Premedication with H1 and H2 blocking agents reduces the incidence of postoperative nausea and vomiting.

OBJECTIVE: Patients undergoing anaesthesia and surgery frequently complain about postoperative nausea and vomiting (PONV). Whether pretreatment with H1 and H2 blocking agents reduces the incidence of PONV remains controversial. To answer this question, we performed a randomised, prospective, placebo-controlled clinical study to evaluate the efficacy of a premedication with H1 and H2 receptor antagonists. MATERIAL AND SUBJECTS: 1149 patients (both sexes) undergoing surgery were randomly assigned to three treatment groups and one control group. Patients in the treatment groups were premedicated with the following H1 + H2 receptor antagonists:Group 1 (n = 335): 5 mg/kg cimetidine i.v. + 0.1 mg/kg dimetindene i.v. 20 min before induction of anaesthesiaGroup 2 (n = 337): 1.25 mg/kg ranitidine i.v. + 0.1 mg/kg dimetindene i.v. 20 min before induction of anaesthesiaGroup 3 (n = 316): 300 mg ranitidine p.o. + 0.1 mg/kg dimetindene i.v. 1 to 2 h before induction of anaesthesiaGroup 4 (n = 161): 20 ml saline solution i.v. 20 min before induction of anaesthesiaPatients from the treatment groups 1, 2 and 3 received regional or general anaesthesia depending on the clinical decision. All control patients received general anaesthesia consisting of fentanyl, a thiobarbiturate, enflurane, nitrous oxide, oxygen, and vecuronium. RESULTS: The incidence of nausea and vomiting was 8.5%, 6.8% and 5.4% in patients from the treatment groups (1, 2 and 3) who underwent general anaesthesia (n = 545), with no statistically significant differences between groups. The incidence of nausea and vomiting in the control group (n = 161) was 28.3% (nausea) and 27.5% (vomiting), respectively. In patients who underwent regional anaesthesia (n = 443), the incidence of nausea and vomiting was 2.5% and 1.1%, respectively. CONCLUSIONS: Premedication with H1 and H2 blocking agents significantly reduces the incidence of postoperative nausea and vomiting.

Propofol in an emulsion of long- and medium-chain triglycerides: the effect on pain.

IMPLICATIONS: In a test of two formulations of propofol for induction, patients experienced less pain with the formulation in Intralipid (Propofol-Lipuro 1%) than with Diprivan 1%.

Reducing myoclonus after etomidate.

BACKGROUND: The authors hypothesized that myoclonus after etomidate is dose-related, could be suppressed when small doses of etomidate were administered before induction, and is unassociated with seizure-like activity on electroencephalogram (EEG). METHODS: Three studies were performed. In the first study, 36 men were randomly assigned to receive 0.025, 0.050, 0.075, 0.100, 0.200, or 0.300 mg/kg of etomidate. In a second crossover study, eight men were randomly allocated to receive either a pretreatment dose of 0.050 mg/kg etomidate or placebo 50 s before 0.300 mg/kg etomidate was injected. EEG was recorded for subjects in the first two studies. In a third study, 60 patients were randomly allocated to one of three pretreatment doses of etomidate: 0.030, 0.050, or 0.075 mg/kg before 0.300 mg/kg was given. RESULTS: In Study 1, myoclonus was not observed after 0.025 or 0.050 mg/kg etomidate. One volunteer had myoclonus after 0.075 mg/kg and another after 0.100 mg/kg etomidate; three had myoclonus after 0.200 mg/kg; and five after 0.300 mg/kg. Incidence of myoclonus was dose-related (P < or = 0.01). In Study 2, two volunteers (25%) with etomidate pretreatment had mild myoclonus compared to six (75%) with placebo pretreatment (P < or = 0.05). EEG changes, other than delta waves, were not seen during myoclonic epochs. In Study 3, myoclonus was less likely after the small pretreatment doses (0.030 or 0.050 mg/kg) than after the large dose (0.075 mg/kg, P < or = 0.01). CONCLUSIONS: Incidence and intensity of myoclonus after induction with etomidate are dose-related, suppressed by pretreatment, and unassociated with seizure-like EEG activity.

Solvent for etomidate may cause pain and adverse effects.

We tested the hypothesis that the solvent for etomidate was a factor in the incidence of pain and other side effects after injection, and that these were associated with histamine release. Nine of 10 volunteers who received etomidate in a propylene glycol formulation reported moderate to severe pain on injection; only one of 10 subjects who received a lipid emulsion formulation reported mild pain (P < 0.05). The incidence of venous sequelae in the injected vein over the next 8 days was 50% in the propylene glycol group and 0% in the lipid emulsion group (P < 0.05). In one volunteer in the propylene group, there was a 13-fold increase in histamine concentrations and in one subject a four-fold increase. In the lipid emulsion group, no volunteer had an increase in histamine concentrations > 1 ng ml-1. We conclude that etomidate formulated in propylene glycol may cause direct injury to vascular endothelium resulting in pain and venous sequelae, whereas etomidate in lipid emulsion does not. There was no relationship between pain or venous sequelae and histamine release.

Onset time, endotracheal intubating conditions, and plasma histamine after cisatracurium and vecuronium administration.

UNLABELLED: Cisatracurium is a nondepolarizing muscle relaxant with a slow onset. We performed a prospective, randomized, double-blind clinical trial in 60 patients (ASA physical status I or II) to assess whether cisatracurium (0.15 or 0.25 mg/kg) or vecuronium (0.15 mg/kg), administered as a bolus immediately after induction of anesthesia with fentanyl and thiopental, would provide a faster onset time and better tracheal intubating conditions than previously reported. We sought to determine whether patients given muscle relaxants in this commonly used induction sequence would exhibit cutaneous, systemic, or chemical evidence of histamine release. Onset time of the relaxants was determined by using mechanomyography. Intubating conditions were scored on a defined interval scale by an anesthesiologist blinded to the relaxant administered. Heart rate and arterial blood pressure were measured noninvasively every minute from 10 min before to 5 min after the application of the muscle relaxant. Mean (+/- SD) onset times for 0.25 mg/kg cisatracurium (68.3 +/- 19.5 s) and for 0.15 mg/kg vecuronium (69.5 +/- 29.2 s) were significantly different from those in the 0.15 mg/kg cisatracurium group (105 +/- 41.2 s). The intubating conditions were better with the larger dose of cisatracurium or vecuronium (P < 0.03). Although plasma histamine levels were not statistically different among groups, levels >1 ng/mL were observed in 5 of 40 patients who received cisatracurium but in none of the 20 patients who received vecuronium. There were no significant hemodynamic differences among the groups. In a dose of 0.25 mg/kg, cisatracurium has as rapid an onset time as vecuronium 0.15 mg/kg, but the former shows evidence of histamine release. IMPLICATIONS: Cisatracurium has been considered a drug with a relatively slow onset but that has the significant benefit of being devoid of chemically mediated histamine release. In this study, we describe an onset time faster than previously reported when cisatracurium was given immediately after thiopental. We also note that several patients had abnormal histamine levels after cisatracurium administration.

Etomidate revisited.

The major advantage of etomidate is its lack of cardiovascular side effects. In addition, etomidate is supposed to be neuroprotective. The side effects of etomidate include adrenal suppression and myocloni. A review of the recent literature on etomidate, its clinical use, its side effects and its mechanism of action was performed. Among others, major recent advances include a new drug preparation devoid of propylene glycol and its side effects, a new pretreatment technique that may reduce the incidence of myocloni, and the identification of its site of action in the central nervous system.

Pharmacokinetics and pharmacodynamics of propofol in a new solvent.

UNLABELLED: Pain on injection is the most commonly reported adverse event after propofol injection. In a randomized, cross-over study in two groups of 12 healthy male volunteers (24-42 yr), we compared the pharmacokinetics and pharmacodynamics of two new propofol formulations (1% and 2% concentrations) in a fat emulsion consisting of medium- and long-chain triglycerides with the standard propofol formulation. After a single intravenous bolus injection of 2 mg/kg, propofol blood levels were measured for 24 h and evaluated according to an open three-compartment model. The derived pharmacokinetic variables were not different among formulations. Additionally, electroencephalographic recordings of the onset and duration of hypnotic action were comparable with all formulations. After propofol 1% in the new formulation, fewer volunteers reported severe or moderate pain on injection (9%) than after the standard formulation (59%) (P < 0.05). We attribute this result to a lower concentration of free propofol in the aqueous phase of the new formulation. IMPLICATIONS: Changing the composition of the carrier fat emulsion for propofol does not have an impact on the pharmacokinetics and efficacy of propofol, but it promises to provide better patient acceptance by lowering the incidence of moderate and severe pain on injection.

Reducing pain during propofol injection: the role of the solvent.

We hypothesized that the concentration of propofol in the aqueous phase may be the most important variable responsible for the pain experienced during injection of the drug. The concentration of propofol in the aqueous phase (18.57 micrograms/mL) can be decreased by increasing the fat content of the solvent. To test this hypothesis, 36 patients were randomly allocated to one of three groups, each receiving a different formulation of propofol. Group A received 20 mL of propofol alone in a commercial preparation (Diprivan(R) with 10 mL of saline); Group B, 20 mL of propofol to which 5 mL of long-chain triglyceride (LCT) fat emulsion and 5 mL of saline and been added; and Group C, 20 mL of propofol and 10 mL of LCT fat emulsion. The propofol emulsion was injected over 30-60 s into a dorsal vein of the hand. Patients reported pain during injection as none, mild, moderate, or severe (almost intolerable). In Group A, 8 of 12 patients reported moderate or severe pain upon injection whereas in Group C only mild pain was reported by 6 of 12 patients. Our results suggest that a smaller concentration of propofol in the aqueous phase of the emulsion reduces pain on injection. With the addition of more lipid (10 mL), a higher percentage of propofol is absorbed by fat particles. If solvents that permit a smaller concentration of the drug in the aqueous phase of oil-in-water emulsions were used for propofol and other drugs that cause pain on injection, pain would be reduced and patient satisfaction may be increased.