Background. Systemic reactivations of herpesviruses may occur in intensive care unit (ICU) patients, even in those without prior immune deficiency. However, the clinical relevance of these events is ...uncertain. Methods. In this study we selected patients admitted with septic shock and treated for more than 4 days from a prospectively enrolled cohort of consecutive adults in the mixed ICUs of 2 tertiary care hospitals in the Netherlands. We excluded patients who had received antiviral treatment in the week before ICU admission and those with known immunodeficiency. We studied viremia episodes with cytomegalovirus (CMV), Epstein–Barr virus (EBV), human herpesvirus 6 (HHV-6), herpes simplex virus types 1 (HSV-1) and 2 (HSV-2), and varicella zoster virus (VZV) by weekly polymerase chain reaction in plasma. Results. Among 329 patients, we observed 399 viremia episodes in 223 (68%) patients. Viremia with CMV, EBV, HHV-6, HSV-1, HSV-2, and VZV was detected in 60 (18%), 157 (48%), 80 (24%), 87 (26%), 13 (4%), and 2 (0.6%) patients, respectively; 112 (34%) patients had multiple concurrent viremia events. Crude mortality in the ICU was 36% in this latter group compared to 19% in remaining patients (P < .01). After adjustment for potential confounders, time-dependent bias, and competing risks, only concurrent CMV and EBV reactivations remained independently associated with increased mortality (adjusted subdistribution hazard ratio, 3.17; 95% confidence interval, 1.41–7.13). Conclusions. Herpesvirus reactivations were documented in 68% of septic shock patients without prior immunodeficiency and frequently occurred simultaneously. Concurrent reactivations could be independently associated with mortality. Clinical Trials Registration. NCT01905033.
Heijnen et al discuss their study which aim to determine whether these subphenotypes and their prognostic and potential for predictive enrichment could be extended to other patients in the ICU, ...irrespective of fulfilling the definition of acute respiratory distress syndrome (ARDS). This is a secondary analysis of a prospective observational study of adult patients admitted to the ICU. We tested the prognostic enrichment of both cluster-derived and latent-class analysis (LCA)-derived biological ARDS subphenotypes by evaluating the association with clinical outcome (ICU-day, 30-day mortality, and ventilator-free days) using logistic regression and Cox regression analysis. We performed a principal component analysis to compare blood leukocyte gene expression profiles between subphenotypes and the presence of ARDS. The results revealed that the prognostic and potential for predictive enrichment of biological ARDS subphenotypes may be extended to mechanically ventilated critically ill patients without ARDS.
ABSTRACTTenascin C (TNC) is an extracellular matrix protein able to modulate the immune response. Knowledge regarding its role during sepsis and general critical illness is still limited. We here ...assessed the temporal dynamics of plasma TNC during sepsis and nonseptic critical illness, its capacity to predict patient outcome, and its specificity toward infection. TNC plasma concentrations were measured in 895 consecutive sepsis patients on ICU admission, day 2 and 4 thereafter, and, in a subset, before ICU discharge. To assess TNC diagnostic value, we compared patients with abdominal sepsis (N = 143) to noninfectious abdominal surgery controls (N = 98), and patients with severe community-acquired pneumonia (CAP, N = 227) to patients whose CAP diagnosis was retrospectively refuted (no-CAP controls, N = 70). Plasma TNC levels were persistently elevated in sepsis patients compared with healthy volunteers throughout the ICU stay. TNC levels varied by the site of infection and increased with the number of organs failing. Association of TNC levels with 30-day mortality could be wholly attributed to differences in disease severity. Noninfectious ICU patients also showed elevated TNC levels, albeit with different temporal dynamics. Although admission TNC was higher in CAP than in no-CAP patients, it performed poorly in distinguishing the 2 groups.TNC plasma levels are persistently elevated during sepsis and nonseptic critical illness. In sepsis patients, they are reflective of disease severity more than independent predictors of mortality. Despite higher levels in patients with infection compared with noninfectious controls, TNC does not perform sufficiently to be used as a standalone biomarker discriminating sepsis from noninfectious critical illness.
Purpose
Sepsis is the most frequent cause of acute kidney injury (AKI). The “Acute Disease Quality Initiative Workgroup” recently proposed new definitions for AKI, classifying it as transient or ...persistent. We investigated the incidence, mortality, and host response aberrations associated with transient and persistent AKI in sepsis patients.
Methods
A total of 1545 patients admitted with sepsis to 2 intensive care units in the Netherlands were stratified according to the presence (defined by any urine or creatinine RIFLE criterion within the first 48 h) and evolution of AKI (with persistent defined as remaining > 48 h). We determined 30-day mortality by logistic regression adjusting for confounding variables and analyzed 16 plasma biomarkers reflecting pathways involved in sepsis pathogenesis (
n
= 866) and blood leukocyte transcriptomes (
n
= 392).
Results
AKI occurred in 37.7% of patients, of which 18.4% was transient and 81.6% persistent. On admission, patients with persistent AKI had higher disease severity scores and more frequently had severe (injury or failure) RIFLE AKI stages than transient AKI patients. Persistent AKI, but not transient AKI, was associated with increased mortality by day 30 and up to 1 year. Persistent AKI was associated with enhanced and sustained inflammatory and procoagulant responses during the first 4 days, and a more severe loss of vascular integrity compared with transient AKI. Baseline blood gene expression showed minimal differences with respect to the presence or evolution of AKI.
Conclusion
Persistent AKI is independently associated with sepsis mortality, as well as with sustained inflammatory and procoagulant responses, and loss of vascular integrity as compared with transient AKI.
Cytomegalovirus (CMV) infection is a well-recognised complication of solid organ and hematopoietic cell transplantation. However, CMV infection also occurs in patients with human immunodeficiency ...virus infection, previously immunocompetent intensive care unit patients, and individuals on immunosuppressive medications for various underlying diseases.
This review describes the comparative effects of CMV infection in distinct types of acquired immunosuppression.
Selected peer-reviewed publications on CMV infections published until December 2021.
CMV infection affects various organ systems through direct cytolytic mechanisms but may also exert indirect effects by promoting pro-inflammatory and immunosuppressive responses. This has been well studied in transplant recipients, for whom antiviral prophylaxis and pre-emptive therapy have now become standard practice. These strategies not only prevent direct CMV disease manifestations but also mitigate various immunopathological processes to reduce graft-vs.-host disease, graft rejection, and the occurrence of secondary bacterial and fungal infections. The efficacy of neither prophylactic nor pre-emptive treatment of CMV infection has been demonstrated for patients with critical illness- or medication-induced immunosuppression. Many observational studies have shown an independent association between CMV reactivation and a prolonged duration of mechanical ventilation or increased mortality in the intensive care unit. Furthermore, data suggest that CMV reactivation may increase pulmonary inflammation and prolong the duration of mechanical ventilation.
A large number of observational and experimental studies suggest attributable morbidity and mortality related to CMV infection, not only in transplant recipients and patients with human immunodeficiency virus infection but also in patients with critically illness- or medication-induced immunosuppression. Adequately powered randomised controlled trials investigating the efficacy of prophylaxis or pre-emptive treatment of CMV infection in these patients are lacking, with a notable exception for transplant recipients.
OBJECTIVE:Intracranial hypertension after severe head injury is associated with case fatality, but there is no sound evidence that monitoring of intracranial pressure (ICP) and targeted management of ...cerebral perfusion pressure (CPP) improve outcome, despite widespread recommendation by experts in the field. The purpose was to determine the effect of ICP/CPP-targeted intensive care on functional outcome and therapy intensity levels after severe head injury.
DESIGN:Retrospective cohort study with prospective assessment of outcome.
SETTING:Two level I trauma centers in The Netherlands from 1996 to 2001.
PATIENTS:Three hundred thirty-three patients who had survived and remained comatose for >24 hrs, from a total of 685 consecutive severely head-injured adults.
INTERVENTIONS:In center A (supportive intensive care), mean arterial pressure was maintained at approximately 90 mm Hg, and therapeutic interventions were based on clinical observations and computed tomography findings. In center B (ICP/CPP-targeted intensive care), management was aimed at maintaining ICP <20 mm Hg and CPP >70 mm Hg. Allocation to either trauma center was solely based on the site of the accident.
MEASUREMENTS AND MAIN RESULTS:We measured extended Glasgow Outcome Scale after ≥12 months. Patient characteristics were well balanced between the centers. ICP monitoring was used in zero of 122 (0%) and 142 of 211 (67%) patients in centers A and B, respectively. In-hospital mortality rate was 41 (34%) vs. 69 (33%; p = .87). The odds ratio for a more favorable functional outcome following ICP/CPP-targeted therapy was 0.95 (95% confidence interval, 0.62–1.44). This result remained after adjustment for potential confounders. Sedatives, vasopressors, mannitol, and barbiturates were much more frequently used in center B (all p < .01). The median number of days on ventilator support in survivors was 5 (25th–75th percentile, 2–9) in center A vs. 12 (7–19) in center B (p < .001).
CONCLUSIONS:ICP/CPP-targeted intensive care results in prolonged mechanical ventilation and increased levels of therapy intensity, without evidence for improved outcome in patients who survive beyond 24 hrs following severe head injury.
Purpose
To quantify the effects of minor variations in the definition and measurement of systemic inflammatory response syndrome (SIRS) criteria and organ failure on the observed incidences of ...sepsis, severe sepsis and septic shock.
Methods
We conducted a prospective, observational study in a tertiary intensive care unit in The Netherlands between January 2009 and October 2010. A total of 1,072 consecutive adults were included. We determined the upper and lower limits of the measured incidence of sepsis by evaluating the influence of the use of an automated versus a manual method of data collection, and variations in the number of SIRS criteria, concurrency of SIRS criteria, and duration of abnormal values required to make a particular diagnosis.
Results
The measured incidence of SIRS varied from 49 % (most restrictive setting) to 99 % (most liberal setting). Subsequently, the incidences of sepsis, severe sepsis and septic shock ranged from 22 to 31 %, from 6 to 27 % and from 4 to 9 % for the most restrictive versus the most liberal measurement settings, respectively. In non-infected patients, 39–98 % of patients had SIRS, whereas still 17–6 % of patients without SIRS had an infection.
Conclusions
The apparent incidence of sepsis heavily depends on minor variations in the definition of SIRS and mode of data recording. As a consequence, the current consensus criteria do not ensure uniform recruitment of patients into sepsis trials.
OBJECTIVES:Correct classification of the source of infection is important in observational and interventional studies of sepsis. Centers for Disease Control and Prevention criteria are most commonly ...used for this purpose, but the robustness of these definitions in critically ill patients is not known. We hypothesized that in a mixed ICU population, the performance of these criteria would be generally reduced and would vary among diagnostic subgroups.
DESIGN:Prospective cohort.
SETTING:Data were collected as part of a cohort of 1,214 critically ill patients admitted to two hospitals in The Netherlands between January 2011 and June 2011.
PATIENTS:Eight observers assessed a random sample of 168 of 554 patients who had experienced at least one infectious episode in the ICU. Each patient was assessed by two randomly selected observers who independently scored the source of infection (by affected organ system or site), the plausibility of infection (rated as none, possible, probable, or definite), and the most likely causative pathogen. Assessments were based on a post hoc review of all available clinical, radiological, and microbiological evidence. The observed diagnostic agreement for source of infection was classified as partial (i.e., matching on organ system or site) or complete (i.e., matching on specific diagnostic terms), for plausibility as partial (2-point scale) or complete (4-point scale), and for causative pathogens as an approximate or exact pathogen match. Interobserver agreement was expressed as a concordant percentage and as a kappa statistic.
INTERVENTIONS:None.
MEASUREMENTS AND MAIN RESULTS:A total of 206 infectious episodes were observed. Agreement regarding the source of infection was 89% (183/206) and 69% (142/206) for a partial and complete diagnostic match, respectively. This resulted in a kappa of 0.85 (95% CI, 0.79–0.90). Agreement varied from 63% to 91% within major diagnostic categories and from 35% to 97% within specific diagnostic subgroups, with the lowest concordance observed in cases of ventilator-associated pneumonia. In the 142 episodes for which a complete match on source of infection was obtained, the interobserver agreement for plausibility of infection was 83% and 65% on a 2- and 4-point scale, respectively. For causative pathogen, agreement was 78% and 70% for an approximate and exact pathogen match, respectively.
CONCLUSIONS:Interobserver agreement for classifying sources of infection using Centers for Disease Control and Prevention criteria was excellent overall. However, full concordance on all aspects of the diagnosis between independent observers was rare for some types of infection, in particular for ventilator-associated pneumonia.
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