Succinylcholine Use and Dantrolene Availability for Malignant Hyperthermia Treatment: Database Analyses and Systematic Review.

Background: Although dantrolene effectively treats malignant hyperthermia (MH), discrepant recommendations exist concerning dantrolene availability. Whereas Malignant Hyperthermia Association of the United States guidelines state dantrolene must be available within 10 min of the decision to treat MH wherever volatile anesthetics or succinylcholine are administered, a Society for Ambulatory Anesthesia protocol permits Class B ambulatory facilities to stock succinylcholine for airway rescue without dantrolene. The authors investigated (1) succinylcholine use rates, including for airway rescue, in anesthetizing/sedating locations; (2) whether succinylcholine without volatile anesthetics triggers MH warranting dantrolene; and (3) the relationship between dantrolene administration and MH morbidity/mortality.

Multifactorial Origin of Exertional Rhabdomyolysis, Recurrent Hematuria, and Episodic Pain in a Service Member with Sickle Cell Trait.

Individuals with Sickle Cell Trait (SCT), generally considered a benign carrier state of hemoglobin S (HbAS), are thought to be at risk for exertional rhabdomyolysis and hematuria, conditions that can also be caused by various other acquired and inherited factors. We report an SCT positive service member with an exertional rhabdomyolysis event, recurrent hematuria with transient proteinuria, and episodic burning pain in the lower extremities. Clinical and genetic studies revealed the multifactorial nature of his complex phenotype.

Pathogenic and rare deleterious variants in multiple genes suggest oligogenic inheritance in recurrent exertional rhabdomyolysis.

Exertional rhabdomyolysis is a metabolic event characterized by the release of muscle content into the circulation due to exercise-driven breakdown of skeletal muscle. Recurrent exertional rhabdomyolysis has been associated with metabolic myopathies and mitochondrial disorders, a clinically and genetically heterogeneous group of predominantly autosomal recessive, monogenic conditions. Although genetics factors are well recognized in recurrent rhabdomyolysis, the underlying causes and mechanisms of exercise-driven muscle breakdown remain unknown in a substantial number of cases.

Should Continuous Subcutaneous Insulin Infusion (CSII) Pumps Be Used During the Perioperative Period? Development of a Clinical Decision Algorithm.

According to the Centers for Disease Control and Prevention, there are 30.3 million Americans with diabetes mellitus (DM). It is estimated that more than 400,000 individuals with DM are using continuous subcutaneous insulin infusion (CSII) pumps as a method to maintain blood glucose control.

Round Table on Malignant Hyperthermia in Physically Active Populations: Meeting Proceedings.

Context:   Recent case reports on malignant hyperthermia (MH)-like syndrome in physically active populations indicate potential associations among MH, exertional heat stroke (EHS), and exertional rhabdomyolysis (ER). However, an expert consensus for clinicians working with these populations is lacking.

Objective:   To provide current expert consensus on the (1) definition of MH; (2) history, etiology, and pathophysiology of MH; (3) epidemiology of MH; (4) association of MH with EHS and ER; (5) identification of an MH-like syndrome; (6) recommendations for acute management of an MH-like syndrome; (7) special considerations for physically active populations; and (8) future directions for research.

Malignant Hyperthermia Susceptibility and Fitness for Duty.

Introduction: Malignant hyperthermia (MH) is an inherited hypermetabolic condition characterized by uncontrolled calcium release from the sarcoplasmic reticulum of skeletal muscle, usually from exposure to inhaled general anesthetics and/or the depolarizing neuromuscular blocking agent succinylcholine. Multiple case reports now reveal that crises may be precipitated by environmental factors such as exercise or high ambient temperatures. Common signs of an MH crisis include life-threatening hyperthermia, metabolic acidosis, muscle rigidity, and tachycardia.

Exome analysis identifies Brody myopathy in a family diagnosed with malignant hyperthermia susceptibility.

Whole exome sequencing (WES) was used to determine the primary cause of muscle disorder in a family diagnosed with a mild, undetermined myopathy and malignant hyperthermia (MH) susceptibility (MHS). WES revealed the compound heterozygous mutations, p.Ile235Asn and p.

Improving awareness of nonanesthesia-related malignant hyperthermia presentations: a tale of two brothers.

A 30-year-old man developed unexplained rhabdomyolysis, persistently increased creatine kinase and severe debilitating muscle cramps. After a nondiagnostic neurologic evaluation, he was referred for a muscle biopsy, to include histology/histochemistry, a myoglobinuria panel, and a caffeine halothane contracture test. Only the caffeine halothane contracture test was positive, and a subsequent ryanodine receptor type 1 gene evaluation revealed a mutation functionally causative for malignant hyperthermia.

Is lymphocyte adenosine a diagnostic marker of clinical malignant hyperthermia? A pilot study.

Objective: Malignant hyperthermia is a pharmacogenetic disorder typically triggered by potent inhalation anesthetics and/or the depolarizing muscle relaxant succinylcholine in malignant hyperthermia-susceptible individuals. Since lymphocytes express the same Ca channel mutation found in malignant hyperthermia-susceptible muscle, we investigated agonist-induced adenosine formation in lymphocytes as an index of sarcoplasmic reticulum Ca-release-induced adenosine 5'-triphosphate turnover as a potential minimally invasive functional malignant hyperthermia assay.

Design: Application of lymphocytes for malignant hyperthermia diagnosis.

Hypersensitivity reactions to intravenous lipid emulsion in swine: relevance for lipid resuscitation studies.

Background: Reports in the recent experimental literature have provided contradicting results in different animal species regarding the efficacy of IV lipid emulsion (ILE) in the reversal of cardiovascular and central nervous system symptoms of local anesthetic and other lipophilic drug overdoses. In particular, ILE seemed to be effective in rats, rabbits, dogs, and humans, but not in swine, for which it not only failed to reverse the adverse effects of anesthetics, but the animals also developed a generalized cutaneous mottling or a dusky appearance immediately after ILE, suggestive of another type of toxicity. The latter symptoms arise in complement (C) activation-related pseudoallergy, a hypersensitivity reaction to particulate drugs and agents.

Exertional rhabdomyolysis: identification and evaluation of the athlete at risk for recurrence.

Exertional rhabdomyolysis (ER) is a common medical condition encountered by primary care and sports medicine providers. Although the majority of individuals with ER follow an expected and unremarkable clinical course without any adverse long-term sequelae or increased risk for recurrence, in others, the condition can serve as an 'unmasker' of an underlying condition that portends future risk. We present two cases of warfighters with a history of recurrent ER who presented to our facility for further evaluation and a return to duty determination.

Delayed onset of suspected malignant hyperthermia during sevoflurane anesthesia in an Afghan trauma patient: a case report.

Malignant hyperthermia (MH) is a rare pathologic hypermetabolic pharmacogenetic disorder of skeletal muscle calcium regulation following exposure to depolarizing muscle relaxants and/or volatile anesthetics. Although its pathogenesis is relatively well understood, there is wide variability in both the time of onset and the presentation of clinical signs and symptoms. In some circumstances the delayed onset of the hypermetabolic state may hinder timely recognition and treatment.

Multiacquisition T1-mapping MRI during tidal respiration for quantification of myocardial T1 in swine with heart failure.

Objective: The purpose of this article is to evaluate a free-breathing pulse sequence to quantify myocardial T1 changes in a swine model of tachycardia-induced heart failure.

Materials And Methods: Yorkshire swine were implanted with pacemakers and were ventricularly paced at 200 beats/min to induce heart failure. Animals were scanned twice with a 1.

Genetic polymorphisms associated with exertional rhabdomyolysis.

Exertional rhabdomyolysis (ER) occurs in young, otherwise healthy, individuals principally during strenuous exercise, athletic, and military training. Although many risk factors have been offered, it is unclear why some individuals develop ER when participating in comparable levels of physical exertion under identical environmental conditions and others do not. This study investigated possible genetic polymorphisms that might help explain ER.

Case report: Death in the emergency department: an unrecognized awake malignant hyperthermia-like reaction in a six-year-old.

A healthy 6-year-old boy developed lower extremity rigidity, trismus, and fever after playing in a splash pool. On arrival in the emergency department, he appeared to be seizing. An endotracheal tube was emergently placed using succinylcholine.

The effect of lipid emulsion infusion on postmortem ropivacaine concentrations in swine: endeavoring to comprehend a soldier's death.

Background: Lipid emulsion (20%) is advocated as a rescue drug for local anesthetic toxicity. No study has measured the impact of lipid emulsion therapy on postmortem local anesthetic serum levels.

Methods: We anesthetized Yorkshire swine (n = 11) and standard monitors were placed.

Fluoroquinolones influence the intracellular calcium handling in individuals susceptible to malignant hyperthermia.

Introduction: The mechanisms of fluoroquinolone-induced myotoxicity are unknown but an involvement of intracellular calcium handling is suspected. An in vitro contracture test used to investigate cellular processes in malignant hyperthermia (MH) can be applied to study the effects of fluoroquinolones.

Methods: With approval of the local ethics committee, muscle biopsies of 18 MH susceptible (MHS) and 12 MHS non-susceptible (MHN) pigs were performed.

Lymphocyte-based determination of susceptibility to malignant hyperthermia: a pilot study in swine.

Background: Malignant hyperthermia susceptibility (MHS) is diagnosed by an invasive in vitro caffeine-halothane contracture test (CHCT) carried out on biopsied skeletal muscle tissue. We are presenting a novel blood test approach for malignant hyperthermia testing in a swine model. Our main aim was to determine whether adenosine production from lymphocytes after 4-chloro-m-cresol (4CmC) stimulation distinguishes homozygous swine carrying the Arg615Cys mutation in the ryanodine receptor type 1 (RyR1) gene (MHS swine) from normal swine.

The relationship between exertional heat illness, exertional rhabdomyolysis, and malignant hyperthermia.

Exertional heat illness, exertional rhabdomyolysis, and malignant hyperthermia (MH) are complex syndromes with similar pathophysiology. All three are hypermetabolic states that include high demand for adenosine triphosphate, accelerated oxidative, chemical, and mechanical stress of muscle, and uncontrolled increase in intracellular calcium. Although there are no controlled clinical studies to support a relationship, there is evidence to suggest an association between unexpected heat/exercise intolerance and MH susceptibility.

Methadone-induced mortality in the treatment of chronic pain: role of QT prolongation.

Methadone is increasingly prescribed for chronic pain, yet the associated mortality appears to be rising disproportionately relative to other opioid analgesics. We review the available evidence on methadone-associated mortality, and explore potential pharmacokinetic and pharmacodynamic explanations for its greater apparent lethality. While methadone shares properties of central nervous system and respiratory depression with other opioids, methadone is unique as a potent blocker of the delayed rectifier potassium ion channel (IKr).

Trauma, systemic inflammatory response syndrome, dietary supplements, illicit steroid use and a questionable malignant hyperthermia reaction.

Background: Malignant hyperthermia (MH) is a pharmacogenetic disorder of skeletal muscle calcium regulation associated primarily, but not exclusively, with mutations in the skeletal muscle ryanodine receptor. Associated environmental factors, however, may also be important for expression of the syndrome.

Methods And Results: A 24-yr-old trauma patient developed a fulminant MH crisis after a 3 minute exposure to sevoflurane.