Abstract
Background: Tight blood pressure control is a cornerstone of postoperative cardiac surgery patients. In addition, plasma lactate levels are frequently monitored in this setting as it is a marker for malperfusion, with early elevated levels being associated with increased morbidity and mortality. Elevations from malperfusion may be due to decreased cardiac output, hypovolemia, or persistent post-bypass vasoplegic response. Here, we investigate whether lower blood pressures, significant changes from baseline, and cardiac perfusion pressures delay the clearance of lactate after cardiac surgery. Methods: This is a retrospective cohort observational study of patients who have undergone coronary artery bypass graft (CABG) and valve replacement or repair surgeries at NYU Langone Long Island Hospital over a 6-month period. Postoperative blood pressures and lactate levels were examined over the first 16 h of care. Primary outcome: The relationship between blood pressure parameters and lactate clearance. Secondary outcomes: ICU length of stay, hospital length of stay, and mortality. Results: A total of 81 patients met inclusion criteria. The average pre-operative mean arterial blood pressure (MAP) was 95.4 mmHg and the average MAP in the first 6 h post-operatively was 78.4 mmHg. The average change in MAP from baseline was a decrease of 16.7%. The average cleared lactate fraction by 16 h postoperatively was 85.9%. Lactate clearance was associated in a statistically significant way only with the need for inotropic support on postoperative day 1, p = 0.03. There was a slight trend toward a delay in lactate clearance in those with lower early systolic blood pressures, p = 0.14. Conclusions: Lactate clearance appears to occur largely independently of postoperative blood pressures in the first 16 h after surgery but may be delayed in those requiring inotropic support through the morning or postoperative day one.
1. Introduction
Optimal hemodynamic management in the immediate timeframe after cardiac surgery is key for limiting complications and ensuring rapid recovery. Often used as a marker for hemodynamic effectiveness, elevations in lactic acid are common after cardiac surgery. This retrospective analysis examines the question of whether lower blood pressures and cardiac perfusion pressures affect the clearance of lactic acid after cardiac surgery to better estimate optimal hemodynamic targets.
There are multiple causes for lactic acidosis after cardiac surgery. These include residual lactate from the globally hypoperfused and tissue hypoxic states that exist while on cardiopulmonary bypass (CPB), increased production triggered by excess catecholamines, cytokines, and cortisol, reperfusion injury after hypoperfusion and hypothermia, impaired hepatic clearance during CPB, and microvascular dysfunction related to a systemic inflammatory response [1,2,3,4]. Early postoperative elevated lactate levels are common after cardiac surgery with incidence of elevations greater than 3 mmol reported to occur in 10–20% of patients [5]. Early elevated levels, measured in the first hour postoperatively, have been shown to be associated with increased rates of complications and increased morbidity and mortality. By comparison, late lactate increases, occurring after the first hour, were shown to be likely benign and transient, without significant worsening of outcomes [6].
Clearance of postoperative lactate depends on adequate perfusion and intact liver function where circulating lactate is converted to pyruvate. While it is common practice to address elevated lactate levels by increasing preload and central venous pressure (CVP), there is no evidence that this practice is effective and there is evidence that volume expansion in this population may be harmful [7,8,9]. Lactate clearance may be correlated to blood pressure targets postoperatively as pressures below the patient’s baseline may result in persistent malperfusion in the setting of hypertensive vascular remodeling. Since hypertension remains the most common comorbidity for coronary artery disease, as much as 80%, the prevalence of hypertensive vascular remodeling in the cardiac surgery population is high [10]. It remains common practice in cardiac surgery, despite an absence of supporting evidence, to maintain strict postoperative blood pressure ceilings to avoid hemorrhage from anastomotic compromise or small vessel bleeding.
Beyond vascular remodeling, organ autoregulatory changes may contribute to a persistent lactate. These mechanisms that promote continuous blood flow for organ perfusion in the setting of non-homogenous vascular beds, are known to be impaired after CPB, potentially leading to local malperfusion or ischemia in susceptible tissues [4,11]. While this rationale is the source of the well-established practice of allowing and inducing higher blood pressures in the setting of acute neurologic injury, this has not become common practice in the cardiac surgery population [12]. In neurologic injury, this practice is designed to ensure adequate cerebral perfusion pressures, defined as mean arterial pressure minus intracranial pressure. Similarly, in cardiac surgery, coronary perfusion pressure (CPP) is defined as diastolic blood pressure minus left ventricular end-diastolic pressure, a pressure that can be estimated from the pulmonary diastolic pressure. The choice of relatively low blood pressure targets after cardiac surgery leads to lower diastolic pressures and consequently CPPs. This could, in theory, create additional myocardial oxygen demand and increased lactate production.
In addition, lower blood pressure targets could also perpetuate local or systemic hypoperfusion and could lead to impaired lactate clearance or persistent lactate production. To investigate this, we examined the relationship between both absolute and baseline-relative blood pressures and lactate clearance as measured by fraction of lactate cleared by the morning after surgery.
While mean arterial pressure (MAP) has traditionally been the primary hemodynamic target for ensuring organ perfusion, this assumption has not been validated in the post-CPB population, in which autoregulation may be impaired in the setting of vasculopathic vessel remodeling. However, our analysis did not focus primarily on MAP but rather on CPP since coronary artery perfusion occurs predominantly during diastole and is, therefore, more dependent on diastolic pressures than on MAP. This approach was intended, in part, to explore whether evidence exists for a diastolic threshold below which coronary perfusion becomes compromised and lactate clearance might be impaired.
2. Materials and Methods
For this study, we performed a retrospective observational chart review study of patients undergoing CABG and valve replacement or repair surgeries at NYU Langone Long Island between 1 January and 1 July 2022, as a convenience sample. This six-month window was chosen because institutional practice pattern changed thereafter, and further inclusion would have resulted in significant heterogeneity. The retrospective design was selected because practice patterns and provider preferences resist intentional manipulation of postoperative pressures in the immediate recovery period after cardiac surgery. This approach was therefore the most pragmatic and feasible for an exploratory question. All cases performed during the time-period were reviewed. Cases were excluded primarily based on the absence of a pulmonary artery catheter or lactate data.
We recorded hemodynamic parameters including systemic and pulmonary blood pressures, lactate levels immediately postoperatively and on the morning of postoperative day (POD) 1, as well as ICU length of stay, hospital length of stay, and mortality. CVP measurements were not included in the primary analysis as the preponderance of evidence suggests that it is not a reliable predictor volume responsiveness and a poor correlate for lactate clearance [7,9]. Patients with baseline pulmonary hypertension or mitral stenosis were excluded, as were patients who did not have pulmonary artery catheters in place or who were missing lactate values, see Table 1. Pulmonary diastolic pressures were used as a proxy from left ventricular end-diastolic pressures (LVEDP) for purposes of CPP calculation. This proxy has been previously validated in patients without pre-existing pulmonary hypertension [13]. The first four hours postoperative with reported as averages due to common fluctuations, and peak and nadir values were identified from the first 16 h.
Table 1.
Baseline Demographics.
Documentation of whether vasoactive agents, including pressors and inotropes, was recorded without respect to dosing, as these were low in all cases. The rationale for this choice was that the variable of interest, the hemodynamic measurement, was the cumulative result of both intrinsic physiology and extrinsic support, and the association of interest related to the absolute number regardless of the relative contributions of these two processes. Of note, as high dose epinephrine is known to potentially increase lactate levels, it must be noted that the only inotropic support used in this sample was dobutamine.
The primary outcome was lactate clearance as determined by the fraction above 1 mmol/L that cleared from the initial lactate to the measurement on the morning of POD 1. One mmol/L was used as a cutoff for a normal value that excluded mild elevations. The calculation used to determine lactate clearance (LC) utilized initial lactate value (ILV) and first postoperative morning lactate value (PMLV).
LC = 1 − [(1 − PMLV)/(1 − ILV)]
Secondary outcomes included length of stay in the ICU and hospital and in-hospital mortality. The data were analyzed using linear regression with a significance level of p = 0.05. All statistical analyses were performed using SPSS Statistics version 28 software (IBM, Armonk, NY, USA). Continuous variables were analyzed using Pearson’s correlation, and categorical variables using linear regression. p-values less than 0.05 were considered significant. Given the sample size, subgroup analyses stratified by vasoactive agent use were not performed, as further divisions of the cohort would have prohibitive limitations to statistical power. Vasoactive therapy was instead treated as a binary variable in the analysis. This study was approved by the institutional review board (IRB) of NYU Langone (s22-00962). As a retrospective observational study, this was granted waiver of consent by the IRB.
3. Results
One-hundred and ninety-three charts were reviewed, of which 81 (42.0%) met inclusion criteria. Sixty-five were excluded for lack of a pulmonary artery catheter, and 47 were excluded for missing data. Of those included, 75.3% were male and 24.7% female. 49 (60.5%) underwent isolated CABG, the remainder were divided among isolated valve replacement, combined bypass and valve and ascending aortic surgery. Twenty-three (28.4%) required pressors through the morning of post-operative day 1, and 29 (35.8%) required inotropic support. See Table 1.
The average pre-operative mean blood pressure was 95.4 mmHg (95% CI: 72.0–119.0) The average postoperative mean arterial pressure in the first 6 h was 78.4 mmHg (95% CI: 63.0–94.0). The mean calculated coronary perfusion pressure during this period was 43.2 mmHg (95% CI: 25.0–62.0). The mean change in MAP from baseline was −16.7% (95% CI: −40.3 to +6.9%). Twenty-three patients (28.4%) required pressors the morning of POD 1. Twenty-nine patients (35.8%) required inotropic support the morning of POD 1. Please see Table 2 for additional detailed blood pressures.
Table 2.
Postoperative blood pressure and perfusion variables (n = 81). Values are expressed as a mean ± standard deviation (SD), range, and 95% confidence internal unless otherwise indicated. All pressures are reported in millimeters of mercury (mmHg). Length of stay are reported in days. In-hospital mortality is expressed as a number (percentage) only, since range and CI are not applicable.
The average ICU and hospital lengths of stay for the group were 3.6 days and 6.5 days, respectively. One patient died within 30 days. 38.3% experienced an increase in lactic acid post-operatively. The average fraction of lactate cleared by 16 h post-op was 85.9% (95% CI 37.7–134.1%, greater than 100% represents a morning lactate of less than 1 mmol/L). On regression analysis, the percent of cleared lactate was negatively associated with the need for inotropic support at 16 h post-op, p = 0.03, but did not reach statistical significance with any of the blood pressure combinations or need for pressors. There was a slight trend toward delayed clearance with lower initial systolic pressures, p = 0.14, See Table 3.
Table 3.
Correlations between postoperative values and percent lactate clearance. Pearson’s correlation coefficients (r) and corresponding p-values for associations between hemodynamic variables and lactate clearance at 16 h postoperatively. Significant correlations are indicated in bold (p < 0.05).
A minority (38.3%) experienced an increase in lactic acid post-operatively. The average fraction of lactate cleared by 18 h post-op was 85.9%, SD 24.1%. On regression analysis, the percent of cleared lactate was negatively associated with the need for inotropic support at 18 h post-operatively but did not reach statistical significance with any of the blood pressure combinations including change from pre-operative baseline, or the need for pressors. A minority (38.3%) experienced an increase in lactic acid post-operatively, see Table 3.
4. Discussion
The data presented in this limited study did not support the experimental hypothesis that lower blood pressures, including diastolic and coronary perfusion pressures, or significant decreases in blood pressures from baseline would result in a statistically significant decreased fraction of lactate clearance. These findings should be interpreted in the context that our cohort maintained MAPs predominantly within established ranges with only a minor (~16%) decrease from baseline. No measured value represented a significant deviation from the normal physiologic limits, and global organ perfusion supported by MAP would therefore be expected to remain intact. Although some patients exhibited lower diastolic pressures, no correlation was observed. This might have been further elucidated through the including of SvO2 data, but they were not consistently recorded in this cohort.
Postoperative lactate fluctuations are complex and depend on microcirculatory recovery, endothelial dysfunction and hepatic clearance in addition to perfusion-dependent lactate production. Because these processes occur simultaneously and interactively, isolating the contribution of any single mechanism is challenging. This process has been well documented in several animal models, and CPB is known to cause a dissociation of macro-hemodynamics and microcirculatory perfusion [4]. While this study attempted to determine whether diastolic pressures and CPP might particularly represent a significant limitation to clearance, the multifactorial nature of the problem may have masked any subtle signal within the largely normal range.
Our study did show a relationship between inotrope use on POD 1 and delayed lactate clearance. As the only inotrope included in the study was dobutamine at a dose at or less than 5 micrograms per kilogram per minute, we speculate that the observed association between inotrope use and slower lactate clearance likely reflects the effects of underlying myocardial dysfunction rather than a direct pharmacologic effect.
Although CVP is widely used to guide fluid resuscitation in response to elevated lactates, prior studies have shown that it is a poor predictor of tissue perfusion or lactate clearance, particularly after cardiac surgery [8,14]. Within this context, failure to show a correlation between lactate clearance and postoperative blood pressures further supports the idea that lactate clearance may be more dependent on metabolic recovery rather than circulatory pressures or preload [15].
To date, no previous studies were identified that have examined this specific topic. Multiple studies exist that show delay or failure of lactate clearance has a strong association with morbidity and mortality after cardiac surgery, but they do not include associative data on blood pressures [4,16]. There are a number of studies, however, that address the formation of lactate based on targeted MAPs while on CBP and include associated outcomes. Targeting higher MAPs while on CPB is associated with less lactate formation which in turn is associated with improved outcomes overall [17,18,19].
Our observed results in respect to blood pressures and lengths of stay are consistent with commonly reported values in U.S. tertiary care cardiac surgery populations [20]. It is, however, important to note that often a common confounder for ICU length of stay is hospital overcrowding and the lack of available non-ICU telemetry beds, and this certainly is the case at our institution. This limits the interpreting utility of this variable in this setting. In contrast, many international sources report significantly shorter ICU lengths of stay.
A 2024 observational study showed that as little as one minute of MAP < 65 mmHg was statistically significantly associated with acute renal injury [21]. Based on the established studies of autoregulation and organ compromise in hypotension, the null result in this study suggests that lactate clearance depends much more on other factors such as liver washout or intra-operative production, than on persistent production from hypoperfusion in the post-operative period.
This study has a number of limitations. Initially, the retrospective observational design limits evaluation to pressures that were actively maintained in a typical normal range and did not include significant extremes that might have shown significance. This was a deliberate choice because extreme pressures in the postoperative period would have posed significant ethical concerns. While this limits causal inference, the design nevertheless can still serve as a basis for further prospective designs. Additionally, this study examined a relatively small sample which increases the likelihood of a type II error. This limited sample size also prevented a subgroup analysis based on specific vasoactive agent use or dose range. The multiple sources of lactate render it a non-specific marker and may not help to establish blood pressure targets. The recorded point values used to capture blood pressure from chart records may not appreciate temporary or limited changes which may have a large effect. Additionally, improved perfusion from new cardiac grafting likely has a significant effect on coronary autoregulation.
Given these data, we can make no specific clinical recommendation based on this negative study. Future studies would be required to elucidate lactate production and clearance based on post-operative perfusion. Additionally, the important clinical endpoint of a relevant target postoperative blood pressure, either absolute or relative to the patient’s known baseline, requires further retrospective and prospective investigations.
5. Conclusions
Within a typical range of postoperative blood pressures after cardiac surgery, we did not identify a relationship between calculated coronary perfusion pressures or mean arterial pressures and lactate clearance. These findings suggest that clearance in the early postoperative period is dependent on other mechanisms than expected variations in perfusion pressures. Larger, prospective studies will be needed to confirm these observations and clarify optimal hemodynamic targets.
Author Contributions
Conceptualization, J.H. and M.K.; methodology, J.H., M.K. and G.E.-B.; software, J.H.; validation, J.H., M.K. and G.E.-B.; formal analysis, J.H.; investigation, J.H., M.K. and G.E.-B.; data curation, J.H.; writing—original draft preparation, M.K. and G.E.-B.; writing—review and editing, J.H.; supervision, J.H.; project administration, J.H. All authors have read and agreed to the published version of the manuscript.
Funding
This research received no external funding.
Institutional Review Board Statement
The study was conducted in accordance with the Declaration of Helsinki, and approved by the Institutional Review Board of NEW YORK UNIVERSITY (protocol s22-00962, 11 February 2024).
Informed Consent Statement
Our study was performed on only retrospective data without any direct patient participation. As such, we applied for and were granted a waiver of consent from the IRB due to the existence of minimal risks to the patient related to inadvertent disclosure of patient information, which did not occur.
Data Availability Statement
The raw data supporting the conclusions of this article will be made available by the authors on request.
Conflicts of Interest
The authors declare no conflicts of interest.
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