Antagonism of suxamethonium-induced jaw muscle contracture in rats.

Masseter muscle rigidity (MMR) induced during general anaesthesia by suxamethonium is a clinical problem that may interfere with tracheal intubation. We have investigated the relation between twitch tension and contracture response to suxamethonium in rats. Rats were anaesthetized with 1% halothane (1.35 MAC). Jaw muscle temperature was maintained at either 37 or 41 degrees C while rectal temperature was kept at 37 degrees C by radiant heat. Twitch tension was produced by nerve stimulation at 0.2 Hz. Rats were pretreated with either a low dose of vecuronium (0.03 mg kg-1) or dantrolene (0.8 mg kg-1). Thereafter suxamethonium 750 micrograms kg-1 was administrated i.v. Low-dose vecuronium pretreatment significantly (90%) decreased suxamethonium-induced jaw muscle contracture (JMC) with minimal (3%) twitch block during local hyperthermia. Low-dose dantrolene pretreatment also reduced JMC (81% at 37 degrees C and 82% at 41 degrees C) while decreasing twitch by 30% at 37 degrees C and 31% at 41 degrees C. Both vecuronium and dantrolene at doses that minimally depressed the twitch response antagonized suxamethonium-induced JMC. We speculate that pretreatment with low-dose vecuronium decreases suxamethonium-induced MMR clinically.

Sufentanil plasma concentrations following lower extremity tourniquet release.

STUDY OBJECTIVE: To investigate whether release of a tourniquet on the lower extremity affects plasma concentrations of sufentanil, as previously demonstrated with fentanyl and midazolam. DESIGN: Prospective. SETTING: University tertiary-care institution with residency program. PATIENTS: 20 ASA status I, II, and III patients undergoing total knee arthroplasty under a tourniquet using a sufentanil, nitrous oxide, relaxant regimen. INTERVENTIONS: Each patient received sufentanil 1 to 2 micrograms/kg at induction of anesthesia and in 12.5 to 25 microgram increments as needed thereafter, until 15 minutes prior to tourniquet release. MEASUREMENTS AND MAIN RESULTS: Plasma sufentanil concentrations were determined before tourniquet inflation, immediately before tourniquet deflation, and 1, 2, 5, 10, 20, 30, and 40 minutes following deflation. A 15% elevation of plasma sufentanil concentration above that predicted by elimination pharmacokinetics defined a secondary peak. Although the aggregate data did not indicate an overall statistically significant rise in plasma concentrations after deflation, 9 (45%) patients exhibited a secondary peak in sufentanil plasma concentration following tourniquet deflation (range of secondary peaks, 16% to 89% above predicted values). No patient experienced clinically significant respiratory depression. CONCLUSION: Release of a tourniquet on the lower extremity may yield a detectable rise in plasma sufentanil concentration.

Desflurane controls the hemodynamic response to surgical stimulation more rapidly than isoflurane.

STUDY OBJECTIVE: To compare the control of hemodynamic response to surgical stimulus of desflurane to that of isoflurane. DESIGN: Prospective randomized study. SETTING: Operating room of a major U.S. teaching hospital. PATIENTS: 59 ASA status I, II, and III patients 18 to 80 years of age and were undergoing orthopedic or intra-abdominal surgical procedures of 1 or more hours in duration. INTERVENTIONS: Group 1 (n = 29) received desflurane in oxygen (O2) for their surgical procedure. Group 2 (n = 30) received isoflurane in O2 for their surgical procedure. Thiopental sodium 4 mg/kg and fentanyl 3 micrograms/kg provided induction; vecuronium 0.1 mg/kg facilitated intubation. Prior to incision the volatile anesthesia drug was titrated to maintain systolic blood pressure (SBP) within 20% of preinduction (baseline) values. Any time after incision, an SBP increase greater than 20% of baseline was treated with a 30% increase in inspired anesthetic concentration for 3 minutes, or until SBP was within 10% of baseline. Another three 30% increases were allowed at 3 minute intervals to return SBP to 10% of baseline. If four 30% increases did not return SBP to 10% of baseline, additional fentanyl up to 5 micrograms/kg or labetalol in 5 mg increments was given. MEASUREMENTS AND MAIN RESULTS: Measurement of hemodynamics and anesthetic concentration occurred every 2 minutes prior to skin incision and every 5 minutes thereafter. Measurement of hemodynamics and anesthetic concentration occurred every minute during treatment of blood pressure (BP) response to surgical stimulus. Desflurane allowed for more rapid control of BP response to surgical stimulus median 2 minutes (range 1 to 12 minutes) for desflurane versus 6 minutes (range 1 to 12 minutes, p = 0.011). The desflurane group required fewer 30% incremental anesthetic increases than the isoflurane group (1.8 versus 2.5, p = 0.016) to control increased SBP. End tidal/inspired drug concentration ratios were closer to unity in the desflurane patients both before (0.94 versus 0.80) and after (0.86 versus 0.70) changes in drug concentration to treat increased SBP. CONCLUSIONS: Anesthetic depth can be more rapidly titrated with desflurane compared to isoflurane. Alveolar/inspired concentration ratio approaches unity more rapidly with desflurane anesthesia.

Effect of different volatile anaesthetics on suxamethonium-induced jaw muscle contracture in rats.

Previous work has demonstrated that the interaction of hyperthermia and halothane may greatly increase the jaw muscle contracture produced by suxamethonium. We have compared the interaction of temperature and suxamethonium in the presence of halothane with the suxamethonium/temperature interaction of two other volatile anaesthetics, isoflurane and desflurane. Rats were anaesthetized with 1.35 MAC of halothane, isoflurane or desflurane. The jaw area was heated to 36-41 degrees C by a heating lamp while rectal temperature was maintained at 37 degrees C. Isometric tension was recorded from the jaw muscles. Suxamethonium 750 micrograms kg-1 i.v. induced a transient jaw muscle contracture (JMC) during halothane, isoflurane and desflurane anaesthesia. JMC exhibited significant dependence on jaw muscle temperature with all three volatile anaesthetics. Increasing the temperature of the jaw area from 37 degrees C to 41 degrees C increased JMC 8.7-fold with halothane, 8.8-fold with isoflurane and 3.1-fold with desflurane. The difference between halothane and desflurane was significant. While suxamethonium-induced JMC was dependent on temperature for all three volatile anaesthetic, the temperature dependence appeared to be less with desflurane.

Halothane and temperature interact to increase succinylcholine-induced jaw contracture in the rat.

BACKGROUND: The agonist actions of succinylcholine (SCh) have recently come under study because of their involvement in the clinical problem of masseter muscle rigidity, and their possible involvement in malignant hyperthermia. The authors investigated factors affecting SCh-induced contractures in an animal preparation. METHODS: Rats were anesthetized with either halothane (1-2%) or pentobarbital. Resting and twitch isometric tension were measured from the jaw muscles. Succinylcholine (500 or 750 micrograms/kg) was administered intravenously, producing increases in resting tension (i.e., contractures). Jaw muscle temperature was controlled by radiant heat. RESULTS: Succinylcholine increased jaw muscle tension for several seconds. These contractures exhibited tachyphylaxis, and were antagonized by vecuronium (0.8-1.5 mg/kg), indicating mediation by acetylcholine receptors (AChR). In the presence of 2% halothane, contractures were tenfold greater at a rectal temperature of 41 degrees C than at 37 degrees C. In contrast, under 50 mg/kg intraperitoneal pentobarbital anesthesia, contractures were not affected by rectal temperature. Neither the half-decay time of contracture nor twitch tension (0.2 Hz, preceding SCh) were increased in the presence of halothane at 41 degrees C. In a set of experiments in which rectal temperature was maintained at 37 degrees C but jaw temperature was varied between 36-41 degrees C, there was a significant regression of SCh-induced jaw contracture on temperature in the presence of halothane. In contrast, there was no significant relationship between jaw temperature and contracture in the presence of pentobarbital. CONCLUSIONS: These results in the rat demonstrate a temperature-dependent interaction between halothane and SCh that has not previously been described.

Elderly patients recover more rapidly from desflurane than from isoflurane anesthesia.

STUDY OBJECTIVE: To compare the hemodynamic, emergence, and recovery characteristics of desflurane-nitrous oxide (N2O) anesthesia with those of isoflurane-N2O anesthesia in elderly patients. DESIGN: Randomized study. SETTING: Main operating room of a major U.S. teaching hospital. PATIENTS: Thirty-four ASA physical status II and III patients aged 65 or older undergoing surgical procedures of greater than 1 hour duration. INTERVENTIONS: Group 1 (17 patients) received desflurane in 60% N2O for their surgical procedure. Group 2 (17 patients) received isoflurane in 60% N2O. Thiamylal 2 mg/kg administered intravenously (IV) induced anesthesia, and succinylcholine 1.5 mg/kg i.v. facilitated intubation. Muscle relaxation was maintained with vecuronium. Titration of the anesthetics maintained hemodynamics to within 20% of the patients' preinduction values. MEASUREMENTS AND MAIN RESULTS: Measurement of hemodynamics occurred every 2 minutes prior to skin incision and every 5 minutes thereafter. The times for discontinuation of inhaled anesthetics to eye opening, hand grip on command, and recall of name and date of birth were measured in a standardized fashion for both groups. The time to discharge from the postanesthesia care unit (PACU) was determined by a blinded PACU nurse using standard published criteria. The two groups did not differ with respect to demographics, hemodynamic stability, and times to eye opening (5 +/- 3 minutes for desflurane vs. 8 +/- 4 minutes for isoflurane), hand grip on command (9 +/- 4 minutes vs. 12 +/- 1 minutes), and recall of name and date of birth (13 +/- 8 minutes vs. 12 +/- 7 minutes). The median duration of PACU stay was significantly shorter (p < 0.03) in the desflurane group (80 minutes) compared to the isoflurane group (128 minutes). CONCLUSIONS: Desflurane may benefit elderly patients by providing a more rapid recovery from anesthesia, leading to a shorter PACU stay.

The effect of etomidate pretreatment on cerebral high energy metabolites, lactate, and glucose during severe hypoxia in the rat.

Etomidate was compared with thiopental with respect to preventing loss of brain high energy metabolites and accumulation of lactate during 20 min of hypoxemia (Pa2 of 16-19 mmHg) in rats with unilateral carotid artery ligation. Male Sprague-Dawley rats, anesthetized with halothane and nitrous oxide (N2O) in oxygen were randomly assigned to one of six groups. A normoxic control group which received 70% N2O in oxygen, a hypoxia group received no iv drug treatment (hypoxia-N2O), and four iv drug treatment groups (N2O was replaced by 70% nitrogen at the start of drug administration). The iv drug groups were treated as follows: hypoxia-etomidate low dose (1 mg.kg-1 iv followed by an infusion at 0.35 mg.kg-1.min-1); hypoxia-etomidate high dose (1 mg.kg-1 then 1.3 mg.kg-1.min-1); hypoxia-thiopental low dose (15 mg.kg-1, then 1.5 mg.kg-1.min-1); and hypoxia-thiopental high dose (15 mg.kg-1, then 5 mg.kg-1.min-1). After hypoxia or a corresponding period in the normoxic group, the brains were frozen in situ for later biochemical analysis. Blood was obtained prior to and at the end of hypoxia and analyzed for glucose. Brain metabolite concentrations on the side ipsilateral to the ligated carotid artery in the normoxia-N2O group were adenosine triphosphate (ATP), 2.76 +/- 0.1, phosphocreatione (PCr) 3.88 +/- 0.12, lactate 2.34 +/- 0.16, and glucose 3.56 +/- 0.28 (mumole.g-1 wet weight, mean +/- SE). There was no significant decrease in ATP in any of the hypoxia groups. PCr decreased by 45% (compared to normoxia-N2O) in the hypoxia-N2O group.(ABSTRACT TRUNCATED AT 250 WORDS)

The influence of fentanyl upon cerebral high-energy metabolites, lactate, and glucose during severe hypoxia in the rat.

The effects of intravenous administration of high-dose fentanyl (100 micrograms.kg-1, loading dose followed by an infusion of 200 micrograms.kg-1.h-1) were compared with those of a barbiturate (pentobarbital sodium 25 mg.kg-1, intraperitoneal) or hypothermia (rectal temperature 32 degrees C) on changes in cerebral cortical tissue levels of adenosine triphosphate (ATP), phosphocreatine (PCr), lactate, and glucose in severely hypoxemic rats (PaO2 13-23 mmHg for 20 min) with unilateral (left side) carotid ligation (10-12 animals in each group). Ligation of the carotid artery alone produced no change in brain high-energy metabolites, lactate, or glucose. The control values on the ligated side (nitrous oxide, 70%, + normoxia group) for cortical ATP, PCr, lactate, and glucose were 2.86 +/- 0.09 (mumol.g-1 wet weight, mean +/- 1 SE), 3.83 +/- 0.11, 1.68 +/- 0.21, and 3.29 +/- 0.47, respectively. Hypoxia (nitrous oxide, 70%, + hypoxia group) produced a significant (P less than 0.05) decrease in ATP (1.83 +/- 0.37) and PCr (1.93 +/- 0.48) and an increase in lactate (15.8 +/- 1.77) compared with the normoxic group, whereas brain glucose was not significantly changed (1.97 +/- 0.65). Fentanyl (fentanyl + hypoxia group) did not prevent the deleterious effects of hypoxia on cortical high energy metabolites (ATP, 2.0 +/- 0.27; PCr, 2.24 +/- 0.3) or lactate (19.33 +/- 3.16); however, fentanyl caused no alteration in high-energy cerebral metabolite concentrations in normoxic rats, nor did fentanyl produce a significant difference in brain tissue glucose or lactate.(ABSTRACT TRUNCATED AT 250 WORDS)

Influence of sufentanil on cerebral metabolism and circulation in the rat.

The authors examined the effects of large intravenous doses of sufentanil (5-160 micrograms/kg) on cerebral blood flow (CBF) and cerebral metabolic rate for oxygen (CMRO2) in rats. CBF and CMRO2 were measured by a modified Kety-Schmidt technique using 133Xenon washout. Progressive decreases in CBF and CMRO2 occurred in animals receiving sufentanil. The maximum decrease was 53% and 40% for CBF and CMRO2 respectively, at a dose of 80 micrograms/kg. The values for CBF and CMRO2 in this group were 105 +/- 10 ml X 100 g-1 X min-1 (mean +/- SEM) and 6.5 +/- 0.5 ml X 100 g-1 X min-1, respectively, compared with 226 +/- 28 ml X 100 g-1 X min-1 and 10.9 +/- 1 ml X 100 g-1 X min-1 in the control group, which received N2O 70% in oxygen. Larger doses of sufentanil did not cause further significant changes in CBF and CMRO2. Sharp waves appeared on the electroencephalogram (EEG) of all the animals following sufentanil injection, and some animals had EEG changes develop consistent with seizure activity. This seizure-like activity appeared to consist of a single episode of short duration in the groups receiving 5, 10, and 20 micrograms/kg sufentanil. The incidence and frequency of seizure activity increased in the groups receiving higher doses of sufentanil, although the duration of seizures was still short. The results of this study indicate that sufentanil causes a significant decrease in CBF and CMRO2 similar to that previously reported for fentanyl, and high doses of sufentanil may cause frequent seizure-like patterns appearing on EEG.

The effects of high-dose fentanyl on cerebral circulation and metabolism in rats.

There is considerable controversy with respect to the effects of narcotics on the cerebral blood flow (CBF) and the cerebral metabolic rate for oxygen (CMRo2). The present study examined the effects of high doses of intravenous fentanyl (25-400 micrograms/kg) on the CBF and CMRo2 in rats. Cerebral cortical blood flow and metabolism were measured using the 133Xenon modification of the Kety-Schmidt technique. Fentanyl produced a dose-related decrease in both the CBF and the CMRo2. CBF and CMRo2 were maximally depressed by 50 and 35%, respectively, in rats given fentanyl 100 micrograms/kg compared with nitrous oxide-oxygen ventilated controls. The values for CBF and CMRo2 were 168 +/- 15 ml . 100 g-1 . min-1 and 10.3 +/- 0.7 ml . 100 g-1 . min-1, respectively in the nitrous oxide controls compared with 85 +/- 3 ml . 100 g-1 . min-1 and 7.1 +/- 0.1 ml . 100 g-1 . min-1 in animals receiving fentanyl 100 micrograms/kg. Higher doses of fentanyl did not further decrease either CBF or CMRo2 (108 +/- 12 ml . 100 g-1 . min-1 and 7.0 +/- 0.4 ml . 100 g-1 . min-1, respectively for fentanyl 400 micrograms/kg); however, seizures activity was noticed in about 25% of the rats receiving either 200 or 400 micrograms/kg fentanyl. The seizures seemed to be related to the narcotic in that they could be abolished by injections of naloxone. The seizure activity appeared to increase the CMRo2 relative to animals who received the same dose of fentanyl but did not have seizures. The CBF was not affected. The results confirm that narcotics in high enough doses may depress the CBF and CMRo2.

Reduction of the cerebral protective effect of hypothermia by oligemic hypotension during hypoxia in the rat.

The effect of arterial hypotension on cerebral cortical tissue levels of adenosine triphosphate (ATP), phosphocreatine (PGr), lactate, and reduced nicotinamide adenine dinucleotide (NADH) was studied in male Wistar rats with unilateral carotid ligation exposed to arterial by hypoxia (PaO2 25 torr) for 20 min. while the body temperature was maintained at 32 degrees C and 27 degrees C. Brain metabolite levels were normal in normotensive hypothermic animals exposed to hypoxia, but reduction in arterial pressure to 75 torr caused a significant (p less than 0.05) decrease in ATP and PCr values and a significant increase in lactate and NADH levels. These changes were comparable to those of normothermic normotensive, hypoxic animals. Furthermore, there was no significant differences in the brain metabolite levels between the two hypotensive hypoxic groups. These results indicate that arterial hypotension severely alters the cerebral protective effect of hypothermia against injury caused by hypoxia, and that further reduction in body temperature (from 32 degrees C to 27 degrees C) will not prevent the harmful effect of hypoxia upon the brain in hypotensive rats.

Effect of high vs. low arterial blood oxygen content on cerebral energy metabolite levels during hypoxia with normothermia and hypothermia in the rat.

The effects of different levels of arterial blood oxygen content (CaO2) on brain tissue adenosine triphosphate (ATP), phosphocreatine (PCr), lactate, and reduced nicotinamide adenine dinucleotide (NADH) were studied during cerebral hypoxia in normothermic and hypothermic male Wistar rats with unilateral carotid ligation. Animals were exposed to hypoxia (PaO2 19--26 torr) for 25 min, and brain tissue metabolite values measured microfluorometrically were compared with those of normothermic normoxic controls. CaO2 was 4.0 +/- 0.2 ml/dl (mean +/- SEM) at PaO2 26 torr in normothermic animals. CaO2 was increased to 8.2 +/- 0.3 ml/dl at PaO2 26 torr by means of bicarbonate infusion producing a leftward shift of the oxyhemoglobin-dissociation curve in one normothermic hypoxic group. In all normothermic hypoxic groups ATP and PCr decreased and lactate and NADH increased significantly compared with control values. There was no significant difference in brain tissue metabolite values among these groups despite an increase in CaO2 by twofold in one group. Hypothermia (32 C) resulted in CaO2 8.4 +/- 0.2 ml/dl at PaO2 26 torr. This was decreased to 4.0 +/- 0.2 ml/dl by decreasing PaO2 to 19 torr in another group at the same temperature. ATP and PCr were well preserved in both groups despite the difference in CaO2s. Although the lactate and NADH levels were increased in the hypothermic group with CaO2 4.0 +/- 0.2 ml/dl, they were significantly lower than those values in normothermic hypoxic groups. These results indicate that the increase in CaO2 produced by hypothermia is not a major determinant in hypothermic protection during cerebral hypoxia.

Cerebral energy levels during trimethaphan-induced hypotension in the rat: effects of light versus deep halothane anesthesia.

Hypotension may be expected to produce less perturbation of metabolism in the brain when cerebral metabolic rate is lowered by deep anesthesia. Male Wistar rats having unilateral carotidartery ligation were exposed to mean arterial pressure (MAP) of 40 torr for 22 min by an intravenous infusion of trimethaphan during anesthesia with halothane, 0.6 or 2 per cent, in oxygen. Cortical tissue metabolite levels on the side of the ligated carotid artery were more abnormal in rats receiving halothane, 0.6 per cent, than in those receiving halothane, 2 per cent. Values at halothane, 0.6 per cent, were adenosine triphosphate (ATP), 1.71 +/- 0.05 (+/-SEM) mumol/g, phosphocreatine (PCr) 1.97 +/- 0.07 mumol/g. and lactate 16.5 +/- 5.1 mumol/g; corresponding values at halothane, 2 per cent, were ATP 2.27 +/- 0.02, PCr 4.02 +/- 0.23, and lactate 4.75 +/- 0.9 mumol/g. ATP and PCr values were significiantly lower (P less than 0.05) and the lactate value was significantly higher with halothane, 0.6 per cent, than with halothane 2 per cent. Cerebral oxygen consumption decreased 47 per cent in rats anesthetized with halothane, 2 per cent. Preservation of cortical metabolite levels in deeply anesthetized animals suggests a protective effect of cerebral metabolic depression.

Cerebral energy metabolite levels and survival following exposure to low inspired oxygen concentration.

To determine the relationship between brain energy metabolites and neurologic status after ischemia-hypoxia, we measured cortical tissue levels of adenosine triphosphate (ATP), phosphocreatine, and lactate. Rats with permanent unilateral carotid occlusion were exposed to 5, 10, and 15 min of hypoxic atmosphere (FIO2 0.048) and, to examine metabolic restitution, 60 min after recovery in rats exposed to the same hypoxic mixture for 15 min. At 5 and 10 min of hypoxia, there were significant reductions in phosphocreatinine and elevations in tissue lactate, but only after 15 min of hypoxia, did ATP levels significantly decrease. By 60 min after recovery, phosphocreatinine values returned to the normal range, ATP values to 15% less than normal, and tissue lactate toward normal. In parallel survival studies, neurological status was examined following hypoxic exposure (PaO2 18 to 19 torr) for 5 an 10 min. Evidence for neurological injury in the form of posthypoxic seizures occurred at a point in time preceding significant changes in brain tissue ATP level. Since injury occurs prior to ATP reduction, changes in brain tissue ATP level may not be an appropirate endpoint for determining brain tissue injury in hypoxia.

Cerebral hypometabolism obtained with deep pentobarbital anesthesia and hypothermia (30 C).

Cerebral metabolic and vascular effects of hypothermia (30 C) and deep pentobarbital anesthesia, separately and combined, were evaluated in 15 mongrel dogs. External cardiovascular support was not used, and mean arterial blood pressures remained greater than 60 torr. Normothermic deep pentobarbital anesthesia, characterized by an electroencephalographic (EEG) frequency of less than 1 Hz, was associated with 30% decreases in cerebral metabolic rates for oxygen (CMRO2) and glucose (CMRG) from lightly anesthetized control values. Hypothermia (30 C) alone caused similar decreases in CMRO2 and CMRG in the presence of an active EEG. The use of pentobarbital anesthesia and hypothermia combined achieved significantly greater (P less than 0.05) decreases in CMRO2 (70%) and CMRG (72%) from the control state. Cerebral vascular resistance (CVR) increased by 70% (P less than 0.05) during hypothermia and about 20% when pentobarbital was administered to normothermic dogs. In hypothermic animals the addition of pentobarbital had a minimal effect on CVR. No alteration in the oxygen-glucose or lactate-glucose index indicative of cerebral hypoxia occurred in any experimental group. This study indicates that barbiturates combined with hypothermia decrease cerebral metabolism to a greater extent than hypothermia or barbiturate alone. When cerebral hypometabolism is therapeutically necessary, barbiturates may be indicated as an adjunct to moderate hypothermia.