B-type natriuretic peptide is predictive of postoperative events in orthopedic surgery

Abstracts

FUNDAMENTO: A avaliação clínica nem sempre é suficiente para predizer complicações cardíacas pós-operatórias (PO). O peptídeo natriurético do tipo B (BNP) tem grande valor prognóstico em pacientes (pts) com insuficiência cardíaca. Seu valor como preditor de eventos em cirurgias ortopédicas ainda não foi testado. OBJETIVO: Avaliar o valor do BNP em predizer complicações cardíacas no PO de cirurgia ortopédica. MÉTODOS: Avaliados de modo prospectivo, 208 pts submetidos à cirurgia para correção de fratura de fêmur e artroplastia de quadril ou de joelho. Foram 149 (71,6%) mulheres e a idade média foi de 72,6 ± 8,8 anos. Os pacientes foram submetidos, no pré-operatório, à avaliação clínica convencional e estimativa do risco cirúrgico pela classificação da American Society of Anesthesiologists (ASA). O BNP foi dosado no pré-operatório e avaliou-se a sua capacidade de predizer eventos cardíacos (morte, infarto agudo do miocárdio, angina instável, fibrilação atrial, taquicardia ventricular ou insuficiência cardíaca) no PO, através de análise multivariada por regressão logística. RESULTADOS: Dezessete (8,0%) pacientes apresentaram eventos cardíacos. A mediana de BNP foi significativamente maior nesses pacientes quando comparada a dos sem eventos cardíacos (93 [variação interquartil 73-424] vs 26,6 [13,2-53,1], p = 0,0001). O BNP foi o principal preditor independente de eventos (p = 0,01). A classificação da ASA não foi preditor independente. A análise de curva ROC demonstrou que para um corte de 60 pg/ml, o BNP apresentou sensibilidade de 76,0% e especificidade de 79,0% para predizer eventos, com área sob a curva de 83,0%. CONCLUSÃO: O BNP é um preditor independente de eventos cardíacos no PO de cirurgias ortopédicas.

Ortopedia; procedimentos cirúrgicos; cuidados pós-operatórios; peptídeo natriurético tipo B

FUNDAMENTO: La evaluación clínica no siempre es suficiente para predecir complicaciones cardíacas postoperatorias (PO). El péptido natriurético del tipo B (BNP) tienen gran valor pronóstico en pacientes (pts) con insuficiencia cardíaca. Su valor como predictor de eventos en cirugías ortopédicas aun no fue testeado. OBJETIVO: Evaluar el valor del BNP para predecir complicaciones cardíacas en el PO de cirugía ortopédica. MÉTODOS: Evaluados de modo prospectivo, 208 pts sometidos a cirugía para corrección de fractura de fémur y artroplastía de cadera o de rodilla. Fueron 149 (71,6%) mujeres y la edad media fue de 72,6 ± 8,8 años. Los pacientes fueron sometidos, en el preoperatorio, a evaluación clínica convencional y estimativa del riesgo quirúrgico por la clasificación de la American Society of Anesthesiologists (ASA). El BNP fue dosado en el preoperatorio y se evaluó su capacidad de predecir eventos cardíacos (muerte, infarto agudo del miocardio, angina inestable, fibrilación atrial, taquicardia ventricular o insuficiencia cardíaca) en el PO, a través de análisis multivariado por regresión logística. RESULTADOS: Diecisiete (8,0%) pacientes presentaron eventos cardíacos. La mediana de BNP fue significativamente mayor en esos pacientes cuando fue comparada a la de los sin eventos cardíacos (93 [variación intercuartil 73-424] vs. 26,6 [13,2-53,1], p = 0,0001). El BNP fue el principal predictor independiente de eventos (p = 0,01). La clasificación de la ASA no fue predictor independiente. El análisis de curva ROC demostró que para un corte de 60 pg/ml, el BNP presentó sensibilidad de 76,0% y especificidad de 79,0% para predecir eventos, con área bajo la curva de 83,0%. CONCLUSIÓN: EL BNP es un predictor independiente de eventos cardíacos en el PO de cirugías ortopédicas.

Ortopedia; procedimientos quirúrgicos; cuidados postoperatorios; péptido natriurético Tipo B

ORIGINAL ARTICLE

B-Type natriuretic peptide is predictive of postoperative events in orthopedic surgery

Humberto Villacorta Junior^I; Isabela Simões de Castro^II; Marise Godinho^II; Camila Mattos^II; Rogério Visconti^II; Maurício Saud^II; Mônica Novais^II; Cláudia Murad^II; Fernanda Nogueira^II

^IUniversidade Federal Fluminense, Niterói

^IIInstituto Nacional de Traumatologia e Ortopedia, Rio de Janeiro, RJ - Brazil

Mailing address

ABSTRACT

BACKGROND: Clinical assessment is not always sufficient to predict postoperative (PO) cardiac complications. B-type natriuretic peptide (BNP) has an important prognostic value in patients with heart failure. Its value as a predictor of events in orthopedic surgeries has not yet been tested.

OBJECTIVE: To assess the value of BNP in predicting cardiac complications in the PO period of orthopedic surgeries.

METHODS: A total of 208 patients undergoing surgical treatment of femur fracture and hip or knee arthroplasty were prospectively evaluated. Of these, 149 (71.6%) were women and the mean age was 72.6 ± 8.8 years. In the preoperative period, the patients underwent conventional clinical assessment and their surgical risk was estimated according to the American Society of Anesthesiologists' (ASA) classification. BNP was determined in the preoperative period, and its ability to predict PO cardiac events (death; acute myocardial infarction; unstable angina; atrial fibrillation; ventricular tachycardia; or heart failure) was analyzed using multivariate logistic regression analysis.

RESULTS: Seventeen patients (8.0%) experienced cardiac events. Median BNP was significantly higher in these patients in comparison to those without cardiac events (93 [interquartile range 73-424] vs 26.6 [13.2-53.1], p = 0.0001). BNP was the main independent predictor of events (p = 0.01). The ASA classification was not an independent predictor. Analysis of the ROC curve demonstrated that for a cut-off point of 60 pg/ml, BNP showed sensitivity of 76.0% and specificity of 79.0% in the prediction of events, with an area under the curve of 83.0%.

CONCLUSION: BNP is an independent predictor of PO cardiac events in orthopedic surgeries. (Arq Bras Cardiol. 2010; [online].ahead print, PP.0-0)

Key words: Orthopedics; orthopedic procedures; postoperative care; natriuretic peptide, B-type.

Introduction

Patients undergoing non-cardiac surgeries may experience cardiac events such as acute myocardial infarction and acute pulmonary edema as postoperative complications^1,2. The identification of patients at risk for these events is important, and clinical assessment alone is not always sufficient. In selected patients, this assessment is usually complemented by non-invasive methods for the analysis of ischemia and cardiac function. However, these methods involve costs, so it is necessary to identify the patients who might be left without this assessment.

B-type natriuretic peptide (BNP) is a marker of cardiac dysfunction and myocardial ischemia of great prognostic value in patients with heart failure and acute coronary syndromes^3-5. Its value in detecting patients at risk for postoperative cardiac complications in orthopedic surgery has not been determined.

The objective of this study was to evaluate the value of BNP in the prediction of postoperative cardiac events in patients undergoing orthopedic surgeries.

Methods

Population

A total of 208 patients undergoing elective surgical treatment of femur fracture, or hip or knee arthroplasty were prospectively included in the period from March 2006 to January 2007.

All patients gave written informed consent and the study was approved by the institutional ethics committee under number 075, in December 15, 2004. Data were collected during preoperative visits and from prospective analysis of the medical records. In the preoperative period, the surgical risk was established using the criteria of the American Society of Anesthesiologists (ASA). The criteria of this classification are well known and patients are classified in ASA I, II, III, IV, V or VI risk status.

In 58 cases (27.8%), preoperative transthoracic echocardiography was performed using a Toshiba Nemio 30 ultrasound scanner, with a 2.5 MHz electronic transducer, and left ventricular ejection fraction (LVEF) was determined using the Teichholz method.

BNP determination

BNP was determined by immunofluorescence, using the Triage method (Biosite Inc, San Diego, CA, USA), point-of-care system. Blood was drawn on the day of surgery or up to 48 hours earlier. Five ml were drawn, and the analysis was carried out in whole blood within four hours of collection. For the analysis of BNP variation with surgery, its levels were also determined 24 h after surgery.

Outcome measures

The patients were followed up during hospitalization (median of 5 days, interquartile range = 4-8) by the study investigators and were evaluated for the presence of postoperative cardiac complications. The following events were considered outcome measures: acute myocardial infarction (AMI); unstable angina; acute pulmonary edema; heart failure; acute atrial fibrillation; sustained ventricular tachycardia; or cardiac death.

Electrocardiographic assessment and chest radiography were obtained from all patients in the pre and postoperative periods. Serial determination of myocardial necrosis markers and echocardiography were additionally performed for patients with chest pain, shortness of breath, sudden hemodynamic changes or supraventricular or ventricular arrhythmias in the postoperative period. Cardiac death was defined as death from cardiac causes during hospitalization. AMI was defined as an elevation of myocardial necrosis markers by two times above the upper limits of normal associated with suggestive symptoms or new Q waves in the electrocardiogram (ECG). Acute pulmonary edema was diagnosed by means of clinical examination and chest radiography; cardiac arrhythmias were diagnosed using electrocardiography.

The first event was considered an outcome measure, with no double counting of events for the same patient.

Statistical analysis

Categorical variables were expressed as absolute number and percentage and analyzed by the chi square test or by the Fischer's exact test, when appropriate. Continuous variables were expressed as mean and standard deviation. BNP values were expressed as median and interquartile range because they were non-normally distributed. Continuous variables were analyzed using the Student's t test, except for BNP, which was analyzed by the Mann-Whitney test because it was non-normally distributed.

The independent variables analyzed were age; gender; previous AMI; history of angina; previous surgical or percutaneous myocardial revascularization; previous heart failure; atrial fibrillation; significant changes on resting electrocardiogram (pathological Q waves; left bundle branch block; left ventricular overload; ST-segment or T-wave changes; atrial fibrillation and frequent premature ventricular complexes); enlarged heart on chest radiography; LVEF on echocardiography; creatinine; hemoglobin; cigarette smoking; chronic obstructive pulmonary disease (COPD); previous stroke; use of drugs (betablockers, angiotensin-converting enzyme inhibitors); ASA classification; systemic hypertension; dyslipidemia; diabetes mellitus; and family history of CAD.

In the univariate analysis, variables with p < 0.10 were included in the multivariate logistic regression model in order to determine the variables independently related to the postoperative outcome measures. The variables BNP and age were dichotomized in the multivariate model, being included as BNP values > 60 pg/ml and age > 70 years. Ejection fraction was not included in the multivariate analysis because it was only available in less then one third of the cases.

Results

Table 1 shows the baseline characteristics of the population as a whole. Sixty-two patients (29.8%) were receiving betablockers, 102 (49.0%) were receiving angiotensin-converting enzyme inhibitors or angiotensin receptor blocker and 73 (35.0%) were taking diuretics. Resting ECG was normal in 120 patients (57.7%); 42 (20.0%) showed Q waves suggestive of previous AMI; left bundle branch block occurred in 11 (5.2%); left ventricular overload in 9 (4.3%); ST-segment or T wave abnormalities occurred in 10 (4.8%); atrial fibrillation in 7 (3.3%); and frequent premature ventricular complexes in 5 (2.5%).

No significant variation was found between preoperative and postoperative BNP levels, with medians and interquartile ranges of 27.9 (13.3-65) vs 23.5 (13.2-63.5), respectively, p = 0.34. Seventeen (8.0%) patients experienced cardiac events. Preoperative median BNP levels were significantly higher in patients who experienced cardiac events in comparison to those who did not (93 [interquartile range 73-424] vs 26.6 [13.2-53.1], p = 0.0001), as shown in Figure 1. The characteristics of patients with and without outcome measures are shown in Table 2.

In the multivariate analysis, preoperative BNP was the main predictor of events (p = 0.01), followed by age (p = 0.042). Previous AMI (p = 0.05) showed a borderline value, as shown in Table 3. The ASA classification was not an independent predictor. The analysis of the ROC curve (Figure 2) demonstrated that for a cut-off point of 60 pg/ml, BNP showed sensitivity of 76.0% and specificity of 79.0% to predict events, with an area under the curve of 83.0%. Table 4 shows the sensitivity and specificity for several BNP cut-off points.

Although pulmonary thromboembolism and fat embolism were not considered outcome measures of the study, it is worthy pointing out that they did not occur in this case series.

Discussion

In the present study, BNP levels determined up to 48 hours prior to surgery were the main independent predictor of postoperative cardiac events, proving superior to conventional clinical parameters and to the ASA classification. The cut-off point of 60 pg/ml showed good accuracy in the detection of cardiac events, with an area under the curve of 83.0%.

The utility of the natriuretic peptides BNP and N-terminal pro-BNP fraction (NT-proBNP) in predicting postoperative cardiac events has been reported in the past years both in studies including several types of non-cardiac surgery and in specific surgeries. In all of them, these markers stood out as the only independent predictor or one of the main independent predictors of the postoperative risk^6-10. Dernellis and Panaretou analyzed the preoperative value of BNP in risk prediction in 1,590 patients undergoing different types of non-cardiac surgery⁶. The clinical variables independently associated with events were LVEF and previous AMI. When BNP was added to the model, these variables lost significance, and BNP > 189 pg/ml was the only independent predictor in the final model. The cut-off point value in that study was three times higher than the one found in the present study. This can be explained by the fact that they studied a population more severely ill than ours in relation to baseline characteristics, with higher prevalences of previous AMI, surgical or percutaneous myocardial revascularization and heart failure.

In another study, BNP was able to predict the mid-term mortality (median follow-up of 654 days) after major non-cardiac surgeries⁸. BNP cut-off point > 35 pg/ml showed sensitivity of 70.0% and specificity of 68.0%. The study population showed baseline characteristics similar to those of the present study, and the cut-off point obtained was closer to that found in our study. Similarly to BNP, NT-proBNP was able to predict cardiac complications in patients undergoing surgical treatment of abdominal aortic aneurysm⁷; in high-risk patients undergoing several types of non-cardiac surgeries¹⁰; and in the prediction of the incidence of atrial fibrillation following thoracic surgery for the treatment of lung cancer⁹. Our study corroborates previous findings in a specific population of patients undergoing orthopedic surgery. However, taking into consideration the data reported in the literature, natriuretic peptides seem to be good predictors of cardiac events in any type of non-cardiac surgery.

In the present study, we did not find a significant variation between preoperative and postoperative BNP levels. This finding differs from that observed in Schutt et al's study,¹⁰ in which 89.0% of the patients presented with increased postoperative NT-proBNP as determined within three days of the surgery, even in the absence of clinically detectable HF. The authors hypothesize that this may have been related to the excess of fluid administered during surgery, but they could not prove this notion in their study.

In the present study, BNP levels were not only predictive of mortality or heart failure, but also of postoperative AMI and angina. This finding corroborates the idea that BNP is a good marker not only of myocardial dysfunction, but also of myocardial ischemia, as previously demonstrated^11,12.

In patients with chest pain who seek the emergency room, it has been described that BNP levels increase even before the elevation of myocardial necrosis markers¹¹. Also, in patients with stable CAD, BNP predicts induced ischemia in stress tests¹².

Therefore, our data suggest that high BNP levels in asymptomatic patients could indicate silent ischemia, and the test could be useful to detect patients eligible for the investigation of myocardial ischemia by means of imaging methods in the preoperative period of non-cardiac surgeries.

In this study, a relevant finding was the fact that the ASA classification could not detect postoperative events. Although this classification is widely used, it is known to have limitations. Its subjectivity results in considerable interobserver variation^13-15. In a Spanish study, a questionnaire containing 10 hypothetical cases was handed out to 333 physicians among residents, anesthesiologists, and chiefs of service. Considerable interobserver disagreement was observed¹³. For this reason, cardiologists have chosen to use the Goldman classification.

Limitations

Echocardiography was performed in only 58 cases, thus limiting the comparison of BNP with echocardiographic information. However, the main objective of this study was to test the performance of BNP in comparison to conventional parameters of the medical history and physical examination. Thus, we conclude that our findings suggest that BNP could help select patients who need additional tests such as echocardiography or myocardial scintigraphy for a better definition of the postoperative cardiac risk. Also, despite the small number of patients undergoing echocardiography, no significant difference was found between the LVEF of patients with or without outcome measures.

Another limitation is that other surgical risk scores, such as Goldman or Lee classification, were not used. However, the ASA classification is the most widely used score in clinical practice in Brazil.

Potential Conflict of Interest

No potential conflict of interest relevant to this article was reported.

Sources of Funding

This study was funded by CNPq.

Study Association

This study is not associated with any post-graduation program.

References

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Publication Dates

• Publication in this collection
  24 Sept 2010
• Date of issue
  Dec 2010

History

• Accepted
  24 May 2010
• Reviewed
  06 May 2010
• Received
  09 Mar 2010