Baruch Krauss, Dean R Hess
Capnography for procedural sedation and analgesia in the emergency department.
Ann Emerg Med. 2007 Aug;50(2):172-81. doi: 10.1016/j.annemergmed.2006.10.016. Epub 2007 Jan 12.
Abstract/Text
Although it is standard of care for patient safety monitoring in anesthesia, capnography is not routinely used for emergency department procedural sedation and analgesia. We discuss the use of capnography as a diagnostic monitoring modality for procedural sedation and analgesia, focusing on the physiology and interpretation of the CO2 waveform and recognition of normal, abnormal, and drug-induced ventilatory patterns.
Jennifer Rossi, Megan C Swan, Eric D Isaacs
The violent or agitated patient.
Emerg Med Clin North Am. 2010 Feb;28(1):235-56, x. doi: 10.1016/j.emc.2009.10.006.
Abstract/Text
Violent and agitated patients are high risk because they may pose a physical threat to the staff, may harm themselves, and may have dangerous comorbidities and illness that are causing the violence. The emergency physician must quickly control these behaviors, and thoroughly identify and treat their etiology, while simultaneously protecting the patients' rights and reducing the risks of injury to themselves, other patients, and medical staff. This article highlights potentially high-risk situations and describes corresponding mitigation tactics.
Michael H Allen, Glenn W Currier, Daniel Carpenter, Ruth W Ross, John P Docherty, Expert Consensus Panel for Behavioral Emergencies 2005
The expert consensus guideline series. Treatment of behavioral emergencies 2005.
J Psychiatr Pract. 2005 Nov;11 Suppl 1:5-108; quiz 110-2.
Abstract/Text
OBJECTIVES: Due to inherent dangers and barriers to research in emergency settings, few data are available to guide clinicians about how best to manage behavioral emergencies. Key constructs such as agitation are poorly defined. This lack of empirical data led us to undertake a survey of expert opinion, results of which were published in the 2001 Expert Consensus Guidelines on the Treatment of Behavioral Emergencies. Several second-generation (atypical) antipsychotics (SGAs) are now available in new formulations for treating behavioral emergencies (e.g., intramuscular [i.m.] olanzapine and ziprasidone; rapidly dissolving tablets of olanzapine and risperidone). Critical questions face the field. The SGAs are significantly different from the FGAs and from each other and have not been studied in unselected patients as were the FGAs. Can the SGAs can be thought of as a class, do all antipsychotics have similar anti-agitation effects in different conditions, and, if equally effective, what limits might their safety profiles impose? Should antipsychotics be used more specifically to treat psychotic conditions, while benzodiazepines (BNZs) alone are used nonspecifically? Few data are available concerning combinations of SGAs and BNZs, and findings concerning the traditional combination of haloperidol plus a BNZ may not be relevant to combinations with SGAs. The culture is also evolving with more emphasis on patient involvement in treatment decisions. An international consensus has been developing that calming rather than sedation is the appropriate endpoint of behavioral emergency interventions. We undertook a new survey of expert opinion to update recommendations from the earlier survey.
METHOD: A written survey of 61 questions (1,020 options) was mailed to 50 experts in the field, 48 (96%) of whom completed it. The survey sought to define level of agitation at which emergency interventions are appropriate, scope of assessment depending on urgency and patients' ability to cooperate, guiding principles for selecting interventions, and appropriate physical and medication strategies at different levels of diagnostic confidence for a variety of provisional diagnoses and complicating conditions. A modified version of the RAND Corporation's 9-point scale for rating appropriateness of medical decisions was used to score most options. Consensus was defined as a non-random distribution of scores by chi-square "goodness-of-fit" test. We assigned a categorical rank (first line/preferred, second line/alternate, third line/usually inappropriate) to each option based on the 95% confidence interval around the mean. Ratings were used to develop guidelines for preferred strategies in key clinical situations. This study received financial support from multiple sponsors, with the panel kept blind to sponsorship to reduce possible bias. Medication ratings were based on responses of only those respondents with direct experience with each drug. In reporting practice patterns, the panel was asked to respond based on actual data rather than estimates.
RESULTS: The expert panel reached consensus on 78% of the options rated on the 9-point scale. The responses suggest that physicians can make provisional diagnoses with some confidence and that pharmacological and nonpharmacological interventions are selected differentially based on diagnosis and other salient demographic and medical features. BNZs are recommended when no data are available, when there is no specific treatment (e.g., personality disorder), or when they may have specific benefits (e.g., intoxication). No single SGA emerges as a nonspecific replacement for haloperidol; instead, different SGAs are preferred in various circumstances consistent with current evidence. To the degree that haloperidol is recommended, it is almost always in combination with a BNZ; haloperidol alone is preferred only in the medically compromised. In contrast, the SGAs are more often recommended for use alone, and the panel would avoid combining BNZs with some SGAs. Oral risperidone alone or combined with a BNZ receives strong support in a variety of situations. Oral olanzapine was rated very similarly to risperidone, with slightly higher ratings than risperidone in situations where it has been studied (e.g., schizophrenia, mania) and slightly lower ratings where it has not been studied or safety may be a concern; there was less support for combining oral olanzapine with a BNZ. For oral treatment of agitation related to schizophrenia or mania, olanzapine alone, risperidone alone or combined with a BNZ, and haloperidol plus a BNZ are first line, with strong support also for combining divalproex with the antipsychotic for presumed mania. Oral ziprasidone and quetiapine generally received similar second-line ratings in most situations. If a parenteral agent is needed, i.m. olanzapine alone received somewhat more support than i.m. ziprasidone alone; however, there was more support for i.m. ziprasidone alone or combined with a BNZ than for i.m. olanzapine plus a BNZ, probably reflecting safety concerns. For example, for a provisional diagnosis of schizophrenia, first-line parenteral options are i.m. olanzapine or ziprasidone alone or i.m. haloperidol or ziprasidone combined with a BNZ. Neither of the new parenteral formulations received as much support as traditional agents (i.m. BNZs, i.m. haloperidol) when no data are available or the diagnosis involves medical comorbidity or intoxication. When initial intervention with risperidone, ziprasidone, or haloperidol is unsuccessful, the panel recommended adding a BZD to the antipsychotic. However, when initial treatment with olanzapine or quetiapine is unsuccessful, increasing the dosage is recommended. Perphenazine was consistently rated second line and droperidol and chlorpromazine received third-line ratings throughout.
CONCLUSIONS: Within the limits of expert opinion and with the expectation that future research data will take precedence, these guidelines suggest that the SGAs are now preferred for agitation in the setting of primary psychiatric illnesses but that BNZs are preferred in other situations.
Peter M Haddad, Sonu G Sharma
Adverse effects of atypical antipsychotics : differential risk and clinical implications.
CNS Drugs. 2007;21(11):911-36.
Abstract/Text
Antipsychotic drugs can be of great benefit in a range of psychiatric disorders, including schizophrenia and bipolar disorder, but all are associated with a wide range of potential adverse effects. These can impair quality of life, cause stigma, lead to poor adherence with medication, cause physical morbidity and, in extreme cases, be fatal. A comprehensive overview of tolerability requires a review of all available data, including randomised controlled trials (RCTs), observational studies and postmarketing surveillance studies. Assessing the relative tolerability of atypical antipsychotics is hampered by the paucity of RCTs that compare these drugs head-to-head, and limited and inconsistent reporting of adverse effect data that makes cross-study comparisons difficult. Despite methodological problems in assessment and interpretation of tolerability data, important differences exist between the atypical antipsychotics in the relative risk of acute extrapyramidal symptoms (highest risk: higher doses of risperidone), hyperglycaemia and dyslipidaemia (highest risk: clozapine and olanzapine), hyperprolactinaemia (highest risk: amisulpride and risperidone), prolongation of heart rate-corrected QT interval (QTc) [highest risk: ziprasidone and sertindole] and weight gain (highest risk: clozapine and olanzapine). Sedation, antimuscarinic symptoms, postural hypotension, agranulocytosis and seizures are more common with clozapine than with other atypical antipsychotics. The variation in their tolerability suggests that it is misleading to regard the atypical antipsychotics as a uniform drug class, and also means that the term 'atypical antipsychotic' has only limited usefulness. Differences between the atypical agents in terms of efficacy and pharmacodynamic profiles also support this view. As tolerability differs between specific conventional and atypical drugs, we conclude that broad statements comparing the relative risk of specific adverse effects between 'atypical' and 'conventional' antipsychotics are largely meaningless; rather, comparisons should be made between specific atypical and specific conventional drugs. Adverse effects are usually dose dependent and can be influenced by patient characteristics, including age and gender. These confounding factors should be considered in clinical practice and in the interpretation of research data. Selection of an antipsychotic should be on an individual patient basis. Patients should be involved in prescribing decisions and this should involve discussion about adverse effects.
James R Miner, William Heegaard, David Plummer
End-tidal carbon dioxide monitoring during procedural sedation.
Acad Emerg Med. 2002 Apr;9(4):275-80.
Abstract/Text
OBJECTIVE: To prospectively determine whether end-tidal carbon dioxide (ETCO2) monitors can detect respiratory depression (RD) and the level of sedation in emergency department (ED) patients undergoing procedural sedation (PS).
METHODS: This was a prospective observational study conducted in an urban county hospital of adult patients undergoing PS. Patients were monitored for vital signs, depth of sedation per the physician by the Observer's Assessment of Alertness/Sedation scale (OAA/S), pulse oximetry, and nasal-sample ETCO2 during PS. Respiratory depression was defined as an oxygen saturation <90%, an ETCO2 >50 mm Hg, or an absent ETCO2 waveform at any time during the procedure. The physician also determined whether protective airway reflexes were lost during the procedure and assisted ventilation was required, or whether there were any other complications. Rates of RD were compared with the physician assessment of airway loss and between agents using chi-square statistics. Spearman's rho analysis was used to determine whether there was a correlation between ETCO2 and the OAA/S score.
RESULTS: Seventy-four patients were enrolled in the study. Forty (54.1%) received methohexital, 21 (28.4%) received propofol, ten (13.5%) received fentanyl and midazolam, and three (4.1%) received etomidate. Respiratory depression was seen in 33 (44.6%) patients, including 47.5% of patients receiving methohexital, 19% receiving propofol (p = 0.008), 80% receiving fentanyl and midazolam, and 66.6% receiving etomidate. No correlation between OAA/S and ETCO2 was detected. Eleven (14.9%) patients required assisted ventilation at some point during the procedure, all of whom met the criteria for RD. Pulse oximetry detected 11 of the 33 patients with RD. Post-hoc analysis revealed that all patients with RD had an ETCO2 >50 mm Hg, an absent waveform, or an absolute change from baseline in ETCO2 >10 mm Hg.
CONCLUSIONS: There was no correlation between ETCO2 and the OAA/S score. Using the criteria of an ETCO2 >50 mm Hg, an absolute change >10 mm Hg, or an absent waveform may detect subclinical RD not detected by pulse oximetry alone. The ETCO2 may add to the safety of PS by quickly detecting hypoventilation during PS in the ED.
A Yildiz, G S Sachs, A Turgay
Pharmacological management of agitation in emergency settings.
Emerg Med J. 2003 Jul;20(4):339-46.
Abstract/Text
OBJECTIVE: To review, firstly, published studies comparing classic antipsychotics, benzodiazepines, and/or combination of both; and secondly, available data on the use of atypical antipsychotic medications in controlling agitation and aggressive behaviour seen in psychiatric patients in emergency.
METHOD: In the first review, studies comparing antipsychotics, benzodiazepines, and combination of both; and in the second review, efficacy trials of atypical antipsychotics that include an active and/or inactive comparator for the treatment of acute agitation were identified and reviewed. Data from clinical trials meeting the inclusion criteria were summarised by recording improvement rates, definition of improvement, and timing of defined improvement for individual studies.
RESULTS: In the first review, 11 trials were identified meeting the inclusion criteria, eight with a blind design. The total number of subjects was 701. These studies taken together suggest that combination treatment may be superior to the either agent alone with higher improvement rates and lower incidence of extrapyramidal side effects. In the review of atypical antipsychotic agents as acute antiagitation compounds, five studies were identified, three with a blind design. The total number of subjects was 711, of which 15% (104) was assigned to the placebo arm. This review found atypical antipsychotics to be as effective as the classic ones and more advantageous in many aspects.
CONCLUSION: Atypical antipsychotics such as risperidone, ziprasidone, and olanzapine with or without benzodiazepines should be considered first in the treatment of acute agitation. If these agents are not available the combination of a classic antipsychotic and a benzodiazepine would be a reasonable alternative. An oral treatment should always be offered first for building up an alliance with the patient and suggesting an internal rather than external locus of control.
M H Allen
Managing the agitated psychotic patient: a reappraisal of the evidence.
J Clin Psychiatry. 2000;61 Suppl 14:11-20.
Abstract/Text
Under intense public pressure, regulatory agencies have recently defined circumstances in which medications will be considered a form of restraint, so-called "chemical restraint." This article proposes that the emergency management of the agitated patient be viewed as a brief departure from the usual physician-patient collaboration. Viewed in this way, the goal is simply to terminate the emergency in the manner most likely to be acceptable to patients and conducive to a more typical dialogue. To that end, the author reviews all controlled studies of medication treatment of agitation that have appeared in English since the advent of the neuroleptic medications. Issues of diagnosis, relative efficacy, dosage, route, onset, offset, safety, tolerability, and consumer preference are considered.
Marc Martel, Ann Sterzinger, James Miner, Joseph Clinton, Michelle Biros
Management of acute undifferentiated agitation in the emergency department: a randomized double-blind trial of droperidol, ziprasidone, and midazolam.
Acad Emerg Med. 2005 Dec;12(12):1167-72. doi: 10.1197/j.aem.2005.07.017. Epub 2005 Nov 10.
Abstract/Text
OBJECTIVES: To compare the efficacy of sedation, need for rescue sedation, rates of respiratory depression, and complications of droperidol, ziprasidone, and midazolam when used for the treatment of emergency department (ED) patients requiring sedation for acute undifferentiated agitation.
METHODS: A prospective, randomized, double-blind trial of agitated ED patients requiring emergent sedation was performed. Patients were randomized to receive droperidol 5 mg, ziprasidone 20 mg, or midazolam 5 mg intramuscularly. Interval measurements were made at 0, 15, 30, 45, 60, and 120 minutes and included Altered Mental Status Scale (AMS) scores, oxygen saturations, and end-tidal carbon dioxide levels.
RESULTS: A total of 144 patients were enrolled; 50 patients received droperidol, 46 received ziprasidone, and 48 received midazolam. Adequate sedation (mean AMS score <0) was achieved at 15 minutes in patients receiving midazolam (mean AMS score, -0.81) and 30 minutes for patients receiving droperidol (mean AMS score, -1.3) and ziprasidone (mean AMS score, -0.74). Rescue medication for sedation was necessary in 38 of 144 patients (droperidol, 5 of 50; ziprasidone, 9 of 46; midazolam, 24 of 48; p < 0.05). No cardiac dysrhythmias were identified in any treatment group. Respiratory depression that clinically required treatment with supplemental oxygen occurred in 21 of 144 patients (droperidol, 4 of 50; ziprasidone, 7 of 46; midazolam, 10 of 48; p = 0.20). No patients required endotracheal intubation.
CONCLUSIONS: Acutely agitated ED patients sedated with droperidol or ziprasidone required rescue medications to achieve adequate sedation less frequently than those sedated with midazolam. The onset of adequate sedation is delayed with ziprasidone, relative to the other agents.
H Thomas, E Schwartz, R Petrilli
Droperidol versus haloperidol for chemical restraint of agitated and combative patients.
Ann Emerg Med. 1992 Apr;21(4):407-13.
Abstract/Text
STUDY OBJECTIVE: To compare two related pharmacological agents used for the chemical restraint of agitated and combative patients.
DESIGN AND SETTING: A randomized, double-blind, prospective study was carried out in patients requiring physical restraint in a university hospital emergency department.
PARTICIPANTS: Sixty-eight violent or agitated adult patients whom the attending physician believed would benefit from chemical restraint to protect the patient and staff and to expedite evaluation.
INTERVENTION: Twenty-one participants were administered 5 mg haloperidol IM; 26 were administered 5 mg droperidol IM; 12 were administered haloperidol IV; and nine were administered 5 mg droperidol IV.
RESULTS: All patients were rated on a five-point combativeness scale at five, ten, 15, 30, and 60 minutes after the study drug was given. Vital signs also were recorded at these times. IM droperidol decreased combativeness significantly more than IM haloperidol at ten (P = .006), 15 (P = .01), and 30 (P = .04) minutes. There was no significant difference between the two drugs when given by the IV route (beta at the 5% confidence level, P = .78).
CONCLUSION: In equal IM doses (5 mg), droperidol results in more rapid control of agitated patients than haloperidol, without any increase in undesirable side effects.
Thomas W Lukens, Stephen J Wolf, Jonathan A Edlow, Samina Shahabuddin, Michael H Allen, Glenn W Currier, Andy S Jagoda, American College of Emergency Physicians Clinical Policies Subcommittee (Writing Committee) on Critical Issues in the Diagnosis and Management of the Adult Psychiatric Patient in the Emergency Department
Clinical policy: critical issues in the diagnosis and management of the adult psychiatric patient in the emergency department.
Ann Emerg Med. 2006 Jan;47(1):79-99. doi: 10.1016/j.annemergmed.2005.10.002.
Abstract/Text
Jonathan C Knott, David McD Taylor, David J Castle
Randomized clinical trial comparing intravenous midazolam and droperidol for sedation of the acutely agitated patient in the emergency department.
Ann Emerg Med. 2006 Jan;47(1):61-7. doi: 10.1016/j.annemergmed.2005.07.003. Epub 2005 Aug 18.
Abstract/Text
STUDY OBJECTIVE: We compare intravenous midazolam and droperidol for the onset of sedation of acutely agitated patients in the emergency department (ED).
METHODS: This was a double-blind, randomized, clinical trial set in the ED of a university teaching hospital. Subjects were adults, acutely agitated because of mental illness, intoxication, or both, who received midazolam or droperidol, 5 mg intravenously, every 5 minutes until sedated. We analyzed time to sedation using survival analysis, median times to sedation, and proportions sedated at 5 and 10 minutes.
RESULTS: Seventy-four patients received midazolam; 79 patients, droperidol. Survival analysis showed no difference in time to sedation (hazard ratio 0.86; 95% confidence interval [CI] 0.61 to 1.23), P=.42. Median time to sedation was 6.5 minutes for midazolam (median dose 5 mg) and 8 minutes for droperidol (median dose 10 mg), P=.075 (effect size 1.5 minutes; 95% CI 0 to 4 minutes). At 5 minutes, 33 of 74 (44.6%) patients from the midazolam group were adequately sedated compared with 13 of 79 (16.5%) patients from the droperidol group, a difference of 28.1% (95% CI 12.9% to 43.4%; P<.001). By 10 minutes, 41 of 74 (55.4%) from the midazolam group were sedated compared to 42 of 79 (53.2%) from droperidol, a difference of 2.2% (95% CI -14.9% to 19.3%; P=.91). Eleven adverse events occurred in the midazolam group and 10 in the droperidol group. Three patients required active airway management (3 patients with assisted ventilation and 1 patient intubated); all received midazolam.
CONCLUSION: There is no difference in onset of adequate sedation of agitated patients using midazolam or droperidol. Patients sedated with midazolam may have an increased need for active airway management.
Scott L Mankowitz, Pat Regenberg, Janina Kaldan, Jon B Cole
Ketamine for Rapid Sedation of Agitated Patients in the Prehospital and Emergency Department Settings: A Systematic Review and Proportional Meta-Analysis.
J Emerg Med. 2018 Nov;55(5):670-681. doi: 10.1016/j.jemermed.2018.07.017. Epub 2018 Sep 7.
Abstract/Text
BACKGROUND: Rapid tranquilization of agitated patients can prevent injuries and expedite care. Whereas antipsychotics and benzodiazepines are commonly used for this purpose, ketamine has been suggested as an alternative.
OBJECTIVE: The aim of this systematic review is to determine the safety and effectiveness of ketamine to sedate prehospital and emergency department (ED) patients with undifferentiated agitation.
METHODS: Studies and case series of patients receiving ketamine for agitation were included. Studies were excluded if ketamine was used for analgesia, procedural sedation, asthma, or induction. Information sources included traditional and gray literature.
RESULTS: The initial search yielded 1176 results from 14 databases. After review of titles and abstracts, 32 studies were reviewed and 18 were included in the analysis, representing 650 patient encounters. The mean dose of ketamine was 315 mg (SD 52) given intramuscularly, with adequate sedation achieved in 7.2 min (SD 6.2, range 2-500). Intubation occurred in 30.5% of patients (95% confidence interval [CI] 27.0-34.1%). In the majority of those patients, ketamine was administered by paramedics during ground transport and the patient was intubated on ED arrival. When ketamine was administered in the ED, the intubation rate was 1.8% (95% CI 0.0-4.4%); in air medical transport, the rate was 4.9% (95% CI 0.0-10.3%). Other reported side effects included: vomiting, 5.2% (2.3-8.1%); hypertension, 12.1% (5.7-18.6%); emergence reactions, 3.5% (1.4-5.6%); transient hypoxia, 1.8% (0.1-3.6%) and laryngospasm, 1.3% (0.3-2.3%).
CONCLUSIONS: Ketamine provides rapid sedation for undifferentiated agitated patients and is associated with higher intubation rates when used by ground Emergency Medical Services paramedics, compared with ED or air medical transport patients. Other side effects are common but usually self-limiting.
Copyright © 2018 Elsevier Inc. All rights reserved.
Natalie Sullivan, Chen Chen, Rebecca Siegel, Yan Ma, Ali Pourmand, Nataly Montano, Andrew Meltzer
Ketamine for emergency sedation of agitated patients: A systematic review and meta-analysis.
Am J Emerg Med. 2020 Mar;38(3):655-661. doi: 10.1016/j.ajem.2019.11.007. Epub 2019 Nov 29.
Abstract/Text
Prior studies suggest that ketamine is effective for acute agitation in the emergency department (ED) and prehospital settings. This systematic review and meta-analysis aims to evaluate the rate of sedation and need for airway management in patients given ketamine for management of acute agitation. Methods: We performed a systematic review of publications describing the use of ketamine to control agitation in the ED and prehospital settings. Studies were included if they included agitated patients, used ketamine to control agitation, occurred in the ED and prehospital setting and measured sedation status or need for airway management. Following data abstraction, a meta-analysis was performed to synthesize the rate of effective sedation and the need for airway management. Result: 13 studies met the inclusion criteria. 10 studies were conducted in the prehospital setting and 3 in the ED setting. The overall proportion of subjects receiving airway management across all 13 studies was 20% (95% CI = 0.0489-1.6505). The estimate of the proportion of subjects that achieved sedation was 85% (95% CI = 0.71-0.93). After synthesizing data from the four studies that compared ketamine to controls, ketamine was associated with increased rates of sedation (RR, 1.95 [CI, 0.47-8.1]) and increased need for intubation (RR, 2.44 [CI, 0.75-7.91]). The differences were not significant by random effects model.
Copyright © 2019 Elsevier Inc. All rights reserved.
Ian S deSouza, Henry C Thode, Pragati Shrestha, Robert Allen, Jessica Koos, Adam J Singer
Corrigendum to "Rapid tranquilization of the agitated patient in the emergency department: A systematic review and network meta-analysis" [American Journal of Emergency Medicine 51 (2022) 363-373].
Am J Emerg Med. 2022 Feb;52:273. doi: 10.1016/j.ajem.2021.11.036. Epub 2021 Nov 29.
Abstract/Text
James R Krenz, Kristin Medeiros, Kathryn Lupez
Retrospective evaluation of ketamine versus droperidol on time to restraint removal in agitated emergency department patients.
Am J Emerg Med. 2023 Jul;69:23-27. doi: 10.1016/j.ajem.2023.03.058. Epub 2023 Apr 3.
Abstract/Text
PURPOSE: Acute agitation and violent behavior in the emergency department (ED) can lead to significant patient morbidity and contribute to the growing problem of workplace violence against health care providers. To our knowledge, there is no available literature directly comparing intramuscular ketamine to intramuscular droperidol in ED patients presenting with undifferentiated agitation. The purpose of this investigation was to compare the effectiveness and safety of these agents for acute agitation in the ED.
METHODS: This was a retrospective observational study conducted at an urban, academic ED. The primary endpoint was time from the first dose of study medication to restraint removal. Safety endpoints included incidence of bradycardia (heart rate < 60 bpm), hypotension (systolic blood pressure < 90 mmHg), hypoxia (oxygen saturation < 90% or need for respiratory support), and incidence of intubation for ongoing agitation or respiratory failure.
RESULTS: An initial 189 patients were screened, of which, 92 met inclusion criteria. The median time from initial drug administration to restraint removal was 49 min (IQR 30, 168) in the ketamine group and 43 min (IQR 30, 80) in the droperidol group (Median difference 6 min; 95% CI [-7, 26]). There was no significant difference in rates of bradycardia (3% vs 3%, 95% CI [-7%, 8%]), hypotension (0% vs 2%, 95% CI [-5%, 2%]), or hypoxia (7% vs 10%, 95% CI [-15%, 9%]) in the ketamine versus droperidol groups respectively. One patient in the ketamine group was intubated for ongoing agitation, and one patient in the droperidol group was intubated for respiratory failure.
CONCLUSIONS: Intramuscular droperidol and intramuscular ketamine were associated with similar times from drug administration to restraint removal in patients presenting to the ED with undifferentiated agitation. Prospective studies are warranted to evaluate IM droperidol and IM ketamine head-to-head as first line agents for acute agitation in the ED.
Copyright © 2023 Elsevier Inc. All rights reserved.
David Barbic, Gary Andolfatto, Brian Grunau, Frank X Scheuermeyer, Bill Macewan, Hong Qian, Hubert Wong, Skye P Barbic, William G Honer
Rapid Agitation Control With Ketamine in the Emergency Department: A Blinded, Randomized Controlled Trial.
Ann Emerg Med. 2021 Dec;78(6):788-795. doi: 10.1016/j.annemergmed.2021.05.023. Epub 2021 Aug 2.
Abstract/Text
STUDY OBJECTIVE: We hypothesized that the use of intramuscular ketamine would result in a clinically relevant shorter time to target sedation.
METHODS: We conducted a randomized clinical trial comparing the rapidity of onset, level of sedation, and adverse effect profile of ketamine compared to a combination of midazolam and haloperidol for behavioral control of emergency department patients with severe psychomotor agitation. We included patients with severe psychomotor agitation measured by a Richmond Agitation Score (RASS) ≥+3. Patients in the ketamine group were treated with a 5 mg/kg intramuscular injection. Patients in the midazolam and haloperidol group were treated with a single intramuscular injection of 5 mg midazolam and 5 mg haloperidol. The primary outcome was the time, in minutes, from study medication administration to adequate sedation, defined as RASS ≤-1. Secondary outcomes included the need for rescue medications and serious adverse events.
RESULTS: Between June 30, 2018, and March 13, 2020, we screened 308 patients and enrolled 80. The median time to sedation was 14.7 minutes for midazolam and haloperidol versus 5.8 minutes for ketamine (difference 8.8 minutes [95% confidence interval (CI) 3.0 to 14.5]). Adjusted Cox proportional model analysis favored the ketamine arm (hazard ratio 2.43, 95% CI 1.43 to 4.12). Five (12.5%) patients in the ketamine arm and 2 (5.0%) patients in the midazolam and haloperidol arm experienced serious adverse events (difference 7.5% [95% CI -4.8% to 19.8%]).
CONCLUSION: In ED patients with severe agitation, intramuscular ketamine provided significantly shorter time to adequate sedation than a combination of intramuscular midazolam and haloperidol.
Copyright © 2021 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.
Gregory A Nuttall, Karen M Eckerman, Kelly A Jacob, Erin M Pawlaski, Susan K Wigersma, Mary E Shirk Marienau, William C Oliver, Bradly J Narr, Michael J Ackerman
Does low-dose droperidol administration increase the risk of drug-induced QT prolongation and torsade de pointes in the general surgical population?
Anesthesiology. 2007 Oct;107(4):531-6. doi: 10.1097/01.anes.0000281893.39781.64.
Abstract/Text
BACKGROUND: The US Food and Drug Administration issued a black box warning regarding the use of droperidol and the potential for torsade de pointes (TdP).
METHODS: The primary objective of this retrospective study was to determine whether low-dose droperidol administration increased the incidence of TdP in the general surgical population during a 3-yr time period before and after the Food and Drug Administration black box warning. A random sample of 150 surgical patients during each time interval was selected to estimate the droperidol use for each time period.
RESULTS: During the time period before the black box warning (July 1, 1998 to June 30, 2001), 2,321/139,932 patients (1.66%) had QT prolongation, TdP, or death within 48 h after surgery. We could identify no patients who clearly developed TdP before the black box warning. There was one patient for whom the cause of death could not positively be ruled out as due to TdP. In the time period after the black box warning (July 1, 2002 to June 30, 2005), 2,207 patients (1.46%) had documented QT prolongation, TdP, or death within 48 h after surgery, including only two cases (<0.1%) of TdP. The incidence of droperidol exposure was approximately 12% (exact 95% confidence interval, 7.3-18.3%) before the black box warning and 0% after placement of the black box warning on droperidol. Therefore, we estimate that approximately 16,791 patients (95% confidence interval, 10,173-25,607) were exposed to droperidol, none of whom experienced documented TdP.
CONCLUSIONS: This indicates that the Food and Drug Administration black box warning for low dose droperidol is excessive and unnecessary.
John H Shale, Christopher M Shale, William D Mastin
A review of the safety and efficacy of droperidol for the rapid sedation of severely agitated and violent patients.
J Clin Psychiatry. 2003 May;64(5):500-5.
Abstract/Text
BACKGROUND: Droperidol had become a standard treatment for sedating severely agitated or violent patients in both psychiatric and medical emergency departments. However, several recent articles have suggested that droperidol may have a quinidine-like effect similar to that of thioridazine in inducing dysrhythmia.
METHOD: In view of the recent U.S. Food and Drug Administration (FDA) position regarding the use of thioridazine, the authors reviewed the literature regarding droperidol and dysrhythmia in a MEDLINE search for the years 1960-2002 using the search terms droperidol, dysrhythmia, QTc interval, and sudden death as well as their own experience in using droperidol in a busy psychiatric emergency department. This review was done before the FDA's very recent and peremptory warning about droperidol.
RESULTS: The authors report that, in treating approximately 12,000 patients over the past decade, they have never experienced a clinically significant adverse dysrhythmic event using droperidol to sedate severely agitated or violent patients.
CONCLUSION: The authors conclude that, in clinical practice, droperidol is an extremely effective and safe method for treating severely agitated or violent patients. While in theory droperidol may prolong the QT interval to an extent similar to thioridazine, in clinical use there is no pattern of sudden deaths analogous to those that provoked the FDA warning about thioridazine.
Wayne A Ray, Cecilia P Chung, Katherine T Murray, Kathi Hall, C Michael Stein
Atypical antipsychotic drugs and the risk of sudden cardiac death.
N Engl J Med. 2009 Jan 15;360(3):225-35. doi: 10.1056/NEJMoa0806994.
Abstract/Text
BACKGROUND: Users of typical antipsychotic drugs have an increased risk of serious ventricular arrhythmias and sudden cardiac death. However, less is known regarding the cardiac safety of the atypical antipsychotic drugs, which have largely replaced the older agents in clinical practice.
METHODS: We calculated the adjusted incidence of sudden cardiac death among current users of antipsychotic drugs in a retrospective cohort study of Medicaid enrollees in Tennessee. The primary analysis included 44,218 and 46,089 baseline users of single typical and atypical drugs, respectively, and 186,600 matched nonusers of antipsychotic drugs. To assess residual confounding related to factors associated with the use of antipsychotic drugs, we performed a secondary analysis of users of antipsychotic drugs who had no baseline diagnosis of schizophrenia or related psychoses and with whom nonusers were matched according to propensity score (i.e., the predicted probability that they would be users of antipsychotic drugs).
RESULTS: Current users of typical and of atypical antipsychotic drugs had higher rates of sudden cardiac death than did nonusers of antipsychotic drugs, with adjusted incidence-rate ratios of 1.99 (95% confidence interval [CI], 1.68 to 2.34) and 2.26 (95% CI, 1.88 to 2.72), respectively. The incidence-rate ratio for users of atypical antipsychotic drugs as compared with users of typical antipsychotic drugs was 1.14 (95% CI, 0.93 to 1.39). Former users of antipsychotic drugs had no significantly increased risk (incidence-rate ratio, 1.13; 95% CI, 0.98 to 1.30). For both classes of drugs, the risk for current users increased significantly with an increasing dose. Among users of typical antipsychotic drugs, the incidence-rate ratios increased from 1.31 (95% CI, 0.97 to 1.77) for those taking low doses to 2.42 (95% CI, 1.91 to 3.06) for those taking high doses (P<0.001). Among users of atypical agents, the incidence-rate ratios increased from 1.59 (95% CI, 1 .03 to 2.46) for those taking low doses to 2.86 (95% CI, 2.25 to 3.65) for those taking high doses (P=0.01). The findings were similar in the cohort that was matched for propensity score.
CONCLUSIONS: Current users of typical and of atypical antipsychotic drugs had a similar, dose-related increased risk of sudden cardiac death.
2009 Massachusetts Medical Society
J Battaglia, S Moss, J Rush, J Kang, R Mendoza, L Leedom, W Dubin, C McGlynn, L Goodman
Haloperidol, lorazepam, or both for psychotic agitation? A multicenter, prospective, double-blind, emergency department study.
Am J Emerg Med. 1997 Jul;15(4):335-40.
Abstract/Text
Rapid tranquilization is a routinely practiced method of calming agitated psychotic patients by use of neuroleptics, benzodiazepines, or both in combination. Although several studies have examined the efficacy of the three approaches, none have compared these treatments in a prospective, randomized, double-blind, multicenter trial. Ninety-eight psychotic, agitated, and aggressive patients (73 men and 25 women) were prospectively enrolled during an 18-month period in emergency departments in five university or general hospitals. Patients were randomly assigned to receive intramuscular injections of lorazepam (2 mg), haloperidol (5 mg), or both in combination. Patients in each treatment group received 1 to 6 injections of the same study drug within 12 hours, based on clinical need. They were evaluated hourly after the first injection until at least 12 hours after the last. Efficacy was assessed on the Agitated Behavior Scale (ABS), a modified Brief Psychiatric Rating Scale (MBPRS), Clinical Global impressions (CGI) scale, and an Alertness Scale. Effective symptom reduction was achieved in each treatment group with significant (P < .01) mean decreases from baseline at every hourly ABS evaluation. Significant (P < .05) mean differences on the ABS (hour 1) and MBPRS (hours 2 and 3) suggest that tranquilization was most rapid in patients receiving the combination treatment. Study event incidence (side effects) did not differ significantly between treatment groups, although patients receiving haloperidol alone tended to have more extrapyramidal system symptoms. The superior results produced by the combination treatment support the use of lorazepam plus haloperidol as the treatment of choice for acute psychotic agitation.
Philip S Wang, Sebastian Schneeweiss, Jerry Avorn, Michael A Fischer, Helen Mogun, Daniel H Solomon, M Alan Brookhart
Risk of death in elderly users of conventional vs. atypical antipsychotic medications.
N Engl J Med. 2005 Dec 1;353(22):2335-41. doi: 10.1056/NEJMoa052827.
Abstract/Text
BACKGROUND: Recently, the Food and Drug Administration (FDA) issued an advisory stating that atypical antipsychotic medications increase mortality among elderly patients. However, the advisory did not apply to conventional antipsychotic medications; the risk of death with these older agents is not known.
METHODS: We conducted a retrospective cohort study involving 22,890 patients 65 years of age or older who had drug insurance benefits in Pennsylvania and who began receiving a conventional or atypical antipsychotic medication between 1994 and 2003. Analyses of mortality rates and Cox proportional-hazards models were used to compare the risk of death within 180 days, less than 40 days, 40 to 79 days, and 80 to 180 days after the initiation of therapy with an antipsychotic medication. We controlled for potential confounding variables with the use of traditional multivariate Cox models, propensity-score adjustments, and an instrumental-variable analysis.
RESULTS: Conventional antipsychotic medications were associated with a significantly higher adjusted risk of death than were atypical antipsychotic medications at all intervals studied (< or =180 days: relative risk, 1.37; 95 percent confidence interval, 1.27 to 1.49; <40 days: relative risk, 1.56; 95 percent confidence interval, 1.37 to 1.78; 40 to 79 days: relative risk, 1.37; 95 percent confidence interval, 1.19 to 1.59; and 80 to 180 days: relative risk, 1.27; 95 percent confidence interval, 1.14 to 1.41) and in all subgroups defined according to the presence or absence of dementia or nursing home residency. The greatest increases in risk occurred soon after therapy was initiated and with higher dosages of conventional antipsychotic medications. Increased risks associated with conventional as compared with atypical antipsychotic medications persisted in confirmatory analyses performed with the use of propensity-score adjustment and instrumental-variable estimation.
CONCLUSIONS: If confirmed, these results suggest that conventional antipsychotic medications are at least as likely as atypical agents to increase the risk of death among elderly persons and that conventional drugs should not be used to replace atypical agents discontinued in response to the FDA warning.
Copyright 2005 Massachusetts Medical Society.
