TERN Top Papers January 2022

Authors: Peter Lynas, Nicola Farrington, Edward Bezant, James Mercer, Govind Oliver / Editors: Robert Hirst / Codes: CMP2, HMP2, CC1, RP3, RP5, SLO1, SLO10, SLO2 / Published: 25/01/2022

This month’s edition of TERN’s top papers series comes from a small team of higher EM trainees in the North West. It looks like we will all experience some rainy days this winter, so we hope you enjoy these summaries of articles that caught our eye. We covered the theme of Cardiovascular and Respiratory and screened close to 1,000 articles. There were a good number of interesting studies in this section, far more than we could manage to cover, but we hope our selected seven has something for you.

Angiography after Out-of-Hospital Cardiac Arrest without ST-Segment Elevation 1

The TOMAHAWK trial was a multi-centre, randomised, open label trial that included adults aged over 30 who had been successfully resuscitated following a cardiac arrest who did not have evidence of a STEMI on their post-ROSC ECG. 

Recruitment was from 31 emergency departments across Germany and Denmark. Shockable and non-shockable rhythms were both included (a major difference between the TOMAHAWK and COACT trials). Patients were randomised to have either immediate angiography or a minimum of a 24-hour delay. Patients could be crossed over in cases of electrical instability, massive troponin rises (>70x the upper limit of normal) or cardiogenic shock. Those who had delayed angiography went to the intensive care unit for further stabilisation. If, following further examination or non-invasive cardiac stress testing a cardiac cause of arrest was deemed unlikely, then coronary angiography could be abandoned. This meant a key difference between the groups was that in the immediate angiography group the vast majority underwent angiography, but in the delayed angiography group only 62% had the procedure. Around 40% of those having angiography in either arm of the trial underwent revascularisation.

There was good separation between the groups with the immediate angiography group having the procedure on average within 3 hours compared to nearly 2 days in the delayed group. The primary outcome was all cause mortality at 30-days, which was higher in the immediate angiography group at 54% vs 46%, which was statistically significant.

There were no significant differences across the secondary outcomes including neurological outcomes, peak troponin elevation or ICU stay.

This was a well conducted, pragmatic study that attempts to answer a real-world question. Suggested reasons for the increased mortality seen in this trial may represent the risks of undergoing angiography itself or the opportunity cost that moving to a remote location (the angiography suite), as opposed to the ICU, entails for resuscitation and diagnostics.

One question not answered by this study is: could immediate revascularisation provide benefits other than mortality? For example, it is plausible that earlier revascularisation could reduce the volume of infarcted myocardium and therefore reduce the long-term morbidity associated with heart failure. This cohort is being followed up with this in mind and this question is being examined in other studies.

Bottom Line

For patients who undergo an out-of-hospital cardiac arrest who do not have a STEMI on their ECG and who do not have adverse features (electrical instability/cardiogenic shock etc) there is no benefit from immediate angiography which can be undertaken in a planned, semi-elective timeframe.

Reference

1 Desch S, Freund A, Akin I, Behnes M, Preusch MR, Zelniker TA, et al. Angiography after Out-of-Hospital Cardiac Arrest without ST-Segment Elevation. N Engl J Med. 2021 Aug 29. doi:10.1056/NEJMoa2101909. Epub ahead of print. 

Randomized clinical trial comparing helmet continuous positive airway pressure (hCPAP) to facemask continuous positive airway pressure (fCPAP) for the treatment of acute respiratory failure in the emergency department 2

In type one acute respiratory failure (T1RF) requiring CPAP there is a tendency to automatically reach for a facemask (fCPAP), with the reassuring statement that its “like sticking your head out of a car window”. In this single centre trial Adi et al address whether helmet CPAP (hCPAP), which has become more widely available because of COVID-19, is as effective in the acute treatment of hypoxia. 

Two hundred and twenty-four patients at a single Malaysian hospital were randomised between the two NIV interfaces, and for obvious reasons, not blinded. The researchers investigated whether the simplicity and improved patient experience of hCPAP improved the efficacy of CPAP. fCPAP is often difficult to fit, uncomfortable, and prone to leaks. 

The primary outcome was improvement in respiratory rate measured over the first hour of treatment in those with COPD and cardiogenic pulmonary oedema only. Researchers looked at secondary outcomes such as side effects and rates of intubation. This was limited to the first hour of treatment, with a focus on ‘time to therapy’ and short-term outcomes in the ED.

Results demonstrated that both fCPAP and hCPAP reduced breathlessness and other relevant physiological parameters. Regarding tolerability, hCPAP had lower rates of mucosal dryness and discomfort. Researchers did not directly measure leak or measures of fCPAP failure, but hCPAP appeared to generate higher levels of PEEP. Crucially, intubation rates were lower in the hCPAP group (4.4% vs. 18%), but it is uncertain whether this was collated with improved tolerance of hCPAP. Does this distinction matter in this context?

Overall, this was an adequately powered single centre study using one brand of NIV interfaces. Its short observation period does focus on immediate benefits for the acutely unwell in the emergency department. hCPAP appeared to be better tolerated and as effective as the more mainstream fCPAP. This is clearly early evidence and further analysis is needed to drive a change in practice, but this piqued our interest. 

Bottom Line

Helmet CPAP is as a good alternative to facemask CPAP in T1RF in COPD and cardiogenic pulmonary oedema and may reduce intubation rates. 

Reference

2 Adi O, Via G, Salleh SH, Chuan TW, Rahman JA, Muhammad NAN, et al. Randomized clinical trial comparing helmet continuous positive airway pressure (hCPAP) to facemask continuous positive airway pressure (fCPAP) for the treatment of acute respiratory failure in the emergency department. Am J Emerg Med. 2021; 49: 385-392. doi:10.1016/j.ajem.2021.06.031. Epub ahead of print. 

A randomized, controlled comparison of electrical versus pharmacological cardioversion for emergency department patients with acute atrial flutter 3

Steil et al. ask whether adding 15 mg/kg of procainamide prior to direct current (DC) cardioversion increased the chance of cardioversion in atrial flutter. Procainamide is an unlicensed sodium channel blocker traditionally used to reveal Brugada syndrome by cardiologists and is listed as “special order” in the BNF. Its use in North America appears relatively common in AF and atrial flutter but remains outside the scope of practice of most British medics. 

This Canadian randomised, blinded, placebo-controlled comparison enrolled 76 patients across 11 sites. Their primary outcome was the conversion of new atrial flutter to sinus rhythm. Importantly cardioversions were undertaken on a semi-elective basis only, in those considered safe for DC cardioversion (<48 hours or anti-coagulated). All clinically emergent cardioversions were excluded.

Participants were randomised and blinded to procainamide then a shock (drug-shock) or a shock alone (shock) regimen. Both therapies were proven to be safe without any recorded major adverse effects, though the drug-shock group had a higher side effect profile. In the context of semi-elective cardioversion for atrial flutter, both regimens appeared to be effective, with drug-shock converting a greater proportion of patient to sinus rhythm (100% vs. 93%), although this finding lacked statistical significance. 

Atrial flutter is less common than atrial fibrillation and rarely receives DC cardioversion in UK EDs. Procainamide, despite evidence of safety and efficacy from the same author, is not routinely stocked in UK hospitals and is not supported by European guidelines. Normal practice would be rate control with a beta-blocker. As there was no statistical benefit to Procainamide authors conclude that “like AF, immediate rhythm control leads to a very high proportion of atrial flutters being discharged in normal sinus rhythm”. Though unrelated to their initial hypothesis, the take home message may be that managing new atrial flutter as aggressively as we treat new AF has a very high likelihood of discharging a patient in sinus rhythm.

Bottom Line

Aggressive rhythm control in new atrial flutter leads to a very high conversion rate to sinus rhythm, and if you can find some procainamide in your hospital, then 15 mg/kg prior to cardioversion marginally increases your chances of success, possibly. 

Reference

3 Stiell IG, Sivilotti MLA, Taljaard M, Birnie D, Vadeboncoeur A, Hohl CM, et al. A randomized, controlled comparison of electrical versus pharmacological cardioversion for emergency department patients with acute atrial flutter. CJEM. 2021; 23(3): 314-324. doi:10.1007/s43678-020-00067-7. 

The prognostic value of emergency department measured hypertension: A systematic review and meta-analysis 4

Could emergency clinicians have a greater role in preventative medicine? This systematic literature review and meta-analysis by Reynard et al. looked at whether hypertension recorded in the ED can be used to predict long-term cardiovascular disease (CVD) outcomes. With increasing ED attendances, access to portions of society underserved by primary care and mountains of routinely collected data, the authors argue that emergency physicians have an excellent opportunity to identify and access longer term high-risk patients. 

The study reviewed and analysed evidence on whether hypertension (values over 140/90mmHg) recorded in ED patients were of prognostic value in long-term CVD outcomes (>12 months.) Cardiovascular outcomes included were acute myocardial infarction, coronary revascularisation, coronary heart disease, angina, stroke, transient ischemic attack, cerebrovascular event, and death (all cause and CVD). From the 1,072 papers identified through searches, 26 studies met the inclusion criteria. 

The estimated pooled prevalence of hypertension in ED patients in the meta-analysis was 31% (95% CI 25% – 37%). Pooled estimates showed that 62% of patients remained hypertensive in the ED and at follow-up in 50%. There was evidence that hypertension recorded in the ED with associated with increased long-term CVD outcomes. 

Methodologically this study is robust; it was prospectively registered, was both conducted and reported in accordance with PRISMA guidelines and assessed included studies for bias. It is quite clear that the lack of uniformity in research and reporting of this area has led to a high degree of heterogeneity which needs to be considered. How these study findings could be used to impact patient care would also clearly need to be considered with pooled attendance to follow-up only 41%.

Bottom Line

Hypertension recorded during routine observations in the ED looks to be prevalent and both persistent and prognostic of increased longer-term cardiovascular disease outcomes. 

Reference

4 Reynard C, van den Berg P, Oliver G, Naguib MP, Sammut-Powell C, McMillan B, et al. The prognostic value of emergency department measured hypertension: A systematic review and meta-analysis. Acad Emerg Med. 2021 Sep 22. doi:10.1111/acem.14324. Epub ahead of print. 

Diagnostic accuracy of lung point-of-care ultrasonography for acute heart failure compared with chest x-ray study among dyspnoeic older patients in the emergency department 5

Two common presentations to the ED include exacerbation of chronic obstructive pulmonary disease (COPD) and acute heart failure. Trying to differentiate between these can be difficult as they present with overlapping signs & symptoms. Traditionally chest x-ray (CXR) has played a key role in this diagnostic challenge but increasingly the role of lung point-of-care ultrasound (POCUS) is being recognised. This single centre cohort study from a tertiary hospital ED in Canada looked to assess the performance of lung POCUS compared to CXR in identifying acute heart failure in this group of patients. 

Over a six-month period, the authors screened patients over the age of 50, presenting with acute shortness of breath or cough with suspected acute heart failure or COPD (n=3538). Of these, 81 underwent lung POCUS and were included in the analysis. Clinicians performing ultrasonography were of varying skill mix, but all scans were electronically documented and reviewed by the Emergency Medicine Ultrasonography team for quality-assurance purposes. The study reported that 70% of the ED staff were accredited for POCUS which included lung POCUS. An 8-zone technique was performed and a positive scan for pulmonary oedema was deemed if there were 2 zones per side with positive findings, and positive findings were defined as at least 3 B-lines. 

Lung POCUS correctly identified acute pulmonary oedema with a sensitivity of 92.5% (95% CI 83.4-97.5%) but a lower specificity of 85.7% (95% CI 57.2-98.2%). This compared to CXR which had a lower sensitivity of 63.6% (95% CI 50.9-75.1%) but a higher specificity of 92.9% 95% CI 66.1.-99.8%). 

The study has not been conducted with the rigour to allow an accurate assessment of diagnostic accuracy. The presence of lung POCUS in only 81 of 3,538 represents significant potential selection bias and there are issues of reliability and accuracy with the study reference standard. The figures reported for the accuracy of CXR are not calculated from the same patient data set but from previous reporting. However, the high reported sensitivity for lung POCUS could help clinicians rule out acute heart failure with negative lung POCUS in the undifferentiated patient.

Bottom Line

Lung POCUS can help clinicians to identify acute heart failure in patients who present to the ED with dyspnoea and may perform with a greater sensitivity than CXR. 

Reference

5 Nakao S, Vaillancourt C, Taljaard M, Nemnom MJ, Woo MY, Stiell IG. Diagnostic Accuracy of Lung Point-Of-Care Ultrasonography for Acute Heart Failure Compared With Chest X-Ray Study Among Dyspneic Older Patients in the Emergency Department. J Emerg Med. 2021; 61(2): 161-168. doi:10.1016/j.jemermed.2021.02.019. 

Early computed tomography coronary angiography in patients with suspected acute coronary syndrome: randomised controlled trial 6

If you have ever wondered whether early CT coronary angiography (CTCA) could improve outcomes for patients we see in the Emergency Department (ED) with suspected acute coronary syndrome (ACS), this study gives you an answer. 

This trial was conducted in the UK at 37 hospitals over four years. It included adults with suspected, or a provisional diagnosis of, ACS and randomised them to either early CTCA and standard care or standard care only. The primary endpoint was all cause death, subsequent non-fatal type 1 (spontaneous) or type 4b (related to stent thrombosis) myocardial infarction at one year.

1,748 participants were enrolled (mean age 62 years, 64% male) with 877 randomised to the early CTCA arm and 871 to standard care. The groups were well balanced in terms of patient demographics, presentation, baseline cardiovascular risk factors, history and treatment. The median time from randomisation to CTCA was 4.2 hours in the intervention arm with the scan being of diagnostic quality in 700 (91.3%) patients. There was less invasive angiography in the CTCA arm 474 (54.0%) compared to 530 (60.8%) in the standard care arm. There was no difference in the primary endpoint with 51 (5.8%) in the CTCA arm and 53 (6.1%) in the standard care arm. There was no overall difference in coronary revascularisation, use of drug treatment for ACS or subsequent preventative treatments. There was a small increase in the length of stay in hospital by a median of 0.21 days in the CTCA arm. 

This is a comprehensive study with robust methodology and reporting that has provided a clear answer to a question directly relevant to our practice of emergency medicine. It is important to note that patient satisfaction was far higher in the CTCA arm.

Bottom Line

The routine use of early CT coronary angiography in patients with suspected acute coronary syndrome seen in the ED is not supported. 

Reference

6 Gray AJ, Roobottom C, Smith JE, Goodacre S, Oatey K, O’Brien R, et al. Early computed tomography coronary angiography in patients with suspected acute coronary syndrome: randomised controlled trial. BMJ. 2021; 374: n2106. doi:10.1136/bmj.n2106. 

Age-adjusted D-dimer cut-off levels to rule out venous thromboembolism in patients with non-high pre-test probability: Clinical performance and cost-effectiveness analysis 7

We have all had an older patient present with a swollen leg or shortness of breath and thought it unlikely that they have venous thromboembolism (VTE) but that rule-out was indicated. Unfortunately, their D-dimer comes back slightly raised so they are referred for further investigations where the risk/benefit of anticoagulating must be considered where diagnostic imaging is not immediately available. This study looked at improving the negative predictive value of D-dimer cut-off levels.

The performance of 6 different D-dimer cut-off level strategies were assessed in a derivation study and then validated using different existing large data sets from international multicentre studies. These strategies were: 

  1. Standard strategy: In Wells’ score high-risk patients, or non-high-risk patients with a D-dimer >500ng/ml fibrinogen equivalent units (FEU), diagnostic testing for VTE was performed. Patients who did not have a high-risk and had a D-dimer <500ng/ml received no anticoagulation and were followed up for 3 months.
  2. Higher fixed D-dimer cut-off, 750ng/ml FEU in patients over 70.
  3. Cut-off based on age, 100ng/ml FEU per 10-year increments over 60 years old.
  4. Age adjusted cut-off by multiplying the patients age by 10 in those over 50.
  5. Inverse age adjusted cut-off in patients below 65. Those 66 and above, cut-off set to 500ng/ml FEU. 65 and below cut-off was 500ng/ml FEU plus 10 times 66 minus the patient’s age.
  6. Clinical probability adjusted D-dimer. Moderate risk cut-off <500ng/ml FEU, low risk cut-off <1000ng/ml FEU.

In the derivation study, 644 patients were not high risk using Wells’scoring and had D-dimers performed. All 5 had slightly lower negative predictive values (NPV) compared to the standard strategy for Pulmonary embolisms (PEs) and deep vein thromboses (DVTs). This would have resulted in strategies 2 – 4 missing 1 DVT each, number 5 missing 3 PEs, and number 6 missing 1 DVT and 1 PE. Overall, strategy 4, or age specific cut-off (Age x 10, in ng/ml) was the highest performing alternative strategy.

In the validation study, the age specific cut-off (Age x 10, in ng/ml) was compared to the standard strategy in 1255 patients. The age adjusted D-dimer cut-off performed with a NPV of 99.8% (95% CI 99.1 – 100) in PE compared to 100% (95% CI 99.3-100) using the standard strategy. 

Bottom line

Age specific cut-off (Age x 10, in ng/ml) appears to be as good as the standard VTE rule out strategy and can be considered for use (In line with the 2020 NICE guidelines NG158 on VTE).

Reference

7 De Pooter N, Brionne-François M, Smahi M, Abecassis L, Toulon P. Age-adjusted D-dimer cut-off levels to rule out venous thromboembolism in patients with non-high pre-test probability: Clinical performance and cost-effectiveness analysis. J Thromb Haemost. 2021; 19(5): 1271-1282. doi:10.1111/jth.15278. 

1 Desch S, Freund A, Akin I, Behnes M, Preusch MR, Zelniker TA, Skurk C, Landmesser U, Graf T, Eitel I, Fuernau G, Haake H, Nordbeck P, Hammer F, Felix SB, Hassager C, Engstrøm T, Fichtlscherer S, Ledwoch J, Lenk K, Joner M, Steiner S, Liebetrau C, Voigt I, Zeymer U, Brand M, Schmitz R, Horstkotte J, Jacobshagen C, Pöss J, Abdel-Wahab M, Lurz P, Jobs A, de Waha-Thiele S, Olbrich D, Sandig F, König IR, Brett S, Vens M, Klinge K, Thiele H; TOMAHAWK Investigators. Angiography after Out-of-Hospital Cardiac Arrest without ST-Segment Elevation. N Engl J Med. 2021 Aug 29. doi: 10.1056/NEJMoa2101909. Epub ahead of print. PMID: 34459570.

2 Adi O, Via G, Salleh SH, Chuan TW, Rahman JA, Muhammad NAN, Atan R, Yunos N. Randomized clinical trial comparing helmet continuous positive airway pressure (hCPAP) to facemask continuous positive airway pressure (fCPAP) for the treatment of acute respiratory failure in the emergency department. Am J Emerg Med. 2021 Jun 22;49:385-392. doi: 10.1016/j.ajem.2021.06.031. Epub ahead of print. PMID: 34271286.

3 Stiell IG, Sivilotti MLA, Taljaard M, Birnie D, Vadeboncoeur A, Hohl CM, McRae AD, Morris J, Mercier E, Macle L, Brison RJ, Thiruganasambandamoorthy V, Rowe BH, Borgundvaag B, Clement CM, Brinkhurst J, Brown E, Nemnom MJ, Wells GA, Perry JJ. A randomized, controlled comparison of electrical versus pharmacological cardioversion for emergency department patients with acute atrial flutter. CJEM. 2021 May;23(3):314-324. doi: 10.1007/s43678-020-00067-7. Epub 2021 Jan 18. PMID: 33959925.

4 Reynard C, van den Berg P, Oliver G, Naguib MP, Sammut-Powell C, McMillan B, Heagerty A, Body R. The prognostic value of emergency department measured hypertension: A systematic review and meta-analysis. Acad Emerg Med. 2021 Sep 22. doi: 10.1111/acem.14324. Epub ahead of print. PMID: 34553441.

5 Nakao S, Vaillancourt C, Taljaard M, Nemnom MJ, Woo MY, Stiell IG. Diagnostic Accuracy of Lung Point-Of-Care Ultrasonography for Acute Heart Failure Compared With Chest X-Ray Study Among Dyspneic Older Patients in the Emergency Department. J Emerg Med. 2021 Aug;61(2):161-168. doi: 10.1016/j.jemermed.2021.02.019. Epub 2021 Mar 29. PMID: 33795166.

6 Gray AJ, Roobottom C, Smith JE, Goodacre S, Oatey K, O’Brien R, Storey RF, Curzen N, Keating L, Kardos A, Felmeden D, Lee RJ, Thokala P, Lewis SC, Newby DE; RAPID-CTCA Investigators. Early computed tomography coronary angiography in patients with suspected acute coronary syndrome: randomised controlled trial. BMJ. 2021 Sep 29;374:n2106. doi: 10.1136/bmj.n2106. PMID: 34588162; PMCID: PMC8479591.

7 De Pooter N, Brionne-François M, Smahi M, Abecassis L, Toulon P. Age-adjusted D-dimer cut-off levels to rule out venous thromboembolism in patients with non-high pre-test probability: Clinical performance and cost-effectiveness analysis. J Thromb Haemost. 2021 May;19(5):1271-1282. doi: 10.1111/jth.15278. Epub 2021 Mar 22. PMID: 33638267.

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