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a Sutter Medical Center, Sacramento, California
b Sutter Institute for Medical Research (SIMR), Sacramento, California
Accepted for publication July 9, 2007.
* Address correspondence to Dr Mainwaring, 5301 F St, Ste 213, Sacramento, CA 95819 (Email: mainwar{at}sutterhealth.org).
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Abstract |
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 Top Abstract IntroductionMaterial and MethodsResultsCommentReferences |
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Methods: The study enrolled 18 infants and children (ages 2 months to 15.6 years) scheduled for surgical repair of their ventricular septal defects. Brain natriuretic peptide levels were drawn preoperatively and then postoperatively at 1, 24, 48, and 72 hours. The amount of shunt (the ratio of pulmonary blood flow [Qp]/systemic blood flow [Qs]) through the ventricular septal defect was determined by saturation levels performed in the catheterization laboratory or intraoperatively.
Results: The preoperative brain natriuretic peptide levels (pg/mL) averaged 78 ± 57, and the postoperative levels were 168 ± 241 at 1 hour, 418 ± 330 at 24 hours, 405 ± 364 at 48 hours, and 391 ± 397 at 72 hours. These differences were significant for each postoperative time point compared with preoperative values. Preoperative brain natriuretic peptide and the Qp/Qs were significantly correlated (age-adjusted R 2 = 0.33, p < 0.001).
Conclusions: Brain natriuretic peptide levels have a close correlation with the physiologic volume load caused by ventricular septal defects. The preoperative brain natriuretic peptide levels were also found to be predictive for the postoperative time course of brain natriuretic peptide level changes. These results suggest that brain natriuretic peptide levels may be a useful clinical marker in infants and children with ventricular septal defects.
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Introduction |
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TopAbstractIntroductionMaterial and MethodsResultsCommentReferences |
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BNP levels have been shown to correlate with the incidence and severity of congestive heart failure in adult patients [3, 4]. This information has led to significant changes in the management of patients admitted to the hospital with congestive heart failure. Specifically, BNP levels provide a quantitative and prognostic measure of the severity of the patients’ heart failure [5, 6]. In addition, intravenous infusions of synthetically produced BNP (Nesiritide, Scios Inc, Mountain View, CA) have positively influenced the course of treatment for these patients [7]. BNP levels have also been shown to rise after cardiopulmonary bypass in adult patients, and there is some anecdotal experience suggesting that BNP infusions may facilitate diuresis and natriuresis in this setting as well [8].
In contrast, far less is known about BNP levels in infants and children born with congenital heart disease. The purpose of the present study was to evaluate BNP levels in infants and children having operations to repair ventricular septal defects (VSDs). We specifically sought to determine the relationship between preoperative BNP levels and the amount of left-to-right shunt through the VSD. In addition, we designed the study to evaluate the changes in BNP levels postoperatively. It was our hypothesis that BNP levels would correlate with the amount of left-to-right shunt attributable to the VSD.
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Material and Methods |
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TopAbstractIntroductionMaterial and MethodsResultsCommentReferences |
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BNP levels were determined preoperatively and then postoperatively at 1, 24, 48, and 72 hours. The preoperative sample was drawn at the time of the preoperative blood testing and cross-match. The postoperative samples were drawn through the existing arterial or venous lines placed at the time of the procedure; thus, no patient required a separate venipuncture solely for the purpose of this study. Each BNP blood sample (2.5 mL) was placed into a purple-top tube that was immediately placed on ice. The samples were centrifuged and the plasma portion was separated in the Sutter Memorial chemistry laboratory.
Quantitative analysis was performed using the Abbott AxSym (Abbot Diagnostics, Abbott Park, IL) immunoassay system (Fig 1). This assay measured N-terminal prohormone BNP (NT-proBNP) with a microparticle enzyme immunoassay (MEIA). The precursor to both NT-proBNP (76 amino acids) and BNP (32 amino acids) is proBNP (108 amino acids). When proBNP is cleaved at the cellular membrane, the result is a 1:1 relationship between NT-proBNP and BNP. However, NT-proBNP has a longer half-life than the active hormone and is more stable in vitro. As a result, NT-proBNP assays are better standardized across platforms, with an interassay variation of less than 10% [9, 10].
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Statistical analysis was performed using analysis of variance to compare preoperative BNP values between patients who were younger and older than age 1. The Wilcoxon test was performed to assess differences between the preoperative and postoperative BNP levels. Correlation coefficients and linear regression analysis were used to assess the association between preoperative BNP and Qp/Qs after adjustment for age (<1 year, 1+ years).
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Results |
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Histograms showed that Qp/Qs and preoperative BNP were normally distributed. The mean Qp:Qs was 3.0 ± 1.84 (range, 1.4 to 5.6). Mean preoperative BNP was 78 ± 57 pg/mL (range, 15 to 175 pg/mL). The mean peroperative levels of BNP were 102 ± 47 pg/mL in patients younger than 1 year old and 57 ± 58 pg/mL in patients who were older than 1 year. These values were not statistically significantly different (p > 0.05). Mean Qp/Qs was 3.80 ± 1.05 for patients younger than age 1 and 2.19 ± 0.65 for patients older than age 1 (p < 0.01).
Postoperatively, BNP levels increased in all patients compared with the preoperative values and remained elevated throughout the study period. BNP levels at all four postoperative periods varied widely and were positively skewed (Table 1). The increase in BNP level was approximately threefold higher by 1 hour postoperatively compared with the preoperative level and was approximately fivefold higher at 24, 48, and 72 hours postoperatively. However, the increase in postoperative BNP levels was far greater in those patients whose preoperative levels were in the higher range. Figure 2 demonstrates the preoperative and postoperative BNP levels for these two groups by using a preoperative BNP level of greater or lesser than 75 pg/mL.
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Comment |
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TopAbstractIntroductionMaterial and MethodsResultsCommentReferences |
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The introduction of plasma BNP to quantitatively assess the degree of heart failure has led to revolutionary changes in the management of adults with this disease [11]. The BNP levels identify early on those patients who are most at risk for poor outcome and allow for changes in their clinical management so that they are no longer at such high risk [12]. Infusions of BNP (nesiritide) for patients with New York Heart Association functional class IV heart failure result in prompt relief of dyspnea, a lowering of the pulmonary capillary wedge pressure, and excretion of sodium and water without adversely affecting renal function [2, 6, 7]. During the past 5 years, there have been more than 500 literature citations regarding BNP or nesiritide in adult patients with congestive heart failure.
In contrast to the adult literature, a very limited number of reports have been published about BNP in children. Costello and colleagues [13] evaluated 25 patients undergoing a variety of different congenital heart operations. Their results indicate that BNP levels were elevated postoperatively and positively associated with the duration of cardiopulmonary bypass. Shih and colleagues [14] studied 51 patients undergoing repair of congenital heart defects and also found that the postoperative BNP were elevated, with the 12-hour postoperative BNP level associated with the duration of mechanical ventilation and presence of a low cardiac output state. Several other articles [15] have documented alterations in plasma BNP levels in children with univentricular hearts and tetralogy of Fallot with pulmonary valve insufficiency and right ventricular dilatation [16].
In the present study, we chose to evaluate patients undergoing VSD repair for a number of reasons. First, VSDs are associated with variable degrees of left-to-right shunt and thus would be amenable to evaluating the relationship between BNP and Qp/Qs.
Second, the surgery for VSD repair is relatively uniform procedure and thus would minimize differences based on the surgical procedure itself. Additional factors that may facilitate achieving some uniformity are that all of the cardiac operations were performed by a single surgeon, and the postoperative management strategy was maintained in a consistent fashion from patient to patient. Thus, many important variables have been obviated, with Qp/Qs remaining the one important uncontrolled variable.
Third, because VSDs are the most common congenital heart defect requiring surgical intervention, enrollment of patients could proceed at a reasonable pace.
The results of the present study are consistent with previously published reports indicating a correlation exists between BNP and Qp/Qs [17, 18]. The strength of the correlation in our study suggests that plasma BNP levels could be used as a substitute for cardiac catheterization for the purpose of quantitative analysis. Specifically, a BNP level could be obtained and the corresponding Qp/Qs calculated from the equation described in Figure 3. The decision whether to recommend surgical intervention could then be based on this quantitative assessment (eg, Qp/Qs > 1.5 would benefit from surgery).
Our study also demonstrated that the plasma BNP levels were significantly elevated in the postoperative period, consistent with the findings of the two studies cited above. However, our study differed from previous studies in that it focused on a single congenital heart defect in patients who were having the same surgical procedure. In this cohort, the degree of postoperative elevation in BNP correlated with the relative increase in preoperative BNP and Qp/Qs. This indicates that the degree of heart failure preoperatively predicts the degree of BNP elevation both preoperatively and postoperatively.
Our results show that BNP levels increase postoperatively. Intuitively, one might anticipate that removing a volume load with the resultant reduction of ventricular size would be associated with a decrease in BNP. The data, however, indicate that the direction of change is opposite to that premise. Possible explanations for this observation include transient ventricular "stunning," diastolic dysfunction induced by perioperative geometric changes in the ventricle, or the effect of circulating mediators. However, the exact pathophysiology cannot be answered by this study.
A second question raised by this study is the length of time that the increase in BNP persists. The fact that the BNP levels are still markedly elevated on the third postoperative day seems surprising considering that many of the patients with lower Qp/Qs ratios were poised to go home on the fourth day. This persistent increase in BNP seems incongruous with the clinical situation. It would be intriguing to know how long the BNP levels remain elevated and whether this is dependent on the preoperative ratio of BNP to Qp/Qs values. Our study, however, was designed to avoid a separate venipuncture solely for the purpose of the study. The vascular access lines in many patients were removed on the third day in preparation for discharge, thus eliminating the possibility of drawing subsequent samples. For these reasons, we are not able to answer the question of how long the BNP levels remain elevated postoperatively.
In summary, the present study has demonstrated a close correlation between preoperative BNP and Qp/Qs, and we have shown that BNP levels are elevated postoperatively and are stratified according to their preoperative BNP levels. These results suggest that BNP levels may provide important clinical data before and after VSD repair. It is likely that BNP will have important diagnostic and therapeutic value in the future in children with congenital heart disease.
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References |
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TopAbstractIntroductionMaterial and MethodsResultsCommentReferences |
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This article has been cited by other articles:
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  N. Yoshimura, R. Henaine, Y. Ootaki, H. Matsuhisa, and T. Misaki Why Does the Preoperative BNP Level Predict the Degree of Postoperative BNP Elevation? Ann. Thorac. Surg., August 1, 2008; 86(2): 694 - 694. [Full Text] [PDF]
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A. M.E. Koch Plasma Levels of Brain Natriuretic Peptide in Children With Left-To-Right Shunt Before and After Cardiac Surgery Ann. Thorac. Surg., August 1, 2008; 86(2): 693 - 694. [Full Text] [PDF]
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