Newsletter 491
The 491st Critical Care Reviews Newsletter, featuring the best critical care literature from the past 7 seven days, is now out.
The feature article is the COAST randomised controlled trial, investigating oxygen therapy and high-flow nasal therapy in African children with pneumonia. Other notable articles are the pilot REVERSE-AKI trial, examining restrictive fluid management in acute kidney injury; and a superb overview on the latest understanding on the pathophysiology and phenotypes of COVID-19.
Added May 9th
Image: Solen Feyissa | UnSplash
eCCR21 Edited Videos are Out
The full set of edited videos from the eCritical Care Reviews Meeting 2021 are now available on the eCCR21 webpage. This includes 4 major trial results, a first-in-field phase II trial result, 16 of the best critical care trials & studies from 2020, 3 discussions on trial design, methodology and publishing, as well as the annual John Hinds Lecture. As always, these are free to view.
Added May 9th
Check out our journal watch, which is updated daily, to stay up-to-date with the latest critical care literature. The weekly newsletter contains a summary of the papers highlighted over the previous 7 days and is emailed to registered users every Sunday night.
Image: Zay Nyi Nyi | Shutterstock
Fluid Balance in Acute Kidney Injury
Randomised Controlled Trial
Image: Victor Josan | Shutterstock
COVID-19 Pathophysiology
Narrative Review
Mechanical Ventilation
Narrative Review
Image: Yaw Niel | Shutterstock
Oxygen Therapy
Randomised Controlled Trial
Image: | Shutterstock
Trauma-induced coagulopathy
Narrative Review
Image: Kotcha K | Shutterstock
Berlin Definition for High Flow Nasal Oxygen
Commentary
Image: JHDT Productions | Shutterstock
Tocilizumab for severe COVID-19
Randomised Controlled Trial
Image: Chansom Pantip | Shutterstock
Suvratoxumab for prevention of Staph aureus VAP
Randomised Controlled Trial
Image: sfam_photo | Shutterstock
CVC Infusion Set Related Infection
Randomised Controlled Trial
Image: Orrathai Poolsawat | Shutterstock
Trauma-Induced Hypercoagulopathy
Guideline
Image: Heather | Wikimedia
Vaccine-Induced Thrombotic Thrombocytopaenia
Case Series
Image: samunella | Shutterstock
Vaccine-Induced Thrombotic Thrombocytopaenia
Case Series
Image: Kiryl Lis | Shutterstock
Liberation from Mechanical Ventilation
Randomised Controlled Trial
Image: Patrik Slezak | Shutterstock
Renal Replacement Therapy Initiation
Randomised Controlled Trial
Image: Tongsai | Shutterstock
Post Cardiac Arrest Care
Guideline
Image: Tho-Ge | Pixabay
International Intubation Practice
Observational Study
Image: tungtaechit | Shutterstock
International Weaning Practice
Observational Study
Image: heskaman306 | Shutterstock
Clinical Research in COVID-19
Editorial
Image: Digital Storm | Shutterstock
Anticoagulation in COVID-19
Randomised Controlled Trial
Image: tungtaechit | Shutterstock
Convalescent Plasma in COVID-19
Narrative Review
Image: New York National Guard | Flickr
Chemical Incident
Narrative Review
Sen. Chemical incidents. BJA Education 2021;21(4):126-132
Added March 22nd
Image: Shutterstock | Brookie Cookie
Anticoagulation in COVID-19
RCT Preprint
Image: Shutterstock | Halfpoint
Convalescent Plasma in COVID-19
RCT Preprint
Myocardial Infarction
Narrative Review
Image: Shutterstock | BelezaPoy
Cardiogenic Shock
Guideline
Image: Shutterstock | theskaman306
COVID-19
Commentary
Image: Shutterstock | KILO LUX
Albumin in Cirrhosis
Randomised Controlled Trial
In 777 patients, albumin infusions to increase the albumin level to a target of 30 g per liter or more did not improve the composite primary outcome of new infection, kidney dysfunction, or death between days 3 and 15, but resulted in increased adverse events
Added March 4th
Image: Shutterstock | Casa nayafana
Hepatorenal Syndrome
Randomised Controlled Trial
In 300 adults with cirrhosis and HRS-1, terlipressin was more effective in improving renal function but resulted in less liver transplantation (23% vs 29%) a higher 90-day mortality (51% vs 45%).
Added March 4th
Image: Shutterstock | J-THE PHOTOHOLIC
Pulmonary Artery Catheter
Narrative Review
Image: Shutterstock
Recovery of Consciousness
Observational Study
In 17,470 patients in the Traumatic Brain Injury Model Systems National Database, 7,547 (57%) suffered an initial loss of consciousness, which persisted to rehabilitation in 2,058 patients (12%). Of this group of 2,058 comatose patients, 82% (n = 1674) subsequently recovered consciousness during inpatient rehabilitation.
Added March 1st
Image: Shutterstock
Convalescent Plasma
Meta Analyses
In a systematic review of 4 published trials including 1060 patients with confirmed or treated COVID-19 in any treatment setting, the use of convalescent plasma was not associated with a significant reduction in all-cause mortality; risk ration 0.93 (95% CI, 0.63 to 1.38).
Added February 27th
Image: Shutterstock
Organ Donation
Position Statement
This International Collaborative Statement aims at expanding cDCDD in the world to help countries progress towards self-sufficiency in transplantation and offer more patients the opportunity of organ donation.
Added February 27th
Image: Shutterstock
RECOVERY - Dexamethasone arm
Randomised Controlled Trial
Originally published in provisional format last Summer, the full paper of the RECOVERY trial - dexamethasone arm, is now out. In 6425 hospitalised patients with COVID-19, treatment with 10 mg IV dexamethasone for up to 10 days resulted in a lower 28-day mortality among those who were receiving either invasive mechanical ventilation or oxygen alone.
Added February 25rd
Image: Shutterstock
The BACLOREA Trial
Randomised Controlled Trial
The BACLOREA trial, initial presented at eCCR21, reported a decrease in agitation-related events with baclofen in 314 mechanically ventilated patients with alcohol misuse disorder (19.7% vs. 29.7% with placebo), but a longer length of mechanical ventilation (9 vs 8 days) and stay in the ICU (14 vs 11 days.
Added February 23rd
Image: Shutterstock
The VICTAS Trial
Randomised Controlled Trial
The VICTAS trial, comparing treatment with vitamin C, thiamine, and hydrocortisone with placebo in 501 patients with septic shock, reported no significant difference in ventilator- and vasopressor-free days (25 vs 26 , respectively) at 30 days. Funding was withdrawn after just 501 out of a planned 2000 patients were recruited.
Added February 23rd
Anticoagulation in COVID-19
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.
TTM post Cardiac Arrest
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.
Balanced IV Fluid Solutions
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.
Latest Major RCTs
Vitamin D for COVID-19
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
Image: Dimitri Karastelev | Unsplash
REALITY Trial
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.
Fluids After Bypass Study
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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MENDS2 Trial
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
Image: Shutterstock
Hypothermia for TBI with refractory intracranial hypertension
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
Resumption of Cardiac Activity after Withdrawal of Life-Sustaining Measures
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
HOT-ICU Trial Results
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
Tocilizumab in patients with severe or critical COVID-19
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
Image: M Morea | Shutterstock
Featured
COVID-19
Tocilizumab & sarilumab reduce mortality in severe COVID-19
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
RECOVERY Trial Halts Convalescent Plasma Arm
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
Therapeutic Anticoagualtion halted across 3 COVID-19 Trials
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.
Other Recent RCTS of Note
Inhaled Heparin for ARDS
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).
Procalcitonin to Reduce Long-Term Infection-associated Adverse Events in Sepsis
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
Ultra-early tranexamic acid after subarachnoid haemorrhage (ULTRA): a randomised controlled trial.
Lancet 2020;epublished December 21st
Risk of Overcorrection in Rapid Intermittent Bolus vs Slow Continuous Infusion Therapies of Hypertonic Saline for Patients With Symptomatic Hyponatremia
JAMA Intern Med 2020;epublished October 26th
Higher or Lower Hemoglobin Transfusion Thresholds for Preterm Infants
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
Surviving Sepsis Campaign COVID-19 Update
Crit Care Med 2021;epublished January 28th
Image: AHMETOZER35 | Shutterstock
Recommended
- In
- Systemic corticosteroids
- Venous thromboprophylaxis
- Out
- Hydroxychloroquine
Suggested
- In
- Dexamethasone as perferred steroid
- Remdesevir in non-ventilated critically ill
- Out
- Convalescent plasma (outside clinical trials)
- Therapeutic anticoagulation (outside clinical trials)
- Remdesevir in ventilated critically ill
- No recommendation
- Awake prone positioning.
