Authors: Etimbuk Umana, James Foley, Andrew Patton, Jeffery Mulcaire, Marcus Jee, Stephen Sheridan / Editors: Rajesh Chatha, Robert Hirst / Codes: CAP30, CAP4, HAP29, HAP3, SLO10 / Published: 17/06/2021
The aim of TERN’s Top Papers is to highlight the top emergency care related papers for emergency physicians. This month is brought to you by the team at Irish Trainee Emergency Research Network (ITERN). This was led by the ITERN lead Etimbuk Umana. They have reviewed over 1000 papers from across the globe over the past twelve months, analysed them and selected their top papers.
The theme this month is toxicology and psychiatry. We hope these synopses will stimulate you to read the full articles and inform your practice.
Randomized Double-blind Trial of Intramuscular Droperidol, Ziprasidone, and Lorazepam for Acute Undifferentiated Agitation in the Emergency Department1
This study compared intramuscular (IM) droperidol to zisprasidone and lorazepam in patients presenting with acute agitation in the emergency department (ED).
This was a single centre prospective, randomized, double-blind trial of adults (>18 years) with acute undifferentiated agitation requiring treatment in the ED between 2004 and 2005.
A convenience sample of patients were randomized to receive 5 mg of droperidol, 10 mg of ziprasidone, 20 mg of ziprasidone, or 2 mg of lorazepam intramuscularly. The primary outcome was the proportion of patients adequately sedated (AMSS ≤ 0) at 15 minutes. The secondary outcomes were need for rescue sedation, ED length of stay and respiratory depression.
115 patients were enrolled to the study with a median age of 40 years (range 26–52) with the majority presenting with alcohol intoxication. Baseline AMSS scores were similar between groups. Adequate sedation at 15 minutes was achieved in 64% of patients with droperidol. Pairwise comparison revealed that 20 mg of ziprasidone was 39% (95% confidence interval [CI] = 3%–54%) less effective, and Lorazepam 2mg was 33% (95% CI 8%–58%) less effective. There was no significant difference between the groups in terms of rescue medication. Respiratory depression was significantly lower (p=0.04) lower in droperidol compared to ziprasidone and lorazepam.
The study has several limitations which make it less generalisable to UK practice. The study is a single US centre study. Data collection was completed 16 years ago because the authors were too busy to publish in 2005 and were spurred on by a change in FDA guidance. This means the study was performed before the emergence of novel psychoactive drugs. Droperidol is not routinely used in the UK and Irish EDs, however it has been shown to have similar effectiveness to Haloperidol intramusularly2. In addition, it was a convenience sample, the age range was relatively young for a sample of patients with undifferentiated agitation, and the majority was secondary to alcohol intoxication (76%) which also suggest that there may have been a degree of selection bias.
This study suggests that droperidol is safe and effective compared to ziprasidone and lorazepam in the management of acute agitation.
- Martel ML, Driver BE, Miner JR, Biros MH, Cole JB. Randomized Double-blind Trial of Intramuscular Droperidol, Ziprasidone, and Lorazepam for Acute Undifferentiated Agitation in the Emergency Department. Acad Emerg Med. 2021 Apr;28(4):421-434. doi: 10.1111/acem.14124. Epub 2020 Oct 5. PMID: 32888340.
- Calver L, Drinkwater V, Gupta R, Page CB, Isbister GK. Droperidol v. haloperidol for sedation of aggressive behaviour in acute mental health: randomised controlled trial. Br J Psychiatry. 2015 Mar;206(3):223-8. doi: 10.1192/bjp.bp.114.150227. Epub 2014 Nov 13. PMID: 25395689.
Economic Evaluation of The Emergency Department After Implementation of an Emergency Psychiatric Assessment, Treatment and Healing Unit3
The aim of this study was the determine the impact of an Emergency Psychiatric Assessment, Treatment and Healing (EmPATH) Unit on ED revenue, ED boarding time and ED length of stay (LOS) for psychiatric and non-psychiatric patients.
This was a before-and-after economic evaluation of a single centre ED with a purpose built 12 bed EmPATH unit, staffed with psychiatric nurses, nursing assistants, social workers, and providers. After implementation of the unit, patients were redirected post ED clinician assessment to the EmPATH unit for psychiatric treatment following being ‘medically cleared for transfer’ Aggressive or violent patients remained in the ED.
A pre-EmPATH and post-EmPATH study periods were defined with the study running for the same period, 1 year apart.
There were 766 patients transferred to the EmPATH during the study period representing 3.3% of all attendances. The ED generated an estimated additional $861,065 annually post-EmPATH.
The median (IQR) boarding time for psychiatric patients in ED decreased from 212 (119–563) minutes to 152 (86–307) minutes and the median (IQR) LOS for psychiatric patients decreased from 351 (204–631) minutes to 334 (212–517) minutes post EmPATH implementation. This was a slight increase in boarding time and LOS for non-psychiatric patients.
Despite an 8.2% increase in psychiatric presentations post-EmPATH (maybe as a result of the better care received) the number of admissions to inpatient psychiatry decreased by 40% as it better treated patients who did not require inpatient care but were not safe for discharge from the ED. Interestingly this paper suggests that this is was an unforeseen disadvantage due to loss of revenue but in the UK and Ireland this would probably be the most compelling argument for such a unit!
An acute psychiatric unit can reduce ED boarding times and length of stay for patients presenting with mental health emergencies whilst reducing the number of inpatient pschiatric admissions.
3. Stamy C, Shane DM, Kannedy L, Van Heukelom P, Mohr NM, Tate J, Montross K, Lee S. Economic Evaluation of the Emergency Department After Implementation of an Emergency Psychiatric Assessment, Treatment, and Healing Unit. Acad Emerg Med. 2021 Jan;28(1):82-91. doi: 10.1111/acem.14118. Epub 2020 Sep 28. PMID: 32869891.
Ketamine for acute suicidality in the emergency department: A systematic review4
Acute mental health is a public health epidemic with an estimated 500,000 patients presenting to EDs in the USA expressing suicidal ideation (SI). This is a vulnerable patient cohort and currently there are no recommended medications to alleviate active suicidality in EDs. Ketamine, a NMDA agonist has been suggested previously to be efficacious in treatment-resistant depression but to date, there is limited knowledge of the usage of ketamine for the treatment of SI.
This systematic review involved two independent authors screening for articles using the MESH terms: “ketamine”, “emergency department”, “emergency room”, “suicidality” and “suicidal ideation”. Studies not based in an ED setting or that focussed primarily on depressive disorders were excluded. Three studies with a total of 61 actively-treated patients were identified using the search strategy. One study attempted randomised, double blind assessments but stopped early after uncertainty in data recording (n=10), one was an uncontrolled single blind trial (n=49), and one was a double-blinded RCT (n=19).
These studies used 0.2mg/kg of ketamine intravenously and measured a change of symptoms over various timepoints post administration using a scale for SI. All studies demonstrated some evidence of initial improvement in symptoms in the first two hours post ketamine administration although the degree of efficacy varied, but not a significant reduction in SI thereafter. No adverse events were reported in any study. In the two studies that used control groups, and SI improved in these groups without pharmacological intervention.
The studies had a number of imitations. They were small single centre studies, and in addition all studies excluded patient with a history of substance abuse. Two excluded patients with co-occurring psychiatric disorder and the other excluded all patients who had taken any medication 2 weeks prior. Therefore, this is not representative of the typical ED population presenting with suicidal ideation!
There is no “quick fix” for those expressing suicidal ideation in the ED. This paper provides weak evidence for ketamine hastening symptom relief, however there is insufficient evidence that suggests benefit over non-pharmacological strategies or the simple passage of time for eliminating suicidal thoughts.
4. Maguire L, Bullard T, Papa L. Ketamine for acute suicidality in the emergency department: A systematic review. Am J Emerg Med. 2021 May;43:54-58. doi: 10.1016/j.ajem.2020.12.088. Epub 2021 Jan 14. PMID: 33524683.
Pediatric somatization in the emergency department: assessing missed opportunities for early management5
This was a retrospective cross-sectional study of presentations by 516-year-olds to a quaternary level paediatric emergency department in Canada with an annual attendance of 50,000. The aim was to estimate the potential hidden burden of somatisation in the paediatric ED.
From a list of 300 randomly generated visits from a 12-month period, they sampled 193 charts applying exclusion criteria to meet their calculated sample size of 150 patients.
The charts were reviewed by a paediatric psychiatry fellow and an adolescent medicine specialist (paediatrician) categorising the somatisation status of the presentations as “probable”, “unclear” (possible) or unlikely.
They assessed 3.3% (95% CI 0.5–6.2) of presentations as probably having a somatisation component; 13.3% as possible but unclear (95% CI 8.0–18.8) and 83.3% (95% CI 77.4–89.3) of visits as unlikely.
Symptoms ongoing for more than one 1 month (OR = 10.5; 95% CI 2.4–46.5) or receiving multiple negative diagnostic tests (OR = 20.9; 95% CI 5.1–86.4) significantly increased the likelihood of ‘probable’ or ‘possible’ somatisation case categorisation.
When assessing paediatric patients, especially with symptoms >1 month duration and negative diagnostic tests, it is important to consider potential somatisation to ensure patients receive appropriate care and avoid unnecessary diagnostic testing and treatment plans.
5. Virk P, Vo DX, Ellis J, Doan Q. Pediatric somatization in the emergency department: assessing missed opportunities for early management. CJEM. 2020 May;22(3):331-337. doi: 10.1017/cem.2019.477. PMID: 32037998.”
Pulmonary Complications of Opioid Overdose Treated with Naloxone6
Pulmonary complications including noncardiogenic pulmonary oedema, aspiration pneumonia and aspiration pneumonitis are frequently reported after opioid overdose.
This retrospective, observational, cross-sectional study looking at patients in the City of Pittsburgh who received naloxone in the out-of-hospital setting and subsequently transported to emergency departments (EDs).
The aim of this paper was to determine whether administration of higher doses of naloxone in the treatment of opioid overdose is associated with increased pulmonary complications.
The primary outcome was a composite outcome for the presence of pulmonary oedema, aspiration pneumonia or aspiration pneumonitis identified on radiological imaging or diagnosed by the treating clinician.
In the study cohort of 1,831 cases, 485 (26.5%) had pulmonary complications.
A univariate analysis demonstrated that pulmonary complications occurred in 42% of patients receiving more than 4.4mg naloxone compared with 26% of cases receiving lower doses (odds ratio [OR] 2.14; 95% CI 1.44–3.18). When 2mg was used as the cut-off for high dose naloxone, there was still a significant association with pulmonary complications (34% vs 15%; OR 1.66; 95% CI 1.33–2.06)
The retrospective nature is the most significant limitation of this study. The multivariate analysis mitigates but cannot eliminate the confounders. In particular when dealing with an obtunded patient they are likely to suffer pulmonary complications due to diminished airway reflexes. The high dose of naloxone might merely be an indication of the level of unconsciousness rather than actually causing the pulmonary complications itself.
Out-of-hospital patients receiving naloxone for opioid overdose had a 26.5% pulmonary complication rate (pulmonary oedema, aspiration pneumonia or pneumonitis). This was increased to 42% for patients receiving more than 4.4mg of naloxone. Due to the retrospective nature of this study, the association identified may or may not be causal.
6. Farkas A, Lynch MJ, Westover R, Giles J, Siripong N, Nalatwad A, Pizon AF, Martin-Gill C. Pulmonary Complications of Opioid Overdose Treated With Naloxone. Ann Emerg Med. 2020 Jan;75(1):39-48. doi: 10.1016/j.annemergmed.2019.04.006. Epub 2019 Jun 8. PMID: 31182316.
Influence of post-COVID-19 deconfinement on psychiatric visits to the emergency department7
COVID-19 has caused a reduction in the number of emergency-department presentations. Conversely, amongst psychiatric patients, symptoms related to anxiety, depression, and post-traumatic stress disorder increased, consistent with previous pandemics necessitating quarantine (such as during the SARS or Ebola pandemics).
The authors hypothesized that deconfinement might have led to changes in the number and profiles of psychiatric presentations to the ED. A retrospective observational study was conducted examining the number of visits the month following deconfinement and comparing them to presentations overs the same month for the previous 4 years.
259 psychiatric visits were analysed over the post-deconfinement month. Through their analysis, they found that average number of ED presentations were low, but the psychiatric presentations remained the same. Hence, increasing the proportion of visits for psychiatric cases by 5.3%, compared to previous years (3.5%; p = 0.013).
The nature of the presentations were as follows: depressive symptoms (29% historically; 32% during deconfinement, p=0.663), suicide attempt (20% historically; 24% during deconfinement, p=0.521), anxiety (14%, both historically and during deconfinement, p=1), and personality/comportment disorder (19% historically, 12% during deconfinement, p=0.234).
This study gives insight on the psychiatric impact of confinement during the COVID-19 pandemic period.
7. Flament, N. Scius, N. Zdanowicz, et al., Influence of post-COVID-19 deconfinement on psychiatric visits to the emergency department, American Journal of Emergency Medicine, https://doi.org/10.1016/j.ajem.2021.05.014
Clinical Characteristics Predict the Yield of Head Computed Tomography Scans among Intoxicated Trauma Patients: Implications for the Initial Work-up8
This paper describes an attempt to harness clinical examination using a clinical computed score for those intoxicated head trauma patients presenting to ED in determining where neuroimaging maybe required.
This was a retrospective study (2013–2017) at a single, level-one United States trauma centre. Patients included were those >14yrs with laboratory or clinical diagnosis of intoxication and brought to hospital as pre-alerted trauma cases. Patients were identified by a blinded data analyst and extracted from an electronic trauma database by two abstractors.
Primary outcomes examined included rates of performed head computed tomography (CT) scans with acute findings, admission, neurosurgical consultation, and intervention. The clinical computed score (CCS) was determined on examination and included: GCS <13, age >50, trauma above the clavicles, amnesia, headache, vomiting and seizures.
408 (93.4%) intoxicated trauma patients had a head CT with acute findings in 30% of scans. 38% of this total required neurosurgical intervention with a mortality of 4.8%.
A CCS result of >1 had an increased odds ratio for acute findings on CT, admission to hospital and neurosurgical consultation and was a greater predictor than GCS <13, age or BAC alone. Trauma above the clavicles had a sensitivity of 93.6%, NPV of 92.5%. GCS <13 had specificity of 93.7% and a PPV of 75%. CCS >1 and GCS<13 had the highest sensitivity and specificity, however on multivariate analysis CCS was the only independent predictor for the primary outcomes.
This was a retrospective study solely examining intoxicated head injury patients, sourced from a trauma database registered on arrival by pre-alerted ambulance. No comparison was against unintoxicated head trauma in evaluating the role of CCS in trauma triage. CCS >1 had high sensitivity on multivariate analysis, however it was derived from composite signs that individually varied across their diagnostic accuracy.
The CCS is not ready for prime time and would require extensive prospective validation in a UK and Irish Cohort prior to consideration of implementation. Most criteria are covered by current UK NICE guidelines9 therefore it is uncertain how this would improve on current UK practice.
This study provides food for thought on certain clinical features to raise our index of suspicion for head injury in intoxicated patients presenting with trauma.
- McIntyre MK, Kumar NS, Tilley EH, Samson DJ, Latifi R. Clinical Characteristics Predict the Yield of Head Computed Tomography Scans among Intoxicated Trauma Patients: Implications for the Initial Work-up. J Emerg Trauma Shock. 2020;13(2):135-141. doi:10.4103/JETS.JETS_74_19
- NICE. (2019). Head injury: assessment and early management. (accessed 10 June 2021)