Delayed-onset malignant hyperthermia in the postanesthetic care unit: a case report

Malignant hyperthermia (MH) is a potentially fatal hypermetabolic syndrome that occurs when susceptible individuals are exposed to triggering agents. Variability in the order and time of occurrence of symptoms often makes clinical diagnosis difficult. A late diagnosis or misdiagnosis of delayed-onset MH may lead to fatal complications. We herein report a case of delayed-onset MH in the postoperative recovery room. A 77-year-old man awoke from anesthesia and was transferred to the recovery room. Ten minutes after his arrival, his mental status became stuporous and he developed masseter muscle rigidity, hyperventilation, and a body temperature of 39.8°C. The patient was suspected to have MH, and 60 mg of dantrolene sodium (1 mg/kg) was administered via intravenous drip with symptomatic treatment. Within 10 minutes of dantrolene administration, the patient’s clinical signs subsided. This case report demonstrates that rapid diagnosis and treatment are crucial to ensure a good prognosis for patients with MH. A high level of suspicion based on clinical symptoms and early administration of therapeutic drugs such as dantrolene will also improve the clinical course. Therefore, suspicion and prompt diagnosis are absolutely essential. This case report emphasizes the importance of continuous education in the diagnosis and treatment of MH.     

恶性高热症的研究进展

恶性高热症 (MalignantHyperthermia ,MH)是一种罕见的常染色体显性疾患 ,此病的易感个体在接触某些麻醉药物时可发生危及生命的高代谢状态。已发现恶性高热症与ryanodine受体基因 (RYR1)缺陷相关。肌肉活检作体外氟烷和咖啡因肌肉收缩试验是诊断MH易感性的唯一可靠方法 ,非特异性肌松药丹妥宁钠是目前已知的根本治疗药物     

Malignant hyperthermia: responses of skeletal muscles to general anesthetics

Anesthetic-induced malignant hyperthermia (MH) originally attracted scientific interest because of the associated high fatality rate. Recently, the introduction of treatment with the muscle relaxant dantrolene sodium has dramatically reduced the frequency of death from MH. Nonetheless, diagnosing MH susceptibility remains a problem because it necessitates a muscle biopsy specimen that must be tested in a specially equipped laboratory. Thus, diagnosis is both expensive and invasive. Development of simpler and less invasive methods would be aided by identification of the primary defect underlying initiation of MH. Our understanding of whole-body responses during MH episodes and the development of treatment with dantrolene sodium have both resulted from studies of porcine MH, which is similar to the syndrome in humans. Investigations of porcine MH have demonstrated that the defect responsible for initiation of MH must be located in skeletal muscle. Many abnormal responses of MH muscle have been identified after exposure to triggering agents. These defects contribute to the maintenance and amplification of the MH episode once it has been initiated. The primary defect responsible for triggering this complex chain of events, however, has thus far eluded definition.     

Acute hyperammonemic coma with chronic valproic acid therapy

OBJECTIVE: To report a case of dose-related hyperammonemic coma without liver failure in a patient receiving chronic valproate therapy. CASE SUMMARY: A 56-year-old woman with poorly controlled epilepsy, receiving valproate at subtherapeutic levels for 6 years, developed a life-threatening hyperammonemic coma following a moderate dosage increase. DISCUSSION: Hyperammonemic coma without associated liver failure is an extremely rare complication of valproate therapy, described primarily in patients with inborn errors of metabolism and occurring idiosyncratically during initial stages of therapy. In our case, family history was suggestive of an X-linked disorder, raising the possibility that our patient may have been an asymptomatic carrier of a urea cycle enzyme deficiency unmasked by valproate therapy. To our knowledge, as of October 24, 2005, only one prior case of hyperammonemic coma in the context of chronic valproate monotherapy has been described. Application of the Naranjo probability scale score suggests that a causal relationship between valproic acid and hyperammonemic coma was probable. CONCLUSIONS: The widespread use of valproic acid emphasizes the need to maintain a high degree of suspicion with respect to this rare but potentially fatal adverse effect at all times, regardless of therapy duration.     

Pathophysiology and therapy of diabetic ketoacidosis and of non-ketoacidotic hyperosmolar diabetic coma

Metabolic derangements in diabetic coma are the sequelae of insulin deficiency. These defects are aggravated by the actions of insulin counteracting ("diabetogenic") hormones and hypertonic dehydration, which both impair insulin action. Conversely, it has been shown that hypo-osmolar rehydration of a hyperosmolar, severely hyperglycaemic diabetic patient reduces insulin resistance and restores biological responsiveness of previously dehydrated insulin-dependent tissues towards insulin. Thus treatment of diabetic coma requires appropriate fluid and electrolyte replacement as a life-saving emergency action alongside insulin replacement. The use of proper rehydration during the past decade might also explain the reported fall in the insulin requirement for the treatment of diabetic coma from approximately 1,000 units per coma to low-dose insulin therapy. In order to guarantee proper treatment of severe hyperglycaemia and normalization of the hyperosmolar state, we feel that hypo-osmolar rehydration has to be initiated in parallel with low-dose insulin therapy (5 to 6 U/h) to restore the physiological response of the respective target tissues to insulin action and to ameliorate glucose utilization. This approach probably avoids a too rapid fall in plasma osmolarity, minimizes the risk of cerebral oedema and hypokalaemia, and improves survival. The development of severe diabetic ketoacidosis or of hyperosmolar non-ketotic diabetic coma should be prevented by advice to patients on the importance of metabolic monitoring, which can be done by proper self-monitoring of blood glucose. In addition, information should be provided on the detrimental metabolic effects of both dehydration and stress.     

Hyperosmolar diabetic non-ketotic coma, hyperkalaemia and an unusual near death experience.

Generally, cardiac arrest due to pulseless electrical activity has a poor outcome, except when reversible factors such as acute hyperkalaemia are identified and managed early. Hyperosmolar diabetic non-ketotic coma may lead to acute hyperkalaemia. Hyperosmolar diabetic non-ketotic coma is a metabolic emergency usually seen in elderly non-insulin dependent diabetics, characterized by severe hyperglycaemia, volume depletion, altered consciousness, confusion and less frequently neurological deficit. Cerebrovascular accident or transient ischaemic attack may be mistakenly diagnosed, particularly if the patient has no history of diabetes mellitus. Delays in diagnosis and management of glycaemic emergencies presenting as a constellation of neurological abnormalities can be avoided by routine early measurement of blood glucose. Hyperosmolar diabetic non-ketotic coma should be considered in any patient with altered consciousness or neurologic deficit in conjunction with hyperglycaemia. As hyperosmolar diabetic non-ketotic coma results in severe fluid depletion, electrolyte disturbance, profound hyperglycaemia and an altered mental state, the guiding principles of therapy include aggressive rehydration, insulin therapy, correction of electrolyte abnormalities and treatment of any underlying illnesses. Treatment of acute hyperkalaemia includes calcium ions, insulin with dextrose, salbutamol and haemodialysis.     

Necrotizing fasciitis precipitating diabetic ketoacidotic coma

Necrotizing fasciitis is a rapidly spreading infection of the subcutaneous tissue and fascia; diabetes mellitus appears to be the most frequent underlying disease. Early diagnosis and immediate aggressive surgical therapy are paramount to curtail morbidity and mortality, but diagnosis is often difficult and unnecessarily delayed. We describe a case of necrotizing fasciitis precipitating diabetic ketoacidotic coma where correct diagnosis was not made until the 14th hospital day. We stress the fact that physicians caring for critically ill patients should be keenly aware of the possibility of necrotizing fasciitis when tending diabetic patients with unexplained fever; failure to recognize the disease can have devastating results. Finally, we believe this to be the first reported case of diabetic ketoacidotic coma precipitated by necrotizing fasciitis.     

Hyperthermia, hypertension, hypertonia, and coma in a massive thioridazine overdose

This report characterizes an atypical presentation of a thioridazine overdose. Clinical manifestations included wide Q.R.S. complex, hyperthermia, hypertension, hypertonia, and coma. Plasma catecholamine levels were markedly elevated. The patient was treated with dantrolene sodium and supportive care. The patient's condition improved over time, with questionable response to dantrolene sodium. Supportive care was the mainstay of treatment.     

Reversible tetraplegia due to polyneuropathy in a diabetic patient with hyperosmolar non-ketotic coma

Critical illness polyneuromypathy has not previously been reported as a complication of diabetic coma. We describe a patient with hyperosmolar non-ketotic coma (HONK) complicating gram-negative sepsis in whom persistent coma and profound tetraplegia caused considerable concern. Although, initially, it was feared that the patient had suffered a central neurological complication such as stroke or cerebral oedema, a diagnosis of critical illness motor syndrome (CIMS) was subsequently confirmed neurophysiologically. Profound limb weakness associated with HONK is not necessarily due to a catastrophic cerebral event, rather it may be a result of CIMS, which has an excellent prognosis for full neurological recovery. Received: 4 June 1999 Accepted: 22 September 1999     

Olanzapine-lnduced hyperglycemic nonketonic coma

OBJECTIVE: To report a case of olanzapine-induced hyperglycemia leading to a hyperosmolar, hyperglycemic, nonketonic coma. CASE SUMMARY: A 51-year-old, 85.5-kg (ideal body weight 79.9 kg), white man presented to a Veterans Affairs hospital with a serum glucose concentration of 1596 mg/dL. Soon thereafter, he went into a hyperosmolar, hyperglycemic, nonketonic coma. Olanzapine therapy had been instituted less than six months prior to this event; approximately two months before this event, his blood glucose was 108 mg/dL. Eight days after stopping olanzapine, the glucose concentration returned to normal, and the patient no longer required insulin nor any other glucose-lowering agents. DISCUSSION: The insulin resistance caused by olanzapine is normally attributed to the weight gain associated with the drug. In this patient, it appears that olanzapine caused hyperglycemia by a mechanism other than weight gain. CONCLUSIONS: This case report and others from the literature suggest that olanzapine therapy may induce hyperglycemia in some patients.     

Sudden coma at the onset of severe refractory thrombotic thrombocytopenic purpura with successful treatment

Most patients develop coma several days after the onset of thrombotic thrombocytopenic purpura (TTP) caused by microvascular occlusion. However, aggravated coma as the first symptom of TTP has rarely been reported. Although plasma exchange (PEX) and steroids have reduced mortality, the prognosis of patients with TTP is still poor. We reported a patient with refractory TTP presenting with aggravated coma on admission. After days of successful PEX, rituximab, and glucocorticoid therapy for clinical remission, the patient regained consciousness and returned to his normal life with a good outcome. Our case highlights that TTP should be considered when coma occurs as the first symptom.     

Clinically inapparent status epilepticus as a cause of coma in the critically ill

Three adult patients presenting to the intensive care unit (ICU) with metabolic encephalopathy are described. Despite the absence of clinical signs of status epilepticus, this diagnosis was made on the basis of electroencephalographic recording and when effectively treated with anticonvulsant therapy, associated stupor or coma resolved. Duration of mechanical ventilation, intubation, and ICU stay were substantially shortened by this recognition and subsequent therapy. The inclusion of status epilepticus in the differential diagnosis of coma and stupor in the critically ill adult patient is emphasized.     

Usefulness of home blood pressure measurement in the morning in type 2 diabetic patients

OBJECTIVE: Recently, repeated home blood pressure (HBP) measurements in the morning for a long period have been shown to have a stronger predictive power for mortality in patients with hypertension than occasional casual/clinic blood pressure (CBP) measurements. We studied whether HBP in the morning in type 2 diabetic patients is useful for prediction of diabetic complications. RESEARCH DESIGN AND METHODS: The occurrence of diabetic complications (nephropathy, retinopathy, coronary heart disease [CHD], and cerebrovascular disease [CVD]) were examined in relation to morning HBP as well as to CBP in 170 type 2 diabetic patients treated with antidiabetic and antihypertensive drugs. Blood pressure was measured at the clinic during the day and at home after awakening in the morning. Clinic hypertension (CH) and morning hypertension (MH) were defined as systolic blood pressure (SBP) > or =130 mmHg and/or diastolic blood pressure (DBP) > or =85 mmHg. The relation of CH and MH to the prevalence of these events was examined. RESULTS: There were no significant differences in the prevalence of nephropathy, retinopathy, CHD, and CVD between the two groups with (n = 131) and without CH (n = 39), whereas the prevalences of these events in the patients with MH (n = 97) were significantly higher (P < 0.05) than in those without MH (n = 73). The prevalence of nephropathy was highly associated with systolic MH. CONCLUSIONS: Elevations of HBP in the morning in diabetic patients are strongly related to microvascular and macrovascular complications, especially nephropathy. It is concluded that the control of MH may prevent vascular complications in type 2 diabetic patients.     

Malignant hyperthermia susceptibility: anaesthetic implications and risk stratification

Malignant hyperthermia (MH) is a rare autosomal dominant trait that predisposes individuals to great danger when exposed to certain anaesthetic triggering agents, such as potent volatile anaesthetics and succinylcholine. Sudden hypermetabolic reaction occurs in skeletal muscle, leading to hyperthermia and massive rhabdomyolysis. Precautions must be taken before the anaesthesia of MH-susceptible patients. No triggering agents should be administered, central body temperature and ETCO2 should be carefully monitored, and dantrolene must be immediately available. In addition, the anaesthesia machine should be carefully washed to remove traces of halogenated agents, and the use of fresh disposable anaesthetic circuits is recommended. Early diagnosis of the syndrome by alert, informed anaesthesiologists, and the immediate administration of dantrolene and other supportive measures, has reduced mortality. Patients with MH susceptibility should be instructed to alert the anaesthesiologist about their condition whenever anaesthesia is needed. Although people diagnosed with MH susceptibility should not change their lifestyle in general, military service is limited.      

Flumazenil and dialysis for gabapentin-induced coma

OBJECTIVE: To describe a case of gabapentin-induced coma that was reversed with flumazenil and hemodialysis. CASE SUMMARY: We describe an 83-year-old dialysis-dependent white man who became comatose after a single dose of gabapentin for phantom limb pain. The patient was successfully revived from the coma with administration of flumazenil, which was then followed by hemodialysis. Serum concentration data before and 4 hours after dialysis document the effectiveness of hemodialysis for gabapentin toxicity. DISCUSSION: An objective causality assessment revealed that this adverse event was probably related to the gabapentin that the patient received. To our knowledge, this is the first documented case of not only gabapentin-induced coma, but also the effectiveness of flumazenil for treatment of this type of coma. Although therapeutic hemodialysis has been previously described, our case report is strengthened by the serum concentration monitoring accompanying it. CONCLUSIONS: This report underscores the importance of initiating gabapentin therapy at low doses in dialysis-dependent patients and introduces a novel treatment for those who experience toxicity.     

A case of black urine and dark skin — cresol poisoning

Introduction. Cresol is a phenol derivative used as a disinfectant worldwide. Acute cresol poisoning is potentially fatal as it may cause multiple organ failure. We present a case of acute cresol intoxication in a male patient to illustrate the effects of cresol poisoning. Case. A 42-year-old male presented with black urine, painless brownish dermal burns, and a strong carbolic acid odor. The patient was immediately resuscitated with adequate oxygenation and aggressive fluid resuscitation. He was subsequently admitted to the intensive care unit, where his treatment course was complicated by pneumonia, gastrointestinal bleeding, hepatic dysfunction, and acute renal failure. After receiving supportive intensive care, the patient recovered and was discharged with no sequelae. Conclusion. The distinctive clinical features of this case may be useful in diagnosis, because laboratory analytical methods for cresols are not routinely available at most hospitals.     

Nonketotic hyperosmolar coma in a patient with type 1 diabetes-related diabetic nephropathy: Case report

Nonketotic hyperosmolar coma (NHC) is characterized by severe hyperglycemia; absence of, or only slight ketosis; nonketotic acidosis; severe dehydration; depressed sensorium or frank coma; and various neurologic signs. This condition is uncommon in type 1 diabetes. Because of little or no osmotic diuresis in patients with diabetic nephropathy, increases in plasma osmolality and therefore the likelihood of neurologic symptoms are limited. A 20-year-old male patient with type 1 diabetes with chronic kidney disease on conservative treatment (glomerular filtration rate [GFR], 18 mL/dk) presented with acute nonketotic hyperosmolar syndrome. The patient was admitted presenting with thirst, fatigue, and drowsiness. Blood biochemistry levels were urea 87 mg/dL, creatinine 5.09 mg/dL, glucose 830 mg/dL, glycosylated hemoglobin (HbA_1c) 8%, C peptide < 0.3 ng/mL, sodium 131 mmol/L, chloride 93 mmol/L, potassium 5.2 mmol/L, and calculated serum osmolality 385 mOsm/kg. The presumptive diagnosis on admission was nonketotic hyperosmolar syndrome precipitated by urinary infection. This is the first case report of hyperosmolar coma in a patient with type 1 diabetes with chronic kidney disease.     

Propofol anesthesia in the malignant hyperthermia susceptible patient

The anesthetic technique chosen for a malignant hyperthermia (MH) susceptible patient should include drugs that do not trigger MH, while providing stress-free conditions. This case report describes a MH susceptible patient who was successfully induced and maintained with propofol for third molar extractions while under general anesthesia. Based on this case report, and the other relative few in the literature, it appears unlikely that propofol will trigger an episode of MH. Propofol provides the anesthetist with an alternative for inducing MH susceptible patients, but continued experience is necessary to document its safety and efficacy in these patients.     

Eosinophilic pleural effusion due to dantrolene: resolution with steroid therapy

A quadriplegic patient with severe spasticity, treated with dantrolene (400 mg daily) for 5 years, had dyspnea, orthopnea, hypoxia, and right-sided opacity of the chest on radiograph. At thoracentesis, an exudative effusion containing 64% eosinophils was documented, with simultaneous peripheral eosinophilia of 11%. An allergic reaction to dantrolene was postulated. Despite withdrawal of the offending medication and repeated thoracenteses, symptomatic recurrence of effusion persisted for 4 days. After institution of prednisone therapy, rapid resolution of symptoms, signs, hypoxia, and radiologic abnormalities was observed. In contrast to five previously reported cases of dantrolene-associated eosinophilic pleural effusion (EPE), ours represents the first in which the patient was treated with steroids and suggests that steroid therapy may be of benefit in drug-related EPE.     

Fulminant diabetes due to immune checkpoint inhibitors in the emergency department

Immune checkpoint inhibitors (ICIs) are of growing importance in new cancer therapies, exposing patients to various and potentially severe immune-related adverse events and placing emergency physicians on the front line when they occur. If endocrine toxicity is a well-known complication of ICIs, fulminant diabetes with diabetic ketoacidosis is exceptional. We present a case of fulminant diabetes after only two cycles of pembrolizumab in a 53-year-old man with a history of metastatic lung cancer who presented to our emergency department with coma and acidosis revealing diabetic ketoacidosis. The patient was rehydrated and treated with insulin and recovered quickly. Lung toxicity was also suspected on CT-scan findings. This rare and life-threatening complication that developed unusually early during the treatment course may be challenging in a cancer patient. Therefore, emergency physicians should investigate symptoms in patients treated with checkpoint inhibitors and consider toxicity when they present to the ED with complaints compatible with an immune-related adverse event.