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Biomedical subjects

G A Gronert

Publications and source records attributed to G A Gronert.

At least 19 recordsLinked to original sources

Plasma electrolyte and metabolite concentrations associated with pentobarbital or pentobarbital-propofol anesthesia during three weeks' mechanical ventilation and intensive care in dogs.

Propofol and pentobarbital were used for deep sedation during prolonged mechanical ventilation (3 weeks) and nutritional supplementation in 17 clinically normal dogs in an intensive care setting. Tolerance developed to both drugs. Propofol, in combination with pentobarbital, at an infusion rate of 75 micrograms/kg of body weight per minute was preferred. Pentobarbital infusion alone, begun at the rate of 5 to 6 mg.kg-1.h-1, was satisfactory. The combination of both drugs provided smooth, stable anesthesia and required minimal interventions by intensive care unit personnel. Blood gas tensions and electrolyte, parathyroid hormone (PTH), and metabolite concentrations were generally stable throughout, unless condition of the dog deteriorated (e.g., infection, pneumothorax). Hematocrit and red blood cell count decreased with time, likely attributable principally to multiple blood sample collections. White blood cell count, alkaline phosphatase, phosphate, fibrinogen, cholesterol, and triglyceride values increased with time, in association with pentobarbital and the combination of pentobarbital and propofol. Some of these changes appear to have been related to generic responses to stress and inflammation, some to altered metabolism, and some to the lipid solvent of propofol. The increase in triglyceride concentration was greater when propofol was used. Mortality was 47%, with death occurring between days 2 and 18.

Anesthesia, Intravenous

Effect of temperature variation (22 degrees C-44 degrees C) on halothane and caffeine contracture testing in normal humans.

BACKGROUND: Malignant hyperthermia (MH) susceptibility is diagnosed using halothane-caffeine contracture testing of a muscle sample maintained at 37 degrees C. However, there has not been a systematic study that examines the effect of different temperatures on the response of normal muscle to halothane and caffeine. We hypothesized that altering bath temperature would modify the contracture responses. METHODS: We obtained muscle samples from 20 patients undergoing surgical procedures of the lower extremities. The samples were dissected into 245 bundles and the bundles were exposed to halothane 3% or incremental caffeine, according to the North American MH group protocol. Several bundles from each patient were simultaneously studied at four different temperatures (22 degrees C, 30 degrees C, 37 degrees C and 44 degrees C). Each bundle was studied at only one temperature, the muscle samples of 3 patients were simultaneously studied at all four temperatures for halothane and caffeine. RESULTS: Maximum contracture to caffeine (32 mM) was highest at 37 degrees C; however, at lower caffeine concentrations (2-4 mM), there was no consistent effect of temperature on contracture response. Likewise, temperature did not alter contracture responses to halothane. The extremes of temperature (22 degrees C and 44 degrees C) were associated with lack of twitch in response to electrical stimulation. For the bundles exposed to halothane at 22 degrees C, the absence of a twitch was associated with the presence of a contracture, although these were never above the diagnostic threshold. CONCLUSIONS: We conclude that temperature has little effect on responses of normal muscle to halothane and caffeine.

Aged

Hyperkalemic cardiac arrest during anesthesia in infants and children with occult myopathies.

In 1992, the Malignant Hyperthermia Association of the United States and The North American Malignant Hyperthermia Registry received reports of cardiac arrest in apparently healthy children given succinylcholine. Using data from 1990 to 1993, this study analyzes: (1) etiology of all reported pediatric arrests and (2) whether survival was associated with certain patient or treatment variables. We reviewed retrospectively all reports of pediatric (age < 18 years) arrests occurring within 24 hours of anesthesia. Etiology of arrests and presence of myopathy were determined. Twenty-five patients (92% male, median 45 months old) arrested; 23/25 (92%) were scheduled for minor surgery. Before receiving a potent inhalational anesthetic (92%) and/or succinylcholine (72%), these patients were evaluated by the anesthesiologist as being healthy with no personal or family history of myopathy. Serum potassium during arrest was measured in 18/25 (72%) patients; hyperkalemia (mean [K+] = 7.4 +/- 2.8, median 7.5 mmol/L) was detected in 13/18 (72%) patients. Postarrest resuscitations lasted a median of 42 minutes (range 10-296). Ten (40%) patients died, 1 (4%) is vegetative, and 14 (56%) returned to baseline neurologic function. A previously unrecognized Duchenne dystrophy (n = 8) or unspecified myopathy (n = 4) was diagnosed in 12 (48%) patients. Eight of these 12 patients' arrests were associated with hyperkalemia. Ten (40%) patients had no postarrest evaluation to exclude occult myopathy. No patient or treatment variables were statistically associated with survival. We conclude that, whenever possible, pediatricians should evaluate their patients (especially male infants and children) preoperatively for the presence of occult myopathy. During perianesthetic resuscitations, the pediatric advanced life support protocol should be modified to detect and treat hyperkalemia, a potentially reversible state even after prolonged resuscitation efforts. Following anesthetic deaths, pathologists should examine body fluid electrolytes and skeletal muscle for myopathy and dystrophin. If a preanesthetic creatine kinase screen for myopathy in male patients and restrictions on succinylcholine had been used, 64% of arrests and 60% of deaths might have been prevented. A formal prospective risk/benefit analysis for preventive measures is needed.

Adolescent

Masseter muscle rigidity and nondepolarizing neuromuscular blocking agents.

Masseter muscle rigidity has been identified as a possible risk factor for malignant hyperthermia (MH) and is usually noted in children receiving intravenously administered succinylcholine chloride after mask induction with halothane. Nondepolarizing muscle relaxants are considered safe for persons susceptible to MH. In this article, we present a case of clinically recognized jaw rigidity in the absence of succinylcholine after administration of a non-depolarizing muscle relaxant that was reported to the Malignant Hyperthermia Association of the United States hot line. The patient had recurrent jaw rigidity during subsequent anesthesia when a different non-depolarizing muscle relaxant was given. The North American MH Registry was then reviewed for similar cases. Three cases of masseter muscle rigidity in the presence of nondepolarizing muscle relaxants were discovered. Two of the patients were not found to be susceptible to MH; however, the third patient had positive findings on muscle biopsy. These cases do not provide enough information to confirm the ability of nondepolarizing muscle relaxants to cause jaw rigidity in the absence of MH.

Adult

Evaluation for malignant hyperthermia susceptibility in black-tailed deer.

To investigate a possible link of malignant hyperthermia to capture myopathy, between June 1990 and July 1993 we anesthetized four black-tailed deer (Odocoileus hemionus columbianus) and challenged them with halothane and succinylcholine. Halothane had no significant effect on oxygen consumption. Succinylcholine significantly (P < 0.05) increased cardiac output (mean +/- SD), from 2.94 +/- 1.05 l/min to 5.26 +/- 1.79 l/min, and oxygen consumption, from 5.5 +/- 2.1 ml/kg/min to 10.1 +/- 2.9 ml/kg/min. Muscle biopsy specimens tested for malignant hyperthermia susceptibility responded normally to halothane and caffeine. We conclude that these deer did not experience malignant hyperthermia; suggesting no link to capture myopathy.

Anesthetics, Inhalation

The changing pharmacodynamics of metocurine identify the onset and offset of canine gastrocnemius disuse atrophy.

BACKGROUND: Immobilization of skeletal muscle results in disuse atrophy and resistance to nondepolarizing muscle relaxants. We studied the pharmacodynamics of metocurine (MTC) to identify the development and recovery of disuse-related resistance to MTC. METHODS: Nineteen dogs underwent cast immobilization of a hind limb for as long as 3 weeks. Before, during, and after casting, dogs were intermittently anesthetized with thiamylal-N2O-fentanyl. The blood concentration of MTC and the corresponding degree of paralysis after a brief infusion were recorded and were used to characterize the pharmacokinetics and pharmacodynamics of MTC. RESULTS: Pharmacodynamic study of the response to MTC demonstrated resistance by the 4th day of casting. The effect-site concentration associated with 50% paralysis of twitch increased after 3 weeks from approximately 250 to 750 ng/ml. After cast removal, resistance persisted for 2 more weeks. Six weeks after cast removal, the effect-site concentration associated with 50% paralysis of twitch was normal in every dog. CONCLUSIONS: Within the context of this study of immobilization disuse atrophy, pharmacokinetic and pharmacodynamic characterization of antagonist responses can be used to infer muscle disuse-related changes in acetylcholine receptors.

Acetylcholine

Metocurine pharmacokinetics and pharmacodynamics in goats.

Non-depolarizing muscle relaxants can facilitate surgery and anaesthesia in numerous species. and volatile inhalational anaesthetics such as isoflurane potentiate their action. We studied the effect of isoflurane on the pharmacodynamics and pharmacokinetics of metocurine in six goats. Each was studied twice: once during barbiturate-opiate anaesthesia and once during isoflurane anaesthesia. The evoked response to sciatic nerve stimulation was measured using a force transducer attached to the hoof. Metocurine was infused until approximately 80-90% blockade. Plasma metocurine concentration was determined by high-performance liquid chromatography. Isoflurane increased the potency of metocurine significantly; IC50 (the concentration in the effect compartment at 50% paralysis) was 70 +/- 15 ng/mL during isoflurane anaesthesia and 129 +/- 42 ng/mL during barbiturate-opiate anaesthesia (P < 0.03). Volume of distribution (63 +/- 18 mL/kg), clearance (1.6 +/- 0.4 mL/min.kg) and elimination half-life (99 +/- 9 min) during barbiturate-opiate anaesthesia were not significantly different during isoflurane anaesthesia: 64 +/- 25 mL/kg, 1.5 +/- 0.7 mL/kg.min, 116 +/- 16 min respectively. We conclude that, relative to barbiturate-opiate anaesthesia, isoflurane potentiates metocurine in goats.

Anesthesia

Caffeine-halothane accuracy in MH testing.

The accuracy and stability of caffeine and halothane concentrations in liquid Krebs medium were examined. Caffeine-Krebs Ringer's solution in incremental concentrations from 0.25 to 10 mM (N = 8 for each concentration) was serially assayed over a three-year period. Storage was at 4 degrees C. For serial testing of halothane during a five month period, halothane 1% or 3% in carbogen was bubbled through a Krebs solution, contained in muscle baths, either using a roller pump (to eliminate vaporizer back pressure) or using carbogen at a line pressure of 4-6 lbs/in2 (27-41 kPa). Halothane in Krebs was assayed by high pressure liquid chromatography. Caffeine concentrations did not vary for 20 weeks. From then, through 60 weeks, concentrations less than 2 mM steadily diminished; after that, through 156 weeks, only 4, 8, and 10 mM were stable. When compared to the halothane concentration in gas entering the muscle baths, halothane concentration in Krebs was predictable regardless of method delivery, as long as a gas analyzer indicated the proper concentration. We conclude that caffeine solutions are stable for 20 weeks when refrigerated, and for three years at concentrations 4 mM or greater.

Caffeine

Femoral and lateral femoral cutaneous nerve block for muscle biopsies in children.

Retrospective chart review (1978-1993) of 179 children less than age 18 (10.0 +/- 3.8 SD yrs) undergoing muscle biopsy for determination of susceptibility to malignant hyperthermia provided data. One hundred and forty-six patients received femoral and lateral femoral cutaneous nerve blocks as their primary anaesthetic. We examined age, weight, duration of surgery, time to discharge from hospital, choice and dosage of local anaesthetics, choice and dosage of sedation, postoperative pain medications, and complications. All children receiving this form of anaesthesia remained outpatients. Between 1978 and 1985 procaine (10 mg.kg-1) with hyaluronidase or 2-chloroprocaine (12 mg.kg-1) provided nerve blockade; after 1985, lignocaine (6.8 mg.kg-1), or a combination of lignocaine or mepivacaine and 2-chloroprocaine, were the preferred agents. More recently the combination of 2-chloroprocaine and bupivacaine has been popular. Three patients required admission to the recovery room postoperatively, due to heavy sedation. Forty-three children (29%) received pain medication during recovery. Femoral and lateral femoral cutaneous block anaesthesia with light to moderate sedation is well tolerated in children undergoing anterior thigh procedures.

Anesthetics, Local