TERN Top Papers September 2021

Following on from the 2013 Targeted Temperature Management (TTM) study which compared a targeted temperature of 33^oC vs. 36^oC in patients with an out-of-hospital cardiac arrest from a presumed cardiac cause³, TTM2 sought to determine whether targeted hypothermia compared with targeted normothermia impacts all-cause mortality. This sought to provide clarity of whether treatment benefit results from targeted temperature management or the avoidance of fever.

It was an international, multicentre, randomised, superiority trail. Pre-specified secondary outcomes, included neurological outcome and health related QOL (which arguably could be considered more important than all-cause mortality, the primary outcome), and subgroup analyses (sex, age, time to ROSC, initial rhythm and whether shock present on admission).

4355 patients were screened with 45% going onto randomisation within the ED. The commonest reasons for exclusion were >180 minutes since ROSC, non-cardiac cause for arrest, not unconscious, or limitations to care in place. 1861 were analysed using an intention to treat (ITT) analysis, with an even split between the normothermia control (physical cooling started at 37.8^oC) and hypothermia groups (70% cooled with external devices and 30% intravascular). Only 11 patients were lost to follow-up. 1862 participants gave a power of 90% ( 0.05, NNT 13.3) to detect an ARR of 7.5% in mortality. This was increased to 1900 to account for loss of follow-up. Pre-defined common standards of management were listed. Of note patients were co-enrolled with the TAME trial, which could potentially be a confounder.

No difference in all-cause mortality or the secondary outcomes was found. Higher rates of arrhythmias with haemodynamic instability were reported in the hypothermia group. However, the time to reaching hypothermia was not achieved until 3 hours post-randomisation, which leaves the question of whether early pre-hospital or ED cooling may be beneficial.

Bottom Line

Although hypothermia as a treatment for conditions where neurological outcomes are important has shown promise in lab-based experiments, TTM2 does not show translation of this to real word practice. Aiming for normothermia is more achievable in an Emergency Department than therapeutic hypothermia. Although questions remain unanswered over the role of early rapid cooling, my practice will be to aim for normothermia and treat fevers 37.8^oC.

References

2. Dankiewicz J, Cronberg T, Lilja G, Jakobson J, et al. Hypothermia versus Normothermia after Out-of-Hospital Cardiac Arrest. N Engl J Med. 2021 Jun 17; 384(24):2283-2294. doi: 10.1056/NEJMoa2100591. PMID: 34133859.
3. Nielsen N, Wetterslev J, Cronberg T, Erlinge D, et al. Targeted Temperature Management at 33 Versus 36 Degrees: A Retrospective Cohort Study. Crit Care Med. 2020 Mar;48(3):362-369.

This observational study looked at the introduction of early whole-body CT as a diagnostic aide post ROSC. The authors coined the term sudden death CT (SDCT) to describe the protocol.

104 patients were recruited who had no clearly identifiable cause of arrest (i,.e. no ST elevation, obvious pneumothorax or known life threatening pre-morbid condition). Patients underwent an SDCT scan consisting of head to pelvis venous phase CT and ECG gated CT-CA.CT findings were then compared to a ranked list of presumed causes compiled by a senior clinician from ED and a senior cardiology doctor (who also had access to the CT findings).

SDCT identified a cause of arrest in 37.5% (39/104) patients but 95% (39/41) of causes that the authors deemed could potentially be identified on CT.
The remaining 65 causes were either: seizure, substance misuse, asthma, electrolyte disturbance or unknown.

13% of patients had a cause of arrest identified on SDCT that could not have been identified without CT. Specifically these identified 2 strokes, 3 abdominal catastrophe, 1 ACS, a pneumonia not previously seen on CXR and 5 PEs.

The protocol called for scans within 6 hours of hospital arrival, however in practice the average time to scan was just 2 hours. Whilst its difficult to verify from the data, the authors felt that SDCT accelerated the time to diagnosis in several cases. Given existing experience with trauma CT its reasonable to assume that CT post ROSC doesnt need to cause delay in other aspects of the patient journey, though this clearly needs further study.

For a large (but not all-encompassing) group of pathologies, SDCT can rapidly identify (potentially intervenable) causes for cardiac arrest. However, given that treating clinicians had access to the CT findings it is unclear how often the SDCT either changed or accelerated a patients treatment.

Bottom Line

Rapid whole body CT post ROSC appears to reliably provide an intervenable diagnosis in a large proportion of cases although an RCT is needed to see if this will actually lead to improved patient outcomes.

Reference

4. Branch KRH, Strote J., Gunn M, Maynard C, et al. Early head-to-pelvis computed tomography in out-of-hospital circulatory arrest without obvious etiology. Acad Emerg Med. 2021; 28(4): 394-403. 2021. doi:10.1111/acem.14228

The CANLEAD trial utilised high-fidelity simulation of cardiac arrest scenarios to perform a non-blinded randomised controlled trial. Their primary intervention was the allocation of a designated nursing team leader, alongside the medical team lead who had a defined, discrete set of tasks to oversee. Their primary outcome was assessment of the cognitive load of the medical team leader as assessed by the NASA task load index (NTLX). Secondary outcomes included team performance, cognitive load of the nursing team leader, and cognitive load of other team members.

A total of 20 simulations were performed with 120 participants. Their key finding was that the medical team leaders in the intervention group had a significantly lower NTLX score than the control group, with no increase in the NLTX score of the senior/lead nurse. The mean demand (used as a proxy for cognitive load comprised of 5 domains in the NTLX) on the medical team lead was found to be 24% lower in the intervention group (p=0.02). There was also improved performance in 9 out of 10 performance indicators measured.

This study does have its limitations it is a non-blinded, two-centre trial, performed in Australia, using simulation instead of real-life scenarios. Participants were also recorded, potentially introducing a further element of performance anxiety. It also used demand as a surrogate for cognitive load, which has not been externally validated. Despite this, it could have significant implications for the management of cardiac arrest within the Emergency Department this simple, easily achievable intervention could provide a reduction in cognitive load for medical team leads, (thus reducing the risk of cognitive overload and allowing concentration on higher-order tasks), as well as improving overall team performance, and potentially patient outcomes.

Bottom Line

Introduction of a nursing team lead during cardiac arrest scenarios could significantly reduce cognitive load of the medical team lead, improve overall team performance and potentially positively impact patient outcomes.

Reference

5. Pallas JD, Smiles JP; Zhang M. Cardiac Arrest Nurse Leadership (CANLEAD) trial: A simulation-based randomised controlled trial implementation of a new cardiac arrest role to facilitate cognitive offload for medical team leaders. Emergency Medicine Journal. 2021; 38(8): 572-578. doi:10.1136/emermed-2019-209298

This was a cluster randomized clinical trial of an initial advanced airway management strategy of supraglottic airway device (SGA) compared to tracheal intubation (TI) in adults with nontraumatic out-of-hospital cardiac arrest.

The patient-focussed primary outcome demonstrated no statistical difference in the Modified Rankin Scale score measure of global disability at hospital discharge or 30 days after out-of-hospital cardiac arrest, whichever occurred sooner. Secondary analysis also demonstrated no significant difference in a number of other outcomes including survival, though the supraglottic airway showed greater early ventilation success.

Of note, those randomised to the tracheal intubation strategy were less likely to ultimately receive any advanced airway management, and of those that did, almost a quarter received a supraglottic device as initial management. Limitations included multiple pragmatic and logistical issues intrinsic to completing a trial of this nature. There was a large crossover between groups, and many in the allocated groups received no advanced airway management.

On the theme of advanced airway management in cardiac arrest, another recent trial noted improved first pass success with video laryngoscopy vs. direct laryngoscopy for tracheal intubation, albeit without improvements in rates of ROSC.⁷

Bottom Line

In this trial, randomisation to either initial advanced airway management with tracheal intubation or supraglottic airway device did not change outcomes. With the perceived relative ease and speed of SGA insertion, particularly compared to tracheal intubation in the pre-hospital environment, practice and guidelines may move to increase their use.

References

6. Benger JR, Kirby K, Black S, Brett SJ, et al. Effect of a strategy of a supraglottic airway device vs tracheal intubation during out-of-hospital cardiac arrest on functional outcome: the AIRWAYS-2 randomized clinical trial. JAMA. 2018; 320(8): 779-91. doi :10.1001/jama.2018.11597

7. Huebinger RM, Stilgenbauer H, Jarvis JL, et al. Video laryngoscopy for out of hospital cardiac arrest. Resuscitation. 2021; 162: 143-8. doi: 10.1016/j.resuscitation.2021.02.031

The aim of this study was to assess the relationship between Emergency Department (ED) occupancy rates and the incidence of in-hospital cardiac arrest (IHCA) during the ED stay – that is, cardiac arrests occurring after arrival to the ED but before hospital admission.

In a single centre (a large university teaching Hospital) in Korea, registry data for all adult non-traumatic in-hospital cardiac arrests for a period of 3.5 years was retrospectively analysed. Four measurements of ED occupancy rate (defined as the ratio of total number of ED patients to the number of beds in the ED) were noted: time of arrival, time of arrest, highest occupancy rate during that patients ED stay and the average occupancy rate during that patients stay. The primary outcome was the association between the incidence of in-hospital cardiac arrest and emergency department occupancy rates.

187 patients suffered IHCA in the ED. The investigators found that as ED occupancy increased, incidence of cardiac arrest also increased. The correlation was strongest with the measurement of the maximum ED occupancy rate during that patients stay. The study did not show any correlation between ED occupancy rates and outcome from IHCA in the ED (mortality or poorer neurological outcomes). The investigators hypothesise that this may be in part because the same amount of medical personnel would attend to a patient in cardiac arrest, regardless of levels of ED crowding.

Bottom Line

This observational study showed a positive correlation between ED occupancy rate and incidence of cardiac arrest in the ED, particularly pertinent given the current level of demand being placed on our service throughout the UK. Although it did not show a relationship between ED occupancy rate and outcome of IHCA, it is something to keep in mind as bed waits and wait to first assessment time increases.

Reference

8. Kim J, Bae H, Sohn, CH, Cho S, et al. Maximum emergency department overcrowding is correlated with occurrence of unexpected cardiac arrest. Critical Care. 2020; 24: 305 (2020).

This was a multicentre trial over 31 sites in Germany and Denmark comprised of 554 randomised patients over 30 years old who were successfully resuscitated after out of hospital cardiac arrest with no evidence of ST elevation on post resuscitation ECG.

Patients were randomised to either immediate angiography or delayed/ selective angiography as a standard practice group. The first group were transferred to a cath lab as soon as possible, whereas the control group were transferred to ICU for further assessment, or if the likelihood of an acute coronary event was high, proceeded to angiography with a minimum of a 24 hour delay. This trial builds on research from the COACT trial¹⁰ by including patients with shockable and non-shockable rhythms.

Set exclusion criteria were applied and all patients accounted for. Clinical discretion was used for excluding patients on the grounds of haemodynamic instability.

The unblinded primary outcome of all-cause mortality at 30 days showed no significant difference between immediate angiography (54%) compared to a delayed or selective approach (46%). Of note most patients in each group died of anoxic brain injury or circulatory collapse.

Secondary outcomes were stated by authors to be hypothesis generating as these were not adjusted for multiplicity. 17% of patients were changed from delayed/selective approach to angiography within 24 hours however the 12% difference in primary outcome groups is likely affected by this.

Alongside the DISCO and ARREST trials this forms an interesting body of work that may in the future inform our practice.

Bottom Line

If you are working in a UK ED without on-site access to a cath lab (the majority of sites), there is no significant benefit in expediting transfer for a haemodynamically stable in terms of 30 day mortality. Further research in a UK population alongside robust follow-up data is needed if we are to consider changing out practice.

References

9. Desch S, Freund A, Akin M, Behnes M, et al. Angiography after out-of-hospital cardiac arrest without ST-segment elevation. N Engl J Med. 2021. DOI:10.1056/NEJMoa2101909. Online ahead of print.
10. Lemkes JS, Janssens GN, van der Hoeven NW et al. Coronary Angiography after Cardiac Arrest without ST-Segment Elevation. N Engl J Med. 2019; 380: 1397-1407 DOI: 10.1056/NEJMoa1816897.

This meta-analysis aimed to examine the relationship between gender and survival and prognosis following out of hospital cardiac arrest (OHCA).

Following a database search, 33 studies out of 1042 articles were selected comprising a total of 1,268,664 patients. The pooled odds ratios and 95% CIs were estimated using a random-effects model.

Overall, females were older than males (69.7 years vs. 65.4 years, p<0.05), were less likely to suffer witnessed OHCA (58.39% vs 62.70%, p<0.05), and were less likely to receive in-hospital interventions than males; this included coronary angiography (CAG) (37.84% vs 42.7%, p<0.05), percutaneous coronary intervention (PCI) (27.63% vs 34.78%, p<0.05) and targeted body temperature management (TTM) (25.05% vs 40.49%, p<0.05).

In addition, the frequency of shockable rhythm in females was lower (25.74% vs 39.62%, p<0.05). There were no differences in bystander resuscitation based on sex (38.82% vs 41.89%, p>0.05) and ROSC (26.97% vs 26.10%, p>0.05) contrary to previously published studies ¹².

No significant difference in survival from OHCA to admission between males and females was found (OR 0.99, 95% CI 0.891.1) However, 9 of the 33 studies analysed were used to look at survival to discharge from admission, and this appeared significantly lower in females than for males (OR 0.59, 95% CI 0.480.73). In addition, females had a lower probability of good neurological prognosis than males (OR 0.62, 95% CI 0.470.83)

Limitations and confounding factors included the use of only 3 databases which may have excluded some relevant studies. All studies were observational. Studies ranged from 1980 to 2018. Post-resuscitation care has changed in this time, specifically use of TTM. A spread of countries with differences in emergency medical systems and varying determinants for resuscitation and levels of nursing care may have impacted significantly on outcomes, more so than differences in male and female physiology.

Bottom Line

No significant difference was found between males and females surviving OHCA and being admitted to hospital, however females fare poorly in terms of survival and neurological outcome following admission. The authors postulate that may be more likely due to differences in medical services and levels of nursing care and these differences could be reduced with better education and improvements in medical and nursing care.

References

11. Hao L, Jiahui H, Leiling L, Danyan X. Sex differences in survival after out-of-hospital cardiac arrest: a meta-analysis. Crit Care. 2020; 24(1): 613. doi: 10.1186/s13054-020-03331-5

12. Blom MT, Oving I, Berdowski J, van Valkengoed IGM, et al. Women have lower chances than men to be resuscitated and survive out-of-hospital cardiac arrest. Eur Heart J. 2019; 40(47): 3824-34. doi: 10.1093/eurheartj/ehz297