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

The inflammatory response to vascular surgery-associated ischaemia and reperfusion in man: Effect on postoperative pulmonary function

Objectives:To characterise the inflammatory response to vascular surgery and ischaemia/reperfusion (I/R) in man, regarding release of inflammatory mediators, recruitment and activation of neutrophils, and their relation to postoperative pulmonary function.Design:Prospective cohort study.Materials and methods:Circulating neutrophil counts and plasma levels of elastase-α1-antitrypsin (AT), a neutrophil degranulation product, were measured before and approx. 2.5 h (group 1, n = 19) after elective abdominal aortic surgery, and approx. 2.9 h after elective peripheral vascular surgery (group 2, n = 6), together with concentrations of neutrophil agonists, including activated complement (C3a), secretory phospholipase A2 (sPLA2), tumor necrosis factor (TNF-α), interleukin (IL)-6, IL-8 and granulocyte colony-stimulating factor (G-CSF). At the time of blood sampling, respiratory variables allowing computation of the lung injury score (LIS) were obtained in patients admitted after surgery in the intensive care unit (ICU), i.e. all group 1 patients and one group 2 patient.Results:Median (range) neutrophil counts rose by 80% (−28–208) and 90% (10–147) in groups 1 and 2, respectively (n.s. between groups). The increase (p<0.05) in elastase-α1-AT level was 121% (−5–439) in group 1 and 82% (18–792) in group 2 (n.s. between groups). There was a rise (p<0.05) in C3a level by 93% (−42–751) and of sPLA2 level by 68% (−40–1400) after surgery for the groups together (n.s. between groups), and the rise of the elastase-α1-AT related to that of the C3a levels. IL-6 and G-CSF concentrations increased more in group 1 than 2. The IL-8 concentration increased in group 1 only, and TNF-α was unchanged in all groups. In ICU patients, the LIS related to the postoperative rise in IL-6 level only, even though the rise in plasma concentrations of cytokines interrelated. No patient developed ARDS and all survived.Conclusions:Vascular surgery and I/R in man activates complement, releases cytokines (except for TNF-α), and induces neutrophil recruitment and degranulation, which may primarily depend on complement activation. In contrast to the latter, the release of cytokines may depend on the extent of I/R and may contribute to transient pulmonary dysfunction after extensive I/R

Global end-diastolic volume increases to maintain fluid responsiveness in sepsis-induced systolic dysfunction

Background: Sepsis-induced cardiac dysfunction may limit fluid responsiveness and the mechanism thereof remains unclear. Since cardiac function may affect the relative value of cardiac filling pressures, such as the recommended central venous pressure (CVP), versus filling volumes in guiding fluid loading, we studied these parameters as determinants of fluid responsiveness, according to cardiac function.Methods: A delta CVP-guided, 90 min colloid fluid loading protocol was performed in 16 mechanically ventilated patients with sepsis-induced hypotension and three 30 min consecutive fluid loading steps of about 450 mL per patient were evaluated. Global end-diastolic volume index (GEDVI), cardiac index (CI) and global ejection fraction (GEF) were assessed from transpulmonary dilution. Baseline and changes in CVP and GEDVI were compared among responding (CI increase ≥10% and ≥15%) and non-responding fluid loading steps, in patient with low (<20%, n = 9) and near-normal (≥20%) GEF (n = 7) at baseline.Results: A low GEF was in line with other indices of impaired cardiac (left ventricular) function, prior to and after fluid loading. Of 48 fluid loading steps, 9 (of 27) were responding when GEF <20% and 6 (of 21) when GEF ≥20. Prior to fluid loading, CVP did not differ between responding and non-responding steps and levels attained were 23 higher in the latter, regardless of GEF (P = 0.004). Prior to fluid loading, GEDVI (and CI) was higher in responding (1007 ± 306 mL/m2) than non-responding steps (870 ± 236 mL/m2) when GEF was low (P = 0.002), but did not differ when GEF was near-normal. Increases in GEDVI were associated with increases in CI and fluid responsiveness, regardless of GEF (P < 0.001).Conclusions: As estimated from transpulmonary dilution, about half of patients with sepsis-induced hypotension have systolic cardiac dysfunction. During dysfunction, cardiac dilation with a relatively high baseline GEDVI maintains fluid responsiveness by further dilatation (increase in GEDVI rather than of CVP) as in patients without dysfunction. Absence of fluid responsiveness during systolic cardiac dysfunction may be caused by diastolic dysfunction and/or right ventricular dysfunction

Neutrophil Gelatinase-Associated Lipocalin as a Diagnostic Marker for Acute Kidney Injury in Oliguric Critically Ill Patients: A Post-Hoc Analysis

__Background:__ Oliguria occurs frequently in critically ill patients, challenging clinicians to distinguish functional adaptation from serum-creatinine-defined acute kidney injury (AKIsCr). We investigated neutrophil gelatinase-associated lipocalin (NGAL)'s ability to differentiate between these 2 conditions. __Methods:__ This is a post-hoc analysis of a prospective cohort of adult critically ill patients. Patients without oliguria within the first 6 h of admission were excluded. Plasma and urinary NGAL were measured at 4 h after admission. AKIsCr was defined using the AKI network criteria with pre-admission serum creatinine or lowest serum creatinine value during the admission as the baseline value. Hazard ratios for AKIsCr occurrence within 72 h were calculated using Cox regression and adjusted for risk factors such as sepsis, pre-admission serum creatinine, and urinary output. Positive predictive values (PPV) and negative predictive values (NPV) were calculated for the optimal cutoffs for NGAL. __Results:__ Oliguria occurred in 176 patients, and 61 (35%) patients developed AKIsCr. NGAL was a predictor for AKIsCr in univariate and multivariate analysis. When NGAL was added to a multivariate model including sepsis, pre-admission serum creatinine and lowest hourly urine output, it outperformed the latter model (plasma p = 0.001; urinary p = 0.048). Cutoff values for AKIsCr were 280 ng/ml for plasma (PPV 80%; NPV 79%), and 250 ng/ml for urinary NGAL (PPV 58%; NPV 78%). __Conclusions:__ NGAL can be used to distinguish oliguria due to the functional adaptation from AKIsCr, directing resources to patients more likely to develop AKIsCr

Procalcitonin to guide taking blood cultures in the intensive care unit; a cluster-randomized controlled trial

AbstractObjectivesWe aimed to study the safety and efficacy of procalcitonin in guiding blood cultures taking in critically ill patients with suspected infection.MethodsWe performed a cluster-randomized, multi-centre, single-blinded, cross-over trial. Patients suspected of infection in whom taking blood for culture was indicated were included. The participating intensive care units were stratified and randomized by treatment regimen into a control group and a procalcitonin-guided group. All patients included in this trial followed the regimen that was allocated to the intensive care unit for that period. In both groups, blood was drawn at the same moment for a procalcitonin measurement and blood cultures. In the procalcitonin-guided group, blood cultures were sent to the department of medical microbiology when the procalcitonin was >0.25 ng/mL. The main outcome was safety, expressed as mortality at day 28 and day 90.ResultsThe control group included 288 patients and the procalcitonin-guided group included 276 patients. The 28- and 90-day mortality rates in the procalcitonin-guided group were 29% (80/276) and 38% (105/276), respectively. The mortality rates in the control group were 32% (92/288) at day 28 and 40% (115/288) at day 90. The intention-to-treat analysis showed hazard ratios of 0.85 (95% CI 0.62–1.17) and 0.89 (95% CI 0.67–1.17) for 28-day and 90-day mortality, respectively. The results were deemed non-inferior because the upper limit of the 95% CI was below the margin of 1.20.ConclusionApplying procalcitonin to guide blood cultures in critically ill patients with suspected infection seems to be safe, but the benefits may be limited.Trial registrationClinicalTrials.gov identifier: ID NCT01847079. Registered on 24 April 2013, retrospectively registered

Targeting urine output and 30-day mortality in goal-directed therapy: A systematic review with meta-analysis and meta-regression.

Background: Oliguria is associated with a decreased kidney- and organ perfusion, leading to orga

Herpes simplex virus type 1 and normal protein permeability in the lungs of critically ill patients: a case for low pathogenicity?

INTRODUCTION: The pathogenicity of late respiratory infections with herpes simplex virus type 1 (HSV-1) in the critically ill is unclear. METHODS: In four critically ill patients with persistent pulmonary infiltrates of unknown origin and isolation of HSV-1 from tracheal aspirate or bronchoalveolar lavage fluid, at 7 (1-11) days after start of mechanical ventilatory support, a pulmonary leak index (PLI) for 67Gallium (67Ga)-transferrin (upper limit of normal 14.1 x 10(-3)/min) was measured. RESULTS: The PLI ranged between 7.5 and 14.0 x 10(-3)/min in the study patients. Two patients received a course of acyclovir and all survived. CONCLUSIONS: The normal capillary permeability observed in the lungs argues against pathogenicity of HSV-1 in the critically ill, and favors that isolation of the virus reflects reactivation in the course of serious illness and immunodepresssion, rather than primary or superimposed infection in the lungs