Procalcitonin and C-reactive protein levels at admission as predictors of duration of acute brain dysfunction in critically ill patients

Abstract

Introduction: Non-intensive care unit (ICU) cohorts have shown an association between inflammatory disturbances and delirium, though these relationships have not been studied in critically ill patients. This study sought to investigate the relationship between two inflammatory biomarkers, procalcitonin and C-reactive protein (CRP), and duration of acute brain dysfunction in ventilated patients.

Methods: Patients enrolled in the Maximizing Efficacy of Targeted Sedation and Reducing Neurological Dysfunction (MENDS) trial were assessed daily for delirium using the Confusion Assessment Method-ICU. Plasma levels of procalcitonin and CRP were obtained within 24 hours of enrollment. Proportional odds logistic regression was used to examine the association between procalcitonin and CRP separately with delirium/coma-free days, adjusting for age, acute physiology score (APS) of the Acute Physiology And Chronic Health Evaluation (APACHE) II, sedation group (dexmedetomidine vs. lorazepam), and sepsis. Secondary analyses examined the association of these markers with other organ dysfunctions and 28-day survival.

Results: Eighty-seven patients were included in this analysis. The median age of the patients was 60 years with APACHE II scores of 28; 68% had sepsis within 48 hours of admission. Higher levels of procalcitonin were associated with fewer delirium/coma-free days [odds ratio (OR), 0.5; 95% confidence interval (CI), 0.3 to 1.0; P = 0.04], whereas higher CRP levels showed trends towards fewer delirium/coma-free days (OR, 0.6; 95% CI, 0.3 to 1.1; P = 0.08). Similar relationships were found regardless of the presence of sepsis. No associations were found between procalcitonin or CRP with 28-day survival (P = 0.40 and 0.16, respectively).

Conclusions: In our pilot study, high baseline inflammatory biomarkers predicted prolonged periods of acute brain dysfunction, implicating inflammation as an important mechanism in the pathophysiology of delirium and coma during critical illness, irrespective of whether patients had sepsis or not.

Figure 1

Association between baseline procalcitonin and delirium/coma-free days. The dark line represents the point estimates for the probability of the outcomes, while the dotted lines represent the confidence intervals. The odds of having more delirium/coma-free days (DCFDs) was significantly reduced with increasing levels of procalcitonin (OR, 0.5; 95% CI, 0.3 to 1.0; P = 0.04). Thus, a patient with a baseline procalcitonin value of 6.7 ng/ml (the 75th percentile value) would have half the odds of having more DCFDs, as a patient with a baseline procalcitonin of 0.4 ng/ml (the 25th percentile value).

Figure 2

Association between baseline C-reactive protein (CRP) and delirium/coma-free days. The dark line represents the point estimates for the probability of the outcomes, while the dotted lines represent the confidence intervals. The odds of having more delirium/coma-free days (DCFDs) was reduced with increasing levels of CRP (OR, 0.6; 95% CI, 0.4 to 1.1; P = 0.08). Thus, a patient with a baseline CRP value of 281.5 mg/L (the 75th percentile value) would have 0.6 times the odds of more DCFDs as a patient with a baseline CRP of 107 mg/L (the 75th percentile value).