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Best Evidence Topic Reports
Towards evidence-based emergency medicine: best BETs from the Manchester Royal Infirmary Edited by Simon Carley
BET 1: EXCITED DELIRIUM SYNDROME AND SUDDEN DEATH Report by: Karl Huesgen, Resident Physician Search checked by: Bryan Judge, Faculty Physician Institution: Grand Rapids Medical Education Partners/Michigan State University, USA
ABSTRACT A short-cut review was carried out to establish whether morbidity and mortality from excited delirium syndrome (EXDS) can be predicted in the emergency department (ED). Seventy-three papers were found of which 11 presented the best evidence to answer the clinical question. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of these best papers are shown in table 1. The clinical bottom line is that the early recognition of EXDS remains paramount as patients may have sudden cardiovascular collapse with little warning. Several authors do describe laboured respiratory efforts before death, so prompt airway and haemodynamic control may be necessary. Patients may benefit from chemical rather than physical restraint. Acidosis and hyperthermia should also be aggressively managed. Law enforcement and prehospital personnel should also be educated regarding potential complications of EXDS. SEARCH STRATEGY THREE-PART QUESTION In (adult patients) presenting to the ED with suspected (EXDS), what are the (clinical features associated with significant morbidity and mortality)?
Medline 1946–05/2013 using OVID interface, Cochrane Library (2013), PubMed clinical queries [(excited delirium.mp) OR (exp overdose AND exp delirium)]. Limit to English language, humans.
SEARCH OUTCOME CLINICAL SCENARIO You are working a shift in an ED, and you receive a call from prehospital providers requesting advice in the management of a violent and incoherent patient with strength far in excess of that expected for his size. This seems consistent with reports you have read of EXDS. You recall reports of sudden death in these patients and wonder if you can prevent this. 958
Seventy-three papers were identified, 11 studies were relevant to the clinical question.
COMMENT(S) EXDS is a clinical presentation of bizarre behaviour, violence and agitation, typically in patients taking illicit stimulant drugs. Patients are often described as having strength in excess of what would
be expected, and often require forcible restraint by multiple law enforcement or medical personnel. This syndrome is infrequent but is associated with significant morbidity and mortality, producing challenges to prehospital and emergency medicine providers. Most notably, some patients have sudden cardiovascular collapse. No convincing data exist regarding mechanism of death, and various authors ascribe mortality to complications of dopaminergic overdrive, autonomic dysregulation, hyperthermia, rhabdomyolysis, cardiac arrhythmia, or impaired respiratory mechanics. Given the lack of consensus about the pathological mechanism, treatment for these patients is challenging. Emerg Med J November 2013 Vol 30 No 11
Author, date and country
Patient group
Study type (level of evidence)
Wetli and Fisbain, 1985, USA
7 Cocaine users with EXDS and sudden death
Systematic retrospective case review of cases with sudden unexplained death and cocaine intoxication
O’Halloran and Lewman, 1993, USA
11 Cases with EXDS and sudden death
Retrospective case analyses
Stratton et al, 1995, USA
Pollanen et al, 1998, Canada
Ross, 1998, USA
Key results
Study weaknesses
Drug(s) EXDS perimortem findings Mechanism of death Drug(s)
Cocaine Hyperthermia, metabolic acidosis pulmonary congestion and oedema, cerebral oedema, mild non-lethal injuries common. Myofibrillar degeneration in 1 of 7. No seizures Death attributed to cardiac dysrhythmia, autonomic dysregulation, or restraint stress Cocaine, methamphetamine, LSD, amantadine, valproate, multiple, or none (3) Axillary hyperthermia reported in one case All cases involved restraint. 2 Cases with CEW. One with myocardial contraction bands
Retrospective case series. No standardised data collection/ reporting
EXDS perimortem findings Mechanism of death 2 Cases of unexpected death and EXDS
All cases unexpected death with EXDS in Ontario, 1988–95, N=25
61 Cases of sudden death-associated EXDS, restrained while in police custody (1988–97)
58 Cases of fatal EXDS, 150 cases of cocaine-associated rhabdomyolysis, 125 cases fatal cocaine toxicity
Retrospective case analyses
Retrospective case analyses
Retrospective case analyses
Case series and literature review (includes data derived from previous reports)
Drug(s) EXDS perimortem findings Mechanism of death Drug(s) EXDS perimortem findings
Mechanism of death Drug(s)
EXDS perimortem findings Mechanism of death Drug(s) EXDS perimortem findings Mechanism of death
1 Patient with no drugs had history neuroleptic malignant syndrome. Cardiac dysrhythmia or respiratory arrest secondary to increased oxygen demand and decreased delivery Amphetamine, cocaine, ethanol Non-lethal blood methamphetamine, cocaine and ethanol level. Pulmonary oedema and congestion noted in one case
Case series without description of how cases collected. Perimortem and autopsy findings inconsistently reported. Inconsistency regarding illicit or therapeutic drugs or mental conditions. Only consistent factor is restraint
Retrospective, small number of cases. Positional asphyxia as cause of death determined by coroner based only on patient position, respiratory arrest, and lack of other apparent cause of death. Minimal physiological data to support conclusion
Positional asphyxia from hogtie position Cocaine (38%) or multiple (5%); psychiatric disorder (57%) Restraint in all cases. No life-threatening injuries noted on autopsy. Conjunctival petechiae after neck compression (N=2), subpleural and epicardial petechiae (N=3). Serum cocaine levels similar to recreational users. Heart disease in 19%. Pepper spray exposure in 19% Positional asphyxia
Retrospective. Minimal perimortem analysis. No quantification of purported mechanism of death, eg, respiratory acidosis. Does not discuss non-lethal cases of EXDS or whether purported mechanism of death increases mortality likelihood
Cocaine, ethanol, methamphetamine, amphetamine, methylphenidate, LSD, THC, lithium, valproate, haloperidol. Schizophrenia and bipolar disorder in some cases Hyperthermia (mean 104°F), mechanical restraints (100%)
Case collection methodology not well explained. Minimal supporting evidence (eg, perimortem findings) for purported mechanism of death. Police custody and restraint was part of selection criteria so causality from position cannot be inferred
Acute drug toxicity, positional asphyxia, cardiorespiratory arrest, exhaustive mania Cocaine Hyperthermia present in 97% of cases of fatal EXDS. Rhabdomyolysis, seizure (27.5%), ethanol, and other drug use more commonly reported in fatal EXDS Rhabdomyolysis,possibly related to hypothalamic dopaminergic temperature dysregulation
Literature review limited to cocaine-associated rhabdomyolysis. Postmortem temperature not recorded routinely unless elevated, possibly producing confirmation bias if not suspected. Proposes EXDS closely linked to rhabdomyolysis but does not report percentage of EXDS with rhabdomyolysis Continued
959
Best Evidence Topic Reports
Ruttenber et al, 1999, USA
Outcomes
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Emerg Med J November 2013 Vol 30 No 11
Table 1 Relevant papers
Author, date and country Stratton et al, 2001, USA
Murray et al, 2012, USA
18 Cases of sudden death in restrained patients with EXDS withnessed by EMS providers
90 Sudden deaths associated with EXDS
1 Case of EXDS and sudden death
Study type (level of evidence) Retrospective case analyses
Outcomes
Key results
Study weaknesses
Drug(s) EXDS perimortem findings
Cocaine and/or amphetamine (14/18); THC (1/18), none (3/18) Wrists and ankles bound behind back (18/18). Chronic disease including cardiac disease, obesity. Initial EKG in 13 of 18 cases, ventricular tachycardia in one case; asystole, sinus tachycardia, bradycardia, junctional and agonal rhythm in remainder Interaction of obesity, chronic disease, stimulant use, restraint asphyxia Cocaine and/or amphetamine (94%); Also ethanol, methamphetamine, MDMA, ephedrine, pseudoephedrine, risperidone and citalopram, or none (N=4) Hyperthermia, elevated heat shock protein and transcript in brains of EXDS patients. Lower amounts of dopamine transporter in brains of patients with EXDS Death attributed to hyperdopaminergic state, neurocardiac dysregulation, and individual phenotype Methylenedioxypyrovalerone (‘bath salts’) Widened QRS with peaked T waves. Initially normothermic but hyperthermic at time of cardiovascular collapse; subsequent rhabdomyolysis, DIC, metabolic acidosis, anoxic brain injury Autonomic dysfunction including hyperthermia secondary to hypothalamic dopaminergic dysregulation
Hobble restraint was standard procedure for all EXDS patients (including 196 non-fatal EXDS during study period), so causation of sudden death by hobble restraint cannot be determined. Temperature not included in data collection. Various initial arrhythmia and asystole recorded, but progression from initial arrhythmia not reported
Mechanism of death Drug(s)
Retrospective analysis, neurochemical analysis
EXDS perimortem findings Mechanism of death Drug(s) EXDS perimortem findings Mechanism of death
Case report
Retrospective. Only includes cases submitted by law enforcement for further review so may be subject to selection bias
Case report. Clinical and toxicological analyses well reported but minimal postmortem data. History of bipolar disorder, which has also been associated with EXDS
CEW, conducted electrical weapon (taser); DIC, disseminated intravascular coagulation; EMS, emergency medical services; EXDS, excited delirium syndrome; MDMA, 3,4-methylenedioxy-N-methylamphetamine; THC, tetrahydrocannabinol.
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Clinical bottom line
Early recognition of EXDS remains paramount as patients may have sudden cardiovascular collapse with little warning. Several authors do describe laboured respiratory efforts before death, so prompt airway and haemodynamic control may be necessary. Patients may benefit from chemical rather than physical restraint. Acidosis and hyperthermia should also be aggressively managed. Law enforcement and prehospital personnel should also be educated regarding the potential complications of EXDS.
Wetli CV, Fisbain DA. Cocaine-induced psychosis and sudden death in recreational cocaine users. J Forensic Sci 1985;30:873–80. O’Halloran RL, Lewman LV. Restraint asphyxiation and excited delirium. Am J Forensic Med Pathol 1993;14:289–95. Stratton SJ, Rogers C, Green K. Sudden death in individuals in hobble restraints during paramedic transport. Ann Emerg Med 1995;25:710–12. Pollanen MS, Chiasson DA, Cairns JT, et al. Unexpected death related to restraint for excited delirium: a retrospective study of deaths in police custody and in the community. CMAJ 1998;158: 1603–7. Ross DL. Factors associated with excited delirium deaths in police custody. Mod Pathol 1998;11: 1127–37. Ruttenber AJ, McAnally HB, Wetli CV. Cocaine-associated rhabdomyoysis and excited delirium: different stages of the same syndrome. Am J Forensic Med Pathol 1999;20:120–7. Stratton SJ, Rogers C, Brickett K, et al. Factors associated with sudden death of individuals requiring restraint for excited delirium. Am J Emerg Med 2001;19:187–91. Mash DC, Duque L, Pablo J, et al. CV brain biomarkers for identifying excited delirium as a cause of sudden death. Forensic Sci Int 2009;190:e13–19. Murray BL, Murphy CM, Beuhler MC. Death following recreational use of designer drug “bath salts” containing 3,4-methylenedioxypyrovalerone (MDPV). J Med Toxicol 2012;8:69–75.
Emerg Med J 2013;30:958–960. doi:10.1136/emermed-2013-203139.1
Emerg Med J November 2013 Vol 30 No 11
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Mash et al, 2009, USA
Patient group
Best Evidence Topic Reports
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Table 1 Continued
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BET 1: Excited delirium syndrome and sudden death Emerg Med J 2013 30: 958-960
doi: 10.1136/emermed-2013-203139.1 Updated information and services can be found at: http://emj.bmj.com/content/30/11/958.2
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