FIBTEM provides early prediction of massive transfusion in trauma

Introduction

Prediction of massive transfusion (MT) among trauma patients is difficult in the early phase of trauma management. Whole-blood thromboelastometry (ROTEM^®) tests provide immediate information about the coagulation status of acute bleeding trauma patients. We investigated their value for early prediction of MT.

Methods

This retrospective study included patients admitted to the AUVA Trauma Centre, Salzburg, Austria, with an injury severity score ≥16, from whom blood samples were taken immediately upon admission to the emergency room (ER). ROTEM^® analyses (extrinsically-activated test with tissue factor (EXTEM), intrinsically-activated test using ellagic acid (INTEM) and fibrin-based extrinsically activated test with tissue factor and the platelet inhibitor cytochalasin D (FIBTEM) tests) were performed. We divided patients into two groups: massive transfusion (MT, those who received ≥10 units red blood cell concentrate within 24 hours of admission) and non-MT (those who received 0 to 9 units).

Results

Of 323 patients included in this study (78.9% male; median age 44 years), 78 were included in the MT group and 245 in the non-MT group. The median injury severity score upon admission to the ER was significantly higher in the MT group than in the non-MT group (42 vs 27, P < 0.0001). EXTEM and INTEM clotting time and clot formation time were significantly prolonged and maximum clot firmness (MCF) was significantly lower in the MT group versus the non-MT group (P < 0.0001 for all comparisons). Of patients admitted with FIBTEM MCF 0 to 3 mm, 85% received MT. The best predictive values for MT were provided by hemoglobin and Quick value (area under receiver operating curve: 0.87 for both parameters). Similarly high predictive values were observed for FIBTEM MCF (0.84) and FIBTEM A10 (clot amplitude at 10 minutes; 0.83).

Conclusions

FIBTEM A10 and FIBTEM MCF provided similar predictive values for massive transfusion in trauma patients to the most predictive laboratory parameters. Prospective studies are needed to confirm these findings.     

Comparison of thrombelastometry with simplified acute physiology score II and sequential organ failure assessment scores for the prediction of 30-day survival: a cohort study

Disseminated intravascular coagulation contributes to mortality of sepsis. The study was performed to investigate thromboelastometry as a potential predictor of 30-day survival in severe sepsis and to compare thromboelastometry to Simplified Acute Physiology Score II (SAPS II) and Sequential Organ Failure Assessment (SOFA) scores. Ninety-eight patients with severe sepsis were included in the cohort study. Thromboelastometry clotting time, clot formation time (CFT), maximum clot firmness (MCF), and α angle as well as SAPS II and SOFA scores were determined at the day of diagnosis. Thromboelastometry variables differed in survivors and nonsurvivors. Mean CFT was prolonged (276 ± 194 vs. 194 ± 109 s, P = 0.021; mean ± SD), and both MCF (52.7 ± 12.1 mm vs. 57.3 ± 11.5 mm, P = 0.042) and α angle (53.4 ± 12.8 degrees vs. 58.9 ± 11.8 degrees, P = 0.028) were reduced in nonsurvivors. Clotting time and SAPS II and SOFA scores were not different. Thromboelastometry values were classified as normal and pathological, respectively, using the median of the variables as the cutoff. Thromboelastometry values were normal if CFT was less than 185 s, MCF was greater than 55 mm, and α was greater than 57.5 degrees. Thirty-day survival was 85.7% when all thromboelastometry variables were normal, but 58.7% when at least one variable was pathological (P = 0.005). Multivariate analysis revealed that the absence or presence of at least one pathological thromboelastometry variable allows for better prediction of 30-day survival in severe sepsis than the SAPS II and SOFA scores (P = 0.01; odds ratio, 4.1), respectively, emphasizing the importance of the coagulation system in sepsis.     

Association between length of storage of red blood cell units and outcome of critically ill children: a prospective observational study

Introduction

Acute kidney injury (AKI) in the ICU is associated with poorer prognosis. Hydroxyethylstarch (HES) solutions are fluid resuscitation colloids frequently used in the ICU with controversial nephrotoxic adverse effects. Our study objective was to evaluate HES impact on renal function and organ failures.

Methods

This observational retrospective study included 363 patients hospitalized for more than 72 hours in our ICU. A hundred and sixty eight patients received HES during their stay and 195 did not. We recorded patients' baseline characteristics on admission and type and volume of fluid resuscitation during the first 3 weeks of ICU stay. We also noted the evolution of urine output, the risk of renal dysfunction, injury to the kidney, failure of kidney function, loss of kidney function and end-stage kidney disease (RIFLE) classification and sepsis related organ failure assessment (SOFA) score over 3 weeks.

Results

Patients in the HES group were more severely ill on admission but AKI incidence was similar, as well as ICU mortality. The evolution of urine output (P = 0.74), RIFLE classification (P = 0.44) and SOFA score (P = 0.23) was not different. However, HES volumes administered were low (763+/-593 ml during the first 48 hours).

Conclusions

Volume expansion with low volume HES 130 kDa/0.4 was not associated with AKI.     

Time course of organ failure in patients with septic shock treated with hydrocortisone: results of the Corticus study

Introduction

Corticosteroids have been proposed to decrease morbidity and mortality in patients with septic shock. An impact on morbidity should be anticipated to be earlier and more easily detected than the impact on mortality.

Methods

Prospective, randomized, double-blind, placebo-controlled study of 28-day mortality in patients with septic shock for <72?h who underwent a short high-dose ACTH test in 52 centers in 9 European countries. Patients received 11-day treatment with hydrocortisone or placebo. Organ dysfunction/failure was quantified by the use of the sequential organ failure assessment (SOFA) score.

Results

From March 2002 to November 2005, 499 patients were enrolled (hydrocortisone 251, placebo 248). Both groups presented a similar SOFA score at baseline (hydrocortisone 10.8?±?3.2 vs. placebo 10.7?±?3.1 points). There was no difference in 28-day mortality between the two treatment groups (hydrocortisone 34.3% vs. placebo 31.5%). There was a decrease in the SOFA score of hydrocortisone-treated patients from day 0 to day 7 compared to the placebo-treated patients (p?=?0.0027), driven by an improvement in cardiovascular organ dysfunction/failure (p?=?0.0005) and in liver failure (p?Conclusion Patients randomized to treatment with hydrocortisone demonstrated a faster decrease in total organ dysfunction/failure determined by the SOFA score, primarily driven by a faster improvement in cardiovascular organ dysfunction/failure. This organ dysfunction/failure improvement was not accompanied by a decreased mortality.     

Gastrointestinal symptoms during the first week of intensive care are associated with poor outcome: a prospective multicentre study

Purpose

The study aimed to develop a gastrointestinal (GI) dysfunction score predicting 28-day mortality for adult patients needing mechanical ventilation (MV).

Methods

377 adult patients from 40 ICUs with expected duration of MV for at least 6 h were prospectively studied. Predefined GI symptoms, intra-abdominal pressures (IAP), feeding details, organ dysfunction and treatment were documented on days 1, 2, 4 and 7.

Results

The number of simultaneous GI symptoms was higher in nonsurvivors on each day. Absent bowel sounds and GI bleeding were the symptoms most significantly associated with mortality. None of the GI symptoms alone was an independent predictor of mortality, but gastrointestinal failure (GIF)—defined as three or more GI symptoms—on day 1 in ICU was independently associated with a threefold increased risk of mortality. During the first week in ICU, GIF occurred in 24 patients (6.4 %) and was associated with higher 28-day mortality (62.5 vs. 28.9 %, P = 0.001). Adding the created subscore for GI dysfunction (based on the number of GI symptoms) to SOFA score did not improve mortality prediction (day 1 AUROC 0.706 [95 % CI 0.647–0.766] versus 0.703 [95 % CI 0.643–0.762] in SOFA score alone).

Conclusions

An increasing number of GI symptoms independently predicts 28 day mortality with moderate accuracy. However, it was not possible to develop a GI dysfunction score, improving the performance of the SOFA score either due to data set limitations, definition problems, or possibly indicating that GI dysfunction is often secondary and not the primary cause of other organ failure.     

Patterns and early evolution of organ failure in the intensive care unit and their relation to outcome

Introduction

Recognition of patterns of organ failure may be useful in characterizing the clinical course of critically ill patients. We investigated the patterns of early changes in organ dysfunction/failure in intensive care unit (ICU) patients and their relation to outcome.

Methods

Using the database from a large prospective European study, we studied 2,933 patients who had stayed more than 48 hours in the ICU and described patterns of organ failure and their relation to outcome. Patients were divided into three groups: patients without sepsis, patients in whom sepsis was diagnosed within the first 48 hours after ICU admission, and patients in whom sepsis developed more than 48 hours after admission. Organ dysfunction was assessed by using the sequential organ failure assessment (SOFA) score.

Results

A total of 2,110 patients (72% of the study population) had organ failure at some point during their ICU stay. Patients who exhibited an improvement in organ function in the first 24 hours after admission to the ICU had lower ICU and hospital mortality rates compared with those who had unchanged or increased SOFA scores (12.4 and 18.4% versus 19.6 and 24.5%, P < 0.05, pairwise). As expected, organ failure was more common in sepsis than in nonsepsis patients. In patients with single-organ failure, in-hospital mortality was greater in sepsis than in nonsepsis patients. However, in patients with multiorgan failure, mortality rates were similar regardless of the presence of sepsis. Irrespective of the presence of sepsis, delta SOFA scores over the first 4 days in the ICU were higher in nonsurvivors than in survivors and decreased significantly over time in survivors.

Conclusions

Early changes in organ function are strongly related to outcome. In patients with single-organ failure, in-hospital mortality was higher in sepsis than in nonsepsis patients. However, in multiorgan failure, mortality rates were not influenced by the presence of sepsis.     

Clopidogrel resistance "Live" – the risk of stent thrombosis should be evaluated before procedures

Background

Endothelial cell dysfunction, by promoting fibrin deposition, has been implicated in the development of multiple organ failure. Altered fibrinolysis during inflammation may participate in microvascular alterations. We sought to determine whether plasma fibrinolysis was related to the severity of organ dysfunction and/or to the levels of von Willebrand factor (vWF antigen), as a marker of endothelium dysfunction, in critically ill patients.

Methods

Forty-nine consecutive patients admitted to an adult medico-surgical intensive care unit (ICU) with (18) or without sepsis (31) were included. C-reactive protein and vWF levels were measured on ICU admission and plasma fibrinolysis was assessed by the Euglobulin Clot Lysis Time (ECLT). The sequential organ failure assessment (SOFA) score and the simplified acute physiology score (SAPS) II were calculated on admission.

Results

ECLT was significantly longer in septic than in non-septic patients [1033 min (871–1372) versus 665 min (551–862), p = 0.001]. There were significant correlations between ECLT and C-reactive protein (CRP) concentrations (r = 0.78, p < 0.001) and the Sequential Organ Failure Assessment (SOFA) score (r = 0.39, p = 0.006). The level of vWF was not correlated with the ECLT (r = -0.06, p = 0.65) or the SOFA score (r = -0.02, p = 0.88).

Conclusion

ECLT measurement at admission could be a marker of organ dysfunction and a prognostic indicator in critically ill patients.     

Treatment effects of recombinant human soluble thrombomodulin in patients with severe sepsis: a historical control study

Introduction

Cross-talk between the coagulation system and inflammatory reactions during sepsis causes organ damage followed by multiple organ dysfunction syndrome or even death. Therefore, anticoagulant therapies have been expected to be beneficial in the treatment of severe sepsis. Recombinant human soluble thrombomodulin (rhTM) binds to thrombin to inactivate coagulation, and the thrombin-rhTM complex activates protein C to produce activated protein C. The purpose of this study was to examine the efficacy of rhTM for treating patients with sepsis-induced disseminated intravascular coagulation (DIC).

Methods

This study comprised 65 patients with sepsis-induced DIC who required ventilatory management. All patients fulfilled the criteria of severe sepsis and the International Society on Thrombosis and Haemostasis criteria for overt DIC. The initial 45 patients were treated without rhTM (control group), and the following 20 consecutive patients were treated with rhTM (0.06 mg/kg/day) for six days (rhTM group). The primary outcome measure was 28-day mortality. Stepwise multivariate Cox regression analysis was used to assess which independent variables were associated with mortality. Comparisons of Sequential Organ Failure Assessment (SOFA) score on sequential days between the two groups were analyzed by repeated measures analysis of variance.

Results

Cox regression analysis showed 28-day mortality to be significantly lower in the rhTM group than in the control group (adjusted hazard ratio, 0.303; 95% confidence interval, 0.106 to 0.871; P = 0.027). SOFA score in the rhTM group decreased significantly in comparison with that in the control group (P = 0.028). In the post hoc test, SOFA score decreased rapidly in the rhTM group compared with that in the control group on day 1 (P < 0.05).

Conclusions

We found that rhTM administration may improve organ dysfunction in patients with sepsis-induced DIC. Further clinical investigations are necessary to evaluate the effect of rhTM on the pathophysiology of sepsis-induced DIC.     

Model for predicting short-term mortality of severe sepsis

Introduction

To establish a prognostic model for predicting 14-day mortality in ICU patients with severe sepsis overall and according to place of infection acquisition and to sepsis episode number.

Methods

In this prospective multicentre observational study on a multicentre database (OUTCOMEREA) including data from 12 ICUs, 2268 patients with 2737 episodes of severe sepsis were randomly divided into a training cohort (n = 1458) and a validation cohort (n = 810). Up to four consecutive severe sepsis episodes per patient occurring within the first 28 ICU days were included. We developed a prognostic model for predicting death within 14 days after each episode, based on patient data available at sepsis onset.

Results

Independent predictors of death were logistic organ dysfunction (odds ratio (OR), 1.22 per point, P < 10^-4), septic shock (OR, 1.40; P = 0.01), rank of severe sepsis episode (1 reference, 2: OR, 1.26; P = 0.10 ≥ 3: OR, 2.64; P < 10^-3), multiple sources of infection (OR; 1.45, P = 0.03), simplified acute physiology score II (OR, 1.02 per point; P < 10^-4), McCabe score ([greater than or equal to]2) (OR, 1.96; P < 10^-4), and number of chronic co-morbidities (1: OR, 1.75; P < 10^-3, ≥ 2: OR, 2.24, P < 10^-3). Validity of the model was good in whole cohorts (AUC-ROC, 0.76; 95%CI, 0.74 to 0.79; and HL Chi-square: 15.3 (P = 0.06) for all episodes pooled).

Conclusions

In ICU patients, a prognostic model based on a few easily obtained variables is effective in predicting death within 14 days after the first to fourth episode of severe sepsis complicating community-, hospital-, or ICU-acquired infection.     

Incidence, organ dysfunction and mortality in severe sepsis: a Spanish multicentre study

Introduction

Sepsis is a leading cause of admission to non-cardiological intensive care units (ICUs) and the second leading cause of death among ICU patients. We present the first extensive dataset on the epidemiology of severe sepsis treated in ICUs in Spain.

Methods

We conducted a prospective, observational, multicentre cohort study, carried out over two 3-month periods in 2002. Our aims were to determine the incidence of severe sepsis among adults in ICUs in a specific area in Spain, to determine the early (48 h) ICU and hospital mortality rates, as well as factors associated with the risk of death.

Results

A total of 4,317 patients were admitted and 2,619 patients were eligible for the study; 311 (11.9%) of these presented at least 1 episode of severe sepsis, and 324 (12.4%) episodes of severe sepsis were recorded. The estimated accumulated incidence for the population was 25 cases of severe sepsis attended in ICUs per 100,000 inhabitants per year. The mean logistic organ dysfunction system (LODS) upon admission was 6.3; the mean sepsis-related organ failure assessment (SOFA) score on the first day was 9.6. Two or more organ failures were present at diagnosis in 78.1% of the patients. A microbiological diagnosis of the infection was reached in 209 episodes of sepsis (64.5%) and the most common clinical diagnosis was pneumonia (42.8%). A total of 169 patients (54.3%) died in hospital, 150 (48.2%) of these in the ICU. The mortality in the first 48 h was 14.8%. Factors associated with early death were haematological failure and liver failure at diagnosis, acquisition of the infection prior to ICU admission, and total LODS score on admission. Factors associated with death in the hospital were age, chronic alcohol abuse, increased McCabe score, higher LODS on admission, ΔSOFA 3-1 (defined as the difference in the total SOFA scores on day 3 and on day 1), and the difference of the area under the curve of the SOFA score throughout the first 15 days.

Conclusions

We found a high incidence of severe sepsis attended in the ICU and high ICU and hospital mortality rates. The high prevalence of multiple organ failure at diagnosis and the high mortality in the first 48 h suggests delays in diagnosis, in initial resuscitation, and/or in initiating appropriate antibiotic treatment.     

The association of near-infrared spectroscopy-derived tissue oxygenation measurements with sepsis syndromes, organ dysfunction and mortality in emergency department patients with sepsis

Introduction

Near-infrared spectroscopy (NIRS) noninvasively measures peripheral tissue oxygen saturation (StO₂). NIRS may be utilized along with a vascular occlusion test, in which limb blood flow is temporarily occluded and released, to quantify a tissue bed's rate of oxygen exchange during ischemia and recovery. The objective of this study was to test the hypothesis that NIRS-derived StO₂ measures (StO₂ initial, StO₂ occlusion and StO₂ recovery) identify patients who are in shock and at increased risk of organ dysfunction (Sequential Organ Failure Assessment (SOFA) score ≥ 2 at 24 hours) and dying in the hospital.

Methods

This prospective, observational study comprised a convenience sample of three cohorts of adult patients (age > 17 years) at three urban university emergency departments: (1) a septic shock cohort (systolic blood pressure < 90 after fluid challenge; the "SHOCK" cohort, n = 58), (2) a sepsis without shock cohort (the "SEPSIS" cohort, n = 60) and emergency department patients without infection (n = 50). We measured the StO₂ initial, StO₂ occlusion and StO₂ recovery slopes for all patients. Outcomes were sepsis syndrome severity, organ dysfunction (SOFA score at 24 hours) and in-hospital mortality.

Results

Among the 168 patients enrolled, mean initial StO₂ was lower in the SHOCK cohort than in the SEPSIS cohort (76% vs 81%), with an impaired occlusion slope (-10.2 and 5.2%/minute vs -13.1 and 4.4%/minute) and an impaired recovery slope (2.4 and 1.6%/second vs 3.9 and 1.7%/second) (P < 0.001 for all). The recovery slope was well-correlated with SOFA score at 24 hours (-0.35; P < 0.001), with a promising area under the curve (AUC) for mortality of 0.81. The occlusion slope correlation with SOFA score at 24 hours was 0.21 (P < 0.02), with a fair mortality AUC of 0.70. The initial StO₂ was significantly but less strongly correlated with SOFA score at 24 hours (-0.18; P < 0.04), with a poor mortality AUC of 0.56.

Conclusions

NIRS measurements for the StO₂ initial, StO₂ occlusion and StO₂ recovery slope were abnormal in patients with septic shock compared to sepsis patients. The recovery slope was most strongly associated with organ dysfunction and mortality. Further validation is warranted.

Trial registration

NCT01062685     

A multicenter trial to compare blood culture with polymerase chain reaction in severe human sepsis

Objective

To assess the presence of microbial DNA in the blood by polymerase chain reaction (PCR) and its association with disease severity and markers of inflammation in severe sepsis and to compare the performance of PCR with blood culture (BC).

Design

Prospective multicentric controlled observational study.

Setting

Three surgical intensive care units in university centers and large teaching hospitals.

Patients

One hundred forty-two patients with severe sepsis and 63 surgical controls.

Interventions

Presence of microbial DNA was assessed by multiplex PCR upon enrollment, and each time a BC was obtained.

Measurements and main results

Controls had both approximately 4% positive PCRs and BCs. In severe sepsis, 34.7% of PCRs were positive compared to 16.5% of BCs (P < 0.001). Consistently, 70.3% of BCs had a corresponding PCR result, while only 21.4% of PCR results were confirmed by BC. Compared to patients with negative PCRs at enrollment, those testing positive had higher organ dysfunction scores [SOFA, median (25th–75th percentile) 12 (7–15) vs. 9 (7–11); P = 0.023] and a trend toward higher mortality (PCR negative 25.3%; PCR positive 39.1%; P = 0.115).

Conclusions

In septic patients, concordance between BC and PCR is moderate. However, PCR-based pathogen detection correlated with disease severity even if the BC remained negative, suggesting that presence of microbial DNA in the bloodstream is a significant event. The clinical utility to facilitate treatment decisions warrants investigation.     

Knee area tissue oxygen saturation is predictive of 14-day mortality in septic shock

Purpose

Thenar eminence tissue oxygen saturation (StO₂) was developed to assess organ perfusion. However, mottling, a strong predictor of mortality in septic shock, develops preferentially around the knee. We aimed to evaluate the prognostic value of StO₂ measured around the knee in septic shock patients and compare it to thenar StO₂.

Methods

This was a prospective observational study in a tertiary teaching hospital. All consecutive patients with septic shock were included. Parameters were recorded when vasopressors were started (H0) and every 6?h during 24?h. Their predictive value was assessed on 14-day mortality.

Results

Fifty-two patients were included. SOFA score was 11 (9–15) and SAPS II was 56 (40–72). At 6?h after ICU admission (H6), mean arterial pressure, cardiac index, and central venous pressure were not different between non-survivors and survivors; but non-survivors had higher arterial lactate level (8.8?±?5.0 vs. 2.2?±?1.5?mmol/l, P?P?2 (62?±?20 vs. 72?±?9?%, P?=?0.03). At H6, StO₂ was lower in non-survivors; this difference was not significant for thenar StO₂ (70?±?15 vs. 77?±?12?%, P?=?0.10) but was very pronounced for knee StO₂ (39?±?23 vs. 71?±?12?%, P?2 was associated with a higher mottling score (P?P?R ²?=?0.2), and a lower urinary output (P?=?0.02, R ²?=?0.12).

Conclusion

After initial septic shock resuscitation, StO₂ measured around the knee is a strong predictive factor of 14-day mortality.     

Evaluation of the SOFA score: a single-center experience of a medical intensive care unit in 303 consecutive patients with predominantly cardiovascular disorders

Objective: To evaluate the use of the Sequential Organ Failure Assessment (SOFA) score, the total maximum SOFA (TMS) score, and a derived variable, the ΔSOFA (TMS score minus total SOFA score on day 1) in medical, cardiovascular patients as a means for describing the incidence and severity of organ dysfunction and the prognostic value regarding outcome. Design: Prospective, clinical study. Setting: Medical intensive care unit in a university hospital. Patients: A total of 303 consecutive patients were included (216 men, 87 women; mean age 62 ± 12.6 years; SAPS II 26.2 ± 12.7). They were evaluated 24 h after admission and thereafter every 24 h until ICU discharge or death between November 1997 and March 1998. Readmissions and patients with an ICU stay shorter than 12 h were excluded. Main outcome measure: Survival status at hospital discharge, incidence of organ dysfunction/failure. Interventions: Collection of clinical and demographic data and raw data for the computation of the SOFA score every 24 h until ICU discharge. Measurements and main results: Length of ICU stay was 3.7 ± 4.7 days. ICU mortality was 8.3 % and hospital mortality 14.5 %. Nonsurvivors had a higher total SOFA score on day 1 (5.9 ± 3.7 vs. 1.9 ± 2.3, p < 0.001) and thereafter until day 8. High SOFA scores for any organ system and increasing number of organ failures (SOFA score ≥ 3) were associated with increased mortality. Cardiovascular and neurological systems (day 1) were related to outcome and cardiovascular and respiratory systems, and admission from another ICU to length of ICU stay. TMS score was higher in nonsurvivors (1.76 ± 2.55 vs. 0.58 ± 1.39, p < 0.01), and ΔSOFA/total SOFA on day 1 was independently related to outcome. The area under the receiver-operating characteristic curve was 0.86 for TMS, 0.82 for SOFA on day 1, and 0.77 for SAPS II. Conclusions: The SOFA, TMS, and ΔSOFA scores provide the clinician with important information on degree and progression of organ dysfunction in medical, cardiovascular patients. On day 1 both SOFA score and TMS score had a better prognostic value than SAPS II score. The model is closely related to outcome and identifies patients who are at increased risk for prolonged ICU stay. Received: 6 August 1999 Final revision received: 3 January 2000 Accepted: 28 March 2000     

Glucose absorption and gastric emptying in critical illness

Introduction

Gallstones are the most common cause of acute pancreatitis worldwide. Patients with severe acute biliary pancreatitis (SABP) constitute a subgroup of severe acute pancreatitis (SAP) patients in whom systemic inflammation may be triggered and perpetuated by different mechanisms. The aim of this prospective investigation was to examine the adrenal response to corticotropin and the relationship between adrenal function and outcome in patients with SABP.

Methods

Thirty-two patients with SABP were enrolled in this study. A short corticotropin (250 μg) stimulation test (SST) was performed within the first 24 hours of admission to the ICU. Critical illness related corticosteroid insufficiency (CIRCI) was defined as follows: baseline value less than 10 μg/dL, or cortisol response less than 9 μg/dL.

Results

CIRCI occurred in 34.4% of patients. The patients with CIRCI were more severely ill as evidenced by higher APACHE II and SOFA scores and numbers of organ system dysfunction on the day of SST. The in-hospital mortality for the entire group was 21.9%. The CIRCI group had a higher hospital mortality rate compared to those with normal adrenal function (45.5% vs. 9.5%, P = 0.032). The hospital survivors had a higher cortisol response to corticotropin (17.4 (8.3–27.1) vs. 7.2 (1.7–12) μg/dL, P = 0.019). The cortisol response to corticotropin inversely correlated with SOFA score and the number of organ dysfunction on the day of SST. The rates of pancreatic necrosis and bacteremia were significantly higher in the CIRCI group (100% vs 42.9%, P = 0.002; 81.8% vs 23.8%, P = 0.003, respectively).

Conclusions

CIRCI is common in patients with SABP. It is associated with bacteremia, multiple organ dysfunction and increased mortality.     

Critical care management of patients with hemophagocytic lymphohistiocytosis

Objective

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening condition associated with multiple organ dysfunction. We sought to describe ICU management and outcomes in HLH patients meeting HLH-2004 criteria and to identify determinants of mortality.

Design

Retrospective study between January 1998 and January 2009.

Setting

Medical ICU of a teaching hospital.

Patients

Among the 72 patients fulfilling the HLH-2004 criteria, we report the 56 patients with complete follow-up and no missing data.

Interventions

None.

Measurements and main results

Clinical and laboratory data were abstracted from the medical records. Median SOFA score at admission was 6.5 (IQR, 4–8). At ICU admission, the number of HLH-2004 criteria was 6 (5–7). Sixty-six precipitating factors were found in 52 patients and consisted of 43 tumoral causes (8 Castleman’s diseases, 18 B cell lymphoma and 17 various malignancies), 13 non-viral infections and 10 viral infections. Underlying immune deficiency was present in 38 (67.8%) patients. Etoposide was used in 45 patients, corticosteroids in 31 and intravenous immunoglobulins in 3. Mechanical ventilation was required in 32 patients, vasoactive agents in 30 and renal replacement therapy in 19. Hospital mortality was 29/56 patients. By multivariate analysis, factors associated with increased hospital death were shock at ICU admission [OR, 4.33; 95% confidence interval (95% CI), 1.11–16.90; P = 0.03] and platelet count <30 g/l (OR, 4.75; 95% CI, 1.20–18.81; P = 0.02). B cell lymphoma [odds ratio (OR), 0.17; 95% CI, 0.04–0.80; P = 0.02] and Castleman’s disease (OR, 0.11; 95% CI, 0.02–0.90; P = 0.04) were associated with increased hospital survival.

Conclusions

Aggressive supportive care combined with specific treatment of the precipitating factor can produce meaningful survival in patients with HLH responsible for multiple organ failures. Survival is highest in patients with HLH related to Castleman’s disease or B cell lymphoma.     

Resuscitation with low volume hydroxyethylstarch 130 kDa/0.4 is not associated with acute kidney injury

Introduction

Acute kidney injury (AKI) in the ICU is associated with poorer prognosis. Hydroxyethylstarch (HES) solutions are fluid resuscitation colloids frequently used in the ICU with controversial nephrotoxic adverse effects. Our study objective was to evaluate HES impact on renal function and organ failures.

Methods

This observational retrospective study included 363 patients hospitalized for more than 72 hours in our ICU. A hundred and sixty eight patients received HES during their stay and 195 did not. We recorded patients'' baseline characteristics on admission and type and volume of fluid resuscitation during the first 3 weeks of ICU stay. We also noted the evolution of urine output, the risk of renal dysfunction, injury to the kidney, failure of kidney function, loss of kidney function and end-stage kidney disease (RIFLE) classification and sepsis related organ failure assessment (SOFA) score over 3 weeks.

Results

Patients in the HES group were more severely ill on admission but AKI incidence was similar, as well as ICU mortality. The evolution of urine output (P = 0.74), RIFLE classification (P = 0.44) and SOFA score (P = 0.23) was not different. However, HES volumes administered were low (763+/-593 ml during the first 48 hours).

Conclusions

Volume expansion with low volume HES 130 kDa/0.4 was not associated with AKI.     

Prevalence of endotoxemia after surgery and its association with ICU length of stay

Introduction

The aim of this observational study was to investigate the prevalence of endotoxemia after surgery and its association with ICU length of stay.

Methods

102 patients admitted to a university ICU after surgery were recruited. Within four hours of admission, functional data were collected and APACHE II severity score calculated. Arterial blood samples were taken and endotoxemia was measured by chemiluminescence (Endotoxin Activity (EA)). Patients were stratified according to their endotoxin levels (low, intermediate and high) and according to their surgical procedures. Differences between endotoxin levels were assessed by ANOVA, accepting P < 0.05 as significant. Data are expressed as mean ± SD.

Results

EA levels were low in 68 (66%) patients, intermediate in 17 (17%) and high in 17 (17%). Age (61 ± 17 years) and APACHE II score 8.3 ± 3.7 (P = 0.542) were not significantly different in the three EA groups. Functional parameters on admission were similar between EA groups: white blood cells 11093 ± 4605 cells/mm³ (P = 0.385), heart rate 76 ± 16 bpm (P = 0.898), mean arterial pressure 88.8 ± 13.6 mmHg (P = 0.576), lactate 1.18 ± 0.77 mmol/L (P = 0.370), PaO₂/FiO₂ 383 ± 109 mmHg (P = 0.474). Patients with high levels of EA were characterized by longer length of stay in the ICU: 1.9 ± 3.0 days in the low EA group, 1.8 ± 1.4 days in intermediate and 5.2 ± 7.8 days in high group (P = 0.038).

Conclusions

17% of our patients were characterized by high levels of endotoxemia as assessed by EA assay, despite their low level of complexity on admission. High levels of endotoxin were associated with a longer ICU length of stay.     

Usefulness of a clinical diagnosis of ICU-acquired paresis to predict outcome in patients with SIRS and acute respiratory failure

Purpose

Neuromuscular abnormalities are common in ICU patients. We aimed to assess the incidence of clinically diagnosed ICU-acquired paresis (ICUAP) and its impact on outcome.

Methods

Forty-two patients with systemic inflammatory response syndrome on mechanical ventilation for ≥48 h were prospectively studied. Diagnosis of ICUAP was defined as symmetric limb muscle weakness in at least two muscle groups at ICU discharge without other explanation. The threshold Medical Research Council (MRC) Score was set at 35 (of 50) points. Activities in daily living were scored using the Barthel Index 28 and 180 days after ICU discharge.

Results

Three patients died before sedation was stopped. ICUAP was diagnosed in 13 of the 39 patients (33%). Multivariate regression analysis yielded five ICUAP-predicting variables (P < 0.05): SAPS II at ICU admission, treatment with steroids, muscle relaxants or norepinephrine, and days with sepsis. Patients with ICUAP had lower admission SAPS II scores [37 ± 13 vs. 49 ± 15 (P = 0.018)], lower Barthel Index at 28 days and lower survival at 180 days after ICU discharge (38 vs. 77%, P = 0.033) than patients without ICUAP. Daily TISS-28 scores were similar but cumulative TISS-28 scores were higher in patients with ICUAP (664 ± 275) than in patients without ICUAP (417 ± 236; P = 0.008). The only independent risk factor for death before day 180 was the presence of ICUAP.

Conclusions

A clinical diagnosis of ICUAP was frequently established in this patient group. Despite lower SAPS II scores, these patients needed more resources and had high mortality and prolonged recovery periods after ICU discharge.     

Prognostic accuracy of age-adapted SOFA,SIRS, PELOD-2, and qSOFA for in-hospital mortality among children with suspected infection admitted to the intensive care unit

Purpose

The Sepsis-3 consensus task force defined sepsis as life-threatening organ dysfunction caused by dysregulated host response to infection. However, the clinical criteria for this definition were neither designed for nor validated in children. We validated the performance of SIRS, age-adapted SOFA, quick SOFA and PELOD-2 scores as predictors of outcome in children.

Methods

We performed a multicentre binational cohort study of patients < 18 years admitted with infection to ICUs in Australia and New Zealand. The primary outcome was ICU mortality. SIRS, age-adapted SOFA, quick SOFA and PELOD-2 scores were compared using crude and adjusted area under the receiver operating characteristic curve (AUROC) analysis.

Results

Of 2594 paediatric ICU admissions due to infection, 151 (5.8%) children died, and 949/2594 (36.6%) patients died or experienced an ICU length of stay ≥ 3 days. A ≥ 2-point increase in the individual score was associated with a crude mortality increase from 3.1 to 6.8% for SIRS, from 1.9 to 7.6% for age-adapted SOFA, from 1.7 to 7.3% for PELOD-2, and from 3.9 to 8.1% for qSOFA (p < 0.001). The discrimination of outcomes was significantly higher for SOFA (adjusted AUROC 0.829; 0.791–0.868) and PELOD-2 (0.816; 0.777–0.854) than for qSOFA (0.739; 0.695–0.784) and SIRS (0.710; 0.664–0.756).

Conclusions

SIRS criteria lack specificity to identify children with infection at substantially higher risk of mortality. We demonstrate that adapting Sepsis-3 to age-specific criteria performs better than Sepsis-2-based criteria. Our findings support the translation of Sepsis-3 into paediatric-specific sepsis definitions and highlight the importance of robust paediatric organ dysfunction characterization.