Key Point

Daily measurement of blood procalcitonin levels may be useful in identifying critically ill patients at increased risk of dying.

COPENHAGEN, DENMARK—Intensivists may be able to accurately determine which ICU patients are at increased risk for death by means of daily measurement of blood procalcitonin (PCT) levels, a recent study suggests. In the study, a high maximum level and a PCT increase for one day were both independent predictors of 90-day all-cause mortality among 472 critically ill patients.¹

In addition, mortality risk for these patients rose for every day that the procalcitonin level climbed. By contrast, there was no relationship between the chances of dying and the concentrations of two biomarkers previously thought to predict mortality in the critically ill: C-reactive protein and white blood cells.

The study findings raised two important questions: "Can PCT increases be prevented by aggressively treating the cause, bacterial infection, with source control and antibiotics?" wondered principal study author Jens Ulrik Jensen, MD. "If PCT increases can be prevented, will this result in reduced mortality?" added Dr. Jensen, Project Coordinator in the Department of Clinical Microbiology at the Copenhagen University Hospital in Copenhagen, Denmark.

Dr. Jensen maintained that, despite the study findings, there is not yet enough evidence to recommend routinely measuring PCT levels in the setting of critical illness. The remaining questions about this practice must first be addressed in a randomized trial, he told Pulmonary Reviews.

The present study linked daily blood PCT levels to the primary outcome measure of 90-day all-cause mortality and to two important secondary end points: 30-day all-cause mortality and the frequency of complications to bacterial infection. A PCT level of greater than 1.0 ng/mL was considered elevated.

The patients in the study ranged in age from 8 months to 92 years, with a median age of 57.4 years. Twenty-eight (5.9%) of the patients were younger than 16 years.

A total of 3,642 procalcitonin measurements were obtained and evaluated (a mean of 7.7 per patient). "Three hundred forty-three patients obtained a maximum PCT level greater than or equal to 1.0 ng/mL, and 287 (83.7%) of these had an initial PCT greater than or equal to 1.0 ng/mL and thereby an early increase in PCT," related the authors.

The proportion of patients with levels below 1.0, 1.0 to 5.0, and greater than 5.0 ng/mL were 27.3%, 29.7%, and 43%, respectively. For patients with sepsis, procalcitonin rose by a median of 8.4 ng/mL versus only 3.7 ng/mL for nonseptic patients.

The 30- and 90-day all-cause and ICU mortality rates were 28.8%, 35.6%, and 19.1%, respectively. "All these mortality rates are different from the mortality rate when PCT maximum remained <1.0 ng/mL while admitted (4.7%)," the authors said. "With a PCT maximum greater than or equal to 1.0 ng/mL, the mortality rate was 24.9%, and when PCT reached a maximum greater than or equal to 5.0 ng/mL, the mortality rate was 33.5%."

Indeed, the higher the maximum PCT level, the greater the risk of death. The maximum PCT level was a median of 2.7 ng/mL for survivors versus 16.0 ng/mL for nonsurvivors, noted the authors.

In a Cox regression analysis, which did not incorporate APACHE II scores because those scores were not consistently obtained, a rise in blood procalcitonin level on the first day after it had exceeded 1.0 ng/mL independently predicted 30- and 90-day all-cause mortality. Increases in C-reactive protein and leukocyte levels did not predict mortality, however, nor did the maximum levels of those biomarkers.

Ninety-day all-cause mortality was 30.7% for patients with unelevated or decreasing PCT levels compared to 56.1% for those whose PCT level increased for one day, the study also found. "The relative risk for 90-day mortality in patients with an increasing PCT for one day was 1.8, a number that increases for every subsequent day the PCT increases," emphasized the authors.

Besides identifying patients at greater risk of death, procalcitonin elevations significantly predicted sepsis, acute renal failure, and peritonitis in the study population. Among patients whose maximum PCT level was 1.0 ng/mL or higher, the relative risks of those complications were 21.6, 13.1, and 10.2, respectively, versus 5.4, 1.6, and 3.1, respectively, for patients whose procalcitonin remained below 1.0 ng/mL.

"Interestingly, the initial PCT level did not predict mortality even though many patients were admitted with a PCT greater than or equal to 1.0 ng/mL," the authors commented. "This suggests that several PCT measurements should be made consecutively to assess the critically ill patient’s infection-related mortality risk (to monitor treatment of infection day-by-day)."

—Timothy Begany

Reference
1. Jensen JU, Heslet L, Jensen TH, et al. Procalcitonin increase in early identification of critically ill patients at high risk of mortality. Crit Care Med. 2006;34:2596-2602.

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