QT prolongation, torsades des pointes, and cardiac arrest after 4 mg of IV ondansetron.

Ondansetron is a commonly used antiemetic in the emergency department despite a 2011 FDA warning regarding dose-related QTc prolongation and torsades des pointes (TdP). Cases of TdP from small ondansetron doses administered in the emergency department are lacking. A 41-year-old-woman with alcohol use disorder on no medications or supplements presented to an emergency department with one day of nausea, vomiting, and epigastric pain. Examination revealed a pulse of 77 beats/min and epigastric tenderness. The patient received 4 mg IV ondansetron, 30 mg IV ketorolac, and was placed on cardiac monitoring. ECG obtained one minute after ondansetron demonstrated premature ventricular contractions with QTc = 653 ms. Thirteen minutes after receiving ondansetron she suffered TdP and cardiac arrest. She received immediate CPR and IV epinephrine with successful defibrillation at one minute. She then received IV magnesium. Post-arrest ECGs demonstrated persistent QTc prolongation immediately and at three hours post-arrest. Laboratory studies, drawn prior to arrest, demonstrated hypokalemia (3.2 mEq/L), hypomagnesemia (1.3 mg/dL), and elevated lipase (4918 IU/L). She received no additional QT-prolonging agents. Transthoracic echocardiogram and troponins were normal; ECG intervals completely normalized within 12 h and she was discharged neurologically intact. The patient returned 18 months later with recurrent pancreatitis and similar electrolyte abnormalities; QT-prolonging drugs were avoided at that time and her course was uncomplicated. QT prolongation with subsequent torsades des pointes and cardiac arrest may occur in high-risk patients receiving small doses of ondansetron. Further studies are warranted to determine the safest antiemetic for use in the emergency department.

A Swine Model of Severe Propranolol Toxicity Permitting Direct Measurement of Brain Tissue Oxygenation.

INTRODUCTION: High-dose insulin (HDI) therapy has been used successfully for beta-blocker toxicity, but needs further study when hypotension persists despite HDI. The objective was to develop a model of propranolol toxicity with persistent hypotension despite HDI and to develop means to measure cerebral oxygen tension (PbrO2). METHODS: Eight anesthetized Yorkshire pigs were instrumented with a tracheostomy, Swan-Ganz catheter, arterial catheter, and intra-cerebral pressure and oxygen monitor. Intravenous propranolol was given until the initial point of toxicity (POT); 25% reduction from baseline mean arterial pressure (MAP) × heart rate (HR). At the initial POT, normal saline (NS) bolus and infusion along with HDI infusion were started. The propranolol infusion was titrated up slowly to induce hypotension. Group 2 pigs received a norepinephrine (NE) infusion after a secondary POT defined as a MAP < 50 mmHg. NE was titrated to maintain subsequent MAPs > 50 mmHg. Cardiac output, HR, MAP, PbrO2, and intracranial pressure were then recorded every 5 min until death or 4 h. Systemic vascular resistance, potassium, and glucose were also measured. Surviving pigs were euthanized. RESULTS: Two pigs received unique doses for protocol development. One pig developed a tachyarrhythmia prior to protocol, one failed to reach secondary POT, leaving 2 pigs in each group reaching secondary POT. The range of PbrO2 recordings for group 1 was 12.7-48.5 mmHg and 9.2-26.2 mmHg for group 2. CONCLUSION: We report a pilot study swine model of propranolol toxicity with hypotension despite HDI, in which physiologic measures including PbrO2 are achieved. Our toxicity model can be used in the future, and the hemodynamic and brain monitoring model may prove important for subsequent research in various contexts.

Physostigmine Reversal of Dysarthria and Delirium After Iatrogenic Atropine Overdose From a Dental Procedure.

BACKGROUND: Sublingual atropine, dosed at 0.4-0.8 mg, is used by dentists as an antisialogogue to facilitate and increase the speed of procedures. Concentrated ophthalmic atropine drops (10 mg/mL) are commonly used off-label for this purpose. These highly concentrated drops may result in medication errors, atropine toxicity, and the antimuscarinic toxidrome. We report a case of a man who suffered acute delirium and dysarthria (from dry mouth) after an iatrogenic overdose from a dental procedure. His symptoms were initially interpreted as a stroke, but they completely resolved with physostigmine. CASE REPORT: A 57-year-old man presented with acute dysarthria and delirium after a dental procedure; 4 hours earlier he was fitted for a temporary replacement of some premolar/molar teeth. He received sublingual atropine to assist in gingival drying for molding of his prosthesis, but a calculation error resulted in the administration of approximately 113 mg. A stroke evaluation was initially planned; however, 2.5 mg of intravenous physostigmine completely reversed his symptoms. His symptoms reoccurred and were successfully treated twice more with physostigmine; the patient was observed overnight with no additional symptoms and safely discharged the next morning. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Ophthalmic atropine drops are highly concentrated and may cause an overdose after ingestion of small amounts. This novel case highlights the importance of considering antimuscarinic poisoning in cases of acute delirium or dysarthria after dental procedures and stands as a reminder to inquire about the use of atropine drops in such cases. Timely recognition of the antimuscarinic toxidrome and appropriate use of physostigmine may prevent unnecessary testing while providing an effective therapy. This case also highlights the need for observation after resolution of delirium treated with physostigmine.

A prospective study of ketamine versus haloperidol for severe prehospital agitation.

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.

Nectar quality perception by honey bees (Apis mellifera ligustica).

In exploring how foragers perceive rewards, we often find that well-motivated individuals are not too choosy and unmotivated individuals are unreliable and inconsistent. Nevertheless, when given a choice we see that individuals can clearly distinguish between rewards. Here we develop the logic of using responses to two-choice problems as a derivative function of perceived reward, and utilize this model to examine honey bee perception of nectar quality. Measuring the derivative allows us to deduce the perceived reward function. The derivative function of the perceived reward equation gives the rate of change of the reward perceived for each reward value. This approach depends on presenting free-flying foragers with a series of two different rewards presented simultaneously (i.e., two-choice, binomial tests). We also examine how honey bees integrate information from a range of reward qualities to formulate a functional response. Results suggest that honey bees overestimate higher quality rewards and that direct comparison is an important step in the integration of information from a range of rewards.

Successful management of excited delirium syndrome with prehospital ketamine: two case examples.

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.

The respiratory, metabolic, and neuroendocrine effects of a new generation electronic control device.

INTRODUCTION: Electronic control devices (ECDs) have become popular in law enforcement because these devices have filled a gap left by other law enforcement devices, tactics, or tools and have been shown to reduce officer and suspect injuries. The TASER X3 is the latest generation device from the manufacturer. This device has the capability of firing three cartridges in a "semi-automatic" mode. This study is the first of the metabolic, neuroendocrine, and respiratory effects of this newer generation device. METHODS: This was a prospective, observational study of human subjects. A master instructor shot subjects with a TASER X3 in the anterior thorax with either one or two cartridges. Each subject received a 10-s exposure from the device. Vital signs were measured before and after the exposure. Venous pH, lactate, electrolytes, and catecholamines were measured before and after the exposure. Creatine kinase (CK) was measured before and at 24h post-exposure. Continuous spirometry was also performed. RESULTS: Fifty-three subjects completed the study. There were no important changes in vital signs or electrolytes. Venous pH, lactate, and catecholamine changes were similar to previous studies on earlier generation devices. There was no evidence of impairment of breathing. CK changes were greater for multiple "circuits". CONCLUSIONS: In our study, the respiratory, metabolic, and neuroendocrine effects were similar to previous generation devices. There was an increase in CK with more probes deployed.

Human cardiovascular effects of a new generation conducted electrical weapon.

OBJECTIVES: The conducted electrical weapon (CEW) is used by law enforcement to control potentially violent people. Much of the research in CEW safety has focused on the TASER X26, which uses a single deployment cartridge. New Generation CEW (NGCEW) technology has been developed that uses a different circuit and multiple cartridges that can be simultaneously deployed. The objective of this study is to examine the cardiovascular effects of the NGCEW in different deployment possibilities. METHODS: This was a prospective study of human subjects during NGCEW training courses. Subjects received a NGCEW probe deployment to the frontal torso in 1 of 3 configurations: 2, 3,or 4 embedded probes and then underwent a 10-s exposure. Before and after vital signs, electrocardiograms (ECGs), and serum troponin I values were obtained. Real-time echocardiography was utilized before, during and after the exposure to evaluate heart rate and rhythm. RESULTS: Initially, a 1st version NGCEW (NGCEWv1) that was in the final stages of manufacturer verification was used at the training courses. It had not been publicly released. During a NGCEWv1 exposure with 2 probes, there was an apparent brief episode of cardiac capture. Testing was halted and the manufacturer was notified. The device was redesigned and the study continued when a redesigned, 2nd version (NGCEWv2) was used. The NGCEW1 was studied in 8 subjects. The NGCEWv2 was studied in 45 subjects with no evidence of cardiac capture. There were no important post-exposure vital sign, troponin I or ECG changes found in any volunteers. CONCLUSIONS: An apparent brief myocardial capture event occurred with the NGCEWv1. This device was not released and was redesigned. The NGCEWv2 appears to exhibit a reasonable degree of cardiac safety with frontal torso exposures and multiple probe combination configurations.

Melittin-induced membrane permeability: a nonosmotic mechanism of cell death.

Derived from honeybees, melittin is a 26-amino acid, alpha-helical, membrane-attack protein that efficiently kills mammalian cells. To investigate the contribution of colloid-osmotic effects to the mechanism of cell death, we studied the effect of melittin on lymphocyte membrane permeability and cell volumes. Melittin concentrations of 0.5 to 2.0 microM induced release of membrane permeability markers without total disruption of the cell membrane. At these melittin concentrations, electrical-impedance cytometry demonstrated melittin-induced changes in red blood cell volumes (P<0.01), but no change in lymphocyte cell volumes (P>0.05). Streaming video microscopy, obtaining images of melittin-treated lymphocytes at 80-ms intervals, demonstrated a loss of optical density (P<0.001) suggesting a flattening of the cell but no significant increase in cell perimeter (P>0.05). Real-time multiparameter flow cytometry of melittin-treated lymphocytes confirmed simultaneous loss of the cytoplasmic marker, calcein, and uptake of the DNA dye, ethidium homodimer, but demonstrated no increase in forward light scatter. Transmission-electron microscopy of melittin-treated lymphocytes showed normal cell volumes but discontinuities in the cell membrane suggesting direct membrane toxicity. We conclude that melittin causes lymphocyte death by a "leaky patch" mechanism that is independent of colloid-osmotic effects.