Early this year, two important conferences outside our specialty unveiled a spate of new findings whose impact will be felt in our practice. Here’s a quick rundown of the most interesting trials presented.
Explore This IssueACEP Now: Vol 39 – No 04 – April 2020
Critical Care Reviews 2020
Held this year in Belfast, Northern Ireland, Critical Care Reviews (CCR) brought to first light several important trials relevant to emergency medicine and critical care. One of the most important, the Vitamin C, Hydrocortisone and Thiamine in Patients With Septic Shock (VITAMINS) trial, was covered in these pages by Jeremy Samuel Faust, MD, MS, MA, FACEP, in February.1 This trial, one of the first to actually rigorously evaluate a treatment protocol for sepsis featuring thiamine, vitamin C, and corticosteroids, was not able to confirm the hoped-for survival advantage.
A second important trial also has implications for emergency care, the concisely and informatively named “65 trial.”2 This trial looks primarily at the enshrined target mean arterial pressure (MAP) of 65 mmHg in patients whose physiology is being supported by vasopressors. Like many things in medicine, this target is based on a combination of observational evidence and opinion, and despite this, it remains a “strong” recommendation in the Surviving Sepsis Campaign (SSC) guidelines.3
The 65 trial was a massive undertaking, with 2,463 patients ultimately included in the primary analysis. In this trial, elderly patients with vasodilatory shock and receiving vasopressors were randomized to either “permissive hypotension” or usual care in line with the SSC guidelines. Permissive hypotension meant patients were targeted to a range between 60 and 65 mmHg rather than titrating care to maintain MAP greater than 65 mmHg.
The topline, unadjusted results demonstrated no significant difference between treatment strategies. Overall mortality at 90 days, the primary outcome, was 41.0 percent in the permissive cohort and 43.8 percent with usual care. This small mortality difference favoring permissive hypotension was insufficient to meet statistical significance, although the prespecified adjusted analysis tipped this finding over the line. It would be erroneous to attribute a reliable mortality advantage to treatment with permissive hypotension, but there is no signal of harm.
These results are not surprising if we realize the MAP is not a measure of blood flow through the capillary bed. We are relying on MAP, the pressure of fluid in those larger muscular arteries and arterioles, as a surrogate for end-organ perfusion. This must be balanced against the potential harmful effects of vasopressors.
Interestingly, the actual treatment received by those in the permissive hypotension arm was not terribly hypotensive. The mean MAP while receiving vasopressors in the permissive arm was still 66.7 mmHg compared to 72.6 mmHg in those receiving usual care. A sizable fraction of those in the trial were treated with metaraminol, a vasopressor with primarily alpha-receptor effects, potentially impacting generalizability to settings where norepinephrine is the preferred first-line agent. However, this study neatly shows you need not exercise vigilance in keeping MAP above 65 mmHg at all times.
Other notable work presented at CCR included a 26,000 patient trial comparing proton pump inhibitors to histamine-2 receptor blockers in ICU patients, cardiac catheterization following out-of-hospital cardiac arrest, and global data on the burden of sepsis.