Journal Club Podcast JUly 2022

Dr Bertha Wu
Dr Laksmi Govindasamy
Dr Myles Sri-Ganeshan
Professor Peter Cameron

Welcome to the July Journal Club Podcast. We are again joined by Professor Peter Cameron, Academic Director for the Alfred Emergency and Trauma Centre and Research Fellow Dr Myles Ganeshan. For our last paper we will also be joined by a special guest Dr Laksmi Govindasamy, our current ACEM Victorian Trainee Representative, a public health physician, and is currently undertaking a PhD exploring gender and leadership development in Emergency Medicine.

We will review 3 papers today, covering topics of effectiveness of three antiepileptic drugs in treating toxin-related status epilepticus, use of Kelly clamps vs fine artery forceps in decompressing traumatic pneumothorax and haemothorax, as well as implicit gender bias during procedural competency assessments of emergency medicine trainees.

Paper 1: Treatment of Toxin-Related Status Epilepticus With Levetiracetam, Fosphenytoin, or Valproate in Patients Enrolled in the Established Status Epilepticus Treatment Trial.

Read it here
Clinical Question

Are levetiracetam, valproate, and fosphenytoin effective in treating toxin-related status epilepticus?

Study Design & PICO
This paper uses data from the Established Status Epilepticus Treatment Trial (ESETT) ESETT was a prospective, randomized, adaptive, double-blinded study performed across 58 EDs in the United States from 2015-2019.
Population (Target)
Inclusion criteria:

  • Age 2yo or more
  • Presenting with convulsive seizures lasting longer than 5 minutes
  • Received adequate doses of benzodiazepines before enrollment
    • In adults or children weighing >32kg, cumulative dose on benzodiazepine was 4mg IV lorazepam, 10mg IV or IM midazolam, or 10mg IV diazepam
    • In children weighing <32kg, 0.1mg/kg IV lorazepam, 0.3mg/kg IV midazolam, or 0.2mg/kg IV diazepam

Exclusion criteria:

  • Pregnancy
  • Imprisonment
  • Seizures related to post-anoxia, cardiac arrest, acute trauma, or hypo/hyperglycaemia
  • Received nonbenzodiazepine anticonvulsant
  • Intubated
  • Hand any known allergies or contraindications to the study medications
Intervention / Comparison
3 different second-line agent administered:

  • Levetiracetam 60mg/kg up to 4500mg, or
  • Fosphenytoin 20mg phenytoin sodium equivalents/kg up to 1500mg phenytoin sodium equavalents, or
  • Valproate 40mg/kg up to 3000mg
Primary outcome:

  • Absence of clinical apparent seizures and improvement in the level of consciousness 1 hour after start of study drug administration
    • without additional administration of antiseizure medication (including RSI induction agents eg propofol and ketamine)
  • Assessed by treating physician
  • 4 neurologist adjudicated the medical records to confirm the primary outcome, ascertain the time before the trial drug was given, time to seizure termination prior Hx of epilepsy, and the seizure precipitant
  • A fifth adjudicator reviewed the medical records of each participant where the seizure precipitant was categorized as toxin-related to determine the specific agent the exposure scenario

Secondary outcome:

  • Time to seizure cessation
  • ICU adm
  • Length of hospital stay

Safety outcomes

  • Composite of life threatening arrhythmias or hypotension
  • Death
  • Adverse events requiring intubation within the first hour
  • Seizure occurrence 1 to 12 hours after the tart of the study drug
  • Respiratory depression at any time
  • Anaphylaxis
  • Out of 249 adults and 229 children enrolled in the ESETT trial toxin related seizures occurred in 29 adults (11.6%) and 1 child (0.4%)
  • Men were more likely to have toxin-related seizures than women (17.2% vs 3.9%)
  • Most common toxin related precipitants were alcohol withdrawal and cocaine, with 11 (37%) of 30 patients in each category
  • For alcohol-related seizures, 64% responded to second-line therapy
    • treatment success was 3/3 (100%) for levetiracetam, 3/6 (50%) for valproate and 1/2 (50%) for fosphenytoin
  • For cocaine related seizures, only 18% responded to second line therapy
    • treatment success was 1/ 7 (14%) for levetiracetam, 0/1 (0%) for valproate, and 1/3 (33%) for fosphenytoin
  • One patient who used cocaine and an opioid received fosphenytoin and developed life-threatening hypotension
Authors’ conclusions
  • Toxin-related benzodiazepine refractory status epilepticus was successfully treated with a single dose of second-line antiseizure medication in 42% of patients.
  • Of the 3 drugs, levetiracetam appears to be the best option for treatment of toxin-related seizures, especially in treating patients with status epilepticus precipitated by alcohol withdrawal as 100% of patients achieved primary outcome.
  • Both fosphenytoin and valproate performed poorly with toxin-related status epilepticus
Journal Club thoughts

It was unfortunate that only a small number of participant (29) recruited despite the study being a part of a large multicentre trial spanning almost 5 years. There was only one paediatric patient when toxin-related seizures are common in the paediatric population. There were also limited toxicological agents – mostly illicit drugs – and few (only 2) prescription drugs studied. Median seizure time before second line drug was given in the study is 55min – waiting for about an hour for seizure cessation is pretty long – in practice the patient would have been intubated. Furthermore, the doses of benzodiazepine given as first line agent in the study – 4mg lorazepam, 10mg midazolam or 10mg diazepam – was much lower than what we would expect to give in real life. In a patient with toxin-related status epilepticus, we’d likely be using double or triple the dose of benzodiazepines used in the study. The main issue raised in the journal club though, is that when treating toxin-related seizures, the general approach should be benzos, benzos and more benzos. Using phenytoin or valproate in toxin-related seizures may make things worse especially when causative agents are not known in polypharmacy overdoses. In this study, type of toxin(s) ingested is mostly based on history and suspicion – many participants had no drug screen done. Using fosphenytoin and valproate on these patients was quite risky, and we wondered whether this was a case of a study limiting good clinical practice.

Bottom Line

This study essentially showed that the second line agents work in half of patients with status epilepticus and doesn’t work for the other half. We are not sure what this study adds. It will not change our current practice where the mainstay of treatment of toxin-related seizures is benzodiazepines.

Paper 2: Pleural decompression procedural safety for traumatic pneumothorax and haemothorax: Kelly clamps versus fine artery forceps. 

Read it here
Clinical Question:

What is difference in force required to puncture simulated pleura comparing Kelly clamps to fine artery forceps?

Study Design & PICO
Single operator, unblinded, simulation study
Population (Target)
A thoracic mannequin fitted with simulated parietal pleura
Using fine artery forceps for parietal pleural puncture
Using Kelly clamps for parietal pleural puncture
The median pleural puncture force using fine artery forceps vs Kelly clamps for parietal pleural puncture
What were the findings

The median pleural puncture force was 52.91N for Kelly clamps and 10.70N for fine artery forceps.

Authors’ conclusions

There is a significant reduction in the force required to puncture simulated parietal pleura when using fine artery forceps compared to when using Kelly clamps. Whilst this was not a in vivo study, it could be argued based on this study that the risk of pulmonary injury can be reduced by using fine artery forceps rather than Kelly clamps when performing emergency pleural puncture

Journal Club thoughts

The study methodology was unfortunately limited by being a single-operator study and using simulated pleura. However, it seems intuitive that if we use fine artery forceps with a smaller tip, less force will be used to puncture the pleura which may reduce the risk of pulmonary injury

Bottom Line

This paper could be practise changing. Our guest speakers and emergency physicians attending journal club suggested using fine artery forceps on patients with a smaller body habitus, and Kelly clamps on patients with larger body habitus. Once the pleura is punctured and lung decompressed, it’s reasonable to then further dissect with Kelly clamp to create a larger space for ICC insertion.

Paper 3: Assessment of Implicit Gender Bias During Evaluation of Procedural Competency Among Emergency Medicine Residents. 

Read it here

Clinical Question

Is there implicit gender bias in assessments of procedural competency in ED trainees? And is the gender of the evaluator associated with identified implicit gender bias?

Study Design & PICO
Cross-sectional, blinded study performed from 2018-2020
Population (Target)
  • Emergency medicine faculty members recruited as evaluators from different states in USA
  • Emergency medicine residents from a single EM residency program served as proceduralists
Intervention/ Comparison
Emergency medicine residents performed 3 procedures (lumbar puncture, thoracostomy tube insertion, internal jugular CVC insertion under ultrasound guidance) in a simulated environment:

  • They were blinded to intent of study
  • Proceduralist were filmed performing each procedure from 2 different viewpoints simultaneously by 2 different cameras
  • One viewpoint was gender blinded (ie hands-only) view
  • The other viewpoint a wide-angle gender-evident (ie whole-body) view

Emergency medicine faculty evaluators viewed videos in random order :

  • assessed procedural competency on a global rating scale (GRS)
  • 6 domains were assessed (respect for tissue, time and motion, knowledge of equipment, instrument handling, flow of procedure, knowledge of procedure)
  • For each procedural video, a score of 1-5 was selected for each domain
Primary outcome:

  • Difference in mean scores obtained from the gender-blinded view and the gender-evident view between male and female proceduralist

Secondary outcome

  • Difference in blinded vs unblinded scores across proceduralist gender according to the gender of the evaluators
  • 10 Emergency medicine residents from a single EM residency program served as proceduralists, consisting of:
    • 5 men (1 PGY1, 2 PGY 2s, 2 PGY 4s)
    • 5 women (2 PGY 1s, 1 PGY2, 1 PGY 3, 1PGY 4)
  • 51 Emergency attending physicians were enrolled from 19 states in USA
    • 22 were male participants (43.1%), 29 were female participants (59.9%)
    • the mean age was 37 years (SD 6.4 years)
    • Each evaluator assessed all 60 procedures (30 gender-blinded, 30 gender-evident)
  • The male proceduralist gender was not associated with greater score difference than the female proceduralist gender
    • The mean score for women in the gender-evident view was 3.65 (SD 0.52), compared with 3.53 (SD 0.67) in the gender-blinded view (difference 0.12, 95% CI -0.04 to 0.29)
    • The mean score for men was 3.75 (SD 0.48) in the gender-evident view, and 3.69 (SD 0.51) in the gender-blinded view (difference 0.06, 95% CI -0.06 to 0.19)
  • The gender of the evaluator was not associated with difference in mean scores
    • Male evaluators scored both female and proceduralists slightly lower when the gender was evident v blinded
Authors’ conclusion
  • There were no differences found in the assessment of procedural competency based on the gender of the proceduralist or the gender of the faculty evaluators
  • The findings suggest that implicit gender bias in the direct observation of simulated procedures is unlikely to be the source of established gender disparities
Journal Club thoughts

It’s great that this study was done in an important area. However, it is surprising that a negative result was found, especially given the authors mentioned at the start of the paper that there is a gap between male and female emergency trainees in achieving performance milestones in USA. There are a few methodological issues that might explain why the study didn’t have a positive finding.  Though the authors made a good effort in trying to conceal gender of the proceduralist in the gender-blinded views, there are likely other subtle clues that will give away whether the proceduralist is a female vs male eg the size of the hand, the way the hand moves etc. The paper also did not comment on whether the evaluators have worked with the proceduralists before. So one can argue the study may not really be blinded… Furthermore, the study looked at procedural competency assessment, and used a very regimented scoring system, which makes it less likely for implicit bias of the evaluator to be in play. However, in real life, trainees also perform assessments that rely on the subjective evaluation of the assessor eg competency and medical expertise as a team leader in a Mini CEX, leadership and prioritisation ability in a Shift Report etc. In these situations, implicit bias of the evaluator is much more likely to affect the trainee’s assessment outcome.

Bottom Line

This is a good effort by the authors. However, the paper doesn’t really add much to what we know about gender dynamics and how this affect workplace performance assessment. Further in vivo studies will add to this area of research.

  1. Coralic Z, Kapur J, Olson KR, et al. Treatment of Toxin-Related Status Epilepticus With Levetiracetam, Fosphenytoin, or Valproate in Patients Enrolled in the Established Status Epilepticus Treatment Trial. Ann Emerg Med 2022 Jun 16;S0196-0644(22)00269-4. doi:10.1016/j.annemergmed.2022.04.020.
  2. Fitzgerald M, Allen T, Bai S, et al. Pleural decompression procedural safety for traumatic pneumothorax and haemothorax: Kelly clamps versus fine artery forceps. Emerg Med Australas. 2022 May 26. doi: 10.1111/1742-6723.14019.
  3. Do AS, Do MP, Aluisio AR, et al. Assessment of Implicit Gender Bias During Evaluation of Procedural Competency Among Emergency Medicine Residents. JAMA Netw Open. 2022;5(2):e2147351. doi:10.1001/jamanetworkopen.2021.47351
Dr Bertha Wu

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