Anesthesia and analgesia
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Anesthesia and analgesia · May 2002
The neuropathologic effects in rats and neurometabolic effects in humans of large-dose remifentanil.
Given in clinically relevant large doses to rats, mu-opioids produce limbic system hypermetabolism and histopathology. This investigation extends these observations, in both rats and humans, for the short-acting drug remifentanil, which allows more precise control and assessment of the effects of duration of opioid exposure. We performed two series of experiments: one in rats for neuropathologic effects and the second in humans for neurometabolic effects. Fifty mechanically ventilated rats received saline solution or remifentanil 20-160 microg x kg(-1) x min(-1) for 3 h, followed by neuropathologic evaluation 7 days later. Four volunteers underwent induction of anesthesia and endotracheal intubation with propofol and rocuronium administration followed by remifentanil infusion at 1-3 microg x kg(-1) x min(-1) with positron emission tomography evaluation of cerebral metabolic rate for glucose. In rats, dose-related electroencephalogram activation was evident and 19 of 40 remifentanil-treated rats showed brain damage, primarily in the limbic system (P < 0.01). In humans, cerebral metabolic rate for glucose in the temporal lobe increased from 6.29 +/- 0.32 to 7.68 +/- 1.05 mg x 100 g(-1) x min(-1) (P < 0.05). These data indicate that prolonged large-dose remifentanil infusion is neurotoxic in rats with congruent metabolic effects with brief infusion in humans and suggest that some adverse effects reported in rats may be clinically relevant. ⋯ This study demonstrates dose-related remifentanil neurotoxicity in physiologically controlled rats with congruent brain metabolic effects in four humans undergoing positron emission tomography evaluation during brief large-dose remifentanil anesthesia. These data suggest that some adverse effects reported in rats may be clinically relevant.
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Anesthesia and analgesia · May 2002
The role of ketamine in preventing fentanyl-induced hyperalgesia and subsequent acute morphine tolerance.
Perioperative opioids increase postoperative pain and morphine requirement, suggesting acute opioid tolerance. Furthermore, opioids elicit N-methyl-D-aspartate (NMDA)-dependent pain hypersensitivity. We investigated postfentanyl morphine analgesic effects and the consequences of NMDA-receptor antagonist (ketamine) pretreatment. The rat nociceptive threshold was measured by the paw-pressure vocalization test. Four fentanyl boluses (every 15 min) elicited a dose-dependent (a) increase followed by an immediate decrease of the nociceptive threshold and (b) reduction of the analgesic effect of a subsequent morphine administration (5 mg/kg): -15.8%, -46.6%, -85.1% (4 x 20, 4 x 60, 4 x 100 microg/kg of fentanyl, respectively). Ketamine pretreatment (10 mg/kg) increased the fentanyl analgesic effect (4 x 60 microg/kg), suppressed the immediate hyperalgesic phase, and restored the full effect of a subsequent morphine injection. Fentanyl also elicited a delayed dose-dependent long-lasting decrease of the nociceptive threshold (days) that was prevented by a single ketamine pretreatment before fentanyl. However, a morphine administration at the end of the fentanyl effects restored the long-lasting hyperalgesia. Repeated ketamine administrations were required to obtain a complete preventive effect. Although ketamine had no analgesic effect per se at the dose used herein, our results indicate that sustained NMDA-receptor blocking could be a fruitful therapy for improving postoperative morphine effectiveness. ⋯ Fentanyl-induced analgesia is followed by early hyperalgesia (hours), acute tolerance to the analgesic effects of morphine, and long-lasting hyperalgesia (days). All these phenomena are totally prevented by repeated administrations of the NMDA-receptor antagonist, ketamine, simultaneously with fentanyl and morphine administration.
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Anesthesia and analgesia · May 2002
Changing allocations of operating room time from a system based on historical utilization to one where the aim is to schedule as many surgical cases as possible.
Many facilities allocate operating room (OR) time based on historical utilization of OR time. This assumes that there is a fixed amount of regularly scheduled OR time, called "block time". This "Fixed Hours" system does not apply to many surgical suites in the US. Most facilities make OR time available for all its surgeons' patients, even if cases are expected to finish after the end of block time. In this setting, OR time should be allocated to maximize OR efficiency, not historical utilization. Then, cases are scheduled either on "Any Workday" (i.e., date chosen by patient and surgeon) or within a reasonable time (e.g., "Four Weeks"). In this study, we used anesthesia billing data from two facilities to study statistical challenges in converting from a Fixed Hours to an Any Workday or Four Weeks patient scheduling system. We report relationships among the number of staffed ORs (i.e., first case of the day starts), length of the regularly scheduled OR workday, OR efficiency, OR staffing cost, and changes in services' OR allocations. These relationships determine the expected changes in each service's OR allocation, when a facility using Fixed Hours considers converting to the Any Workday or Four Weeks systems. ⋯ We investigated the complex relationships among the number of surgical services, number of staffed operating rooms (ORs), length of the regularly scheduled OR workday, efficiency of use of OR time, OR staffing cost, and changes in each services' allocated OR time.
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Anesthesia and analgesia · May 2002
The effects of acute normovolemic hemodilution on left ventricular systolic and diastolic function in the absence or presence of beta-adrenergic blockade in dogs.
Acute normovolemic hemodilution (ANH) increases cardiac output because of a reduction in blood viscosity and enhancement of left ventricular (LV) contractility. The status of LV function, especially LV diastolic function during ANH, remains controversial. We therefore examined LV systolic and diastolic function during ANH. Sixteen dogs were anesthetized with isoflurane in the absence (Group 1) and presence (Group 2) of beta-adrenergic blockade (propranolol 1 mg/kg). LV contractility was quantified by the slope (M(w)) of the stroke work and end-diastolic volume relation. Diastolic function was evaluated with the time constant of LV relaxation (T), chamber stiffness constant (K(c)), peak LV diastolic filling rate during early filling (peak E) and atrial contraction (peak A), and ratio of peak E to peak A (E/A). Normovolemic exchange of blood (50 mL/kg) for 6% hydroxyethyl starch (ANH50) significantly increased M(w) in Group 1 but not in Group 2. In both groups, ANH50 significantly decreased T. ANH50 significantly increased peak E in both groups and peak A in Group 1, and it did not change the E/A ratio or K(c) in either group. ANH causes positive inotropic effects and enhances diastolic function without beta-blockade. Even after beta-adrenergic blockade, ANH improves diastolic function through the reduction of LV ejection impedance. ⋯ Acute normovolemic hemodilution enhances LV (left ventricular) diastolic function by alterations in the LV loading condition produced by hemodilution, which mainly contributes to a compensatory increase in cardiac output.