Delirium is an acute disorder of consciousness and cognition that occurs in 60% to 80% of mechanically ventilated intensive care unit (ICU) patients (1–3) Among these patients, this manifestation of acute brain dysfunction conveys profound risk for morbidity and mortality, as it is associated with self-extubation (4), prolonged hospital stays (5, 6), and increased mortality (1, 6, 7) It is estimated, in addition, that ICU delirium is associated with health care costs ranging between $6 to $20 billion annually in the United States alone (8)

Despite its numerous deleterious effects, no placebo-controlled clinical trials exist to support the use of pharmacologic agents solely intended to treat delirium in the ICU In fact, the majority of delirious patients receive no specific treatment for this neuropsychiatric syndrome, in large part because it frequently remains unrecognized in clinical practice (9, 10) When diagnosed, delirium should first prompt the identification and management of potential underlying causes Then, to prevent harmful sequelae, the Society of Critical Care Medicine (SCCM) has recommended the use of haloperidol for the treatment of delirium in critically ill patients (11), despite its unproven efficacy and the absence of Food and Drug Administration (FDA) approval for this indication In keeping with this recommendation, haloperidol is currently the medication most widely used to treat ICU delirium (12) In recent years, however, newer “atypical” antipsychotics (eg, risperidone, olanzapine, quetiapine, and ziprasidone) have also gained popularity (13), though only olanzapine has been studied in the ICU (14)

Given the lack of compelling evidence supporting the use of antipsychotics for delirium in critically ill patients and the potential adverse effects associated with these medications, including torsades de pointes and sudden cardiac death (15, 16), hypotension (17), neuroleptic malignant syndrome (18), and extrapyramidal symptoms (19), placebo-controlled clinical trials are greatly needed to evaluate the efficacy of antipsychotic medications in reducing the burden of delirium in the ICU Thus, to demonstrate the feasibility of a randomized, placebo-controlled trial of antipsychotics in mechanically ventilated ICU patients, we conducted the Modifying the INcidence of Delirium (MIND) Trial, a multicenter, randomized, double-blind, placebo-controlled trial We hypothesized that both haloperidol and ziprasidone would be efficacious and safe for the treatment of ICU delirium This work has been presented in abstract form (20)

Feasibility, efficacy, and safety of antipsychotics for intensive care unit delirium: The MIND randomized, placebo-controlled trial

Rhabdomyolysis is a potentially life-threatening syndrome that can develop from a variety of causes; the classic findings of muscular aches, weakness and tea-coloured urine are non-specific and may not always be present. The diagnosis therefore rests upon the presence of a high level of suspicion of any abnormal laboratory values in the mind of the treating physician. An elevated plasma creatine kinase (CK) level is the most sensitive laboratory finding pertaining to muscle injury; whereas hyperkalaemia, acute renal failure and compartment syndrome represent the major life-threatening complications. The management of the condition includes prompt and aggressive fluid resuscitation, elimination of the causative agents and treatment and prevention of any complications that may ensue. The objective of this review is to describe the aetiological spectrum and pathophysiology of rhabdomyolysis, the clinical and biological consequences of this syndrome and to provide an appraisal of the current data available in order to facilitate the prevention, early diagnosis and prompt management of this condition.

/pdf/rhabdomyolysis-a-review-of-the-literature-2lb9251ogb.pdf

Rhabdomyolysis: a review of the literature.

Neuroleptic malignant syndrome

NEUROLEPTIC drugs, also known as antipsychotic agents and "major" tranquilizers, are among the most commonly prescribed medications in use today. In 1983 six neuroleptic agents were among the 200 most prescribed drugs in the United States.1 Neuroleptic drugs are used extensively in the treatment of psychotic illnesses and are widely employed in general medicine as antiemetics, for dissociative anesthesia, and to treat diseases such as Tourette's syndrome. They have many well-known side effects —e.g., extrapyramidal effects.2 The neuroleptic malignant syndrome (NMS), however, a hyperpyrexic syndrome that is frequently fatal, is not widely recognized. In fact, one popular, authoritative textbook makes . . .

Neuroleptic Malignant Syndrome

Neuroleptic malignant syndrome (NMS) is a life-threatening idiosyncratic reaction to antipsychotic drugs characterized by fever, altered mental status, muscle rigidity, and autonomic dysfunction. It has been associated with virtually all neuroleptics, including newer atypical antipsychotics, as well as a variety of other medications that affect central dopaminergic neurotransmission. Although uncommon, NMS remains a critical consideration in the differential diagnosis of patients presenting with fever and mental status changes because it requires prompt recognition to prevent significant morbidity and death. Treatment includes immediately stopping the offending agent and implementing supportive measures, as well as pharmacological interventions in more severe cases. Maintaining vigilant awareness of the clinical features of NMS to diagnose and treat the disorder early, however, remains the most important strategy by which physicians can keep mortality rates low and improve patient outcomes.

Neuroleptic Malignant Syndrome: A Review for Neurohospitalists

The in vitro halothane and caffeine contracture tests have been performed on muscle tissue from six survivors of the neuroleptic malignant syndrome. The results, which are expressed in accordance with the criteria of the European MH Group, defined five of the subjects as MHN and one patient as MHE. It is concluded that there is no common pathophysiological link between the neuroleptic malignant syndrome and malignant hyperthermia.

NEUROLEPTIC MALIGNANT SYNDROME AND MALIGNANT HYPERTHERMIA In Vitro Comparison with Halothane and Caffeine Contracture Tests

Neuroleptic Malignant Syndrome and Malignant Hyperthermia: in Vitro Comparison with Halothane and Caffeine Contracture Tests

The aim of this study was to verify whether a relationship exists between neuroleptic malignant syndrome (NMS) and anaesthetic-induced malignant hyperthermia (MH) or not. The in vitro halothane-caffeine tests were performed on muscle tissue obtained from 32 patients with documented NMS episodes. The diagnosis of NMS relied on Levenson's criteria. The results, expressed in accordance with the criteria of the European MH Group, defined 29 subjects as MH non-susceptible. Three patients were classified as MH equivocal. These findings demonstrate the lack of any link between NMS and MH. Therefore, patients with a history of NMS are not likely to be at risk of developing MH and special measures against MH are not required for anaesthesia in these patients.

Absence de sensibilité à l'hyperthermie maligne peranesthésique chez 32 patients ayant développé un syndrome malin des neuroleptiques

We have studied the effects of the calcium agonist BAY K 8644 on the in vitro halothane test in 10 malignant hyperthermia-susceptible (MHS), 12 MH "equivocal" to halothane (MHEh), 30 MH non-susceptible (MHN) and 10 control patients. BAY K 8644 potentiated the halothane-induced contracture in muscle strips from both MHS and MHEh patients. The drug produced a more obvious difference in contracture responses between the MHEh group compared with the MHN and control groups.

Use of the calcium agonist bay k 8644 for in vitro diagnosis of susceptibility to malignant hyperthermia

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