Original contribution
Hydroxyethyl starch (HES) does not directly affect renal function in patients with no prior renal impairment

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Abstract

Study Objective: To examine the effects of hydroxyethyl starch (HES) on renal function.

Design: Randomized, controlled trial.

Setting: Operating theatre of a university hospital.

Patients: 60 ASA physical status I and II male patients undergoing middle ear surgery.

Interventions: Patients received either lactated Ringer’s solution (LRS) or one of three HES solutions. The HES solutions were administered in a dose of 15 mL/kg bodyweight (bw), the Ringer’s solution in a dose of 60 mL/kg bw, after induction of anesthesia over a period of one hour.

Measurements: Blood and urine samples for hormone and enzyme tests were obtained at defined times before, during, and after surgery. Urine excretion, glomerular filtration rate (GFR), renal plasma flow, and routine hemodynamic parameters were measured simultaneously.

Main Results: There were no significant intergroup differences regarding GFR, renal plasma flow, or tubular and glomerular integrity as measured by specific proteins and enzymes (α-1-microglobulin, Tamm-Horsfall-protein, immunoglobulin G, and N-acetyl-β-D-glucosaminidase). Arginine vasopressin decreased in all groups during and following anesthesia, aldosterone and plasma renin activity decreased only in the HES groups, and angiotensin II decreased only in the HES 200/0.5 group. Central venous pressure increased during fluid administration in the LRS group and returned to baseline sooner in the HES groups.

Conclusions: Hydroxyethyl starch administration appears to be risk-free with regard to renal function in patients without preexisting renal dysfunction who undergo general anesthesia. The relevance of the decrease in aldosterone following HES therapy needs further investigation.

Introduction

The influence of colloid therapy such as hydroxyethyl starch (HES) on renal function remains largely unclear.1, 2, 3, 4 Possible disadvantages may include alteration in coagulation and organ function, but available studies are few and confined mostly to critically ill patients, whose renal functions were already impaired before the colloids were administered, and to histologic investigations. In a retrospective analysis of patients undergoing kidney transplantation who were treated with HES, kidney lesions with the characteristic of osmotic nephrosis were seen.3 These lesions, however, had no negative influence on graft function or serum creatinine three and six months after transplantation. In another study, acute renal failure was reported when patients with impaired renal function received very high molecular weight (Mw) HES (Mw 450,000 D, DS 0.7).5 Thus, HES preparations may, under certain circumstances, have detrimental consequences for renal function.

To date, there is little concrete evidence of renal dysfunction following HES therapy in low-risk patients. German case studies have reported increased creatinine levels as well as clinical kidney problems (such as pain in the renal area and swelling of the kidney parenchyma) in patients undergoing dilution therapy, but several control trials showed no evidence of renal dysfunction in terms of serum urea and creatinine changes.∗,†∗, † A disadvantage of all these studies is their use of markers that may have been too insensitive to detect initial or discrete changes in renal function. Only a few studies employed tests that could detect renal damage at a high level of sensitivity; for instance, those that measure the urinary excretion of kidney-specific enzymes and proteins.1, 2, 3, 4

In this controlled, randomized study, we investigated the possible influence of HES-solutions on the renal function in (otherwise healthy) subjects undergoing otological surgery. The effects of three different HES solution regimes (HES 200/0.5, 200/0.62, and 450/0.7) were compared with those of lactated Ringer’s solution (LRS). Renal function was assessed by measuring both commonly used parameters of renal function as well as changes in a number of specific hormones. Except for the fluid replacement volume used, the experimental conditions were identical in the four groups.

Section snippets

Subjects

The study included 60 ASA physical status I and II male patients who were scheduled to undergo middle ear surgery. Eligibility criteria were an expected operation time of more than three hours, the absence of hepatic or renal dysfunction, diabetes mellitus, and recent exposure to contrast media. Patients were prospectively randomized via sealed envelope assignment into four groups of 15 patients each to receive either lactated Ringer’s solution or different HES-solutions (Table 1). The study

Results

All patients were able to be discharged from the hospital between 10 and 14 days after surgery. There were no significant differences among the study groups concerning age, height, body weight, duration of anesthesia, or blood loss (Table 2). Neither were there differences in heart rate (HR) or electrolytes among the groups during the preoperative and postoperative periods (data not presented).

Urine excretion significantly increased in the group receiving LRS, an effect that lasted until the

Discussion

The results of this study are reassuring in that HES does not seem to impair renal function in ASA physical status I and II patients, even when renal damage has been assessed by the most sensitive markers available. In a different context, changes in urinary enzymes had been demonstrated only after a 24- to 48-hour delay after therapy.18, 19, 20 We therefore performed tests up to two days after surgery. For most parameters, either no difference among study groups and the control group, or no

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    Supported by the Else-Kröner-Fresenius Foundation, Bad Homburg, Germany.

    Staff Anesthesiologist

    Research Associate

    Professor of Anesthesiology and Chairman, Department of Anesthesiology and Intensive Care Medicine

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