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BMC Anesthesiology - Latest Articles
The latest research articles published by BMC Anesthesiology

  • Reversal of profound vecuronium-induced neuromuscular block under sevoflurane anesthesia: sugammadex versus neostigmine
    Background: Acetylcholinesterase inhibitors cannot rapidly reverse profound neuromuscular block. Sugammadex, a selective relaxant binding agent, reverses the effects of rocuronium and vecuronium by encapsulation. This study assessed the efficacy of sugammadex compared with neostigmine in reversal of profound vecuronium-induced neuromuscular block under sevoflurane anesthesia. Methods: Patients aged [greater than or equal to]18 years, American Society of Anesthesiologists class 1-4, scheduled to undergo surgery under general anesthesia were enrolled in this phase III, multicenter, randomized, safety-assessor blinded study. Sevoflurane anesthetized patients received vecuronium 0.1 mg/kg for intubation, with maintenance doses of 0.015 mg/kg as required. Patients were randomized to receive sugammadex 4 mg/kg or neostigmine 70 mug/kg with glycopyrrolate 14 mug/kg at 1-2 post-tetanic counts. The primary efficacy variable was time from start of study drug administration to recovery of the train-of-four ratio to 0.9. Safety assessments included physical examination, laboratory data, vital signs, and adverse events. Results: Eighty three patients were included in the intent-to-treat population (sugammadex, n = 47; neostigmine, n = 36). Geometric mean time to recovery of the train-of-four ratio to 0.9 was 15-fold faster with sugammadex (4.5 minutes) compared with neostigmine (66.2 minutes; p 0.0001) (median, 3.3 minutes with sugammadex versus 49.9 minutes with neostigmine). No serious drug-related adverse events occurred in either group. Conclusions: Recovery from profound vecuronium-induced block is significantly faster with sugammadex, compared with neostigmine. Neostigmine did not rapidly reverse profound neuromuscular block (Trial registration number: NCT00473694).

  • Effect of nitrous oxide on cisatracurium infusion demands: a randomized controlled trial
    Background: Recent studies have questioned our previous understanding on the effect of nitrous oxide on muscle relaxants, since nitrous oxide has been shown to potentiate the action of bolus doses of mivacurium, rocuronium and vecuronium. This study was aimed to investigate the possible effect of nitrous oxide on the infusion requirements of cisatracurium. Methods: 70 ASA physical status I-III patients aged 18-75 years were enrolled in this randomized trial. The patients were undergoing elective surgery requiring general anesthesia with a duration of at least 90 minutes. Patients were randomized to receive propofol and remifentanil by target controlled infusion in combination with either a mixture of oxygen and nitrous oxide (Nitrous oxide/TIVA group) or oxygen in air (Air/TIVA group). A 0.1 mg/kg initial bolus of cisatracurium was administered before tracheal intubation, followed by a closed-loop computer controlled infusion of cisatracurium to produce and maintain a 90% neuromuscular block. Cumulative dose requirements of cisatracurium during the 90-min study period after bolus administration were measured and the asymptotic steady state rate of infusion to produce a constant 90% block was determined by applying nonlinear curve fitting to the data on the cumulative dose requirement during the study period. Results: Controller performance, i.e. the ability of the controller to maintain neuromuscular block constant at the setpoint and patient characteristics were similar in both groups. The administration of nitrous oxide did not affect cisatracurium infusion requirements. The mean steady-state rates of infusion were 0.072 +/- 0.018 and 0.066 +/- 0.017 mg * kg-1 * h-1 in Air/TIVA and Nitrous oxide/TIVA groups, respectively. Conclusions: Nitrous oxide does not affect the infusion requirements of cisatracurium.Trial registrationClinicalTrials.gov NCT01152905; European Clinical Trials Database at http://eudract.emea.eu.int/2006-006037-41.

  • Temporal artery versus bladder thermometry during adult medical-surgical intensive care monitoring: an observational study
    Background: We sought to evaluate agreement between a new and widely implemented method of temperature measurement in critical care, temporal artery thermometry and an established method of core temperature measurement, bladder thermometry as performed in clinical practice. Methods: Temperatures were simultaneously recorded hourly (n = 736 observations) using both devices as part of routine clinical monitoring in 14 critically ill adult patients with temperatures ranging ?1°C prior to consent. Results: The mean difference between temporal artery and bladder temperatures measured was -0.44°C (95% confidence interval, -0.47°C to -0.41°C), with temporal artery readings lower than bladder temperatures. Agreement between the two devices was greatest for normothermia (36.0°C to 38.3°C) (mean difference -0.35°C [95% confidence interval, -0.37°C to -0.33°C]). The temporal artery thermometer recorded higher temperatures during hypothermia ( 36°C) (mean difference 0.66°C [95% confidence interval, 0.53°C to 0.79°C]) and lower temperatures during hyperthermia (?38.3°C) (mean difference -0.90°C [95% confidence interval, -0.99°C to -0.81°C]). The sensitivity for detecting fever (core temperature ?38.3°C) using the temporal artery thermometer was 0.26 (95% confidence interval, 0.20 to 0.33), and the specificity was 0.99 (95% confidence interval, 0.98 to 0.99). The positive likelihood ratio for fever was 24.6 (95% confidence interval, 10.7 to 56.8); the negative likelihood ratio was 0.75 (95% confidence interval, 0.68 to 0.82). Conclusions: Temporal artery thermometry produces somewhat surprising disagreement with an established method of core temperature measurement and should not to be used in situations where body temperature needs to be measured with accuracy.

  • Bradykinin and adenosine receptors mediate desflurane induced postconditioning in human myocardium: role of reactive oxygen species
    Background: Desflurane during early reperfusion has been shown to postcondition human myocardium, in vitro. We investigated the role of adenosine and bradykinin receptors, and generation of radical oxygen species in desflurane-induced postconditioning in human myocardium. Methods: We recorded isometric contraction of human right atrial trabeculae hanged in an oxygenated Tyrodes solution (34 degrees Celsius, stimulation frequency 1 Hz). After a 30-min hypoxic period, desflurane 6% was administered during the first 5 min of reoxygenation. Desflurane was administered alone or with pretreatment of N-mercaptopropionylglycine, a reactive oxygen species scavenger, 8-(p-Sulfophenyl)theophylline, an adenosine receptor antagonist, HOE140, a selective B2 bradykinin receptor antagonist. In separate groups, adenosine and bradykinin were administered during the first minutes of reoxygenation alone or in presence of N-mercaptopropionylglycine. The force of contraction of trabeculae was recorded continuously. Developed force at the end of a 60-min reoxygenation period was compared (mean ± standard deviation) between the groups by a variance analysis and post hoc test. Results: Desflurane 6% (84 ± 6% of baseline) enhanced the recovery of force after 60-min of reoxygenation as compared to control group (51 ± 8% of baseline, P 0.0001). N-mercaptopropionylglycine (54 ± 3% of baseline), 8-(p-Sulfophenyl)theophylline (62 ± 9% of baseline), HOE140 (58 ± 6% of baseline) abolished desflurane-induced postconditioning. Adenosine (80 ± 9% of baseline) and bradykinin (83 ± 4% of baseline) induced postconditioning (P 0.0001 vs control), N-mercaptopropionylglycine abolished the beneficial effects of adenosine and bradykinin (54 ± 8 and 58 ± 5% of baseline, respectively). Conclusions: In vitro, desflurane-induced postconditioning depends on reactive oxygen species production, activation of adenosine and bradykinin B2 receptors. And, the cardioprotective effect of adenosine and bradykinin administered at the beginning of reoxygenation, was mediated, at least in part, through ROS production.

  • Design and Organization of the Dexamethasone, Light Anesthesia and Tight Glucose Control (DeLiT) Trial: a factorial trial evaluating the effects of corticosteroids, glucose control, and depth-of-anesthesia on perioperative inflammation and morbidity from major non-cardiac surgery
    Background: The perioperative period is characterized by an intense inflammatory response. Perioperative inflammation promotes postoperative morbidity and increases mortality. Blunting the inflammatory response to surgical trauma might thus improve perioperative outcomes. We are studying three interventions that potentially modulate perioperative inflammation: corticosteroids, tight glucose control, and light anesthesia.Methods/DesignThe DeLiT Trial is a factorial randomized single-center trial of dexamethasone vs placebo, intraoperative tight vs. conventional glucose control, and light vs deep anesthesia in patients undergoing major non-cardiac surgery. Anesthetic depth will be estimated with Bispectral Index (BIS) monitoring (Aspect medical, Newton, MA). The primary outcome is a composite of major postoperative morbidity including myocardial infarction, stroke, sepsis, and 30-day mortality. C-reactive protein, a measure of the inflammatory response, will be evaluated as a secondary outcome. One-year all-cause mortality as well as post-operative delirium will be additional secondary outcomes. We will enroll up to 970 patients which will provide 90% power to detect a 40% reduction in the primary outcome, including interim analyses for efficacy and futility at 25%, 50% and 75% enrollment.DiscussionThe DeLiT trial started in February 2007. We expect to reach our second interim analysis point in 2010. This large randomized controlled trial will provide a reliable assessment of the effects of corticosteroids, glucose control, and depth-of-anesthesia on perioperative inflammation and morbidity from major non-cardiac surgery. The factorial design will enable us to simultaneously study the effects of the three interventions in the same population, both individually and in different combinations. Such a design is an economically efficient way to study the three interventions in one clinical trial vs three.Trial registrationThis trial is registered at Clinicaltrials.gov #: NTC00433251

  • First administration to man of Org 25435, an intravenous anaesthetic: A Phase 1 Clinical Trial
    Background: Org 25435 is a new water-soluble alpha-amino acid ester intravenous anaesthetic which proved satisfactory in animal studies. This study aimed to assess the safety, tolerability and efficacy of Org 25435 and to obtain preliminary pharmacodynamic and pharmacokinetic data. Methods: In the Short Infusion study 8 healthy male volunteers received a 1 minute infusion of 0.25, 0.5, 1.0, or 2.0 mg/kg (n = 2 per group); a further 10 received 3.0 mg/kg (n = 5) or 4.0 mg/kg (n = 5). Following preliminary pharmacokinetic modelling 7 subjects received a titrated 30 minute Target Controlled Infusion (TCI), total dose 5.8-20 mg/kg. Results: Within the Short Infusion study, all subjects were successfully anaesthetised at 3 and 4 mg/kg. Within the TCI study 5 subjects were anaesthetised and 2 showed signs of sedation. Org 25435 caused hypotension and tachycardia at doses over 2 mg/kg. Recovery from anaesthesia after a 30 min administration of Org 25435 was slow (13.7 min). Pharmacokinetic modelling suggests that the context sensitive half-time of Org 25435 is slightly shorter than that of propofol in infusions up to 20 minutes but progressively longer thereafter. Conclusions: Org 25435 is an effective intravenous anaesthetic in man at doses of 3 and 4 mg/kg given over 1 minute. Longer infusions can maintain anaesthesia but recovery is slow. Hypotension and tachycardia during anaesthesia and slow recovery of consciousness after cessation of drug administration suggest this compound has no advantages over currently available intravenous anaesthetics.

  • Fenoldopam use in a burn intensive care unit: a retrospective study
    Background: Fenoldopam mesylate is a highly selective dopamine-1 receptor agonist approved for the treatment of hypertensive emergencies that may have a role at low doses in preserving renal function in those at high risk for or with acute kidney injury (AKI). There is no data on low-dose fenoldopam in the burn population. The purpose of our study was to describe our use of low-dose fenoldopam (0.03-0.09 ?g/kg/min) infusion in critically ill burn patients with AKI. Methods: We performed a retrospective analysis of consecutive patients admitted to our burn intensive care unit (BICU) with severe burns from November 2005 through September 2008 who received low-dose fenoldopam. Data obtained included systolic blood pressure, serum creatinine, vasoactive medication use, urine output, and intravenous fluid. Patients on concomitant continuous renal replacement therapy were excluded. Modified inotrope score and vasopressor dependency index were calculated. One-way analysis of variance with repeated measures, Wilcoxson signed rank, and chi-square tests were used. Differences were deemed significant at p 0.05. Results: Seventy-seven patients were treated with low-dose fenoldopam out of 758 BICU admissions (10%). Twenty (26%) were AKI network (AKIN) stage 1, 14 (18%) were AKIN stage 2, 42 (55%) were AKIN stage 3, and 1 (1%) was AKIN stage 0. Serum creatinine improved over the first 24 hours and continued to improve through 48 hours (p 0.05). There was an increase in systolic blood pressure in the first 24 hours that was sustained through 48 hours after initiation of fenoldopam (p 0.05). Urine output increased after initiation of fenoldopam without an increase in intravenous fluid requirement (p 0.05; p = NS). Modified inotrope score and vasopressor dependency index both decreased over 48 hours (p 0.0001; p = 0.0012). Conclusions: These findings suggest that renal function was preserved and that urine output improved without a decrease in systolic blood pressure, increase in vasoactive medication use, or an increase in resuscitation requirement in patients treated with low-dose fenoldopam. A randomized controlled trial is required to establish the efficacy of low-dose fenoldopam in critically ill burn patients with AKI.

  • Effect of cigarette smoking on the washout time of sevoflurane anesthesia
    Background: Cigarette smoking affects the pharmacodynamic and pharmacokinetic behavior of many drugs and causes deterioration of pulmonary mechanics. We have evaluated the effect of cigarette smoking on washout time after one minimum alveolar concentration-h (1 MAC-h) of sevoflurane anesthesia. Methods: We investigated the washout time of sevoflurane in 30 non-smoking and 30 healthy cigarette smoking (?20 cigarettes/day for1 year) ASA I-II physical status patients, aged 18-63 years, who were candidates for otorhinolaryngologic elective surgery under 1MAC-h standardized sevoflurane anesthesia. At the end of the surgery, the sevoflurane vaporizer was turned off and the time taken for the sevoflurane concentration to decrease to MAC-awake (0.3) and 0.1 MAC levels were recorded. In addition, the ratio of the fractions of inspired concentration (Fi) and expired concentration of sevoflurane (Fexp) at 1 MAC and Fexp of sevoflurane at 0.1MAC were recorded. The patients were mechanically ventilated during the washout time. Results: We found no difference between the 2 study groups with regard to washout time of sevoflurane. The times of 1MAC down to MAC-awake (106 ± 48 sec in non-smokers vs 97 ± 37 sec in smokers, p 0.05) and down to 0.1MAC (491 ± 187 sec in non-smokers vs 409 ± 130 sec in smokers, p 0.05) were similar. Similarly, there were no significant differences in the ratios of Fi/Fexp at 1MAC (1.18 in non-smokers vs. 1.19 in smokers, p 0.05) and Fexp of sevoflurane at 0.1MAC (0.26 in non-smokers vs. 0.25 in smokers, p 0.05). Conclusions: Washout time of 1MAC-h sevoflurane anesthesia is not appear to be effected by cigarette smoking in patients without significant pulmonary disease.

  • A randomized comparison between three types of irrigating fluids during transurethral resection in benign prostatic hyperplasia.
    Background: Central nervous system changes, circulatory and electrolyte imbalances are the main complications of endoscopic transurethral resection of the prostate (TURP) which is known as transurethral resection (TUR) syndrome, which occurs as result of excessive absorption of irrigating fluid. We compare glycine 1.5% versus glucose 5% and normal saline 0.9% as irrigating solutions during TURP in patients with moderate to severe bladder outlet obstruction due to benign prostatic hyperplasia (BPH). Methods: Three hundred sixty patients with symptomatic BPH were randomized into a prospective, controlled trial comparing the three irrigation modalities. One-hundred twenty patients used glycine 1.5% solution as irrigating fluid (glycine group), 120 patients used glucose 5% solution (glucose group) and 120 patients used normal saline 0.9% solution (saline group). Patients demographics, operation time, hospital stay, postoperative amino acid glycine assay, postoperative serum cardiac troponin I and perioperative complications were noted. Results: No difference was found between the groups in the immediate postoperative levels of hemoglobin and hematocrite. A high glycine level was associated with the TUR syndrome. Seventeen patients had TUR syndrome; all were in glycine group and they had the highest postoperative amino acid glycine levels. Slight increase in serum sodium (142.6 ± 12.6 mmol/l) was detected in saline group. Transient Hyperglycemia (170 ± 35.9 mg/dl) and hypokalemia (3.67 ± 0.92 mmol/l) occurred in the immediate postoperative period in the glucose group. Conclusion: Endoscopic TURP performed using either glucose 5% or saline 0.9% irrigating solution during and after surgery is associated with lower incidence of TUR syndrome, lower catheterization period, shorter hospital stay and no cardiac toxicity in comparison with glycine 1.5% solution.Trial RegistrationThis clinical trail had been approved and registered in PACT Registry; with identification number for the registry is ATMR2010010001793131.

  • Attitudes to drug trials among relatives of unconscious intensive care patients
    Background: In many countries relatives are asked to consent on behalf of ICU patients prior to inclusion in clinical trials. However, the attitudes to drug trials among relatives of unconscious ICU patients are largely unknown. Methods: We performed a prospective questionnaire survey at two university hospital ICUs of the next-of-kin to 50 unconscious adult patients. They were asked to complete a questionnaire within 48 hours of the patients acute ICU admission. Results: Forty-two relatives returned the questionnaire of which 41 were completed by direct family members and in one case by a friend to the patient.The majority of relatives (36/42) were positive/positive with some scepticism towards performing drug trials in unconscious ICU patients and 30/42 would most likely accept trial-participation by their relative. The majority (30/42) agreed that they should decide if their relative was to participate in a drug trial and 24 of these found that the treating clinician/ICU consultant should also consent. The majority (27/42) found that deferred consent would be acceptable if there was a limited time frame for initiation of treatment, however 8 respondents found this unacceptable when the intervention was a new drug.The majority of relatives stipulated that adherence to legislation, treatment benefit for the study patient and for future patients, no patient-risk or -discomfort and development of new drugs were important factors if their relative was to participate in an ICU drug trial. When questioned about doctors motives for performing drug trials the wish for drug development and better patient care were highly rated among relatives. Conclusions: In general, relatives to unconscious ICU patients expressed positive attitudes to drug trials in the ICU and the inclusion of their relative in drug trials. Consent by next-of-kin and deferred consent was acceptable to the majority of relatives.


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