Anesthetic Requirements For Halothane Research Articles

The effect of imidazoline receptors and alpha2-adrenoceptors on the anesthetic requirement (MAC) for halothane in rats.

Recent evidences have documented that several pharmacologic actions of alpha2-adrenoceptor agonists are mediated via activation of not only alpha2-adrenoceptors, but also by imidazoline receptors, which are nonadrenergic receptors in the central nervous system. However, the effect of imidazoline receptors on the anesthesia is not well known, and it is important to clarify the effects of both receptors on anesthesia. Seventy-two rats were anesthetized with halothane, and the anesthetic requirement for halothane was evaluated as minimum alveolar concentration (MAC). The MAC for halothane was determined in the presence of dexmedetomidine (0, 10, 20, and 30 microg/kg, intraperitoneally [IP]), a selective alpha2-adrenoceptor agonist with weak affinity for imidazoline receptors. Then, the authors evaluated the inhibitory effect of rauwolscine (20 mg/kg, IP), an alpha2-adrenoceptor antagonist with little affinity for imidazoline receptors, on the MAC-reducing action of dexmedetomidine (30 microg/kg). Further, the effect of rilmenidine (20, 50, 100, 1000 microg/kg, IP), a selective imidazoline receptor agonist, on the MAC for halothane was also investigated. Dexmedetomidine decreased the MAC for halothane dose-dependently, and this MAC-reducing action of dexmedetomidine was completely blocked by rauwolscine. Rilmenidine alone did not change the MAC for halothane. The present data indicate that the anesthetic sparing action of dexmedetomidine is most likely mediated through alpha2- adrenoceptors, and the stimulation of imidazoline receptors exerts little effect on the anesthetic requirement for halothane.

Halothane anesthetic requirements are not affected by aminophylline treatment in rats and dogs.

The authors determined the effects of aminophylline on the anesthetic requirements for halothane in rats and dogs. MAC for halothane was determined in rats (n = 24) before and after aminophylline, 100 mg X kg-1 ip, or an equal volume of saline. Because changes in central noradrenergic neurotransmission have been linked to drug-induced changes in the depth of the anesthetic state, we investigated the effect of aminophylline on the turnover of norepinephrine in discrete brain regions of halothane-anesthetized rats. To facilitate testing at steady-state aminophylline conditions and to permit frequent blood sampling, halothane MAC was determined in dogs (n = 7) before and after a therapeutic level of aminophylline (15 +/- 2 micrograms X ml-1) was obtained. Neither in the rats (1.0 vs. 1.0%) nor in the dogs (1.04 +/- 0.14 vs. 1.01 +/- 0.14%) was halothane MAC affected by aminophylline treatment. Commensurate with the lack of change of anesthetic depth, aminophylline treatment did not affect noradrenergic neurotransmission in the brain of halothane-anesthetized rats. Furthermore, the anticipated increase in circulating catecholamines following aminophylline treatment in dogs did not materialize. The authors conclude that halothane anesthetic requirements are not altered by aminophylline treatment, possibly because of the attenuation of the putative sympathomimetic effects of aminophylline by halothane.

Anesthetic Requirements for Halothane in Young Children 0???1 Month and 1???6 Months of Age

In a previous study, the authors found that infants, in the first 6 months of life, required the highest minimum alveolar concentration (MAC) of any age group (1.09% halothane). Because only two neonates (0-31 days of age) were included in the original study and because profound depression of blood pressure and heart rate have been reported in neonates, the authors determined 1) whether the MAC of halothane in neonates (n = 12) differs from that in infants (1-6 months of age) (n = 12) and 2) whether the blood pressure and heart rate responses in neonates differ from those in infants at approximately 1 MAC. The authors found that the MAC of halothane in neonates, 0.87% +/- 0.03 SEM, was significantly lower (P less than 0.01) than that in infants, 1.20% +/- 0.06 SEM. With induction of anesthesia, the systolic blood pressure decreased 23% in neonates (P less than 0.05) and 34% in infants (P less than 0.005) from awake values. Similarly, the heart rate decreased 12% in neonates and 22% in infants (P less than 0.05). The incidence of hypotension (greater than 30% decrease in systolic blood pressure from awake) in neonates, 33%, was not significantly different from that in infants, 44%. The authors conclude that the MAC of halothane in neonates is 25% less than that in infants and significantly less than was thought previously. The MAC in infants is the highest of any age group. The decrease in blood pressure and the incidence of hypotension in neonates are similar to those in infants at approximately 1 MAC of halothane.

Anesthetic requirements for halothane in young children 0-1 month and 1-6 months of age.

In a previous study, the authors found that infants, in the first 6 months of life, required the highest minimum alveolar concentration (MAC) of any age group (1.09% halothane). Because only two neonates (0-31 days of age) were included in the original study and because profound depression of blood pressure and heart rate have been reported in neonates, the authors determined 1) whether the MAC of halothane in neonates (n = 12) differs from that in infants (1-6 months of age) (n = 12) and 2) whether the blood pressure and heart rate responses in neonates differ from those in infants at approximately 1 MAC. The authors found that the MAC of halothane in neonates, 0.87% +/- 0.03 SEM, was significantly lower (P less than 0.01) than that in infants, 1.20% +/- 0.06 SEM. With induction of anesthesia, the systolic blood pressure decreased 23% in neonates (P less than 0.05) and 34% in infants (P less than 0.005) from awake values. Similarly, the heart rate decreased 12% in neonates and 22% in infants (P less than 0.05). The incidence of hypotension (greater than 30% decrease in systolic blood pressure from awake) in neonates, 33%, was not significantly different from that in infants, 44%. The authors conclude that the MAC of halothane in neonates is 25% less than that in infants and significantly less than was thought previously. The MAC in infants is the highest of any age group. The decrease in blood pressure and the incidence of hypotension in neonates are similar to those in infants at approximately 1 MAC of halothane.

Verapamil decreases MAC for halothane in dogs.

Verapamil hydrochloride is a calcium entry blocking drug that is being prescribed with increasing frequency for cardiovascular disorders in the perioperative setting. Verapamil's calcium channel blocking effect is not selective, because it also exerts activity on the sodium channel. Because of the well-described effects of sodium channel blockers on anesthetic requirements, the authors studied the MAC for halothane in dogs before and after a therapeutic dose of verapamil 0.5 mg . kg-1. There was a 25% reduction in halothane MAC from 0.97-0.72% (P less than 0.01) when a therapeutic plasma level of verapamil (64 ng . ml-1) was present. Anesthetic requirements for halothane are reduced by dl-verapamil possibly on the basis of its local anesthetic-like sodium channel blocking properties. Adjustments in anesthetic dosage may be necessary in patients receiving verapamil.

Physostigmine and anesthetic requirement for halothane in dogs.

To investigate the effect of physostigmine on central nervous system (CNS) depression produced by halothane, control halothan minimum alveolar concentration (MAC) measured over 1 hour in 7 dogs was compared to MAC 30 minutes after each sequential IV dose of 0.04, 0.4, and 4 mg/kg physostigmine. MAC decreased 6.8, 11.1 (p less than 0.05), and 35.9 (p less than 0.01) percent, respectively. Six dogs were observed for an acute increase in halothane requirement in the first 30 minutes after administration of physostigmine. All 6 showed such a response at 1 or more dose levels, beginning within 1 to 5 minutes after administration and lasting 2 to 30 minutes (p less than 0.05). Five other dogs were tested with neostigmine in the same doses and showed respective decreases in MAC of 7.9, 16.6 (p less than 0.01), and 17.5 ( less than 0.01) percent. No dog showed an acute increase in anesthetic requirement. Intravenous atropine 0.5 mg/kg failed to further alter MAC after 4 mg/kg neostigmine. Physostigmine transiently antagonizes halothane anesthesia, presumably by facilitating cholinergic transmission in the CNS; neostigmine does not. After this initial response, both drugs decrease anesthetic requirement. If these data may be extrapolated to patients, they suggest that physostigmine is not an effective antagonist to postoperative somnolence due to halothane.

Determination of anesthetic requirement in rats.

Estimates of anesthetic requirement based on inspired anesthetic gas concentrations assume equilibration with alveolar, and consequently brain, anesthetic gas tensions. This assumption may be rendered invalid by the solubility of the anesthetic agent and its effects on ventilation. To test this assumption, ED50 values of anesthesia using halothane and a less soluble anesthetic, isoflurane, were determined in rats with and without tracheostomies. Alveolar ED50 or MAC for halothane and isoflurane were 1.11 ± 0.03 per cent and 1.38 ± 0.02 per cent, respectively. Inspired ED50 values 2–3 hours after induction in non-tracheostomized rats were 14 and 17 per cent greater, respectively, than alveolar ED50 values 2–3 hours following tracheostomy during halothane and isoflurane anesthesia in the same animals. These data demonstrate that previous studies in which the anesthetic requirement for halothane was determined using inspired gas samples are inaccurate. Inspired ED50 values for halothane and isoflurane in rats without tracheostomies were 2 and 11 per cent greater, respectively, than inspired ED50 values in the same animals with tracheostomies. Even after 3 hours of anesthesia in tracheostomized rats, measurements of inspired-to-alveolar differences in anesthetic gas tension revealed 9 and 3 per cent differences for halothane and isoflurane, respectively. Thus, the use of inspired concentration for this purpose in rats should be limited to inhalation anesthetics with low blood–gas partition coefficients and with minimal effects on ventilation. A moderately or highly soluble anesthetic agent or one which results in significant respiratory depression necessitates the direct measurement of “alveolar” anesthetic gas tension to determine anesthetic requirement.

The effects of hypoxia and isovolemic anemia on the halothane requirement (MAC) of dogs. I. The effect of hypoxia.

Using the anesthetic requirement for halothane (MAC) to follow central nervous system depression in dogs, acute hypoxia reduced MAC starting at Pao2 38 mm Hg. The decrease in MAC related to both arterial oxygen content (Cao2) and arterial pH (group 1). Therefore, acute hypoxia to Pao2 30 mm Hg was induced in two groups of dogs during hypocapnia (group 2) and normocapnia (group 3). MAC decreased far more rapidly during normocapnic hypoxia than during hypocapnic hypoxia. Respiratory alkalosis maintained pH at 7.39 in group 2, and Cao2 remained at 10 vol per cent In group 3, arterial pH fell progressively, reducing Cao2 to 7.4 vol per cent at a constant Pao2 of 30 mm Hg. Significant regression lines correlated arterial and mixed venous oxygen contents, arterial oxygen transport, and arterial pH with the decreases in MAC in groups 2 and 3. Serial CSF pH determinations in both groups correlated poorly with the reductions in MAC.