UMEM Educational Pearls - By Lindsay Ritter

Takeaways

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. 

Population: 

• Up to 21 days after main randomization, regardless of treatment, RECOVERY trial patients with progressive COVID-19 were eligible for tocilizumab. 

Inclusion: 

• April 23rd 2020 to Jan 24th 2021-- 21,550 patients with hypoxia (<92% on RA or requiring O2), systemic inflammation (CRP > 75 mg/L) eligible for standard care or standard care plus toci 400-800 mg (dosing based on weight), second dose 12-24 hours later if no improvement

Outcomes: 

• Primary outcome 28 day mortality followed by:
• Hospital discharge within 28 days
• Rate of mechanical ventilation 

Results: 

• 621 (31%) tocilizumab patients and 729 (35%) of usual care patients died within 21 days (RR 0.85, p=0.0028). Consistent even in those receiving steroids (83%).
• Tocilizumab group more likely to be discharged from the hospital, less likely to receive invasive mechanical ventilation (35% vs 42%).

Conclusion: 

• Tocilizumab improved survival and other clinical outcomes- by 1/3 for those on simple oxygen, and by ½ for those receiving invasive mechanical ventilation.
• Added to the additional benefit of steroids. 
• Findings support the earlier REMAP-CAP trial on the effectiveness of tocilizumab for ICU COVID patients 

 

Show More In-Depth Information

Show References

Takeaways

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. 

Important facts: 

• Demographics: Mean age 69 years, 35% female
• Initial cardiac rhythm: shockable 19%, Non-shockable 78%, Undetermined 2%
• Cause of Cardiac Arrest: Medical 91% Traumatic 2%, Drowning 0.2%, substance overdose 2%, Asphyxia 3%, missing data 2%
• Witness of cardiac arrest: none 37%, Paramedic 11%, Bystander 50%, missing data 1%
• CPR Performed by: Paramedic 11%, bystander 59%, missing data 2%
• Time from: emergency call to ambulance arrival 6min, emergency call to administration of drug 22 min, arrival to ambulance departure 50 min

 

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. 

Show More In-Depth Information

Show References

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.

 

Show References

Takeaways

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.

Methods:

-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 

 

Results:

-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 

 

Conclusion:

-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? 

 

Limitations:

-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

Show More In-Depth Information

Show References

Takeaways

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)

Design:

-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 

 

Results:

-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%)

 

Pitfalls:

-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) 

 

Takeaway:

-TXA should not be used in the management of GI bleeds

-Increased venous thromboembolic events associated with TXA administration for GI bleeds

Show More In-Depth Information

Show References