Intravenous Haloperidol Research Articles

Comparing the cardiorespiratory safety of parenteral olanzapine and benzodiazepines to parenteral haloperidol/droperidol and benzodiazepines in emergency department patients

IntroductionThis study sought to assess the cardiorespiratory safety of parenteral olanzapine and benzodiazepine combination treatment compared to parenteral droperidol or haloperidol and benzodiazepine combination treatment. Materials and methodsThis was a retrospective chart review conducted in adult emergency department patients who received intramuscular (IM) or intravenous (IV) droperidol, haloperidol, or olanzapine within one hour of IM or IV benzodiazepine. Patients were stratified into groups based on whether they received either olanzapine in combination with a benzodiazepine (n = 48) or droperidol or haloperidol in combination with a benzodiazepine (n = 48). ResultsPatients in each group had a decrease in their systolic blood pressure (SBP) after IM/IV olanzapine and IM/IV droperidol or haloperidol when used in combination with an IM/IV benzodiazepine ((Olanzapine + benzodiazepine (mmHg), median (IQR): Pre-SBP: 132 (117–151) vs. Post-SBP: 117 (99–131), p < 0.01) (Droperidol or haloperidol + benzodiazepine (mmHg), median (IQR): Pre-SBP: 138 (122–149) vs. Post-SBP: 106 (98–127), p < 0.01)). Both groups had similar percent SBP decreases post-combination treatment (Olanzapine + benzodiazepine (15.6 %) vs. Droperidol or haloperidol + benzodiazepine (15.2 %); p = 0.55). We did not observe any statistically significant between group differences for hypotension (Olanzapine + benzodiazepine: 1/48, 2.1 % vs. Droperidol or haloperidol + benzodiazepine: 3/48, 6.3 %; p = 0.62)), escalation in oxygen requirements (Olanzapine + benzodiazepine: 7/48, 14.6 %) vs. Droperidol or haloperidol + benzodiazepine: 5/48, 10.4 %; p = 0.76)), or intubation due to cardiorespiratory depression (Olanzapine + benzodiazepine: 0/0, 0 % vs. Droperidol or haloperidol + benzodiazepine: 0/0, 0 %; p = 1.00)). ConclusionThis study found decreases in SBP after administering parenteral olanzapine and parenteral droperidol or haloperidol in combination with a parenteral benzodiazepine. The percent change in SBP and the frequency of hypotensive episodes post-combination treatment were not different between groups. There were also no differences between groups in need of increased oxygen requirements post-combination treatment or need for intubation due to cardiorespiratory depression. This study suggests parenteral olanzapine in combination with a parenteral benzodiazepine may have comparable cardiorespiratory safety versus parenteral droperidol or haloperidol in combination with a parenteral benzodiazepine when treating agitation in the adult ED.

Long-term outcomes after treatment of delirium during critical illness with antipsychotics (MIND-USA): a randomised, placebo-controlled, phase 3 trial

Delirium is common during critical illness and is associated with long-term cognitive impairment and disability. Antipsychotics are frequently used to treat delirium, but their effects on long-term outcomes are unknown. We aimed to investigate the effects of antipsychotic treatment of delirious, critically ill patients on long-term cognitive, functional, psychological, and quality-of-life outcomes. This prespecified, long-term follow-up to the randomised, double-blind, placebo-controlled phase 3 MIND-USA Study was conducted in 16 hospitals throughout the USA. Adults (aged ≥18 years) who had been admitted to an intensive care unit with respiratory failure or septic or cardiogenic shock were eligible for inclusion in the study if they had delirium. Participants were randomly assigned-using a computer-generated, permuted-block randomisation scheme with stratification by trial site and age-in a 1:1:1 ratio to receive intravenous placebo, haloperidol, or ziprasidone for up to 14 days. Investigators and participants were masked to treatment group assignment. 3 months and 12 months after randomisation, we assessed survivors' cognitive, functional, psychological, quality-of-life, and employment outcomes using validated telephone-administered tests and questionnaires. This trial was registered with ClinicalTrials.gov, NCT01211522, and is complete. Between Dec 7, 2011, and Aug 12, 2017, we screened 20 914 individuals, of whom 566 were eligible and consented or had consent provided to participate. Of these 566 patients, 184 were assigned to the placebo group, 192 to the haloperidol group, and 190 to the ziprasidone group. 1-year survival and follow-up rates were similar between groups. Cognitive impairment was common in all three treatment groups, with a third of survivors impaired at both 3-month and 12-month follow-up in all groups. More than half of the surveyed survivors in each group had cognitive or physical limitations (or both) that precluded employment at both 3-month and 12-month follow-up. At both 3 months and 12 months, neither haloperidol (adjusted odds ratio 1·22 [95% CI 0·73-2.04] at 3 months and 1·12 [0·60-2·11] at 12 months) nor ziprasidone (1·07 [0·59-1·96] at 3 months and 0·94 [0·62-1·44] at 12 months) significantly altered cognitive outcomes, as measured by the Telephone Interview for Cognitive Status T score, compared with placebo. We also found no evidence that functional, psychological, quality-of-life, or employment outcomes improved with haloperidol or ziprasidone compared with placebo. In delirious, critically ill patients, neither haloperidol nor ziprasidone had a significant effect on cognitive, functional, psychological, or quality-of-life outcomes among survivors. Our findings, along with insufficient evidence of short-term benefit and frequent inappropriate continuation of antipsychotics at hospital discharge, indicate that antipsychotics should not be used routinely to treat delirium in critically ill adults. National Institutes of Health and the US Department of Veterans Affairs.

Antipsychotics and the QTc Interval During Delirium in the Intensive Care Unit

Antipsychotic medications, often prescribed for delirium in intensive care units (ICUs), may contribute to QTc interval prolongation. To determine whether antipsychotics increase the QTc interval in patients with delirium in the ICU. An a priori analysis of a randomized clinical trial in medical/surgical ICUs within 16 centers across the US was conducted. Participants included adults with delirium in the ICU with baseline QTc interval less than 550 ms. The study was conducted from December 2011 to August 2017. Data analysis was performed from April 25 to August 18, 2021. Patients were randomized 1:1:1 to intravenous haloperidol, ziprasidone, or saline placebo administered twice daily until resolution of delirium, ICU discharge, or 14 days. Twelve-lead electrocardiograms were used to measure baseline QTc before study drug initiation and telemetry was used to measure QTc before each subsequent dose of study drug. Unadjusted day-to-day changes in QTc were calculated and multivariable proportional odds regression was used to estimate the effects of antipsychotics vs placebo on next-day maximum QTc interval, adjusting for prespecified baseline covariates and potential interactions with sex. Safety end points, including the occurrence of torsade de pointes, were evaluated. All analyses were conducted based on the intention to treat principle. A total of 566 patients were randomized to haloperidol (n = 192), ziprasidone (n = 190), or placebo (n = 184). Median age was 60.1 (IQR, 51.4-68.7) years; 323 were men (57%). Baseline median QTc intervals across the groups were similar: haloperidol, 458.0 (IQR, 432.0-479.0) ms; ziprasidone, 451.0 (IQR, 424.0-472.0) ms; and placebo, 452.0 (IQR, 432.0-472.0) ms. From day 1 to day 2, median QTc changed minimally: haloperidol, -1.0 (IQR, -28.0 to 15.0) ms; ziprasidone, 0 (IQR, -23.0 to 20.0) ms; and placebo, -3.5 (IQR, -24.8 to 17.0) ms. Compared with placebo, neither haloperidol (odds ratio [OR], 0.95; 95% CI, 0.66-1.37; P = .78) nor ziprasidone (OR, 1.09; 95% CI, 0.75-1.57; P = .78) was associated with next-day QTc intervals. Effects were not significantly modified by sex (P = .41 for interaction). There were 2 occurrences of nonfatal torsade de pointes, both in the haloperidol group. Neither was associated with study drug administration. The findings of this trial suggest that daily QTc interval monitoring during antipsychotic use may have limited value in patients in the ICU with normal baseline QTc and few risk factors for QTc prolongation. ClinicalTrials.gov Identifier: NCT01211522.

Neutrophil-Lymphocyte Ratio in Patients With Acute Schizophrenia.

Introduction Schizophrenia symptom severity is linked to neuroinflammation. Certain blood cell indexes such as neutrophil-lymphocyte ratio (NLR) and neutrophil-albumin ratio (NAR) have been used as biomarkers in various diseases, including schizophrenia. In acute clinical practice, it is challenging to decide whether to provide intravenous antipsychotic treatment in some cases due to the lack of objective biomarkers of psychiatric symptoms. The NLR of individuals with schizophrenia is thought to be associated with disease severity, and changes in NLR may reflect a patient's response to antipsychotic treatment. We investigated the application of NLR as a biomarker for identifying acute severity and determining acute treatment response in patients withschizophrenia. Methods We retrospectively examined 251 inpatients diagnosed with schizophrenia and classified them according to treatment (intravenous haloperidol vs. oral antipsychotic medication during the acute phase) and investigated their NLR and NAR while receiving inpatient care. Results A total of 48 inpatients were given intravenous haloperidol to manage their acute symptoms; 208 were given oral antipsychotics. The intravenous haloperidol group experienced more severe symptoms, such as agitation and disorganized thinking, during the acute phase. Further, those who received intravenous haloperidol had significantly higher Clinical Global Impression-Severity (CGI-S) scores than the oral antipsychotic group. NLR and NAR were also significantly higher in the haloperidol intravenous group. Conclusion Elevated NLR and NAR could be easily measured in patients with psychomotor agitation who should be treated at any facility. Further, they are useful biomarkers for determining disease severity and the effects of treatment on psychomotor excitement in patients who require intravenous haloperidol.

Risk Stratification of QTc Prolongation in Critically Ill Patients Receiving Antipsychotics for the Management of Delirium Symptoms.

Patients experiencing significant agitation or perceptual disturbances related to delirium in an intensive care setting may benefit from short-term treatment with an antipsychotic medication. Some antipsychotic medications may prolong the QTc interval, which increases the risk of potentially fatal ventricular arrhythmias. In this targeted review, we describe the evidence regarding the relationships between antipsychotic medications and QTc prolongation and practical methods for monitoring the QTc interval and mitigating arrhythmia risk. Searches of PubMed and Cochrane Library were performed to identify studies, published before February 2023, investigating the relationships between antipsychotic medications and QTc prolongation or arrhythmias. Most antipsychotic medications commonly used for the management of delirium symptoms (eg, intravenous haloperidol, olanzapine, quetiapine) cause a moderate degree of QTc prolongation. Among other antipsychotics, those most likely to cause QTc prolongation are iloperidone and ziprasidone, while aripiprazole and lurasidone appear to have minimal risk for QTc prolongation. Genetic vulnerabilities, female sex, older age, pre-existing cardiovascular disease, electrolyte abnormalities, and non-psychiatric medications also increase the risk of QTc prolongation. For individuals at risk of QTc prolongation, it is essential to measure the QTc interval accurately and consistently and consider medication adjustments if needed. Antipsychotic medications are one of many risk factors for QTc prolongation. When managing agitation related to delirium, it is imperative to assess an individual patient's risk for QTc prolongation and to choose a medication and monitoring strategy commensurate to the risks. In intensive care settings, we recommend regular ECG monitoring, using a linear regression formula to correct for heart rate. If substantial QTc prolongation (eg, QTc > 500 msec) is present, a change in pharmacologic treatment can be considered, though a particular medication may still be warranted if the risks of discontinuation (eg, extreme agitation, removal of invasive monitoring devices) outweigh the risks of arrhythmias. This review aims to summarize the current literature on relationships between antipsychotic medications and QTc prolongation and to make practical clinical recommendations towards the approach of antipsychotic medication use for the management of delirium-related agitation and perceptual disturbances in intensive care settings.

Efficacy of haloperidol to decrease the burden of delirium in adult critically ill patients: the EuRIDICE randomized clinical trial

BackgroundThe role of haloperidol as treatment for ICU delirium and related symptoms remains controversial despite two recent large controlled trials evaluating its efficacy and safety. We sought to determine whether haloperidol when compared to placebo in critically ill adults with delirium reduces days with delirium and coma and improves delirium-related sequelae.MethodsThis multi-center double-blind, placebo-controlled randomized trial at eight mixed medical-surgical Dutch ICUs included critically ill adults with delirium (Intensive Care Delirium Screening Checklist ≥ 4 or a positive Confusion Assessment Method for the ICU) admitted between February 2018 and January 2020. Patients were randomized to intravenous haloperidol 2.5 mg or placebo every 8 h, titrated up to 5 mg every 8 h if delirium persisted until ICU discharge or up to 14 days. The primary outcome was ICU delirium- and coma-free days (DCFDs) within 14 days after randomization. Predefined secondary outcomes included the protocolized use of sedatives for agitation and related behaviors, patient-initiated extubation and invasive device removal, adverse drug associated events, mechanical ventilation, ICU length of stay, 28-day mortality, and long-term outcomes up to 1-year after randomization.ResultsThe trial was terminated prematurely for primary endpoint futility on DSMB advice after enrolment of 132 (65 haloperidol; 67 placebo) patients [mean age 64 (15) years, APACHE IV score 73.1 (33.9), male 68%]. Haloperidol did not increase DCFDs (adjusted RR 0.98 [95% CI 0.73–1.31], p = 0.87). Patients treated with haloperidol (vs. placebo) were less likely to receive benzodiazepines (adjusted OR 0.41 [95% CI 0.18–0.89], p = 0.02). Effect measures of other secondary outcomes related to agitation (use of open label haloperidol [OR 0.43 (95% CI 0.12–1.56)] and other antipsychotics [OR 0.63 (95% CI 0.29–1.32)], self-extubation or invasive device removal [OR 0.70 (95% CI 0.22–2.18)]) appeared consistently more favorable with haloperidol, but the confidence interval also included harm. Adverse drug events were not different. Long-term secondary outcomes (e.g., ICU recall and quality of life) warrant further study.ConclusionsHaloperidol does not reduce delirium in critically ill delirious adults. However, it may reduce rescue medication requirements and agitation-related events in delirious ICU patients warranting further evaluation.Trial registration: ClinicalTrials.gov (#NCT03628391), October 9, 2017.

Intravenous haloperidol and cocaine alter the distribution of T CD3+ CD4+ , non-T/NK and NKT cells in rats.

The modulation of dopamine transmission evokes strong behavioural effects that can be achieved by commonly used psychoactive drugs such as haloperidol or cocaine. Cocaine non-specifically increases dopamine transmission by blocking dopamine active transporter (DAT) and evokes behavioural arousal, whereas haloperidol is a non-specific D2-like dopamine receptor antagonist with sedative effects. Interestingly, dopamine has been found to affect immune cells in addition to its action in the central nervous system. Here, we address the possible interactions between haloperidol and cocaine and their effects on both immune cells and behaviour in freely moving rats. We use an intravenous model of haloperidol and binge cocaine administration to evaluate the drugs' impact on the distribution of lymphocyte subsets in both the peripheral blood and the spleen. We assess the drugs' behavioural effects by measuring locomotor activity. Cocaine evoked a pronounced locomotor response and stereotypic behaviours, both of which were completely blocked after pretreatment with haloperidol. The results suggest that blood lymphopenia, which was induced by haloperidol and cocaine (except for natural killer T cells), is independent of D2-like dopaminergic activity and most likely results from the massive secretion of corticosterone. Haloperidol pretreatment prevented the cocaine-induced decrease in NKT cell numbers. Moreover, the increased systemic D2-like dopaminergic activity after cocaine administration is a significant factor in retaining T CD3+ CD4+ lymphocytes and non-T/NK CD45RA+ cells in the spleen.

Non-opioid Intravenous Drugs for Pain Management in Patients Presenting with Acute Migraine Pain in the Emergency Department: A Comprehensive Literature Review.

Migraine is one of the most common causes of disability worldwide and the sixth cause of loss of life years due to disability. Migraine is reported mainly in young and middle-aged people, so it can cause a person to face many problems in doing daily tasks. The emergency department annually accepts 1.2 million patients with migraine. Therefore, timely diagnosis of the disease, knowledge of valuable drugs in an emergency, knowing how to use them, and finally, early treatment can play an essential and decisive role in improving patients' symptoms and reducing the disability caused by the disease. An essential and valuable drug category in the emergency department to manage pain is non-opioid intravenous (IV) drugs. Therefore, this study aimed to evaluate non-opioid IV drugs to manage pain in patients with acute migraines in the emergency department. This study conducted a comprehensive literature review to access the latest scientific studies and documents using keywords (acute migraine, non-opioid IV drugs, pain management) in reliable databases such as PubMed, Scopus, Web of Science, Cochrane, and Google Scholar. We reviewed 87 articles, 53 of which were evaluated and compared. A review study considers intravenous acetaminophen as a suitable option for the first-line treatment of acute migraine in the emergency department if the patient does not tolerate aspirin and non-steroidal anti-inflammatory drugs (NSAIDs). Various studies have obtained positive effects of NSAIDs and dihydroergotamine (DHE) in treating acute migraine. Prescribing anti-dopaminergic drugs can effectively reduce associated symptoms such as nausea and vomiting. Dexamethasone and magnesium sulfate are effective in preventing migraine and severe attacks. Intravenous sodium valproate is effective in moderate to severe migraine attacks or treatment-resistant migraines. In the emergency department, prescribing intravenous haloperidol, lidocaine, and propofol can help manage migraine and improve other associated symptoms, such as nausea or vomiting. Non-opioid IV drugs are essential to manage pain and improve other migraine symptoms in the emergency setting. Knowing the above drugs and their optimal use has a decisive role in managing patients with acute migraine in the emergency department.

Haloperidol for the Treatment of Delirium in ICU Patients

BackgroundHaloperidol is frequently used to treat delirium in patients in the intensive care unit (ICU), but evidence of its effect is limited.MethodsIn this multicenter, blinded, placebo-controlled trial, we randomly assigned adult patients with delirium who had been admitted to the ICU for an acute condition to receive intravenous haloperidol (2.5 mg 3 times daily plus 2.5 mg as needed up to a total maximum daily dose of 20 mg) or placebo. Haloperidol or placebo was administered in the ICU for as long as delirium continued and as needed for recurrences. The primary outcome was the number of days alive and out of the hospital at 90 days after randomization.ResultsA total of 1000 patients underwent randomization; 510 were assigned to the haloperidol group and 490 to the placebo group. Among these patients, 987 (98.7%) were included in the final analyses (501 in the haloperidol group and 486 in the placebo group). Primary outcome data were available for 963 patients (97.6%). At 90 days, the mean number of days alive and out of the hospital was 35.8 (95% confidence interval [CI], 32.9 to 38.6) in the haloperidol group and 32.9 (95% CI, 29.9 to 35.8) in the placebo group, with an adjusted mean difference of 2.9 days (95% CI, −1.2 to 7.0) (P=0.22). Mortality at 90 days was 36.3% in the haloperidol group and 43.3% in the placebo group (adjusted absolute difference, −6.9 percentage points [95% CI, −13.0 to −0.6]). Serious adverse reactions occurred in 11 patients in the haloperidol group and in 9 patients in the placebo group.ConclusionsAmong patients in the ICU with delirium, treatment with haloperidol did not lead to a significantly greater number of days alive and out of the hospital at 90 days than placebo. (Funded by Innovation Fund Denmark and others; AID-ICU ClinicalTrials.gov number, NCT03392376; EudraCT number, 2017-003829-15.)

Intravenous Haloperidol Has a Limited Role in the Modern Emergency Department

Haloperidol is a butyrophenone-class antipsychotic agent with more than 6 decades of clinical use across most disciplines of medicine. In the emergency department (ED), haloperidol is commonly used to facilitate chemical sedation of acutely agitated patients, ameliorate symptoms of nausea and vomiting, reduce hallucinations and delirium associated with ethanol withdrawal, and more. Only the intramuscular (IM) route is Food and Drug Administration (FDA)-approved for parenteral use, but the same formulation has been used intravenously (IV) for many years.

Haloperidol vs. Dexamethasone in Lowering Postoperative Nausea and Vomiting and Pain in Adult After Laparoscopy

Abstract Background: The incidence of PONV (Postoperative Nausea and Vomiting) and pain are still one of the most common symptoms of post-surgery and prophylaxis to reduce the event is needed. Therefore, we wanted to know the effectiveness of 1 mg intravenous haloperidol compared to 5 mg intravenous dexamethasone to prevent the occurrence of nausea and vomiting and to control pain in adult patients after laparoscopic surgery. Materials and Methods: Eighty subjects (n = 40 for each group) scheduled for laparoscopic-assisted surgery were enrolled in a randomized double-blind clinical trial. One milligram intravenous haloperidol was given one hour before the end of surgery, while 5 mg intravenous dexamethasone was given right after induction. The occurrence of PONV and VAS pain score were recorded. Results: This study showed a significant difference in the incidence of nausea between haloperidol and dexamethasone at 2–6 hours (5% vs 25%, P = 0.012), 6–12 hours (10% vs 24%, P = 0.012), and 12–24 hours (12.5% vs 60%, P &lt; 0.001) after laparoscopic surgery. The incidence of vomiting after laparoscopic surgery between two groups was not significantly different (P &gt; 0,05). However, haloperidol group resulted in lower VAS pain score at every postoperative period with statistically significant result. Conclusion: The administration of 1 mg intravenous haloperidol is significantly better than 5 mg intravenous dexamethasone to prevent the occurrence of nausea and to lower the pain, but not significantly different to prevent the incidence of postoperative vomiting in adult patients after laparoscopic surgery.

Pharmacokinetics of Haloperidol in Critically Ill Patients: Is There an Association with Inflammation?

Haloperidol is considered the first-line treatment for delirium in critically ill patients. However, clinical evidence of efficacy is lacking and no pharmacokinetic studies have been performed in intensive care unit (ICU) patients. The aim of this study was to establish a pharmacokinetic model to describe the PK in this population to improve insight into dosing. One hundred and thirty-nine samples from 22 patients were collected in a single-center study in adults with ICU delirium who were treated with low-dose intravenous haloperidol (3–6 mg per day). We conducted a population pharmacokinetic analysis using Nonlinear Mixed Effects Modelling (NONMEM). A one-compartment model best described the data. The mean population estimates were 51.7 L/h (IIV 42.1%) for clearance and 1490 L for the volume of distribution. The calculated half-life was around 22 h (12.3–29.73 h) for an average patient. A negative correlation between C-Reactive Protein (CRP) and haloperidol clearance was observed, where clearance decreased significantly with increasing CRP up to a CRP concentration of 100 mg/L. This is the first step towards haloperidol precision dosing in ICU patients and our results indicate a possible role of inflammation.

Comparison of Haloperidol versus Midazolam for Prevention of Sevoflurane Emergence Agitation in Pediatric patients undergoing Inguinal Surgeries

Abstract Background Emergence agitation (EA) in children early after sevoflurane anaesthesia is a common postoperative problem, with incidence ranging up to 80%, It is characterized by behavior that can include crying, disorientation, excitation and delirium, several drugs have been tried in this regard including but not limited to propofol, midazolam, ketamine and ketorolac among other drugs. Aim of the Work To compare the effect of intravenous Midazolam vs intravenous Haloperidol &amp; in prevention of Sevoflurane Emergence Agitation in pediatric patients undergoing Inguinal Surgeries. Patients and Methods This prospective randomized study was done after approval of institutional ethics committee in Ain Shams university Hospitals for 6 months and obtaining an informed written consent from parents. It was designed to include sixty-two pediatric patients, aged 3 to 12 years of both genders, with physical status ASA Ι and ASA ІІ. All surgical procedures were elective of an expected duration of 30 - 60 minutes e.g. inguinal hernia repair, hydrocele, orcheopexy under general anesthesia and caudal block to relief pain. All operations were performed in supine position. Results Our study was applied on age group between 3- 12 years old Haloperidol was associated with 24% EA and was also associated with significant delay in eye opening and time till discharge from PACU when compared to Midazolam. Conclusion I.V Midazolam is more efficient than I.V Haloperidol for prevention of Sevoflurane Emergence agitation in pediatric patients undergoing inguinal surgeries.

AGITATED, ALTERED, AND ELONGATED: THE RISKS OF DIPHENHYDRAMINE OVERDOSE

TOPIC: Critical Care TYPE: Medical Student/Resident Case Reports INTRODUCTION: Overdose has become a leading cause of injury-related death in the United States. Rapid recognition of a toxidrome is vital in determining management. CASE PRESENTATION: A young, unknown female was brought to the ED after being found agitated and combative. Evaluation was notable for tachycardia, mydriasis and diaphoresis. She received intramuscular diphenhydramine (DPH), haloperidol and lorazepam for agitation.She developed a wide QRS complex with polymorphic ventricular tachycardia (VT) concerning for Torsades de pointes, terminated by precordial thump. She was intubated for airway protection. Magnesium and sodium bicarbonate (NaHCO) pushes were administered for sustained monomorphic VT with return to sinus tachycardia. Electrocardiogram was significant for prolonged QTc of 607ms and QRS >150ms. Initial toxicology was negative for acetaminophen, salicylate and ethanol.NaHCO infusion with goal pH 7.5 to maintain a narrow QRS was started. She had persistently prolonged QT interval. Overdrive transcutaneous pacing was unsuccessful, so isoproterenol (IPN) infusion was started. NaHCO and IPN infusions were discontinued at 48 hours with no further arrhythmias. Extended toxicology screen was positive for DPH. On extubation, she endorsed consumption of >1.25g DPH. DISCUSSION: Classic anticholinergic symptoms of tachycardia, mydriasis and delirium are also the toxidrome for DPH overdose. Severe toxicity is observed after ingestion of >1.0g (1). Cardiac toxicity is exhibited as widening of QRS and QTc intervals (1-3). Similar to TCA overdose, QRS widening is manifested from blockade of the fast-closing myocardial sodium channels (2-3). Treatment for QRS widening with NaHCO is anecdotally recommended (2-3). In this case, bolus and infusion of NaHCO successfully shortened the patient's QRS duration. One case report suggested using lipid emulsion therapy(3); however, DPH intoxication was not suspected initially thereby limiting its use. Since presenting symptoms of DPH and anticholinergic toxicity overlap, physostigmine must be avoided due to QRS prolonging effects (2). This case reminds of cautious administration of the "B52" cocktail for agitated patients. The use of intravenous DPH, haloperidol and lorazepam can be used to calm acutely agitated or aggressive patients; yet, it should be avoided with unknown ingestions.Further, QT prolongation and polymorphic VT can result from DPH's ability to weakly block the delayed rectifier potassium channels (2). Traditionally resolving this includes overdrive pacing and magnesium supplementation, which were administered in this case. However, failed overdrive transcutaneous pacing led to IPN infusion to induce tachycardia-associated QTc shortening. CONCLUSIONS: High suspicion and familiarity with toxidromes can lead to early diagnosis and intervention for critically ill patients presenting with agitated altered mental status. REFERENCE #1: Radovanovic D, Meier PJ, Guirguis M, Lorent JP, Kupferschmidt H. Dose-dependent toxicity of diphenhydramine overdose. Hum Exp Toxicol. 2000 Sep;19(9):489-95. doi: 10.1191/096032700671040438 REFERENCE #2: Jang DH, Manini AF, Trueger NS, et al. Status epilepticus and wide-complex tachycardia secondary to diphenhydramine overdose. Clin Toxicol (Phila). 2010;48(9):945-948. doi:10.3109/15563650.2010.527850 REFERENCE #3: Abdi A, Rose E, Levine M. Diphenhydramine overdose with intraventricular conduction delay treated with hypertonic sodium bicarbonate and i.v. lipid emulsion. West J Emerg Med. 2014;15(7):855-858. doi:10.5811/westjem.2014.8.23407 DISCLOSURES: No relevant relationships by Joy Ayyoub, source=Web Response No relevant relationships by Lauren Catalano, source=Web Response No relevant relationships by Sydney Emerson, source=Web Response No relevant relationships by Shahrzad Zonoozi, source=Web Response

Assessment and Management of Delirium in the Pediatric Intensive Care Unit: A Review.

Many critically ill patients suffer from delirium which is associated with significant morbidity and mortality. There is a paucity of data about the incidence, symptoms, or treatment of delirium in the pediatric intensive care unit (PICU). Risk factors for delirium are common in the PICU including central nervous system immaturity, developmental delay, mechanical ventilation, and use of anticholinergic agents, corticosteroids, vasopressors, opioids, or benzodiazepines. Hypoactive delirium is the most common subtype in pediatric patients; however, hyperactive delirium has also been reported. Various screening tools are validated in the pediatric population, with the Cornell Assessment of Pediatric Delirium (CAPD) applicable to the largest age range and able to detect signs and symptoms consistent with both hypo- and hyperactive delirium. Treatment of delirium should always include identification and reversal of the underlying etiology, reserving pharmacologic management for those patients without symptom resolution, or with significant impact to medical care. Atypical antipsychotics (olanzapine, quetiapine, and risperidone) should be used first-line in patients requiring pharmacologic treatment owing to their apparent efficacy and low incidence of reported adverse effects. The choice of atypical antipsychotic should be based on adverse effect profile, available dosage forms, and consideration of medication interactions. Intravenous haloperidol may be a potential treatment option in patients unable to tolerate oral medications and with significant symptoms. However, given the high incidence of serious adverse effects with intravenous haloperidol, routine use should be avoided. Dexmedetomidine should be used when sedation is needed and when clinically appropriate, given the positive impact on delirium. Additional well-designed trials assessing screening and treatment of PICU delirium are needed.

Delirium in the NICU: Risk or Reality?

Delirium is a frequent complication of critical illness in adult and pediatric populations and is associated with significant morbidity and mortality. Little is known about the incidence, risk, symptoms, or treatment of delirium in the NICU. Only 4 cases of NICU delirium have been reported, but many pediatric studies include infants. The Cornell Assessment of Pediatric Delirium tool has been validated in neonatal and infant populations for identification of delirium. Initial treatment should focus on identification and reversal of the cause, with pharmacologic management reserved for patients with symptoms that do not resolve or that significantly impact medical care. Routine use of intravenous haloperidol should be avoided because of the high incidence of serious adverse effects, but it may be considered in patients with significant symptoms who are unable to take oral medications. Atypical antipsychotics (olanzapine, quetiapine, and risperidone) appear to be efficacious with a low incidence of adverse effects. Risperidone has weight-based dosing and a liquid dosage form available, making it a good option for use in the NICU. Additional data from large cohorts of NICU patients routinely screened for delirium, and treated as indicated, are needed.

A Retrospective Comparison of the Effectiveness and Safety of Intravenous Olanzapine Versus Intravenous Haloperidol for Agitation in Adult Intensive Care Unit Patients.

Intravenous (IV) olanzapine could be an alternative to first-generation antipsychotics for the management of agitation in intensive care unit (ICU) patients. We compared the effectiveness and safety of IV olanzapine to IV haloperidol for agitation management in adult patients in the ICU at a tertiary academic medical center. A retrospective cohort study was conducted. The primary outcome was the proportion of patients who achieved a Richmond Agitation Sedation Scale (RASS) score of < +1 within 4 hours of IV olanzapine or IV haloperidol administration. Secondary outcomes included the proportion of patients who required rescue medications for agitation within 4 hours of initial IV olanzapine or IV haloperidol administration, incidence of adverse events and ICU length of stay. In the 192 patient analytic cohort, there was no difference in the proportion of patients who achieved a RASS score of < +1 within 4 hours of receiving IV olanzapine or IV haloperidol (49% vs. 42%, p = 0.31). Patients in the IV haloperidol group were more likely to receive rescue medications (28% vs 55%, p < 0.01). There was no difference in the incidence of respiratory events or hypotension between IV olanzapine and IV haloperidol. Patients in the IV olanzapine group experienced more bradycardia (11% vs. 3%, p = 0.04) and somnolence (9% vs. 1%, p = 0.02) compared to the IV haloperidol group. Patients in the IV olanzapine group had a longer median ICU length of stay (7.5 days vs. 5 days, p = 0.04). In this retrospective cohort study, there was no difference in the effectiveness of IV olanzapine compared to IV haloperidol for the management of agitation. IV olanzapine was associated with an increased incidence of bradycardia and somnolence.

Intravenous haloperidol for the treatment of intractable vomiting, cyclical vomiting, and gastroparesis.

Intravenous haloperidol for the treatment of intractable vomiting, cyclical vomiting, and gastroparesis.

Intravenous Haloperidol Versus Ondansetron for Cannabis Hyperemesis Syndrome (HaVOC): A Randomized, Controlled Trial

Little is known about the cause or optimal treatment of hyperemesis in habitual cannabis users. Anecdotal evidence supports the use of haloperidol over traditional antiemetics for this newly recognized disorder. We compare haloperidol with ondansetron for cannabis hyperemesis syndrome. We randomized cannabis users with active emesis to either haloperidol (with a nested randomization to either 0.05 or 0.1 mg/kg) or ondansetron 8 mg intravenously in a triple-blind fashion. The primary outcome was the reduction from baseline in abdominal pain and nausea (each measured on a 10-cm visual analog scale) at 2 hours after treatment. Although the trial allowed for crossover, the primary analysis used only the first treatment period because few subjects crossed over. We enrolled 33 subjects, of whom 30 (16 men, aged 29 years [SD 11 years] using 1.5 g/day [SD 0.9 g/day] since age 19 years [SD 2 years]) received at least 1 treatment (haloperidol 13, ondansetron 17). Haloperidol at either dose was superior to ondansetron (difference 2.3 cm [95% confidence interval 0.6 to 4.0 cm]; P=.01), with similar improvements in both pain and nausea, as well as less use of rescue antiemetics (31% versus 59%; difference -28% [95% confidence interval -61% to 13%]) and shorter time to emergency department (ED) departure (3.1 hours [SD 1.7] versus 5.6 hours [SD 4.5]; difference 2.5 hours [95% confidence interval 0.1 to 5.0 hours]; P=.03). There were 2 return visits for acute dystonia, both in the higher-dose haloperidol group. In this clinical trial, haloperidol was superior to ondansetron for the acute treatment of cannabis-associated hyperemesis. The efficacy of haloperidol over ondansetron provides insight into the pathophysiology of this now common diagnosis in many EDs.

Efficacy of halopeRIdol to decrease the burden of Delirium In adult Critically ill patiEnts (EuRIDICE): study protocol for a prospective randomised multi-centre double-blind placebo-controlled clinical trial in the Netherlands

IntroductionDelirium in critically ill adults is associated with prolonged hospital stay, increased mortality and greater cognitive and functional decline. Current practice guideline recommendations advocate the use of non-pharmacological strategies to...