Michael A. Downes

Randomized controlled trial of intramuscular droperidol versus midazolam for violence and acute behavioral disturbance: the DORM study.

STUDY OBJECTIVE We determine whether droperidol, midazolam, or the combination is more effective for intramuscular sedation in violent and acute behavioral disturbance in the emergency department (ED). METHODS We conducted a blinded randomized controlled trial of intramuscular sedation for violent and acute behavioral disturbance, comparing droperidol (10 mg), midazolam (10 mg), and droperidol (5 mg)/midazolam (5 mg). Inclusion criteria were patients requiring physical restraint and parenteral sedation. The primary outcome was the duration of the violent and acute behavioral disturbance, defined as the time security staff were required. Secondary outcomes included time until additional sedation was administered, staff and patient injuries, further episodes of violent and acute behavioral disturbance, and drug-related adverse effects. RESULTS From 223 ED patients with violent and acute behavioral disturbance, 91 patients were included; 33 received droperidol, 29 received midazolam, and 29 received the combination. There was no difference in the median duration of the violent and acute behavioral disturbance: 20 minutes (interquartile range [IQR] 11 to 37 min) for droperidol, 24 minutes (IQR 13 to 35 minutes) for midazolam, and 25 minutes (IQR 15 to 38 minutes) for the combination. Additional sedation was required in 11 (33%; 95% confidence interval [CI] 19% to 52%) droperidol patients, 18 (62%; 95% CI 42% to 79%) midazolam patients, and 12 (41%; 95% CI 24% to 61%) in the combination group. The hazard ratio for additional sedation in the midazolam versus droperidol group was 2.31 (95% credible interval 1.01 to 4.71); for the combination versus droperidol, 1.18 (95% credible interval 0.46 to 2.50). Patient and staff injuries and number of further episodes of violent and acute behavioral disturbance did not differ between groups. There were two adverse effects for droperidol (6%; 95% CI 1% to 22%), 8 for midazolam (28%; 95% CI 13% to 47%), and 2 for the combination (7%; 95% CI 1% to 24%). An abnormal QT occurred in 2 of 31 (6%; 95% CI 1% to 23%) droperidol patients, which was not different from the other groups. CONCLUSION Intramuscular droperidol and midazolam resulted in a similar duration of violent and acute behavioral disturbance, but more additional sedation was required with midazolam. Midazolam caused more adverse effects because of oversedation, and there was no evidence of QT prolongation associated with droperidol compared with midazolam.

Structured team approach to the agitated patient in the emergency department

Objective:  Behavioural disturbance and aggression in the ED is an increasing problem. The present study describes the characteristics of patients with acute behavioural disturbance and their emergent treatment in an ED with a structured team approach.

The Safety and Effectiveness of Droperidol for Sedation of Acute Behavioral Disturbance in the Emergency Department.

STUDY OBJECTIVE We investigate the safety and effectiveness of droperidol for sedation of acute behavioral disturbance in the emergency department (ED). METHODS This was a prospective observational study in 6 EDs (August 2009 to April 2013). Adult patients requiring parenteral sedation for acute behavioral disturbance received droperidol 10 mg. If this did not sedate the patient within 15 minutes, further sedation was allowed but droperidol 10 mg was recommended as part of a sedation protocol. The primary outcome was the proportion of patients with an abnormal QT interval, defined by the at-risk line on the QT nomogram. Secondary outcomes were effectiveness determined by the time to sedation measured on the Sedation Assessment Tool, use of additional sedation, adverse events, and injury to staff or patients. RESULTS There were 1,009 patients with an ECG performed within 2 hours of droperidol administration, with a median dose of 10 mg (interquartile range [IQR]10 to 17.5 mg). Thirteen of the 1,009 patients had an abnormal QT (1.3%; 95% confidence interval 0.7% to 2.3%), but 7 of these had another cause attributed for prolonged QT (methadone, escitalopram, amiodarone, or preexisting). In 1,403 patients sedated with a median total dose of droperidol of 10 mg (IQR 10 to 20 mg), the median time to sedation was 20 minutes (IQR 10 to 30 minutes) and 97% were sedated within 120 minutes. Additional sedation was required for 435 patients (31.0%; 95% confidence interval 28.6% to 33.5%). Adverse events occurred in 70 patients (5%) and oversedation without complications in 109 (8%), the latter more common for patients receiving benzodiazepines as additional sedation (16/109 [15%]). There were no cases of torsades de pointes. Injuries occurred in 34 staff members and 4 patients. CONCLUSION The study supports the use of high-dose droperidol as a safe sedating agent for patients with acute behavioral disturbance in the ED. There is no evidence of increased risk for QT prolongation with the doses used in this study.

The impact of a standardised intramuscular sedation protocol for acute behavioural disturbance in the emergency department

BackgroundAcute behavioural disturbance (ABD) is an increasing problem in emergency departments. This study aimed to determine the impact of a structured intramuscular (IM) sedation protocol on the duration of ABD in the emergency department.MethodsA historical control study was undertaken comparing 58 patients who required physical restraint and parenteral sedation with the structured IM sedation protocol, to 73 historical controls treated predominantly by intravenous sedation, according to individual clinician preference. The primary outcome was the duration of the ABD defined as the time security staff were required. Secondary outcomes were the requirement for additional sedation, drug related-adverse effects and patient and staff injuries.ResultsThe median duration of the ABD in patients with the new sedation protocol was 21 minutes (IQR: 15 to 35 minutes; Range: 5 to 78 minutes) compared to a median duration of 30 minutes (IQR: 15 to 50 minutes; Range: 5 to 135 minutes) in the historical controls which was significantly different (p = 0.03). With IM sedation only 27 of 58 patients (47%; 95% CI: 34% to 60%) required further sedation compared to 64 of 73 historical controls (88%; 95%CI: 77% to 94%). There were six (10%) drug-related adverse events with the new IM protocol [oxygen desaturation (5), oxygen desaturation/airway obstruction (1)] compared to 10 (14%) in the historical controls [oxygen desaturation (5), hypoventilation (4) and aspiration (1)]. Injuries to staff occurred with three patients using the new sedation protocol and in seven of the historical controls. Two patients were injured during the new protocol and two of the historical controls.ConclusionThe use of a standardised IM sedation protocol was simple, more effective and as safe for management of ABD compared to predominantly intravenous sedation.

A prospective observational study of a novel 2-phase infusion protocol for the administration of acetylcysteine in paracetamol poisoning

Abstract Context: The current 3-phase acetylcysteine infusion for paracetamol poisoning delivers half the dose over 15–60 min and frequently results in adverse reactions. Objective: We aimed to determine adverse reaction frequency with a modified 2-phase infusion protocol with a longer initial infusion. Materials and methods: A prospective observational study of a modified 2-phase acetylcysteine protocol was undertaken at two hospitals. Acetylcysteine was commenced on admission and ceased if paracetamol concentrations were low-risk (below the nomogram line). The first infusion was 200 mg/kg over 4–9 h based on ingestion time or 4 h for staggered/chronic ingestions. The second infusion was 100 mg/kg over 16 h. Pre-defined outcomes were frequency of adverse reactions (systemic hypersensitivity reactions or gastrointestinal); proportion with alanine transaminase (ALT) > 1000 U/L or abnormal ALT. Results: 654 paracetamol poisonings were treated with the new protocol; median age 29 y (15–98 y); 453 females; 576 acute and 78 staggered/chronic ingestions. In 420 (64%) acetylcysteine was stopped for low-risk paracetamol concentrations. An adverse reaction occurred in 229/654 admissions (35%; 95% CI: 31–39%): 173 (26.5%; 95% CI: 23–30%) only gastrointestinal, 50 (8%; 95% CI: 6–10%) skin only systemic hypersensitivity reactions; and three severe anaphylaxis (0.5%; 95% CI: 0.1–1.5%; all hypotension). Adverse reactions occurred in 111/231 (48%) receiving full treatment compared to 116/420 (28%) in whom the infusion was stopped early (absolute difference 20%; 95% CI: 13–28%; p < 0.0001). In 200 overdoses < 10 g, one had toxic paracetamol concentrations, but 53 developed reactions. Sixteen patients had an ALT > 1000 U/L and 24 an abnormal ALT attributable to paracetamol; all but one had treatment commenced >12 h post-ingestion. Conclusion: A 2-phase acetylcysteine infusion protocol results in a fewer reactions in patients with toxic paracetamol concentrations, but is not justified in patients with low-risk paracetamol concentrations.

Intralipid therapy does not improve level of consciousness in overdoses with sedating drugs: A case series

To assess the effect of intralipid emulsion therapy (ILE) in sedating drugs presenting to an urban emergency department.

QTc abnormalities in deliberate self-poisoning with moclobemide

Abstract

Acute behavioural disturbance associated with phenibut purchased via an internet supplier

Abstract Context. Toxicity from recreational substances marketed for other purposes is a well-documented clinical entity. We present two cases of phenibut toxicity procured via the internet. Case Details. A 20-year-old female presented to the emergency department (ED) having used phenibut the prior day. The main finding was a decreased level of consciousness, however when roused she became delirious. Supportive care only was required with no specific intervention. The patient made a full recovery over a 24-hour period and admitted to use of phenibut purchased online. Plasma phenibut concentration was 29.7 μg/ml. A 38-year-old male presented to ED with an agitated delirium. The prior evening he had used tetrahydrocannabinol or THC, alcohol and phenibut, the latter purchased via the internet. His behavioural state had a suboptimal response to parenteral sedation. He was subsequently intubated for airway protection in the context of ongoing sedation to optimally manage his behavioural state. Post extubation the next morning he admitted using phenibut. Plasma phenibut concentration was 36.5 μg/ml. Discussion. Altered mental status was the predominant manifestation of phenibut toxicity in these cases. Clinicians to be aware of how phenibut toxicity may present as the internet has widened access to such substances.

Clinical features of serum sickness after Australian snake antivenom

Serum sickness is a delayed immune reaction in which the immune system responds to a protein in antiserum as a potentially harmful substance and mounts an IgG-mediated antibody response. A 32 year-old female patient had systemic envenoming following a bite by a red-bellied black snake (Pseudechis porphyriacus). She was treated with Tiger snake antivenom and recovered over 24 h and did not develop myotoxicity. She then presented with local pain, itching and swelling, which was partially treated with antihistamines. Eleven days after the bite she presented again with symptoms of worsening serum sickness including rash on the upper legs, joint and muscle pain in arms, ankles and knees, and nausea. The patient was prescribed five days of prednisone 50 mg/day, antihistamine 10 mg/day and analgesia 1000 mg/day and improved over 2 days. She had no further problems on follow up at 4 months. This case highlights that serum sickness can cause significant effects after the treatment of snake envenoming. It develops 5-14 days after antivenom administration and has characteristic clinical and laboratory features. Severe cases of serum sickness can result in morbidity but it appears to respond well to corticosteroid treatment.

Catecholamine-induced cardiomyopathy resulting from life-threatening funnel-web spider envenoming.

Wepresent twocasesof cardiomyopathy in life-threatening funnel-webspider envenoming.A33-yearoldman bitten by amale Sydney funnel-web spider developed autonomic and neuromuscular excess, pulmonary oedema, hypotension and cardiogenic shock. Hewas treatedwith antivenom, dobutamine, noradrenaline and high-dose insulin, and recovered over 4 days. Echocardiograms showed severe systolic dysfunction, andhigh catecholamineconcentrationsweremeasured in his blood. A 13-year-old girl developed cardiogenic shock after a funnel-web spider bite, confirmed on echocardiogram treated with antivenom and dobutamine. Funnel-web spider envenoming appears to cause catecholamineinduced cardiomyopathy and cardiogenic pulmonary oedema resulting from catecholamine excess. Antivenom did not reverse the cardiomyopathy.