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Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet].

Safety of modern starches used during surgery

P Van Der Linden, M James, M Mythen, and RB Weiskopf.

Review published: 2013.

Link to full article: [Journal publisher]

CRD summary

This review concluded that there were no indications that tetrastarches, given during or immediately after surgery, were associated with increases in blood loss, allogeneic red cell transfusion, kidney impairment/failure incidence, or mortality. Limitations of the evidence base and the review's methodology suggest that the authors' conclusions should be treated with caution.

Authors' objectives

To evaluate the safety of tetrastarches when used during surgery.

Searching

MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), and EMBASE were searched from 1997 to December 2011. Search terms were reported in an appendix. No language restrictions were imposed. Eligible studies that were already known to the authors, which were not picked up by the searches, were also assessed for inclusion.

Study selection

Eligible studies were phase 1 to phase 4 trials and randomised controlled trials (RCTs) performed in volunteers or patients, which compared the safety of one of two tetrastarches (waxy maize-derived hydroxyethyl starch 130/0.4 or potato-derived hydroxyethyl starch 130/0.42) versus another intervention (such as a colloid, a crystalloid, blood product, vasoactive drug, no treatment). Patient populations had to consist of adults or children undergoing general and/or regional anaesthesia for elective and emergency surgery, for trauma or burns. Volunteer studies were included only if the tetrastarch and comparator were given to the volunteer. The clinical outcomes of interest were coagulation function, renal function (both defined in the review), and mortality. Exclusion criteria were stated in the review.

Most of the included trials were performed in adult populations who underwent various surgeries including cardiac, cancer, major abdominal, and major orthopaedic surgeries. Most of the trials administered the waxy maize-derived hydroxyethyl starch (130/0.4) as the intervention. Comparators varied and included human serum albumin, modified fluid gelatin, crystalloids, and other types of hydroxyethyl solutions. The volumes of the solutions administered also varied.

It appeared that multiple reviewers selected the studies for inclusion.

Assessment of study quality

The authors did not state whether they performed any quality assessment of the studies.

Data extraction

Data on the outcomes (proportions or odds ratios and 95% confidence intervals) were extracted.

The authors did not state how many reviewers extracted the data.

Methods of synthesis

The results were mainly reported in a narrative synthesis. Trials also appear to have been pooled by finding the total number of events in the tetrastarch and comparator groups across all trials, and calculating the odds ratio for the comparison between groups.

Results of the review

Fifty-nine trials were included in the review (4,529 patients): 2,139 patients were treated with tetrastarch and 2,390 were treated with comparator solutions.

Mortality (21 trials): Mortality was statistically significantly higher among comparator groups compared with groups which received tetrastarches (OR 0.51, 95% CI 0.24 to 1.05; 21 trials).

Coagulation (50 trials): In comparison with other treatments, the use of a tetrastarch was not associated with increased perioperative blood loss, an increase in allogeneic blood volume transfused, or exposure to allogeneic blood products when compared with other colloids or crystalloids. In the two trials on trauma patients, results were mixed (reported fully in the review).

Renal replacement therapy (seven trials): Patients receiving tetra-starch treatment had lower rates of renal replacement therapy then comparator groups; this difference was not statistically significant.

Creatinine (21 trials): All but three trials demonstrated no differences between groups in peak creatinine concentrations or nadir creatinine clearances during the postoperative period. The remaining three trials showed statistically significant benefit with the use of tetrastarch (two trials), or a lower creatinine concentration with a crystalloid comparator (one trial).

Urine output (35 trials): No statistically significant differences were observed between the tetrastarch and comparator groups.

Authors' conclusions

There were no indications that the use of tetrastarches, administered intraoperatively or in the immediate postoperative period, were associated with the adverse clinical outcomes of increased blood loss, increased use of allogeneic red cells, increased incidence of renal impairment/failure, or increased mortality.

CRD commentary

The review question and inclusion criteria were both broadly defined. Relevant databases were searched and no language restrictions were imposed, which reduced the likelihood of potentially relevant studies being missed. It was unclear whether any of the review processes were performed in duplicate, so there was a potential risk for reviewer error and/or bias.

No formal quality assessment of the included trials appeared to have been performed, which made it difficult to judge whether there were any possible biases within the trials that could have influenced the overall findings. The results appear to have been pooled using an approach that could not be recommended, as both the randomisation and possible differences in incidence across trials were ignored; as such the results may be misleading. The authors acknowledged that the duration of follow-up in the trials was relatively short, and that most of the trials had small sample sizes.

The authors' conclusions reflected the evidence, but limitations of the evidence base and the review's methodology mean that these conclusions should be treated with caution.

Implications of the review for practice and research

Practice: The authors did not state any implications for future clinical practice, but emphasised that their conclusions apply only to the use of tetrastarches in surgical settings.

Research: The authors stated that it might be worthwhile collecting additional data on adverse events during the immediate postoperative period. They stated that it would be an inappropriate use of resources to conduct an RCT, but instead suggested that examination of data from existing databases and registries would be sufficient.

Funding

Fresenius-Kabi Deutschland GmbH.

Bibliographic details

Van Der Linden P, James M, Mythen M, Weiskopf RB. Safety of modern starches used during surgery. Anesthesia and Analgesia 2013; 116(1): 35-48. [PubMed: 23115254]

Indexing Status

Subject indexing assigned by NLM

MeSH

Blood Coagulation; Blood Loss, Surgical; Blood Transfusion /statistics & numerical data; Confidence Intervals; Erythrocyte Transfusion /statistics & numerical data; Humans; Hydroxyethyl Starch Derivatives /adverse effects /therapeutic use; Intraoperative Care; Odds Ratio; Plasma Substitutes /adverse effects /therapeutic use; Prospective Studies; Randomized Controlled Trials as Topic; Safety; Surgical Procedures, Operative /methods /mortality

AccessionNumber

12013007215

Database entry date

23/06/2014

Record Status

This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.

CRD has determined that this article meets the DARE scientific quality criteria for a systematic review.

Copyright © 2014 University of York.

PMID: 23115254