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LETTER TO THE EDITOR

Aprotinin and Sevoflurane Do Not Affect Renal Function During Single-Ventricle Palliative Surgery

University of California; San Francisco, CA; graciegirl{at}earthlink.net

To the Editor:

A recent study of aprotinin in adult cardiac surgery is rekindling interest in its renal toxicity (1). Single-ventricle, palliative surgery entails low oxygen delivery and bleeding, which are attenuated by aprotinin (2,3). After University IRB approval, we retrospectively reviewed medical records of 18 children having Sano-Norwood, 28 bidirection cavopulmonary Glenn shunts, and 15 Fontans from August 2002 to April 2004, roughly corresponding to the time that aprotinin use became standard. We gave a test dose of aprotinin, 700 U/kg, at prebypass, a pump prime bolus of 30,000 U/kg, and an infusion during bypass of 10,000 U/kg/h. The demographics of the children are summarized in Table 1.

The outcomes were peak creatinine during the first 7 postoperative days, postbypass partial pressure of oxygen (inspired oxygen 100%), liver function tests, and time spent in the operating room. Table 2 shows the outcome variables, including those groups whose means differed at P < 0.05, uncorrected for the number of statistical tests. Although several P values did reach statistical significance, as expected with this many comparisons without Bonferroni correction, in no case was worse outcome associated with use of aprotinin. Table 3 shows the relationship between increase in serum exposure and sevoflurane exposure, stratified by operation. Again, the P tests were not corrected for repeated measures, and as expected, a single test identified a relationship between sevoflurane exposure and postoperative serum creatinine increase. As was the case with aprotinin, the data weakly suggest that sevoflurane exposure is associated with reduced risk of postoperative renal dysfunction, as patients with evidence of renal dysfunction are those who had lower, not higher, exposure to sevoflurane.

Although this is a very small study, peak creatinine and amounts of transfusions were not related to administration of aprotinin or sevoflurane. In general, oxygen partial pressure was improved with aprotinin in Fontans, as reported by Tweddell et al. who described an improved transpulmonary pressure gradient (3). Many studies show the potential for thrombosis with aprotinin, but unfortunately data are sparse regarding renal dysfunction (4).

The key point of these data is that we did not see evidence of clinical concern in this population of children with either aprotinin or sevoflurane. If anything, our data support the safety of these drugs for use in children undergoing repair of congenital cardiac defects.

REFERENCES

1. Mangano DT, Tudor IC, Dietzel C. The risk associated with aprotinin in cardiac surgery. N Engl J Med 2006;354:353–65.[Abstract/Free Full Text]
2. Alexi-Meskishvilli V, Stiller B, Koster A, et al. Correction of congenital heart defects in Jehovah’s Witness children. Thorac Cardiovasc Surg 2004;52:141–6.[Web of Science][Medline]
3. Tweddell JS, Berger S, Frommelt PC, et al. Aprotinin improves outcome of single ventricle palliation. Ann Thorac Surg 1996; 62:1329–35.[Abstract/Free Full Text]
4. Shiga T, Wajima Z, Inoue T, Sakamoto A. Aprotinin in major orthopedic surgery: a systematic review of randomized controlled trials. Anesth Analg 2005;101:1602–7.[Abstract/Free Full Text]

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