Category: Critical Care
Keywords: COVID-19, tocilizumab, ICU, mechanical ventilation (PubMed Search)
RECAP: RECOVERY trial is a large, randomized, open label, adaptive trial studying different treatments on COVID-19. Most well known is the use of dexamethasone which reduced mortality by 1/3 in COVID patients requiring mechanical ventilation and by 1/5 in those requiring oxygen, with no benefit on those patients not requiring oxygen.
They recently published results in the Lancet on the use of tocilizumab.
Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial. Lancet. : 1637-1645
Category: Critical Care
The PARAMEDIC2 trial in NEJM 2018 studied the outcomes of the use of epinephrine in outside hospital cardiac arrest (OHCA) on survival and neurological outcome.
Methods: Conducted in Britain, randomized 8007 patients to receive either epinepherine 1mg (n=4012) or placebo (n=3995) as part of standard CPR for out-of-hosptial arrest. Their primary outcome was survival at 30 days and their secondary outcomes included length of stay as well as neurological outcomes at 30 days and 3 months.
Results: The epinepherine group had improved survival to hospital admission (23% vs. 8%), at 30 days (3.2% vs. 2.4%) or at 3 months (3% vs. 2.2%). Favourable neurological outcomes, however, had no statistical difference at both hospital discharge and at 3 months.
Bottom line: Epinephrine improves ROSC, though with poor neurological outcomes.
Recently, a follow up of the PARAMEDIC2 trial was completed in Resuscitation.
They reported long-term survival, quality of life, functional and cognitive outcomes at 3, 6 and 12-months.
Results: At 6 months, 78 (2.0%) of the patients in the adrenaline group and 58 (1.5%) of patients in the placebo group had a favourable neurological outcome (adjusted odds ratio 1.35 [95% confidence interval: 0.93, 1.97]). 117 (2.9%) patients were alive at 6-months in the adrenaline group compared with 86 (2.2%) in the placebo group (1.43 [1.05, 1.96], reducing to 107 (2.7%) and 80 (2.0%) respectively at 12-months (1.38 [1.00, 1.92]). Measures of 3 and 6-month cognitive, functional and quality of life outcomes were reduced, but there was no strong evidence of differences between groups.
Bottom line: Epinephrine improves survival at 12 months, but poor neurological outcomes remain.
Haywood KL, Ji C, Quinn T, Nolan JP, Deakin CD, Scomparin C, Lall R, Gates S, Long J, Regan S, Fothergill RT, Pocock H, Rees N, O'Shea L, Perkins GD. Long term outcomes of participants in the PARAMEDIC2 randomised trial of adrenaline in out-of-hospital cardiac arrest. Resuscitation. 2021 Mar;160:84-93. doi: 10.1016/j.resuscitation.2021.01.019. Epub 2021 Jan 30. PMID: 33524488.
Perkins GD, Ji C, Deakin CD, Quinn T, Nolan JP, Scomparin C, Regan S, Long J, Slowther A, Pocock H, Black JJM, Moore F, Fothergill RT, Rees N, O'Shea L, Docherty M, Gunson I, Han K, Charlton K, Finn J, Petrou S, Stallard N, Gates S, Lall R; PARAMEDIC2 Collaborators. A Randomized Trial of Epinephrine in Out-of-Hospital Cardiac Arrest. N Engl J Med. 2018 Aug 23;379(8):711-721. doi: 10.1056/NEJMoa1806842. Epub 2018 Jul 18. PMID: 30021076.
Category: Critical Care
Ever wonder what to tell the families regarding prognosis of the sickest COVID-19 patients you intubate in the ED or ICU?
Introduction: Case fatality rates (CFR) for COVID-19 patients requiring invasive mechanical ventilation have been widely variable. A study in the Blue Journal (AJRCCM) examined patients requiring intubation in a systemic review and meta-analysis.
The case fatality risk of an infection is represented by the proportion of patients who die among all infected cases in a population over a period of time.
Methods: 69 studies axross 23 countries for a total of 57,420 patients with COVID-19 who required mechanical ventilation were included in analysis.
Results: Overall case fatality rate was 45%, or about 1 death for every two intubated patients.. Among studies that included age stratification, pooled estimates of CFR were 47.9% in patients <40 (CI 46.4-49.4%) and 84.4% in patients >80 (CI 83.3-85.4%). Overall heterogeneity is high (I 2 .90%),
In early COVID epicenters, CFR was 70% among patients aged more than 60 years of age. CFR increased exponentially with increasing age.
Specifically in the US across 21 studies (3,811 intubated patients), CFR was 47% (95% CI, 36–57%). Studies from New York reported a CFR of 54% (95% CI, 36–72%) whereas other regions in the United States reported a CFR of 41% (95% CI, 30–53%).
Definitive hospital CFR (aka for those with hospital discharge outcomes, 13,120 patients) was 56% (CI 47-65%).
Conclusion: Almost half of patients with COVID-19 receiving IMV died based on the reported CFR. The reported CFR was higher in older patients and in early pandemic epicenters, which may be influenced by limited ICU resources.
Limitations: Overall CFR of 45% still included patients in the hospital. Definitive hospital outcomes were only for 13,120 patients (36.6%). Significant variation in CFR exists between studies.
Lim ZJ, Subramaniam A, Ponnapa Reddy M, Blecher G, Kadam U, Afroz A, Billah B, Ashwin S, Kubicki M, Bilotta F, Curtis JR, Rubulotta F. Case Fatality Rates for Patients with COVID-19 Requiring Invasive Mechanical Ventilation. A Meta-analysis. Am J Respir Crit Care Med. 2021 Jan 1;203(1):54-66.
Angriman F, Scales DC. Estimating the Case Fatality Risk of COVID-19 among Mechanically Ventilated Patients. Am J Respir Crit Care Med. 2021 Jan 1;203(1):3-4.
Category: Critical Care
Keywords: Cardiac arrest, transport, EMS (PubMed Search)
Historically, there has been debate on transporting outside hospital cardiac arrests, as well a trauma, with the question of whether to "scoop and run" or "stay and play".
Could hasty transportation of cardiac arrest patients put a damper on resuscitation quality?
A recent propensity-matched study in JAMA analyzed 192 EMS agencies across 10 N American sites.
-Resuscitation Outcomes Consortium Cardiac Epidemiologic Registry, which counted 43,969 consecutive cases of nontraumatic adult EMS-treated OHCA (median age 67, 37% of whom were women) in 2011-2015.
-25% of these patients were transported to the hospital
-Matched 1:1 with patients in refractory arrest who were resuscitated on scene
-Primary outcome was survival to hospital discharge, secondary outcome survival to hospital discharge with a favorable neurological status
-Duration of out-of-hospital resuscitation was only 6 minutes longer in the intra-arrest transport group (29.1 and 22.9 minutes; not a statistically significant difference)
-Survival to hospital discharge was 3.8% for patients who underwent intra-arrest transport and 12.6% for those who received on-scene resuscitation
-In the propensity-matched cohort, which included 27,705 patients, survival to hospital discharge occurred in 4.0% of patients who underwent intra-arrest transport vs 8.5% who received on-scene resuscitation (risk difference, 4.6% [95% CI, 4.0- 5.1])
-Favorable neurological outcome occurred in 2.9% of patients who underwent intra-arrest transport vs 7.1% who received on-scene resuscitation (risk difference, 4.2% [95% CI, 3.5%-4.9%])
-Intra-arrest transport during resuscitation was associated with worse odds of survival to hospital discharge compared to on-scene resuscitation (4% vs 8.5%, RR 0.48, CI 0.43-0.54)
-Findings persisted across subgroups of initial shockable rhythm vs. non-shockable rhythms (most common initial rhythm was aystole), as well as EMS witness arrests vs. unwitnessed arrests
-This study does not support the routine transportation of patients in cardiac arrest during rescuscitation.
-The neurologically intact survival benefit associated with on-scene resuscitation is both impressive and intriguing.
-However, what implications could this have on ECPR?
-Potential bias due to observational nature of study
-Duration of resuscitations very similar, unknown exactly how long transport times were or if this was in urban or rural populations
-External validity not generalizable due to heterogeneity of patient populations and EMS systems
-Further randomized clinical trials are required
Grunau B, Kime N, Leroux B, et al. Association of Intra-arrest Transport vs Continued On-Scene Resuscitation With Survival to Hospital Discharge Among Patients With Out-of-Hospital Cardiac Arrest. JAMA. 2020;324(11):1058–1067. doi:10.1001/jama.2020.14185
Category: Critical Care
Keywords: gastrointestinal bleeding, TXA (PubMed Search)
Prior to this study, a Cochrane review and meta-analysis of TXA for upper GI bleeds with 7 trials (1654 patients), showed a large reduction in mortality with TXA (RR 0.61, 95% CI 0.42-0.98, p=0.01)
-Randomized, international, multicentre, placebo-controlled trial at 164 hospitals in 15 countries Juy 2013-2019
->16/18 years old with upper or lower GI bleeding
-1 g TXA IV over 10 minutes followed by maintenance dose 3 g TXA over 24 hours
-Main outcome death due to bleeding within 5 days
-4% (222/5994) died in TXA group vs 4% (226/5981) placebo risk ratio RR 0.99, 95% CI 0.82-1.18
-Arterial thromboembolic events MI/CVA similar in both groups (0.7% vs 0.8%)
-Venous thromboembolic events PE/DVT higher in TXA group (0.8% vs 0.4%)
-Initially calculated all cause mortality until realization that over half deaths were due to non-bleeding causes, changed to death related to bleeding, allowing study appropriate power to detect difference
-Majority of patients had UGIB/variceal bleeding due to liver disease, over 75% deaths in those with liver disease
-Only 16% patients randomized in <3 hours, most >8 hours (CRASH-2 trial found benefit TXA in trauma patients only <3 hrs to administration)
-TXA should not be used in the management of GI bleeds
-Increased venous thromboembolic events associated with TXA administration for GI bleeds
HALT-IT Trial Collaborators. Effects of a high-dose 24-h infusion of tranexamic acid on death and thromboembolic events in patients with acute gastrointestinal bleeding (HALT-IT): an international randomised, double-blind, placebo-controlled trial. Lancet. 2020;395(10241):1927-1936. doi:10.1016/S0140-6736(20)30848-5
Gluud LL, Klingenberg SL, Langholz E. Tranexamic acid for upper gastrointestinal bleeding. Cochrane Database Syst Rev. 2012;1