A multicenter evaluation of the time-course of action of two doses of rapacuronium after early and late reversal with neostigmine.

UNLABELLED: Early reversal of rapacuronium may accelerate return of neuromuscular function. This study was designed to compare early (2 min after rapacuronium) or late (at 25% recovery of the first twitch [T1] of train-of-four) reversal of rapacuronium with neostigmine. We studied 119 subjects between the ages of 18 and 75 yr. Anesthesia was induced with fentanyl and thiopental and maintained with nitrous oxide, propofol, and fentanyl. Mechanomyographic neuromuscular monitoring was performed by using train-of-four stimulation of the ulnar nerve. Two groups received 1.5 mg/kg rapacuronium followed by neostigmine (50 microg/kg) and glycopyrrolate (10 microg/kg) either at 2 min after rapacuronium bolus or at 25% T1 recovery. The other two groups received 2.0 mg/kg rapacuronium, after which neostigmine was similarly given. For each rapacuronium dose, the time from the administration of rapacuronium to the start of T1 recovery or 25% T1 recovery was significantly shorter in subjects who received the reversal 2 min after rapacuronium. However, late recovery, defined by times from administration of rapacuronium to 70%, or 80% T4/T1 recovery, was not influenced by early reversal administration. We conclude that initial recovery is accelerated by early administration of neostigmine. Time to full recovery after rapacuronium administration is, however, dose-dependent and not significantly altered by early administration of neostigmine. IMPLICATIONS: "Rescue reversal," which includes the administration of neostigmine shortly after the administration of rapacuronium, may accelerate the return of spontaneous breathing (early recovery), but does not shorten the time to complete recovery of upper airway function.

The efficacy and safety of EMLA cream for awake fiberoptic endotracheal intubation.

EMLA Cream (EC; Astra, Westborough, MA) has been widely used as a local anesthetic. Limited safety information is available with respect to the application of EC to the oral mucous membranes. The purpose of this pilot study was to evaluate the efficacy and safety of EC when applied to oral mucosa for fiberoptic intubation. Twenty ASA physical status I-IV patients (11 women and 9 men), 28-57 yr old, who were scheduled for awake, fiberoptic, intubation participated in this open-label study. A total of 4 g of EC was used for 5 min until the patient showed no evidence of a gag reflex (this was evaluated clinically by the patient's acceptance of the William's airway and considered the endpoint for assessing adequate topicalization of the oropharynx). The measured peak plasma concentration of lidocaine or prilocaine did not reach toxic levels in any patient. Methemoglobin levels did not exceed normal values (1.5%) in any patient, and there was no relationship between methemoglobin levels and patient weight, amount of EC used, measured peak plasma concentration, or times to measured peak concentrations of prilocaine or lidocaine. We conclude that EC provided satisfactory topical anesthesia allowing for successful oral fiberoptic intubation in all patients and should be considered a safe alternative for anesthetizing the airway of patients requiring awake oral fiberoptic intubation.

Relationship between benign prostatic hyperplasia and history of coronary artery disease in elderly men.

STUDY OBJECTIVE: To assess the relationship between the occurrence of benign prostatic hyperplasia (BPH), an androgen-dependent disease, and coronary artery disease (defined as history of coronary artery bypass grafting, coronary angioplasty, myocardial infarction) in elderly men. DESIGN: Retrospective chart review. SETTING: Urology practice. PATIENTS: Seven hundred two elderly men aged 65-80 years. INTERVENTION: The men's charts were reviewed for data pertaining to coronary artery disease, risk factors for coronary artery disease, and serum prostate-specific antigen (PSA) levels. Men who had medical conditions, pharmacologic interventions, or surgical procedures that could alter PSA, and those taking lipid-lowering agents were not included. MEASUREMENTS AND MAIN RESULTS: PSA levels correlate positively with prostatic volume of BPH. In men with levels under 1.0 pg/L (no BPH) and over 1.0 microg/L (BPH present), the frequency of coronary artery disease was 9% and 29%, respectively (p<0.03). No significant differences were noted between groups in other accepted risk factors for coronary artery disease including age, smoking, diabetes mellitus, or hypertension. CONCLUSION: Smooth muscle proliferation is an important and possibly androgen-dependent step in the development of atherosclerosis and BPH. Prospective studies are required to assess the effect of antiandrogens on atherosclerosis.

Clinical pharmacology of rapacuronium bromide, a new short-acting neuromuscular blocking agent.

Rapacuronium is a new steroidal, nondepolarizing, neuromuscular blocking agent. It appears to be the least potent of all available nondepolarizing muscle relaxants. Its onset of action resembles that of succinylcholine, and its recovery times are shorter than those of other nondepolarizing agents. The clinical duration of rapacuronium can be shortened significantly with early (2 min) administration of neostigmine, which may be beneficial in patients with difficult airway or failed intubation. Rapacuronium appears to be free of significant cardiovascular complications.

Peripheral neuropathy in healthy men volunteers anesthetized with 1.25 MAC sevoflurane for 8 hours.

Two men volunteers developed peripheral neuropathy after prolonged anesthesia with 1.25 minimum alveolar concentration sevoflurane at an inflow rate of 2 L/minute of fresh gas that caused concurrent administration of relatively large doses (ppm-hrs) of the degradation product of sevoflurane, compound A. Other similarly treated volunteers had lesser degrees of transient neuropathy. This result does not prove but raises the question of whether compound A or other factors associated with sevoflurane anesthesia can predispose patients to peripheral neuropathy.

Dose of compound A, not sevoflurane, determines changes in the biochemical markers of renal injury in healthy volunteers.

UNLABELLED: Administration of sevoflurane in a circle absorption system generates Compound A, a nephrotoxin in rats. Reports examining the potential of Compound A to produce renal injury in humans have provided conflicting results. We tested the possibility that there is a threshold to Compound A-induced renal injury in humans and that, above this threshold, renal injury increases with increasing doses of Compound A. Eleven volunteers received 3% sevoflurane for 8 h at 2 L/min, and three volunteers received 3% sevoflurane for 8 h at 4-6 L/min. We measured inspired and expired concentrations of Compound A and urinary excretion of albumin, alpha-glutathione-S-transferase (GST), and glucose. The median urinary excretion of albumin, glucose, and alpha-GST for the first 3 days after anesthesia increased significantly from preanesthetic values in the 2-L/min group. Compound A doses < 240 ppm-h resulted in normal urinary excretion of albumin, glucose, and alpha-GST. Five of seven subjects who received doses > 240 ppm-h had abnormal excretion of albumin, and six of seven had abnormal alpha-GST urinary excretion (P < 0.05). Urinary excretion of albumin, alpha-GST, and glucose was normal by 14 days after exposure. We conclude that sevoflurane administration for 8 h at 2 L/min results in albuminuria and enzymuria when the dose of Compound A exceeds 240 ppm-h. That is, a Compound A concentration of 30 ppm breathed for > or = 8 h may produce transient renal injury. IMPLICATIONS: We examined the dose-response relationship of sevoflurane/Compound A and urinary excretion of albumin, glucose, and alpha-GST. Sevoflurane exposure for 8 h at a 2-L/min inflow rate produces transient albuminuria and enzymuria in healthy volunteers when the dose of Compound A exceeds 240 ppm-h (30 ppm for 8 h).

High-quality filtration allows reuse of anesthesia breathing circuits resulting in cost savings and reduced medical waste.

STUDY OBJECTIVES: To determine if the new Filta-Therm filter prevents contamination and allows the reuse of breathing circuit with considerable cost and environmental savings. DESIGN: Prospective study. PATIENTS: 52 ASA physical status I, II, III, and IV patients, aged 18 to 75 years. INTERVENTIONS: Each morning a new breathing circuit was assembled. The Filta-Therm filter (Intersurgical, Inc., Liverpool, NY) elbow, and mask, but not the circuit, were changed between patients. The filter was placed between the Y-piece and the elbow of the breathing circuit. Prior to anesthesia, samples were obtained at the Y-piece, and the inspiratory and expiratory ports of breathing circuit. Following anesthesia, samples were obtained at the Murphy eye of endotrachael tube, and at the Y-piece. The samples were incubated, and the results examined at 24 and 48 hours. MEASUREMENTS AND MAIN RESULTS: Prior to anesthesia, cultures of the Y-piece and the inspired and expired ports samples showed no growth. Following anesthesia, all 52 samples obtained at the endotracheal tube were contaminated with various organisms, while all 52 Y-piece samples showed negative growth. CONCLUSIONS: The single use of Filta-Therm filter prevents bacterial contamination and allows reuse of breathing circuit at least twice, resulting in significant cost savings ($50,778 per year). Further studies are needed to establish the safety of reusing breathing circuits when appropriate bacterial filters are used.

Perioperative hypertension.

Increased activity or inadequate inhibition of the autonomic nervous system is often the cause of perioperative hypertension. The goal of treatment is to maintain an adequate balance between myocardial oxygen supply and demand. Newer agents, such as nicardipine and fenoldopam, may offer potential advantages over older agents. The cost:benefit ratio of therapy with these newer agents must also be considered. Despite the fact that perioperative hypertension is aggressively treated, there are no long-term, large-scale study data indicating that this treatment affects long-term patient outcomes.

Double-blind comparison of two doses of rocuronium and succinylcholine for rapid-sequence intubation.

STUDY OBJECTIVE: To compare the pharmacodynamics of two commonly recommended doses of rocuronium bromide (0.7 mg/kg and 0.9 mg/kg) and succinylcholine (1.5 mg/kg) when used for rapid-sequence intubation. DESIGN: Prospective, double-blind, randomized study. SETTING: Operating rooms at a university hospital. PATIENTS: 45 ASA physical status I and II adult patients scheduled for elective surgeries under general anesthesia. INTERVENTIONS: Nonpremedicated patients were anesthetized with fentanyl 2 mcg/kg followed by thiopental sodium 4 to 5 mg/kg and muscle relaxant using rapid-sequence technique. Group 1 (n = 15) received rocuronium bromide 0.7 mg/kg. Group 2 (n = 16) received rocuronium bromide 0.9 mg/kg, and Group 3 (n = 14) received succinylcholine 1.5 mg/kg. Intubation was performed 60 seconds after the administration of muscle relaxant. MEASUREMENTS AND MAIN RESULTS: The case of intubation was scored using a scale of 1 to 4. Blood pressure and heart rate were measured beginning one minute before induction of anesthesia up to 5 minutes after intubation. Intubation scores were similar in groups 2 and 3 and were noted as good or excellent in all patients. Group 1 displayed a significantly lower intubation score than the other two groups; 60% were rated as poor. No significant differences in hemodynamic data were seen among the three groups. CONCLUSIONS: Rocuronium bromide at a dose of 0.9 mg/kg provides intubating conditions similar to succinylcholine 1.5 mg/kg at 1 minute. Intubating conditions at 1 minute following a 0.7 mg/kg dose of rocuronium are not as good as those following a 0.9 mg/kg dose of rocuronium or a 1.5 mg/kg dose of succinylcholine.

Recovery parameters after sevoflurane and isoflurane anesthesia.

We compared recovery times in patients with American Society of Anesthesiologists physical status I-III receiving sevoflurane or isoflurane during surgical procedures longer than 1 hour in duration. Of the 50 patients enrolled, 23 received sevoflurane and 27 received isoflurane. Anesthetic gases were discontinued abruptly at the end of the surgical procedure. The following parameters were recorded: time to emergence (opens eyes), time to extubation, response to verbal command (squeezes hand of observer), and orientation (time and place). Exposure times to the agents were similar. The time to emergence was significantly less with sevoflurane than with isoflurane (5.6 vs 11.2 min, respectively). There were no significant differences in time to extubation, response to verbal command, or orientation between the groups. Our data support more rapid emergence with sevoflurane than with isoflurane in surgical procedures longer than 1 hour in duration.

Treatment of opioid-induced pruritus with ondansetron: report of four patients.

Pruritus is a common side effect after neuraxial administration of the opioids; particularly morphine sulfate. Ondansetron has been used to treat the pruritus in patients with cholestatic diseases or renal insufficiency, suggesting that pruritus may be mediated by serotonin. We administered ondansetron to four patients suffering from pruritus due to the perioperative administration of opioids. Pruritus disappeared within few minutes in three of these patients. Future studies are necessary to evaluate the efficacy of ondansetron for the treatment as well as the prevention of this opioid-induced effect.

Sevoflurane versus isoflurane for maintenance of anesthesia: are serum inorganic fluoride ion concentrations of concern?

Sevoflurane administration can result in increased serum inorganic fluoride ion concentrations, which have been associated with inhibition of renal concentrating ability. We measured serum fluoride levels, renal function, and recovery variables as a function of time in ASA grade I-III patients administered general anesthesia with isoflurane or sevoflurane for at least 1 h. Fifty patients were exposed to sevoflurane (< or = 2.4% inspired concentration) or isoflurane (< or = 1.9% inspired concentration) for maintenance of anesthesia as part of a multicenter trial. Blood was collected for determination of serum fluoride ion concentration, electrolytes, blood urea nitrogen, and creatinine at various time points pre- and postoperatively. Mean serum fluoride levels were significantly increased in sevoflurane versus isoflurane groups at all time points; the mean peak serum levels were 28.2 +/- 14 mumol/L at 1 h for sevoflurane and 5.08 +/- 4.35 mumol/L at 12 h for isoflurane. Sevoflurane-mediated increases in serum fluoride levels peaked at 1 h and, in general, decreased rapidly after discontinuation of the anesthesia. Three of 24 patients exposed to sevoflurane had one or more fluoride levels > 50 mumol/L. One of these patients had a serum inorganic fluoride ion level > 50 mumol/L at 12 h after sevoflurane, and an additional patient had fluoride levels > 33 mumol/L for up to 24 h after sevoflurane discontinuation. Those two patients also demonstrated an increase in serum blood urea nitrogen and creatinine at 24 h after sevoflurane administration compared with baseline. The elimination half-life of serum fluoride ion was 21.6 h. The results of this study suggest the possibility of sevoflurane induced nephrotoxicity.

The effect of isoflurane versus balanced anesthesia on rocuronium's pharmacokinetics and infusion requirement.

STUDY OBJECTIVE: To compare the effects of two anesthetic techniques, balanced and isoflurane anesthesia, on the response to an intubating dose and an infusion of rocuronium, and on rocuronium's pharmacokinetics. DESIGN: Randomized, open-label study. SETTING: A university-affiliated hospital. PATIENTS: Twenty-two healthy adults undergoing elective surgery. INTERVENTIONS: The patients were anesthetized with a balanced technique (nitrous oxide, fentanyl, midazolam) or isoflurane (nitrous oxide, isoflurane 0.5-1.0%). Rocuronium was administered initially as a 500-micrograms/kg bolus, then by infusion to maintain approximately 86-94% depression of twitch tension. Plasma samples to determine rocuronium concentrations were obtained before, during, and after the infusion. Pharmacokinetics were determined using a population-based approach. MEASUREMENTS AND MAIN RESULTS: Onset time and initial recovery after the bolus dose were similar for the two groups. Infusion requirements also were similar. Plasma clearance was greater during isoflurane than during balanced anesthesia (4.48 vs 3.49 ml/kg/min). Distribution clearances and volumes of distribution were similar for the two groups. CONCLUSIONS: The similarity of response to an intubating dose and an infusion of rocuronium suggests that clinicians need not alter the dose or rate of rocuronium administration during isoflurane anesthesia with a of duration less than 1 hour. However, the greater clearance of rocuronium, in light of the similarity of infusion requirements, suggests that isoflurane potentiates rocuronium compared with balanced anesthesia.

Postoperative nystagmus and nausea.

OBJECTIVE: To evaluate the presence and the relationship between postoperative nystagmus and nausea. DESIGN: Open-label study. SETTING: University hospital. PATIENTS: Sixty-six patients recovering from general anesthesia following elective ambulatory surgeries. INTERVENTIONS: Patients were tested postoperatively for nystagmus using an electronystagmography, and were monitored for nausea and vomiting for the first postoperative day. MAIN OUTCOME MEASURES: A comparison of the incidence of nausea was made among patients with and without postoperative nystagmus. RESULTS: Twenty-four patients (36 percent) experienced postoperative nausea and 28 patients (42 percent) had nystagmus. There were no significant differences in age, weight, height, dosage of fentanyl, or postoperative use of narcotics between those who experienced postoperative nausea or had nystagmus than those who did not. A significantly greater percentage of female patients compared with male patients had nausea during the first postoperative day. Sixty percent of patients with nystagmus experienced nausea in the hospital compared with 18 percent of the patients without nystagmus (p < 0.01, 95 percent confidence interval [CI] of the difference = 11.3 to 61.3 percent). Twenty-two patients (78 percent) with nystagmus experienced nausea during the first postoperative day compared with 14 patients (36 percent) with no nystagmus (p < 0.01, 95 percent CI of the difference = 20.1 to 63.3 percent). Eighty-three percent of the nauseated patients experienced vomiting during the first postoperative day. CONCLUSIONS: The presence of nystagmus in the early part of recovery from general anesthesia is associated with a higher incidence of nausea and vomiting during the first postoperative day.

The effect of desmopressin acetate on postoperative hemorrhage in patients receiving aspirin therapy before coronary artery bypass operations.

It has been suggested that desmopressin acetate has been effective in reducing hemorrhage after coronary artery bypass grafting in patients receiving aspirin before operation. We conducted a prospective, randomized, placebo-controlled, double-blind trial to determine the effectiveness and safety of desmopressin in these patients. Sixty-five patients pretreated with aspirin within 7 days before their scheduled elective coronary artery bypass grafting were randomized to receive desmopressin (0.3 micrograms/kg) or placebo after cessation of bypass and reversal of heparin with protamine. The demographic characteristics and last dose of aspirin were similar in both groups. There was a significant reduction in postoperative blood loss noted between groups for both chest tube blood loss (833 +/- 311 ml for the 1-desamino-8-D-arginine vasopressin [desmopressin] group versus 1176 +/- 674 ml for the placebo group; p = 0.016) and total blood loss (1215 +/- 381 ml for the desmopressin group versus 1637 +/- 761 ml for the placebo group; p = 0.0097). Despite the differences in blood loss between the two groups, the red cell transfusions were not significantly different, but the use of platelets was less in the desmopressin group and almost achieved statistical significance (p = 0.053). Neither was there a difference in the occurrence of thrombotic complications between groups. It appears that desmopressin in this specific subgroup of patients receiving preoperative aspirin is effective as a prophylactic agent for reduction of postsurgical hemorrhage.

Continuous noninvasive cardiac output as estimated from the pulse contour curve.

We developed a noninvasive computer-based system for estimating continuous cardiac output by a modified pulse contour method using a finger pressure waveform. The method requires no individual patient calibration or baseline cardiac output. First, we calibrated the system in a "learn" group of 20 patients. The computer-based cardiac output was then compared with thermodilution cardiac output in 27 patients undergoing coronary artery bypass surgery. A total of 94 cardiac outputs were performed (three averaged per determination) at four predetermined time periods: preinduction, postinduction, prebypass, and postbypass. During determination of each thermodilution cardiac output, the pulse wave data were simultaneously recorded on cassette tape. The patients had cardiac outputs ranging from 2.9 to 6.4 L/min. The correlation coefficient was 0.75. The average thermodilution cardiac output was 4.50 (+/- 0.83 SD) L/min, while the cardiac output derived from the finger pressure wave was 4.48 (+/- 0.7 SD) L/min (95% confidence interval [CI] of difference, 0-3.2%). The mean difference between the two methods was 0.02 (+/- 0.55 SD) L/min. The 95% CI for the bias was 0.0001 to 0.036 L/min. The 95% CI for the lower limit of agreement was -1.12 to -1.06 L/min; the upper limit for the 95% CI was 1.09 to 1.16 L/min. The program demonstrated that information about cardiac output can be obtained by using the Finapres device (Ohmeda, Boulder, CO). The cardiac output values obtained by this continuous noninvasive technique were within +/- 20% of the simultaneous thermodilution values 87% of the time. This was true over the narrow range of cardiac outputs (2.9 to 6.4 L/min) and wide range of heart rates (45 to 140 beats/min).