Vasopressor-free Days Research Articles

Retrospective outcomes of glucose control in critically ill children.

Hyperglycemia is a significant problem for critically ill children. Treatment for hyperglycemia remains controversial. This study explores the effect of controlling blood glucose (BG) in hyperglycemic critically ill children. A retrospective cohort of nondiabetic critically ill children (defined as requiring mechanical ventilation and/or vasopressors) with BG persistently ≥ 150 mg/dl and treated with insulin (treatment group) were compared with a historical cohort of similar children who did not receive interventions to control hyperglycemia (baseline group). There were 130 children in the treatment group and 137 children in the baseline group. Mean BG in the treatment group was 140 ± 24 mg/dl compared with 179 ± 47 mg/dl in the baseline group (p < .001). After adjusting for patient characteristics, cointerventions, and glucose metrics, patients in the treatment group had 2.5 fewer intensive care unit (ICU)-free days (i.e., number of days alive and discharged from ICU within 28 days after inclusion) than the baseline group (p = .023). Glucose control was not independently associated with duration of ICU stay, ventilator-free days, vasopressor-free days, or mortality. Blood glucose control appears associated with worse outcomes in critically ill children. Our data combined with conflicting results in adults leads us to strongly advocate for the conduct of randomized trials on glucose control in critically ill children.

Recombinant human soluble thrombomodulin in sepsis-induced disseminated intravascular coagulation: a multicenter propensity score analysis

PurposeEvidence of efficacy and safety of, and especially mortality related to, recombinant human thrombomodulin (rhTM) treatment for sepsis-induced disseminated intravascular coagulation (DIC) is limited. We hypothesized that patients with sepsis-induced DIC receiving treatment with rhTM would have improved mortality compared with those with similar acuity who did not.MethodsThis retrospective cohort study conducted in three tertiary referral hospitals in Japan between January 2006 and June 2011 included all patients with sepsis-induced DIC who required ventilator management. Primary endpoint was in-hospital mortality, with duration of intensive care unit treatment, changes in DIC scores and rate of bleeding complications as secondary endpoints. Regression technique was used to develop a propensity model adjusted for baseline imbalances between groups.ResultsEligible were 162 patients with sepsis-induced DIC; 68 patients received rhTM and 94 did not. Patients receiving rhTM had higher severity of illness according to baseline characteristics. After adjusting for these imbalances by stratified propensity score analysis, treatment with rhTM was significantly associated with reduced in-hospital mortality (adjusted hazard ratio, 0.45; 95 % confidential interval, 0.26–0.77; p = 0.013). An association between rhTM treatment and higher numbers of intensive care unit-free days, ventilator-free days, and vasopressor-free days were observed. DIC scores were significantly decreased in the rhTM group compared with the control group in the early period after rhTM treatment, whereas the incidence of bleeding-related adverse events did not differ between the two groups.ConclusionsTherapy with rhTM may be associated with reduced in-hospital mortality in adult mechanically ventilated patients with sepsis-induced DIC.

Adverse cardiac events during catecholamine therapy: a role for hydrocortisone?

Dear Editor, We read with great interest the study by Schmittinger et al. [1] hypothesizing that adverse cardiac events frequently occur during catecholamine vasopressor therapy and that catecholamine vasopressor support is associated with both morbidity and mortality. In this prospective observational study, 54 of 112 surgical intensive care unit patients with cardiovascular failure developed a total of 114 adverse cardiac events during catecholamine vasopressor therapy, an incidence of 48.2 % (95 % CI, 38.8–57.6 %). The two adverse cardiac events most frequently observed in this study were tachyarrhythmia and prolonged elevated heart rate, both of which were correlated with significant morbidity and mortality. Sepsis was observed in a total of 44 (39 %) patients. In the Patients and Methods section, the authors detailed that ‘‘hydrocortisone (200–300 mg/ day) was added as a continuous infusion if escalating norepinephrine dose could not stabilize hemodynamic function.’’ Unfortunately, we did not find any details about the dose, the duration and the weaning for hydrocortisone therapy in the results or in the discussion sections. There is still an ongoing debate about hydrocortisone therapy during septic shock: the CORTICUS study conducted by Sprung et al. [2] did not find a significant reduction in mortality in the hydrocortisone group, but Moreno et al. [3] observed a significant reduction of SOFA scores mainly represented by a faster decrease in the cardiovascular component. The hydrocortisone-treated group had a higher mean number of vasopressor-free days in the first 7 days (2.5 ± 2.4) compared with the placebo group (1.4 ± 2.4) (p 0.0001). In a meta-analysis, Sligl et al. [4] also demonstrated a significant difference in the incidence of shock reversal at 7 days between patients who received corticosteroids and those who did not [64.9 % (314 of 484 patients) vs. 47.5 % (228 of 480); RR, 1.41; 95 % CI, 1.22–1.64]. Additionally, Annane et al. performed a systematic review on the benefits of corticosteroids in the treatment of severe sepsis and septic shock in adults. A favorable effect of treatment on shock reversal at 7 and 28 days was shown [5]. Indeed, shock reversal (as defined by a stable hemodynamic status for [24 h after withdrawal of vasopressor therapy) at 7 days for treated patients was 308 of 485 (63.5 %) versus 226 of 480 (47.1 %) (RR, 1.35; 95 % CI, 1.16–1.57; p 0.001) in the control group. Similar results were found at 28 days for treated patients with 322 of 481 (66.9 %) of shock reversal vs. 276 of 471 (58.6 %) (RR, 1.12; 95 % CI, 1.02–1.23; p = 0.02) in the control group. To conclude, as far as hydrocortisone therapy reducing the time exposure to vasopressor support, we would like to know if the authors could describe their results more precisely and provide their opinion concerning the use of corticoids in their study, specifically regarding the adverse cardiac events during vasopressor therapy in patients with sepsis and septic shock.

Intra-abdominal pressure and abdominal perfusion pressure in cirrhotic patients with septic shock.

BackgroundThe importance of intra-abdominal pressure (IAP) and abdominal perfusion pressure (APP) in cirrhotic patients with septic shock is not well studied. We evaluated the relationship between IAP and APP and outcomes of cirrhotic septic patients, and assessed the ability of these measures compared to other common resuscitative endpoints to differentiate survivors from nonsurvivors.MethodsThis study was a post hoc analysis of a randomized double-blind placebo-controlled trial in which mean arterial pressure (MAP), central venous oxygen saturation (ScvO2) and IAP were measured every 6 h in 61 cirrhotic septic patients admitted to the intensive care unit. APP was calculated as MAP - IAP. Intra-abdominal hypertension (IAH) was defined as mean IAP ≥ 12 mmHg, and abdominal hypoperfusion as mean APP < 60 mmHg. Measured outcomes included ICU and hospital mortality, need for renal replacement therapy (RRT) and ventilator- and vasopressor-free days.ResultsIAH prevalence on the first ICU day was 82%, and incidence in the first 7 days was 97%. Compared to patients with normal IAP, IAH patients had significantly higher ICU mortality (74.0% vs. 27.3%, p = 0.005), required more RRT (78.0% vs. 45.5%, p = 0.06) and had lower ventilator- and vasopressor-free days. On a multivariate logistic regression analysis, IAH was an independent predictor of both ICU mortality (odds ratio (OR), 12.20; 95% confidence interval (CI), 1.92 to 77.31, p = 0.008) and need for RRT (OR, 6.78; 95% CI, 1.29 to 35.70, p = 0.02). Using receiver operating characteristic curves, IAP (area under the curve (AUC) = 0.74, p = 0.004), APP (AUC = 0.71, p = 0.01), Acute Physiology and Chronic Health Evaluation II score (AUC = 0.71, p = 0.02), but not MAP, differentiated survivors from nonsurvivors.ConclusionsIAH is highly prevalent in cirrhotic patients with septic shock and is associated with increased ICU morbidity and mortality.

Etomidate and mortality in cirrhotic patients with septic shock

BackgroundClinical effects and outcomes of a single dose etomidate prior to intubation in the intensive care setting is controversial. The aim of this study is to evaluate the association of a single dose effect of etomidate prior to intubation on the mortality of septic cirrhotic patients and the impact of the subsequent use of low dose hydrocortisone.MethodsThis is a nested-cohort study within a randomized double blind placebo controlled study evaluating the use of low dose hydrocortisone in cirrhotic septic patients. Cirrhotic septic patients ≥ 18 years were included in the study. Patients who received etomidate prior to intubation were compared to those who did not receive etomidate for all cause 28-day mortality as a primary outcome.ResultsSixty two intubated patients out of the 75 patients randomized in the initial trial were eligible for this study. Twenty three of the 62 intubated patients received etomidate dose prior to intubation. Etomidate use was not associated with all cause 28-day mortality or hospital mortality but was associated with significantly higher ICU mortality (91% vs. 64% for etomidate and controls groups, respectively; p = 0.02). Etomidate patients who received subsequent doses of hydrocortisone required lower doses of vasopressors and had more vasopressor-free days but no improvement in mortality.ConclusionsIn this group of septic cirrhotic patients with very high mortality, etomidate increased ICU mortality. Subsequent use of hydrocortisone appears to have no benefit beyond decreasing vasopressor requirements. The lowest mortality was observed in patients who did not receive etomidate but received hydrocortisone.

Activated Protein C and Septic Shock: A Propensity-Matched Cohort Study,

Abstract 3307▪▪This icon denotes a clinically relevant abstract Background:Septic shock is a highly inflammatory and pro-coagulant state associated with high mortality. In a single randomized controlled clinical trial, recombinant human activated protein C (rhAPC, drotrecogin alfa) reduced mortality in patients with severe sepsis at high risk of death. Further clinical trials in patients with a lower severity of illness and in children have failed to reproduce these results, and the effectiveness of rhAPC remains the subject of ongoing debate. Insufficient data exists regarding the use of rhAPC outside of a clinical trial. Objective:To evaluate the effectiveness of rhAPC on mortality in a cohort of patients with septic shock. Methods:We conducted a retrospective, propensity-matched, multi-center cohort study in 28 academic and community intensive care units in 3 countries. Propensity scores were based more 33 variables that were either known or suspected to be associated with rhAPC use. Our primary outcomes were mortality over 30 days and 30-day mortality stratified by APACHE II quartile. Secondary outcomes were hospital and ICU mortality and length of stay, ventilator free and vasopressor free days, and the use of acute dialysis. Results:Using a propensity matched Cox proportional hazard model we observed a 5.9% absolute reduction in 30-day mortality associated with activated protein C use [115/342 (33.6%) vs. 135/342 (39.5%), HR 0.83, 95% CI 0.65–1.07, p=0.15]; however this reduction failed to reach statistical significance. Similarly, we observed non-significant reductions in mortality among the 3 lowest APACHE II quartiles (APACHE II <20: 12.5% vs. 18.2%, HR 0.66, 95%CI 0.29 – 1.49, p=0.32; APACHE II 21–25: 20% vs 33.3%, HR 0.55, 95% CI 0.30–1.02, p=0.06; and APACHE II 26–30: 36.7% vs. 48.7%, HR 0.73, 95% CI 0.45 – 1.19, p=0.21). Hospital mortality (40.6% vs. 46.8%, HR 0.83, 95%CI 0.66–1.04, p=0.10) and ICU mortality (31.0 vs. 35.1%, HR 0.87, 95%CI 0.67–1.13, p=0.28) were not significantly reduced among patients who received rhAPC compared to matched controls. The use of rhAPC was not associated with significant differences in ICU or hospital length of stay, ventilator free days, vasopressor free days or the use of acute dialysis. Conclusion:In this retrospective, multi-center propensity matched cohort study, the use of rhAPC in patients with septic shock was not associated with statistically significant reductions in 30-day mortality. However, the absolute reduction in 30-day mortality was in similar to that observed in previously published clinical trials. Prospective clinical trials evaluating the efficacy of rhAPC are currently ongoing and will serve to define the role of rhAPC in patients with septic shock. Disclosures:Kumar:Pfizer: Research Funding; Astellas: Research Funding; GSK: Research Funding; Roche: Research Funding.

γ-globulin levels in patients with community-acquired septic shock

Polyclonal intravenous immunoglobulins (IVIGs) can modulate the host immune response and may improve outcomes in some patients. In this prospective, noninterventional study, we assessed the time-course of gamma-globulin concentrations in 21 patients with septic shock and evaluated the relationship of gamma-globulin concentrations to disease severity and outcome. Six patients (28.5%) died. Sixteen patients (76%) had hypo-gamma-globulinemia at admission: 12 (57%) had low IgG concentrations (G650 mg/dL), 2 had low IgA concentrations (G70 mg/dL), and 9 had low IgM concentrations (G40 mg/dL). Two patients had low concentrations of all three gamma-globulins; these patients both died from refractory shock within 2 days. Patients with low IgG concentrations were indistinguishable at baseline from patients with normal IgG concentrations but had fewer vasopressor-free days (over 28 days) and more frequently developed acute lung injury/acute respiratory distress syndrome (3/9 vs. 10/12; P = 0.02). All deaths occurred in the patients with low IgG concentrations (6/ 12 vs. 0/9). There was a variable increase in kappa and lambda free light chains, a marker of gamma-globulin synthesis, over time with no significant difference between low and normal IgG groups. This pilot study indicates that low concentrations of gamma-globulins, especially IgG, are common in patients with community-acquired septic shock and persist over time even when sepsis resolves. Despite similar presentation, patients with hypo-IgG had greater vasopressor requirements, were more likely to develop acute lung injury/acute respiratory distress syndrome, and had higher mortality. Patients with low IgG concentrations may represent a logical target group to study the effects of Ig supplementation in septic shock.

SHOULD I GIVE MY SEPTIC PATIENTS POLYCLONAL γ-GLOBULINES IF THEY ARE HYPOGAMMAGLOBULINEMIC?

SHOULD I GIVE MY SEPTIC PATIENTS POLYCLONAL γ-GLOBULINES IF THEY ARE HYPOGAMMAGLOBULINEMIC?

APCAP - activated protein C in acute pancreatitis: a double-blind randomized human pilot trial

IntroductionPrevious human studies have shown low activity of protein C (APC) in severe acute pancreatitis (SAP). This, together with the findings in animal models, suggests that activated protein C (APC) may protect against pancreatic injury and ameliorate the disease. We, therefore, evaluated its effect on multiple organ dysfunction (MOD) measured by the SOFA (Sequential Organ Failure Assessment) and on organ-failure-free days, and the safety of APC in SAP.MethodsA prospective double blind randomized pilot study was use. The study occurred in one university hospital tertiary intensive care unit (ICU) with eight beds. The patients were chosen according to the following inclusion criteria: 1) Those admitted to the hospital < 96 h from the onset of pain, 2) Those who had a three-fold increase in serum amylase over normal upper range or/and in whom computed tomography (CT) verification of SAP was noted, 3) Those who had one or more organ dysfunction (OD), and 4) Those in whom less than 48 hours had passed since their first OD. Of a total of 215 adult patients with SAP screened between June 2003 and August 2007, 158 fulfilled the study inclusion criteria. After exclusions 32 patients were randomized to the study. The intervention consisted of APC (N = 16) administered intravenously for 96 hours with a dose of 24 μg/kg/hour or placebo (N = 16) with a similar infusion rate. The sample size for the study was calculated according to the primary end-point: the change in SOFA during study drug infusion (Days 0 and 5). Comparisons between the study groups were performed using patient-related changes and calculation of difference in means (DIM, 95% CIs) and regarding categorical variables with Fisher's exact test. For all comparisons P < 0.05 was considered significant.ResultsNo serious bleeding was detected clinically or by CT scans in either group. No significant difference in SOFA score change between the APC and placebo groups was found (difference in means (DIM) +2.3, 95% CI -0.7 to +5.3). Treatment with APC was associated with an increase in serum levels of both total and conjugated bilirubin. No differences in ventilator-free days, in renal replacement therapy-free days, in vasopressor-free days, or in days alive outside the hospital were detected.ConclusionsNo serious bleeding or differences in the evolution of MOD were detected between APC and the placebo. Instead we found an increase in serum bilirubin in the APC group compared to the placebo group in patients with SAP.Trial registrationClinicalTrials.gov NCT01017107.

γ-GLOBULIN LEVELS IN PATIENTS WITH COMMUNITY-ACQUIRED SEPTIC SHOCK

Polyclonal intravenous immunoglobulins (IVIGs) can modulate the host immune response and may improve outcomes in some patients. In this prospective, noninterventional study, we assessed the time-course of gamma-globulin concentrations in 21 patients with septic shock and evaluated the relationship of gamma-globulin concentrations to disease severity and outcome. Six patients (28.5%) died. Sixteen patients (76%) had hypo-gamma-globulinemia at admission: 12 (57%) had low IgG concentrations (G650 mg/dL), 2 had low IgA concentrations (G70 mg/dL), and 9 had low IgM concentrations (G40 mg/dL). Two patients had low concentrations of all three gamma-globulins; these patients both died from refractory shock within 2 days. Patients with low IgG concentrations were indistinguishable at baseline from patients with normal IgG concentrations but had fewer vasopressor-free days (over 28 days) and more frequently developed acute lung injury/acute respiratory distress syndrome (3/9 vs. 10/12; P = 0.02). All deaths occurred in the patients with low IgG concentrations (6/ 12 vs. 0/9). There was a variable increase in kappa and lambda free light chains, a marker of gamma-globulin synthesis, over time with no significant difference between low and normal IgG groups. This pilot study indicates that low concentrations of gamma-globulins, especially IgG, are common in patients with community-acquired septic shock and persist over time even when sepsis resolves. Despite similar presentation, patients with hypo-IgG had greater vasopressor requirements, were more likely to develop acute lung injury/acute respiratory distress syndrome, and had higher mortality. Patients with low IgG concentrations may represent a logical target group to study the effects of Ig supplementation in septic shock.