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Dr. Bertha Wu

JOURNAL CLUB - JUNE 2022

Updated: Nov 3, 2023

Journal Club Podcast June 2022

Dr Bertha Wu Dr Rob Mitchell Prof Peter Cameron



WELCOME TO THE JUNE JOURNAL CLUB PODCAST. WE ARE JOINED BY PROFESSOR PETER CAMERON, ACADEMIC DIRECTOR FOR THE ALFRED EMERGENCY AND TRAUMA CENTRE, AND EMERGENCY PHYSICIAN DR ROB MITCHELL.


We will discuss 3 papers this month, covering: delays to inpatient admission from ED and risk of death, use of anti-dopaminergic antiemetics and stroke risk, and the use of CT scans to rule out subarachnoid haemorrhages.


PAPER 1: ASSOCIATION BETWEEN DELAYS TO PATIENT ADMISSION FROM THE EMERGENCY DEPARTMENT AND ALL-CAUSE 30-DAY MORTALITY.

READ IT HERE


CLINICAL QUESTION:

Do delays to inpatient admission from EDs increase the risk of death?


DESIGN

Cross sectional, retrospective observational study


POPULATION (TARGET)

  • All patients admitted from every major ED in England between April 2016 and March 2018

  • Only a patient’s first admission in the study period was included.

  • Patients who waited in the ED for longer than 12 hours were excluded


INTERVENTION / COMPARISON

  • No intervention/comparator as observational study

  • Looked at exposure

    • The time admitted patients spent in ED, up to 12 hours after arrival

    • Times were measured from the patients’ arrival at the ED until their transfer to an inpatient bed


OUTCOME

Death from all causes within 30 days of admission

FINDINGS

  • Between April 2016 and March 2018, 26 738 514 people attended an ED, with 7 472 480 patients admitted. 5 249 891 individual patients data was included in the study

  • Total of 433 962 deaths occurred within 30 days

  • Overall crude mortality rate was 8.71% (95% CI 8.69% – 8.74%)

  • Patients on average spent 5 hours in ED

  • Of the admitted patients, 38% breached the 4-hour rule, which the paper used as a proxy for ED crowding. This is the variable with the largest OR for 30-d mortality of 1.35 (1.33-1.37, p<0.001)

  • Lower socioeconomic status (measured on a patient deprivation decile of 1-10, with 1=least and 10=most deprived) was also associated with higher 30-d mortality with OR 1.20 for a deprivation decile of 7 and 1.32 for a decile of 10.

  • Increased standardised mortality rate for patients admitted to hospital after 5 hours

  • There is a dose-dependent association between time in excess of 5 hours in the ED for admitted patients and all-cause mortality

    • The standardised mortality rate (SMR) increases in an approximately linear fashion from this point until 12 hours after which accurate data is unavailable


There is a 10% increase in the SMR within 30 days for admitted patients remaining in ED between 8-12 hours in comparison with those who leave the ED within 6 hours.


AUTHORS' CONCLUSIONS

Delays to hospital inpatient admission for patients in excess of 5 hours from time of arrival at the ED are associated with an increase in all-cause 30-day mortality.

JOURNAL CLUB THOUGHTS

This paper’s findings are consistent with those from previous literature. From a methodological point of view, being a retrospective observational study, many confounders could have contributed to the paper’s findings. It was good that the authors addressed the possible mechanisms that may have accounted for patients’ prolonged stay in ED. However, there are nuances and complexities that were not mentioned by the paper. For example, disadvantaged patients like the elderly and confused or the complex medical patients are the ones who are usually get left behind, lingering for hours in ED waiting for an inpatient bed.


BOTTOM LINE

At the end of the day, access block is not an Emergency Department problem. It is a systemic problem that requires addressing with good leadership and a change of culture hospital-wide.


PAPER 2: RISK OF FIRST ISCHAEMIC STROKE AND USE OF ANTIDOPAMINERGIC ANTIEMETICS: NATIONWIDE CASE-TIME-CONTROL STUDY.

READ IT HERE

CLINICAL QUESTION:

Does the use of antidopaminergic antiemetics increase the risk of first stroke?


DESIGN

Case-time control study


POPULATION (TARGET)

  • >/= 18 years

  • Diagnosis of first ischaemic stroke between 2012 and 2016

  • No history of cerebrovascular disease

  • Had at least one reimbursement for the antidopaminergic antiemetics (ADA) studied – domperidone, metopimazine and metoclopramide – in the 70 days before stroke

  • Were affiliated with the major health insurance scheme at least during the year of outcome occurrence. Eligible participants were all patients registered on the French health insurance database which contains information on at least 99% of the French population, and where reimbursements to outpatients for dispensed drugs can be found Included:

Excluded:

  • History of cancer

  • Hospital admission in the observation period

  • Had at least once reimbursement for the fixed association metoclopramide aspirin in the observation period on in the year before

INTERVENTION / COMPARISON

  • The two arms of the study are the case group (participants had first ischaemic stroke during study period), and the exposure time trend control group (participants who didn’t have an ischaemic stroke)

  • Controls were recruited at the same time as the patients with stroke to take into the account of time trend of ADA use eg natural increase or decrease use of ADA over time

  • This study looked at the two groups ‘ exposure to the studied ADAs over 4 periods: days -14 to -1 before stroke (the risk period), and days -70 to -57, -56 to -43, and -42 to -29 before stroke (reference periods)

OUTCOME

  • Association between ADA use and risk of ischaemic stroke

  • Assessed by estimating the ratio of the odds ratios of exposure evaluated in patients with stroke and in controls

WHAT WERE THE FINDINGS

  • Amongst 2612 patients with incident stroke, 1250 received an ADA in the risk period, and 1060 in the reference periods

  • The comparison with 5128 and 13165 respective controls who received an ADA in the same periods yielded a ration of adjusted odds ratio of 3.12 (95% CI 2.85-3.42)

  • Analysis stratified by age, sex and history of dementia showed similar results

  • Ratio of adjusted OR for analyses stratified by ADA was 2.51 (2.18-2.88) for domperidone, 3.62 (3.11-4.23) for metopimazine, and 3.53 for metoclopramide

  • Sensitivity analysis suggested that the risk would be higher in the first days of use


AUTHORS' CONCLUSIONS

There is an increased risk of ischaemic stroke with recent ADA use. The highest increase was found for metopimazine and metoclopramide.

JOURNAL CLUB THOUGHTS

It was a great effort by the authors as there were a large number of participants. It was interesting that patients who had intravenous ADAs weren’t included, as one would imaging drugs given via the IV route would have the most intended or unintended effect. Further, the study did not detail why the patients required the ADA to being with.


Was it because the patient developed vertigo as a prodrome of a posterior circulation stroke? Or that the patient had a significant illness that precipitated the stroke? The authors called this “protopathic bias” and did attempt to correct for this with a sensitivity analysis. However, this remains a design flaw that we’re not convinced can be adjusted for with statistical maneuvers.


BOTTOM LINE

The study findings are not convincing at a biological and clinical level, and won’t change our current practice.


PAPER 3: SENSITIVITY OF MODERN MULTISLICE CT FOR SUBARACHNOID HAEMORRHAGE AT INCREMENTAL TIMEPOINTS AFTER HEADACHE ONSET: A 10-YEAR ANALYSIS.

READ IT HERE

CLINICAL QUESTION:

Is it possible to extend the timeframe from headache onset within which modern multislice CT can be used to rule out aneurysmal subarachnoid haemorrhage (SAH)?


DESIGN

Single centre, retrospective cohort study


POPULATION (TARGET)

  • Patients who had diagnosis of subarachnoid haemorrhage presenting to Christchurch Hospital between 2007 and 2017Excluded:

    • Traumatic SAH

    • Repeat SAH admission during the study time period

    • SAH found on postmortem in whom no MSCT was performed

    • The day of onset of headache was not recorded

    • Patient transferred to Christchurch Hospital from another hospital

    • Patients with lost or destroyed records

    • Cases miscoded as SAH


INTERVENTION / COMPARISON

Exposure: Imaging with multislice CT (MSCT) head


OUTCOMES

  • Primary: Proportion of patients with spontaneous aneurysmal SAH that had a positive MSCT

  • Secondary: The proportion of patients with any type of spontaneous SAH that had a positive MSCT

FINDINGS

  • Out of 347patients with a SAH, 260 had an aneurysmal SAH

  • MSCT identified 253 (97.3%) of all aneurysmal SAH and 332 (95.7%) of all SAH

    • Of the 15 (2.7%) of patients not identified with MSCT, 7 (47%) were aneurysmal SAH diagnosed with SAH using a combination of LP and/or MRI


  • Coroners mortality database was examined – no sudden deaths with SAH where patients had a recent related ED presentation where a head MSCT was performed

  • There were 224 patients where the time of headache onset was not recorded

    • Of these , onset was the same day as arrival in the ED in 148 (66%) of patients

    • For these patients, the time of headache onset was imputed as 30min prior to arrival time for analysis to maximise the number of early false negatives

    • For patients with headache onset during the preceding day, a time of 23:59 was imputed for analysis

  • At 24 hours after headache onset, the sensitivity of MSCT for aneurysmal SAH was 100% (95% CI 98.3-100)

  • At 48 hours after headache onset, the sensitivity of MSCT was 99.6% (95% CI 97.6-100) for aneurysmal SAH and 99% (95% CI 97.1-99.8) for all SAH

The sensitivity of MSCT for all SAH decreased as time to MSCT increased


AUTHORS' CONCLUSIONS

It may be possible to extend the timeframe from headache onset within which modern MSCT can be used to rule out aneurysmal SAH

JOURNAL CLUB THOUGHTS

This study supports what many Emergency Physicians are doing currently. We know that with improvement of technology over the years, the sensitivity of CT brains and their ability to detect a subarachnoid haemorrhage beyond the 6 hours mark has also improved. Our experienced guest speakers recommended using clinical judgement when you decide what to do next after a negative CTB performed after 6 hours. There is little added benefit of performing a lumbar puncture. If there is a high pre-test probability of the patient having a subarachnoid haemorrhage, then a CT angiogram should be considered.


BOTTOM LINE

When a CTB is done beyond 6 hours of headache onset, whether any subsequent tests is required to rule out a SAH as the cause of the headache should be based on clinical judgement of pretest probability, taking into account that modern CT scanners have much better sensitivity to detect SAH.


REFRENCES

  • Jones S, Moulton C, Swift S, et al. Association between delays to patient admission from the emergency department and all-cause 30-day mortality. Emerg Med J 2022 Mar;39(3):168-173.

  • Benard-Laribiere A, Hucteau E, Debette S, et al. Risk of first ischaemic stroke and use of antidopaminergic antiemetics: nationwide case-time-control study. BMJ 2022;376:e066192.

  • Vincent A, Pearson S, Pickering JW, et al. Sensitivity of modern multislice CT for subarachnoid haemorrhage at incremental timepoints after headache onset: a 10-year analysis. Emergency Medicine Journal. Published Online First: 24 November 2021. 

DR BERTHA WU

Emergency Registrar

MBBS, CCPU (eFAST, AAA, BELS). Emergency Medicine Advanced Trainee and Intensive Care Medicine Trainee in Melbourne, Australia. Particular interests in POCUS, medical education and health care in resource-poor settings. Twitter: @berthawu29



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