A critique of fluid bolus resuscitation in severe sepsis.

Crit Care. 2012 Jan 25;16(1):302

Authors: Hilton AK, Bellomo R

Abstract
ABSTRACT: Resuscitation of septic patients by means of one or more fluid boluses is recommended by guidelines from multiple relevant organizations and as a component of surviving sepsis campaigns. The technique is considered a key and life-saving intervention during the initial treatment of severe sepsis in children and adults. Such recommendations, however, are only based on expert opinion and lack adequate experimental or controlled human evidence. Despite these limitations, fluid bolus therapy (20 to 40 ml/kg) is widely practiced and is currently considered a cornerstone of the management of sepsis. In this pointof-view critique, we will argue that such therapy has weak physiological support, has limited experimental support, and is at odds with emerging observational data in several subgroups of critically ill patients or those having major abdominal surgery. Finally, we will argue that this paradigm is now challenged by the findings of a large randomized controlled trial in septic children. In the present article, we contend that the concept of large fluid bolus resuscitation in sepsis needs to be investigated further.

PMID: 22277834 [PubMed - as supplied by publisher]

Clinical utility of biomarkers of endothelial activation in sepsis - a systematic review.

Crit Care. 2012 Jan 16;16(1):R7

Authors: Xing K, Murthy S, Liles WC, Singh JM

Abstract
ABSTRACT: INTRODUCTION: A strong biologic rationale exists for targeting markers of endothelial cell (EC) activation as clinically informative biomarkers to improve diagnosis, prognostic evaluation or risk-stratification of patients with sepsis. METHODS: The objective was to review the literature on the use of markers of EC activation as prognostic biomarkers in sepsis. MEDLINE was searched for publications using the keyword 'sepsis' and any of the identified endothelial-derived biomarkers in any searchable field. All clinical studies evaluating markers reflecting activation of ECs were included. Studies evaluating other exogenous mediators of EC dysfunction and studies of patients with malaria and febrile neutropenia were excluded. RESULTS: Sixty-one studies were identified that fulfilled the inclusion criteria. Overall, published studies report positive correlations between multiple EC-derived molecules and the diagnosis of sepsis, supporting the critical role of EC activation in sepsis. Multiple studies also reported positive associations for mortality and severity of illness, although these results were less consistent than for the presence of sepsis. Very few studies, however, reported thresholds or receiver operating characteristics that would establish these molecules as clinically-relevant biomarkers in sepsis. CONCLUSIONS: Multiple endothelial-derived molecules are positively correlated with the presence of sepsis in humans, and variably correlated to other clinically-important outcomes. The clinical utility of these biomarkers is limited by a lack of assay standardization, unknown receiver operating characteristics and lack of validation. Additional large-scale prospective clinical trials will be required to determine the clinical utility of biomarkers of endothelial activation in the management of patients with sepsis.

PMID: 22248019 [PubMed - as supplied by publisher]

Plasma neutrophil gelatinase-associated lipocalin for the prediction of acute kidney injury in acute heart failure.

Crit Care. 2012 Jan 7;16(1):R2

Authors: Breidthardt T, Socrates T, Drexler B, Noveanu M, Heinisch C, Arenja N, Klima T, Zusli C, Reichlin T, Potocki M, Twerenbold R, Steiger J, Mueller C

Abstract
ABSTRACT: INTRODUCTION: The accurate prediction of acute kidney injury (AKI) in patients with acute heart failure (AHF) is an unmet clinical need. Neutrophil gelatinase-associated lipocalin (NGAL) is a novel sensitive and specific marker of AKI. METHODS: A total of 207 consecutive patients presenting to the emergency department with AHF were enrolled. Plasma NGAL was measured in a blinded fashion at presentation and serially thereafter. The potential of plasma NGAL levels to predict AKI was assessed as the primary endpoint. We defined AKI according to the AKI Network classification. RESULTS: Overall 60 patients (29%) experienced AKI. These patients were more likely to suffer from pre-existing chronic cardiac or kidney disease. At presentation, creatinine (median 140 [IQR, 91-203] umol/l vs. 97 [76-132] umol/l, p<0.01) and NGAL (114.5 [67.1-201.5] ng/ml vs. 74.5 [60-113.9] ng/ml, p<0.01) levels were significantly higher in AKI compared to Non-AKI patients. The prognostic accuracy for measurements obtained at presentation, as quantified by the area under the receiver operating characteristic curve was mediocre and comparable for the two markers (creatinine 0.69; 95%CI 0.59-0.79 vs. NGAL 0.67; 95%CI 0.57-0.77). Serial measurements of NGAL did not further increase the prognostic accuracy for AKI. Creatinine, but not NGAL, remained an independent predictor of AKI (HR 1.15; 95%CI 1.01-1.31; p=0.04) in multivariable regression analysis. CONCLUSION: Plasma NGAL levels do not adequately predict AKI in patients with AHF.

PMID: 22226205 [PubMed - as supplied by publisher]

Three-year mortality among alcoholic patients after intensive care: A population-based cohort study.

Crit Care. 2012 Jan 8;16(1):R5

Authors: Christensen S, Johansen MB, Pedersen L, Jensen R, Larsen KM, Larsson A, Tonnesen E, Christiansen CF, Sorensen HT

Abstract
ABSTRACT: BACKGROUND: Alcoholic patients comprise a large proportion of patients in intensive care units (ICUs). However, data are limited on the impact of alcoholism on mortality following intensive care. METHODS: We conducted a cohort study among 16,848 first-time ICU patients between 2001 and 2007 to examine 30-day and 3-year mortality among alcoholic patients. Alcoholic patients with and without complications of alcohol misuse (e.g., alcoholic liver disease) were identified from previous hospital contacts for alcoholism-related conditions or redemption of a prescription for alcohol deterrents. Data on medication use, demographics, hospital diagnoses, and comorbidity were obtained from medical databases. We computed 30-day and 3-year mortality and mortality rate ratios (MRR) using Cox regression analysis, controlling for covariates. RESULTS: A total of 1,229 (7.3%) ICU patients were current alcoholics. Among alcoholic patients without complications of alcoholism (n=785, 4.7% of the cohort), 30-day mortality was 15.9% compared with 19.7% among non-alcoholic patients. Compared with non-alcoholic patients, the adjusted 30-day MRR was 1.04 (95% confidence interval (CI): 0.87-1.25). Three-year mortality was 36.2% compared with 40.9% among non-alcoholic patients, corresponding to an adjusted 3-year MRR of 1.16 (95% CI: 1.03-1.31). For alcoholic patients with complications (n=444, 2.6% of the cohort), 30-day mortality was 33.6% and 3-year mortality was 64.5%, corresponding to adjusted MRRs, with non-alcoholics as the comparator, of 1.64 (95% CI: 1.38-1.95) and 1.67 (95% CI: 1.48-1.90), respectively. CONCLUSION: Alcoholic ICU patients with chronic complications of alcoholism have substantially increased 30-day and three year mortality. In contrast, alcoholics without complications have no increased 30-day and only slightly increased three year mortality.

PMID: 22226344 [PubMed - as supplied by publisher]

Early initiation of low-dose corticosteroid therapy in the management of septic shock: a retrospective observational study.

Crit Care. 2012 Jan 7;16(1):R3

Authors: Park HY, Suh GY, Song JU, Yoo H, Jo IJ, Shin TG, Lim SY, Woo S, Jeon K

Abstract
ABSTRACT: INTRODUCTION: The use of low-dose steroid therapy in the management of septic shock has been extensively studied. However, the association between the timing of low-dose steroid therapy and the outcome has not been evaluated. Therefore, we evaluated whether early initiation of low-dose steroid therapy is associated with mortality in patients with septic shock. METHODS: We retrospectively analyzed the clinical data of 178 patients who received low-dose corticosteroid therapy for septic shock between January 2008 and December 2009. Time-dependent Cox regression models were used to adjust for potential confounding factors in the association between the time to initiation of low-dose corticosteroid therapy and in-hospital mortality. RESULTS: The study population consisted of 107 men and 71 women with a median age of 66 (interquartile range, 54-71) years. The 28-day mortality was 44% and low-dose corticosteroid therapy was initiated within a median of 8.5 (3.8-19.1) hours after onset of septic shock-related hypotension. Median time to initiation of low-dose corticosteroid therapy was significantly shorter in survivors than in non-survivors (6.5 hours vs. 10.4 hours; P = 0.0135). The mortality rates increased significantly with increasing quintiles of time to initiation of low-dose corticosteroid therapy (P = 0.0107 for trend). Other factors associated with 28-day mortality were higher Simplified Acute Physiology Score (SAPS) 3 (P < 0.0001) and Sequential Organ Failure Assessment (SOFA) scores (P = 0.0007), dose of vasopressor at the time of initiation of low-dose corticosteroid therapy (P < 0.0001), need for mechanical ventilation (P = 0.0001) and renal replacement therapy (P < 0.0001), while the impaired adrenal reserve did not affect 28-day mortality (81% vs. 82%; P = 0.8679). After adjusting for potential confounding factors, the time to initiation of low-dose corticosteroid therapy was still significantly associated with in-hospital mortality (adjusted OR 1.025, 95% CI 1.007-1.044, P = 0.0075). The early therapy group (administered within 6 hours after the onset of septic shock, n = 66) had a 37% lower mortality rate than the late therapy group (administered after 6 hours after the onset of septic shock, n = 112) (32% vs. 51%, P = 0.0132). CONCLUSIONS: Early initiation of low-dose corticosteroid therapy was significantly associated with decreased mortality.

PMID: 22226237 [PubMed - as supplied by publisher]

Hypoglycemia in critically ill adults - association yes, causation not proven.

Crit Care. 2011 Nov 30;15(6):1012

Authors: Finfer S

Abstract
ABSTRACT: Hypoglycemia is consistently associated with an increased risk of death in hospital patients in general, patients treated in intensive care units, and type II diabetes patients recruited to large randomized controlled trials. In 1965, Sir Austin Bradford Hill elucidated nine characteristics that help establish a causal relationship between exposure to a potentially harmful substance or event (in this context, hypoglycemia) and disease onset or death; hypoglycemia exhibits some of those characteristics but others remain to be explored. While we await data that address the outstanding issues, common sense dictates that clinicians avoid causing hypoglycemia whenever possible.

PMID: 22188732 [PubMed - as supplied by publisher]

Does dalteparin PROTECT better than heparin?

Crit Care. 2011 Dec 8;15(6):315

Authors: Przybysz T, Huang D

Abstract
EXPANDED ABSTRACT: CITATION: The PROTECT Investigators for the Canadian Critical Care Trials Group and the Australian and New Zealand Intensive Care Society Clinical Trials Group: Dalteparin versus Unfractionated Heparin in Critically Ill Patients. N Engl J Med 2011, 364:1305-1314. BACKGROUND: It is unclear whether there is a clinically significant advantage to prophylactic low-molecular-weight heparin (LMWH) versus unfractionated heparin (UFH) in mixed medical/surgical critically ill adult patients. METHODS: Objective: To compare once daily dalteparin with twice daily unfractionated heparin for primary prophylaxis of proximal deep venous thrombosis in critically ill adults.Design: A superiority randomized double-blinded controlled trial from 2006 to 2010 in both medical and surgical ICUs. (ClinicalTrials.gov registration number: NCT00182143)Setting: Multi-center, international medical and surgical intensive care units (ICUs)Subjects: Critically ill adults expected to remain in the ICU for at least 3 days.Intervention: Patients were randomized to either twice daily UFH or daily dalteparin for the duration of ICU admission.Outcomes: The primary endpoint was proximal leg deep venous thrombosis (DVT), at least three days after randomization, detected on twice weekly screening ultrasound. Secondary endpoints were: any DVT, pulmonary embolism (PE), venous thromboembolism (VTE), death, heparin-induced thrombocytopenia (HIT), major bleeding, and composite death/VTE. RESULTS: Three thousand seven hundred and forty-six subjects were included in the intention-to-treat analysis. Proximal leg DVT occurred in 96 of 1873 (5.1%) patients randomized to dalteparin versus 109 of 1873 (5.8%) patients randomized to UFH (hazard ratio in the dalteparin group, 0.92; 95% confidence interval [CI], 0.68 to 1.23; P = 0.57). The incidence of PE was 1.3% in the dalteparin group compared to 2.3% in the UFH group (hazard ratio, 0.51; 95% CI, 0.30 to 0.88; P = 0.01). There was no mortality difference and no difference in major bleeding between the two study arms. There was a statistically significant decrease in incidence of HIT in the dalteparin group in the per-protocol analysis, but not in the intention-to-treat analysis. LIMITATIONS: Comparing the incidence of PE was a secondary endpoint and the study was not appropriately powered for this conclusion. CONCLUSIONS: Among critically ill adult patients, dalteparin was not superior to UFH at preventing proximal lower extremity DVTs. There is a suggestion that dalteparin might be superior to UFH at preventing pulmonary embolism but a larger trial is necessary to confirm this result.

PMID: 22152126 [PubMed - as supplied by publisher]

Clinical review: optimizing enteral nutrition for critically ill patients - a simple data-driven formula.

Crit Care. 2011 Nov 30;15(6):234

Authors: Hegazi RA, Wischmeyer PE

Abstract
ABSTRACT: In modern critical care, the paradigm of 'therapeutic nutrition' is replacing traditional 'supportive nutrition'. Standard enteral formulas meet basic macro- and micronutrient needs; therapeutic enteral formulas meet these basic needs and also contain specific pharmaconutrients that may attenuate hyperinflammatory responses, enhance the immune responses to infection, or improve gastrointestinal tolerance. Choosing the right enteral feeding formula may positively affect a patient's outcome; targeted use of therapeutic formulas can reduce the incidence of infectious complications, shorten lengths of stay in the ICU and in the hospital, and lower risk for mortality. In this paper, we review principles of how to feed (enteral, parenteral, or both) and when to feed (early versus delayed start) patients who are critically ill. We discuss what to feed these patients in the context of specific pharmaconutrients in specialized feeding formulations, that is, arginine, glutamine, antioxidants, certain ?-3 and ?-6 fatty acids, hydrolyzed proteins, and medium-chain triglycerides. We summarize current expert guidelines for nutrition in patients with critical illness, and we present specific clinical evidence on the use of enteral formulas supplemented with anti-inflammatory or immune-modulating nutrients, and gastrointestinal tolerance-promoting nutritional formulas. Finally, we introduce an algorithm to help bedside clinicians make data-driven feeding decisions for patients with critical illness.

PMID: 22136305 [PubMed - as supplied by publisher]

Urine sTREM-1 assessment in diagnosing sepsis and sepsis-related acute kidney injury.

Crit Care. 2011 Nov 30;15(6):1013

Authors: Derive M, Gibot S

Abstract
ABSTRACT: The triggering receptor expressed on myeloid cells-1 (TREM-1) is an immunoreceptor whose role is to amplify the inflammatory response mediated by the engagement of Toll-like and NOD-like receptors. As the expression of TREM-1 is believed to be upregulated during infection, this protein has been studied as a sepsis biomarker. In the previous issue of Critical Care, Su and colleagues reported on the usefulness of urinary soluble TREM-1 in diagnosing sepsis and assessingits severity. Importantly, the authors describe, for the first time, that urinary soluble TREM-1 measurement is able to predict the development of sepsis-associated acute kidney injury (AKI). If these results were to be confirmed by larger studies, urinary soluble TREM-1 would possibly become a new biomarker for sepsis-associated AKI.

PMID: 22136371 [PubMed - as supplied by publisher]

Teamwork and team training in the ICU: Where do the similarities with aviation end?

Crit Care. 2011 Nov 30;15(6):313

Authors: Reader TW, Cuthbertson BH

Abstract
ABSTRACT: The aviation industry has made significant progress in identifying the skills and behaviors that result in effective teamwork. Its conceptualization of teamwork, development of training programs, and design of assessment tools are highly relevant to the intensive care unit (ICU). Team skills are important for maintaining safety in both domains, as multidisciplinary teams must work effectively under highly complex, stressful, and uncertain conditions. However, there are substantial differences in the nature of work and structure of teams in the ICU in comparison with those in aviation. While intensive care medicine may wish to use the advances made by the aviation industry for conceptualizing team skills and implementing team training programs, interventions must be tailored to the highly specific demands of the ICU.

PMID: 22136283 [PubMed - as supplied by publisher]

Risk factors for invasive fungal disease in critically ill, adult patients: a systematic review.

Crit Care. 2011 Nov 29;15(6):R287

Authors: Muskett H, Shahin J, Eyres G, Harvey S, Rowan K, Harrison D

Abstract
ABSTRACT: INTRODUCTION: Over 5,000 cases of invasive Candida species infections occur in the UK each year and around 40% of these occur in critical care units. Invasive fungal disease (IFD) in critically-ill patients is associated with increased morbidity and mortality at a cost to both the individual and the health service. This paper reports the results of a systematic review performed to identify and summarise the important risk factors from published multivariable analyses, risk prediction models and clinical decision rules, for IFD in critically ill, adult patients to inform the primary data collection for the Fungal Infection Risk Evaluation (FIRE) Study. METHODS: An electronic search was performed to identify articles which investigated risk factors, risk prediction models or clinical decisions rules for IFD in critically ill, adult patients. Eligible articles were identified in a staged process and were assessed by two investigators, independently. The methodological quality of the reporting of the eligible articles was assessed using a set of questions addressing both general and statistical methodology. RESULTS: Thirteen articles met the inclusion criteria, of which eight articles examined risk factors, four developed a risk prediction model or clinical decision rule, and one evaluated a clinical decision rule. Studies varied in terms of objectives, risk factors, definitions and outcomes. The following risk factors were found in multiple studies to be significantly associated with IFD: surgery, total parenteral nutrition, fungal colonisation, renal replacement therapy, infection/sepsis, mechanical ventilation, diabetes, and APACHE II or APACHE III score. Several other risk factors were also found to be statistically significant in single studies only. Risk factor selection process and modelling strategy also varied across studies, and sample sizes were inadequate for obtaining reliable estimates. CONCLUSION: This review has shown a number of risk factors to be significantly associated with the development of IFD in critically ill adults. Methodological limitations were identified in the design and conduct of studies in this area, and caution should be used in their interpretation.

PMID: 22126425 [PubMed - as supplied by publisher]

Septic acute kidney injury: hemodynamic syndrome, inflammatory disorder, or both?

Crit Care. 2011 Nov 18;15(6):1008

Authors: Lipcsey M, Bellomo R

Abstract
ABSTRACT: Septic acute kidney injury (S-AKI) is the most common cause of kidney injury in the ICU. Decreased renal blood flow and inflammation have both been suggested as mechanisms of S-AKI. Benes and colleagues present a study of S-AKI in which sepsis is induced by fecal peritonitis and bacterial infusion. In this study, although decreased renal blood flow and increased renal vascular resistance were present in some of the animals that developed S-AKI, inflammatory activation without decreased renal blood flow and increased renal vascular resistance was seen in other animals. Systemic hemodynamic findings provided little information on renal hemodynamics or risk of S-AKI. The study highlights the extraordinary complexity of S-AKI and the need for clinicians to recognize our limited understanding of its pathogenesis and the weakness of the decreased perfusion paradigm as the sole explanation for the loss of renal function seen in severe sepsis.

PMID: 22112533 [PubMed - as supplied by publisher]

Rapid response systems: you won't know there is a problem until you measure it.

Crit Care. 2011 Oct 28;15(5):1001

Authors: Hillman KM

Abstract
ABSTRACT: The rapid response system concept is one of the first patient-centered and organizational-wide systems aimed at preventing deaths and serious adverse events. It has been strongly argued that we need a benchmark that reflects the care of a deteriorating patient across the organization using a 'score to door time'; that is, the time from the first vital sign abnormality to admission to the ICU. The study by Oglesby and colleagues highlights serious issues, especially delays, which could adversely impact on patient care, and the study proposes that we concentrate more on measuring patient care from a broad perspective.

PMID: 22112380 [PubMed - as supplied by publisher]

Duration of antibiotic therapy for bacteremia: a systematic review and meta-analysis.

Crit Care. 2011 Nov 15;15(6):R267

Authors: Havey TC, Fowler R, Daneman N

Abstract
ABSTRACT: INTRODUCTION: The optimal duration of antibiotic therapy for bloodstream infections is unknown. Shorter durations of therapy have been demonstrated to be as effective as longer durations for many common infections; similar findings in bacteremia could enable hospitals to reduce antibiotic utilization, adverse events, resistance and costs. METHODS: A search of the MEDLINE, EMBASE and COCHRANE databases was conducted for the years 1947-2010. Controlled trials were identified that randomized patients to shorter versus longer durations of treatment for bacteremia, or the infectious foci most commonly causing bacteremia in critically ill patients (catheter-related bloodstream infections (CRBSI), intra-abdominal infections, pneumonia, pyelonephritis and skin and soft-tissue infections (SSTI)). RESULTS: Twenty-four eligible trials were identified, including one trial focusing exclusively on bacteremia, zero in catheter related bloodstream infection, three in intra-abdominal infection, six in pyelonephritis, 13 in pneumonia and one in skin and soft tissue infection. Thirteen studies reported on 227 patients with bacteremia allocated to 'shorter' or 'longer' durations of treatment. Outcome data were available for 155 bacteremic patients: neonatal bacteremia (n=66); intra-abdominal infection (40); pyelonephritis (9); and pneumonia (40). Among bacteremic patients receiving shorter (5-7 days) versus longer (7-21 days) antibiotic therapy, no significant difference was detected with respect to rates of clinical cure (45/52 versus 47/49, risk ratio 0.88, 95% confidence interval [CI] 0.77-1.01), microbiologic cure (28/28 versus 30/32, risk ratio 1.05, 95% CI 0.91-1.21), and survival (15/17 versus 26/29, risk ratio 0.97, 95% CI 0.76-1.23). CONCLUSIONS: No significant differences in clinical cure, microbiologic cure and survival were detected among bacteremic patients receiving shorter versus longer duration antibiotic therapy. An adequately powered randomized trial of bacteremic patients is needed to confirm these findings.

PMID: 22085732 [PubMed - as supplied by publisher]

Reduction in hospital-wide mortality following implementation of a rapid response team: a long-term cohort study.

Crit Care. 2011 Nov 15;15(6):R269

Authors: Beitler JR, Link N, Bails DB, Hurdle K, Chong DH

Abstract
ABSTRACT: INTRODUCTION: Rapid response teams (RRTs) have been shown to reduce cardiopulmonary arrests outside the intensive care unit (ICU). Yet the utility of RRTs remains in question, as most large studies have failed to demonstrate a significant reduction in hospital-wide mortality following RRT implementation. METHODS: A cohort design with historical controls was used to determine the effect on hospital-wide mortality of an RRT in which clinical judgment, in addition to vital signs criteria, was widely promoted as a key trigger for activation. All non-prisoner patients admitted to a tertiary referral public teaching hospital from 2003 through 2008 were included. A total of 77,021 admissions preintervention (2003 through 2005) and 79,013 admissions postintervention (2006 through 2008) were evaluated. The a priori primary outcome was unadjusted hospital-wide mortality. A Poisson regression model was then used to adjust for hospital-wide mortality trends over time. Secondary outcomes defined a priori were unadjusted out-of-ICU mortality and out-of-ICU cardiopulmonary arrest codes. RESULTS: A total of 855 inpatient RRTs (10.8 per 1,000 hospital-wide discharges) were activated during the three-year postintervention period. Forty-seven percent of RRTs were activated for reasons of clinical judgment. Hospital-wide mortality decreased from 15.50 to 13.74 deaths per 1,000 discharges following RRT implementation (relative risk 0.887, 95% CI 0.817-0.963; p=0.004). After adjusting for inpatient mortality trends over time, the reduction in hospital-wide mortality remained statistically significant (relative risk 0.825, 95% CI 0.694-0.981; p=0.029). Out-of-ICU mortality decreased from 7.08 to 4.61 deaths per 1,000 discharges (relative risk 0.651, 95% CI 0.570-0.743; p<0.001). Out-of-ICU cardiopulmonary arrest codes decreased from 3.28 to 1.62 codes per 1,000 discharges (relative risk 0.493, 95% CI 0.399-0.610; p<0.001). CONCLUSIONS: Implementation of an RRT in which clinical judgment, in addition to vital signs criteria, was widely cited as a rationale for activation was associated with a significant reduction in hospital-wide mortality, out-of-ICU mortality, and out-of-ICU cardiopulmonary arrest codes. The frequent use of clinical judgment as a criterion for RRT activation was associated with high RRT utilization.

PMID: 22085785 [PubMed - as supplied by publisher]