05 Mar 11

Update on the comparative safety of colloids: a systematic review of clinical studies

Posted in Fluid management at 17:42 by Laci

By A Groeneveld, R Navickis, M Wilkes

Ann Surg 2011;253:470-483

To provide an updated systematic review on the comparative safety of colloids based on recent clinical studies.
Background: Recent investigations, including large-scale randomized trials and meta-analyses, have sought to determine the effects of colloids on mortality and morbidity. Hypothesized differences in safety profile between hydroxyethyl starch (HES) solutions have also been evaluated in randomized trials.

Methods

Clinical studies reported since 2002 with safety data for acutely ill patients receiving HES, gelatin, dextran, or albumin were sought by computer searches and other methods. Safety endpoints included mortality, morbidity, bleeding and impaired coagulation, and acute kidney injury (AKI). Data extracted from the included study reports were qualitatively summarized.

Results
Sixty-nine clinical studies were included. Of those, 42 were randomized controlled trials (RCTs) with 10,382 total patients. New safety data, since 2002, predominantly concerned albumin or HES. A large RCT of intensive care unit patients showed that albumin does not adversely affect survival. Acute kidney injury and a dose-dependent increase in mortality were observed in a large RCT of patients with severe sepsis or septic shock receiving HES. Impaired coagulation and clinical bleeding were frequently reported after HES infusion, especially in cardiac surgery. In head-to-head randomized comparisons of different HES solutions, observed effects on coagulation and renal function were similar. Gelatin showed less impairment of coagulation than HES. Very few safety data related to dextran were identified.

Conclusions
Albumin displayed a more favorable safety profile than HES. Available evidence does not support the existence of consistent safety differences between HES solutions.

26 Feb 11

Out-of-hospital hypertonic resuscitation after traumatic hypovolemic shock

Posted in Fluid management at 1:40 by Laci

By E Bulger, Eileen, S May, J Kerby, S Emerson, I Stiell, M Schreiber at al for the ROC investigators

Ann Sug 2011:253;431-441

To determine whether out-of-hospital administration of hypertonic fluids would improve survival after severe injury with hemorrhagic shock.

Background
Hypertonic fluids have potential benefit in the resuscitation of severely injured patients because of rapid restoration of tissue perfusion, with a smaller volume, and modulation of the inflammatory response, to reduce subsequent organ injury.

Methods
Multicenter, randomized, blinded clinical trial, May 2006 to August 2008, 114 emergency medical services agencies in North America within the Resuscitation Outcomes Consortium. Inclusion criteria: injured patients, age >= 15 years with hypovolemic shock (systolic blood pressure <= 70 mm Hg or systolic blood pressure 71-90 mm Hg with heart rate >= 108 beats per minute). Initial resuscitation fluid, 250 mL of either 7.5% saline per 6% dextran 70 (hypertonic saline/dextran, HSD), 7.5% saline (hypertonic saline, HS), or 0.9% saline (normal saline, NS) administered by out-of-hospital providers. Primary outcome was 28-day survival. On the recommendation of the data and safety monitoring board, the study was stopped early (23% of proposed sample size) for futility and potential safety concern.

Results
A total of 853 treated patients were enrolled, among whom 62% were with blunt trauma, 38% with penetrating. There was no difference in 28-day survival-HSD: 74.5% (0.1; 95% confidence interval [CI], -7.5 to 7.8); HS: 73.0% (-1.4; 95% CI, -8.7-6.0); and NS: 74.4%, P = 0.91. There was a higher mortality for the postrandomization subgroup of patients who did not receive blood transfusions in the first 24 hours, who received hypertonic fluids compared to NS [28-day mortality-HSD: 10% (5.2; 95% CI, 0.4-10.1); HS: 12.2% (7.4; 95% CI, 2.5-12.2); and NS: 4.8%, P < 0.01].
Conclusion: Among injured patients with hypovolemic shock, initial resuscitation fluid treatment with either HS or HSD compared with NS, did not result in superior 28-day survival. However, interpretation of these findings is limited by the early stopping of the trial.

01 Jan 10

HES130/0.4 impairs haemostasis and stimulates pro-inflammatory blood platelet function

Posted in Fluid management at 13:37 by Laci

By M Sossdorf, S Marx, B Schaarschmidt, G Otto,  R Claus, K Reinhart, C Hartog and W Loesche

Critical Care 2009, 13:R208

Hydroxyethyl starch (HES) solutions are widely used for volume replacement therapy but are also known to compromise coagulation, impair renal function and increase long-term mortality. To test the hypotheses that HES 130/0.4 has less adverse effects than HES 200/0.5 and exerts anti-inflammatory properties we compared the effects of HES130/0.4, HES200/0.5 and saline on in vitro haemostasis and pro-inflammatory platelet function.

Methods
Whole blood samples from healthy volunteers were mixed with 6% HES130/0.4, 10% HES200/0.5, or normal saline to achieve a final haemodilution rate of 10 % or 40 %. Haemostatic capacity was characterised by thromboelastography (ROTEM) and measurement for FXIIIa activity. Platelet activation and pro-inflammatory platelet functions were characterised by flow cytometry measuring the platelet activation marker CD62P and binding of fibrinogen to platelets as well as the formation of heterotypic platelet-leukocyte conjugates.

Results
Compared to saline, HES130/0.4 dose-dependently impaired formation and firmness of the fibrin clot but did not affect the fibrin-crosslinking activity of FXIIIa. At 40 % but not at 10 % haemodilution rate HES200/0.5 also increased platelet fibrinogen binding and both HES solutions increased expression of CD62P, the main receptor for platelet-leukocyte adhesion. HES130/0.4 but not HES200/0.5 increased formation of platelet-neutrophil conjugates and, to a lesser degree, platelet-monocyte conjugates.
HES130/0.4 impairs haemostasis and stimulates pro-inflammatory blood platelet function
Conclusions
Our data demonstrate that HES130/0.4 has similar adverse effects as HES200/0.5. In particular, both types of HES impair coagulation capacity and stimulate rather than attenuate pro-inflammatory platelet function.

05 Nov 09

Postoperative fluid overload: Not a benign problem

Posted in Fluid management at 1:21 by Laci

By J Lowell, C Schifferdecker, D Driscoll, P Benotti, B Bistrian

Crit Care Med 1990;18:728

The incidence and consequences of fluid overload in the surgical ICU (SICU) have not been well defined, but may influence length of stay, days requiring mechanical ventilation, and mortality. Forty-eight consecutive patients admitted to our SICU were prospectively monitored for acute changes in weight and its impact on clinical management and outcome. When defined as a gain >10% from their preoperative or premorbid weight (or an approximately 20% increase in total body water), 40% of patients had fluid overload. Patients were divided into three groups: those who had gained <=10%, those with a weight gain between 11% and 20%, and those with >20% increase in weight. Significant differences were found with respect to vasopressor dependence, colloid administration, and mortality. When indexed by initial Acute Physiology and Chronic Health Evaluation (APACHE H) mortality prediction scores, all groups had similar degrees of illness. On average, presumably due to volume limitations, patients were inadequately nourished during 85% of their SICU stay. Our results suggest that the morbidity of fluid overload can be significant, and warrants a fresh look at the methods of intraoperative fluid resuscitation.

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