Jon B. Cole

Successful Management of Excited Delirium Syndrome with Prehospital Ketamine: Two Case Examples

Abstract Excited delirium syndrome (ExDS) is a medical emergency usually presenting first in the prehospital environment. Untreated ExDS is associated with a high mortality rate and is gaining recognition within organized medicine as an emerging public safety problem. It is highly associated with male gender, middle age, chronic illicit stimulant abuse, and mental illness. Management of ExDS often begins in the field when first responders, law enforcement personnel, and emergency medical services (EMS) personnel respond to requests from witnesses who observe subjects exhibiting bizarre, agitated behavior. Although appropriate prehospital management of subjects with ExDS is still under study, there is increasing awareness of the danger of untreated ExDS, and the danger associated with the need for subject restraint, whether physical or chemical. We describe two ExDS patients who were successfully chemically restrained with ketamine in the prehospital environment, and who had good outcomes without complication. These are among the first case reports in the literature of ExDS survival without complication using this novel prehospital sedation management protocol. This strategy bears further study and surveillance by the prehospital care community for evaluation of side effects and unintended complications.

Lactate and pH evaluation in exhausted humans with prolonged TASER X26 exposure or continued exertion.

OBJECTIVE Safety concerns about TASER Conducted Electrical Weapon (CEW) use and media reports of deaths after exposure have been expressed. CEWs are sometimes used on exhausted subjects to end resistance. The alternative is often a continued struggle. It is unclear if CEW use is metabolically different than allowing a continued struggle. We sought to determine if CEW exposure on exhausted humans caused worsening acidosis when compared with continued exertion. METHODS This was a prospective study of human volunteers recruited during a CEW training course. Volunteers were from several different occupations and represented a wide range of ages and body mass index characteristics. Medical histories, baseline pH and lactate values were obtained. Patients were assigned to one of four groups: 2 control groups consisting of Exertion only and CEW Exposure only, and the 2 experimental groups that were Exertion plus CEW Exposure and Exertion plus additional Exertion. Blood sampling occurred after Exertion and after any CEW exposure. This was repeated every 2-min until 20 min after protocol completion. Descriptive statistics were used to compare the four groups. The experimental groups and the control groups were compared individually at each time point using Wilcoxon rank sum tests. Lactate and pH association was assessed using multiple linear regression. RESULTS Forty subjects were enrolled. There were no median pH or lactate differences between CEW Exposure groups at baseline, or between Exertion protocol groups immediately after completion. The CEW Exposure only group had higher pH and lower lactate values at all time points after exposure than the Exertion only group. After completing the Exertion protocol, there was no difference in the pH or lactate values between the continued Exertion group and the CEW Exposure group at any time points. CONCLUSION Subjects who had CEW Exposure only had higher pH and lower lactate values than subjects who completed the Exertion protocol only. CEW exposure does not appear to worsen acidosis in exhausted subjects any differently than briefly continued exertion.

A prospective study of ketamine versus haloperidol for severe prehospital agitation

Abstract Context: Ketamine is an emerging drug for the treatment of acute undifferentiated agitation in the prehospital environment, however no prospective comparative studies have evaluated its effectiveness or safety in this clinical setting. Objective: We hypothesized 5 mg/kg of intramuscular ketamine would be superior to 10 mg of intramuscular haloperidol for severe prehospital agitation, with time to adequate sedation as the primary outcome measure. Methods: This was a prospective open label study of all patients in an urban EMS system requiring chemical sedation for severe acute undifferentiated agitation that were subsequently transported to the EMS system’s primary Emergency Department. All paramedics were trained in the Altered Mental Status Scale and prospectively recorded agitation scores on all patients. Two 6-month periods where either ketamine or haloperidol was the first-line therapy for severe agitation were prospectively compared primarily for time to adequate sedation. Secondary outcomes included laboratory data and adverse medication events. Results: 146 subjects were enrolled; 64 received ketamine, 82 received haloperidol. Median time to adequate sedation for the ketamine group was 5 minutes (range 0.4–23) vs. 17 minutes (range 2–84) in the haloperidol group (difference 12 minutes, 95% CI 9–15). Complications occurred in 49% (27/55) of patients receiving ketamine vs. 5% (4/82) in the haloperidol group. Complications specific to the ketamine group included hypersalivation (21/56, 38%), emergence reaction (5/52, 10%), vomiting (5/57, 9%), and laryngospasm (3/55, 5%). Intubation was also significantly higher in the ketamine group; 39% of patients receiving ketamine were intubated vs. 4% of patients receiving haloperidol. Conclusions: Ketamine is superior to haloperidol in terms of time to adequate sedation for severe prehospital acute undifferentiated agitation, but is associated with more complications and a higher intubation rate.

A blinded, randomized, controlled trial of three doses of high-dose insulin in poison-induced cardiogenic shock

Background. High dose insulin (HDI) has proven superior to glucagon and catecholamines in the treatment of poison-induced cardiogenic shock (PICS) in previous animal studies. Standard recommendations for dosing of insulin vary and the optimal dose of HDI in PICS has not been established. Our hypothesis was a dose of 10 U/kg/hr of HDI would be superior to 1 U/kg/hr with cardiac output (CO) as our primary outcome measure in pigs with propranolol-induced PICS. Methods. This was a blinded, prospective, randomized trial with 4 arms consisting of 4 pigs in each arm. The arms were as follows: placebo (P), 1 U/kg/hr (HDI-1), 5 U/kg/hr (HDI-5), and 10 U/kg/hr (HDI-10). Cardiogenic shock was induced with a bolus of 0.5 mg/kg of propranolol followed by an infusion of 0.25 mg/kg/min until the point of toxicity, defined as 0.75 x (HR x MAP) was reached. At this point the propranolol infusion was decreased to 0.125 mg/kg/min and a 20 mL/kg bolus of normal saline (NS) was administered. The protocol was continued for 6 hours or until the animals died. Results. 2 pigs died in the P arm, 1 pig died each in the HDI-1 and HDI-5 arms, and all pigs lived in the HDI-10 arm. There was a statistically significant difference in dose by time interaction on CO of 1.13 L/min over the 6 hr study period (p = < 0.001). There was also a statistically significant difference in dose by time interaction on MAP, HR, and systemic vascular resistance (SVR). No statistically significant difference was found between any of the arms regarding glucose utilization. Conclusion. HDI was statistically and clinically significantly superior to placebo in this propranolol model of PICS. Furthermore a dose response over time was found where CO increased corresponding to increases in doses of HDI.

Effect of an Electronic Control Device Exposure on a Methamphetamine-intoxicated Animal Model

OBJECTIVES Because of the prevalence of methamphetamine abuse worldwide, it is not uncommon for subjects in law enforcement encounters to be methamphetamine-intoxicated. Methamphetamine has been present in arrest-related death cases in which an electronic control device (ECD) was used. The primary purpose of this study was to determine the cardiac effects of an ECD in a methamphetamine intoxication model. METHODS Sixteen anesthetized Dorset sheep (26-78 kg) received 0.0 mg/kg (control animals, n = 4), 0.5 mg/kg (n = 4), 1.0 mg/kg (n = 4), or 1.5 mg/kg (n = 4) of methamphetamine hydrochloride as a slow intravenous (IV) bolus during continuous cardiac monitoring. The animals received the following exposures in sequence from a TASER X26 ECD beginning at 30 minutes after the administration of the drug: 1) 5-second continuous exposure, 2) 15-second intermittent exposure, 3) 30-second intermittent exposure, and 4) 40-second intermittent exposure. Darts were inserted at the sternal notch and the cardiac apex, to a depth of 9 mm. Cardiac motion was determined by thoracotomy (smaller animals, < or = 32 kg) or echocardiography (larger animals, > 68 kg). Data were analyzed using descriptive statistics and chi-square tests. RESULTS Animals given methamphetamine demonstrated signs of methamphetamine toxicity with tachycardia, hypertension, and atrial and ventricular ectopy in the 30-minute period immediately after administration of the drug. Smaller animals (n = 8, < or = 32 kg, mean = 29.4 kg) had supraventricular dysrhythmias immediately after the ECD exposures. Larger animals (n = 8, > 68 kg, mean = 72.4) had only sinus tachycardia after the exposures. One of the smaller animals had frequent episodes of ventricular ectopy after two exposures, including runs of delayed onset, nonsustained six- to eight-beat unifocal and multifocal ventricular tachycardia that spontaneously resolved. This animal had significant ectopy prior to the exposures as well. Thoracotomy performed on three smaller animals demonstrated cardiac capture during ECD exposure consistent with previous animal studies. In the larger animals, none of the methamphetamine-intoxicated animals demonstrated cardiac capture. Two control sheep showed evidence of capture similar to the smaller animals. No ventricular fibrillation occurred after the exposure in any animal. CONCLUSIONS In smaller animals (32 kg or less), ECD exposure exacerbated atrial and ventricular irritability induced by methamphetamine intoxication, but this effect was not seen in larger, adult-sized animals. There were no episodes of ventricular fibrillation after exposure associated with ECD exposure in methamphetamine-intoxicated sheep.

Wide complex tachycardia in a pediatric diphenhydramine overdose treated with sodium bicarbonate.

Introduction Diphenhydramine is an antihistamine commonly implicated in overdose. It has many pharmacologic effects, including sodium channel blockade. Overdoses in toddlers causing QRS prolongation are only rarely reported and never with effective use of sodium bicarbonate. We report a diphenhydramine overdose in a toddler with multiple markers of sodium channel blockade effectively treated with sodium bicarbonate. Methods A 13-month-old infant girl was brought in by the emergency medical service for a witnessed tonic-clonic seizure. Two hours previously, the child had been found with an open bottle of 25-mg diphenhydramine tablets, 24 of which were missing. Midazolam was administered with seizure resolution. Examination revealed 4-mm reactive pupils; nystagmus; warm, dry, flushed skin; and altered mental status. Initial electrocardiograms revealed sinus tachycardia at a rate of 180 beats per minute, a prolonged QRS of 130 milliseconds (from a baseline of 65 milliseconds), and a positive terminal R wave in aVR, which later resolved after sodium bicarbonate treatment. The patient was discharged home the following day with no sequelae. Results and Discussion Diphenhydramine toxicity is a common poisoning in children. Toxicity typically presents with signs and symptoms of the anticholinergic toxidrome. Diphenhydramine also has sodium channel–blocking properties, and this can be shown in the form of prolonged QRS and a terminal R wave in aVR. QRS prolongation and aVR abnormalities from diphenhydramine ingestion in a toddler have been reported, but effective use of sodium bicarbonate has not. Conclusions Electrocardiographic finding consistent with sodium channel blockade should be recognized as a complication of pediatric diphenhydramine overdose, and they seem responsive to hypertonic sodium bicarbonate.

Intubation of Profoundly Agitated Patients Treated with Prehospital Ketamine

BACKGROUND Profound agitation in the prehospital setting confers substantial risk to patients and providers. Optimal chemical sedation in this setting remains unclear. OBJECTIVE The goal of this study was to describe intubation rates among profoundly agitated patients treated with prehospital ketamine and to characterize clinically significant outcomes of a prehospital ketamine protocol. METHODS This was a retrospective cohort study of all patients who received prehospital ketamine, per a predefined protocol, for control of profound agitation and who subsequently were transported to an urban Level 1 trauma center from May 1, 2010 through August 31, 2013. Identified records were reviewed for basic ambulance run information, subject characteristics, ketamine dosing, and rate of intubation. Emergency Medical Services (EMS) ambulance run data were matched to hospital-based electronic medical records. Clinically significant outcomes are characterized, including unadjusted and adjusted rates of intubation. RESULTS Overall, ketamine was administered 227 times in the prehospital setting with 135 cases meeting study criteria of use of ketamine for treatment of agitation. Endotracheal intubation was undertaken for 63% (85/135) of patients, including attempted prehospital intubation in four cases. Male gender and late night arrival were associated with intubation in univariate analyses (χ2=12.02; P=.001 and χ2=5.34; P=.021, respectively). Neither ketamine dose, co-administration of additional sedating medications, nor evidence of ethanol (ETOH) or sympathomimetic ingestion was associated with intubation. The association between intubation and both male gender and late night emergency department (ED) arrival persisted in multivariate analysis. Neither higher dose (>5mg/kg) ketamine nor co-administration of midazolam or haloperidol was associated with intubation in logistic regression modeling of the 120 subjects with weights recorded. Two deaths were observed. Post-hoc analysis of intubation rates suggested a high degree of provider-dependent variability. CONCLUSIONS Prehospital ketamine is associated with a high rate of endotracheal intubation in profoundly agitated patients; however, ketamine dosing is not associated with intubation rate when adjusted for potential confounders. It is likely that factors not included in this analysis, including both provider comfort with post-ketamine patients and anticipated clinical course, play a role in the decision to intubate patients who receive prehospital ketamine. Olives TD , Nystrom PC , Cole JB , Dodd KW , Ho JD . Intubation of profoundly agitated patients treated with prehospital ketamine. Prehosp Disaster Med. 2016;31(6):593-602.

A Prospective Observational Study of Patients Receiving Intravenous and Intramuscular Olanzapine in the Emergency Department

Study objective: Parenteral olanzapine is an emerging therapy for a variety of conditions in the emergency department (ED). Intramuscular administration is standard; however, intravenous administration has been proposed as a safe alternative route. We investigate the safety and efficacy of both intramuscular and intravenous olanzapine in the ED when used for a variety of indications. Methods: This was a prospective observational study of patients presenting to an urban Level I trauma center ED. Trained research associates screened the ED for patients receiving parenteral olanzapine. The primary outcome of the study was incidence of respiratory depression measured with standard markers. Secondary outcomes included use of additional doses or sedatives, corrected QT interval (QTc) data, time to nadir sedation, adverse events, and physician assessment of efficacy. Results: There were 784 patients included in the final analysis. Intravenous olanzapine was administered to 295 patients; 489 received intramuscular olanzapine. Respiratory depression occurred in 11 of 295 patients (3.7%; 95% confidence interval [CI] 1.6% to 5.9%) receiving intravenous olanzapine and 10 of 489 (2.0%; 95% CI 0.8% to 3.3%) receiving intramuscular olanzapine. Seven patients required intubation, 2 in the intravenous group and 5 in the intramuscular group. Nonrespiratory complications occurred in 8 patients, 6 of 295 (2.0%; 95% CI 0.4% to 3.6%) in the intravenous group and 2 of 489 (0.4%; 95% CI 0% to 0.96%) in the intramuscular group. Dysrhythmias were isolated to 2 episodes of bradycardia requiring only supportive care. Conclusion: These data suggest that, with proper monitoring, administration of olanzapine, both intramuscular and intravenous, is safe for several indications in the ED.

Unsuspected Critical Illness Among Emergency Department Patients Presenting for Acute Alcohol Intoxication

Study objective: Emergency department (ED) visits for acute alcohol intoxication are common, but this population is at risk for decompensation and occult critical illness. The purpose of this study is to describe the incidence and predictors of unsuspected critical illness among patients with acute alcohol intoxication. Methods: This was a retrospective observational study of ED patients from 2011 to 2016 with acute alcohol intoxication. The study cohort included patients presenting for alcohol intoxication, whose initial assessment was uncomplicated alcohol intoxication without any other active acute medical or traumatic complaints. The primary outcome was defined as the unanticipated subsequent use of critical care resources during the encounter or admission to an ICU. We investigated potential predictors for this outcome with generalized estimating equations. Results: We identified 31,364 eligible patient encounters (median age 38 years; 71% men; median breath alcohol concentration 234 mg/dL); 325 encounters (1%) used critical care resources. The most common diagnoses per 1,000 ED encounters were acute hypoxic respiratory failure (3.1), alcohol withdrawal (1.7), sepsis or infection (1.1), and intracranial hemorrhage (1.0). Three patients sustained a cardiac arrest. Presence of the following had an increased adjusted odds ratio (aOR) of developing critical illness: hypoglycemia (aOR 9.2), hypotension (aOR 3.8), tachycardia (aOR 1.8), fever (aOR 7.6), hypoxia (aOR 3.8), hypothermia (aOR 4.2), and parenteral sedation (aOR 2.4). The initial blood alcohol concentration aOR was 1.0. Conclusion: Critical care resources were used for 1% of ED patients with alcohol intoxication who were initially assessed by physicians to have low risk. Abnormal vital signs, hypoglycemia, and chemical sedation were associated with increased odds of critical illness.

Hyperbaric oxygen therapy for the prevention of arterial gas embolism in food grade hydrogen peroxide ingestion

Abstract Food grade hydrogen peroxide ingestion is a relatively rare presentation to the emergency department. There are no defined guidelines at this time regarding the treatment of such exposures, and providers may not be familiar with the potential complications associated with high concentration hydrogen peroxide ingestions. In this case series, we describe four patients who consumed 35% hydrogen peroxide, presented to the emergency department, and were treated with hyperbaric oxygen therapy. Two of the four patients were critically ill requiring intubation. All four patients had evidence on CT or ultrasound of venous gas emboli and intubated patients were treated as if they had an arterial gas embolism since an exam could not be followed. After hyperbaric oxygen therapy each patient was discharged from the hospital neurologically intact with no other associated organ injuries related to vascular gas emboli. Hyperbaric oxygen therapy is an effective treatment for patients with vascular gas emboli after high concentration hydrogen peroxide ingestion. It is the treatment of choice for any impending, suspected, or diagnosed arterial gas embolism. Further research is needed to determine which patients with portal venous gas emboli should be treated with hyperbaric oxygen therapy.