Leonie Calver

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.

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.

Randomized controlled trial of intravenous antivenom versus placebo for latrodectism: The second redback antivenom evaluation (RAVE-II) study

STUDY OBJECTIVE Latrodectism is the most important spider envenomation syndrome worldwide. There remains considerable controversy over antivenom treatment. We aimed to investigate whether antivenom resulted in resolution of pain and systemic effects in patients with latrodectism who received standardized analgesia. METHODS In a multicenter randomized placebo-controlled trial of redback spider antivenom for latrodectism, 224 patients (>7 years) with a redback spider bite and severe pain, with or without systemic effects, were randomized to receive normal saline solution (placebo) or antivenom after receiving standardized analgesia. The primary outcome was a clinically significant reduction in pain 2 hours after trial medication compared with baseline. A second primary outcome for the subgroup with systemic features of envenomation was resolution of systemic features at 2 hours. Secondary outcomes were improved pain at 4 and 24 hours, resolution of systemic features at 4 hours, administration of opioid analgesics or unblinded antivenom after 2 hours, and adverse reactions. RESULTS Two hours after treatment, 26 of 112 patients (23%) from the placebo arm had a clinically significant improvement in pain versus 38 of 112 (34%) from the antivenom arm (difference in favor of antivenom 10.7%; 95% confidence interval -1.1% to 22.6%; P=.10). Systemic effects resolved after 2 hours in 9 of 41 patients (22%) in the placebo arm and 9 of 35 (26%) in the antivenom arm (difference 3.8%; 95% confidence interval -15% to 23%; P=.79). There was no significant difference in any secondary outcome between antivenom and placebo. Acute systemic hypersensitivity reactions occurred in 4 of 112 patients (3.6%) receiving antivenom. CONCLUSION The addition of antivenom to standardized analgesia in patients with latrodectism did not significantly improve pain or systemic effects.

Risperidone Overdose Causes Extrapyramidal Effects But Not Cardiac Toxicity

Objective: The aim of this study was to describe the clinical and electrocardiographic features of risperidone overdose, including the frequency of dystonic reactions. Methods: A consecutive series of admissions for risperidone overdose (>6 mg) were identified from a prospective database of poisoning admissions to a regional toxicology service. Data extracted included patient demographics, details of ingestion, clinical features including neurological findings and evidence of dystonias, electrocardiographic parameters (heart rate [HR], QRS, and QT intervals), complications, and medical outcomes including intensive care unit admission. In addition to descriptive statistics, visual inspection of plots of QT-HR pairs compared with the QT nomogram was performed. Results: There were 107 patients with 157 presentations, including 38 patients with 45 risperidone-alone overdoses. Of the 38 patients who ingested risperidone alone, the median age was 25 years (interquartile range [IQR],16-31 years), and 19 (50%) were female. The median dose ingested was 33 mg (IQR, 15-75 mg; range, 8-248 mg). Median length of stay was 16 hours (IQR, 8-18 hours), and none was ventilated or admitted to the intensive care unit. There were 5 cases (11%) with dystonic reactions, 26 (58%) with tachycardia (HR ≥100 beats/min), and no cases with hypotension (blood pressure <90 mm Hg). Only 1 patient (2%) recorded a decreased Glasgow Coma Scale score of 14, and there were no seizures or deaths. On review of electrocardiograms in 41 of the 45 cases where risperidone was ingested alone, there were no acute dysrhythmias. In 4 electrocardiograms (10%), there was an abnormal QT-HR pair, but all bar one were associated with an HR of greater than 110 beats/min. The median maximum QRS width was 80 milliseconds (IQR, 80-80 milliseconds; range, 40-120 milliseconds). Conclusions: Risperidone taken alone in overdose causes minimal effects. Tachycardia and dystonic reactions were the main features of toxicity. Significant cardiac and other neurological features seem to be uncommon.

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.

Droperidol v. haloperidol for sedation of aggressive behaviour in acute mental health: randomised controlled trial

BACKGROUND Agitation and aggression are significant problems in acute psychiatric units. There is little consensus on which drug is most effective and safest for sedation of these patients. AIMS To compare the effectiveness and safety of haloperidol v. droperidol for patients with agitation and aggression. METHOD In a masked, randomised controlled trial (ACTRN12611000565943) intramuscular droperidol (10 mg) was compared with intramuscular haloperidol (10 mg) for adult patients with acute behavioural disturbance in a psychiatric intensive care unit. The primary outcome was time to sedation within 120 min. Secondary outcomes were use of additional sedation, adverse events and staff injuries. RESULTS From 584 patients, 110 were randomised to haloperidol and 118 to droperidol. Effective sedation occurred in 210 (92%) patients within 120 min. There was no significant difference in median time to sedation: 20 min (interquartile range 15-30, range 10-75) for haloperidol v. 25 min (IQR 15-30, range 10-115) for droperidol (P = 0.89). Additional sedation was used more often with haloperidol (13% v. 5%, P = 0.06), but adverse effects were less common with haloperidol (1% v. 5%, P = 0.12). There were 8 staff injuries. CONCLUSIONS Both haloperidol and droperidol were effective for sedation of patients with acute behavioural disturbance.

Sedation assessment tool to score acute behavioural disturbance in the emergency department.

Objective: The objective of the study was to evaluate the effectiveness of the sedation assessment tool (SAT) in assessing patient response to treatment for acute behavioural disturbance (ABD).

High dose droperidol and QT prolongation: analysis of continuous 12-lead recordings.

Aims To investigate the QT interval after high dose droperidol using continuous 12-lead Holter recordings. Methods This was a prospective study of patients given droperidol with a continuous Holter recording. Patients were recruited from the DORM II study which included patients with aggression presenting to the emergency department. Patients initially received 10 mg droperidol as part of a standardized sedation protocol. An additional 10 mg dose was given after 15 min if required and further doses at the clinical toxicologists discretion. Continuous 12-lead Holter recordings were obtained for 2–24 h utilizing high resolution digital recordings with automated QT interval measurement. Electrocardiograms were extracted hourly from Holter recordings. The QT interval was plotted against heart rate (HR) on the QT nomogram to determine if it was abnormal. QTcF (Fridericias HR correction) was calculated and >500 ms was defined as abnormal. Results Forty-six patients had Holter recordings after 10–40 mg droperidol and 316 QT–HR pairs were included. There were 32 abnormal QT measurements in four patients, three given 10 mg and one 20 mg. In three of the four patients QTcF >500 ms but only in one taking methadone was the timing of QTcF >500 ms consistent with droperidol dosing. Of the three other patients, one took amphetamines, one still had QT prolongation 24 h after droperidol and one took a lamotrigine overdose. No patient given >30 mg had a prolonged QT. There were no arrhythmias. Conclusion QT prolongation was observed with high dose droperidol. However, there was little evidence supporting droperidol being the cause and QT prolongation was more likely due to pre-existing conditions or other drugs.

Digital Holter measurement of QT prolongation in ziprasidone overdose

Objective. QT prolongation is an important complication in drug overdose, particularly with some antidepressants and antipsychotics. There are problems with the accurate measurement of the QT interval and determining for what QT interval patients should be monitored, because of the risk of torsades des pointes (TdP). We report a case of ziprasidone overdose with QT prolongation, demonstrating different methods of measuring the QT interval. Case report. A 47-year-old female presented after taking 1.2 g of ziprasidone and 250 mg of diazepam. She was taking propranolol and venlafaxine therapeutically. She developed bradycardia and QT prolongation (540 msec). She was transferred to a telemetry bed and observed for 48 h until her QT interval returned to normal (460 msec). QT intervals were extracted from (1) 12-lead digital Holter recordings (gold standard); (2) automated measurements on standard electrocardiograms (ECGs); and (3) manual measurements on standard ECGs, and compared on a QT versus time plot. An abnormal QT was determined based on the QT nomogram. Manual QT measurements showed a clear temporal association between ziprasidone overdose and a long QT, consistent with accurate QT measurements using continuous 12-lead Holter recordings with automatic QT measurements. However, standard automated measurements did not indicate an abnormal QT. Conclusions. Manual measurement of the QT interval appeared to be similar to the more accurate measurement of the QT by automated digital Holter recordings and better than standard automated measurements. Manual QT measurements would be more appropriate in clinical assessment of patients.

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.