poikles 2010-2-2 11:41
利尿劑加ACE抑制劑不會增加孩童的急性腎臟損傷
作者：Deborah Brauser
出處：WebMD醫學新聞
January 14, 2010 (邁阿密) — 根據發表於重症照護醫學會第39屆重症研討會壁報組的一篇回溯回顧結果，在孩童心臟手術之後，使用furosemide以及血管收縮素轉化酶(ACE)抑制劑，並不會增加急性腎臟損傷(acute kidney injury，AKI)的風險。
科羅拉多Aurora兒童醫院心臟加護病房醫師Jon Kaufman 表示，有心臟病的新生兒、嬰兒與孩童容易發生AKI，通常是因為不佳的系統性灌注、進行體外循環或腎毒性藥物的結果。
他指出，AKI會造成延長加護病房住院，且與增加死亡率有關。
Kaufman醫師表示，其他研究曾經著眼於ACE抑制劑與先天性心臟病孩童的AKI發生率，但是就我所知，這是首次探討每個孩童在進行循環手術之後幾乎都會使用之利尿劑的影響研究。
他接著表示，ACE抑制劑在這些病患的使用相當普遍，不只是因為術後高血壓，也為了重建單一心室的理論效果，因此，我們希望可以解答以下問題：我們使用ACE抑制劑與相當高劑量的利尿劑是否會造成腎臟損傷？
研究者檢視了319名小於2歲孩童的資料，包括了單用furosemide者(n= 149人；平均年紀5個月) 或併用ACE抑制劑，如captopril或enalapril/enalaprilat者 (n= 170人；平均年紀3.7個月) ，研究期間為2007年3月至2008年9月，於心臟手術之後在該所兒童醫院的重症照護病房住院。
蒐集的資料包括體外循環、主動脈夾住、循環停止等時間；最初與最高的血清肌酸酐值；另外使用一些常見的腎毒性藥物，包括ketorolac、gentamicin、cyclosporine與其他利尿劑。
使用修改版Schwartz準則(Modified Schwartz criteria)計算血清肌酸酐清除率，根據「小兒風險、傷害、衰竭、損失和末期腎臟病（pediatric Risk, Injury, Failure, Loss, and End-Stage Kidney Disease[pRIFLE]）」分數進行AKI的最大程度分類。
【結果】
結果顯示，雖然併用組pRIFLE最大分數「F (腎衰竭)」的發生率比單一治療組高(分別是31% vs 20%；勝算比為1.75；P= .033)，校正病患年紀、手術期間使用的循環停止、術後需要葉克膜－體外循環維生系統、使用gentamicin等之後，並未發現使用ACE抑制劑會增加發生F分數的機會(P= 0.85)。
整體而言，pRIFLE分數為F的機會在以下情況會增加，手術期間循環停止(P= .002)、使用gentamicin (P= .012)、chlorothiazide (P= .044)或cyclosporine (P= .012)，年紀較大則與pRIFLE分數為F的機會降低有關(P< .0001)。
最後，那些同時接受furosemide以及ACE抑制劑者，體外循環(P= .04)和主動脈夾住(P= .03)的時間顯著較久，但是術後肌酸酐清除率比單用furosemide者低(54.4 vs 64.3 mL/min/1.73 m2；P= .01) 。
Kaufman醫師表示，當我們將這些因素全部納入考量時，我們發現兩組之間在腎臟損傷方面沒有差異，此外，同時使用ACE抑制劑與furosemide的小孩沒有人需要腎臟替代治療 ，該組的死亡率也沒有增加。
我認為，本研究顯示，使用ACE抑制劑與利尿劑對於這些羸弱的病患是安全的，我也認為這些發現將改變我們的實務，在使用上將可以較不擔心。
他指出，因為pRIFLE分數有一些限制，未來可以考慮使用其他方法如腎臟損傷之生物標記來探討此一議題。
【安全，但仍需要監測】
重症照護研討會共同主席、紐約康乃爾大學Weill醫學院小兒重症照護醫學組主任、小兒科臨床教授Bruce Greenwald醫師表示，這是一個合理的比較觀點，因為多數的嬰兒病患在心臟手術之後的確會需要使用furosemide，不過，沒有像需要ACE抑制劑那麼多。
他指出，考量這是個回溯研究，我認為研究者在確認這兩個比較組之間的腎功能差異研究上做得很好，併用ACE抑制劑與furosemide是安全可行的實務。
不過，Greenwald醫師也提出一點警告，依舊需要密切的監控，對於醫師而言，病患接受可能有腎毒性的藥物時，就一定要監測腎功能，這些研究發現不應使醫師的警戒降低，而是確保他們可以根據這些資料，對此一類型病患合理的併用這兩種藥物。
Kaufman醫師與Greenwald醫師皆宣告沒有相關財務關係。
重症照護醫學會(SCCM)第39屆重症研討會：摘要 417。發表於2010年1月11日。
Diuretic Plus ACE Inhibitor Does Not Increase Acute Kidney Damage in Children
By Deborah Brauser
Medscape Medical News
January 14, 2010 (Miami Beach, Florida) — Using furosemide and angiotensin-converting-enzyme (ACE) inhibitors concurrently after cardiac surgery does not increase the risk for acute kidney injury (AKI) in young children, according to the results of a retrospective review presented here during a poster session at the Society of Critical Care Medicine 39th Critical Care Congress.
"Neonates, infants, and children with heart disease are vulnerable to [AKI], which may occur as a result of poor systemic perfusion, the effects of cardiopulmonary bypass, or nephrotoxic medications," said Jon Kaufman, MD, cardiac intensive care physician at The Children's Hospital in Aurora, Colorado.
He noted that AKI can lead to an increased stay in the intensive care unit and has been linked to increased mortality.
"Other studies have looked at ACE inhibitors and the incidence of [AKI] in children with congenital heart disease. But to my knowledge, this is the first one that also looked at the co-use of diuretic therapy, which is given to almost every child that comes out of the [operating room] for bypass," said Dr. Kaufman.
He continued: "ACE inhibitors are used very freely in these patients, not only for postoperative hypertension, but also for the theoretical benefits of remodeling of the single ventricle. So we wanted to answer the question: Does our use of ACE inhibitors in conjunction with very high doses of diuretics lead to kidney injury?"
The investigators examined data on 319 patients younger than 2 years who received furosemide alone (n?= 149; mean age, 5 months) or in combination with the ACE inhibitors captopril or enalapril/enalaprilat (n?= 170; mean age, 3.7 months) while in The Children's Hospital critical intensive care unit after undergoing cardiac surgery between March 2007 and September 2008.
Data collected included cardiopulmonary bypass, cross-clamp, and circulatory arrest time; initial and peak serum creatinine; and use of additional common nephrotoxic medications, including ketorolac, gentamicin, cyclosporine, and other diuretics.
Modified Schwartz criteria were used to calculate serum creatinine clearance, and maximal degree of AKI was classified by pediatric Risk, Injury, Failure, Loss, and End-Stage Kidney Disease (pRIFLE) score.
Results
Results showed that although the combination group had a higher incidence of the pRIFLE maximum score of "F" (renal failure) than the monotherapy group (31% vs 20%, respectively; odds ratio, 1.75; P?= .033), the use of an ACE inhibitor was not found to increase the chance of receiving the F score (P?= 0.85), after adjustment for patient age, the use of circulatory arrest during the operative course, the need for extracorporeal membrane oxygenation in the postoperative period, and the administration of gentamicin.
Overall, the chance of a pRIFLE score of F increased for circulatory arrest during surgical repair (P?= .002) and the use of gentamicin (P?= .012), chlorothiazide (P?= .044), or cyclosporine (P?= .012). Older age was associated with a decreased chance of a pRIFLE F score (P?< .0001).
Finally, those receiving both furosemide and ACE inhibitors had significantly longer cardiopulmonary bypass (P?= .04) and cross-clamp (P?= .03) times, but a lower postoperative creatinine clearance (54.4 vs 64.3?mL/min per 1.73?m2; P?= .01) than those receiving furosemide alone.
"When we accounted for all these other factors, we found no difference between the groups for kidney injury," said Dr. Kaufman. "Plus, none of the kids on both the ACE inhibitors and furosemide went on to require renal replacement therapy, and there was no increased mortality in that group."
"I think this study shows that using ACE inhibitors with diuretics is safe in this fragile and vulnerable patient population, and I think the findings will change our practice, in that we'll be less concerned about using them."
He added: "Given some of the limitations of the pRIFLE criteria, it would be interesting to next look at this in a different way, such as using biomarkers of renal injury."
Safe, but Monitoring Still Needed
"This was a reasonable comparison review, as a majority of patients in infancy following cardiac surgery do require furosemide at some point, although not as many require ACE inhibitors," said Critical Care Congress cochair Bruce Greenwald, MD, FCCM, FAAP, professor of clinical pediatrics and chief of the Division of Pediatric Critical Care Medicine at Cornell University Weill Medical College in New York City.
He added: "Considering the limitations of a retrospective study, I think [the investigators] did well in determining that there were no glaring differences in renal function between the 2 comparison groups, suggesting that the practice of using ACE inhibitors in combination with furosemide is safe."
However, Dr. Greenwald cautioned that close monitoring is still needed. "It's always important for clinicians to monitor renal function in patients who are receiving drugs that have the potential to be nephrotoxic. These findings should not cause clinicians to let their guard down, but it should reassure them that starting the 2 drugs together in this patient population is a reasonable thing to do based on these data."
Dr. Kaufman and Dr. Greenwald have disclosed no relevant financial relationships.
Society of Critical Care Medicine (SCCM) 39th Critical Care Congress: Abstract?417 Presented January?11, 2010.