TERN Top Papers August 2022

Authors: Richard Grimwood, Mike Penn, Sabbir Islam, Robert Darke, Josh Pinedo, Rachel Graham, Yousuf Akbari, Rishad Jiffry, Matt Stokle, Nikhil Tambe, Josh Beck / Editor: Robert Hirst / Codes: / Published: 18/08/2022

This months TERN Top Papers is brought to you by a group of emergency medicine trainees from the North-East led by Richard Grimwood, the TERN North East Regional Rep.

This months TERN Top Papers covers papers on critical care. We have reviewed over 1300 studies to produce this final edit of 10 papers worth reading from the last year.

The association between end-tidal CO2 and return of spontaneous circulation after out-of-hospital cardiac arrest with pulseless electrical activity1


Crickmer et al. carried out a retrospective cohort study of 208 out of hospital cardiac arrest patients with an initial rhythm consistent with pulseless electrical activity (PEA) in Ontario, Canada. Their primary outcome was to examine the association between change in end-tidal carbon dioxide (ETCO2) during resuscitation and likelihood of return of spontaneous circulation (ROSC). Their secondary objective was to compare the predictive value of delta ETCO2 for ROSC with that of the initial and final ETCO2 value. Delta ETCO2 was defined as the difference between the initial ETCO2 recording 1 minute after placement of an advanced airway, and the final recording 1 minute before ROSC or termination of resuscitation.

Results identified a positive linear association between delta ETCO2 and subsequent prehospital ROSC in PEA with an odds ratio of 1.74 (95% CI 1.35-2.24, p<0.001) for every 10mmHg increase in delta ETCO2. Furthermore, a delta ETCO2 greater than 20mmHg had a specificity of 95% (95% CI 0.680.83) for attaining ROSC in PEA.

There were limitations to this study. Firstly, the retrospective design of this study means strong conclusions cannot be drawn. Secondly, study numbers were low and potentially overestimates the significance of ETCO2 in this patient cohort. Lastly, values were only recorded after insertion of an endotracheal tube. Several patients (180) were not intubated and therefore not included, and the decision to intubate could have resulted in selection bias. This is suggested by their higher than previously documented rate of ROSC (32% compared with 17.8% on previous studies), potentially due to intubating only those patients that were more likely to survive.

Nevertheless, this study provides evidence that positive ETCO2 changes during a cardiac arrest situation are favourable for ROSC and should be used to inform decision making processes

Bottom Line

Up-trending changes in ETCO2 during a PEA cardiac arrest suggest a more favourable outcome and should encourage continuation of a resuscitation attempt unless there is a clear indication to stop.


Crickmer M, Drennan IR, Turner L, Cheskes S. The association between end-tidal CO2 and return of spontaneous circulation after out-of-hospital cardiac arrest with pulseless electrical activity. Resuscitation 2021; 167: 76-81. doi: 10.1016/j.resuscitation.2021.08.014.

Targeted temperature management following out-of-hospital cardiac arrest: a systematic review and network meta-analysis of temperature targets2


Fernando et al. conducted a systemic review and meta-analysis of randomised controlled trials comparing various degrees of hypothermia (31-32 C, 33-34 C, 35-36 C) to normothermia (37-37.8 C) in comatose patients who had achieved return to spontaneous circulation (ROSC) following out of hospital cardiac arrest.

Six databases were searched from inception until June 2021. The primary outcome was survival with good functional outcome (using four different indices). Secondary outcomes included survival at discharge and up to 6 months post discharge and adverse events related to targeted temperature management (TTM) during hospitalisation. 10 RCTs with a combined total of 4218 patients were included, involving data from HYPERION, TT2M and CAPITAL-CHILL trials.

The results identified that compared to normothermia (37-37.8 C), there was no effect on survival with good functional outcome using deep (31-32 C) (OR 1.30 [95% CI 0.73-2.30]), moderate (33-34 C) (OR 1.34 [95% CI 0.92-1.94]) or mild (35-36 C) hypothermia (OR 1.44 [95% CI 0.74-2.80]). Furthermore, compared to moderate hypothermia, there was no effect of deep hypothermia (OR 0.97 [95% CI 0.61-1.54], low certainty).

Looking at secondary outcomes, compared to normothermia, there was no effect on overall survival using deep (OR 1.27 [95% CI 0.70-2.32]), moderate (OR 1.23 [95% CI 0.86-1.77]) or mild hypothermia (OR 1.26 [95% CI 0.64-2.49]). Compared to normothermia, arrhythmia was more common among patients receiving moderate (OR 1.45 [95% CI 1.08-1.94]) and deep hypothermia (OR 3.58 [95 % CI 1.77-7.26]).

The strengths of this review encompass a broad search, use of unpublished data from study authors and pre-registered protocols including GRADE guidance used to assess the certainty of evidence for comparisons. Several important limitations exist, however. Within almost all trials, treating clinicians could not be blinded to temperature target group allocation. In the interests of heterogeneity nearly 20 years between the first and most recent trials would harbour variability in ALS protocols, improvements in system care and equipment available.

Bottom Line

The review overall is consistent with the results of TT2M, finding temperatures of 33-34 C did not improve survival or functional outcome, trending away from the current European Resuscitation Council guidelines.


Fernando SM, Di Santo P, Sadeghirad B, Lascarrou JB, Rochwerg B, et al., Targeted temperature management following out-of-hospital cardiac arrest: a systematic review and network meta-analysis of temperature targets. Intensive Care Med. 2021 Oct;47(10):1078-1088. doi: 10.1007/s00134-021-06505-z.

Outcomes after Prehospital Traumatic Cardiac Arrest in the Netherlands: A Retrospective Cohort Study3


Traumatic cardiac arrest (TCA) is a challenging clinical situation, and optimal management and prognostication remains uncertain. A retrospective observational study from the Netherlands looked at 915 prehospital adult TCAs attended to by the Helicopter Emergency Medical Services (HEMS). Data was obtained from review of the medical databases of the three involved HEMS stations.

The primary outcome was survival to hospital discharge, with 36 (3.9%) patients meeting this endpoint. 17/36 (47.2%) survivors had good neurological outcome (Glasgow outcome scale 5). Secondary outcomes included return of spontaneous circulation (ROSC) and was achieved in 261 (28.5%) patients. The study observed that age >70 years was associated with a statistically significant lower survival compared with those <70 years (0.7% vs 5.2%, p=0.041). Survival was also more likely in patients with a shockable rhythm on initial electrocardiogram (ECG). 13.3% with a shockable rhythm survived, compared with 1% in those with asystole (Odds ratio 0.28, 95%CI 0.09-0.90, p = 0.032). 63 patients underwent thoracotomy with 2 survivors (both had cardiac tamponade) making good neurological recovery. No patients with blunt thoracic trauma receiving prehospital thoracotomy survived, nor did patients arriving at hospital without ROSC. No difference in survival was seen for prehospital endotracheal intubation, type of receiving hospital (trauma centre vs non-trauma centre), or any prehospital intervention.

The conclusions that can be drawn from this study are limited by its design. There is limited information about methodology, authors were involved in study design, data collection, and analysis which increases the risk of bias. The aetiology of TCA in surviving patients was hypoxia due to traumatic brain injury in 17/36 (45.5%) patients and several other TCA subgroups were excluded, which limits generalisability. Similarly, this study looks at TCA attended to by highly skilled HEMS teams and may not be applicable to non-HEMS.

Despite the limitations of this study, it offers insight into prognostic factors for prehospital TCA. Interestingly, no prehospital intervention reached statistical significance for improved survival. Given ethical and practical limitations observational data may be all that is available to inform management of prehospital TCA. The Trauma Emergency Thoracotomy for Resuscitation in Shock (TETRIS) is an upcoming UK national audit project likely to further contribute to knowledge in this field.

Bottom Line

In patients with prehospital TCA there is an association with increased survival in patients younger than 70 years old, and patients with initial shockable rhythm on ECG.


Houwen T, Popal Z, de Bruijn MAN, Leemeyer AR, et al., Outcomes after Prehospital Traumatic Cardiac Arrest in the Netherlands: a Retrospective Cohort Study. Injury. 2021 May;52(5):1117-1122. doi: 10.1016/j.injury.2021.02.088.

Awareness with paralysis in mechanically ventilated patients in the emergency department and intensive care unit: a systematic review and meta-analysis4


Anaesthetic awareness has been well studied in patients undergoing surgery in theatre and is linked with significant psychological sequelae. Awareness in ventilated patients in Emergency Department (ED)/Intensive Care Unit (ICU) settings has not been extensively explored. Ventilated patients in ED may receive under-dosed induction agents or delayed sedation, increasing the risk of awareness. This paper hypothesised that incidence of awareness is higher in the ED/ICU population than in theatre.

This systematic review examined RCTs, cohort studies or case series reporting on awareness in mechanically ventilated patients in ED/ICU through April 2020. 4,454 papers were identified, with seven studies (n= 941 patients) included in the final analysis. Four studies related to the ED population (n=304), all being single-centre studies from highly developed countries (three US, one Australia), with significant study size range (n=11-191). Data were summarised using random effects meta-analysis. Bias risk and study quality were assessed using Cochrane Collaboration tool, Newcastle-Ottawa scale or Moga Quality Appraisal checklist depending on study type.

The primary outcome was presence of awareness. Secondary outcomes included the survey methods used to detect awareness. Meta-analysis of the ED studies reports incidence of awareness in this population to be 14.2%. Only one ED study used a validated survey (modified Brice questionnaire) to detect awareness. The authors conclude that the incidence of awareness in mechanically ventilated patients in the ED and ICU is much higher than the theatre population, quoting an incidence in the theatre population of 0.1-0.2% based on previous RCTs.

This review has several limitations and weaknesses. All but one of the ED studies were deemed to be poor quality. There was significant heterogeneity of results, study design (with only one RCT, and this being an ICU vs ED study), sedation and neuromuscular blocking agents used, and survey tool (if any) utilised across studies. There was a paucity of included studies with small total patient numbers, especially ED patients.

Bottom Line

The authors raise an important question, perhaps even more poignant in our age of long bed waits and ever-increasing demands on our departments: is there the potential for increased risk of awareness in ventilated patients in ED compared to the controlled environment of the operating theatre? This review suggests that this is the case but draws upon a small amount of poor quality and heterogenous literature further large, multi-centre, and more rigorously executed research into this area is required.


Pappal RD, Roberts BW, Winkler W, Yaegar LH, Stephens RJ, Fuller BM. Awareness With Paralysis in Mechanically Ventilated Patients in the Emergency Department and ICU: A Systematic Review and Meta-Analysis. Crit Care Med. 2021 Mar 1;49(3):e304-e314. doi: 10.1097/CCM.0000000000004824.

Fentanyl versus placebo with ketamine and rocuronium for patients undergoing rapid sequence intubation in the emergency department: The FAKT studyA randomized clinical trial5


This Australian multi-centre, double blind placebo-controlled randomised trial included adult patients requiring rapid sequence induction (RSI) in the emergency department (ED) over a two-year period. The primary outcome was whether the addition of fentanyl alongside a standardised RSI sequence of ketamine and rocuronium resulted in a post induction change in systolic blood pressure (SBP) outside the target range of 100-150mmHg. Secondary outcomes included laryngoscopy grade, tachycardia, hypoxia, and mortality at 30 days.

302 patients were randomised to receive either fentanyl or placebo, in addition to ketamine and rocuronium. Patient characteristics between the two groups were similar.

Fentanyl was given in a dose proportional to the ketamine dose (e.g. fentanyl made up to 10mcg/ml, if administering 100mg ketamine would administer 100mcg fentanyl) and those in the placebo group received the same volume of 0.9% sodium chloride. Patients then received either a standard dose of ketamine (1-2mg/kg) or reduced (0.5-1mg/kg) and rocuronium (1.5mg/kg). Drugs were delivered in the order of study drug (fentanyl or placebo), followed by ketamine and then rocuronium.

Intubations were standardised including monitoring, preoxygenation, position, use of an airway checklist and intubation attempted 60 seconds post rocuronium with additional use of sedatives discouraged. Observations were recorded every 2 minutes for ten minutes looking at systolic BP outside the range of 100-150 or >10% change if SBP already outside of this baseline.

There was no statistical difference in SBP outside of the pre-specified range between the two groups. However, there was a trend suggesting that there was a higher rate of hypotension in the fentanyl group compared to placebo (SBP < 100): 29% vs 16% Difference 13% (95% CI 3%-23%).

There was a higher rate of hypertension (SBP>150): 55% vs 69%, difference 14% (95% CI 3%-24%) and tachycardia in the placebo group (HR 120): 48% vs 61%, difference 13% (95% CI 2%-25%). Of note there was no difference in 30-day mortality between either group.

Although well designed, there were limitations. This is not a patient centred primary outcome as the long-term clinical significance of transient haemodynamic changes is not clear in current literature. Additionally, a fixed ratio of fentanyl to ketamine and discouragement in giving further sedation post induction for management of hypertension may not reflect clinicians practice and therefore may have affected the outcomes.

Bottom line

Fentanyl, when given in a fixed ratio with ketamine, may result in an increased risk of peri-intubation hypotension, therefore selecting doses of induction agents should be based on patient haemodynamics, underlying pathology and the co-induction agent used.


Ferguson I, Buttfield A, Burns B, Reid C, Shepherd S, Milligan J, Harris IA, Aneman A; Australasian College for Emergency Medicine Clinical Trials Network. Fentanyl versus placebo with ketamine and rocuronium for patients undergoing rapid sequence intubation in the emergency department: The FAKT study-A randomized clinical trial. Acad Emerg Med. 2022 Jun;29(6):719-728. doi: 10.1111/acem.14446.

Isolated traumatic brain injury: Routine intubation for Glasgow Coma Scale 7 or 8 may be harmful!5


Intubation has been the standard practice in patients with a GCS <9 in trauma. This study explores the possible downfalls of this reflexive practice in isolated head injury with a GCS of 7 or 8. It also examines the factors influencing the decision to intubate.

This retrospective study analysed the data of 2727 patients across 750 trauma-centres over a 4-year period with isolated blunt head injury and a GCS of 7 or 8 on admission. They were classified into those who were intubated immediately (<1-hour of admission), underwent delayed intubation (>1-hour of admission) and those who werent intubated.

The primary outcome was in-hospital mortality. Secondary outcomes included overall complications, ventilator days, and ITU and hospital lengths of stay. Other variables were recorded including age, sex, comorbidities, tachycardia, alcohol/ illegal drug use, and the head injury severity reflected by the Abbreviated Injury Scale (AIS) score.

The majority (68.4%) were intubated within the first hour of admission and 23.4% were never intubated. 8.2% requiring delayed intubation were analysed as a separate group and found to have worse outcomes. Immediate intubation was independently associated with higher mortality (95% CI 1.31-2.44; p < 0.001) and increasing complications (95% CI 1.62-3.73; p < 0.001). Interestingly the study showed that alcohol above legal limits was a protective factor overall. It also identified that younger age, higher AIS, tachycardia and GCS of 7 were independent factors influencing the decision to intubate.

There are limitations associated with the retrospective study design, the inability to distinguish emergency versus routine intubation or the specific cause of death from the database, all of which may act as confounders.

Bottom Line

In this study immediate intubation of GCS 7 or 8 in head injury was independently associated with a higher mortality and more overall complications. The study suggests that being aged 45 years, AIS score 5, and GCS 7 would help reduce the number of delayed intubations (high-specificity) which could potentially aid as a better guide to intubation than the knee-jerk practice guided by GCS alone.


Jakob DA, Lewis M, Benjamin ER, Demetriades D. Isolated traumatic brain injury: Routine intubation for Glasgow Coma Scale 7 or 8 may be harmful! J Trauma Acute Care Surg. 2021 May 1;90(5):874-879. doi: 10.1097/TA.0000000000003123.

Effects of cardiopulmonary resuscitation on direct versus video laryngoscopy using a mannequin model7


This study aimed to determine the best intubation technique during CPR; direct laryngoscopy (DL) versus video laryngoscopy (VL) with either a C-MAC or GlideScope. A mannequin model undergoing chest compressions delivered by a LUCAS device was used to simulate CPR.

Fifty emergency physicians intubated a mannequin using each technique both with and without ongoing compressions. The order physicians used each technique was varied to avoid temporal bias. The average length of post-graduate emergency medicine experience amongst the physicians was 9.8 years and they most commonly reported increased comfort with DL.

Time to intubation during CPR was significantly quicker with the C-MAC (22.49 seconds) compared to both DL (28.55 seconds, p=0.007) and the Glidescope (30.92 seconds, p=0.039). The average Cormack-Lehane laryngeal view obtained during CPR was 1.04 for C-MAC, 1.07 for Glidescope but fell to 1.74 for DL. The improved views with both VL techniques were significant when compared to DL (p<0.0001). Moreover, intubation was perceived to be easier when using VL both with and without ongoing compressions. The success rate for intubation was 100% with VL, whereas it was only 94% for DL.

Although a robust design, this was a small study limited by use of a mannequin model with results that are dependent on physicians level of skill and familiarity with the intubation techniques in question. This evidence does not show that VL improves patient-centred outcomes.

Bottom line

When intubating during CPR, the use of video laryngoscopy may increase your likelihood of success if you are familiar with this technique.


Kei J, Mebust DP. Effects of cardiopulmonary resuscitation on direct versus video laryngoscopy using a mannequin model. Am J Emerg Med. 2021 Dec;50:587-591. doi: 10.1016/j.ajem.2021.09.031.

Effect of Use of a Bougie vs Endotracheal Tube with Stylet on Successful Intubation on the First Attempt Among Critically Ill Patients Undergoing Tracheal Intubation8


Driver et al carried out a multicentre, pragmatic, randomised clinical trial in the US across 15 sites, including seven emergency departments (EDs) and eight intensive care units (ICUs). They excluded patients who were pregnant, incarcerated, did not have time for randomisation and bougie or stylet contraindicated as determined by the operator.

All adult patients undergoing intubation using sedation and a non-hyperangulated laryngoscope blade were included. Primary outcome was first pass intubation using an endotracheal tube (ETT) with bougie or with stylet while a single secondary outcome measure was incidence of severe hypoxemia (SpO2<80%).

1102 patients were enrolled in the study. 42% had one or more difficult airway features (e.g. obesity, cervical spine immobilisation). Video laryngoscopy was used for 75.7% in the bougie group and 73.8% in the stylet group. There was no significant difference in successful intubation on the first attempt between the groups (adjusted OR 0.88, 95% CI, 0.64 to 1.22).

This is a robust study with wide inclusion criteria and baseline traits evenly distributed amongst groups. The study involved intubating under certain specific conditions so may not be replicable in different circumstances. 61.6% of operators were resident physicians which may influence the success rate of first pass intubations. It is also noteworthy that this is a US based study where emergency physicians will more routinely intubate patients compared to their counterparts in the UK. As such, we cannot directly apply these results to UK practice. Any patient who the doctor thought might benefit from a bougie or who had a contraindication was not included in the study’s randomisation, therefore potentially excluding individuals who would gain more benefit from its use, which may have affected outcomes.

Bottom Line

In this US based study in an ED and ICU setting, there was no significant difference with the use of ETT with bougie over stylet for first pass intubation.


Driver BE, Semler MW, Self WH, Ginde AA, Trent SA, Gandotra S, Smith LM, Page DB, Vonderhaar DJ, et al., Effect of Use of a Bougie vs Endotracheal Tube With Stylet on Successful Intubation on the First Attempt Among Critically Ill Patients Undergoing Tracheal Intubation: A Randomized Clinical Trial. JAMA. 2021 Dec 28;326(24):2488-2497. doi: 10.1001/jama.2021.22002.

Emergency physicians experience of stress during resuscitation and strategies for mitigating the effects of stress on performance9


Goombridge et al. performed a two-centre sequential exploratory mixed methods study. Their aims were to investigate which resuscitation scenarios emergency physicians (EPs) find stressful and perceive as affecting their performance, and which strategies these physicians employ to mitigate the impact of stress on their performance.

Seven experienced EPs with a relevant interest self-presented and were asked open questions in a focus group. Their answers, alongside concepts derived from a recent systematic review, informed the design of an online survey of EPs at two large tertiary urban EDs. 82/102 participants responded (80.4%).

Top stressors were paediatric (81%) and pregnant (71%) resuscitations, undifferentiated or unfamiliar scenarios (65% each), conflict with and lack of confidence in a team member (71% and 51%). Top mitigation strategies were verbalising plans (81%), applying a standardised approach (70%) and asking for help (55%). The same stressors were reported equally often regardless of experience, but mental rehearsal and verbalising to the team were more commonly used by juniors (62% vs 22% and 92% vs 72%). A disparity between genders is noted with women more frequently stressed by unfamiliar procedures (71% vs 35%) and previous similar bad experiences (58% vs 20%), while men ask for help less (47% vs 79%). Curiously, while nobody denied experiencing stress, five employed no mitigating techniques; these were mostly more experienced and universally male.

Although there was near equal gender representation in the focus group, more than twice as many men responded to the survey. It isnt stated if this is representative of the departments. Subjectively markedly improved performance increased until stress became extreme when performance precipitously fell and markedly impaired performance was more commonly reported. Whilst interesting, it should be noted that self-reported, retrospective data is often unreliable and partially contradicts the deleterious effects of stress on performance described by the focus group.

Bottom line

In this small study amongst emergency physicians in Melbourne, similar scenarios were found to stress clinicians regardless of experience. Stress mitigation strategies displayed common themes and were more often used by those with less experience.


Groombridge CJ, Maini A, Ayton D, et al., Emergency physicians’ experience of stress during resuscitation and strategies for mitigating the effects of stress on performance. Emerg Med J. 2021 Dec 14:emermed-2021-211280. doi: 10.1136/emermed-2021-211280.

Impact of prehospital airway interventions on outcome in cardiac arrest following drowning: A study from the CARES Surveillance Group10


This US study uses the Cardiac Arrest Registry to Enhance Survival (CARES) database to retrospectively analyse 2388 drowning patients between 2013-2018.

They reviewed three different airway interventions the bag valve mask (BVM), endotracheal tube (ETT), and supraglottic airway (SGA – which included a range of devices) comparing survival to hospital admission, survival to hospital discharge and survival to discharge with favourable neurological outcome (a Cerebral Performance Score of 1 or 2).

When focusing on survival to hospital discharge with favourable neurological outcome, there was no significant difference between the three airway interventions. Whilst yielding similar results to AIRWAYS-2 (a large multicentre cluster randomised trial from 2018 looking at airway interventions in out-of-hospital cardiac arrest), this is perhaps surprising as many clinicians would assume an ETT is superior to correct the pathophysiology in a cardiac arrest secondary to drowning.

Although the results were adjusted for variables such as age, gender, and bystander CPR, the retrospective nature of this study means it is limited by the data that has been recorded in the CARES database. Other factors which are known to influence survival in drowning such as submersion time, water temperature and time to first CPR were not recorded. The order in which airways were used or number of attempts required were also not mentioned.

Bottom Line

This retrospective study looking at airway interventions in cardiac arrest secondary to drowning showed no difference in neurological outcomes between the use of a BVM, SGA, or ETT. However, it is limited by its retrospective design meaning many variables have not been accounted for.


Ryan KM, Bui MD, Dugas JN, Zvonar I, Tobin JM. Impact of prehospital airway interventions on outcome in cardiac arrest following drowning: A study from the CARES Surveillance Group. Resuscitation. 2021 Jun;163:130-135. doi: 10.1016/j.resuscitation.2020.12.027.

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