Peripheral Perfusion Fails to Cut Septic Shock Mortality

SAN DIEGO — A peripheral perfusion–targeted strategy was not superior to lactate level–targeted resuscitation in lowering mortality for septic shock patients, the ANDROMEDA-SHOCK trial found.

In a randomized study of 424 patients with septic shock, the 28-day mortality was 34.9% in the peripheral perfusion group compared with 43.4% in the lactate level group (HR 0.75, 95% CI 0.55-1.02, P=0.06), Glenn Hernández, MD, PhD, of Pontificia Universidad Católica of Chile, reported here at the Society of Critical Care Medicine meeting.

Although the study narrowly missed its primary endpoint, Hernández told MedPage Today that peripheral perfusion, which was assessed in the trial by serial capillary refill time (CRT) examinations, can still be a legitimate method of resuscitation in some cases, as improvements with the strategy were seen for certain secondary outcomes.

“Patients with peripheral perfusion received less intense treatment, less fluids, less vasopressor testing, and they had some advantages in terms of organ dysfunction,” he said.

With a mean Sequential Organ Failure Assessment (SOFA) score of 5.6 with peripheral perfusion versus 6.6 with the lactate level approach, peripheral perfusion–targeted resuscitation was associated with less organ dysfunction after 72 hours (mean difference -1.00, 95% CI -1.97 to -0.02, P=0.045), according to the findings, which were also published simultaneously in JAMA.

As noted, the peripheral perfusion group received less resuscitation fluids within the first 8 hours (mean difference -408 mL, 95% CI -705 to -110, P=0.01).

The 2016 Surviving Sepsis Guidelines state that previous trials have demonstrated “significant reduction in mortality with lactate-guided resuscitation,” and that if elevated, lactate levels should be frequently assessed to “guide resuscitation to normalize lactate in patients with elevated lactate levels as a marker of tissue hypoperfusion.”

However, Derek Angus, MD, MPH, of the University of Pittsburgh, noted in an accompanying editorial that elevated serum lactate levels can be a symptom of other conditions and in some cases might not be a symptom of septic shock. Additionally, “lactate clearance is often considered too slow to provide timely feedback to clinicians regarding the consequences of their treatment decisions.”

Peripheral perfusion might be an alternative approach, therefore, since “in response to shock, the body will attempt to restrict blood flow to peripheral vascular beds,” he wrote.

Angus also noted that although the authors required a 15% absolute reduction in this study to achieve statistical significance, it’s possible the minimal clinically important difference could be smaller.

“It seems quite likely that the CRT-guided approach is, at a minimum, not inferior to the lactate level–guided approach,” he wrote.

ANDROMEDA-SHOCK was conducted at 28 hospitals in Argentina, Chile, Colombia, Ecuador, and Uruguay. Adult patients (≥18 years) admitted to the intensive care unit with septic shock were recruited within 4 hours. Those with bleeding, severe acute respiratory distress syndrome, or do-not-resuscitate status were excluded. Septic shock was defined as having an infection, hyperlactatemia (≥2.0 mmol/L), and needing vasopressors to maintain a mean arterial pressure ≥65 mm Hg after an intravenous fluid load of ≥20 mL/kg over 60 minutes.

Patients were randomly assigned to either the peripheral perfusion (n=212) or lactate group (n=212), and all treatment centers were trained to assess CRT with a standardized technique. Lactate levels were measured every 2 hours, while CRT was measured every 30 minutes until it normalized, after which it was measured every hour across 8 hours. Clinicians aimed to normalize CRT in the peripheral perfusion group and to normalize or decrease lactate levels by 20% every 2 hours in the other group.

Patients had a mean age of 63 and were roughly split between men and women. Both groups had similar characteristics at baseline, with 71% of patients admitted from the emergency department, 17% from wards, 7% from step-down units, and 5% directly from the operating room.

There was no significant difference between the two groups for six other secondary outcomes, including intra-abdominal hypertension and use of renal replacement therapy. Although 12 patients experienced serious adverse reactions, there was no between-group difference.

The authors noted that the study is limited because it is a non-blinded design, the randomization was not stratified by center, and it may be underpowered to exclude meaningful differences between groups. The authors also did not measure interrater variability of CRTs and only delegated current recommended interventions into a stepwise protocol. Lastly, the results of the study may not be generalizable to critically ill patients at other sites, since this study took place only in the intensive care unit.

last updated 02.19.2019