30.1 (23.9-43.7) (KOH-free Sodasorb), 23.3 (20.0-29.2) (Sodasorb), 1.6 (1.3-2.1)* (lithium hydroxide), and 1.3 (1.1-1.8)* (Amsorb) parts per million (*P < 0.01 vs. Sodasorb). After reaching their peak concentration, a decrease for Sofnolime, KOH-free Sodasorb, and Sodasorb until 240 min was found. The median (minimum-maximum) highest values for T degrees(out) were 39 (38-40), 40 (39-42), 41 (40-42), 46 (44-48)*, and 39 (38-41) degrees C (*P < 0.01 vs. Sodasorb), respectively.

Conclusions

With KOH-free (but sodium hydroxide [NaOH]-containing) soda limes even higher compound A concentrations are recorded than with standard Sodasorb. Only by eliminating KOH as well as NaOH from the absorbent (Amsorb and lithium hydroxide) is no compound A produced.
Randomized Study Comparing the “Sniffing Position” with Simple Head Extension for Laryngoscopic View in Elective Surgery Patients
Authors: Adnet Frédéric , Baillard Christophe , Borron Stephen W. , Denantes Christophe , Lefebvre Laurent , Galinski Michel , Martinez Carmen , Cupa Michel , Lapostolle Frédéric
Published: November 2003

Background

The "sniffing position" is recommended for optimization of glottic visualization under direct laryngoscopy. However, no study to date has confirmed its superiority over simple head extension. In a prospective, randomized study, the authors compared the sniffing position with simple head extension in orotracheal intubation.

Methods

The study included 456 consecutive patients. The sniffing position was obtained by placement of a 7-cm cushion under the head of the patient. The extension position was obtained by simple head extension. The anesthetic procedure included two Laryngoscopies without paralysis: the first was used for topical glottic anesthesia. During the second direct laryngoscopy, intubation of the trachea was performed. The head position was randomized as follows: group A was in the sniffing position during the first Laryngoscopy and the extension position during the second, group B was in the extension position during the first laryngoscopy and the sniffing position during the second. Glottic exposure was assessed by the Cormack scale.

Results

The sniffing position improved glottic exposure (decreased the Cormack grade) in 18% of patients and worsened it (increased the Cormack grade) in 11% of patients, in comparison with simple extension. The Cormack grade distribution was not significantly modified between the two groups. Multivariate analysis showed that reduced neck mobility and obesity were independently related to improvement in laryngoscopic view with application of the sniffing position.

Conclusions

Routine use of the sniffing position appears to provide no significant advantage over simple head extension for tracheal intubation in this setting. The sniffing position appears to be advantageous in obese and head extension-limited patients.
Drug-induced Amnesia Is a Separate Phenomenon from Sedation
Authors: Veselis Robert A. , Reinsel Ruth A. , Feshchenko Vladimir A.
Published: November 2003

Background

Sedative-hypnotic drugs not only increase sedation, but also impair memory as serum concentration increases. These drugs also produce profound changes in the auditory event-related potential (ERP). The ability of various ERP components to predict changes in sedation and memory produced by various drugs was tested.

Methods

Sixty-five healthy volunteers randomly received intravenous placebo, midazolam, propofol, thiopental, fentanyl with ondansetron, or ondansetron alone at five different stable target concentrations (three increasing, two decreasing) using a computer-controlled infusion pump to produce varying degrees of sedation without loss of consciousness. ERPs were recorded while volunteer participants detected a deviant auditory stimulus and made a button-press response to a target tone (standard oddball paradigm, 80:20 ratio, to elicit a P3 response). At each target concentration, volunteers learned a list of 16 words. The predictive probabilities (Pk) of various ERP components were determined for word recognition at the end of the day (memory) and log reaction time to the deviant stimulus (sedation).

Results

The N2 latency of the ERP consistently predicted log reaction time in all groups (Pk +/- SE from 0.58 +/- 0.04 to 0.71 +/- 0.04). The N2P3 amplitude of the ERP was the best predictor of memory performance for midazolam (Pk, 0.63 +/- 0.04), propofol (Pk, 0.62 +/- 0.05), and thiopental (Pk, 0.66 +/- 0.04). There was a differential ability to predict memory performance from sedation for midazolam and propofol.

Conclusions

Midazolam and propofol affect memory differentially from their sedative effects, and these are indexed by specific components of the auditory ERP. These components of the ERP are associated with specific, but not necessarily unique, neuroanatomic structures. Thus, these drugs act by additional mechanisms beyond general central nervous system depression to produce the effects of sedation and memory impairment.
Combined Spinal–Epidural versus Epidural Labor Analgesia
Authors: Norris Mark C. , Fogel Steven T. , Conway-Long Carol
Published: November 2003

Background

Despite the growing popularity of combined spinal-epidural analgesia in laboring women, the exact role of intrathecal opioids and the needle-through-needle technique remains to be determined. The authors hypothesized that anesthetic technique would have little effect on obstetric outcome or anesthetic complications.

Methods

Data were prospectively collected from 2,183 laboring women randomly assigned to have labor analgesia induced with either 10 microg intrathecal sufentanil with or without 2.0 mg bupivacaine (n = 1,071) or 10 microg epidural sufentanil and 12.5-25.0 mg bupivacaine (n = 1,112). Immediately after induction, a continuous epidural infusion of 0.083% bupivacaine plus 0.3 microg/ml sufentanil was begun in all patients and continued until delivery. Labor was managed by nurses, obstetricians, and obstetric residents who were unaware of the anesthetic technique used.

Results

Anesthetic technique lacked impact on our primary outcome: mode of delivery or labor duration. Infants whose mothers were allocated to the combined spinal-epidural group had a slightly higher umbilical artery carbon dioxide partial pressure (54.2 +/- 10.4 vs. 53.2 +/- 10.2 mmHg). However, only achieving at least 5 cm cervical dilation before induction of analgesia and having a cesarean delivery were independent risk factors for elevated umbilical artery carbon dioxide partial pressure. The frequencies of accidental dural puncture, failed epidural analgesia, headache, and epidural blood patch were low and similar in the two groups.

Conclusions

Labor progress and outcome are similar among women receiving either combined spinal-epidural or epidural analgesia. The difference in neonatal outcome appears related to the presence of confounding variables. The combined spinal-epidural technique is not associated with an increased frequency of anesthetic complications. Either technique can safely provide effective labor analgesia.