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Department of Anesthesiology and Intensive Care, University of Münster, Münster, Germany
To the Editor:
We have read with interest the study of Nuttall and colleagues in which they tried to optimize the dosing of aprotinin by weight-adjustment (1). Weight-adjustment, however, neglects the prime-volume of the cardiopulmonary bypass (CPB) system as well as the pump prime dose. Given a normal adult (65 kg body weight) the only difference between the 250 KIU/mL group in Nuttall’s study and the "Full-Dose" group is the pump prime load (88 mg vs. 280 mg). Furthermore, an 88-mg pump prime load results in a far lower concentration than the 4.4 mg/kg bolus given intravenously. Besides the pump prime load, the volume of the CPB system is of special interest, especially in pediatric cardiac surgery where the volume of the CPB system is several fold higher than the circulating blood volume. The smaller the patient the greater is this discrepancy, leading to aprotinin plasma levels that are ineffective in terms of blood loss reduction in pediatric patients (2).
Given these considerations, it may be more appropriate to base the aprotinin dose on the estimated circulating blood volume during bypass (CBVbypass = patient’s estimated blood volume + CPB prime-volume), rather than simply basing it on the patient’s body weight. By multiplying CBVbypass with the desired concentration of aprotinin in plasma and the hematocrit (see formula below), the needed amount of aprotinin can easily be calculated, no matter whether it is an adult patient or a pediatric patient:equation
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This initial loading dose is then to be followed by a maintanance infusion as described by Nuttall and colleagues (1).
While in the study of Nuttall et al. the measured plasma concentrations were up to some 70% higher than the desired aprotinin plasma levels (1), dosing aprotinin according to the above-mentioned formula would prevent this happening.
References
Mayo Clinic, Rochester, MN
In Response:
We would like to thank Drs. Schmidt et al. for their thoughtful letter. We would like to respond to their comments point-by-point. First, neglecting the prime volume of the CPB system as well as pump prime dose: Our first manuscript on weight-based aprotinin dosing provides rationale regarding all of the dosing used in our study (1). The effects of pump prime volume and the derivation of the pump prime dose are described in this manuscript. In brief, we assumed a volume of distribution of aprotinin in the plasmanate prime volume was the prime volume, equivalent to 1 L/kg, and added 25% to account for potential tubing binding, whereas the volume of distribution of aprotinin for the patients was 0.12 L/kg (2). If you combine the two volumes of distribution, as estimated in the "estimated circulating volume during bypass," you will have a dose of aprotinin that is incorrect and illogical. Furthermore, incorporating an estimate of circulating blood volume into drug dosing adds subjectivity and variability to the drug dosing. The goal of the pump prime dose in our study was to achieve the goal concentration of aprotinin in the pump prime volume. Since the goal of our dosing of aprotinin in the patient is the same concentration as the prime concentration, mixing the two volumes results in no change in concentration. The old fixed dosing protocol of 280 mg has been demonstrated in many studies to result in supratherapeutic concentrations of aprotinin in the patient. As to pediatric patients and aprotinin dosing, we have completed a study in this patient population and our manuscript is in process. A final point about the "estimated circulating volume during bypass," the volume of distribution of aprotinin is not the same as the blood volume of the patient either before, during, or after CPB.
References
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