bluuebunny/crossref_metadata_2025_split huggingface dataset:
Influence of Respiratory Rate on Stroke Volume Variation in Mechanically Ventilated Patients
Authors: De Backer Daniel , Taccone Fabio Silvio , Holsten Roland , Ibrahimi Fayssal , Vincent Jean-Louis 
Published: May 2009

Background
Heart-lung interactions are used to evaluate fluid responsiveness in mechanically ventilated patients, but these indices may be influenced by ventilatory conditions. The authors evaluated the impact of respiratory rate (RR) on indices of fluid responsiveness in mechanically ventilated patients, hypothesizing that pulse pressure variation and respiratory variation in aortic flow would decrease at high RRs.

Methods
In 17 hypovolemic patients, thermodilution cardiac output and indices of fluid responsiveness were measured at a low RR (14-16 breaths/min) and at the highest RR (30 or 40 breaths/min) achievable without altering tidal volume or inspiratory/expiratory ratio.

Results
An increase in RR was accompanied by a decrease in pulse pressure variation from 21% (18-31%) to 4% (0-6%) (P < 0.01) and in respiratory variation in aortic flow from 23% (18-28%) to 6% (5-8%) (P < 0.01), whereas respiratory variations in superior vena cava diameter (caval index) were unaltered, i.e., from 38% (27-43%) to 32% (22-39%), P = not significant. Cardiac index was not affected by the changes in RR but did increase after fluids. Pulse pressure variation became negligible when the ratio between heart rate and RR decreased below 3.6.

Conclusions
Respiratory variations in stroke volume and its derivates are affected by RR, but caval index was unaffected. This suggests that right and left indices of ventricular preload variation are dissociated. At high RRs, the ability to predict the response to fluids of stroke volume variations and its derivate may be limited, whereas caval index can still be used.
Effect of Flumazenil on Bispectral Index Monitoring in Unpremedicated Patients
Authors: Dahaba Ashraf A. , Bornemann Helmar , Rehak Peter H. , Wang Geng , Wu Xin Min , Metzler Helfried 
Published: May 2009

Background
Flumazenil is an imidazobenzodiazepine that promptly reverses via competitive inhibition the hypnotic/sedative effects of benzodiazepines on gamma-aminobutyric acid receptors. Endogenous benzodiazepine ligands (endozepines) were isolated in urine, cerebrospinal fluid, and breast milk of women who had not received benzodiazepines. The bispectral index (BIS), an electroencephalographically derived parameter widely used for monitoring the effects of anesthetic/hypnotic drugs, was shown to correlate to various conditions that could influence electroencephalography. The authors examined the hypothesis that 0.5 mg of flumazenil administered to healthy unpremedicated patients during deep surgical remifentanil/propofol anesthesia would increase the BIS value and might expedite recovery from anesthesia.

Methods
Sixty healthy unpremedicated patients were randomly allocated to the flumazenil or control groups. After study drug administration, the authors compared BIS values and various recovery parameters in the flumazenil and control groups.

Results
BIS baseline values in the flumazenil group (38.7 +/- 3.8) increased 15 min after flumazenil administration (53.2 +/- 4.7), with a significant difference over time (P < 0.0001) between the two groups. Mean recovery parameters time, comprising time to spontaneous breathing, eye opening/hand squeezing on verbal command, extubation, and date of birth recollection, was significantly shorter (P = 0.0002) in the flumazenil group (6.9 +/- 2.6 min) compared with the control group (9.8 +/- 2.9 min).

Conclusions
This study demonstrates that flumazenil given to healthy unpremedicated patients during propofol/remifentanil anesthesia significantly increased the BIS value and allowed earlier emergence from anesthesia. This may indicate that flumazenil could be used on a case-by-case basis to reverse endogenous or exogenous endozepines that might play a role during anesthesia.
Individual Probability of Allogeneic Erythrocyte Transfusion in Elective Spine Surgery
Authors: Lenoir Brigitte , Merckx Paul , Paugam-Burtz Catherine , Dauzac Cyril , Agostini Marie-Madeleine , Guigui Pierre , Mantz Jean 
Published: May 2009

Background
The aim of this study was to generate a score based on preoperative characteristics and predictive of the individual probability of allogeneic erythrocyte transfusion in patients undergoing elective thoracolumbar spine surgery.

Methods
Two hundred thirty consecutive patients were retrospectively included over a 15-month period (derivation set). Preoperative independent predictors of erythrocyte transfusion from the day of surgery until postoperative day 5 were determined by multivariable analysis, from which a model of individual probability of transfusion was derived and prospectively validated in 125 additional patients (validation set).

Results
Four preoperative independent predictors were associated with transfusion: age older than 50 yr (adjusted odds ratio = 4.9 [2-13.5]), preoperative hemoglobin level less than 12 g/dl (adjusted odds ratio = 6.9 [3.1-17.2]), fusion of more than two levels (adjusted odds ratio = 6.7 [3.1-15.2]), and transpedicular osteotomy (adjusted odds ratio = 19.9 [5.6-98.2]). A 0-4 score (0 = no risk, 4 = maximum risk) predictive of allogeneic transfusion was derived by weighting estimate parameters for each variable in a multivariable logistic regression model. Discriminating capacity of the score was 0.86 [0.81-0.92] in the receiver operating characteristics in the derivation sample and 0.83 [0.75-0.91] in the validation sample. The observed transfusion rates in the validation set and the individual probabilities of erythrocyte transfusion from the score were well correlated (y = 0.98x + 0.04; P < 0.0001), and the observed differences were not statistically different (goodness-of-fit chi-square, P = 0.125). The score was also correlated with the number of erythrocyte units transfused (Spearman rho = 0.61; P < 0.0001).

Conclusion
The Predictive Model of Transfusion in Spine Surgery may be useful in clinical practice to identify patients undergoing spine surgery at risk of massive bleeding and encourage erythrocyte-saving strategies in these patients.
Ampakine CX717 Protects against Fentanyl-induced Respiratory Depression and Lethal Apnea in Rats
Authors: Ren Jun , Ding Xiuqing , Funk Gregory D. , Greer John J. 
Published: May 2009

Background
The use of fentanyl as a potent analgesic is contradicted by marked respiratory depression among a subpopulation of patients. The commonly used approach of reversing fentanyl-induced respiratory depression with mu-opiate receptor antagonists such as naloxone has the undesirable effect of blocking analgesia. Here, the authors report a clinically feasible pharmacological solution for countering fentanyl-induced respiratory depression via a mechanism that does not interfere with analgesia. Specifically, to determine if the ampakine CX717, which has been proven metabolically stable and safe for human use, can prevent and rescue from severe fentanyl-induced apnea.

Methods
Plethsymographic recordings were performed from young and adult rats. Varying doses of fentanyl were administered either intraperitoneally or intravenously to induce moderate to life-threatening apneas. CX717 was administered either before or after fentanyl administration. In addition, phrenic nerve recordings were performed from in situ working heart brainstem preparations from juvenile rats.

Results
Preadministration of CX717 markedly attenuated fentanyl-induced respiratory depression. Postadministration of CX717 rescued animals from a lethal dose of fentanyl. Significantly, CX717 countered fentanyl-induced depression of respiratory frequency without suppressing analgesia. The effective dose of CX717 was in the range deemed safe on the basis of clinical trials examining its efficacy for cognitive disorders. In situ, fentanyl-induced depression in respiratory frequency and amplitude was alleviated by CX717.

Conclusions
CX717 is an agent that enhances the safety of using opiate drugs while preserving the analgesic effects. This advancement could significantly improve pain management in a variety of clinical settings.
Rifampin Greatly Reduces the Plasma Concentrations of Intravenous and Oral Oxycodone
Authors: Nieminen Tuija H. , Hagelberg Nora M. , Saari Teijo I. , Pertovaara Antti , Neuvonen Mikko , Laine Kari , Neuvonen Pertti J. , Olkkola Klaus T. 
Published: May 2009

Background
Oxycodone is a mu-opioid receptor agonist that is metabolized mainly in the liver by cytochrome P450 3A and 2D6 enzymes. Rifampin is a strong inducer of several drug-metabolizing enzymes. The authors studied the interaction of rifampin with oxycodone. Their hypothesis was that rifampin enhances the CYP3A-mediated metabolism of oxycodone and attenuates its pharmacologic effect.

Methods
The protocol was a four-session, paired crossover. Twelve volunteers were given 600 mg oral rifampin or placebo once daily for 7 days. Oxycodone was given on day 6. In the first part of the study, 0.1 mg/kg oxycodone hydrochloride was given intravenously. In the second part of the study, 15 mg oxycodone hydrochloride was given orally. Concentrations of oxycodone and its metabolites noroxycodone, oxymorphone, and noroxymorphone were determined for 48 h. Psychomotor effects were characterized for 12 h by several visual analog scales. Analgesic effects were characterized by measuring the heat pain threshold and cold pain sensitivity.

Results
Rifampin decreased the area under the oxycodone concentration-time curve of intravenous and oral oxycodone by 53% and 86%, respectively (P < 0.001). Oral bioavailability of oxycodone was decreased from 69% to 21% (P < 0.001). Rifampin greatly increased the plasma metabolite-to-parent drug ratios for noroxycodone and noroxymorphone (P < 0.001). Pharmacologic effects of oral oxycodone were attenuated.

Conclusions
Induction of cytochrome P450 3A by rifampin reduced the area under the oxycodone concentration-time curve of intravenous and oral oxycodone. The pharmacologic effects of oxycodone were modestly attenuated. To maintain adequate analgesia, dose adjustment of oxycodone may be necessary, when used concomitantly with rifampin.
Impaired Upper Airway Integrity by Residual Neuromuscular Blockade: Increased Airway Collapsibility and Blunted Genioglossus Muscle Activity in Response to Negative Pharyngeal Pressure
Authors: Herbstreit Frank , Peters Jürgen , Eikermann Matthias 
Published: May 2009

Background
Residual neuromuscular blockade increases the risk to develop postoperative complications. The authors hypothesized that minimal neuromuscular blockade (train-of-four [TOF] ratio 0.5-1) increases upper airway collapsibility and impairs upper airway dilator muscle compensatory responses to negative pharyngeal pressure challenges.

Methods
Epiglottic and nasal mask pressures, genioglossus electromyogram, respiratory timing, and changes in lung volume were measured in awake healthy volunteers (n = 15) before, during (TOF = 0.5 and 0.8 [steady state]), and after recovery of TOF to unity from rocuronium-induced partial neuromuscular blockade. Passive upper airway closing pressure (negative pressure drops, random order, range +2 to -30 cm H2O) and pressure threshold for flow limitation were determined.

Results
Upper airway closing pressure increased (was less negative) significantly from baseline by 54 +/- 4.4% (means +/- SEM), 37 +/- 4.2%, and 16 +/- 4.1% at TOF ratios of 0.5, 0.8, and 1.0, respectively (P < 0.01 vs. baseline for any level). Phasic genioglossus activity almost quadrupled in response to negative (-20 cm H2O) pharyngeal pressure at baseline, and this increase was significantly impaired by 57 +/- 44% and 32 +/- 6% at TOF ratios of 0.5 and 0.8, respectively (P < 0.01 vs. baseline). End-expiratory lung volume, respiratory rate, and tidal volume did not change.

Conclusion
Minimal neuromuscular blockade markedly increases upper airway closing pressure, partly by impairing the genioglossus muscle compensatory response. Increased airway collapsibility despite unaffected values for resting ventilation may predispose patients to postoperative respiratory complications, particularly during airway challenges.
Pharmacological Characteristics of the Inhibition of Nondepolarizing Neuromuscular Blocking Agents at Human Adult Muscle Nicotinic Acetylcholine Receptor
Authors: Fagerlund Malin Jonsson , Dabrowski Michael , Eriksson Lars I. 
Published: May 2009

Background
Nondepolarizing neuromuscular blocking agents (NMBAs) are classic competitive-inhibitors at the muscle nicotinic acetylcholine receptor (nAChR). Although the fetal subtype muscle nAChR has been extensively studied at a molecular level, less is known about the interaction between nondepolarizing NMBAs and the human adult muscle nAChR. The aim of this study was to investigate the effect of clinically used nondepolarizing NMBAs at human adult muscle nAChRs and the mechanisms behind the inhibition.

Methods
Human subunits for the adult alpha(1)beta(1)delta(epsilon) muscle nAChR were cloned and expressed into Xenopus oocytes and thereafter studied with two-electrode voltage clamp. The effect of the clinically used nondepolarizing NMBAs, including atracurium, cis-atracurium, mivacurium, pancuronium, rocuronium, vecuronium, and d-tubocurarine, on acetylcholine-induced and dimethylphenylpiperazinium-induced currents were investigated.

Results
All nondepolarizing NMBAs tested inhibited acetylcholine- and dimethylphenylpiperazinium-induced currents in human adult alpha(1)beta(1)delta(epsilon) muscle nAChRs, and no receptor activation was seen. Interestingly, acetylcholine desensitized the human adult alpha(1)beta(1)delta(epsilon) muscle type receptor and attenuated the inhibition caused by nondepolarizing NMBAs, as evident by lack of increase in IC(50) values for the nondepolarizing NMBAs with increased concentrations of acetylcholine. In contrast, dimethylphenylpiperazinium-induced currents were competitively inhibited by the nondepolarizing NMBAs.

Conclusions
This study demonstrates that nondepolarizing NMBAs inhibit human adult muscle nAChRs expressed in Xenopus oocytes by mixed mechanisms. When using the nondesensitizing agonist dimethylphenylpiperazinium, inhibition by the NMBA is competitive, whereas activation with high concentrations of acetylcholine in combination with NMBA induces a noncompetitive inhibition, which the authors speculate can involve receptor desensitization similar to that observed in the neuromuscular junction.
Does a Higher Positive End Expiratory Pressure Decrease Mortality in Acute Respiratory Distress Syndrome?
Authors: Phoenix Susan I. , Paravastu Sharath , Columb Malachy , Vincent Jean-Louis , Nirmalan Mahesh 
Published: May 2009

Background
Positive end expiratory pressure (PEEP) is an important component of therapy in patients with acute lung injury or acute respiratory distress syndrome. The independent effect of PEEP on mortality is currently unknown.

Methods
A systematic review and meta-analysis of randomized controlled clinical trials comparing the use of higher and lower levels of PEEP.

Results
Six trials with a total of 2,484 patients from 102 intensive care units and 9 countries met the eligibility criteria. In three trials, the effect of different levels of PEEP was compared in groups receiving comparable tidal volumes. Three trials accounted for more than 85% of total weighting in the meta-analyses. The pooled relative risk obtained from these three trials showed a trend towards improved mortality with high PEEP, even though the difference did not reach statistical significance: Pooled cumulative risk of 0.90 (95% CI 0.72-1.02, P = 0.077). The reduction in absolute risk of death was approximately 4%. There was no evidence of a significant increase in baro-trauma in patients receiving high PEEP, with a pooled risk of 0.95 (95% CI 0.62-1.45, P = 0.81).

Conclusion
High PEEP strategy may have a clinically relevant independent mortality benefit. Despite a possible increase in baro-trauma, the benefits far outweigh potential risks. Current evidence therefore favors the use of high PEEP as the preferred option when ventilating patients with severe acute respiratory distress syndrome. As the reduction in absolute risk of death is less than 5%, a future clinical trial aimed at demonstrating statistical significance is likely to pose considerable financial and ethical burdens.
Experimental Ventilator-induced Lung Injury
Authors: Villar Jesús , Herrera-Abreu Maria Teresa , Valladares Francisco , Muros Mercedes , Pérez-Méndez Lina , Flores Carlos , Kacmarek Robert M. 
Published: May 2009

Background
Previous experimental studies of ventilator-induced lung injury have shown that positive end-expiratory pressure (PEEP) is protective. The authors hypothesized that the application of PEEP during volume-controlled ventilation with a moderately high tidal volume (VT) in previously healthy in vivo rats does not attenuate ventilator-induced lung injury if the peak airway pressure markedly increases during the application of PEEP.

Methods
Sixty healthy, male Sprague-Dawley rats were anesthetized and randomized to be mechanically ventilated for 4 h at (1) VT of 6 ml/kg, (2) VT of 20 ml/kg, or (3) VT of 20 ml/kg plus 10 cm H2O of PEEP. Peak airway pressures, gas exchange, histologic evaluation, mortality, total lung tissue cytokine gene expression, and serum cytokine concentrations were analyzed.

Results
Peak airway pressures exceeded 30 cm H2O with high VT plus PEEP. All lungs ventilated with high VT had perivascular edema and inflammatory infiltrates. In addition, those ventilated with PEEP had small hemorrhages foci. Five animals from the high VT plus PEEP group died (P = 0.020). Animals ventilated with high VT (with or without PEEP) had a substantial increase in serum interleukin-6 (P = 0.0002), and those ventilated with high VT plus PEEP had a 5.5-fold increase in systemic levels of tumor necrosis factor-alpha (P = 0.007).

Conclusions
In contrast to previous reports, PEEP exacerbated lung damage and contributed to fatal outcome in an in vivo, mild overdistension model of ventilator-induced lung injury in previously healthy rats. That is, the addition of high PEEP to a constant large VT causes injury in previously healthy animals.
Reduction in Intraoperative Bacterial Contamination of Peripheral Intravenous Tubing Through the Use of a Novel Device
Authors: Koff Matthew D. , Loftus Randy W. , Burchman Corey C. , Schwartzman Joseph D. , Read Megan E. , Henry Elliot S. , Beach Michael L. 
Published: May 2009

Background
Hand hygiene is a vital intervention to reduce health-care associated infections, but compliance remains low. The authors hypothesized that improvements in intraoperative hand hygiene compliance would reduce transmission of bacteria to surgical patients and reduce the incidence of postsurgical healthcare-associated infections.

Methods
The authors performed a controlled before-and-after study over 2 consecutive months. One hundred fourteen operative cases were enrolled. Two predesignated sites on the anesthesia machine were selected, decontaminated, and cultured via aseptic technique. These sites and the peripheral intravenous stopcock were cultured again after completion of the surgery. The treatment phase used a novel personal hand-decontamination device capable of recording hand-decontamination events.

Results
There were no significant differences in patient location, age, or case duration and procedure type between groups. Use of the Sprixx GJ device (Harbor Medical Inc., Santa Barbara, CA) increased hourly hand decontamination events by 27-fold as compared with baseline rates (P < 0.002; 95% confidence interval, 3.3-13.4). Use of the device was associated with a reduction in contamination in the anesthesia work area and peripheral intravenous tubing. Intravenous tubing contamination was identified in 32.8% of cases in the control group versus 7.5% in the treatment group (odds ratio, 0.17; 95% confidence interval, 0.06-0.51; P < 0.01). Healthcare-associated infections rates were reduced in the device group (3.8%) as compared with the control group (17.2%) (odds ratio, 0.19; 95% confidence interval, 0.00-0.81; P = 0.02).

Conclusions
Improved hand hygiene compliance through the use of a novel hand sanitation strategy reduces the risk of intraoperative bacterial transmission. The intervention was associated with a reduction in healthcare-associated infections.
Circadian Disruption of Body Core Temperature and Rest–Activity Rhythms after General (Propofol) Anesthesia in Rats
Authors: Dispersyn Garance , Pain Laure , Touitou Yvan 
Published: May 2009

Background
General anesthesia is commonly associated with sleep disorders, fatigue, drowsiness, and mood alterations in patients. The authors examined whether general (propofol) anesthesia can impact the circadian temporal structure by disturbing circadian rest-activity and body temperature rhythms under normal light-dark conditions (light-dark 12:12 h) in rats.

Methods
A group of rats was anesthetized with propofol, and another was injected with 10% Intralipid, which was used as a control lipidic solution. The authors examined six groups of rats according to the Zeitgeber time of intraperitoneal administration (ZT6, ZT10, ZT16) and the substance injected (propofol or Intralipid).

Results
On the day after anesthesia, propofol induced a significant 60- to 80-min phase advance of both rest-activity and body temperature rhythms. A significant 45- to 60-min phase advance of body temperature and a significant 20-min phase advance of rest-activity were still observed on the second day after anesthesia. The amplitudes of both rest-activity and body temperature rhythms were decreased on the first and second days after anesthesia. The 24-h mean rest-activity rhythm was decreased on the day after anesthesia, whereas the 24-h mean body temperature rhythm was not modified.

Conclusion
The results demonstrate the disturbing effects of propofol anesthesia on the circadian time structure in rats under normal light conditions.
Coagulopathy during Induced Severe Intracranial Hypertension in a Porcine Donor Model
Authors: Barklin Anne , Tønnesen Else , Ingerslev Jørgen , Sørensen Benny , Fenger-Eriksen Christian 
Published: May 2009

Background
Development of coagulopathy is a serious complication arising from isolated traumatic brain injury, and it predicts poor outcome. The underlying mechanism has not yet been established, although coagulopathy arising from brain tissue injury and the release of tissue factor may represent the pathophysiology. The authors investigated dynamic whole-blood clot formation (ROTEM) in a recently developed porcine model of induced severe intracranial hypertension.

Methods
In this prospective, randomized experimental study, 17 pigs were designated for severe intracranial hypertension or sham operation. Intracranial hypertension was induced by inflation of an intracranial balloon. Whole-blood clot formation was assessed by clot initiation, and clot propagation and clot strength through thrombelastometry. The authors also assessed thrombin generation and prothrombin time, which were obtained at baseline, immediately after intervention, and 5 h after intervention.

Results
A dramatic shortening in time to clot initiation and an increase in clot propagation were observed after induction of intracranial hypertension as compared to the control group. These results were further substantiated by a pronounced increase in thrombin generation and a significantly shortened prothrombin time in the intervention group. No difference in clot strength was detected between the groups.

Conclusions
In a porcine model, induction of increased intracranial pressure causing severe intracranial hypertension was associated with a pronounced activation of the coagulation system. Taken together, the various results indicate that tissue factor probably represents the main trigger of hypercoagulopathy found in these pigs.