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Abstract
Objectives Worldwide, an estimated 10 million adults annually experience significant myocardial injury after non-cardiac surgery. Our aim is to assess whether preoperative and postoperative serum B-type natriuretic peptides levels (BNP) could be used as a predictor of postoperative complications in hypertensive and diabetic patients post non-cardiac surgery.
Design Prospective observational study.
Setting Single tertiary-care centre in northern India.
Participants This study included 260 adult participants with known hypertension and diabetes who were planned for elective non-cardiac surgery.
Interventions A preoperative BNP level (baseline BNP) was measured within 24 hours of surgery and another postoperative BNP level was measured within 24 hours of surgery.
Main outcome measures The primary outcome was the change in BNP levels (delta BNP) between the postoperative and the preoperative BNP levels (baseline BNP) with respect to the baseline BNP and the development of postoperative complications within 30 days of surgery.
Results The study established a correlation between delta BNP and baseline BNP (Pearson’s correlation coefficient=0.60; p=0.01). Our study found an increased serum BNP both in the preoperative period and the postoperative period in the patient group that developed complications, respectively (152.02 pg/mL±106.56 vs 44.90 pg/mL±44.22; t=4.120; p≤0.001); (313.99 pg/mL±121.29 vs 83.95 pg/mL±70.19; t=7.73; p≤0.001).
Conclusions We found that an increased serum baseline and postoperative BNP is potentially important predictor for the development of postoperative complications. Serum BNP has the potential to emerge as a cost-effective test for risk-stratification for postoperative complications in patients undergoing non-cardiac surgery. It has promising prognostic advantages including modification of surgical procedures, deferral of surgery and the ability to tailor therapy postoperatively.
- cardiac surgery
- echocardiography
- cardiac rehabilitation
- coronary artery bypass
Data availability statement
Data are available on reasonable request. All data relevant to the study are included in the article or uploaded as online supplemental information.
This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.
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WHAT IS ALREADY KNOWN ON THIS TOPIC
Preoperative serum B-type natriuretic peptides (BNP) is an independent predictor of perioperative cardiovascular complications.
WHAT THIS STUDY ADDS
Role of serum BNP as a predictive marker for postoperative surgical complications in non-cardiac surgery.
HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY
Serum BNP can substitute the existing array of expensive preoperative tests for risk-stratification of patients.
Need for further research with a larger population to elucidate the role of BNP in predicting surgical prognosis.
Introduction
Worldwide, an estimated 10 million adults annually experience significant myocardial injury after non-cardiac surgery.1 To mitigate this risk, strategies are needed that provide appropriate preoperative medical and surgical measures with postoperative surveillance and management.1 B-type natriuretic peptides (BNPs) are released from myocardial tissues in response to multiple physiological stimuli, including myocardial stretch, inflammation, myocardial ischaemia and other neuroendocrine stimuli. The 32-amino acid polypeptide BNP is secreted and attached to a 76-amino acid N-terminal fragment in the prohormone NT-proBNP (BNPT), which is biologically inactive. The biological half-life of BNP, however, is twice as long as that of atrial natriuretic peptide (ANP), making it a better target than ANP for diagnostic blood testing. The physiological actions of BNP include a decrease in systemic vascular resistance and central venous pressure as well as an increase in natriuresis. The net effect of these peptides is a decrease in blood pressure. Additionally, the actions of BNP results in a decrease in cardiac output due to a reduction in blood volume that follows natriuresis and diuresis.
Multiple studies have demonstrated that elevated preoperative serum BNP concentrations are powerful independent predictors of perioperative cardiovascular complications like mortality, myocardial infarction (MI) and heart failure.2 3 These are potentially avoidable causes of morbidity and mortality in patients undergoing non-cardiac surgery. The pre-existing data demonstrated that patients undergoing non-cardiac surgery with cardiac clinical risk factors should have preoperative NP testing as part of risk stratification.4
Hypertension and diabetes are risk factors for potential coronary artery disease. Thus, evaluation of the cardiovascular system in patients with hypertension is important to predict perioperative morbidity and mortality before undertaking non-cardiac surgery. At present, we lack a gold standard tool to effectively predict the perioperative or postoperative complications, length of hospital stay or mortality in hypertensive and patients with diabetes undergoing non-cardiac surgery. Preoperative evaluations of the cardiovascular system that use chest radiography, ECG, echocardiography and laboratory studies are limited. Furthermore, data on the relationship between preoperative and postoperative BNP levels and prognosis after non-cardiac surgery are scarce. The purpose of our study was to assess the role of BNP as predictors of postoperative complications in hypertensive and diabetic patients undergoing non-cardiac surgery.
Methods
The study was conducted in the Department of General Surgery at Paras HMRI Hospital, Patna, India, from December 2019 to June 2021. In this prospective observational study, we included 260 adult patients less than 70 years with known hypertension and diabetes who were scheduled to undergo elective non-cardiac surgery. The exclusion criteria for recruiting the patients in the study protocol were age <18 years and >70 years, normotensive and non-diabetic patients, patients undergoing cardiac surgeries, patients undergoing emergency non-cardiac surgeries, patients with left ventricle dysfunction (ejection fraction <40%), patients with baseline troponin positivity and immunocompromised patients. We excluded patients over the age of 70 years, as old age is independently associated with adverse surgical outcomes.
Collection of data
Each patient fulfilling the inclusion criteria was included in the study. Baseline BNP levels were measured preoperatively within 24 hours of non-cardiac surgery. The postoperative BNP levels were measured within 24 hours of the surgery. The measurement of BNP was performed in the same laboratory for all patients.
STrengthening the Reporting of OBservational studies in Epidemiology checklist for cohort reporting was completed.5 The corresponding author had full access to all data in the study and takes responsibility for its integrity and the data analysis.
Outcome measures
The primary outcome was the change in BNP levels (delta BNP) between the postoperative and the preoperative BNP levels (baseline BNP) with respect to the baseline BNP and the development of postoperative complications within 30 days of surgery. We defined a postoperative complication as one or more of the following events like surgical procedure-related complications and cardiac complications. Surgical procedure-related complications include haemorrhage, shock, wound infection, sepsis, embolism, deep vein thrombosis, urinary retention or lung problems. Cardiac complications include death, congestive heart failure, MI, acute coronary syndrome, unstable angina, cardiac arrest, cardiac arrhythmia resulting in haemodynamic instability requiring urgent intervention.
Data management and statistical analysis
Statistical analysis was performed with the help of IBM SPSS software. All continuous variables were expressed as the mean±SD. The t-test was used to compare mean, while the Mann-Whitney U test was used for median. Categorical variables were expressed as frequencies with respective percentages. A p-value of 0.05 was considered statistically significant. The correlation between preoperative BNP levels and delta BNP was calculated using Pearson’s correlation coefficient.
Results
Age versus sex distribution
In our study of 260 patients, the maximum number of cases was in the age group of 60–70 years in both male (74.02%) and females (70.75%) groups. The demographic data including body mass index and American Society of Anaesthesiologists (ASA) grade is shown in table 1.
Showing demographic data including BMI and ASA grade
In our study, 168 patients (64.6%) underwent surgery under general anaesthesia (GA), while 92 patients (35.4%) under spinal anaesthesia (SA). The open surgery was performed for 169 patients (65%), followed by laparoscopic approach in 87 patients (33.5%) and combined approach was employed in 4 patients only (1.5%) shown in table 2. The mean intraoperative duration was 1 hour with range from 30 min to 90 min. The intraoperative blood transfusion was done in seven patients only.
Showing type of surgeries
Baseline BNP levels versus complications
Postoperative complications were encountered in 17 patients (6.53%) . In these patients, the preoperative BNP level (baseline BNP) was found to be markedly high compared with those patients in whom complications were not seen (152.02 pg/mL±106.56 vs 44.90 pg/mL±44.22; t=4.120, p≤0.001) shown in table 3. To determine the significance of the difference in the mean, a t-test for independent samples was performed, which was significant (p≤0.001) at the 0.1% confidence level.
Baseline BNP versus complications
Postoperative BNP levels versus complications
Like baseline BNP, the postoperative BNP level was also found to be markedly high and statistically significant (p≤0.001) as compared with those patients in whom postoperative complications were not seen (313.99 pg/mL±121.29 vs 83.95 pg/mL±70.19; t=7.73, p≤0.001), which has been shown in table 4.
Postoperative BNP versus complications
Correlation between baseline BNP levels and delta BNP
To determine the relation between baseline BNP levels and Delta BNP, Pearson’s correlation coefficient was computed. Using Pearson’s correlation coefficient, it was concluded that baseline BNP levels and delta BNP were correlated. The value of Pearson’s correlation coefficient was found to be 0.60, which was statistically significant (p=0.01) as shown in table 5.
Correlation between preoperative BNP levels and delta BNP
The baseline BNP levels are not normally distributed across complication status as visually seen by Q-Q plot (figure 1). The median difference of 77 pg/mL in baseline BNP across two groups is statistically significant (p<0.001) as shown in table 6.
Q-Q Plot showing normality of baseline BNP across complication status. BNP, B-type natriuretic peptides.
Baseline BNP across complication status (n=260)
Postoperative complication
In our study, the postoperative complications were wound infection, sepsis, haemorrhage, arrhythmia, pneumonia and atelectasis as shown in table 7 and figure 2 . The 10-point surgical APGAR score (considering the estimated blood loss, lowest mean arterial pressure and lowest heart) was used to predict the postoperative complications. On this score out of 260 patients, 5 patients had an APGAR score of 6 and 2 had score of 7. The raised BNP level was found in all these seven patients.
Distribution of postoperative complications
(Bar diagram) showing postoperative complications.
In our study, metabolic equivalent to task score more than 10 was seen in only 10 patients as shown in table 8 while cardiac risk factors of the participants has been shown in table 9. The Revised Cardiac Risk Index (Lee score) was also used. As per this index, 125 patients underwent high risk surgery, 45 patients with diabetes were on insulin, while 22 patients with diabetes on insulin underwent high-risk surgery with low risk in first two groups, and moderate risk in last group of patients, respectively, as shown in table 10.
Showing MET score
Showing cardiac risk factors
Showing significant Lee score
Discussion
Statement of principal findings
In our study, the average age of the patients ranged between 58 and 68 years out of 260 patients. Seventeen patients (6.53%) experienced postoperative complications, including surgical and cardiovascular. Our study found increased serum BNP levels both in the preoperative and the postoperative period in the patient group that developed complications. The decision-making tree according to the BNP level has been shown in figure 3. Interestingly, the delta BNP level was also observed to be related to complications in the patient population compared with the group that did not develop complications. In our study, we also demonstrated that delta BNP has a significant correlation with the baseline BNP level.
Showing the decision-making tree according to the BNP level. BNP, B-type natriuretic peptides; CXR, chest X-ray; CBC, complete blood count; ECHO, echocardiogram; MET, metabolic equivalent to task; PFT, pulmonary function test.
Strengths and weaknesses of the study
Strengths of the study
The timing of the BNP sampling was kept uniform within 24 hours pre and post non-cardiac surgery.
The measurement of BNP was performed in the same laboratory for all patients.
The study was successful in obtaining individual-level data on 260 patients.
Our study results are consistent with other similar studies conducted.
Weaknesses/limitations of the study
First, the study was conducted on an adult population, thus it may not apply to the extreme age group (<18 years and >70 years).
Second, our research was observational, thus we were able to show a correlation but not prove causality.
Also, data collection by a single investigator may have been associated with investigator bias.
The study was conducted in a single centre with a patient follow-up period for up to 30 days post non-cardiac surgery. Thus, the results may not be generalised to other centres.
Strengths and weaknesses in relation to other studies, discussing important differences in results
In our study of 260 patients, 17 patients (6.53%) experienced postoperative complications. A study by Cuthbertson et al6 observed a cut-off point of 40 pg/mL for preoperative BNP levels as a predictor of perioperative death or acute myocardial injury in patients undergoing non-cardiac surgery. It differentiated patients with a sevenfold increased risk of cardiac events in the early postoperative period. A preoperative BNP level above this threshold was also associated with an increased postoperative hospital stay.6 In our study, the mean baseline BNP was 152.02 pg/mL with SD 106.56 pg/mL (range: 45.46–258.58 pg/mL). A study by Karthikeyan et al included a total of 3281 patients, among whom 314 (9.5%) patients experienced a perioperative cardiovascular complication.3 The decision threshold for BNP used in the study varied widely between 40 pg/mL and 189 pg/mL. The study demonstrated that a preoperative BNP measurement was an independent predictor of cardiovascular complications within 30 days of non-cardiac surgery. According to Goetze et al, the ability of BNP to predict outcomes in the peri-operative setting likely relates to its exquisite sensitivity to changes in ventricular function, both systolic and diastolic.7 The potential for serum BNP measurement in preoperative risk stratification lies in its ability to integrate the impact of multiple preoperative pathophysiological processes into a single measurement.8 9 Recent evidence also suggests that among patients with chronic stable coronary disease, serum BNP levels have the potential to reflect the presence and severity of the underlying cardiac pathology.10 The NT-proBNP is also an alternative marker to predict the perioperative cardiac complications supported by many studies.11 12 But in our set up especially in the low/middle-income countries such as India where cost is the major constraint and ease to get the result quickly, definitely BNP becomes a better option as compared to NT-proBNP. Previous meta-analyses suggest that a single elevated preoperative BNP level is highly predictive of serious cardiovascular complications after non-cardiac surgery and may be a better predictor of these events. Measuring BNP in adults undergoing major non-cardiac surgery thus significantly improves preoperative risk stratification and could easily be incorporated into clinical practice, particularly in patients undergoing major intraperitoneal, intrathoracic, orthopaedic or vascular surgery, and would allow clinicians to strategise prophylactic measures in patients identified as high-risk patients. A preoperative BNP test might represent a cost-effective way of assisting in the identification of patients who would benefit from more intensive, and costly, preoperative testing and facilitate targeted interventions that may reduce morbidity and mortality.
Unanswered questions and future research
Further work is needed to determine the utility of BNP in combination with existing risk stratification tools. Research is needed to statistically establish BNP thresholds and to determine the cut-off point. This requires the evaluation of a large number of patients across the spectrum of perioperative risk undergoing a broad range of surgical procedures. Similarly, it is crucial to identify that the prognostic data obtained from the measurement of BNP remain imperfect. The predictive accuracy of existing methods might improve with more knowledge regarding BNP levels with further studies such that a strategy combining simple clinical parameters and BNP will be the most appropriate.
Conclusion
We found that an increased serum baseline and postoperative BNP is an independent predictor for the development of postoperative complications. Serum BNP has the potential to emerge as a cost-effective test for risk stratification for the postoperative complications in patients undergoing non-cardiac surgery. It has promising prognostic advantages including modification of surgical procedures, deferral of surgery and the ability to tailor therapy postoperatively. We can measure BNP preoperatively and postoperatively for every patients with hypertension and diabetes undergoing major surgery to pick up any silent pan-cardiac pathology, and also to risk-stratify patients deemed at high risk to develop surgical complications.
Data availability statement
Data are available on reasonable request. All data relevant to the study are included in the article or uploaded as online supplemental information.
Ethics statements
Patient consent for publication
Ethics approval
This study involves human participants and was approved by Scientific Research Committee, Paras HMRI Hospital, Patna.SRC/IEC/PHMRI/Faculty/139/2021 dated 27/08/2021Institutional Ethics committee Paras, HMRI Hospital for Biomedical and Health researchSRC/IEC/PHMRI/Faculty/140/2021 dated 28/08/2021. Participants gave informed consent to participate in the study before taking part.
References
Footnotes
Twitter @surgeonsingh, @anil4aiims
Contributors AS, AK, AAH, MM, NT and PKS contributed to the conception or design of the work. All coauthors contributed to the acquisition, analyses or interpretation of data for the work. AK drafted the manuscript. All co-authors critically revised the manuscript. All gave final approval and agreed to be accountable for all aspects of work ensuring integrity and accuracy. The corresponding author (AK) had full access to all data in the study and takes responsibility for its integrity and the data analysis. AK acts as the guarantor, and accepts full responsibility for the work and conduct of the study, had access to the data and controlled the decision to publish.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed.