Lack of effect of ondansetron on the pharmacokinetics and analgesic effects of morphine and metabolites after single-dose morphine administration in healthy volunteers.

AIMS: The purpose of this investigation was to study the influence of ondansetron on the single-dose pharmacokinetics and the analgesic effects elicited by morphine and the 3- and 6-glucuronide metabolites of morphine in healthy volunteers. METHODS: This was a randomized, double-blind, placebo-controlled, two-way crossover study in which six male and six female subjects were administered a single 10 mg intravenous dose of morphine sulphate, followed 30 min later by a single 16 mg intravenous dose of ondansetron hydrochloride or placebo. Serum and urine concentrations of morphine, morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) samples were quantified over 48 h using high performance liquid chromatography with detection by mass spectrometry. Analgesia was assessed in the volunteers with a contact thermode device to provide a thermal pain stimulus. Four analgesic response variables were measured including thermal pain threshold, thermal pain tolerance, temporal summation of pain and mood state. RESULTS: The two treatments appeared to be equivalent based on the 90% confidence intervals (0.6, 1.67) of the least squares means ratio. All least squares means ratio confidence intervals for each parameter, for each analyte fell within the specified range, demonstrating a lack of an interaction. CONCLUSIONS: The results of this study suggest that administration of ondansetron (16 mg i.v.) does not alter the pharmacokinetics of morphine and its 3- or 6-glucuronide metabolites to a clinically significant extent, nor does it affect the overall analgesic response to morphine as measured by the contact thermode system.

Transmission of viral disease in the operating room setting.

The transmission of viral disease in the operating room is an evolving problem. Advances in transfusion medicine have made blood supply safer than ever, whereas changes in transfusion practice have minimized the amount of blood transfused. The epidemiology of viral infection is changing in both the general population and among healthcare workers. Vaccination and prevention hold the key to future risk reduction for patients and providers.

Multicenter study of contaminated percutaneous injuries in anesthesia personnel.

BACKGROUND: Anesthesia personnel are at risk for occupational infection with bloodborne pathogens from contaminated percutaneous injuries (CPIs). Additional information is needed to formulate methods to reduce risk. METHODS: The authors analyzed CPIs collected during a 2-yr period at 11 hospitals, assessed CPI underreporting, and estimated risks of infection with human immunodeficiency virus and hepatitis C virus. RESULTS: Data regarding 138 CPIs were collected: 74% were associated with blood-contaminated hollow-bore needles, 74% were potentially preventable, 30% were considered high-risk injuries from devices used for intravascular catheter insertion or obtaining blood, and 45% were reported to hospital health services. Corrected for injury underreporting, the CPI rate was 0.27 CPIs per yr per person; per full-time equivalent worker, there were 0.42 CPIs/yr. The estimated average 30-yr risks of human immunodeficiency virus or hepatitis C virus infection per full-time equivalent are 0.049% and 0.45%, respectively. Projecting these findings to all anesthesia personnel in the United States, the authors estimate that there will be 17 human immunodeficiency virus infections and 155 hepatitis C virus infections in 30 yr. CONCLUSIONS: Performance of anesthesia tasks is associated with CPIs from blood-contaminated hollow-bore needles. Thirty percent of all CPIs would have been high-risk for bloodborne pathogen transmission if the source patients were infected. Most CPIs were potentially preventable, and fewer than half were reported to hospital health services. The results identify devices and mechanisms responsible for CPIs, provide estimates of risk levels, and permit formulation of strategies to reduce risks.

Nociceptive mechanisms modulate ozone-induced human lung function decrements.

We have previously suggested that ozone (O3)-induced pain-related symptoms and inhibition of maximal inspiration are due to stimulation of airway C fibers (M. J. Hazucha, D. V. Bates, and P. A. Bromberg. J. Appl. Physiol. 67: 1535-1541, 1989). If this were so, pain suppression or inhibition by opioid-receptor agonists should partially or fully reverse O3-induced symptomatic and lung functional responses. The objectives of this study were to determine whether O3-induced pain limits maximal inspiration and whether endogenous opioids contribute to modulation of the effects of inhaled O3 on lung function. The participants in this double-blind crossover study were healthy volunteers (18-59 yr) known to be "weak" (WR; n = 20) and "strong" O3 responders (SR; n = 42). They underwent either two 2-h exposures to air or two 2-h exposures to 0. 42 parts/million O3 with moderate intermittent exercise. Immediately after post-O3 spirometry, the WR were randomly given either naloxone (0.15 mg/kg iv) or saline, whereas SR randomly received either sufentanil (0.2 microgram/kg iv) or saline. O3 exposure significantly (P < 0.001) impaired lung function. In SR, sufentanil rapidly, although not completely, reversed both the chest pain and spirometric effects (forced expiratory volume in 1 s; P < 0.0001) compared with saline. Immediate postexposure administration of saline or naloxone had no significant effect on WR. Plasma beta-endorphin levels were not related to an individual's O3 responsiveness. Cutaneous pain variables showed a nonsignificant weak association with O3 responsiveness. These observations demonstrate that nociceptive mechanisms play a key role in modulating O3-induced inhibition of inspiration but not in causing lack of spirometric response to O3 exposure in WR.

Alteration of renal blood flow during epidural anesthesia in normal subjects.

The cardiovascular consequences of epidural anesthesia secondary to sympathetic blockade are well documented; however, their repercussions on renal hemodynamics in humans have not been reported. We investigated the effect of epidural anesthesia on renal blood flow (RBF) in 13 healthy volunteers 18-45 yr of age. RBF was measured using paraaminohippurate clearance before and after bilateral T6 epidural sensory block (to ensure adequate sympathetic renal nerve blockade). Epidural anesthesia was established using 22 +/- 3 mL of 2% plain lidocaine (without epinephrine) via L1-L2 epidural catheter; urine output was measured using a three-way Foley catheter. Mean arterial pressure remained > or = 70 mm Hg in all subjects without any pharmacologic intervention. Mean RBF before epidural anesthesia was 16.1 +/- 6.8 mL.kg-1.min-1 and 14.3 +/- 2.9 mL.kg-1.min-1 after bilateral T6 epidural blockade. We conclude that the institution of epidural anesthesia in healthy subjects does not result in a significant change in RBF (P > 0.25).