Early goal-directed therapy in the treatment of severe sepsis and septic shock

Objective
Circulatory shock is a life-threatening syndrome resulting in multiorgan failure and a high mortality rate. The aim of this consensus is to provide support to the bedside clinician regarding the diagnosis, management and monitoring of shock.

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Consensus on circulatory shock and hemodynamic monitoring. Task force of the European Society of Intensive Care Medicine

‘This review is published as a Cochrane Review in the Cochrane Database of Systematic Reviews 2004, Issue 4. Cochrane Reviews are regularly updated as new evidence emerges and in response to comments and criticisms, and the Cochrane Database of Systematic Reviews should be consulted for the most recent version of the Review.’ Roberts, I., Alderson, P., Bunn, F., Chinnock, P., Ker, K., Schierhout, G. 'Colloids versus crystalloids for fluid resuscitation in critically ill patients' Cochrane Database of Systematic Reviews 2004 (4) CD000567. DOI:10.1002/14651858.CD000567.pub2

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Colloids versus crystalloids for fluid resuscitation in critically ill patients

Importance Hydroxyethyl starch is commonly used for volume resuscitation yet has been associated with serious adverse events, including acute kidney injury and death. Clinical trials of hydroxyethyl starch are conflicting. Moreover, multiple trials from one investigator have been retracted because of scientific misconduct. Objectives To evaluate the association of hydroxyethyl starch use with mortality and acute kidney injury. Data Sources Randomized controlled trials from MEDLINE, EMBASE, CENTRAL, Global Health, HealthStar, Scopus, Web of Science, the International Clinical Trials Registry Platform (inception to October 2012), reference lists of relevant articles, and gray literature. Study Selection Two reviewers independently identified randomized controlled trials comparing hydroxyethyl starch with other resuscitation fluids in critically ill patients receiving acute volume resuscitation. Data Extraction Two reviewers independently extracted trial-level data including population characteristics, interventions, outcomes, and funding sources. Risk of bias was assessed using the risk of bias tool; the strength of evidence was adjudicated using the GRADE methodology. Results We included 38 eligible trials comparing hydroxyethyl starch to crystalloids, albumin, or gelatin. The majority of trials were categorized as having an unclear risk or high risk of bias. For the 10 880 patients in studies contributing mortality data, the risk ratio (RR) for death among patients randomized to receive hydroxyethyl starch was 1.07 (95% CI, 1.00 to 1.14; I 2 , 0%; absolute risk [AR], 1.20%; 95% CI, −0.26% to 2.66%). This summary effect measure included results from 7 trials performed by an investigator whose subsequent research had been retracted because of scientific misconduct. When we excluded these 7 trials that involved 590 patients, hydroxyethyl starch was found to be associated with increased mortality among 10 290 patients (RR, 1.09; 95% CI, 1.02 to 1.17; I 2 , 0%; AR, 1.51%; 95% CI, 0.02% to 3.00%), increased renal failure among 8725 patients (RR, 1.27; 95% CI, 1.09 to 1.47; I 2 , 26%; AR, 5.45%; 95% CI, 0.44% to 10.47%), and increased use of renal replacement therapy among 9258 patients (RR, 1.32; 95% CI, 1.15 to 1.50; I 2 , 0%; AR, 3.12%; 95% CI, 0.47% to 5.78%). Conclusion and Relevance In critically ill patients requiring acute volume resuscitation, use of hydroxyethyl starch compared with other resuscitation solutions was not associated with a decrease in mortality. Moreover, after exclusion of 7 trials performed by an investigator whose research has been retracted because of scientific misconduct, hydroxyethyl starch was associated with a significant increased risk of mortality and acute kidney injury. Clinical use of hydroxyethyl starch for acute volume resuscitation is not warranted due to serious safety concerns.

https://jamanetwork.com/journals/jama/articlepdf/1653505/jce130004_678_688.pdf

Association of Hydroxyethyl Starch Administration With Mortality and Acute Kidney Injury in Critically Ill Patients Requiring Volume Resuscitation: A Systematic Review and Meta-analysis

Objectives: Sepsis induces microvascular alterations that may play an important role in the development of organ dysfunction. However, the relationship of these alterations to systemic variables and outcome is still not well defined. We investigated which factors may influence microcirculatory alterations in patients with severe sepsis and whether these are independently associated with mortality. Design: Analysis of prospectively collected data from previously published studies by our group. Setting: A 36-bed, medicosurgical university hospital Department of Intensive Care. Patients: A total of 252 patients with severe sepsis in whom the sublingual microcirculation was visualized using orthogonal polarization spectral or sidestream darkfield imaging techniques. Measurements and Main Results: Microcirculatory measurements were obtained either early, within 24 h of the onset of severe sepsis (n = 204), or later, after 48 h (n = 48). When multiple measurements were obtained, only the first was considered. Although global hemodynamic variables were relatively preserved (mean arterial pressure 70 [65–77] mm Hg, cardiac index 3.3 [2.7–4.0] L/min.m 2 , and Svo 2 68.3 [62.8–74.7]%),

Microcirculatory alterations in patients with severe sepsis: impact of time of assessment and relationship with outcome.

Introduction Our goal was to assess the effects of titration of a norepinephrine infusion to increasing levels of mean arterial pressure (MAP) on sublingual microcirculation. Methods Twenty septic shock patients were prospectively studied in two teaching intensive care units. The patients were mechanically ventilated and required norepinephrine to maintain a mean arterial pressure (MAP) of 65 mmHg. We measured systemic hemodynamics, oxygen transport and consumption (DO 2 and VO 2 ), lactate, albumin-corrected anion gap, and gastric intramucosal-arterial PCO2 difference (ΔPCO2). Sublingual microcirculation was evaluated by sidestream darkfield (SDF) imaging. After basal measurements at a MAP of 65 mmHg, norepinephrine was titrated to reach a MAP of 75 mmHg, and then to 85 mmHg. Data were analyzed using repeated measurements ANOVA and Dunnett test. Linear trends between the different variables and increasing levels of MAP were calculated. Results Increasing doses of norepinephrine reached the target values of MAP. The cardiac index, pulmonary pressures,

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Increasing arterial blood pressure with norepinephrine does not improve microcirculatory blood flow: a prospective study

Comparison of 6% hydroxyethyl starch 130/0.4 and saline solution for resuscitation of the microcirculation during the early goal-directed therapy of septic patients.

Christian A. Casabella

Papers

Increasing arterial blood pressure with norepinephrine does not improve microcirculatory blood flow: a prospective study

Comparison of 6% hydroxyethyl starch 130/0.4 and saline solution for resuscitation of the microcirculation during the early goal-directed therapy of septic patients.