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G A Gronert

Publications and source records attributed to G A Gronert.

At least 19 recordsLinked to original sources
PubMed1995

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↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1995

Allometry of pharmacokinetics and pharmacodynamics of the muscle relaxant metocurine in mammals.

We investigated the effects of body size on the pharmacokinetics and pharmacodynamics of the renally cleared muscle relaxant metocurine. We hypothesized that pharmacokinetics of the drug would change allometrically in proportion to physiological time [infinity Mb0.25, where Mb is body mass] and that pharmacodynamics would be independent of size because of the highly conserved structure of the acetylcholine receptor. Metocurine effects during general anesthesia were examined in 17 rats, 8 cats, 6 dogs, 5 pigs, 7 sheep, and 12 horses. Allometric analysis demonstrated size dependence for pharmacokinetics, which were affected by physiological time (Mb0.25). Pharmacodynamics were size independent, except for the value for effect compartment concentration associated with 50% twitch paralysis (IC50). Data from individual species had a bimodal distribution that was significant: pigs and sheep were more sensitive than other large species, and their IC50 appeared size independent. IC50 was size dependent in more active species (horse, dog, cat, rat). Although the mechanism is unknown, we speculate that this trend might relate to receptor density within the end plate. Thus pharmacokinetics changed in proportion to physiological time, and pharmacodynamics were in part size independent.

Anesthesia, General↗
PubMed1994

A clinical grading scale to predict malignant hyperthermia susceptibility.

BACKGROUND: The diagnosis of an acute malignant hyperthermia reaction by clinical criteria can be difficult because of the nonspecific nature and variable incidence of many of the clinical signs and laboratory findings. Development of a standardized means for estimating the qualitative likelihood of malignant hyperthermia in a given patient without the use of specialized diagnostic testing would be useful for patient management and would promote research into improved means for diagnosing this disease. METHODS: Using the Delphi method and an international panel of 11 experts on malignant hyperthermia, a multifactor malignant hyperthermia clinical grading scale comprising standardized clinical diagnostic criteria was developed for classification of existing records and for application to new patients. RESULTS: This scale ranks the qualitative likelihood that an adverse anesthetic event represents malignant hyperthermia (malignant hyperthermia event rank) and that, with further investigation of family history, an individual patient will be diagnosed as malignant hyperthermia susceptible (malignant hyperthermia susceptibility rank). The assigned rank represents a lower bound on the likelihood of malignant hyperthermia. The clinical grading scale requires the anesthesiologist to judge whether specific clinical signs are appropriate for the patient's medical condition, anesthetic technique, and surgical procedure. CONCLUSIONS: The malignant hyperthermia clinical grading scale is recommended for use as an aid to the objective definition of this disease. It use may improve malignant hyperthermia research by allowing comparisons among well-defined groups of patients. This clinical grading system provides a new and comprehensive clinical case definition for the malignant hyperthermia syndrome.

Adult↗
PubMed1994

Ultrasonography: not useful in detecting susceptibility to malignant hyperthermia.

MH is a rare, potentially fatal complication of general anesthesia. Halothane-caffeine contracture testing of a muscle biopsy is the only accepted diagnostic test for MH. A previous report indicated that ultrasonography may aid in diagnosis of MH. Using sonographic examination of the thigh and calf, we evaluated eight patients with proved susceptibility to MH and eight control patients. Two radiologists independently evaluated the sonograms for echogenicity and definition of fascial planes. We detected no consistent and reliable differences between control and MH patients. We conclude that, in our hands, ultrasonography is not useful in differentiating patients with MH from normal persons.

Adipose Tissue↗
PubMed1993

Prolonged duration of succinylcholine in patients receiving anticonvulsants: evidence for mild up-regulation of acetylcholine receptors?

Succinylcholine (SCh) normally causes a small increase in serum potassium concentration, but certain conditions may predispose to severe hyperkalaemia. This is due to "up-regulation" of skeletal muscle acetylcholine receptors (AChR), which also results in resistance to non-depolarizing muscle relaxants (NDMR). Anticonvulsant therapy causes NDMR resistance because of sub-clinical blockade, and diminished release, of acetylcholine. We studied nine patients chronically receiving anticonvulsants (phenytoin and/or carbamazepine) and nine control patients. Anaesthesia was induced typically with thiopentone or propofol; isoflurane and N2O were used for maintenance. The ulnar nerve was supramaximally stimulated and mechanical twitch height was measured with a force transducer at the adductor pollicis, before and after SCh 1 mg.kg-1, until return to baseline height. Plasma potassium concentration was measured before and at three, five, and ten minutes following SCh. Mean maximum potassium rise was 0.2 mEq.L-1 in each group. The time for return to baseline twitch height was 14.3 +/- 2.3 min (mean +/- SD) in the anticonvulsant group and 10.0 +/- 1.6 min in the control group, P = 0.001. The recovery index (time for 25% to 75% recovery) was 2.6 +/- 0.9 min in the anticonvulsant group and 1.4 +/- 0.3 min in the control group, P < 0.01. The normal potassium response coupled with prolonged duration suggests a hypersensitivity to SCh that is consistent with an anticonvulsant-induced mild up-regulation of AChR.

Acetylcholine↗
PubMed1993

No dantrolene protection in a dog model of complete cerebral ischaemia.

Intracellular free calcium is believed to play a major role in the ischaemic cascade which leads to cell death. Calcium channel blockers, which in part inhibit the influx of extracellular calcium, have been shown to be neuroprotective in both complete and focal cerebral ischaemia models. Dantrolene, an agent used in the treatment of malignant hyperthermia, is known to inhibit the release of stored intracellular calcium. Assuming that reduced levels of intracellular free calcium would improve neurologic outcome, we studied the neuroprotective potential of dantrolene. A complete cerebral ischaemia model was used to examine ten anesthetized dogs. Five were given intravenous dantrolene and five were given equal volumes of saline prior to the ischaemic event. Simultaneous occlusion of the venae cavae and ascending aorta provided eleven minutes of complete cerebral ischaemia as monitored by electroencephalography. Arterial blood gases and serum glucose levels were drawn prior to ischaemia, 5 and 20 minutes post-ischaemia, and following extubation. Forty-eight hours following the ischaemic event, neurologic outcomes were scored. No significant differences were observed between the two groups. All ten dogs had equally significant increases in serum glucose levels at 5 and 20 minutes post-ischaemia. The average neurologic outcome of the five dantrolene-treated dogs equalled the average of the five controls. These results suggest that dantrolene, alone, is not neuroprotective during complete cerebral ischaemia.

Animals↗
PubMed1993

Succinylcholine causes profound hyperkalemia in hemorrhagic, acidotic rabbits.

Two recent clinical reports suggested that succinylcholine (SCh) may cause severe hyperkalemia in hemorrhagic, acidotic humans. To investigate this, we anesthetized rabbits with halothane and N2O, and inserted venous and arterial catheters. Control rabbits (Group C, n = 4) remained anesthetized and undisturbed. Hemorrhage/profound acidosis (HPA) was accomplished by withdrawal of 25-30 mL/kg of blood and waiting until pHa approximately 7.05 (Group HPA, n = 5). Hemorrhage/minimal acidosis (HMA) was accomplished by withdrawal of 25-30 mL/kg of blood, but acidosis was minimized by not waiting for it to occur and by administering NaHCO3 0-1.4 mEq/kg (Group HMA, n = 4). In a metabolic acidosis group (n = 4), HCl was infused until pHa approximately 7.05. Respiratory acidosis (n = 4) was accomplished by partial obstruction of the endotracheal tube until PaCO2 approximately 120 mm Hg and pHa approximately 7.05. Potassium levels were determined before the above interventions (baseline), immediately before (pre-SCh), and 1, 3, 5, 7, 10, and 13 min after SCh 1 mg/kg intravenously. In Group C, potassium gradually increased from 3.5 +/- 0.2 mEq/L to 4.8 +/- 0.2 mEq/L 13 min after SCh. In Group HPA, potassium increased from 3.8 +/- 0.3 to 7.0 +/- 1.8 mEq/L after hemorrhage/acidosis and then to 11.4 +/- 1.7 mEq/L at 13 min after SCh. The metabolic acidosis group was significantly different from Group C at 7, 10, and 13 min after SCh (maximum at 13 min, 6.8 +/- 1.2 mEq/L).(ABSTRACT TRUNCATED AT 250 WORDS)

Acidosis↗
PubMed1992

Absence of malignant hyperthermia contractures in Becker-Duchenne dystrophy at age 2.

Two 2-year-old males underwent muscle biopsy that established the histopathologic diagnosis of Becker dystrophy in one, and Duchenne dystrophy in the other. Concomitant contracture testing with caffeine or halothane was normal for malignant hyperthermia (MH). The results suggest that acute hypermetabolism or acute rhabdomyolysis during anesthesia, in patients with these disorders, is related to the X-linked myopathy and its associated muscle deterioration, rather than to the autosomal dominant MH.

Age Factors↗
PubMed1992

Up-and-down regulation of skeletal muscle acetylcholine receptors. Effects on neuromuscular blockers.

Multiple factors alter the interaction of muscle relaxants with the NMJ. This review has focused on the aberrant responses caused principally by alterations in AChRs (table 1). Many pathologic states increase (up-regulate) AChR number. These include upper and lower motor neuron lesions, muscle trauma, burns, and immobilization. Pre- or postjunctional inhibition of neurotransmission by drugs or toxins also up-regulate AChRs. These include alpha- and beta-BT, NDMR, anticonvulsants, and clostridial toxins. We speculate that other bacterial toxins also up-regulate AChR. With proliferation of AChRs, agonist drug dose-response curves are shifted to the left. The exaggerated release of potassium when depolarization occurs with the use of agonists such as SCh and decamethonium can be attributed to the increased number of AChR. Thus, SCh should be avoided in patients who are in the susceptible phase (see section V). In the presence of increased AChR, the requirement for NDMR is markedly increased. Thus, the response to NDMR may be used as an indirect estimator of increased sensitivity to SCh (table 1). The most extensively studied pathologic state in which there is a decrease in AChRs is myasthenia gravis; there is immunologically mediated destruction and/or functional blockade of AChRs. The pathophysiologic and pharmacologic changes in LEMS are quite distinct from those of myasthenia gravis. Decreased AChRs in myasthenia gravis result in resistance to agonists and increased sensitivity to competitive antagonists. In conditioning exercise, the perturbed muscles show sensitivity to NDMR that may be due to decreased AChRs. Chronic elevations of ACh observed with organophosphorus poisoning or chronic use of reversible cholinesterase inhibitors results in down-regulation of AChRs. In this condition, SCh should be avoided because its metabolic breakdown would be impaired; the requirement for NDMR may be decreased. All of the varied responses to SCh and NDMR, which are associated with concomitant changes in AChRs, are analogous to drug-receptor interactions observed in other biologic systems.

Animals↗