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Evidence summaries

Hydroxyethyl Starch (Hes) Versus other Fluid Therapies: Effects on Kidney Function

Hydroxyethyl starch colloids for fluid resuscitation appear to decrease kidney function and increase the risk in acute kidney injury and renal replacement therapy in all patient populations compared to cristalloids. Level of evidence: "B"

A Cochrane review [Abstract] 1 included 42 studies with a total of 11 399 subjects. Hydroxyethyl starches (HES) are synthetic colloids commonly used for fluid resuscitation. In septic and in non-septic patients, kidney failure (author-defined) was increased in treatment with HES compared to other fluid therapies (RR 1.59, 95% CI 1.26 to 2.00; 15 studies, n=1361) as well as failure requiring renal replacement therapy (RR 1.31, 95% CI 1.16 to 1.49; 19 studies, n=9857).Only limited data was obtained for analysis of kidney outcomes by the RIFLE criteria; level of acute kidney dysfunction (Risk, Injure,Failure) as well as duration of requirement of renal replacement therapy (Loss of kidney function, End-stage kidney disease). The data about safety between different HES products are insufficient. The RR of AKI based on RIFLE-F (failure) criteria also showed an increased risk of AKI in individuals treated with HES products (RR 1.14, 95% CI 1.01 to 1.30; 15 studies, n=8402). A more robust effect was seen for the RIFLE-I (injury) outcome, with a RR of AKI of 1.22 (95% CI 1.08 to 1.37; 8338 patients). No differences between subgroups for the RRT and RIFLE-F based outcomes were seen between sepsis versus non-sepsis patients, high molecular weight (MW) and degree of substitution (DS) versus low MW and DS (HASH(0x2fcfe80) 200 kDa and > 0.4 DS versus 130 kDa and 0.4 DS) HES solutions, or high versus low dose treatments (i.e. HASH(0x2fcfe80) 2 L versus < 2 L).

A Cochrane review [Abstract] 1 included 69 studies with 30 020 participants comparing colloids to crystalloids in patients requiring volume replacement. There was no clear evidence that colloids (starches, dextrans, gelatins, and albumin) reduce the risk of death, compared to crystalloids, in patients with trauma, burns or following surgery (table T1). Hydroxyethyl starch slightly increased the need for blood transfusion and renal replacement therapy (table T1).

Starches compared to crystalloid for fluid resuscitation

OutcomeRelative effect(95% CI)Risk with crystalloidsRisk with starches (95% CI)Number of participants(studies)Certainty of the evidence
All-cause mortality (at end of follow-up)RR 0.97(0.86 to 1.09)233 per 1000226 per 1000(201 to 254)11 177(24)Moderate
All-cause mortality (at 90 days)RR 1.01(0.90 to 1.14)238 per 1000241 per 1000(214 to 272)10 415(15) Moderate
Transfusion of blood productsRR 1.19(1.02 to 1.39)299 per 1000356 per 1000(305 to 416)1917(8) Moderate
Renal replacement therapyRR 1.30(1.14 to 1.48)82 per 1000106 per 1000(93 to 121)8527(9) Moderate

Another meta-analysis 3 including 10 trials (n=4624 assessed whether resuscitation with hydroxyethyl starches (HES) compared with crystalloids affects outcomes in patients with sepsis. An increased incidence of acute kidney injury (AKI) (RR 1.24, 95% CI 1.13 to 1.36), and need of RRT (RR 1.36, 95% CI 1.17 to 1.57] was found in patients who received resuscitation with HES. It was also associated with increased transfusion of RBC (RR 1.14, 95% CI 1.01 to 1.93), but not fresh frozen plasma (RR 1.47, 95% CI 0.97 to 2.24). Furthermore, while intensive care unit mortality (RR 0.74, 95% CI 0.43 to 1.26), and 28-day mortality (RR 1.11, 95% CI 0.96 to 1.28) was not different, 90-day mortality (RR 1.14, 95% CI 1.04 to 1.26) was higher with HES compared with crystalloids.

An analysis 4 of a nationwide trauma registry in Germany included 48 484 patients with mean age of 49 years and mean injury severity score of 23 points; 72.3% were male and 95.5% had blunt trauma. Risk-adjusted analyses revealed that patients receiving over 1 000 ml synthetic colloids experienced an increase of renal failure and renal replacement therapy rates (OR 1.42 and 1.32, respectively, both p HASH(0x2fd0288) 0.006). Any synthetic colloid use was associated with an increased risk of multiple organ failure (p < 0.001), but there was no effect on hospital mortality (p = 0.594).

Comment: The quality of evidence is downgraded by study quality (unclear allocation concealment and blinding in half of the studies).

    References

    • Mutter TC, Ruth CA, Dart AB. Hydroxyethyl starch (HES) versus other fluid therapies: effects on kidney function. Cochrane Database Syst Rev 2013;(7):CD007594. [PubMed]
    • Lewis SR, Pritchard MW, Evans DJ et al. Colloids versus crystalloids for fluid resuscitation in critically ill people. Cochrane Database Syst Rev 2018;(8):CD000567. [PubMed]
    • Serpa Neto A, Veelo DP, Peireira VG et al. Fluid resuscitation with hydroxyethyl starches in patients with sepsis is associated with an increased incidence of acute kidney injury and use of renal replacement therapy: a systematic review and meta-analysis of the literature. J Crit Care 2014;29(1):185.e1-7.[PubMed]
    • Hilbert-Carius P, Schwarzkopf D, Reinhart K et al. Synthetic colloid resuscitation in severely injured patients: analysis of a nationwide trauma registry (TraumaRegister DGU). Sci Rep 2018;8(1):11567. [PubMed]

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