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Biomedical subjects

G A Gronert

Publications and source records attributed to G A Gronert.

At least 37 records · Page 2Linked to original sources
PubMed1997

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↗
PubMed1997

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↗
PubMed1996

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↗
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↗