Journal Club Podcast for December 2021
Prof Peter Cameron Dr David McCreary Dr Eanna Mac Suibhne
Editor: Dr David McCreary
Welcome to the Journal Club Podcast for December 2021. You can listen to the podcast above and have a read at our summary below, courtesy of our senior registrar for research, Dr Eanna Mac Suibhne.
December's Journal Club discussed four papers covering a variety of topics relevant to daily practice. We would encourage you to read the papers for yourselves and draw your own conclusions but, for a brief snapshot and our thoughts, read on.
The first paper we discussed is from the Emergency Medicine Journal by Michelle Angus et al. concerning Cauda equina syndrome and what clinical features in patients with back pain make its diagnosis more likely.
Covid inevitably featured with our second paper by Munch et al. in JAMA assessed outcomes between two different doses of dexamethasone in patients with hypoxemia due to COVID infection.
The third paper we looked at explored the role of vasopressin and methylprednisolone for in-hospital cardiac arrest and was another offering from JAMA by Anderson et al.
Finally, our last paper by Ebadi et al. in the Journal of Thrombosis and Haemostasis looks at predicting PE in pregnancy.
PAPER 1: DETERMINATION OF POTENTIAL RISK CHARACTERISTICS FOR CAUDA EQUINA COMPRESSION IN EMERGENCY DEPARTMENT PATIENTS PRESENTING WITH ATRAUMATIC BACK PAIN: A 4- YEAR RETROSPECTIVE COHORT ANALYSIS WITHIN A TERTIARY REFERRAL NEUROSCIENCES CENTRE
READ IT HERE
CLINICAL QUESTION:
What clinical features in patients with back pain make a diagnosis of cauda equina more likely?
FINDINGS
This was a retrospective review of cases, undertaken at the largest tertiary spinal referral centre in the UK. 111 patients were identified with radiological evidence of Cauda equina compression (CEC) within the cohort referred for definitive imaging, of whom 109 underwent operative intervention. Patients with CEC were more likely to present with bilateral leg pain, dermatomal sensory loss and bilateral absent ankle or ankle and knee jerks. There was no relationship between Digital Rectal Examination (DRE) and final diagnosis of CEC?
AUTHORS' CONCLUSIONS
Factors independently associated with a CEC diagnosis on MRI included bilateral leg pain and dermatomal sensory loss. Loss of lower limb reflexes was strongly suggestive of CEC. The findings raise questions about the diagnostic utility of invasive DRE.
JOURNAL CLUB THOUGHTS
Atraumatic back pain and consideration of CEC is a very common presentation to the ED.
In terms of the studies limitations, this was conducted at a single centre, the largest spinal centre in the UK, and as such may not be generalisable to the typical ED population. Selection bias may have featured as it is unclear how many patients were referred into the major spinal centre and ultimately included in the study group. Also, not all patients who presented to the ED with atraumatic back pain got an MRI; thus, there was no data on these patients to determine clinical outcomes.
While it is certainly interesting to know which symptoms correlate most often to CEC, it might be equally important to note that the evidence also demonstrated the relative lack of importance of each individual factor when it comes to specificity and sensitivity. When the individual clinical tests are described for sensitivity and specificity then the individual performance of all the tests was poor, with the highest sensitivity being 50% for loss of perineal sensation. Specificity was only in clinically useful levels for loss of ankle jerks. Clinicians should not solely rely on the presence or absence of specific clinical symptoms or signs to rule in or rule out CEC.
So again, it comes down to a constellation of findings that make the diagnosis more likely, which is reflective of daily practice. The best indicators are bilateral leg pain (with or without back pain), objective sensory loss (in a dermatomal distribution) and loss of bilateral ankle jerks.
PAPER 2: EFFECT OF 12 MG VS 6 MG OF DEXAMETHASONE ON THE NUMBER OF DAYS ALIVE WITHOUT ALIVE WITHOUT LIFE SUPPORT IN ADULTS WITH COVID-19 AND SEVERE HYPOXEMIA. THE COVID STEROID 2 RANDOMIZED TRIAL
READ IT HERE
CLINICAL QUESTION:
What is the effect of 12 mg vs 6 mg of dexamethasone on the number of days alive without life support at 28 days in patients with COVID-19 and severe hypoxemia?
FINDINGS
The primary outcome was the number of days alive without life support (invasive mechanical ventilation, circulatory support, or kidney replacement therapy) at 28 days after randomization. 1000 patients with COVID-19 and severe hypoxemia were included and after randomisation, treatment with 12 mg/d of dexamethasone resulted in 22.0 days alive without life support at 28 days compared with 20.5 days in those receiving 6 mg/d of dexamethasone This difference was not statistically significant.
AUTHORS' CONCLUSIONS
Among patients with COVID-19 and severe hypoxemia, 12 mg/d of dexamethasone compared with 6 mg/d of dexamethasone did not result in statistically significantly more days alive with-out life support at 28 days. However, the trial may have been underpowered to identify a significant difference.
JOURNAL CLUB THOUGHTS
This study was brought to us by an unusual alliance of countries- Denmark, Sweden, India and Switzerland. There were no statistically significant findings or likely change to our practice and further confirmation that we are doing the right thing for our patients.
In terms of strengths, this was a pragmatic trial involving a relatively large number of patients and was conducted across 2 different continents reflecting good external validity. Internal validity was assured by the blinding, allocation concealment and good follow up rate. The severity of illness seemed to be equally spread across the 2 groups, in terms of NIV, HFNO, ICU etc.
The presumed difference in outcomes between groups (15% relative reduction in the 28-day mortality, 10% relative reduction in the time requiring life support) may have been too large. And the sample size may have been too small allowing the possibility of type II error.
Concomitant use of other medications such as tocilizumab halfway through may have confounded the results.
PAPER 3: EFFECT OF VASOPRESSIN AND METHYLPREDNISOLONE VS PLACEBO ON RETURN OF SPONTANEOUS CIRCULATION IN PATIENTS WITH IN-HOSPITAL CARDIAC ARREST; A RANDOMIZED CLINICAL TRIAL
READ IT HERE
CLINICAL QUESTION:
Does the combination of vasopressin and methylprednisolone administered during in-hospital cardiac arrest improve return of spontaneous circulation?
FINDINGS
This was a multicentre, randomized, double-blind, placebo-controlled trial conducted at 10 hospitals in Denmark. A total of 512 adult patients with in-hospital cardiac arrest were included between October 15, 2018, and January 21, 2021.
The primary outcome was return of spontaneous circulation. Secondary outcomes included survival and favourable neurologic outcome at 30 days.
501 patients with in-hospital cardiac arrest were included and the proportion of patients who achieved return of spontaneous circulation was 42% in the vasopressin and methylprednisolone group and 33% in the placebo group.
AUTHORS' CONCLUSIONS
Among patients with in-hospital cardiac arrest, administration of vasopressin and methylprednisolone compared with placebo significantly increased the likelihood of return of spontaneous circulation, but it is uncertain whether there is benefit or harm for long-term survival.
JOURNAL CLUB THOUGHTS
This study involved in-hospital arrests so not generalisable to our patient population. That being said, it is not a well-studied population so an important clinical question. They are a different beast in comparison to out of hospital cardiac arrest in terms of the times to effective bedside CPR, access to medications, defib and the cause of arrest is often clear.
This was a well-conducted study. It exhibited excellent internal validity. It was multicentred, double-blinded, placebo-controlled, had a good randomisation strategy, had balanced baseline characteristics, and displayed good adherence to protocol.
With respect to the primary outcome; not necessarily a patient-centred one. ROSC as an end goal doesn’t necessarily result in better patient outcomes, it’s the QOL afterwards which would be preferred.
As mentioned in the podcast, the majority of these arrests were PEA. And as we know, often the cause for PEA are reversible causes and there are confounding factors here that would contribute to ROSC. Now vasopressin in cardiac arrest came under the radar for most people but looking into it, theoretically, those patients with normal conduction (i.e. PEA) may benefit more from high doses of vasopressors as opposed to shockable rhythms.
All in all, this was an interesting study but doesn’t change the rules of engagement for the time being and it may be (Ed - and hopefully will be!) some time before this makes it into CPG’s.
PAPER 4: ASSESSING THE CLINICAL PROBABILITY OF PULMONARY EMBOLISM DURING PREGNANCY: THE PREGNANCY-ADAPTED GENEVA (PAG) SCORE
READ IT HERE
CLINICAL QUESTION:
Does the pregnancy adapted Geneva score enhance the clinical probability of PE during pregnancy?
FINDINGS
The authors used data from a previous multi-centre study, with 395 women with suspected PE, in whom pre-test probability was assessed using the Geneva score. They removed items that were present in none of the patients (cancer, age >65 years) and added to it, an age of 40 years or older and a heart rate >110 beats per minute. The ROC curves showed an area under the curve of 0.795 for the Pregnancy adapted Geneva score compared to 0.684 for the Geneva score.
AUTHORS' CONCLUSIONS
In pregnant women with suspected PE, the PAG Score shows a high discriminative power to identify patients at low, intermediate, or high PTP. It has the strength of being a fully objective decision rule, is clinically relevant, easy to compute, and should now be tested in a prospective outcome study.
JOURNAL CLUB THOUGHTS
This cohort of patients is always challenging, and we are always looking for ways to confidently assess the likelihood of PE, so it is an important area of study.
The initial study that this paper was based on was a diagnostic or management strategy to deal with pregnant women presenting with chest pain with no alternative cause or acute shortness of breath. There were 395 patients included in that study with 28 patients identified as having a pe. Using their strategy, they scanned 328 Patients.
With regard to this revised score, it was noted that clinical gestalt was an important omission and one which is a key consideration when confronted with this patient cohort.
The numbers here are small, only 28 patients. A difficult patient group to study which ultimately means that it’s a small number of positive patients to base a modified score on.
The goal of these tests is to reduce unnecessary exposure to excessive radiation and to confidently state that with the information available, a PE is not present. When they used this adapted PAG score they reduced the patients who would have received a CTPA by 0.3%, from 11.6 to 11.3%. Bigger patient numbers would be needed to display a greater difference.
The question of D-dimers appeared again. The authors state that D-dimer was negative more often in the 1st > 2nd > 3rd trimester but was still clinically useful, ruling out disease without imaging in 11.7% of the patients. In the right hands, D-dimers can be your ally!
REFERENCES
Angus M, Curtis-Lopez CM, Carrasco R, Currie V, Siddique I, Horner DE. Determination of potential risk characteristics for cauda equina compression in emergency department patients presenting with atraumatic back pain: a 4-year retrospective cohort analysis within a tertiary referral neurosciences centre. Emerg Med J. 2021;emermed-2020-210540.
Group TCS 2 T, Russell L, Uhre KR, Lindgaard ALS, Degn JF, Wetterslev M, et al. Effect of 12 mg vs 6 mg of Dexamethasone on the Number of Days Alive Without Life Support in Adults With COVID-19 and Severe Hypoxemia. Jama. 2021;326(18):1807–17.
Andersen LW, Isbye D, Kjærgaard J, Kristensen CM, Darling S, Zwisler ST, et al. Effect of Vasopressin and Methylprednisolone vs Placebo on Return of Spontaneous Circulation in Patients With In-Hospital Cardiac Arrest. Jama. 2021;326(16).
Robert Ebadi H, Elias A, Sanchez O, Moigne EL, Schmidt J, Gall CL, et al. Assessing the clinical probability of pulmonary embolism during pregnancy: The Pregnancy-Adapted Geneva (PAG) score. J Thromb Haemost. 2021;19(12):3044–50.
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