Wednesday September 29th
Chief investigator Lars Andersen joins Rob Mac Sweeney to address some of the questions and comments that arose following the presentation and publication of the VAM-IHCA trial results, investigating vasopressin and methylprednisolone for in-hospital cardiac arrest.
Added October 13th, 2021
How do we interpret a trial with an apparent substantial mortality effect, but which fails to reach the predefined level of statistical significance?
With a faculty consisting of trialists, clinicians, methodologists, and a statistician, we have the perfect group to discuss the implications of the COVID STEROID-2 trial.
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Critical care trials are fascinating to ponder. Some report findings of benefit, many report an inconclusive answer or apparent lack of efficacy. Some report harm. This blog will explore the why of critical care trials - why was this intervention successful, why was this intervention ineffective, why was the intervention harmful.
If you'd like to join us for a weekly in-depth exploration of the latest major critical care trials, then please register for the free weekly newsletter here
First up for review at the blog is the REST trial. Why did the REST trial¹ fail to clearly demonstrate benefit with the addition of an ECCO₂R device in invasively mechanically ventilated patients with acute hypoxaemic respiratory failure?
Added October 4th
Dale. Effect of oral chlorhexidine de-adoption and implementation of an oral care bundle on mortality for mechanically ventilated patients in the intensive care unit (CHORAL): a multi-center stepped wedge cluster-randomized controlled trial. Intensive Care Med 2021;epublished October 5th
Prof Alistair Nichol talks about the latest investigative agent to be added to the REMAP-CAP portfolio - ivermectin. With a huge amount of controversy surrounding this agent worldwide, Prof Nichol elequently describes why this major international trial has decided it is worth a valuable place in this platform trial.
Dexamethasone 12 mg versus 6 mg for patients with COVID-19 and severe hypoxia: an international, randomized, blinded trial
Plasma-Lyte 148® versUs Saline Study
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Typically 90 minutes to 2 hours in length
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This Brazilian 2x2 factorial trial will randomise ICU patients at moderate to high risk for death or AKI to receive a balanced crystalloid solution (Plasma-Lyte®) or 0.9% saline and to receive crystalloids by rapid bolus infusion (999 mL/h) or slow infusion (333 mL/h) whenever plasma expansion is needed.
Tuesday, August 10th, 18:30 UTC
To date, it's been unclear how patients with severe COVID-19 requiring non-invasive respiratory support should be managed. With over 1200 patients, the UK RECOVERY-RS trial is now the largest global non-invasive respiratory support trial for COVID-19, and compares CPAP with high flow nasal oxygen with standard care.
Thursday, August 5th, 18:30 UTC
The ACTIV4-a, ATTACC, & REMAP-CAP investigators will present the results of this multi-platform trial, in which critically ill adults were randomized to receive therapeutic anticoagulation with heparin or pharmacological thromboprophylaxis as per local usual care.The preprint of the main paper was published on March 12th in MedRxiv.
Wednesday, August 4th, 20:30 UTC
The 512th Critical Care Reviews Newsletter, featuring the best critical care literature from the past 7 seven days, is now out.
Added October 3rd
Image: Solen Feyissa | UnSplash
We'll bring these important results to you live and free
The ACTIV4-a, ATTACC, & REMAP-CAP investigators will present the results of this multi-platform trial examining therapeutic & prophylactic anti- coagulation in patients with COVID-19. The interim analysis was released January 28th and is available via the link below.
Originally planned for CCR21, which became eCCR21, but delayed into the Spring, the long awaited results of the follow-up trial to the landmark targeted temperature management after out-of-hospital cardiac arrest is out soon. Is the avoidance of fever the critical aspect of TTM? The results are due very soon.
This massive 11,000 patient trial from Brazil was also scheduled for CCR21, but was unavoidably delayed due to the pandemic. Comparing Plasma-Lyte 148 with 0.9% saline, it's almost ready for release now and we're delighted to be hosting this major trial result later this Spring.
In a Brazilian two-centre, blinded RCT in 240 patients with moderate or severe COVID-19, Murai and colleagues reported that a single oral dose of 200 000 IU vitamin D3 did not significantly change the median (IQR) length of hospitalisation; vitamin D3 group, 7.0 (4.0-10.0) days, vs. placebo group, 7.0 (5.0-13.0) days; log-rank, P = 0.59; unadjusted HR, 1.07; 95% CI, 0.82-1.39; P = 0.62.
JAMA 2021;epublished February 17th
In 668 patients with acute myocardial infarction and a hemoglobin level between 7 and 10 g/dL, a red cell transfusion threshold of ≤8 g/dL was found to be non-inferior to a threshold of ≤10 g/dL, with the composite MACE outcome (all-cause death, stroke, recurrent myocardial infarction, or emergency revascularization) at 30 days occurring in 11% vs 14%, respectively.
In 715 patients undergoing cardiopulmonary bypass and randomised to a protocol-guided strategy, using stroke volume variation to guide the administration of bolus fluids, or to usual care fluid administration, until desedation or up to 24 hours, there was no difference in the primary outcome of ICU length of stay; (median/IQR) intervention group; 27.9 hr (21.8–53.5 hr) vs control, 25.6 hr (21.9–64.6 hr); p = 0.95.
Crit Care Med 2021;epublished January 28th
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In 432 ventilated adults with sepsis, randomised to receive IV sedation with either dexmedetomidine (0.2 to 1.5 μg/kg/hr) or propofol (5 to 50 μg/kg/min), there was no difference between groups in the primary outcome of days alive without delirium or coma during the 14-day intervention period; 10.7 vs. 10.8 days; OR, 0.96; 95% CI, 0.74 to 1.26; respectively. There were also no differences in secondary outcomes, including mortality.
N Engl J Med 2021;epublished February 2nd
In adult patients suffering a traumatic brain injury, with a GCS score of 4 to 8, and initial ICP ≥ 25 mm Hg, the implementation of long-term mild hypothermia group (34–35 °C for 5 days), in comparison with normothermia group at 37 °C, did not improve the proportion with a favorable outcome (OR 1·55, 95%CI 0·91–2·64; P = 0·105) or mortality (P = 0·111) at 6 months.
EClinicalMedicine 2021;epublished January 28th
In a prospective study in 20 ICUs in 3 countries, amongst 631 patients who underwent continued monitoring after planned withdrawal of life-sustaining support, 14% of patients had a resumption of cardiac activity after a period of pulselessness. Just 1 percent were observed clinically. The longest period to resumption of cardaic activity was 4 minutes 20 seconds.
N Engl J Med 2021; 384:345-352 | January 28th, 2021
Image: SURIYO CINNABUT | Shutterstock
In a Danish led, international, multi-centre, randomised controlled trial trial in 2928 adults with acute hypoxaemic respiratory failure, targetting a PaO2 of 8 kPa, in comparison with 12 kPa, did not improve the primary outcome of 90-day mortality (42.9% vs 42.4%; adjusted risk ratio, 1.02; 95% CI, 0.94 to 1.11; P=0.64).
Presented at eCCR21. Video available at eCCR21 webpage
N Engl J Med 2021;epublished January 20th
Image: AndaPhoto | Shutterstock
In a Brazilian randomised controlled trial involving 9 hospitals, the use of tocilizumab as a single intravenous infusion of 8 mg/kg plus standard care (n=65) versus standard care alone (n=64), resulted in suimilar levels of mechanical ventilation at day 15 (28% vs. 20; (odds ratio 1.54, 95% CI0.66 to 3.66; P=0.32).), respectively, and increased mortality (17% vs. 3%; odds ratio 6.42, 95% CI,1.59 to 43.2).
BMJ 2021;372:n84, published January 20th
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In a pre-print paper, the REMAP-CAP trial investigators have reported efficacy with interleukin 6 receptor anatgonists in critically ill patients with COVID-19. Hospital mortality was 28.0% (98/350) for tocilizumab, 22.2% (10/45) for sarilumab and 35.8% (142/397) for control.
Preprint January 7th
In 10,406 randomised patients, with 1873 reported deaths, there was no significant difference in the primary endpoint of 28-day mortality -18% convalescent plasma vs. 18% usual care alone; risk ratio 1.04 [95% confidence interval 0.95-1.14]; p=0.34.
Prof Peter Horby, Tweet, Jan 15th
Three large randomised controlled trials, ATTACC, @ACTIV4a, and REMAP-CAP, have, for futility, halted recruitment to their therapeutic anticoagulation arms in critically ill patients with COVID-19.
In this multi-centre, blinded Australian trial, 25 000 IU of nebulised heparin administered 6 hourly while invasively ventilated, did not significantly alter the primary outcome of functional outcomes (SF-36) at 60 days; survivors in the heparin group (n=97) mean 53·6 vs control 48·7; difference 4·9 [95% CI –4·8 to 14·5]; p=0·32).
In this trial PCT-guided antimicrobial treatment in sepsis was effective in reducing infection-associated adverse events like infections by multidrug-resistant organisms and Clostridioides difficile, as well as in-hospital and 28-day mortality.
Am J Respir Crit Care Med 2021;202(3):202–210
January 17th 2021
Lancet 2020;epublished December 21st
JAMA Intern Med 2020;epublished October 26th
In 1824 infants born prematurely between 22 and 26 weeks and weighing less than 1000 g, a higher hemoglobin threshold for red-cell transfusion did not improve survival without neurodevelopmental impairment at 22 to 26 months of age, corrected for prematurity
N Engl J Med 2020;383:2639-2651
Crit Care Med 2021;epublished January 28th
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