Conference Coverage

Peripheral perfusion fails septic shock test, but optimism remains



– During resuscitation of patients with septic shock, a simple strategy of timing the refilling of peripheral capillaries trended toward better 28-day survival than using lactate level targeting, but missed statistical significance.

Jim Kling/MDedge News

Dr. Glenn Hernández (left) and Dr. Jan Bakker

Although the paper, published online in JAMA, concludes that normalization of capillary refill time cannot be recommended over targeting serum lactate levels, Glenn Hernández, MD, PhD, sounded more optimistic after presenting the study at the Critical Care Congress sponsored by the Society of Critical Care Medicine. “I think it’s good news to develop techniques that, even though they have this integrated variability, they can provide a signal that is also very close to the [underlying] physiology,” Dr. Hernández, who is a professor of intensive medicine at Pontifical Catholic University in Santiago, Chile. The Peripheral perfusion was also associated with lower mean Sequential Organ Failure Assessment (SOFA) Score at 72 hours.

The technique involves pressing a glass microscope slide to the ventral surface of the right index finger distal phalanx, increasing pressure and maintaining pressure for 10 seconds. After release, a chronometer assessed return of normal skin color, with refill times over 3 seconds considered abnormal. Clinicians applied the technique every 30 minutes during until normalization (every hour after that), compared with every 2 hours for the lactate arm of the study.

The ANDROMEDA-SHOCK randomized clinical trial was conducted at 28 hospitals in five countries (Argentina, Chile, Colombia, Ecuador, Uruguay). The trial did not demonstrate superiority of capillary refill, and it was not designed for noninferiority. It nevertheless seems unlikely that assessment of capillary refill is inferior to lactate levels, according an accompanying editorial by JAMA-associated editor Derek Angus, MD, who also is a professor of critical care medicine at the University of Pittsburgh. The simplicity of using a capillary refill could be particularly useful in resource-limited settings, since it can be accomplished visually.

It also a natural marker for resuscitation. The body slows fluid flow to peripheral tissues until vital organs are well perfused. Normal capillary refill time “is an indirect signal of reperfusion,” said Dr. Hernández.

The researchers are not calling for this technique to replace lactate measurements, noting that in many ways the techniques can be complementary, since lactate levels are a good indicator of the patient’s overall improvement. In any case, it would take more research to prove superiority of the capillary refill, and that’s not something Dr. Hernández is planning to undertake. The current study had no external funding and required about half of his time over a 2-year period. Getting the work done at all “was sort of a miracle. We would not repeat this,” he said.

The researchers randomized 416 patients with septic shock (mean age, 63 years; 53% of whom were women) to be managed by peripheral perfusion or lactate measurement. By day 28, 43.4% in the lactate group had died, compared with 34.9% in the peripheral perfusion group (hazard ratio, 0.75; P = .06). At 72 hours, the peripheral perfusion group had less organ dysfunction as measured by SOFA (mean, 5.6 vs. 6.6; P = .045). Six other secondary outcomes revealed no between-group differences.

The peripheral perfusion group received an average of 408 fewer mL of resuscitation fluids during the first 8 hours (P = .01).

That result fits with the greater responsiveness of peripheral perfusion measurements, and it’s relevant because some septic shock patients who are unresponsive to fluids often receive fluids anyway. “The general knowledge, though not correct, is that you treat lactate or blood pressure with fluids,” said coauthor Jan Bakker, MD, PhD, who is a professor at New York-Presbyterian Hospital Columbia University, and Erasmus University Rotterdam, the Netherlands.

After a series of observational studies suggested that warm, well-perfused patients were doing well, the idea was tested in a small interventional trial in which physicians were forbidden from giving fluids once patients were warm and well perfused. Patients did better than did those on standard of care. “We have said, if the patient is warm and well perfused, even if they are hypotensive, don’t give fluids, it won’t benefit them anymore. Give vasopressors or whatever, but don’t give fluids,” said Dr. Bakker.

The latest research also reinforced a signal from the earlier, smaller trial. “You get less organ failure if you use [fewer] fluids,” Dr. Bakker added.

The study received no external funding. Dr. Hernández and Dr. Bakker had no relevant financial disclosures. Dr. Angus received consulting fees from Ferring Pharmaceutical, Bristol-Myers Squibb, Bayer AG, and others outside the submitted work; he also has patents pending for compounds, compositions, and methods for treating sepsis and for proteomic biomarkers.

SOURCE: Hernández G et al. JAMA 2019 Feb 17. doi: 10.1001/jama.2019.0071.

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