Serial inflammatory biomarkers of the severity, course and outcome of late onset acute respiratory distress syndrome in critically ill patients with or at risk for the syndrome after new-onset fever.

AIM: Accurate biomarkers of the acute respiratory distress syndrome (ARDS) may help risk stratification and management. We assessed the relation between several biomarkers and the severity, course and outcome of late onset ARDS in 101 consecutive critically ill patients with new onset fever. MATERIALS AND METHODS: On study days 0, 1, 2 and 7 we measured angiopoietin-2 (ANG2), pentraxin-3 (PTX3), interleukin-6 (IL-6), procalcitonin (PCT) and midregional proadrenomedullin (proADM). ARDS was defined by the Berlin definition and by the lung injury score (LIS). RESULTS: At baseline, 48% had ARDS according to the Berlin definition and 86% according to the LIS. Baseline markers poorly predicted maximum Berlin categories attained within 7 days, whereas ANG2 best predicted maximum LIS. Depending on the ARDS definition, the day-by-day area under the receiver operating characteristic curves suggested greatest monitoring value for IL-6 and PCT, followed by ANG2. ANG2 and proADM predicted outcome, independently of disease severity. CONCLUSION: Whereas IL-6 and PCT had some disease monitoring value, ANG2 was the only biomarker capable of both predicting the severity, monitoring the course and predicting the outcome of late onset ARDS in febrile critically ill patients, irrespective of underlying risk factor, thereby yielding the most specific ARDS biomarker among those studied.

Albumin rather than C-reactive protein may be valuable in predicting and monitoring the severity and course of acute respiratory distress syndrome in critically ill patients with or at risk for the syndrome after new onset fever.

BACKGROUND: We studied the value of routine biochemical variables albumin, C-reactive protein (CRP) and lactate dehydrogenase (LDH) to improve prediction and monitoring of acute respiratory distress syndrome (ARDS) severity in the intensive care unit. METHODS: In 101 critically ill patients, with or at risk for ARDS after new onset fever, data were collected on days (D) 0, 1, 2, and 7 after inclusion. ARDS was defined by the Berlin definition and lung injury score (LIS). RESULTS: At baseline, 48 patients had mild to severe ARDS according to Berlin and 87 according to LIS (Rs = 0.54, P < 0.001). Low baseline albumin levels were moderately associated with maximum Berlin and LIS categories within 7 days; an elevated CRP level was moderately associated with maximum Berlin categories only. The day-by-day Berlin and LIS categories were inversely associated with albumin levels (P = 0.01, P < 0.001) and directly with CRP levels (P = 0.02, P = 0.04, respectively). Low albumin levels had monitoring value for ARDS severity on all study days (area under the receiver operating characteristic curve, AUROC, 0.62-0.82, P < 0.001-0.03), whereas supranormal CRP levels performed less . When the Berlin or LIS category increased, albumin levels decreased ≥1 g/L (AUROC 0.72-0.77, P = 0.001) and CRP increased ≥104 mg/L (only significant for Berlin, AUROC 0.69, P = 0.04). When the LIS decreased, albumin levels increased ≥1 g/L (AUROC 0.68, P = 0.02). LDH was higher in 28-day non-survivors than survivors (P = 0.007). CONCLUSIONS: Overall, albumin may be of greater value than CRP in predicting and monitoring the severity and course of ARDS in critically patients with or at risk for the syndrome after new onset fever. Albumin levels below 20 g/L as well as a decline over a week are associated with ARDS of increasing severity, irrespective of its definition. LDH levels predicted 28-day mortality.

Rising C-reactive protein and procalcitonin levels precede early complications after esophagectomy.

BACKGROUND: Elective esophagectomy with gastric tube reconstruction carries a high risk for complications. Early and accurate diagnosis could improve patient management. Increased C-reactive protein (CRP) levels may be associated with any, surgical or infectious, complication and procalcitonin (PCT) specifically with infectious complications. METHODS: We measured CRP and PCT on post-operative days 0, 1, 2, and 3 in 45 consecutive patients. Complications were recorded up to 10 days post-esophagectomy. RESULTS: Twenty-eight patients developed a post-operative complication (5 surgical, 14 infectious, 9 combined surgical/infectious, including anastomotic leakage), presenting on day 3 or later. Elevated days 2 and 3 and a rise in CRP preceded the diagnosis of general or combined surgical/infectious complications (minimum area under the receiver operating characteristics curve (AUROC) 0.75, P = 0.006). Elevated day 3 PCT preceded combined complications (AUROC 0.86, P < 0.001). High day 1 and 3 PCT levels preceded anastomotic leakage (minimum AUROC 0.76, P = 0.005), as did the day 3 CRP levels and their increases (minimum AUROC 0.78, P = 0.002). CONCLUSIONS: This small study suggests that high or increasing CRP levels may precede the clinical diagnosis of general or surgical/infectious complications after esophagectomy. Elevated PCT levels may more specifically and timely precede combined surgical/infectious complications mainly associated with anastomotic leakage.

Changes in circulating procalcitonin versus C-reactive protein in predicting evolution of infectious disease in febrile, critically ill patients.

OBJECTIVE: Although absolute values for C-reactive protein (CRP) and procalcitonin (PCT) are well known to predict sepsis in the critically ill, it remains unclear how changes in CRP and PCT compare in predicting evolution of: infectious disease, invasiveness and severity (e.g. development of septic shock, organ failure and non-survival) in response to treatment. The current study attempts to clarify these aspects. METHODS: In 72 critically ill patients with new onset fever, CRP and PCT were measured on Day 0, 1, 2 and 7 after inclusion, and clinical courses were documented over a week with follow up to Day 28. Infection was microbiologically defined, while septic shock was defined as infection plus shock. The sequential organ failure assessment (SOFA) score was assessed. RESULTS: From peak at Day 0-2 to Day 7, CRP decreased when (bloodstream) infection and septic shock (Day 0-2) resolved and increased when complications such as a new (bloodstream) infection or septic shock (Day 3-7) supervened. PCT decreased when septic shock resolved and increased when a new bloodstream infection or septic shock supervened. Increased or unchanged SOFA scores were best predicted by PCT increases and Day 7 PCT, in turn, was predictive for 28-day outcome. CONCLUSION: The data, obtained during ICU-acquired fever and infections, suggest that CRP may be favoured over PCT courses in judging response to antibiotic treatment. PCT, however, may better indicate the risk of complications, such as bloodstream infection, septic shock, organ failure and mortality, and therefore might help deciding on safe discontinuation of antibiotics. The analysis may thus help interpreting current literature and design future studies on guiding antibiotic therapy in the ICU.

Old and new biomarkers for predicting high and low risk microbial infection in critically ill patients with new onset fever: a case for procalcitonin.

OBJECTIVES: Fever suggests the presence of microbial infection in critically ill patients. The aim was to compare the role of old and new biomarkers in predicting absence or presence of microbial infection, its invasiveness and severity in critically ill patients with new onset fever. METHODS: We prospectively studied 101 patients in the intensive care unit with new onset fever (>38.3 °C). Routine infection parameters, lactate, procalcitonin (PCT), midregional pro-adrenomedullin (MR proADM), midregional pro-atrial natriuretic peptide (MR proANP) and copeptin (COP) were measured daily for three days after inclusion. Likelihood, invasiveness (by bloodstream infection, BSI) and severity of microbial infection were assessed by cultures, imaging techniques and clinical courses. RESULTS: All patients had systemic inflammatory response syndrome; 45% had a probable or proven local infection and 12% a BSI, with 20 and 33% mortality in the ICU, respectively. Only peak PCT (cutoff 0.65 ng/mL at minimum) was of predictive value for all endpoints studied, i.e. BSI, septic shock and mortality (high risk infection) and infection without BSI, shock and mortality (low risk infection), at areas under the receiver operating characteristic curves varying between 0.67 (P = 0.003) and 0.72 (P < 0.001). In multivariable analysis, the combination of C-reactive protein and lactate best predicted high risk infection, followed by PCT. For low risk infection, PCT was the single best predictor. CONCLUSIONS: In critically ill patients with new onset fever, plasma PCT as a single variable, among old and new biomarkers, best helps, to some extent, to predict ICU-acquired, high risk microbial infection when peaking above 0.65 ng/mL and low risk infection when peaking below 0.65 ng/mL.