Introduction
Excited delirium is described as marked agitation and disorientation with sympathomimetic surge and incessant physical struggle, despite futility, which may lead to profound pathophysiologic changes and sudden death. Severe metabolic derangements, including lactic acidosis and hyperthermia, lead to a rapid cessation of struggle which coincides with cardiovascular collapse. An entity similar to excited delirium was first described in 1849 as “Bell’s mania,” which was reported initially among psychotic patients.Reference Scaggs, Glass, Hutchcraft and Weir 1 Their symptoms included superhuman strength, continued struggle despite an overwhelming force, and persecutory delusions. Excited delirium has become more common among users of sympathomimetic or hallucinogenic drugs.Reference Scaggs, Glass, Hutchcraft and Weir 1 The term “excited delirium syndrome” (ExDS) was coined by Wetli et al.Reference Scaggs, Glass, Hutchcraft and Weir 1 Excited delirium may lead to an in-custody death or disability. Such incidences are tragic for patients and their families and are often fraught with politically charged accusations and become a media maelstrom for police, firefighters, Emergency Medical Services (EMS), and emergency department (ED) personnel.
The pathophysiology of excited delirium is a subject of ongoing basic science and clinical research. Positive associations with ExDS include male gender, polysubstance abuse, mental health disorders, and violence.Reference Wetli and Fishbain 2 - Reference Scheppke, Braghiroli, Shalaby and Chait 4 Excited delirium typically presents in the prehospital setting with disruptive bizarre behavior. First responders, law enforcement officers, and EMS personnel often struggle to sedate and restrain the patient safely without causing further harm to themselves and the patient. An ideal medication would be easy to administer via intramuscular (IM) route, would be rapid with predictable onset, and would have a good safety profile.
Benzodiazepines, like midazolam, often are used for sedation of patients with extreme agitation. However, the relatively long onset (18 minutes) of these medications and the predictability of their effects in patients with severe behavioral disturbance can vary.Reference Burnett, Salzman, Griffith, Kroeger and Frascone 5 - Reference Isbister, Calver, Page, Stokes, Bryant and Downes 8 The side effects of benzodiazepines include airway compromise and decreased respiratory drive.Reference Nobay, Simon, Levitt and Dresden 6 , Reference Spain, Crilly, Whyte, Jenner, Carr and Baker 7 Antipsychotic medications can cause QTc prolongation,Reference Takeuchi, Ahern and Henderson 9 which is posited as a mechanism of the sudden death associated with ExDS.Reference Haddad and Anderson 10 As such, these medications are not ideal for sedating an excited delirium patient.
Ketamine is a dissociative anesthetic that has rapid onset via IM route within three to four minutes, has predictable effectiveness when administered by IM injection, and has a reasonable side effect profile.Reference Isbister, Calver, Page, Stokes, Bryant and Downes 8 Ketamine does not negatively affect airway control reflexes, respiratory drive, or hemodynamic status.Reference Isbister, Calver, Page, Stokes, Bryant and Downes 8 The following describes the protocol development with Illinois (USA) state EMS officials, the collaboration with police, and the use of ketamine 5 mg/kg IM by paramedics in this EMS system to sedate patients with ExDS from July 2008 through January 2014.
Methods
This retrospective case series was approved by the Carle Foundation (Urbana, Illinois USA) Institutional Review Board. Data were maintained in accordance with their policies on a secured drive that only the investigators could access. The patients described were treated for excited delirium from July 2008 through January 2014 and were identified on retrospective chart review. The EMS Medical Director reviewed each of these cases for quality assurance and then identified the cases to be included in the database for this study. Patient consent could not be obtained at the time of treatment due to the nature of the illness. At the recommendation of the Institutional Review Board to preserve confidentiality further, the date and year on which these patients presented were redacted. The time was not included as there was a higher incidence at night. The patients received ketamine 5 mg/kg IM by paramedics per the Carle Arrow Ambulance (Champaign, Illinois USA) Prehospital Protocol “Sedation of the Extremely Agitated Patient.” Table 1 is the protocol, which was approved by the Illinois Department of Public Health (IDPH; Rockford, Illinois USA) in 2008. Table 2 is an assessment form that the paramedic was to complete to document use of the protocol.
Table 1 Sedation of the Extremely Agitated Patient
Abbreviations: EMS, Emergency Medical Services; IM, intramuscular; IV, intravenous.
Table 2 EMS Excited Delirium Form
Abbreviations: ED, emergency department; EMS, Emergency Medical Services.
As a means of quantifying the efficacy of the ketamine sedation, a modified sedation scale to more objectively describe the condition of the excited delirium patient was used. The Scaggs Scale is a modified version of the Richmond Agitation Sedation Scale (Table 3).Reference Bozeman, Ali and Winslow 11 This is based on extrapolation of the agitated portion of the scale to include a state of “Excited Delirium,” which was assigned a “+4” rating.
Table 3 Scaggs Scale
Report
Since July of 2008, 13 cases were deemed by EMS providers in this system to be excited delirium. One patient was excluded since ED data from the hospital to which he was transported were unavailable. Of the remaining 12 patients, eight received ketamine, and the authors unanimously agreed that seven of these patients had ExDS (aggregate data are shown in Table 4). Calculations were made using Microsoft Excel, version 14.0.7140.5002, (Microsoft Corporation; Redmond, Washington USA).
Table 4 Aggregate Data for 7 Cases, Unless Noted
Abbreviations: CK, creatinine kinase; EMS, Emergency Medical Services; HR, heart rate.
Case 1 of 7
At 1:13 am, police discovered a 41-year-old, 69 kg, male sitting in his undamaged vehicle along a ditch. Police suspected “Driving Under the Influence/DUI” because the patient was confused but calm and cooperative. Emergency Medical Services arrived and the subject vomited while explaining his circumstances. The subject agreed to transport to the hospital. His gait was unsteady as the crew assisted him into the ambulance.
No trauma was noted on primary and secondary survey, subject’s vitals were: pulse (P) 128 beats/minute, blood pressure (BP) 130/palp, respirations (R) 16 breaths/minute, oxygen saturation (SpO2) 99% room air, pupils were sluggish, and he was still cooperative. Midway during transport, the subject sat up from the gurney, screamed, and started to swing his fists erratically and strike the EMS personnel. The subject displayed unlimited endurance, decreased pain sensation, and disorientation. The ambulance had to be assisted by another EMS crew and police. It was noted that the patient had “an extreme amount of strength” and was “very strong and throwing [the crew] around” the back of the ambulance (+3 Scaggs).
The EMS team determined that their safety was at risk and brought the subject’s behavior under control with a 450 mg ketamine IM injection in the right thigh (6.5 mg/kg). The EMS providers reported excellent sedation within 90 seconds of administering ketamine and the patient remained sedated the remainder of transport (−4 Scaggs). No adverse effects of the ketamine were noticed during the transport and there was no trauma to the patient.
On ED arrival, he was noted to be sedated, unresponsive, with emesis on his chest. It could not be determined if he had any prior mental history. His vitals were: BP 140/90, P 116 beats/minute, R 20 breaths/minute, and SpO2 88% on room air. His physical exam was unremarkable. Analysis of the subject’s labs was performed in the ED and the following were of interest in this case: white blood cells (WBC) 12,320 units, creatinine kinase (CK)-total 385 units/L, urine positive for cannabinoids, serum alcohol 430 mg/dL, bicarbonate test (carbon dioxide; CO2) 21 mmol/L, and blood urea nitrogen (BUN)/creatinine (Cr) 19 mg/dL/1.7 mg/dL. He had a Foley placed and was kept in observation in the ED for eight hours with plan to discharge when sober.
Case 2 of 7
At 1:11 am, an 18-year-old, 50 kg, white female with bipolar disorder and poly-substance abuse was discovered by her parents to be acting incoherently after being at a Narcotic Anonymous meeting. She was walking into walls and had moments of calm interrupted by outbursts of hysteria with violence and paranoid thoughts and statements. Emergency Medical Services noted she was partially naked, delusional, and aggressive towards objects. She would yell “I didn’t kill anybody!” Her skin was hot, and she was tachycardic. There was an empty, unlabeled bottle next to her bed. Her father remarked that he had restrained her earlier in the day.
Paramedics reported she had brief, catatonic movements, followed by relapses into severe agitation. She could not be calmed and started to become extremely combative (+3 Scaggs). Based on the escalating threat of the situation, EMS decided to intervene physically prior to police arrival. The patient was administered 250 mg IM ketamine (5 mg/kg). Within 30 seconds, the patient showed signs of sedation and was sedated completely by two minutes as measured by her response to deep painful stimuli (−4 Scaggs). There were no adverse effects noted due to ketamine administration. The patient was transferred to the ED without further incident.
Upon arrival at the ED, she remained sedated from the ketamine. Her vitals were: BP 123/74, P 110 beats/minute, R 16 breaths/minute, SpO2 95%, and temperature (T) 36.5°C. Physical exam revealed multiple healed scars on her left forearm, which appeared to be self-inflicted. Her ED laboratory values were significant only for positive cannabinoids. Her parents spoke at length with the ED physician and noted that she was prescribed quetiapine and paroxetine. In regards to the recent events, the mother said, “I didn’t know if I should call an exorcist or an ambulance.” The patient was admitted to the Internal Medicine service under step-down observation. She was discharged the following day after 34 hours in the hospital.
Case 3 of 7
At 12:21 am, EMS responded to a residence where police units were on scene with a violent, 19-year-old, 73 kg, white male patient with hallucinations who was displaying aggressive behavior towards police and inanimate objects. The officers believed the patient smoked marijuana laced with another drug. The patient was found partially naked, delusional with incoherent speech, and displayed superhuman strength while wrestling with the five officers (+4 Scaggs). He was immediately administered 300 mg ketamine IM (4.1 mg/kg) and continued fighting until the ketamine took effect. There were no adverse effects noted secondary to ketamine administration. Without further incident, the police officers were able to carry the patient to the ambulance and secure him on the EMS cot with shoulder and seat belts (−2 Scaggs). Emergency Medical Services obtained vital signs: BP 130/palp, P 144 beats/minute, R 16 breaths/minute, and SpO2 99% and continued Advanced Life Support protocol.
Upon arrival at the ED, the patient still was sedated with vitals: BP 176/68, P 135 beats/minute, R 20 breaths/minute, and SpO2 97%. Patient was examined and found to be non-toxic appearing and in no apparent distress. Marked nystagmus was noted on eye exam as well as a rapid heart rate with normal heart sounds. Labs from the ED showed: WBC 19,530, glucose 184, CK 303, urinalysis was negative, and urine drug screen positive for marijuana. Patient was placed in observation status for continued evaluation. The patient’s condition significantly improved during this period and was found to be suitable for discharge after five hours.
Case 4 of 7
At 12:15 am, EMS responded to a call for a 20-year-old, white male patient with violent behavior after taking three hits of acid. Upon arrival, EMS was advised that the subject was extremely violent, had decreased sensation to pain, and displayed superhuman strength as demonstrated by the requirement of six police officers to physically restrain the patient in handcuffs. Once in the squad car, the patient began banging his head on the interior cage and windows. Visual assessment of the patient revealed that he was extremely sweaty and his clothes were soaked “as if he had just gone swimming.” He was thrashing and yelling about and the crew began to fear for his safety (+4 Scaggs).
It took six officers to remove the patient and restrain him on a blanket on the ground. While the officers restrained the patient, a paramedic administered 500 mg ketamine IM (no weight reported). The patient immediately became sedated and was no longer a threat to himself or officers (−4 Scaggs). Of note, approximately eight minutes after ketamine dose, the patient had a full body seizure that lasted 20 seconds. Emergency Medical Services reported that they did not know if the seizure was secondary to the medication administration or from head trauma. After the seizure, the patient was transferred to the ambulance cot, secured, and transported to the hospital.
As the patient was sedated, EMS was able to perform primary and secondary surveys en route. Vital signs where: BP 144/90, P 130 beats/minute, R 24 breaths/minute, and SpO2 98%. Upon arrival to the ED, the patient was still unconscious from the ketamine. History was unobtainable due to the patient’s sedation. Vital signs were taken in the ED: BP 121/62, P 119 beats/minute, R 24 breaths/minute, SpO2 92%, and T 38.7°C. Physical exam revealed abrasions to the right side of patient’s head and face, small lacerations on patient’s wrist, moist mucous membranes with some foaming on the left side of mouth, and generalized shivering. Although he was unconscious at arrival, he became combative as the effects of ketamine wore off. Relevant results of ED labs were: WBC 20,020 units, glucose 229 mg/dL, CK 774 U/L, and urine drug screen positive for cannabinoids. The patient was given lorazepam due to his seizure-like activity. He was diagnosed with rhabdomyolysis and was given 1 L of intravenous (IV) fluid. His wrist wound was sutured and bandaged. As the patient began waking up, he became more combative and required 4-point leather restraints as he still seemed to be under the influence of the illicit substance. The patient had a psychiatric consult and was discharged from the ED after six hours with diagnoses of: LSD reaction, rhabdomyolysis, unspecified fever, agitation, wrist laceration, and abrasions.
Case 5 of 7
At 12:32 am, EMS responded to a university campus bar where multiple police officers were restraining a 20-year-old, 102 kg, white male for extremely violent and aggressive behavior. Before their arrival, he broke through the bar door, ran through a crowd of people, began attacking objects, and attempted to attack others in the area. Upon EMS arrival, more than ten police officers were required to restrain the patient in the prone position with multiple sets of handcuffs (+4 Scaggs). The patient was believed to have been under the influence of ethanol (ETOH) and had reported taking “six hits of acid” for the first time earlier that evening. The patient was noted to be diaphoretic and warm on physical exam.
He was administered 200 mg ketamine IM, which was only 2 mg/kg. Emergency Medical Services noted a decrease in level of agitation (+3 Scaggs) with this lower dose; however, the patient remained agitated and attempted to spit on and yell at providers intermittently. There were no adverse effects noted secondary to ketamine administration. At this decreased level of agitation, EMS and police were able to transport the patient via long spine board to the ambulance. Intravenous access and vital signs were obtained at this time: BP 180/palp, P 170 beats/minute, R 30 breaths/minute.
Upon arrival to the ED, the patient was given additional midazolam, haloperidol, and ketamine as he remained agitated (+3 Scaggs). At the time of arrival, the patient’s vital signs were: BP 197/98, P 158-190 beats/minute, R 20 breaths/minute, and T of 38.9°C. The physical exam remained unchanged from EMS providers’ assessment. The patient’s laboratory markers were pertinent for: WBC 21,770 units, CK 938 U/L, lactic acid 2.4 mmol/L, venous CO2 of 16.6 mmol/L, creatinine 1.92 mg/dL, and urine drug screen and serum ETOH level were negative. The patient was admitted for rhabdomyolysis and encephalopathy. By the following day, the patient’s mental status and laboratory levels normalized so he was discharged.
Case 6 of 7
At 5:39 am, EMS responded to a residence for a patient with altered mental status. Police reported to EMS that they had responded to this address previously that evening, when the patient had been previously “normal.” They requested medical personnel because the patient, a 25-year-old, 95 kg, white male was displaying odd behaviors. He was extremely agitated, aggressive, and was yelling and rambling in a nonsensical, incoherent pattern. Officers and EMS personnel describe the patient as having “the look of fear on his face,” flailing his arms about wildly, and making spastic body movements. Six people were required to restrain him, including police officers, firefighters, and EMS personnel (+4 Scaggs). He was reported to be talking to invisible people during this incident. Family reported that he had been drinking ETOH overnight at a bar. It was unknown if he had consumed other drugs; however, the 911 caller reported that the patient “might have been drugged.”
At this time, he was administered 400 mg ketamine IM (4.2 mg/kg) and was successfully sedated to the point where he would no longer be a threat to himself or personnel (−4 Scaggs). Emergency Medical Services providers noted no adverse effects secondary to ketamine administration. He was transported to the ambulance via long spine board. Emergency Medical Services providers noted the patient to be diaphoretic on physical exam. Intravenous access and vital signs were obtained as the patient had been sedated: BP 190/110, P 114 beats/minute, R 16 breaths/minute, and SpO2 100%.
Upon arrival to the ED, the patient was sedated, but angry upon waking and appeared toxic. Vital signs at the time of arrival were: BP 101/57, P 111 beats/minute, R 13 breaths/minute, and T 37.3°C. The patient’s laboratory was pertinent for an ETOH level of 106 mg/dL, urine drug screen positive for amphetamine and cannabinoids, venous CO2 17 mmol/L, and a creatinine of 1.4 mg/dL. He was given additional midazolam in the ED to keep sedated. He was noted to be in a hyperadrenergic state by the ED physician and was given a diagnosis of altered mental status, ETOH intoxication, marijuana intoxication, and amphetamine abuse. Upon waking, he told providers he was drugged when drinking at a bar. After three hours of IV hydration, he improved and was discharged.
Case 7 of 7
At 7:48 pm, in Fall 2013, EMS responded for multiple police officers struggling to restrain a 22-year-old male who was running around naked after breaking into a house and assaulting someone. Emergency Medical Services noted that he was not following commands, was fighting against multiple police officers, and was yelling nonsensical phrases (+4 Scaggs, post-hoc analysis). The patient yelled to officers that he was “on acid.”
Since the patient was already exposed, EMS providers were able to perform a clean stick of 300 mg IM ketamine (no weight reported). No adverse effects were reported following the sedation protocol. Within two minutes, the patient was reported to be “successfully sedated” and was carried to a cot via emergency personnel (−3 Scaggs, post-hoc analysis). Emergency Medical Services providers noted the patient was hot, flushed, and diaphoretic with labored breathing. He also had evidence of minor trauma following the excited delirium state, including facial and arm abrasions. Intravenous access and vital signs were obtained when the patient was stable: P 130 beats/minute, R 28 breaths/minute, and SpO2 100%.
Upon arrival to the ED, the patient was intermittently agitated and received as needed lorazepam to maintain his and staff safety. Physical exam revealed facial erythema secondary to being pepper sprayed earlier that evening. Vital signs were: BP 132/76, R 24 breaths/minute, SpO2 100%, and T 39.4°C. The patient’s laboratory was pertinent for leukocytosis of 20,730 units, CK 441 U/L, and creatinine 1.41 mg/dL. Urinalysis was positive for hematuria and proteinuria. Urine drug screen was positive for cannabinoids; serum ETOH was negative. The patient eventually informed ED staff that he had ingested LSD, mushrooms, and marijuana the previous evening. The patient was given a diagnosis of and treated for polysubstance intoxication, rhabdomyolysis, and acute renal failure; over a period of eight hours, he returned to baseline and was suitable for discharge.
Discussion
Excited delirium syndrome, recognized by the National Association of Medical Examiners (NAME; Walnut Shade, Missouri USA) and American College of Emergency Physicians (ACEP; Irving, Texas USA), is a potentially deadly disorder involving predominantly law enforcement, EMS, and the Emergency Physician.Reference Sessler, Gosnell and Grap 12 The incidence of ExDS has risen since the 1980’s, corresponding to the increase in cocaine use in the US, and ExDS has become much more publicized.Reference Gerold, Gibbons, Fisette and Alves 13 , 14 By definition, a syndrome is a collection of signs and symptoms without a known cause. Other syndromes (eg, Down’s syndrome) have had etiologies discovered and become actual diseases. Although excited delirium is not, per se, a diagnosis listed in the ICD-9 or ICD-10 codes, it certainly can be described by the codes 296.00S (Manic Excitement), 292.81Q (Delirium, drug induced), 799.2AM (Psychomotor Excitement), and 799.2V (Psychomotor Agitation), to name a few. Nevertheless, ExDS is a real disorder that can lead to sudden death of the patient.
Although the cause is unknown, it is known there is a cascade of events marked by severe struggle and adrenaline surge on the part of the patient that ultimately can lead to their sudden cardiorespiratory collapse. Once this occurs, the patient rarely can be resuscitated.Reference Vilke, Payne-James and Karch 15 Stopping this cascade is the goal of treatment and prevents sudden death. The means of stopping the cascade of events remains controversial as there are many possible means to do so. It is maintained that ketamine is the safest, most efficacious medication to use in this setting, yet many physicians shy away from its use in the prehospital arena.
There are multiple possible etiologies for sudden death associated with ExDS. Among them are metabolic acidosis, profound hyperthermia, stimulant-induced MI/arrhythmia, and hyperkalemia.Reference Hick, Smith and Lynch 16 Although rhabdomyolysis and stimulant-induced cardiomyopathy may be seen in the patient with ExDS, these entities generally would not be the direct cause of sudden death. Despite a case report discussing the possibility of long QT syndrome as a possible etiology,Reference Haddad and Anderson 10 this seems to be an unlikely cause since long QT syndrome has not been shown to be present consistently in the multitude of ExDS patients. Given that the sudden death of the ExDS patient follows a similar pattern of prolonged struggle and excitement, metabolic acidosis with or without resulting stimulant-induced arrhythmia and profound hyperthermia remain, in this author’s opinion, the candidates, possibly in combination, although possibly alone, that may result in this outcome. Carle EMS teaches law enforcement personnel to try to avoid any type of restraint prior to EMS arrival on potential ExDS patients as struggling appears to exacerbate ExDS pathophysiology.
The perfect sedative that will rapidly sedate an ExDS patient and stop the cascade of events would be one that is: (1) IM; (2) rapid onset; (3) effective; (4) reliable; and (5) safe. Ketamine is the only sedative that meets these criteria. Midazolam, for example, is not nearly as fast, effective, reliable, or safe given the vast experience with both medications. There are essentially no contraindications for use of ketamine, nor will it harm those with another diagnosis in the differential of ExDS. Ketamine causing clinically significant increased intracranial pressure essentially has been disproved.Reference Vilke, DeBard and Chan 17 Laryngospasm, although not common, generally is relieved easily with positive pressure ventilation via bag valve mask ventilation.Reference Cohen, Athaide, Wickham, Doyle-Waters, Rose and Hohl 18 Although ketamine directly increases heart rate and BP, it appears that the net effect of sedation for the patient with adrenaline surge from ExDS would lead to decreased heart rate and BP. Emergence reactions should be treated easily with benzodiazepines.
The Champaign county-wide ExDS multi-disciplinary response protocol was developed after a sudden unexpected in-custody death (SUICD) in Urbana (Illinois, USA) in November 2007. The county-wide protocol was formed after discussion with the various stakeholders, to discuss how this “medical emergency that presents itself as a law enforcement problem” could be handled more effectively. Emergency Medical Services Medical Directors, ED nursing managers, and paramedics discussed a field sedation protocol that would work in conjunction with law enforcement/corrections officers to rapidly sedate the ExDS subject that fit within the protocol. The idea of using ketamine for the suspected ExDS subject was suggested at a national law enforcement conference in 2007. Local EMS Medical Directors then wrote the sedation protocol, and training with law enforcement, EMS, corrections, and telecommunicators took place in early 2008. The county-wide response protocol went live on July 1, 2008, and as of February 2015, there have been over 90 responses to suspected ExDS subjects in this EMS system and the other EMS system in this municipality, many of whom have been sedated with ketamine as well as midazolam. Another benefit of this type of response protocol is the heightened communication and trust between law enforcement and EMS.
Although treatment for an ExDS patient with ExDS rapid cooling measures, aggressive fluid replacement, and sodium bicarbonate makes intuitive sense, Carle EMS was unable to gain approval in 2008 from the IDPH for these therapies. Since ExDS was not yet looked upon as an accepted diagnosis, the state did not want EMS making such a diagnosis in the field and, therefore, would not allow these other measures in the protocol. Even though these measures would “do no harm,” IDPH staff viewed these as treating a specific diagnosis, which they wanted to avoid. They also would not allow the protocol to be called “excited delirium syndrome,” as that name is “diagnosis based.” Despite the fact that there were many other protocols which were diagnosis based (eg, congestive heart failure/CHF), the appeals went unheeded.
Typical ExDS patients are male (95%), have a median age of 36 years, with cocaine concentrations similar to or lower than the typical recreational user. 14 , Reference Burnett, Watters, Barringer, Griffith and Fascone 19 This profile suggests a patient exposed to long-term cocaine use and repeated binges. 14 Research done by Dr. Deborah Mash also demonstrated a post-mortem intracranial heat shock protein marker among ExDS subjects.Reference Burnett, Watters, Barringer, Griffith and Fascone 19
The mean age of the patients in this report was 24 (SD=7.4) years old. This is younger than in other studies and may reflect the demographics of this community in which there are two colleges. Substance abuse by history or laboratory studies was present in all of the patients in this series, which is consistent with other reports.Reference Wetli and Fishbain 2 - Reference Scheppke, Braghiroli, Shalaby and Chait 4 Mean CK levels were 484.33 (SD=291.61) U/L, reflecting rhabdomyolysis. Six of seven patients (86%) had urine drug screens positive for cannabinoids, and in five of those six (83%), marijuana was the only agent detected on urine 10 drug screen. One of those five was concurrently intoxicated with a serum ETOH of 430 mg/dL. The prevalence of cannabinoid metabolites on urine drug screen may have been from use of natural and/or synthetic marijuana. There are case reports that link synthetic marijuana use to “severe agitation.”Reference Mash, Duque and Pablo 20 , Reference Schwartz, Trecki, Edison, Steck, Arnold and Gerona 21 Only two of the seven patients (29%) were admitted to the hospital, although the other five were observed for a mean time of 6.14 hours in the ED. Since July 2008 when the multi-disciplinary response protocol began in Champaign County, there have been no deaths from ExDS in the prehospital, ED, or hospital settings.
Emergency department data, including serum lactate, were obtained inconsistently in the ED, secondary to variations in practice. An order set to facilitate the rapid and appropriate acquisition of ED data on ExDS patients was developed.
Certainly, this case series shows that ketamine is fast, effective, reliable, and safe when given in the proper 5 mg/kg IM dose. Whether or not any of these cases using ketamine prevented an actual sudden death would be impossible to predict. A prospective 2-arm study (ketamine vs midazolam or placebo) potentially would be detrimental to patients in the placebo or control arms and might be unacceptable to an institutional review board.
The EMS Medical Director reviews each chart of patients who have received prehospital ketamine for presumed ExDS. None of the patients who received ketamine had any EMS or ED side effects of laryngospasm, hypersalivation, need for airway protection, or other significant adverse events. Four other patients who EMS considered to have possible ExDS did not receive prehospital ketamine. The patient who was taken to a nearby ED had received ketamine 5.6 mg/kg IM and suffered no side effects in the prehospital setting. One patient, whose weight was estimated to be 90 kg, was given ketamine 1 mg/kg IV. This patient had been found sleepy, confused, and combative at home. His wife later described to the ED staff how she had seen him seize before EMS arrived. He had a negative head CT, negative lumbar puncture, and unrevealing laboratory studies. Although he received ketamine by EMS, it was not at the 1.5 mg/kg IV, as per the protocol. He was diagnosed as “headache” and “new onset seizure” and was discharged home. He remains neurologically intact based on subsequent visits reviewed in the electronic medical record.
The rapid and cooperative response from local law enforcement and EMS, with sedation using ketamine 5 mg/kg IM, likely has reduced the severity of the presentations of the ExDS patients. This may have led to decreased morbidity and mortality. This also may have led to relatively lower levels of CK, less severe illness at the time of ED arrival, less hyperthermia, fewer hospital admissions, and might have reduced morbidity and mortality. There is a possibility that those cases treated may have represented a less severe form of ExDS. From the descriptions of EMS providers, it does sound as though these cases were assessed accurately in the prehospital setting as ExDS.
Conclusion
It was demonstrated that ketamine administered by paramedics in the prehospital setting is a safe and effective treatment for ExDS. Ketamine may very well be the most effective, reliable, and safe sedative with rapid onset and should be considered first line treatment for ExDS.
