Interact CardioVasc Thorac Surg 2009;8:474-478. doi:10.1510/icvts.2008.199448
© 2009 European Association of Cardio-Thoracic Surgery
Best evidence topic - Cardiac general |
Could atrial natriuretic peptide be a useful drug therapy for high-risk patients after cardiac surgery?
Jagdish Ambwania,*,
Dolly Ubhranib,
Rasheed Saadc and
Joel Dunningc
a Department of Pediatrics, Children's Hospital of New Jersey, Newark Beth Israel Medical Center, 201 Lyons Avenue, Newark, NJ 07112, USA
b Department of Pediatrics, Children's Hospital at Monmouth Medical Center, Long Branch, NJ 07740, USA
c Department of Cardiothoracic Surgery, James Cook University Hospital, Middlesbrough, UK
Received 24 November 2008;
received in revised form 5 January 2009;
accepted 8 January 2009
*Corresponding author. Tel.: +1-732-582-6339.
E-mail address: jagdish.ambwani{at}gmail.com (J. Ambwani).
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Abstract
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A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was whether atrial natriuretic peptide (ANP) or brain natriuretic peptide (BNP) could be a useful alternative diuretic for patients post cardiac surgery. Altogether more than 250 papers were found using the reported search, of which eight RCTs represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. We conclude that the RCTs consistently showed a diuretic effect with increased creatinine clearance, and increased urine volume and reduced usage of conventional diuretics. Lower urea and creatinine levels were also found postoperatively and also reduced decreases in glomerular filtration rate compared to placebo, both in studies of patients with preoperatively normal renal function and those who had impaired function. In addition, two studies found a reduction in the incidence of AF, and renin/aldosterone levels were lower. The NAPA trial of 272 CABG patients with LV dysfunction was the only study to show a shorter ICU stay and reduced early mortality with nesiritide compared to placebo.
Key Words: Brain natriuretic peptide; Atrial natriuretic factor; Renal function; Thoracic surgery; Coronary artery bypass
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1. Introduction
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A best evidence topic was constructed according to a structured protocol. This is fully described in the ICVTS [1].
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2. Three-part question
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In [postoperative cardiac surgery patients] is [recombinant human BNP] superior to [conventional diuretics] for [optimization of renal function]?
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3. Clinical scenario
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You are with a cardiothoracic surgeon in a pediatric intensive care unit seeing a 10-year-old boy who is one-day post-coarction repair. You go through his labs and total intake/output chart and see that his urine output is poor and he is in positive fluid balance. The surgeon elects to commence nesiritide. You ask him why he chose nesiritide instead of furosemide; he replies that nesiritide has better suppression of the renin-aldosterone system in addition to inducing diuresis after cardiopulmonary bypass. You resolve to see what studies have been performed to support his hypothesis.
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4. Search strategy
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Medline 1950 to August 2008 using OVID interface and EMBASE [exp Thoracic surgery/OR cardiac surgery.mp OR heart surgery.mp OR exp coronary artery bypass/or CABG.mp] AND [exp Atrial Natriuretic Factor/OR exp Natriuretic Peptide, Brain/OR BNP.mp or rhBNP.mp. or rhANP.mp. or hBNP.mp. or hANP.mp. or nesiritide.mp or carperitide.mp]
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5. Search outcome
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Two hundred and fifty papers were found using the reported search. From these eight RCTs provided the best evidence to answer the question. These are presented in Table 1.
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6. Results
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Mitaka et al. [2] randomized 40 patients undergoing abdominal aortic aneurysm repair to two groups, human ANP (hANP) infusion (n=20) and placebo (n=20). Blood and urine samples were collected perioperatively to measure serum sodium, creatinine, urea, plasma ANP and BNP. Urine volume and urinary concentrations of N-acetyl-[beta]-D-glucosaminidase (NAG), sodium, and creatinine were measured. The mean serum concentrations of creatinine and urea were significantly (P<0.05) lower in the hANP group. The mean urine volume and mean creatinine clearance were significantly (P<0.05) higher in the treatment group. The mean urinary NAG/creatinine ratio was significantly (P<0.05) lower in the hANP group. Authors have previously published a similar study on hANP induced improvement in renal failure after suprarenal abdominal aortic cross-clamping in a dog model [9].
Sward et al. [3] reported an RCT of 63 patients in shock, on inotropes, with renal impairment undergoing cardiopulmonary bypass (CBP). In the treatment group (infusion of hANP at 50 ng/kg/min) creatinine clearance three days after starting treatment was higher than placebo (P=0.04). Six (21%) patients in the h-ANP group compared with 14 (47%) in the placebo group needed dialysis before or at day 21 (P=0.009). Eight (28%) patients in the hANP group compared with 17 (57%) in the placebo group suffered from the combined end-point dialysis or death before or at day 21 (P=0.017). There were no significant differences in both groups for total length of ICU stay, ICU mortality after 21 days, incidence of hypotension and incidence of atrial fibrillation.
Chen et al. [4] studied 40 patients with pre-existing renal insufficiency undergoing CPB. Treatment group received low-dose nesiritide (n=20; 0.005 µg/kg/min of human BNP), after induction of anesthesia and before CPB for 24 h in the postoperative period. Patients in the treatment group had lower cystatin levels at 48 h, 72 h vs. 24 h after starting nesiritide (P<0.05). Aldosterone levels were significantly higher in placebo group at the end of the 24 h infusion. Estimated creatinine clearance was significantly higher in treatment group at the end of 48 h, 72 h vs. 24 h after starting therapy and use of diuretics was much lower in nesiritide group (P=0.06). There was no significant difference in adverse events between nesiritide vs. placebo (26% vs.15%, P=0.45), but the study population was small.
Mentzer et al. [5] led the NAPA trial in which 272 patients with underlying left ventricular dysfunction CABG using CPB were randomized to nesiritide or placebo. Significant primary outcomes were peak increase in serum creatinine 0.15 mg/dl in nesiritide group vs. 0.34 mg/dl in placebo (P<0.001), and there was a smaller decrease in glomerular filtration rate (GFR) (–10.2 in nesiritide group vs. –17.8 placebo, P=0.001). Urine output in 24 h postoperative period was significantly higher in treatment group (2926±1179 ml vs. 2350±1066 ml, P<0.001). Mean ICU stay in nesiritide group was shorter as compared to placebo group (9.1±6.1 vs. 11.5±9.8 days, P=0.043). Thirty and 180-day mortality was significantly less in nesiritide group (P=0.046) calculated via log rank test, however, 30–180-day mortality end points were added very late in the study, so many patients did not have follow-up. Incidence of atrial fibrillation was higher in the placebo group (P=0.05).
Hayashi et al. [6] studied 40 patients undergoing open-heart surgery with CPB who received either hANP infusion immediately after termination of CPB (n=16) or were controls (n=14). Twenty-four hours after operation, the CVP, mean pulmonary arterial pressure, and pulmonary capillary wedge pressures were significantly lower in treatment group and the cardiac index was significantly higher in the treatment group (P<0.01). Total volume of plasma, dose of furosemide, and dose of potassium chloride required in the postoperative period after CPB was significantly smaller in treatment group, P<0.05, P<0.01 and P<0.01, respectively. On the first postoperative day plasma renin activity and aldosterone levels were also lower in the treatment group (P<0.01).
Brackbill et al. [7] compared the perioperative use of nesiritide vs. milrinone in high-risk coronary artery patients. Forty patients with EF <40% or left ventricular dysfunction undergoing elective CABG surgery were randomized into two groups to receive either nesiritide or milrinone bolus followed by 24 h infusion in the postoperative period. Patients receiving nesiritide had a mean±S.D. postoperative intensive care unit stay of 50.6±46.8 h compared with 44.1±23.5 h in those receiving milrinone (P=0.578). Incidence of postoperative heart failure was also not significantly different between the drugs (P=0.259). Thirty-day follow-up confirmed no difference in hospital readmission rates between nesiritide and milrinone (P=0.661). No differences in mortality were observed during hospitalization or 30 days of follow-up. In summary, nesiritide did not decrease postoperative ICU stay or other clinical parameters compared with milrinone in high-risk patients with hemodynamically stable left-ventricular function undergoing CABG surgery.
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7. Clinical bottom line
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We found eight RCTs in this area. The RCTs consistently showed a diuretic effect with increased creatinine clearance, and increased urine volume and reduced usage of conventional diuretics. Lower urea and creatinine levels were also found postoperatively and also reduced decreases in glomerular filtration rate compared to placebo both in studies of patients with pre-operatively normal renal function and those who had impaired function. In addition, two studies found a reduction in the incidence of AF, and renin/aldosterone levels were lower. The NAPA trial of 272 CABG patients with LV dysfunction was the only study to show a shorted ICU stay and reduced early mortality with nesiritide compared to placebo.
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References
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- Dunning J, Prendergast B, Mackway-Jones K. Towards evidence-based medicine in cardiothoracic surgery: best BETS. Interact CardioVasc Thorac Surg 2003;2:405–409.[Abstract/Free Full Text]
- Mitaka C, Kudo T, Jibiki M, Sugano N, Inoue Y, Makita K, Imai T. Effects of human atrial natriuretic peptide on renal function in patients undergoing abdominal aortic aneurysm repair. Crit Care Med 2008 Mar;36:745–751.[CrossRef][Medline]
- Sward K, Valsson F, Odencrants P, Samuelsson O, Ricksten SE. Recombinant human atrial natriuretic peptide in ischemic acute renal failure: a randomized placebo-controlled trial. Crit Care Med 2004 Jun;32:1310–1315.[CrossRef][Medline]
- Chen H, Sundt TM, Cook DJ, Heublein DM, Burnett JC Jr. Low dose nesiritide and the preservation of renal function in patients with renal dysfunction undergoing cardiopulmonary-bypass surgery: a double-blind placebo-controlled pilot study. Circulation 2007 Sep 11;116:I-134–I-138.[Medline]
- Mentzer RM Jr, Oz MC, Sladen RN, Graeve AH, Hebeler RF Jr, Luber JM Jr, Smedira NG, NAPA Investigators. Effects of perioperative nesiritide in patients with left ventricular dysfunction undergoing cardiac surgery: the NAPA trial. J Am Coll Cardiol 2007;49:716–726.[Abstract/Free Full Text]
- Hayashi Y, Ohtani M, Hiraishi T, Kobayashi Y, Nakamura T. Synthetic human [alpha]-atrial natriuretic peptide infusion in management after open heart operations. ASAIO J 2003, May/Jun;49:320–324.[CrossRef][Medline]
- Brackbill ML, Stam MD, Schuller-Williams RV, Dhavle AA. Perioperative nesiritide versus milrinone in high-risk coronary artery bypass graft patients. Ann Pharmacother 2007;41:427–432.[Abstract/Free Full Text]
- Sezai A, Hata M, Wakui S, Niino T, Takayama T, Hirayama A, Saito S, Minami K. Efficacy of continuous low-dose hANP administration in patients undergoing emergent coronary artery bypass grafting for acute coronary syndrome. Circulation Journal 2007;71:1401–1407.[CrossRef][Medline]
- Mitaka C, Hirata Y, Habuka K, Narumi Y, Yokoyama K, Makita K, Imai T. Atrial natriuretic peptide infusion improves ischemic renal failure after suprarenal abdominal aortic cross-clamping in dogs. Crit Care Med 2003;31:2205–2210.[CrossRef][Medline]
- Belenkie I. Nesiritide administration in patients with left ventricular dysfunction undergoing coronary artery bypass surgery. J Am Coll Cardiol 2007;49:727–728.[Free Full Text]
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Abstract
1. Introduction