The interaction of intramuscularly injected ketamine and its N-demethylated metabolite (metabolite I) with halothane was evaluated in rats. Five, 10, 20, or 50 mg/kg of ketamine alone or 20, 50, or 100 mg/kg of metabolite I alone produced less than 10 minutes of hypnosis. However, halothane anesthetic requirement (i.e., MAC) was depressed in a dose-dependent fashion as much as 56% 1-2 hours and as much as 14% 5-6 hours after injection of ketamine, 50 mg/kg, im.
The conditions under which prolongation of halothane-induced sleeping time in the mouse may be used as a test for centrally acting drugs are described. The test can be recommended for its practical advantages over methods using barbiturates to induce hypnosis; due cognizance must be taken of a diurnal variation in the response of mice to halothane. To assess the usefulness of the test the effects of amphetamine, chlorpromazine, histamine, morphine, nikethamide, pentobarbitone and SKF 525A have been investigated.
The uricosuric agent, probenecid, when administered prior to systemic administration of pentobarbital led to a decreased latency, to loss of righting reflex and to a potentiation of the duration of hypnosis. This potentiation was dose-related and doses of probenecid below 50 mg/kg (i.p.) were without effect. Pretreatment of rats with sulfinpyrazone, another uricosuric agent, yielded similar results. Pretreatment of animals with probenecid shortened the latency to onset of hypnosis induced by halothane (i.p.) and increased the duration of loss of righting reflex, 3-fold.
We studied 94 healthy ASA physical status I or II children to determine the end-expired concentration of halothane associated with eye opening on emergence from anesthesia, and to determine if parenteral opioid therapy or regional analgesia significantly altered this concentration. In our study, anesthesia was maintained with halothane in an air-oxygen mixture. After the surgical procedure was completed, the inspired concentration of halothane was adjusted to zero and the end-expired concentrations were permitted to decrease spontaneously.
BACKGROUND: In humans the ventilatory response to isocapnic hypoxia is biphasic: an initial increase in minute ventilation (VE) from baseline, the acute hypoxic response, is followed after 3-5 min by a slow ventilatory decay, the hypoxic ventilatory decline, and a new steady state, 25-40% greater than baseline VE, is reached in about 15-20 min. The transition from 20 min of isocapnic hypoxia into normoxia results in a rapid decrease in VE, the off-response. In humans, halothane, at subanesthetic concentrations, is known to decrease the acute hypoxic response.
BACKGROUND: The mammalian gamma-aminobutyric acid type A (GABA(A)) receptor, a likely target of anesthetic action, exhibits remarkable subunit heterogeneity. In vitro expression studies suggest that there is subunit specificity to anesthetic responses at the GABA(A) receptor. The authors tested whether genetically engineered mice that lack the beta3 subunit of the GABA(A) receptor differed in their sensitivities to several general anesthetic agents.
We used two mouse lines with glycine receptor mutations to determine whether glycine receptors might play an important role in anesthetic responses in vivo. Spastic (spA) mutants were slightly more sensitive (P = 0.02) to enflurane in the loss-of-righting reflex assay (50% effective concentration [EC(50)] = 1.17 +/- 0.06 atm for controls versus 0.97 +/- 0.06 atm for spA) but were also substantially more resistant (P = 0.01) to enflurane in the tail clamp assay (EC(50) = 1.96 +/- 0.10 atm for controls versus 2.58 +/- 0.25 atm for spA).
FASEB journal: official publication of the Federation of American Societies for Experimental Biology
General anesthetics are widely used in clinical practice. On the molecular level, these compounds have been shown to modulate the activity of various neuronal ion channels. However, the functional relevance of identified sites in mediating essential components of the general anesthetic state, such as immobility and hypnosis, is still unknown. Using gene-targeting technology, we generated mice harboring a subtle point mutation (N265M) in the second transmembrane region of the beta3 subunit of the GABA(A) receptor.
We hypothesized that like bispectral index, entropy may be anesthetic agent specific. We carried out a study to assess the entropy values of different anesthetics at equi-minimal alveolar concentrations (MACs) with air and nitrous oxide as carrier gases. Thirty adult patients undergoing spine surgery were randomized to receive halothane, isoflurane, or sevoflurane, in 2 stages, (a) with air/oxygen mixture (2:1) and (b) in nitrous oxide/oxygen (2:1). Heart rate, mean arterial blood pressure, response entropy (RE), and state entropy (SE) were noted at 1.0 and 1.5 MACs for each agent.