Irwin Gratz

Comparison of Ondansetron Versus Placebo to Prevent Postoperative Nausea and Vomiting in Women Undergoing Ambulatory Gynecologic Surgery

BackgroundPostoperative nausea and emesis, especially in ambulatory surgical patients, remains a troublesome problem. This study was performed to compare the incidence of nausea and emesis during the 24-h postoperative period in ondan-setron-treated patients versus placebo-treated patients. MethodsUsing a randomized prospective double-blind study design, women between the ages of 18 and 70 yr undergoing gynecologic surgical procedures with general opioid anesthesia on an outpatient basis were enrolled. Ondansetron or placebo was administered prior to induction of anesthesia. Patients were stratified according to history of nausea and emesis during previous exposure to general anesthesia and randomized to dose received. ResultsData from the 544 women showed that all doses of intravenous ondansetron tested (1, 4, and 8 mg) were significantly more effective (62%, 76%, and 77%, respectively) than placebo (46%) in reducing the incidence of emesis following surgery until 24 h after recovery room entry. All these doses were more effective than placebo in patients with no prior history of emesis following surgery and the 4− and 8-mg doses were more effective than placebo in patients with a prior history of emesis following surgery. All doses of ondansetron tested were generally well tolerated with adverse events, clinical laboratory tests, and recovery room vital signs similar to those of placebo. Serum aspartate transaminase (AST) was increased in five patients (1 mg, 2 patients; 4 mg, 1 patient; 8 mg, 2 patients). In the three patients in whom subsequent analysis were performed, the serum AST had decreased to preoperative levels. ConclusionsOndansetron given intravenously to prevent postoperative nausea and emesis was highly effective in the 4− and 8-mg doses in women having ambulatory gynecologic surgery.

A Phase III, Double-blind, Placebo-controlled, Multicenter Study on the Efficacy of Recombinant Human Antithrombin in Heparin-resistant Patients Scheduled to Undergo Cardiac Surgery Necessitating Cardiopulmonary Bypass

Background:The study evaluated the efficacy of recombinant human antithrombin (rhAT) for restoring heparin responsiveness in heparin resistant patients undergoing cardiac surgery. Methods:This was a multicenter, randomized, double-blind, placebo-controlled study in heparin-resistant patients undergoing cardiac surgery with cardiopulmonary bypass. Heparin resistance was diagnosed when the activated clotting time was less than 480 s after 400 U/kg heparin. Fifty-four heparin-resistant patients were randomized. One cohort received 75 U/kg rhAT, and the other received normal saline. If the activated clotting time remained less than 480 s, this was considered treatment failure, and 2 units fresh frozen plasma was transfused. Patients were monitored for adverse events. Results:Only 19% of patients in the rhAT group received fresh frozen plasma, compared with 81% of patients in the placebo group (P < 0.001). During their hospitalization, 48% of patients in the rhAT group received fresh frozen plasma, compared with 85% of patients in the placebo group (P = 0.009). Patients in the placebo group required higher heparin doses (P < 0.005) for anticoagulation. There was no increase in serious adverse events associated with rhAT. There was increased blood loss 12 h postoperatively (P = 0.05) with a trend toward increased 24-h bleeding in the rhAT group (P = 0.06). There was no difference between the groups in blood and platelet transfusions. Conclusion:Treatment with 75 U/kg rhAT is effective in restoring heparin responsiveness and promoting therapeutic anticoagulation in the majority of heparin-resistant patients. Treating heparin-resistant patients with rhAT may decrease the requirement for heparin and fresh frozen plasma.

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).

The effects of the menstrual cycle on the incidence of emesis and efficacy of ondansetron.

Postoperative nausea and vomiting after general anesthesia remains a complex and perturbing phenomenon associated with several factors.In women, the phase of the menstrual cycle as a factor in postoperative nausea and emesis is controversial. This retrospective study was performed to assess the effects of the menstrual cycle and efficacy of the antiemetic ondansetron on postoperative emesis. A total of 1169 ASA grade I-II patients from two double-blind, placebo-controlled studies were enrolled in 18 centers. Patients with irregular cycles or taking estrogens or progesterones were excluded from the analysis, leaving 873 patients eligible for this study. The patients were stratified on the basis of their last menses into four groups: 1) 1-8, 2) 9-16, 3) 17-28, and 4) 29-35 days. All patients received a general anesthetic with endotracheal intubation. Patients received either 1, 4, or 8 mg ondansetron or placebo given intravenously before induction of anesthesia. All patients were studied for a 24-h period. Emesis rates were compared with respect to the phase of the menstrual cycle and between menstruating and nonmenstruating patients. There was no relationship (P = 0.100) between the incidence of emesis and the phase of the menstrual cycle in the group receiving the placebo. There was, however, a significant reduction (P < 0.001) in emesis for the ondansetron-treated patients regardless of the phase of the menstrual cycle. In addition, ondansetron had a similar dose-response curve in both menstruating and nonmenstruating women. (Anesth Analg 1996;83:565-9)

Clinical Pharmacology of Propofol: An Intravenous Anesthetic Agent

Propofol is a 2,6-diisopropylphenol with sedative-hypnotic properties. Because of its slight solubility in water, the drug is formulated as an emulsion for clinical use. It is highly lipophilic and distributes extensively in the body. The blood concentration-time profile of propofol after an iv bolus injection follows a three-compartment model with half-lives of 2–4 min, 30–45 min, and 3–63 h, respectively. Propofol is extensively metabolized by the liver prior to its elimination by the kidney. Following an iv dose of 2–2.5 mg/kg, loss of consciousness occurs in less than one minute and lasts for approximately five minutes. Hypnosis can be maintained by propofol blood concentrations of 1.5–6 μg/mL in the presence of N2O/O2 (60:40 ratio) or other anesthetic agents. During induction, propofol decreases the systolic and diastolic blood pressure by approximately 20–30 percent with minimal change in heart rate; apnea is also common. The cardiovascular and respiratory effects of propofol, however, should not cause major concern in otherwise healthy patients. By virtue of its pharmacokinetic profile, the drug lends itself to continuous infusion for maintenance of anesthesia. When used as the main anesthetic agent, it produces satisfactory anesthesia with rapid recovery and without major adverse effects in healthy individuals. In continuous infusion propofol can be used as an alternative to inhalation anesthetics.

Clinical Pharmacology of the Neuromuscular Blocking Agents

Neuromuscular blocking agents are among the most commonly used drugs during general anesthesia. They compete with acetylcholine and interfere with the transmission of nerve impulses resulting in skeletal muscle relaxation. Based on their mechanism of action, neuromuscular blocking agents are classified as either depolarizing or nondepolarizing. Succinylcholine is a short-acting depolarizing agent. Commonly used nondepolarizing agents are curare (long-acting), pancuronium (long-acting), atracurium (intermediate-acting), and vecuronium (intermediate-acting). Neuromuscular blocking agents are used clinically to facilitate endotracheal intubation and to provide skeletal muscle relaxation during surgery. This article provides an overview of the physiology of the neuromuscular transmission and summarizes our current knowledge on the use of these agents during general anesthesia.

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. Implications EMLA® Cream (Astra, Westborough, MA) provides satisfactory topical anesthesia of the oropharynx and should be considered a safe and effective alternative for anesthetizing the airway for awake oral fiberoptic intubation.

Entrapment of an exchange wire by an inferior vena caval filter: a technique for removal

The anesthesiology literature does not describe entrapment of a guidewire by an inferior vena caval filter. Because anesthesiologists are involved in central access in various perioperative and intraoperative settings, consideration of this complication is important. A case of guidewire entrapment by an inferior vena caval filter and a unique technique for removal of the entrapped wire is presented.

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.

Comparative Evaluation of the Neuromuscular and Cardiovascular Effects of Pipecuronium, Pancuronium, Atracurium, and Vecuronium Under Isoflurane Anesthesia

The neuromuscular and cardiovascular effects of intubating doses of pipecuronium 80 μg/kg, pancuronium 100 μg/kg, atracurium 500 μg/kg, and vecuronium 100 μg/kg were compared in 62 patients under isoflurane (end‐tidal concentration = 0.5–1%) anesthesia. Pipecuronium, pancuronium, and vecuronium had no significant effect on systolic or diastolic blood pressure. In one patient the administration of atracurium resulted in significant hypotension. Heart rate was significantly increased only after the administration of pancuronium. The neuromuscular‐blocking effect of pipecuronium and pancuronium appears to be twice as long as that of vecuronium and atracurium. Administration of neostigmine resulted in significantly faster recovery of muscle function in patients receiving vecuronium or atracurium. Although pipecuroniums neuromuscular‐blocking effect is similar to that of pancuronium, its lack of cardiovascular effects more closely resembles that of vecuronium.