Influence of hemorrhagic shock on remifentanil: a pharmacokinetic and pharmacodynamic analysis.

BACKGROUND: Hemorrhagic shock is known to alter significantly the pharmacokinetics of fentanyl, an opioid that requires delivery to the liver for metabolism. The authors hypothesized that the pharmacokinetics and pharmacodynamics of remifentanil, an esterase metabolized opioid that does not require delivery to a metabolic organ, would be altered less by hemorrhagic shock that those of fentanyl. METHODS: Sixteen pigs were assigned randomly to control and shock groups. The shock group was bled using an isobaric hemorrhage model. Remifentanil 10 microg x kg(-1) x min(-1) was infused for 10 min to both groups. Arterial samples were collected for remifentanil concentration assay. Pharmacokinetic parameters were estimated using a three-compartment model. The electroencephalogram spectral edge was used as a measure of drug effect. The pharmacodynamics were characterized using a sigmoid inhibitory maximal effect model. RESULTS: Remifentanil blood levels were higher in the shocked group. The central clearance was slower and the central compartment was smaller in shocked animals. No difference between groups was observed in the magnitude or time course of the remifentanil-induced decrease in spectral edge. CONCLUSIONS: Hemorrhagic shock altered the pharmacokinetics of remifentanil, suggesting that less remifentanil would be required to maintain a target plasma concentration. However, because of its rapid metabolism, the impact of hemorrhagic shock on the concentration decline of remifentanil after termination of the infusion was minimal. Hemorrhagic shock did not alter the pharmacodynamics of remifentanil.

Effects of intrathecal morphine on the ventilatory response to hypoxia.

BACKGROUND: Intrathecal administration of morphine produces intense analgesia, but it depresses respiration, an effect that can be life-threatening. Whether intrathecal morphine affects the ventilatory response to hypoxia, however, is not known. METHODS: We randomly assigned 30 men to receive one of three study treatments in a double-blind fashion: intravenous morphine (0.14 mg per kilogram of body weight) with intrathecal placebo; intrathecal morphine (0.3 mg) with intravenous placebo; or intravenous and intrathecal placebo. The selected doses of intravenous and intrathecal morphine produce similar degrees of analgesia. The ventilatory response to hypercapnia, the subsequent response to acute hypoxia during hypercapnic breathing (targeted end-tidal partial pressures of expired oxygen and carbon dioxide, 45 mm Hg), and the plasma levels of morphine and morphine metabolites were measured at base line (before drug administration) and 1, 2, 4, 6, 8, 10, and 12 hours after drug administration. RESULTS: At base line, the mean (+/-SD) values for the ventilatory response to hypoxia (calculated as the difference between the minute ventilation during the second full minute of hypoxia and the fifth minute of hypercapnic ventilation) were similar in the three groups: 38.3+/-23.2 liters per minute in the placebo group, 33.5+/-16.4 liters per minute in the intravenous-morphine group, and 30.2+/-11.6 liters per minute in the intrathecal-morphine group (P=0.61). The overall ventilatory response to hypoxia (the area under the curve) was significantly lower after either intravenous morphine (20.2+/-10.8 liters per minute) or intrathecal morphine (14.5+/-6.4 liters per minute) than after placebo (36.8+/-19.2 liters per minute) (P=O.003). Twelve hours after treatment, the ventilatory response to hypoxia in the intrathecal-morphine group (19.9+/-8.9 liters per minute), but not in the intravenous-morphine group (30+/-15.8 liters per minute), remained significantly depressed as compared with the response in the placebo group (40.9+/-19.0 liters per minute) (P= 0.02 for intrathecal morphine vs. placebo). Plasma concentrations of morphine and morphine metabolites either were not detectable after intrathecal morphine or were much lower after intrathecal morphine than after intravenous morphine. CONCLUSIONS: Depression of the ventilatory response to hypoxia after the administration of intrathecal morphine is similar in magnitude to, but longer-lasting than, that after the administration of an equianalgesic dose of intravenous morphine.

Delays in the detection of hypoxemia due to site of pulse oximetry probe placement.

STUDY OBJECTIVES: To determine if there were any differences in the time to detect hypoxemia related to the site of peripheral pulse oximetry (ear, hand, and foot) during the rapid induction of hypoxemia in healthy volunteers. DESIGN: Repeated-measures, longitudinal, observational study. SETTING: Anesthesia clinical research area of the Department of Anesthesiology. PATIENTS: 13 healthy volunteers, aged 18 to 44 years. INTERVENTIONS: Nellcor N-200 (Nellcor, Inc., Pleasanton, CA) oximeter probes were placed at the ear, hand, and foot. All units were turned on simultaneously with averaging times set for 5 seconds and signals sampled at 2 Hz. A computer-controlled anesthesia circuit was employed to induce mild hypercapnia and hyperoxia (end-tidal gas partial pressures: PETCO2 = 42 +/- 2 mmHg and PETO2 = 130 mmHg) for 5 minutes. PETO2 was then decreased to 45 +/- 2 mmHg over 60 seconds and held at that value for 5 minutes. MEASUREMENTS AND MAIN RESULTS: The mean differences in time (sec) for pulse oximeters to detect hypoxemia (read less than 90%) between probe sites were determined and compared. The following mean differences in time (sec) for pulse oximeters to detect hypoxemia (read less than 90%) between probe sites were found: ear-hand = 6; hand-foot = 57; ear-foot = 63. Paired t-tests revealed statistically significant mean time delay differences of 51 seconds (p < 0.005) and 57 seconds (p < 0.005) for ear-hand versus hand-foot and for ear-hand versus ear-foot, respectively. CONCLUSIONS: In healthy volunteers, significant delays in the detection of acute hypoxemia by pulse oximetry occur when pulse oximeters are placed at the toe as compared with probes at either the ear or hand.

Intrathecal lipophilic opioids as adjuncts to surgical spinal anesthesia.

BACKGROUND AND OBJECTIVES: Lipophilic opioids, especially fentanyl and sufentanil, are increasingly being administered intrathecally as adjuncts to spinal anesthesia. This review analyzes the efficacy of these opioids for subarachnoid anesthesia. METHODS: Medline search of the literature from 1980 to the present and a survey of recent meeting abstracts are reviewed. RESULTS: A significant number of citations regarding intrathecal lipophilic opioids as adjuncts to spinal anesthesia were found: 59 are cited in this review. Most clinical experience has been in obstetric surgery, but lipophilic spinal opioid administration is being used with greater frequency for other surgical procedures as well. The benefits include reduction of minimal alveolar concentration (MAC) when general anesthesia is combined with spinal anesthesia and enhancement of the quality of spinal anesthesia without prolongation of motor block. Intrathecal fentanyl and sufentanil allow clinicians to use smaller doses of spinal local anesthetic, yet still provide excellent anesthesia for surgical procedures. Furthermore, lipophilic opioid/local anesthetic combination permits more rapid motor recovery; short outpatient procedures are therefore more amenable to spinal anesthesia. Finally, the side-effect profiles of intrathecal lipophilic opioids are now well characterized and appear less troublesome than intrathecal morphine. CONCLUSIONS: The anesthesia-enhancing properties and side-effect profile of lipophilic opioids administered intrathecally suggest significant roles for these agents as adjuncts to spinal anesthesia for obstetric and outpatient procedures.