Blog with interesting cases and/or problems related to anesthesia with discussion based on best evidence in the literature.

August 9, 2016

elevated preoperative BNP, what do I do now?

A rather unhealthy and unkept gentleman of about 54 years of age presented to the ER after a 'fall'.  He presented to the preop area as an add for intertrochanteric nail by our friendly orthopedic surgeon.

I was assigned the case and went over to look through the chart.

I noted a cardiology note that indicated that his troponin levels were very slightly elevated and an echocardiogram was recommended by the cardiology NP. Since this gentleman, had an injury that was better treated sooner than later (more discussion on this below), and he did not have an EKG with any indication of ischemia, I was not convinced that delaying his surgery for an additional day to perform an echo was absolutely required.  I continued to look for more information to determine the liklihood that an his slight bump in troponins represented something truly sinister, or was perhaps more benign in nature.  It was known that he was likely homeless, dehydrated, and had a mild elevation in his BUN and creatinine consistent with pre renal azotemia in a dehydrated (hypovolemia) patient.

A further review of his chart revealed that he also had a BNP of over 1200 pg and lasix had been ordered by the ER physician, but not yet administered due to various logistical issues.  At this point, I decided to call the Ortho surgeon and have a conversation with him.  After discussing it with him, a decision was made to cancel the surgery until his volume level could be better determined, and optimized.
Patients in heart failure are poor candidates for surgery.  Post operative morbidity and mortality is significantly higher; and any elective surgery is contraindicated when if patients are in failure.  is predictor of poor outcome in non cardiac surgery.  Typically, it is best to post pone non emergent surgery in patients suspected or known to be in hear failure.  Unfortunately, clinical signs of heart failure (dyspnea, jugular vein distention, leg swelling etc) are not perfect indicators of a patient's status.  Current evidence suggests that hip fracture patients have better outcomes when the fracture is repaired within 24 hours of admission.  Therefore, an anesthesiologist who makes a decision to delay hip fracture surgery may potentially increase overall  risk to the patient in an attempt to improve the patients perceived short term risks.

Atrial Natriuretic Peptide (ANP) was originally isolated from rat atrial myocardium. In humans, it is secreted predominantly by atrial myocytes.  BNP was subsequently isolated from porcine brains. In humans it is secreted by both atrial and ventricular myocytes, but it is predominantly the ventricular myocytes that secrete BNP. These natriuretic peptides have several functions in normal physiology. When cardiac myocytes are stretched due to increased load or volume, secretion of these peptides results in: 1) down regulation of the sympathetic nervous system, and the renin-angiotensin-aldosterone system, 2) improved natriuresis and diuresis via afferent and efferent hemodynamic mechanisms of the distal tubule of the kidney, 3) decreasing peripheral vascular resistance via relaxation of smooth muscle. A BNP precursor is secreted by left ventricular myocytes which is synthesized into proBNP.  This short lived molecule is cleaved into the biologically active C terminal portion and biologically inactive N-terminal (NT-proBNP) portion.

In a observational study, BNP was found to be an independent predictor of increased cardiac events after non cardiac surgery and performed better than a preoperative scoring system after abdominal surgery [1].
It is known that BNP levels correlate with demodynamic parameters such as right atrial pressure, PCWP, and left ventricular end diastolic pressures.   Echo studies looking at the correlation of BNP levels with ventricular function have also been done.  Usuing the NYHA classificaiton system we find that in class I, BNP averages 240 pg, II 390 pg, III; 640 pg and IV 820 pg.  This indicates that higher levels do seem to correlate with more significant cardiac dysfunction.

In 2002, the national breathing not properly (BNP) trial was completed and was able to show that plasma BNP measurement was able to differentiate between CHF  and non CHF causes of dyspnea (area under receiver operating characteristic curve = 0.91) [2]. In this trial, a single BNP measurement was also more accurate than two commonly used methods of determining cardiac causes of SOB, the National Health and Nutritional Examination score and Franghiham (see below).

Using data from this same study, a patient presenting with SOB, and a BNP less than 50 pg/mL has an 7% chance that the cause is heart failure. If the BNP is between 50 pg/mL and 150 pg/mL, the chance that heart failure is the causes rises to 36%.  With a BNP of greater than 150 pg/mL, there is an 83% chance of heart failure. Later, another study concluded that if the BNP level was less than 100 pg/mL, there was a low liklihood for congestive heart failure.  Alternatively, in this study, they concluded that blood levels greater than 500 pg/mL made a diagnosis of heart failure extremely likely [3].

In another smaller study, dao et al. showed that a BNP of less than 80 pg/mL had a 98% negative predictive value. In this same trial, patients  with dyspnea and diagnosed with CHF had a mean BNP of 1076 pg/mL while patients who had dyspnea but were found not to be in heart failure had a mean BNP of only 38 pg/mL.  
A study of patients undergoing non cardiac surgery found that an elevated BNP measurement was an independent predictor of postoperative cardiac events. In this study, BNP measurements outperformed the goldman multifactorial clinical index in predicting cardiac adverse events after non cardiac surgery.  (fee figures below for a great summary of this study).

They showed that a BNP level of 0 to 100 pg/mL had zero risk,  BNP levels of 201-300 pg/mL was considered low risk (5% event rate),  intermediate risk (12% event rate) was from 200 to 300 pg/mL, and high risk (greater than 300 pg/mL) had an event rate of 81% [4]. This was followed up with another study that was able to demonstrate that BNP levels greater than 40 pg/mL was associated with a seven fold increase in cardiac events in the early post operative period and longer hospital stay [5]. Yeh et al. found that pre operative NT pro-BNP independently predicted cardiac complications in non cardiac surgery (greater than 450 ng/L) with 100% sensitivity and 83% specificy [6].

The clinician should recognize that there are several causes other than heart failure that can result in elevated BNP levels.  These include renal failure (decreased clearance), pulmonary embolism, pulmonary hypertension, and chronic hypoxia.  Furthermore, BNP increases along with age. A trial was able to determine five independent predictors of elevated BNP in patients without heart failure.  They were 1) low hemoglobin values, 2) low BMI, 3) history of A fib 4) radiographic cardiomegaly, and 5) advanced age. This is why this test has been found to have very good sensitivity, but not great specificity.  Put another way, if the BNP is normal, the clinician has very high confidence that the patient is not currently in CHF or that cardiac complications will be low.  However, the opposite is not true; if the BNP is elevated, the clinician cannot be as confident that the case should be cancelled or delayed because of certain CHF in the patient.  However, ruling out the above other causes of elevated BNP can aid the clinician in ruling out other sources of an elevated BNP.

BNP also tracks appropriate therapy.  Therefore, patients being treated with ACE inhibitors and diuretics will have lower than typical BNP levels, while other medications may increase BNP (beta blockers and digoxin).

Unfortunately, at this point, rigorous testing in the preoperative setting to determine cut off points for BNP levels in order to determine whether cases should be cancelled or not have not been done.  In "up to date" the following quote relays the current recommendations regarding the use of BNP in the preoperative period to aid in evaluation of the patient: "However, it is unknown whether or which changes in perioperative management would improve outcomes in surgical patients with elevated BNP or NT-proBNP levels".

Determining when to delay or cancel hip fracture surgery is often a challenge for the anesthesiologist. Particularly since this population of patients generally have significant co morbidities that would result in cancelation or delay in purely elective surgery.  Orthopedists are becoming more aggressive in trying to bring their patients to surgery within 24 hours of injury because of numerous observational trials indicating that early hip fracture surgical repair leads to better functional outcome and lower rates of complications and mortality. In fact, current guidelines recommend surgery within 24 hours of injury [6].  Early surgery has also been included as a quality marker in the highly disseminated set of Inpatient Quality Indicators from the Agency for Healthcare Research and Quality [7].  So, would my patient be better off, overall,  if I had administered lasix in the holding area, and proceeded to surgery within the next 30 minutes to hour?
Observational trials are prone to selection bias, attrition and detection bias.  Prospective observational trials are more robust generally than retrospective trials, but a recent systematic review found that currently, 65% of studies addressing this issue are retrospective, and therefore, subject to confounding and biased ascertainment of outcomes. One of the most obvious problems with retrospective observational trials is that patient who are sicker are more likely to be delayed and therefore, have a larger time delay between the injury and the surgery.  Therefore, it is likely that patients will have better outcomes in the 'early' surgery group vs. the later surgery group because the early surgery group is a healthier cohort.  As an example, a recent large [8] retrospective observational trial in Spain looked at over 81,000 patients who had hip fracture surgery.  They found a positive correlation with early surgery and lower in hospital mortality.  However, after correcting for a multitude of variables, they found that indeed, patients at much higher risk had delayed surgery, and after correcting for this, there was no longer any effect on mortality from delaying surgery.  In another study, the authors were able to demonstrate that individualizing the timing of surgery to medically optimize patients at higher risk led to improved outcomes [9]. Vidan et al. and Khan et al also showed that when controlling for medical co-morbidities, timing of surgery ceased to be a factor in mortality difference between groups [10,11]. Still, while it seems difficult to say that mortality is improved with early surgery after injury (within 24 hours), other important metrics may be apt for improvement.  Investigators have found that time to discharge was 10.9 days earlier  if surgery is performed within 48 hours [12], and another study concluded that surgery within 24 hours decreased LOS by 4 days [13].  Other clinically relevant benefits found with early surgery include a decrease in the incidence of decubitus ulcer formation and an increased likelihood of return to independent living.
In summary, at this point, due to lack of prospective RCTs, it is not clear that early surgery (within 24 to 48 hours of injury) can reduce mortality.  However, other parameters, such as LOS, pressure ulcer formation and long term functional recovery may be improved by early surgery.  While guidelines recommend that patients go to the OR for operative repair within 24 to 48 hours of injury, the anesthesiologist should feel confident that a delay in surgery to allow for medical optimization of severe evolving medical conditions is warranted.  Each case should be judged by its own merits and the anesthesiologists should play a role in not obstructing early surgery unless truly necessary. As an example, I recently reported on a case where a patient with a hip fracture was admitted for operative repair, but the gastroenterologist recommended a transfer because the patient had severe liver dysfunction.  The orthopedist called me and I recommended proceeding with surgery given the enormous delay caused by a transfer and lack of evidence that further optimization could improve the patients outcome.  This case proceeded as scheduled, although, the gastroenterologist, inked in the chart that he recommended a spinal which created a medico legal issue for the anesthesiologist.

1. Mercantini P, et al. Preoperative brain natriuretic peptide (BNP) is a better predictor of adverse cardiac events compared to preoperative scoring system in patients who underwent abdominal surgery.  World J Surg 2012 Jan;36(1):24-30.
2. Maisel AM, Krishnaswamy P, Nowak R, et al. Bedside B-type natriuretic peptide in the emergency diagnosis of heart failure: primary results from the Breathing Not Properly (BNP) Multinational study. Paper presented at: 51st Annual Scientific Session of the American College of Cardiology;March 17–20,2002; Atlanta, Ga.

  • 3. Mueller C
  • Scholer A
  • Laule-Kilian K
  • et al
  • Use of B-type natriuretic peptide in the evaluation and management of acute dyspneaN Engl J Med 2004;350:647-54.

    1. 4.  Dernellis J
    2. Panaretou 
    Assessment of cardiac risk before non-cardiac surgery: brain natriuretic peptide in 1590 patients. Heart 2006;92:1645-50
    1. 5. Cuthbertson BH
    2. Amiri AR
    3. Croal BL
    4. et al
    The utility of B-type natriuretic peptide in predicting perioperative cardiac events in patients undergoing major non-cardiac surgeryBr J Anaesth 2007;99:170-6.Yeh HM, Lau HP, Lin JM, et al. Preoperative plasma N-terminal pro-brain natriuretic peptide as a marker of cardiac risk in patients undergoing elective non-cardiac surgery. Br J Surg2005;92:1041–5
    6.  Fractured neck of femur. Prevention and management. Summary and recommendations of a report of the royal college of physicians.  J R Coll Physicians Lond 1989 Jan:23(1):8-12
    7. Department of Health and Human Services. Agency for Healthcare Research and Quality: AHRQ Quality Indicators. Guide to Inpatient Quality Indicators: Quality of Care in Hospitals - Volume, Mortality, and Utilization. Version 3.1, March 12, 2007
    9.  Zagrodnick J, Kaufner HK. Decreasing risk by individualized timing of surgery of para-articular femoral fractures of the hip in the elderly.
    10.  Vidán MT, Sánchez E, Gracia Y, Marañón E, Vaquero J, Serra JA.. Causes and effects of surgical delay in patients with hip fracture: a cohort studyAnn Intern Med. 2011;155(4):226–233
    11.  Khan SK, Kalra S, Khanna A, Thiruvengada MM, Parker MJ.. Timing of surgery for hip fractures: a systematic review of 52 published studies involving 291,413 patientsInjury. 2009;40(7):692–697
    12. Siegmeth AW, Gurusamy K, Parker MJ.. Delay to surgery prolongs hospital stay in patients with fractures of the proximal femurJ Bone Joint Surg Br. 2005;87(8):1123–1126
    13. Al-Ani AN, Samuelsson B, Tidermark J, et al. . Early operation on patients with a hip fracture improved the ability to return to independent living. A prospective study of 850 patientsJ Bone Joint Surg Am. 2008;90(7):1436–1442

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