Supraspinal, not spinal, alpha(2) adrenoceptors are involved in the anesthetic-sparing and hemodynamic-stabilizing effects of systemic clonidine in rats

Clonidine, an alpha(2) agonist, reduces the anesthetic requirement and attenuates harmful hemodynamic responses to noxious stimuli. We examined the responsible sites of action in the central nervous system for the minimum alveolar anesthetic concentration (MAC) and MAC blocking adrenergic response (MAC-BAR) reducing effects of systemically administered clonidine in halothane-anesthetized rats. The MAC for halothane was determined by the tail clamp method, and MAC-BAR was defined as the MAC which attenuated hemodynamic responses within 10% after the tail clamp. We examined the effect of IV clonidine in the presence of rauwolscine, an alpha(2) antagonist given through IV, intrathecal (IT), intracisternal (IC), or intracerebroventrical (ICV) routes. IV clonidine reduced MAC and MAC-BAR dose-dependently. IV and ICV rauwolscine antagonized the MAC-reducing effect of clonidine, whereas IC and IT rauwolscine did not. In comparison, IV, ICV, and IC rauwolscine antagonized the MAC-BAR-reducing effect of clonidine; IT rauwolscine had no effect. Our data demonstrate that the alpha(2) adrenoceptors in the regions above mesencephalon and both the regions above mesencephalon and the lower brainstem are responsible for the MAC and MAC-BAR-reducing effect of systemic clonidine in rats, respectively. However, the spinal alpha(2) adrenoceptors were not involved in these effects of clonidine. IMPLICATIONS: In the regions above mesencephalon, alpha(2) adrenoceptors were the most responsible for the minimum alveolar concentration-reducing effect and both the lower brainstem and regions above mesencephalon were involved in the minimum alveolar concentration blocking adrenergic response-reducing effect of clonidine. The spinal alpha(2) adrenoceptors did not significantly contribute to these effects of clonidine.     

Halothane and propofol differentially affect electroencephalographic responses to noxious stimulation

Background. Anaesthetics blunt neuronal responses to noxiousstimulation, including effects on electroencephalographic (EEG)responses. It is unclear how anaesthetics differ in their abilityto modulate noxious stimulation-evoked EEG activation. We investigatedthe actions of propofol and halothane on EEG responses to noxiousstimuli, including repetitive electrical C-fibre stimulation,which normally evokes neuronal wind-up. Methods. Rats were anaesthetized with halothane (n=8) or propofol(n=8), at 0.8x or 1.2x the amount required to produce immobilityin response to tail clamping [minimum alveolar concentration(MAC) for halothane and median effective dose (ED₅₀) for propofol].We recorded EEG responses to repetitive electrical stimulustrains (delivered to the tail at 0.1, 1 and 3 Hz) as well assupramaximal noxious tail stimulation (clamp; 50 Hz electricalstimulus, each for 30 s). Results. Under halothane anaesthesia, noxious stimuli evokedan EEG activation response manifested by increased spectraledge frequency (SEF) and median edge frequency (MEF). At 0.8MAC halothane, the tail clamp increased the MEF from     

The Potentiation of Halothane Anaesthesia by Clonidine

The antihypertensive agent, clonidine, has a marked sedative effect. We studied whether clonidine also deepens halothane anaesthesia. Eight rabbits were anaesthetized with and without clonidine premedication in a cross-over study. Clonidine premedication (50 microgram/kg subcutaneously) was administered three times daily for 3 days. Tolerance to pain during halothane anaesthesia was tested by compressing the ear with a vessel clamp. Halothane concentrations were determined by gas chromatography. The rabbits premedicated with clonidine tolerated painful stimuli without reactions at lower halothane concentrations in arterial blood and inspired air than unpremedicated rabbits. MAC calculated from blood concentrations was 1.29% for unpremedicated and 1.09% for clonidine-premedicated rabbits. The results suggest that clonidine diminishes the anaesthetic requirement in halothane anaesthesia.     

Intrathecal picrotoxin minimally alters electro-encephalographic responses to noxious stimulation during halothane and isoflurane anesthesia

BACKGROUND: Isoflurane and halothane act in the spinal cord to blunt ascending transmission of impulses to the brain resulting from noxious stimulation. Because intrathecal picrotoxin (an antagonist at the gamma-aminobutyric acid-A receptor) partially reverses the immobilizing effect of isoflurane and halothane, we hypothesized that the electroencephalographic response to noxious stimulation would likewise be partially reversed by intrathecal picrotoxin. METHODS: Rats were anesthetized with isoflurane (n = 8) or halothane (n = 8) and a laminectomy performed. Following determination of minimum alveolar concentration (MAC), the electroencephalogram (EEG) was recorded during separate applications of a hindpaw clamp, tail clamp and electrical current to the tail at 0.8 and 1.2 MAC. Picrotoxin was then applied to the exposed spinal cord and the EEG response to noxious stimulation again determined. RESULTS: The EEG was more active during halothane anesthesia than isoflurane (spectral edge frequency for 95% power: 25.6 +/- 2.1 Hz vs. 23.1 +/- 1.6 Hz, P < 0.05). Noxious stimulation usually caused the EEG to shift to higher frequencies (e.g. for 0.8 MAC halothane, median edge frequency for 50% power: from 7.6 +/- 3.1 Hz to 10.7 +/- 2.6 Hz, P < 0.05). Picrotoxin minimally affected this response. CONCLUSIONS: Noxious stimulation evokes an EEG response that is minimally altered by intrathecal picrotoxin. This suggests that isoflurane and halothane do not have GABAergic actions in the spinal cord that indirectly suppress the EEG response.     

Reduction in halothane anesthetic requirement by clonidine, an alpha-adrenergic agonist

The effects of clonidine, a potent central alpha-adrenergic agonist, and of tolazoline, an alpha-adrenergic antagonist, on the minimal anesthetic concentration (MAC) of halothane were studied in male mongrel dogs. Control halothane MAC was 0.8 +/- 0.04 vol% (determined in each dog by gas chromatography of arterial blood, n = 30). Clonidine, 5 microgram/kg (n = 10) and 20 microgram/kg (n = 10), give slowly intravenously, maximally reduced MAC by 42% (at 2.3 hours after clonidine) and 48% (at 2.6 hours after clonidine) for each dose. In another set of animals (n = 5) an alpha-adrenergic antagonist, tolazoline, 5 mg/kg IV, reversed the clonidine-induced reduction in halothane MAC rapidly and completely. Tolazoline alone, 5 mg/kg, (n = 5) had no significant effect on halothane MAC. Thus, the administration of the central alpha-adrenergic agonist clonidine decreased the required anesthetic concentration of halothane, as defined by MAC, by almost half. This effect, as it is reversed by tolazoline, is likely to be mediated through a central alpha-adrenergic receptor mechanism.     

The effect of neuromuscular blockade with vecuronium on hemodynamic responses to noxious stimuli in the rat

The effect of neuromuscular blockade with vecuronium on the hemodynamic responses to a noxious stimulus was investigated in male Sprague-Dawley rats. The rats were anesthetized with either halothane (group 1, n = 10), or isoflurane (group 2, n = 10). The maximum values for heart rate and mean arterial pressure during the noxious stimulus (base-tail clamp) were measured, and the maximum changes in these values (maximum minus prestimulation) were calculated. The responses were measured at two different anesthetic concentrations (0.6 X MAC, 0.75 X MAC), before and after vecuronium 1.0 mg.kg-1 iv. It was found that neuromuscular blockade with vecuronium did not reduce any of the hemodynamic responses measured, at either anesthetic concentration, in either the halothane or the isoflurane group. However, increasing the anesthetic concentration from 0.6 X MAC to 0.75 X MAC produced statistically significant (P less than 0.01) reductions in several of the responses measured. The inability of vecuronium to reduce hemodynamic responses to noxious stimuli in this study suggests that neuromuscular blockade does not alter anesthetic depth in the rat. A knowledge of this "absence of effect" may be important for investigators who need to induce muscle relaxation in laboratory animals prior to examining the effect of anesthetic agents on hemodynamic responses to noxious stimuli. The results also question the ability of neuromuscular blockade to reduce anesthetic requirement, and support the view that neuromuscular blockade does not contribute to the anesthetic state.     

Effects of oral clonidine premedication on the heart rate response to intravenous atropine during propofol anesthesia

BACKGROUND: Propofol induces suppression of the sympathetic nervous activity, and attenuates the heart rate responses to intravenous atropine. Similarly, clonidine suppresses the heart rate response to intravenous atropine under awake and enflurane-anesthetized patients. The purpose of this study is to evaluate effects of clonidine on the heart rate response to atropine under propofol anesthesia. METHODS: Thirty-two adults patients were randomly assigned to one of two groups. Clonidine group (n=16) patients received oral clonidine 5 microg x kg(-1) and famotidine 20 mg, and the control group (n=16) patients received oral famotidine alone 90 minutes before anesthesia. After tracheal intubation, anesthesia was maintained with propofol at the effect site concentration of 3 microg x ml(-1) in air and oxygen using the TCI system. All patients received incremental doses of IV atropine 5 microg x kg(-1) over 5 s at 2-min intervals until heart rate increased > 20 beats x min(-1) from baseline values or until atropine 40 microg x kg(-1) was given. RESULTS: Although heart rate response to atropine 5-25 microg kg(-1) was similar between the two groups, heart rate response to atropine 30 microg x kg(-1) in the clonidine group was smaller than that in the control group (P<0.05). When the atropine 40 microg x kg(-1) was administered, heart rate increased > 20 beats x min(-1) in all patients of the control group, but 62.5% of patients in the clonidine group (P< 0.05). CONCLUSIONS: Oral clonidine premedication attenuates the heart rate responses to IV atropine under propofol anesthesia.     

Halothane suppression of spinal sensory neuronal responses to noxious peripheral stimuli is mediated,in part,by both GABA(A) and glycine receptor systems

BACKGROUND: A major effect of general anesthesia is lack of response in the presence of a noxious stimulus. Anesthetic depression of spinal sensory neuronal responses to noxious stimuli is likely to contribute to that essential general anesthetic action. The authors tested the hypothesis that gamma-aminobutyric acid receptor type A (GABA(A)) and strychnine-sensitive glycine receptor systems mediate halothane depression of spinal sensory neuronal responses to noxious stimuli. METHODS: Extracellular activity of single spinal dorsal horn wide dynamic range (WDR) neurons was recorded in decerebrate, spinal cord transected rats. Neuronal responses to noxious (thermal and mechanical) and nonnoxious stimuli were examined in the drug-free state. Subsequently, cumulative doses (0.1-2.0 mg/kg) of bicuculline (GABA(A) antagonist) or strychnine (glycine antagonist) were administered intravenously in the absence or presence of 1 minimum alveolar concentration (MAC) of halothane. RESULTS: Halothane, 1.1%, depressed the response of WDR neurons to both forms of noxious stimuli. Antagonists, by themselves, had no effect on noxiously evoked activity. However, bicuculline and strychnine (maximum cumulative dose, 2.0 mg/kg) partially but significantly reversed the halothane depression of noxiously evoked activity. Similar results were seen with most, but not all, forms of nonnoxiously evoked activity. In the absence of halothane, strychnine significantly increased neuronal responses to low threshold receptive field brushing. CONCLUSION: Halothane depression of spinal WDR neuronal responses to noxious and most nonnoxious stimuli is mediated, in part, by GABA(A) and strychnine-sensitive glycine systems. A spinal source of glycine tonically inhibits some forms of low threshold input to WDR neurons.     

Halothane Suppression of Spinal Sensory Neuronal Responses to Noxious Peripheral Stimuli Is Mediated, in Part, by Both GABAA and Glycine Receptor Systems

Background: A major effect of general anesthesia is lack of response in the presence of a noxious stimulus. Anesthetic depression of spinal sensory neuronal responses to noxious stimuli is likely to contribute to that essential general anesthetic action. The authors tested the hypothesis that [gamma]-aminobutyric acid receptor type A (GABAA) and strychnine-sensitive glycine receptor systems mediate halothane depression of spinal sensory neuronal responses to noxious stimuli.

Methods: Extracellular activity of single spinal dorsal horn wide dynamic range (WDR) neurons was recorded in decerebrate, spinal cord transected rats. Neuronal responses to noxious (thermal and mechanical) and nonnoxious stimuli were examined in the drug-free state. Subsequently, cumulative doses (0.1-2.0 mg/kg) of bicuculline (GABAA antagonist) or strychnine (glycine antagonist) were administered intravenously in the absence or presence of 1 minimum alveolar concentration (MAC) of halothane.

Results: Halothane, 1.1%, depressed the response of WDR neurons to both forms of noxious stimuli. Antagonists, by themselves, had no effect on noxiously evoked activity. However, bicuculline and strychnine (maximum cumulative dose, 2.0 mg/kg) partially but significantly reversed the halothane depression of noxiously evoked activity. Similar results were seen with most, but not all, forms of nonnoxiously evoked activity. In the absence of halothane, strychnine significantly increased neuronal responses to low threshold receptive field brushing.     

The effects of magnesium sulphate on sevoflurane minimum alveolar concentrations and haemodynamic responses

BACKGROUND AND OBJECTIVE: Magnesium administered before anaesthesia induction results in a significant reduction in intravenous anaesthetic consumption. The purpose of this study was to evaluate whether the dose of intravenous magnesium sulphate reduces the minimum alveolar anaesthetic concentration of sevoflurane for endotracheal intubation (MACEI) and skin incision (MAC), and attenuates haemodynamic responses. METHODS: We studied 60 patients who were scheduled for elective surgery. Patients were not premedicated before induction of anaesthesia and were randomly assigned to receive intravenous saline 0.9% (Group I, n = 20) or magnesium sulphate 30 mg kg(-1) bolus + 10 mg kg(-1) h(-1) continuous infusion (Group II, n = 20) or 50 mg kg(-1) bolus + 10 mg kg(-1) h(-1) continuous infusion (Group III, n = 20). RESULTS: Median and 95% confidence limits for sevoflurane MACEI were 2.68 (2.48-2.85), 2.88 (2.70-3.06) and 2.96 (2.70-3.16), and for sevoflurane MAC were 2.08 (1.76-2.40), 2.26 (2.08-2.47) and 2.40 (2.19-2.68) in Groups I, II and III, respectively. The differences in MACEI and MAC among groups were not statistically significant, except Group III in MAC study (P < 0.05). Mean arterial pressures and heart rate did not increase in Groups II and III after endotracheal intubation and skin incision. CONCLUSIONS: Magnesium sulphate administered before induction of anaesthesia increases MAC of sevoflurane and reduces cardiovascular responses to intubation.     

The efficacy of clonidine for reducing perioperative haemodynamic changes and volatile anaesthetic requirements in children

Background: Oral clonidine given as a premedicant in adults has been shown to reduce intraoperative inhalation anaesthetic requirements and provide perioperative haemodynamic stability. We conducted the current study to ascertain whether or not these beneficial effects of clonidine can be reproduced in children. Methods: In a prospective, randomized, double-blind, controlled clinical trial, 60 children (ASA I) aged 5–11 yr, received placebo (control), 2 μg kg^-1 clonidine, or 4 μg kg^-1 clonidine orally 105 min before induction of anaesthesia. Anaesthesia was induced with halothane, nitrous oxide in oxygen via mask and maintained with halothane and 60% nitrous oxide in oxygen. The halothane concentration was titrated to the concentration required to maintain haemodynamic stability (defined as 20% of blood pressure (BP) and heart rate (HR)) for maintenance of anaesthesia. The end-tidal concentration of halothane was monitored throughout anaesthesia. On completion of surgery, nitrous oxide and halothane were discontinued. Following confirmation of recovery from anaesthesia and muscle relaxation, the endotracheal tube was removed. Results: Higher inspired concentrations of halothane (%) were required in the control and 2 μg kg^-1 clonidine-treated groups (mean SD: 1.1 ±0.2 and 1.0±0.2, respectively) than in the 4 μg kg^-1 clonidine-treated group (0.6±0.1) for haemodynamic stability (P<0.05). Clonidine, 4 μg kg^-1, significantly reuced the intraoperative lability (coefficient of variation) of systolic and diastolic BP and HR compared with the other two regimens. Conclusion: Oral clonidine premedication at a dose of 4 μg kg^-1 provided intraoperative haemodynamic stability and reduced anaesthetic requirements in children. However, we are unable to extrapolate these observations to younger children and infants.     

Fentanyl Augments the Blockade of the Sympathetic Response to Incision (MAC-BAR) Produced by Desflurane and Isoflurane: Desflurane and Isoflurane MAC-BAR without and with Fentanyl

Background: Heart rate (HR) or mean arterial blood pressure (MAP) may increase in response to incision despite the absence of a motor response. The authors hypothesized that the MAC-BAR (minimum alveolar concentration of an anesthetic that blocks adrenergic response to incision) for isoflurane would exceed that for desflurane, and that fentanyl would decrease the MAC-BAR for each anesthetic in a dose-dependent manner.

Methods: Seventy-one patients were randomly allocated to one of six groups: desflurane or isoflurane without fentanyl or with 1.5 or 3 micro gram/kg fentanyl given intravenously 5 min before surgical incision. Anesthesia was induced with 2 mg/kg propofol given intravenously, and tracheal intubation facilitated with 0.1 mg/kg given intravenously. The first patient in each group received 1 MAC (end-tidal) of the inhaled anesthetic in 60% nitrous oxide (0.55 MAC), balance oxygen, maintained for at least 10 min before incision. The response was considered positive if the HR or MAP increased 15% or more. If the response was positive, the end-tidal concentration given to the next patient was 0.3 MAC greater; if the response was negative, the end-tidal concentration was 0.3 MAC less. The MAC-BAR level was calculated as the mean of four independent cross-over responses in each group.

Results: Desflurane and isoflurane anesthesia with 60% nitrous oxide did not change HR (P > 0.05) and decreased MAP (P < 0.05) before incision. Plasma epinephrine and norepinephrine concentrations after anesthesia and before incision were normal in all groups. The MAC-BAR level, without fentanyl, did not differ (P > 0.05) between desflurane (1.30 +/- 0.34 MAC [mean +/- SD]) and isoflurane (1.30 +/- 0.18 MAC). Fentanyl given at 1.5 micro gram/kg intravenously equivalently (P > 0.05) reduced the MAC-BAR for desflurane (to 0.40 +/- 0.18 MAC; P <0.05) and isoflurane (to 0.55 +/- 0.00 MAC; P < 0.05), but a further increase in fentanyl to 3 micro gram/kg caused no greater decrease in the MAC-BAR for desflurane (0.48 +/- 0.16 MAC) and isoflurane (0.40 +/- 0.30 MAC).     

The Effect of Fentanyl on Sevoflurane Requirements for Somatic and Sympathetic Responses to Surgical Incision

Background: Fentanyl produces a reduction in the minimum alveolar concentration (MAC) of isoflurane and desflurane needed to blockade adrenergic response (BAR) to surgical incision in 50% of patients (MAC-BAR). MAC-BAR of sevoflurane and the reduction in MAC-BAR of sevoflurane by fentanyl have not been described previously. The purpose of this study was to determine the MAC and MAC-BAR reduction of sevoflurane by fentanyl with and without nitrous oxide (N2 O).

Methods: Two hundred twenty-six patients were randomly assigned to one of two groups: a sevoflurane group and a sevoflurane/N2 O group. Patients in each group were randomly assigned to one of five different fentanyl concentration subgroups. Patients were anesthetized with sevoflurane and fentanyl in the sevoflurane group and with sevoflurane, fentanyl, and N (2) O (66 vol%) in the sevoflurane/N2 O group. Somatic and sympathetic responses to surgical incision were observed for MAC and MAC-BAR assessment at predetermined concentrations of sevoflurane.

Results: Fentanyl produced an initial steep reduction in the MAC and MAC-BAR of sevoflurane, with 3 ng/ml resulting in a 61% reduction in MAC and an 83% reduction in MAC-BAR. A ceiling effect was observed for MAC and MAC-BAR, with 6 ng/ml fentanyl providing only an additional 13% and 9% reduction in MAC and MAC-BAR, respectively. In the presence of 66 vol% N2 O, MAC and MAC-BAR of sevoflurane were reduced with increasing concentrations of fentanyl. A ceiling effect was not observed for reduction in MAC and MAC-BAR in the presence of N2 O.     

Comparison of haemodynamic changes induced by sevoflurane and halothane in paediatric patients

The purpose of this study is to investigate the haemodynamic effects of 1 MAC and 2 MAC of sevoflurane in children in comparison with halothane. Thirty-eight children (aged from one to six years, average age; 3.6± 0.2 yr) were randomly assigned to four groups, depending on the dose and agent (1 and 2 MAC of sevoflurance: SI and S2; 1 and 2 MAC of halothane: H1 and H2, respectively). After collecting control data during 0.2 MAC of either anaesthetic, end-expired anaesthetics were kept at 1 MAC or 2 MAC for 15 min. Mean blood pressure (mBP) and stroke volume index (SV1), measured by impedance cardiometry, decreased in all groups without differences between groups. Heart rate (HR) increased in groups S1, S2 and H2 but not in group H1. The HR in S2 was higher than that in H2. The cardiac index (CI), a product of SVI and HR, tended to decrease but not significantly in all groups. These results suggested that the haemodynamic depressant effects of sevoflurane in children were similar to those of equipotent halothane concentration except for HR.     

Pretreatment with dexmedetomidine: altered indices of anesthetic depth for halothane in the neuraxis of cats

The sedative and anesthetic-sparing ability of the alpha2-adrenergic agonist dexmedetomidine is well documented. In this study, we identified the effects of halothane, with and without dexmedetomidine, on hemodynamic and electroencephalographic (EEG) variables and quantified the concentration of halothane resulting in various anesthetic depth indices mediated through the central nervous system (CNS) in chronically instrumented cats. Halothane was given alone or after dexmedetomidine (15 microg/kg p.o.). In both groups, four indices of anesthetic depth--minimum alveolar anesthetic concentration (MAC; no movement to noxious stimuli), MAC(BAR) (no autonomic response to noxious stimuli), MAC(BS) (EEG burst suppression), and MAC(ISOELECTRIC) (EEG isoelectricity)--were determined. Halothane decreased arterial blood pressure, heart rate, and higher frequency components of the EEG before the onset of burst suppression and isoelectricity. Dexmedetomidine pretreatment augmented the actions of halothane on arterial pressure, heart rate, and the EEG. Dexmedetomidine reduced the halothane concentrations resulting in MAC (from 1.22% +/- 0.06% to 0.89% +/- 0.08%) and MAC(BAR) (from 1.81% +/- 0.05% to 1.1% +/- 0.10%), but not those resulting in MAC(BS) (3.01% +/- 0.17% vs 3.14% +/- 0.10%) or MAC(ISOELECTRIC) (4.39% +/- 0.26% vs 4.65% +/- 0.12%). These results suggest that dexmedetomidine does not alter various CNS-mediated indices of anesthetic action to equivalent degrees and that there are dissimilar degrees of an anesthetic-sparing action at different levels of the neuraxis. IMPLICATIONS: The anesthetic adjuvant dexmedetomidine seems to differentially alter central nervous system-mediated indices of anesthetic action. Lower brainstem or spinal determinants of anesthetic depth (movement and hemodynamic responses) are more attenuated than those of higher brain functions, such as the electroencephalogram.     

Anesthetic Doses of Sevoflurane To Block Cardiovascular Responses to Incision when Administered with Xenon or Nitrous Oxide

Background: The authors' previous study demonstrated that xenon (Xe) and nitrous oxide (N2 O) in combination with sevoflurane can attenuate cardiovascular responses to skin incision. To quantitatively evaluate their suppressive effects on cardiovascular responses, the authors compared the MAC-BAR (minimum alveolar concentration that blocks adrenergic or cardiovascular response to incision) values of sevoflurane when administered with Xe or N2 O.

Methods: Forty-three patients received sevoflurane with one of three anesthetics; 1 MAC Xe, 0.7 MAC Xe and 0.7 MAC N2 O. The MAC-BAR of sevoflurane was determined in each anesthetic using the "up and down" method. The response was considered positive if the heart rate or mean arterial pressure increased 15% or more. The end-tidal sevoflurane concentration given to the next patient was increased or decreased by 0.3 MAC if the response was positive or negative in the previous patient, respectively. The MAC-BAR was calculated as the mean of four independent cross-over responses.

Results: The MAC-BAR of sevoflurane, including the contribution of Xe or N2 O, was 2.1 +/- 0.2 MAC and 2.7 +/- 0.2 MAC when administered with 1 MAC Xe, respectively, and 2.6 +/- 0.4 MAC when administered with 0.7 MAC N (2) O (mean +/- SD).     

Halothane and isoflurane have additive minimum alveolar concentration (MAC) effects in rats

Studies suggest that at concentrations surrounding MAC (the minimum alveolar concentration suppressing movement in 50% of subjects in response to noxious stimulation), halothane depresses dorsal horn neurons more than does isoflurane. Similarly, these anesthetics may differ in their effects on various receptors and ion channels that might be anesthetic targets. Both findings suggest that these anesthetics may have effects on movement in response to noxious stimulation that would differ from additivity, possibly producing synergism or even antagonism. We tested this possibility in 20 rats. MAC values for halothane and (separately) for isoflurane were determined in duplicate before and after testing the combination (also in duplicate; six determinations of MAC for each rat). The sum of the isoflurane and halothane MAC fractions for individual rats that produced immobility equaled 1.037 +/- 0.082 and did not differ significantly from a value of 1.00. That is, the combination of halothane and isoflurane produced immobility in response to tail clamp at concentrations consistent with simple additivity of the effects of the anesthetics. These results suggest that the immobility produced by inhaled anesthetics need not result from their capacity to suppress transmission through dorsal horn neurons. IMPLICATIONS: Despite differences in their capacities to inhibit spinal dorsal horn cells, isoflurane and halothane are additive in their ability to suppress movement in response to a noxious stimulus.     

Anesthetic doses of sevoflurane to block cardiovascular responses to incision when administered with xenon or nitrous oxide.

BACKGROUND: The authors' previous study demonstrated that xenon (Xe) and nitrous oxide (N2O) in combination with sevoflurane can attenuate cardiovascular responses to skin incision. To quantitatively evaluate their suppressive effects on cardiovascular responses, the authors compared the MAC-BAR (minimum alveolar concentration that blocks adrenergic or cardiovascular response to incision) values of sevoflurane when administered with Xe or N2O. METHODS: Forty-three patients received sevoflurane with one of three anesthetics; 1 MAC Xe, 0.7 MAC Xe and 0.7 MAC N2O. The MAC-BAR of sevoflurane was determined in each anesthetic using the "up and down" method. The response was considered positive if the heart rate or mean arterial pressure increased 15% or more. The end-tidal sevoflurane concentration given to the next patient was increased or decreased by 0.3 MAC if the response was positive or negative in the previous patient, respectively. The MAC-BAR was calculated as the mean of four independent cross-over responses. RESULTS: The MAC-BAR of sevoflurane, including the contribution of Xe or N2O, was 2.1+/-0.2 MAC and 2.7+/-0.2 MAC when administered with 1 MAC and 0.7 MAC Xe, respectively, and 2.6+/-0.4 MAC when administered with 0.7 MAC N2O (mean +/- SD). CONCLUSIONS: Although 1 MAC Xe has a more potent suppressive effect on cardiovascular responses to incision than 0.7 MAC Xe or N2O, Xe and N2O have a similar suppressive effect at 0.7 MAC.     

Pretreatment with oral clonidine attenuates cardiovascular responses to tracheal extubation in children

This study was designed to evaluate the effects of diazepam and clonidine orally given preoperatively on cardiovascular responses to tracheal extubation in children. Fifty children, ASA physical status I, aged 4-10 years, undergoing minor elective surgery (inguinal hernia, phimosis) received orally, in a randomized, double-blind manner, diazepam 0.4 mg.kg-1 or clonidine 4 microgram.kg-1 (n=25 of each). These drugs were administered 105 min before an inhalational induction of anaesthesia. The same standard general anaesthetic technique was employed throughout. The maximum changes in heart rate (HR), systolic blood pressure (SBP) and diastolic blood pressure (DBP) were less in patients who had received clonidine than in those who had received diazepam (HR, 12 vs 24; SBP, 14 vs 26; DBP, 9 vs 16; mean, P < 0.05). In conclusion, compared to diazepam given orally, pretreatment with oral clonidine attenuates haemodynamic changes associated with tracheal extubation in children.     

Analgesia for paediatric tonsillectomy and adenoidectomy with intramuscular clonidine

BACKGROUND: After undergoing tonsillectomy and adenoidectomy (T&A), children may experience significant pain. Clonidine, an alpha2 agonist, exhibits significant analgesic properties. The current investigation sought to determine whether intramuscular (I.M.) clonidine would decrease pain in paediatric patients undergoing T&A. METHODS: Thirty-nine children undergoing elective T&A were studied. Following inhalational anaesthetic induction, fentanyl (2 microg x kg(-1)) was given intravenously, acetaminophen (paracetamol) (30 mg.kg-1) was given rectally and the children then randomly received an i.m. injection of either normal saline or clonidine (2 microg x kg(-1)). Perioperative analgesic requirements in the postanaesthesia care unit and at home following hospital discharge were evaluated. RESULTS: There were no significant demographic, analgesic consumption, haemodynamic or pain score differences between the groups. CONCLUSIONS: We do not recommend adding i.m. clonidine (2 microg x kg(-1)) to the analgesic regimen of children undergoing tonsillectomy and adenoidectomy.