Minimum Alveolar Anesthetic Concentration Of Halothane Research Articles

Rat Dorsal Horn Nociceptive-Specific Neurons Are More Sensitive Than Wide Dynamic Range Neurons to Depression by Immobilizing Doses of Volatile Anesthetics: An Effect Partially Reversed by the Opioid Receptor Antagonist Naloxone

The mechanism and site of action within the spinal cord by which volatile anesthetics produce immobility are not well understood. Little work has been done directly comparing anesthetic effects on neurons with specific functional characteristics that mediate transfer of nociceptive information within the spinal cord. Adult male rats were anesthetized and prepared for extracellular single-unit recordings from the lumbar dorsal horn. Nociceptive-specific (NS) and wide dynamic range (WDR) neurons were identified and noxious heat-evoked neuronal spike rates evaluated at 0.8 and 1.2 anesthetic minimum alveolar anesthetic concentration (MAC) halothane or isoflurane. In another group, noxious heat-evoked responses from NS neurons were evaluated at 0.8, 1.2 MAC halothane, and 1.2 MAC halothane plus IV naloxone (0.1 mg/kg). Increasing halothane from 0.8 to 1.2 MAC reduced the heat-evoked neuronal responses of NS neurons (n = 9) from 827 +/- 122 (mean +/- se) to 343 +/- 48 spikes/min (P < 0.05) but not WDR neurons (n = 9), 617 +/- 79 to 547 +/- 78 spikes/min. Increasing isoflurane from 0.8 to 1.2 MAC reduced the heat-evoked neuronal response of NS neurons (n = 9) from 890 +/- 339 to 188 +/- 97 spikes/min (P < 0.05) but did not alter the response of WDR neurons (n = 9) in which evoked spike rate went from 576 +/- 132 to 601 +/- 119 spikes/min. In a separate group, the response of NS neurons went from 282 +/- 60 to 74 +/- 32 spikes/min (P < 0.05) when halothane was increased from 0.8 to 1.2 MAC. IV administration of naloxone increased the heat-evoked response to 155 +/- 46 spikes/min (P < 0.05). NS but not WDR neurons in the lumbar dorsal horn are depressed by peri-MAC increases of halothane and isoflurane. This depression, at least with halothane, can be partially reversed by the opioid antagonist naloxone. Given that opioid receptors are not likely involved in the mechanisms by which volatile anesthetics produce immobility, this suggests that, although the neuronal depression is of substantial magnitude and occurs concurrent to the production of immobility, it may not play a major role in the production of this anesthetic end point.

Ilioinguinal/Iliohypogastric Blocks in Children: Where Do We Administer the Local Anesthetic Without Direct Visualization?

Ultrasonographic observation of peripheral nerve blocks enables direct visualization of the spread of local anesthetic around the targeted nerves. Similarly, ultrasonography may be used to determine the site of local anesthetic placement when landmark-based techniques are used. We performed a study to determine the actual location of local anesthetic when ilioinguinal/iliohypogastric nerve blocks are performed using landmark-based techniques in children in an attempt to explain a failed block. After induction of general anesthesia (1 minimum alveolar anesthetic concentration halothane and laryngeal mask airway), 62 children scheduled for inguinal surgery received an ilioinguinal/iliohypogastric nerve block based on standard anatomical landmarks. Ultrasonography was then used to determine the actual location of local anesthetic placement. The anesthesiologist performing the block was blinded to the ultrasonographic investigation. Successful blocks were recorded either when the local anesthetic surrounded the nerves or were based on clinical signs after skin incision. In 14% of the blocks, the local anesthetic was administered correctly around the nerves resulting in successful blocks. In the remaining 86%, the local anesthetic was administered in adjacent anatomical structures (iliac muscle 18%, transverse abdominal muscle 26%, internal oblique abdominal muscle 29%, external oblique abdominal muscle 9%, subcutaneous 2%, and peritoneum 2%), and 45% of these blocks failed. Accurate placement of local anesthetic around the ilioinguinal/iliohypogastric nerves in children is seldom possible when landmark-based techniques are used. In the majority of patients, the local anesthetic was inaccurately placed in adjacent anatomical structures with unpredictable block results.

The Differential Effects of Halothane and Isoflurane on Windup of Dorsal Horn Neurons Selected in Unanesthetized Decerebrated Rats

Halothane and isoflurane, in the peri-minimum alveolar anesthetic concentration (MAC) range, exert differential effects on spinal nociceptive neurons, whereby halothane further depresses their responses from 0.8 to 1.2 MAC, whereas isoflurane does not. We presently investigated if these anesthetics differentially affect windup, the progressive increase in neuronal responses to repetitive noxious stimuli, over a broad concentration range from 0 to 1.2 MAC. In decerebrated rats, single-unit recordings were made from dorsal horn neurons exhibiting windup to 20 1-Hz C-fiber strength electrical stimuli. Halothane and isoflurane (0, 0.4, 0.8, and 1.2 MAC) were tested in a counterbalanced crossover protocol. Increasing halothane and isoflurane from 0 to 1.2 MAC progressively suppressed the response to the first stimulus, as well as summed responses to all stimuli (to 34% +/- 8% and 50% +/- 8%, respectively; P < 0.05). Absolute windup (summed response minus 20x the first response) was suppressed by both anesthetics from 0 to 0.8 MAC, with further depression by halothane but not isoflurane at 1.2 MAC. Responses of neurons isolated at 0 MAC were partially, but never totally, depressed at 0.8 MAC. The dose-dependent suppression of windup is consistent with reduced temporal summation of pain. Further depression at 1.2 MAC halothane, but not isoflurane, suggests different sites of immobilizing action for these two anesthetics. Immobility seems to not be mediated by severe anesthetic depression of a subpopulation of nociceptive neurons.

Inhibition of spinal protein kinase C-epsilon or -gamma isozymes does not affect halothane minimum alveolar anesthetic concentration in rats.

Anesthetic effects on receptor or ion channel phosphorylation by enzymes such as protein kinase C (PKC) have been postulated to underlie some aspects of anesthesia. In vitro studies show that anesthetic effects on several receptors are mediated by PKC. To test the importance of PKC for the immobility produced by inhaled anesthetics, we measured the effect of intrathecal injections of PKC-epsilon and -gamma inhibitors on halothane minimum alveolar anesthetic concentration (MAC) in 7-day-old and 21-day-old Sprague-Dawley rats. The inhibitors were made as solutions of 100 pmol/5 microL and were given in a volume of 5 microL (7-day-old [P7] rats) or 10 microL (21-day-old [P21] rats). Controls were saline injections or injections of the peptide carrier at the same concentration and volumes; there were six animals in each group. In P7 rats, MAC values (in percentage of an atmosphere) were 1.63 +/- 0.0727 (mean +/- SEM) in saline controls, 1.55 +/- 0.141 in carrier controls, 1.54 +/- 0.0800 in rats given PKC-epsilon, and 1.69 +/- 0.0554 in rats given PKC-gamma. In P21 animals, the values were 1.20 +/- 0.0490, 1.31 +/- 0.0124, 1.27 +/- 0.0367, and 1.15 +/- 0.0483, respectively. Injection of the inhibitors did not change MAC in either age group. These results do not support an anesthetic effect on phosphorylation as a mechanism underlying the capacity of inhaled anesthetics to prevent movement in response to noxious stimulation, and they indirectly support a direct action on receptors or ion channels.

Halothane Minimum Alveolar Anesthetic Concentration and Neuronal Nitric Oxide Synthase Activity of the Dorsal Horn and the Locus Ceruleus in Rats

Halothane Minimum Alveolar Anesthetic Concentration and Neuronal Nitric Oxide Synthase Activity of the Dorsal Horn and the Locus Ceruleus in Rats

Halothane and Isoflurane Alter Calcium Dynamics in Rat Cerebrocortical Synaptosomes

An increase in synaptosomal Ca2+ triggers neurotransmitter release and volatile anesthetics have been shown to inhibit neurotransmitter release by inhibition of Ca2+ entry.We have examined the effect of isoflurane and halothane on the kinetics of increase and decrease of Ca2+ in rat cerebrocortical synaptosomes ([Ca2+]in). We have also used specific Ca2+ antagonists to examine the role of L-, N-, and P-type Ca2+ channels. Synaptosomal [Ca2+]in was measured spectrofluorometrically using fura-2 as a Ca2+ reporter; Ca2+ transients were initiated by depolarization with 40 mM KCl. We found that <or=to1 minimum alveolar anesthetic concentration halothane and isoflurane decreased peak [Ca2+]in by approximately 40%, that both anesthetics decreased the rate of [Ca2+]in increase and decrease, that specific voltage-dependent calcium channel antagonists had little effect on peak or plateau [Ca2+]in, and that the volatile anesthetics increased the permeability of synaptosomal membranes to Ca2+. These results suggest that the volatile anesthetics, at clinically relevant concentrations, can alter Ca2+ homeostasis in the synapse. Implications: Clinically relevant concentrations of halothane and isoflurane markedly depress K+ -evoked increases in rat cerebrocortical synaptosomal calcium (Ca2+) unrelated to L-, N-, and P-type voltage-dependent calcium channels and increase the Ca2+ permeability of the synaptosomal membrane. These changes in Ca2+ dynamics could have profound effects on Ca2+ signaling in the synapse. (Anesth Analg 1998;87:701-10)

Halothane and isoflurane alter calcium dynamics in rat cerebrocortical synaptosomes.

An increase in synaptosomal Ca2+ triggers neurotransmitter release and volatile anesthetics have been shown to inhibit neurotransmitter release by inhibition of Ca2+ entry. We have examined the effect of isoflurane and halothane on the kinetics of increase and decrease of Ca2+ in rat cerebrocortical synaptosomes ([Ca2+]in). We have also used specific Ca2+ antagonists to examine the role of L-, N-, and P-type Ca2+ channels. Synaptosomal [Ca2+]in was measured spectrofluorometrically using fura-2 as a Ca2+ reporter; Ca2+ transients were initiated by depolarization with 40 mM KCl. We found that < or = 1 minimum alveolar anesthetic concentration halothane and isoflurane decreased peak [Ca2+]in by approximately 40%, that both anesthetics decreased the rate of [Ca2+]in increase and decrease, that specific voltage-dependent calcium channel antagonists had little effect on peak or plateau [Ca2+]in, and that the volatile anesthetics increased the permeability of synaptosomal membranes to Ca2+. These results suggest that the volatile anesthetics, at clinically relevant concentrations, can alter Ca2+ homeostasis in the synapse. Clinically relevant concentrations of halothane and isoflurane markedly depress K+-evoked increases in rat cerebrocortical synaptosomal calcium (Ca2+) unrelated to L-, N-, and P-type voltage-dependent calcium channels and increase the Ca2+ permeability of the synaptosomal membrane. These changes in Ca2+ dynamics could have profound effects on Ca2+ signaling in the synapse.

The effect of nitrous oxide on chest wall function in humans and dogs.

The purpose of this study was to determine the effects of nitrous oxide (N2O) on the chest wall of anesthetized humans and dogs. Six human subjects and six mongrel dogs were studied during 1 minimum alveolar anesthetic concentration halothane anesthesia before and during the substitution of 70% N2O for 70% N2 in the inspired gas mixture. On a separate occasion, measurements also were made in pentobarbital-anesthetized dogs. Respiratory muscle activity was measured using electromyographic (EMG) electrodes. Chest wall configuration was determined by using fast three-dimensional computed tomography in dogs and by using respiratory impedance plethysmography in humans. N2O consistently decreased inspiratory ribcage displacement, a decrease attributable in dogs to decreased inspiratory activation of parasternal intercostal muscles; parasternal intercostal activity was not present in anesthetized humans. The decrease in ribcage motion decreased the tidal volume in humans, but not in dogs, because displacement of the diaphragm was better preserved in dogs, in association with changes in diaphragm EMG activation. N2O significantly increased phasic expiratory muscle activity in halothane-anesthetized humans and pentobarbital-anesthetized dogs. Thus, as has been demonstrated for other anesthetics, the actions of N2O are caused by alterations in the distribution and timing of neural drive to the respiratory muscles, rather than by a global depression of respiratory motoneuron drive. In this study, we examined the effects of nitrous oxide on breathing in halothane-anesthetized dogs and humans. Nitrous oxide affected breathing by changing the distribution and timing of neural drive to the respiratory muscles in a species-dependent manner, rather than by causing a global depression of their activity.

Effects of Epidural and Intravenous Buprenorphine on Halothane Minimum Alveolar Anesthetic Concentration and Hemodynamic Responses

There is limited information regarding the effects of epidural or intravenous (IV) buprenorphine on minimum alveolar anesthetic concentration (MAC) of volatile anesthetic and hemodynamic responses to tracheal intubation and surgical incision.This study was conducted to find the effects of IV and epidural buprenorphine required for postoperative pain relief on halothane MAC and hemodynamic responses to tracheal intubation and surgical incision in 126 female patients. Patients were randomly assigned to the four groups: Group I received IV and epidural saline as a control; Group II was given buprenorphine 4 micro g/kg IV; and Groups III and IV received buprenorphine 2 and 4 micro g/kg epidurally, respectively. Groups II-IV were divided into two subgroups according to the timing of administration, either at induction of anesthesia in the operating room (OR) (OR group) or 90 min before anesthetic induction in the ward (Ward group). Anesthesia was induced with only halothane in oxygen, and the trachea was intubated without other drugs. Halothane MAC was determined by logistic regression analysis and the Dixon up-and-down method. Halothane MAC in the seven study groups was as follows: 0.75% +/- 0.05% (mean +/- SE) in Group I; 0.49% +/- 0.03% and 0.59% +/- 0.04%, respectively, in Groups II OR and Ward; 0.65% +/- 0.003% and 0.49% +/- 0.07%, respectively, in Groups III OR and Ward; and 0.51% +/- 0.07% and 0.37% +/- 0.02%, respectively, in Groups IV OR and Ward. Halothane MAC decreased significantly (P < 0.05) in groups that received buprenorphine except Group III-OR compared with Group I. Systolic blood pressure did not change significantly in Groups II-OR and IV-OR after tracheal intubation and in Groups III-Ward and IV-Ward after surgical incision but increased significantly (P < 0.05) in the remaining groups in response to noxious stimuli. Heart rate responses to tracheal intubation and surgical incision were similar to those in systolic blood pressure. These results indicate that preanesthetic administration of epidural or IV buprenorphine required for postoperative analgesia reduces halothane MAC and attenuates hemodynamic responses to tracheal intubation and surgical incision according to the dose, route, and timing of administration. (Anesth Analg 1997;84:100-5)

Prior hypothermia attenuates malignant hyperthermia in susceptible swine.

This study was designed to determine the extent by which mild or moderate hyperthermia attenuates the triggering of malignant hypothermia (MH) induced by the combined administration of halothane and succinylcholine. Sixteen susceptible swine were initially anesthetized with nontriggering drugs and then either kept normothermic (approximately equal to 38 degrees C, n = 6) or cooled to induce mild (approximately equal to 35 degrees C, n = 6), or moderate (approximately equal to 33 degrees C, n = 4) hypothermia. Next, after a 30-min control period, the normothermic and mildly hypothermic animals were administered 1 minimum alveolar anesthetic concentration (MAC) halothane followed by a bolus dose of succinylcholine (2 mg/kg). Within 10 min all normothermic animals developed fulminant MH, whereas the onset of MH was slowed or was absent in the mildly hypothermic group. To test whether moderate hypothermia could more effectively minimize the signs of a MH episode, this group of animals was exposed to 1.5 MAC halothane followed 10 min later by a 3-mg/kg bolus of succinylcholine. MH was not induced and anesthesia was then changed to nontriggering drugs (ketamine and pancuronium). The animals were then aggressively rewarmed to 38 degrees C: a slight increase in the ETCO2 was detected, but MH episodes did not spontaneously occur. Subsequently, the readministration of halothane and succinylcholine rapidly provoked fulminant MH. We concluded that the induction of mild hypothermia impairs triggering and reduces the progression of MH induced by the combined administration of halothane and succinylcholine, whereas moderate hypothermia was completely protective and thus could be considered for prophylaxis.

Hemodynamic Effects of Intravenous Ephedrine in Infants and Children Anesthetized with Halothane and Nitrous Oxide

The aim of this study was to evaluate the effect of age on the hemodynamic responses to intravenous (IV) ephedrine in pediatric patients anesthetized with halothane, nitrous oxide, and oxygen. One hundred ten pediatric patients, ranging in age from 0.1 to 15 yr, were assigned to receive 0.1 mg/kg (n = 55) or 0.2 mg/kg (n = 55) IV ephedrine. General anesthesia was maintained with 1.0 minimum alveolar anesthetic concentration (MAC) of halothane and 67% nitrous oxide in oxygen after tracheal intubation. Measurements of arterial blood pressure and heart rate were made at 1-min intervals for 10 min after ephedrine 0.1 or 0.2 mg/kg was injected IV as a bolus. Significant correlations were noted between age and changes in mean blood pressure (r = 0.37, P < 0.01 for the subjects receiving ephedrine 0.1 mg/kg; r = 0.63, P < 0.001 for the subjects receiving ephedrine 0.2 mg/kg), but not between age and changes in heart rate. The present results indicate that age correlates with the pressor but not the chronotropic effects of ephedrine in pediatric patients anesthetized with 1 MAC halothane and nitrous oxide.

Hemodynamic Effects of Intravenous Ephedrine in Infants and Children Anesthetized with Halothane and Nitrous Oxide

The aim of this study was to evaluate the effect of age on the hemodynamic responses to intravenous (IV) ephedrine in pediatric patients anesthetized with halothane, nitrous oxide, and oxygen.One hundred ten pediatric patients, ranging in age from 0.1 to 15 yr, were assigned to receive 0.1 mg/kg (n = 55) or 0.2 mg/kg (n = 55) IV ephedrine. General anesthesia was maintained with 1.0 minimum alveolar anesthetic concentration (MAC) of halothane and 67% nitrous oxide in oxygen after tracheal intubation. Measurements of arterial blood pressure and heart rate were made at 1-min intervals for 10 min after ephedrine 0.1 or 0.2 mg/kg was injected IV as a bolus. Significant correlations were noted between age and changes in mean blood pressure (r = 0.37, P < 0.01 for the subjects receiving ephedrine 0.1 mg/kg; r = 0.63, P < 0.001 for the subjects receiving ephedrine 0.2 mg/kg), but not between age and changes in heart rate. The present results indicate that age correlates with the pressor but not the chronotropic effects of ephedrine in pediatric patients anesthetized with 1 MAC halothane and nitrous oxide. (Anesth Analg 1996;82:568-73)

Nitric oxide: physiology and pharmacology.

Nitric oxide: physiology and pharmacology.

Nitric Oxide

Nitric Oxide

Chronic treatment with nitric oxide synthase (NOS) inhibitor profoundly reduces cerebellar NOS activity and cyclic guanosine monophosphate but does not modify minimum alveolar anesthetic concentration.

We previously found that acute administration of a nitric oxide synthase (NOS) inhibitor (N omega-nitro-L-arginine methyl ester [L-NAME]) does not reduce the minimum alveolar anesthetic concentration (MAC) of halothane in rats. However, a recent study has suggested that brain NOS activity could not be inhibited by more than approximately 50% by acute administration of L-NAME. To investigate the effect of marked inhibition of NOS activity on the MAC of halothane, we measured cerebellar NOS activity, cerebellar cyclic guanosine monophosphate (cGMP) levels, and halothane MAC in rats chronically treated with L-NAME and compared the results to those of the saline-treated control group. Although the cerebellar NOS activity and cGMP levels were significantly decreased (14% and 2.7% of control, respectively) by L-NAME, the value of the halothane MAC was not significantly affected. These results suggest that the anesthetic action of halothane, as measured by its MAC in rats, is not related to NOS activity or cGMP levels in the brain.

The Effects of Halothane and Isoflurane on Cerebrocortical Microcirculation and Autoregulation as Assessed by Laser-Doppler Flowmetry

The effects of volatile anesthetics on red blood cell flow in the cerebral microcirculation have not been compared. We used laser-Doppler flowmetry, which measures red blood cell flow in the microcirculation to compare the effects of differing concentrations of isoflurane and halothane on cerebrocortical microcirculation. Sprague-Dawley rats were anesthetized with pentobarbital (65 mg/kg intraperitoneally). The animals were tracheotomized, paralyzed, and artificially ventilated. In the first protocol laser-Doppler flow (LDF) was recorded at 0.5, 1, 1.5, and 2 minimum alveolar anesthetic concentration (MAC) halothane or isoflurane, with blood pressure controlled by intravenous phenylephrine infusion (0.5-5 micrograms.kg-1.min-1). In the second protocol the effects of 0.5 and 1.5 MAC halothane and isoflurane on LDF changes in response to changes in mean arterial blood pressure (MABP) were compared. MABP was increased by phenylephrine infusion and decreased by hemorrhage. LDF increased with each 0.5 MAC increase in halothane and isoflurane concentration (P < 0.05). LDF was greater at 1.5 and 2 MAC isoflurane than at equi-MAC halothane (P < 0.01). Autoregulation of LDF was present but attenuated at MABP of 60-140 mm Hg at low halothane and isoflurane concentrations. LDF was increased at 1.5 MAC vs 0.5 MAC for both drugs (P < 0.01). The autoregulation coefficients (percent LDF change/mm Hg MABP change) were 0.41 +/- 0.10, 0.42 +/- 0.07, 0.27 +/- 0.04, and 0.20 +/- 0.05 at 0.5 MAC halothane, 0.5 MAC isoflurane, 1.5 MAC halothane, and 1.5 MAC isoflurane, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Nitric oxide synthase inhibitor does not reduce minimum alveolar anesthetic concentration of halothane in rats.

Nitric oxide (NO) synthase inhibitor (N omega-nitro-L-arginine methyl ester [L-NAME]) has been reported to reduce minimum alveolar anesthetic concentration (MAC) of halothane when administered intravenously (i.v.) and to reduce thermal hyperalgesia, or produce antinociception in the formalin test, when administered intracerebroventricularly (ICV) or intrathecally (IT). This study attempts to identify the site(s) in the central nervous system (CNS) where L-NAME acts to reduce the halothane MAC. For this purpose, we examined the effects of i.v., ICV, and IT administration of L-NAME on the halothane MAC in rats. In contrast to an earlier study, we did not observe any decrease in the halothane MAC after i.v. (10-30 mg/kg) administration of L-NAME. ICV (100 micrograms) and IT (100 micrograms and 1 mg) administration of L-NAME also did not alter the halothane MAC. These findings indicate that the L-arginine-NO pathway is not involved in the mechanism of action of halothane to suppress mechanical nociceptive response or in the nociceptive neural mechanism of mechanical stimulation.

Effect of Chloride Transport Blockade on the MAC of Halothane in the Rat

There is a growing evidence that central nervous system chloride transport via gamma-aminobutyric acid (GABAA) related Cl- conductance or Cl-/HCO3- exchange affects anesthetic requirements. To delineate the effects of GABAA-related Cl- conductance blockade versus Cl-/HCO3- exchange inhibition, we determined the change in minimum alveolar anesthetic concentration (MAC) of halothane in rats after intracisternal infusion of 4,4'-diisothiocyano-2,2'-disulfonic acid stilbene (DIDS). DIDS inhibits Cl-/HCO3- exchange transport in concentrations greater than 1 microM and in GABAA-related Cl- channels in concentrations greater than 0.1 mM. After control MAC determination, rats were given intracisternal mock cerebrospinal fluid (n = 6), 1.0 microM DIDS (n = 8), or 1 mM DIDS (n = 8) at a rate of 2 microL/min for 30 min. Mock cerebrospinal fluid did not change the MAC of halothane. The MAC of halothane increased significantly (P less than 0.001) from 0.96% +/- 0.02% to 1.11% +/- 0.03% (mean value +/- SEM) with 1 microM DIDS and from 0.94% +/- 0.02% to 1.16% +/- 0.04% with 1 mM DIDS. The increases in MAC with 1 microM and 1 mM DIDS were not statistically different. This suggests that Cl-/HCO3- exchange inhibition increases halothane requirements, whereas GABAA-related Cl- channel blockade does not.

Ketorolac Does Not Decrease the MAC of Halothane or Depress Ventilation in Rats

To determine the effects of intravenous (IV) ketorolac on anesthesia and the mechanisms involved, we evaluated its effects on minimum alveolar anesthetic concentration (MAC) and ventilation in halothane-anesthetized rats. Ketorolac in clinical (0.2 and 2 mg/kg) and large (20 and 40 mg/kg) IV doses did not affect the MAC of halothane (0.82% +/- 0.02%). Resting end-tidal CO2 tension (5.1% +/- 0.1%) and the slope of the CO2 response curves (70 +/- 6 mL.min-1.%-1) were also unaffected by IV ketorolac. The mean arterial blood pressure did not significantly change after ketorolac in doses of 0.2, 2, or 20 mg/kg but decreased significantly (P less than 0.05) after 40 mg/kg (placebo 99 +/- 8 mm Hg; ketorolac 87 +/- 6 mm Hg). This study demonstrates that MAC, ventilation, and mean arterial blood pressure are unaffected by clinical doses of IV ketorolac. Furthermore, the lack of effect on MAC and ventilation from larger doses suggests that ketorolac does not have mechanisms of action in the central nervous system.

Thiopental Reduces Halothane MAC in Rats

The anesthetic contribution of specific plasma concentrations of thiopental has not been previously defined in laboratory animals. The plasma thiopental concentrations needed to reduce the anesthetic requirement for halothane by fractions of the minimum alveolar anesthetic concentration (MAC) were assessed in the rat. After steady-state thiopental plasma concentrations were established with a constant infusion, the tail-clamp technique was used to determine control MAC and the MAC of halothane with increasing concentrations of thiopental. We observed progressive reductions in halothane MAC. This required logarithmic increases in thiopental concentration rather than linear ones. A nonlinear reduction in anesthetic requirement was noted with an approximate 50% reduction in MAC at a thiopental plasma concentration of 7.4 micrograms/mL and an approximate 90% reduction at 32 micrograms/mL. Thiopental appears to provide essentially complete anesthesia in the rat model with a logarithmic contribution of increasing plasma concentrations.