Critical Care - Latest Articles

Early versus late parenteral nutrition in ICU patients: cost analysis of the EPaNIC trial

Simon Vanderheyden — 2012-05-25T00:00:00Z

IntroductionThe EPaNIC randomized controlled multicentre trial showed that postponing initiation of parenteral nutrition (PN) in ICU-patients to beyond the first week (Late-PN) enhanced recovery, as compared with Early-PN. This was mediated by fewer infections, accelerated recovery from organ failure and reduced duration of hospitalization. Now, the trial's preplanned cost analysis (N=4640) from the Belgian healthcare payers' perspective is reported. Methods: Cost data were retrieved from individual patient invoices. Undiscounted total healthcare costs were calculated for the index hospital stay. A cost tree based on acquisition of new infections and on prolonged length-of-stay was constructed. Contribution of 8 cost categories to total hospitalization costs was analyzed. The origin of drug costs was clarified in detail through the Anatomical Therapeutic Chemical (ATC) classification system. The potential impact of Early-PN on total hospitalization costs in other healthcare systems was explored in a sensitivity analysis. Results: ICU-patients developing new infection (24.4%) were responsible for 42.7% of total costs, while ICU-patients staying beyond one week (24.3%) accounted for 43.3% of total costs. Pharmacy-related costs represented 30% of total hospitalization costs and were increased by Early-PN (+608.00 EUR/patient, p=0.01). Notably, costs for ATC-J (anti-infective agents) (+227.00 EUR/patient, p=0.02) and ATC-B (comprising PN) (+220.00 EUR/patient, p=0.006) drugs were increased by Early-PN. Sensitivity analysis revealed a mean total cost increase of 1,210.00 EUR/patient (p=0.02) by Early-PN, when incorporating the full PN costs. Conclusions: The increased costs by Early-PN were mainly pharmacy-related and explained by higher expenditures for PN and anti-infective agents. The use of Early-PN in critically ill patients can thus not be recommended for both clinical (no benefit) and cost-related reasons.Trial registration: ClinicalTrials.gov NCT00512122

Blood transfusions increase circulating plasma free hemoglobin levels and plasma nitric oxide consumption: a prospective observational pilot study

Iris Vermeulen Windsant — 2012-05-25T00:00:00Z

IntroductionThe increasing number of reports on the relation between transfusion of stored red blood cells (RBC) and adverse patient outcome has sparked an intense debate on the benefits and risks of blood transfusions. Meanwhile, the pathophysiological mechanisms underlying this postulated relation remain unclear. The development of hemolysis during storage might contribute to this mechanism by release of free hemoglobin (fHb), a potent nitric oxide (NO) scavenger, which may impair vasodilation and microcirculatory perfusion after transfusion. The objective of this prospective observational pilot study was to establish whether RBC transfusion results in increased circulating fHb levels and plasma NO-consumption. In addition, the relation between increased fHb values and circulating haptoglobin, its natural scavenger, was studied. Methods: 30 patients electively received one (N=8) or two (N=22) stored packed red blood cell units. Blood samples were drawn to analyze plasma levels of fHb levels, haptoglobin, and NO-consumption prior to transfusion, and 15minutes, 30minutes, 60minutes, 120minutes, and 24hours after transfusion. Differences were compared using Pearson Chi-square or Fisher's exact test for dichotomous variables, or independent sample t-test or Mann-Whitney-U-test for continuous data. Continuous, multiple time-point, data were analyzed using the repeated one-Way ANOVA or Kruskall-Wallis test. Correlations were analyzed using the Spearman or Pearson correlation. Results: Storage duration correlated significantly with fHb concentrations and NO-consumption within the storage medium (r = 0.51, P<0.001,and r=0.62, P=0.002). FHb also significantly correlated with NO-consumption directly (r=0.61, P=0.002). Transfusion of 2 red blood cell units significantly increased circulating fHb and NO-consumption in the recipient (P <0.001 and P <0.05, respectively), in contrast to transfusion of 1 stored red blood cell unit. Storage duration of the blood products did not correlate with changes in fHb and NO-consumption in the recipient. In contrast, pre-transfusion recipient plasma haptoglobin levels inversely influenced post-transfusion fHb concentrations. Conclusions: These data suggest that RBC transfusion can significantly increase post-transfusion plasma fHb levels and plasma NO-consumption in the recipient. This may contribute to the potential pathophysiological mechanism underlying the much discussed adverse relation between blood transfusions and patient outcome. This observation may be of particular importance for patients with substantial transfusion requirements.

Assessment of hemodynamic efficacy and safety of 6% hydroxyethylstarch 130/0.4 versus 0.9% NaCl fluid replacement in patients with severe sepsis: The CRYSTMAS study

Bertrand Guidet — 2012-05-24T00:00:00Z

IntroductionInadequate initial treatment and delayed hemodynamic stabilization (HDS) may be associated with increased risk of death in severe sepsis patients. Methods: in order to compare the hemodynamic efficacy and safety of 6% HES 130/0.4 and NaCl 0.9% for HDS in patients with severe sepsis, we designed a prospective, multicenter, active-controlled, double-blind, randomized study in Intensive care units. Results: 174 out of 196 patients reached HDS (88 and 86 patients for HES and NaCl, respectively). Significantly less HES was used to reach HDS versus NaCl (1,379 886 ml in the HES group and 1,709 1,164 ml in the NaCl group [Mean difference = -331 1,033, 95% CI -640 to -21, p=0.0185). Time to reach HDS was 11.8 10.1 hours versus 14.3 11.1 hours for HES and NaCl, respectively. Total quantity of study drug infused over four consecutive days, ICU and hospital LOS, and area under the curve of SOFA Score were comparable. Acute renal failure occurred in 24 (24.5%) and 19 (20%) patients for HES and NaCl, respectively (p=0.454). There was no difference between AKIN and RIFLE criteria among groups and no difference in mortality, coagulation, or pruritus up to 90 days after treatment initiation. Conclusion: Significantly less volume was required to achieve HDS for HES versus NaCl in the initial phase of fluid resuscitation in severe sepsis patients without any difference for adverse events in both groups.

Contrast-induced nephropathy: attributable incidence and potential harm

Lilian do Carmo — 2012-05-23T00:00:00Z

Contrast-induced nephropathy is a common form of hospital-acquired acute kidney injury. Incidence is low in patients with normal renal function but increases in high-risk patients. Patients with contrast-induced nephropathy have higher in-hospital complication rates and mortality. Critically ill patients have been assumed to be a high-risk group for contrast-induced nephropathy. In the previous issue of Critical Care, Cely and colleagues showed an unexpectedly low incidence of contrast-induced nephropathy in critically ill patients receiving radiographic contrast material for computerized tomography. We should note that it is difficult to establish the true frequency and impact of the contrast nephrotoxicity because of many other causes for acute kidney injury in this population. Moreover, the impact on long-term kidney function and the possible effect of this insult on the recovery of renal function when associated with other causes of acute kidney injury are unknown.

Effects of non-neurological complications on traumatic brain injuryoutcome

Kimberly Meyer — 2012-05-23T00:00:00Z

Traumatic brain injury (TBI) affects over 1.5 million Americans annually and consumes a significant amount of healthcare dollars. Identification of complications and factors that impact recovery from TBI is important in improving outcome and allocating appropriate resources. Understanding the role of non-neurologic complications such as sepsis, acute kidney injury, and respiratory problems on TBI outcome and mortality is critical.

Implications of endotracheal tube biofilm in ventilator-associated pneumonia response: a state of concept

Sara Gil-Perotin — 2012-05-23T00:00:00Z

IntroductionBiofilm in endotracheal tubes (ETT) of ventilated patients has been suggested to play a role in the development of ventilator-associated pneumonia (VAP). Our purpose was to analyse the formation of ETT biofilm and its implication in the response and relapse of VAP. Methods: We performed a prospective, observational study in a medical intensive care unit. Patients mechanically ventilated for more than 24 hours were consecutively included. We obtained surveillance endotracheal aspirates (ETA) twice weekly and, at extubation, ETTs were processed for microbiological assessment and scanning electron microscopy. Results: Eighty-seven percent of the patients were colonized based on ETA cultures. Biofilm was found in 95% of the ETTs. In 56% of the cases, the same microorganism grew in ETA and biofilm. In both samples the most frequent bacteria isolated were Acinetobacter baumannii and Pseudomonas aeruginosa. Nineteen percent of the patients developed VAP (N=14), and aetiology was predicted by ETA in 100% of the cases. Despite appropriate antibiotic treatment, bacteria involved in VAP were found in biofilm (50%). In this situation, microbial persistence and impaired response to treatment (treatment failure and relapse) were more frequent (100% vs 29%, P=0.021; 57% vs 14%, P=0.133). Conclusions: Airway bacterial colonization and biofilm formation on ETTs are early and frequent events in ventilated patients. There is microbiological continuity between airway colonization, biofilm formation and VAP development. Biofilm stands as a pathogenic mechanism for microbial persistence, and impaired response to treatment in VAP.

New strategies to manage complicated pleural effusions

David Huang — 2012-05-22T00:00:00Z

Expanded abstractCitationRahman NM, Maskell NA, West A, Teoh R, Arnold A, Mackinlay C, Peckham D, Davies CW, Ali N, Kinnear W, Bentley A, Kahan BC, Wrightson JM, Davies HE, Hooper CE, Lee YC, Hedley EL, Crosthwaite N, Choo L, Helm EJ, Gleeson FV, Nunn AJ, Davies RJ: N Engl J Med 2011, 365:518-26. PMID: 21830966, available on www.pubmed. gov Background: More than 30% of patients with pleural infection either die or require surgery. Drainage of infected fluid is the key to successful treatment, but intrapleural fibrinolytic therapy did not improve outcomes in an earlier, large, randomized trial therapy (Multicenter Intrapleural Sepsis Trial [MIST1]). Methods: Objective: To evaluate the efficacy and safety of intrapleural DNase alone, alteplase alone, or the combination of both, to improve pleural drainage.Design: Multicenter, double-blind, double-dummy, 2 × 2 factorial randomized trial.Setting: Eleven centers in the United Kingdom (UK).Subjects: Adult patients (mean age 59 years, 72% men), who had clinical evidence of infection, and pleural fluid that had macroscopic purulence, a positive culture or Gram stain for bacteria, or a pH < 7.2.Intervention: Patients were assigned to 1 of the 4 study interventions for 3 days: double placebo, intrapleural tissue plasminogen activator (t-PA) and DNase, t-PA and placebo, or DNase and placebo.Outcomes: The primary outcome was the change in pleural opacity, measured as the percentage of the hemithorax occupied by effusion, on chest radiography on day 7 as compared with day 1. Secondary outcomes included referral for surgery, duration of hospital stay, and adverse events. Results: The mean (± SD) change in pleural opacity was greater in the t-PA-DNase group than in the placebo group (-29.5 ± 23.3% vs. -17.2 ± 19.6%; difference, -7.9%; 95% confidence interval [CI], -13.4 to -2.4; P = 0.005). The change observed with t-PA alone and with DNase alone (-17.2 ± 24.3 and -14.7 ± 16.4%, respectively) was not significantly different from that observed with placebo. The frequency of surgical referral at 3 months was lower in the t-PA-DNase group than in the placebo group (2 of 48 patients [4%] vs. 8 of 51 patients [16%]; odds ratio for surgical referral, 0.17; 95% CI, 0.03 to 0.87; P = 0.03) but was greater in the DNase group (18 of 46 patients [39%]) than in the placebo group (odds ratio, 3.56; 95% CI, 1.30 to 9.75; P = 0.01). Combined t-PA-DNase therapy was associated with a reduction in the hospital stay, as compared with placebo (difference, -6.7 days; 95% CI, -12.0 to -1.9; P = 0.006). Hospital stay with either agent alone was not significantly different from that with placebo. The frequency of adverse events did not differ significantly among the groups. Conclusions: Intrapleural t-PA-DNase therapy improved fluid drainage in patients with pleural infection and reduced the frequency of surgical referral and the duration of hospital stay. Treatment with DNase alone or t-PA alone was ineffective.

Association of gender with outcomes in critically ill patients

Kamran Mahmood — 2012-05-22T00:00:00Z

IntroductionThe influence of gender on mortality and other outcomes of critically ill patients is not clear. Different studies have been performed in various settings and patient populations often yielding conflicting results. We wanted to assess the relationship of gender and intensive care unit (ICU) outcomes in the patients included in the acute physiology and chronic health evaluation (APACHE) IV database (Cerner Corporation, USA). Methods: We performed a retrospective review of the data available in APACHE IV database. 261,255 consecutive patients admitted to adult ICUs in United States from 1/1/2004 to 12/31/2008 were included. The readmissions were excluded from the analysis. The primary objective of the study was to assess the relationship of gender with ICU mortality. The secondary objective was to evaluate the association of gender with the active therapy, mechanical ventilation, length of stay in ICU, readmission rate and the hospital mortality. The gender related outcomes for disease subgroups including acute coronary syndrome, coronary artery bypass graft (CABG) surgery, sepsis, trauma and chronic obstructive pulmonary disease (COPD) exacerbation were assessed as well. Results: ICU mortality was 7.2% for men and 7.9% for women, odds ratio (OR) for death for women was 1.07 (95% confidence interval [CI]: 1.04-1.1). There was a statistically significant interaction between gender and age. In patients younger than 50 years of age, women had a reduced ICU mortality compared with men, after adjustment for acute physiology score, ethnicity, co-morbid conditions, pre-ICU length of stay, pre-ICU location and hospital teaching status (Adjusted OR 0.83, 95 % CI: 0.76-0.91). But among 50 years of age or older patients, there was no significant difference in ICU mortality between men and women (Adjusted OR 1.02, 95% CI: 0.98-1.06).A higher proportion of men received mechanical ventilation, emergent surgery, thrombolytic therapy and CABG surgery. Men had a higher readmission rate and longer length of ICU stay. The adjusted mortality of women compared to men was higher with CABG, while it was lower with COPD exacerbation. There was no significant difference in mortality in acute coronary syndrome, sepsis and trauma. Conclusions: Among the critically ill patients, women less than 50 years of age had a lower ICU mortality compared to men, while 50 years of age or older women did not have a significant difference compared to men. Women had a higher mortality compared to men after the CABG surgery, and lower mortality with COPD exacerbation. There was no difference in mortality in acute coronary syndrome, sepsis and trauma.

Plasma sRAGE enables prediction of acute lung injury following cardiac surgery in children

XiWang Liu — 2012-05-22T00:00:00Z

IntroductionAcute lung injury (ALI) following cardiac surgery is associated with a high postoperative morbidity and mortality, but there are few predictors for the occurrence of the complication. This study was to evaluate whether elevated plasma levels of soluble receptor for advanced glycation end products (sRAGE) and S100A12 reflected impaired lung function in infants and young children after cardiac surgery necessitating cardiopulmonary bypass (CPB). Methods: Consecutive children aged <3 years old following cardiac surgery were prospectively enrolled and assigned into ALI and non-ALI groups according to the American-European Consensus Criteria. Plasma concentrations of sRAGE and S100A12 were measured at baseline, before and immediately after CPB, as well as 1 h, 12 h and 24 h after operation. Results: Fifty-eight patients were enrolled and 16 (27.6%) developed postoperative ALI. Plasma sRAGE and S100A12 levels increased immediately after CPB and kept significantly higher in the ALI group even 24 h after operation (P<0.01). In addition, a one-way MANOVA revealed that the overall sRAGE and S100A12 levels were higher in the ALI group than in the non-ALI group immediately after CPB (P<0.001). The multivariate logistic regression analysis showed that plasma sRAGE level immediately after CPB was an independent predictor for postoperative ALI (OR 1.088, 95%CI 1.011-1.171, P=0.025). Increased sRAGE and S100A12 levels immediately after CPB were significantly correlated with lower PaO2/FiO2 ratio (P<0.01) and higher radiographic lung injury score (P<0.01), as well as longer mechanical ventilation time (sRAGEN: r=0.405, P=0.002; S100A12N: r=0.322, P=0.014), longer surgical intensive care unit stay (sRAGEN: r=0.421, P=0.001; S100A12N: r=0.365, P=0.005) and hospital stay (sRAGEN: r=0.329, P=0.012; S100A12N: r=0.471, P=0.001). Conclusions: Elevated sRAGE and S100A12 levels correlate with impaired lung function, and sRAGE is a useful early biomarker of ALI in infants and young children undergoing cardiac surgery.

Elevated plasma levels of heparin-binding protein in intensive care unit patients with severe sepsis and septic shock

Adam Linder — 2012-05-21T00:00:00Z

IntroductionRapid detection of and optimized treatment for severe sepsis and septic shock is crucial for successful outcome. Heparin-binding protein (HBP), a potent inducer of increased vascular permeability, is a potentially useful biomarker for predicting outcome in patients with severe infections. Our aim was to study the systemic release and dynamics of HBP in plasma of patients with severe sepsis and septic shock in the intensive care unit (ICU). Methods: A prospective study of two patient cohorts treated in the ICU at Karolinska University Hospital Huddinge in Sweden. 179 patients were included, of whom 151 had sepsis (126 with septic shock and 25 patients with severe sepsis) and 28 a non-septic critical condition. Blood samples were collected at five time points during six days after admission. Results: HBP levels were significantly higher in the sepsis group as compared to the control group. At admission to the ICU, a plasma HBP concentration of [greater than or equal to]15 ng/mL and/or a HBP (ng/mL) / White blood cell count (109/L) ratio of >2 was found in 87.2% and 50.0% of critically ill patients with sepsis and non-septic illness, respectively. A lactate level of >2.5 mmol/L was detected in 64.9% and 56.0% of the same patient groups. Both in the sepsis group (n=151) and in the whole group (n=179), plasma HBP concentrations at admission and in the last measured sample within the 144 hour study period were significantly higher among 28-day non-survivors as compared to survivors, and in the sepsis group, an elevated HBP-level at baseline was associated with an increased case-fatality rate at 28 days. Conclusions: Plasma HBP levels were significantly higher in patients with severe sepsis or septic shock compared to patients with non-septic illness in the ICU. HBP was associated with severity of disease, and an elevated HBP at admission was associated with an increased risk of death. HBP that rises over time may identify patients with a deteriorating prognosis.Thus, repeated HBP measurement in the ICU may help monitor treatment and predict outcome in patients with severe infections.