Ann Thorac Surg 2005;79:835-836
© 2005 The Society of Thoracic Surgeons
INVITED COMMENTARY
Eric W. Young, MD,
Marvin M. Kirsh, MD
VA Ann Arbor Healthcare System, 2215 Fuller Rd, Ann Arbor, MI 48105
(E-mail: marvink{at}umich.edu).
In 1998, we reported a higher incidence of renal dysfunction and overt renal failure among cardiac surgery patients who were treated with intravenous diltiazem compared with a historical control group who did not receive diltiazem. Our analysis was prompted by a clinical perception of increased renal dysfunction after routine adoption of diltiazem therapy. The formal results were surprising because most prior studies had reported beneficial effects of diltiazem on kidney function. Nonetheless, we abandoned the routine use of diltiazem and published our experience both to inform others of a potential problem and to suggest the need for additional studies.
Subsequently, several investigators apparently agreed that the matter deserved further study. Uniformly contrary results have been published by Yavuz and colleagues (reference 5), Amar and colleagues (reference 6), and now Manabe and associates. Amar and coworkers actually executed a randomized trial of diltiazem versus placebo in thoracic surgery patients, a noteworthy accomplishment that we could not match owing to the difficulty of recruiting patients into a trial with an undesirable primary outcome. These and earlier studies (including another study from the Tokyo group by Amano and colleagues) tend to refute the alleged harmful renal effects of intravenous diltiazem in this setting. Repetition of findings is one of the most important criteria for establishing the veracity of observational findings.
At least three general explanations can be offered to account for the different study findings. First, qualitatively different results could be explained by different patient (eg, incidence or degree of hypotension) or treatment (eg, diltiazem dose, duration) conditions. Second, the negative studies might have been relatively underpowered to detect differences in the incidence of renal failure, which is a relatively rare event. Power and sample size considerations are much more important for studies that fail to show group differences. Third, the results of nonrandomized studies could be confounded by unmeasured differences between the noncontemporaneous treatment groups. Of these explanations, we suspect confounding but we are hard pressed to identify other factors that may have changed when we started the routine use of diltiazem. Additional negative studies would provide further reassurance about the safety of using diltiazem in this setting.
The study by Manabe and colleagues constitutes a valuable part of the pathway from clinical observation to targeted analysis, repeated study, and potential resolution. The work of other investigators appears not to uphold our findings about adverse renal effects of diltiazem. Nonetheless, we admire the elegance and efficiency of a process of inquiry that began as a clinical observation and culminated in scientifically guided clarification.
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Effects of the Postoperative Administration of Diltiazem on Renal Function After Coronary Artery Bypass Grafting
- Susumu Manabe, Hiroyuki Tanaka, Tomoya Yoshizaki, Noriyuki Tabuchi, Hirokuni Arai, and Makoto Sunamori
Ann. Thorac. Surg. 2005 79: 831-835.
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