Authors: Karen Zhao (1Faculty of Health Sciences, McMaster University, Hamilton, Canada), Renée Fournier (1Faculty of Health Sciences, McMaster University, Hamilton, Canada), Kevin Kennedy (2School of Population and Public Health, University of British Columbia, Vancouver, Canada), Hilary Grocott (3Department of Anesthesiology, Pharmacology, and Therapeutics, University of British Columbia, Vancouver, Canada), Emilie Belley-Côté (4Population Health Research Institute, Hamilton, Canada; 5Department of Medicine (Cardiology), McMaster University, Hamilton, Canada; 6Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Canada; 7World Health Research Trust, Hamilton, Canada), Matthew Cameron (8Department of Anesthesia, McGill University, Montreal, Canada), Richard P. Whitlock (4Population Health Research Institute, Hamilton, Canada; 6Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Canada; 7World Health Research Trust, Hamilton, Canada; 9Department of Surgery (Cardiac Surgery), McMaster University, Hamilton, Canada), C. Scott Brudney (10Department of Anesthesia, University of Manitoba, Winnipeg, Canada; 11Department of Medicine (Critical Care), University of Manitoba, Winnipeg, Canada), Allison M. Janda (12Department of Anesthesiology, University of Michigan, Ann Arbor, USA), Eric Jacobsohn (10Department of Anesthesia, University of Manitoba, Winnipeg, Canada; 11Department of Medicine (Critical Care), University of Manitoba, Winnipeg, Canada), David Mazer (13Department of Anesthesia and Li Ka Shing Knowledge Institute, St. Michael’s Hospital, Toronto, Canada; 14Departments of Anesthesiology and Pain Medicine, Physiology, and Pharmacology and Toxicology, University of Toronto, Toronto, Canada), François Lamontagne (15Departement d’anesthésiologie, Université de Sherbrooke, Sherbrooke, Canada), Christie Smith (16Department of Clinical Perfusion, Trillium Health Centre, Mississauga, Canada), Gordon Guyatt (6Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Canada; 17Department of Medicine, McMaster University, Hamilton, Canada), Jessica Spence (4Population Health Research Institute, Hamilton, Canada; 6Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Canada; 7World Health Research Trust, Hamilton, Canada; 18Department of Anesthesia and Critical Care, McMaster University, Hamilton, Canada)
Categories: Article
Source: Canadian journal of anaesthesia = Journal canadien d'anesthesie
Authors: Karen Zhao, Renée Fournier, Kevin Kennedy, Hilary Grocott, Emilie Belley-Côté, Matthew Cameron, Richard P. Whitlock, C. Scott Brudney, Allison M. Janda, Eric Jacobsohn, David Mazer, François Lamontagne, Christie Smith, Gordon Guyatt, Jessica Spence
Clinicians presume a relationship between the management of blood pressure during cardiac surgery and postoperative morbidity and mortality. With limited evidence to inform practice, we surveyed Canadian cardiac anesthesiologists, perfusionists, and cardiac surgeons. We sought to solicit information to inform a trial evaluating blood pressure management approach on outcomes after cardiac surgery.
We iteratively developed a survey assessing the lowest and highest blood pressures respondents would target, the narrowest feasible blood pressure range to achieve, the range of blood pressure observed in clinical practice, and factors influencing targeted blood pressure before, during, and after cardiopulmonary bypass(CPB). We contacted leads from every Canadian hospital providing cardiac surgery to distribute the survey via computerized link. We used a modified Dillman approach to optimize response rate. Responses were analyzed descriptively.
Of 819 clinicians surveyed, 532(65.0%) responded. Respondents’ lowest pooled mean (SD) mean arterial pressure (MAP) target was 59(6) mmHg before CPB, 55(7) mmHg during CPB, and 60(5) mmHg after CPB. Respondents’ highest pooled mean (SD) MAP target was 92(10) mmHg before CPB, 84(7) mmHg during CPB, and 75(6) mmHg after CPB. The narrowest feasible MAP range all respondents believed could be achieved was mean (SD) 19(7) mmHg before CPB, 16(7) mmHg during CPB, and 20(7) mmHg after CPB
The responses to our survey support the clinical acceptability of a trial examining blood pressure target thresholds at the extreme ends of the range recommended by existing guidelines and the feasibility of maintaining blood pressure within a narrow target range.
Intraoperative blood pressure during on-pump cardiac surgery is managed through the joint effort of the anesthesiologist and clinical perfusionist, with additional input from the cardiac surgeon. Intraoperative blood pressure can be manipulated using vasopressors, inotropes, volume administration, depth of anesthesia, and changes in flow rate during cardiopulmonary bypass (CPB). There is a presumed relationship between the management of intraoperative blood pressure and postoperative morbidity and mortality.^1,2^ However, there is limited evidence to inform the optimal intraoperative blood pressure target prior to, during, and after CPB, resulting in vague guideline recommendations.^3,4^
Although there is limited evidence about the relationship of blood pressure with patient outcomes, several pathophysiologic principles may inform a clinician’s choice of blood pressure management strategy during cardiac surgery. Clinicians may be concerned that a lower blood pressure could result in inadequate end organ tissue perfusion. Conversely, clinicians may avoid higher blood pressure targets due to concerns about bleeding, increased extra-coronary collateral blood flow with impaired cardioplegic myocardial preservation, and associations with adverse atheroembolic events. Finally, clinicians may forgo a singular blood pressure target altogether and, instead, favor an individualized approach based on baseline blood pressure, pre-existing comorbidities, or tissue oxygenation monitoring (i.e., cerebral oximetry).
Given the limited evidence to support any specific management approach, we surveyed practicing Canadian cardiac anesthesiologists, perfusionists, and cardiac surgeons to characterize current practice patterns of blood pressure management during cardiac surgery. We specifically sought to solicit information that could be used to inform the design of a trial evaluating the use of blood pressure management strategies on patient-important outcomes after cardiac surgery. We hypothesized that most clinicians would be willing to target mean arterial blood pressures between 50-80 mmHg, consistent with current recommendations by the European Association of Cardiothoracic Anesthesiologists (EACTA) guidelines for the management of CPB,^4^ supporting the feasibility of conducting a large randomized controlled trial comparing the two extremes of this range.
This survey was designed and reported according to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines.^5^ Prior to data collection, we obtained local research ethics board approval. We developed a survey which assessed five broad (1) the lowest blood pressure that respondents would be willing to target before, during, and after CPB; (2) the highest blood pressure that respondents would be willing to target before, during, and after CPB; (3) the narrowest feasible blood pressure range that could be achieved before, during, and after CPB; (4) the blood pressure range observed in routine care before, during, and after CPB; and (5) factors influencing choice of blood pressure target. Survey items were developed iteratively by a multidisciplinary group, including cardiac anesthesiologists, clinical perfusionists, cardiac surgeons, critical care physicians, and research methodologists. We specifically designed questions to inform the choice of blood pressure target for a trial evaluating the effect of intraoperative blood pressure management strategy on postoperative patient-important outcomes. We piloted the survey with clinicians to ensure clarity and ease of completion.
We included cardiac anesthesiologists, cardiac surgeons, and clinical perfusionists practicing at any Canadian hospital providing cardiac surgery. We excluded all trainees. Before disseminating the survey, we contacted cardiac anesthesia, cardiac surgery, and perfusion leads from every Canadian hospital providing cardiac surgery to establish an agreement for their group to participate in the study, ascertain the number of each type of practitioner, and develop a plan for survey distribution. A modified Dillman approach was used for survey distribution to optimize response rate.^6^
We distributed the survey between November/2021 and July/2022. A computerized link to the anonymous survey was distributed via email to each departmental contact, who then forwarded it to eligible faculty. The email also included information regarding the purpose of the study, a statement regarding its voluntary nature, and information about the confidentiality of participation. We sent three follow-up emails every two weeks and distributed non-binding incentives (gift cards) to all potential participants to encourage survey completion. Study data were collected using the REDCap (Research Electronic Data Capture), a secure web-based application which assists in data capture. No names, email addresses, or IP addresses were collected. Data was securely stored in an encrypted form that only study staff could access.
Responses to the survey were analyzed descriptively using Stata version 12 (StataCorp, College Station, TX). Response rates were calculated by dividing the number of responses by the total number of survey respondents. Continuous variables were described using mean (standard deviation [SD]) or median (interquartile range [IQR]) as appropriate. Figures were created using GraphPad Prism version 10.0 for Windows (GraphPad Software, Boston, Massachusetts, USA, www.graphpad.com).
We contacted the 31 cardiac surgery centres across Canada and obtained a commitment to distribute the survey from all of them (100%). The 31 cardiac surgery centres sampled consisted of 819 clinicians - 418 cardiac anesthesiologists, 142 cardiac surgeons, and 259 clinical perfusionists. In total, 532/819 (65.0%) clinicians responded to the survey, with no statistically significant difference in response rate between professional groups. The largest proportion of respondents were cardiac anesthesiologists (222/532; 41.7%); 71/532 (13.3%) of respondents did not disclose their profession. Survey respondents are described in detail in Table 1.
Table 2, Figures 1 and 2, and Appendix 1 describe the acceptable low and high blood pressure targets (defined using either mean arterial pressure [MAP] or systolic blood pressure [SBP]), the narrowest feasible blood pressure to target, and the blood pressure range observed in routine practice before, during, and after the cardiopulmonary bypass period, as per survey respondents. Responses were similar across professions (Appendix 1). The lowest mean (SD) MAP target that respondents identified was 59 (6) mmHg before CPB, 55 (7) mmHg during CPB, and 60 (5) mmHg after CPB. In contrast, the highest mean (SD) MAP target identified by respondents was 92 (10) mmHg before CPB, 84 (7) mmHg during CPB, and 75 (6) mmHg after CPB. The lowest mean (SD) SBP that respondents would target before and after CPB was 89 (9) and 89 (9). The highest mean (SD) SBP that respondents would target before and after CPB was 136 (13) and 129 (12).
The narrowest feasible blood pressure range that respondents believed could be achieved during surgery ranged from a mean (SD) MAP of 16 (7) mmHg during CPB to 20 (7) mmHg after CPB (Table 2, Figure 1). When asked about the blood pressure ranges commonly observed in routine cardiac surgery, respondents reported wider blood pressure ranges than those they believed could be feasibly achieved, ranging from a mean (SD) MAP 36 (10) mmHg during CPB to 28 (9) mmHg before CPB and a mean (SD) SBP of 45 (14) mmHg after CPB to 47 (14) mmHg before CPB (Table 2, Figure 2).
Figure 3 and Appendices 2–4 depict how respondents rated the likelihood that a particular factor would result in their targeting a lower or higher blood pressure intraoperatively, as well as the monitors they used to guide the blood pressure they targeted. Most respondents replied that intraoperative bleeding (345/532; 65%) or procedures on the thoracic aorta (328/532; 62%) would surely or probably result in their targeting a lower blood pressure. Most respondents (407/532; 77%) indicated that a patient history of carotid stenosis would surely or probably lead them to target a higher blood pressure. Respondents also endorsed that a patient history of hypertension (286/532; 65%), stroke (301/532, 57%), or chronic kidney disease (300/532, 56%), in addition to the presence of high-risk anatomical features (279/532, 52%), would probably lead them to target a higher blood pressure. Concerning the factors that respondents used in nearly all cases to guide blood pressure management (Figure 3), most reported using CPB flow rates or cardiac output (249/532, 47%), followed by venous oxygen saturation (167/532, 31%), urine output (119/532, 22%), cerebral oximetry (91/531, 17%), or some other form of monitoring (22/532, 4%).
We surveyed Canadian cardiac anesthesiologists, cardiac surgeons, and clinical perfusionists regarding their opinions about the management of blood pressure during cardiac surgery. During CPB, the lowest MAP that respondents were willing to target was 55 mmHg and the highest MAP that respondents were willing to target was 84 mmHg. During the pre- and post-CPB periods, respondents identified slightly higher targets, with a MAP ranging from 59 to 92 mmHg and a SBP from 89 to 136 mmHg. Across practitioner groups, there was no difference between the responses of cardiac anesthesiologists, cardiac surgeons, and clinical perfusionists. Respondents believed that both MAP and SBP could feasibly be maintained within a relatively narrow range but, in contrast, reported a wide range of blood pressures that they observed in routine care, up to a mean (SD) MAP range of 28 (9) mmHg and an SBP range of 47 (14) mmHg. Respondents were generally consistent regarding the factors contributing to the decision to target a higher or lower blood pressure target, although more varied regarding the intraoperative monitors used to guide blood pressure targets.
The responses to our survey were varied and wide-ranging, but consistent with existing clinical practice guidelines. The Perioperative Quality Initiative (POQI) consensus statement on intraoperative blood pressure for elective surgery recommended that, for cardiac surgery specifically, intraoperative systolic blood pressures be maintained below 140 mmHg but does not specify a lower limit of intraoperative blood pressure nor specify an acceptable MAP range during CPB.^3^ In contrast, guidelines published by the European Association of Cardiothoracic Anesthesiologists (EACTA) recommend a MAP range between 50 to 80 mmHg during CPB but make no recommendations for an acceptable blood pressure before or after CPB.^4^ The American Society of ExtraCorporeal Technology (AmSECT) guidelines state that “The Perfusionist, in collaboration with the physician-in-charge, shall define and communicate the intended treatment algorithm for blood pressure management prior to CPB, including acceptable ranges for blood pressure,” but do not specify an acceptable range or define which patient and surgical factors should influence the parameters of an acceptable blood pressure range.^7^
The lack of clear guidance concerning blood pressure management during cardiac surgery is likely related to the limitations of the available evidence. A recent systematic review of 8 randomized controlled trials (n=1,116) observed no difference in delirium, cognitive decline, stroke, acute kidney injury, or mortality when high compared to low blood pressure targets were used during CPB (very-low to low-quality evidence) but did identify moderate quality evidence that higher blood pressure targets may increase the risk of blood transfusion (three trials; n=456 participants; relative risk 1.4; 95% confidence interval 1.1 to 1.9; P=0.01).^8^ Several trials have evaluated the effect of a personalized blood pressure target on postoperative outcomes but have generated mixed results. A single-centre RCT of 412 patients undergoing coronary artery bypass grafting found no difference in mortality, quality of life, or major neurologic, cardiac, and cardiac complications when a custom MAP target (based on patients’ baseline blood pressure) compared to a “high” MAP target (80 mm Hg) was used.^9^ In contrast, a single-centre nested RCT comparing a personalized target based on the lower limit of cerebral autoregulation with usual care found that the incidence of postoperative delirium was significantly lower among patients managed according to a personalized target (Odds Ratio 0.55; 95% Confidence Interval [CI] 0.31 to 0.97; P=0.04).^10^
Numerous observational studies have suggested that intraoperative blood pressure has an important association with postoperative morbidity and mortality. De la Hoz et al conducted a retrospective cohort study of 4,984 patients and found that each 10 minutes of hypotension (defined as a MAP less than 65 mm Hg) before, during, and after CPB was associated with an increased odds of a composite outcome of stroke, acute kidney injury, and mortality (adjusted odds ratio 1.06; 95% CI 1.03 to 1.10; P=0.001).^11^ Reich et al. conducted a retrospective study of 2,149 patients undergoing CABG and identified a 30% increase in the odds of in-hospital mortality in patients with increased time during CPB with a MAP below 50 mmHg.^12^ Sun et al found that every ten minutes with a sustained MAP between 55 and 64 mmHg during CPB was associated with a 13% increase in the odds of postoperative stroke (adjusted odds ratio 1.13; 95% CI 1.05 to 1.21) and that every ten minutes that MAP was less than 55 mm Hg was associated with a 16% increase in the odds of stroke (adjusted odds ratio 1.16; 95% CI 1.08 to 1.23).^13^ Ngu et al conducted a retrospective cohort study of 6,523 patients to define an intraoperative hypotension threshold that was associated with postoperative renal replacement therapy, and found that each 10 minute period with a MAP less than 55 mm Hg after CPB was associated with an adjusted odds ratio of 1.13 (95% CI 1.05 to 1.23; P=0.002), and each 10 minute period with a MAP between 55 and 64 mm Hg after CPB was associated with an adjusted odds ratio of 1.12 (95% CI 1.06 to 1.18; P=0.0001). However, the authors did not observe an association between hypotension before or during CPB with renal replacement therapy.^14^
Because of its relationship to end organ perfusion, many believe that the management of blood pressure during cardiac surgery can potentially affect multiple end-organ systems, including the brain and the kidney.^2,3^ However, how this translates into practice is mixed. Consistent with our results, a 2020 survey administered to the membership of the Society of Cardiovascular Anesthesiologists regarding the use of neuroprotective strategies during cardiac anesthesia found that 55.3% of respondents (n=526) worked in centres with no standardized institutional approach to the management of blood pressure during cardiac anesthesia or CPB.^2^ Regarding a blood pressure target in cardiac surgery patients at risk of postoperative cerebral injury, the majority (41.3%) of respondents targeted a blood pressure >65 mm Hg during CPB, although responses ranged from >45 mm Hg to >85 mm Hg.^2^ In a separate 2021 survey of members of the Society of Cardiovascular Anesthesiologists (n=202), the renoprotective strategy most frequently reported by respondents was the use of an intraoperative blood pressure target (and relative hypotension avoidance, although no threshold was quantified) (79% of respondents; 95% CI 72 to 85).^1^ Despite the limitations in the existing evidence and variability in choice of blood pressure threshold, 79% of respondents believed that the evidence supporting the renoprotective benefits of an intraoperative blood pressure target was of high or moderate quality.^1^
Our survey has several strengths. We used a rigourous approach to define our sampling frame, systematically approached cardiac anesthesiologists, clinical perfusionists, and cardiac surgeons, and achieved an excellent (65%) response rate. Our survey has several limitations. First, we surveyed only Canadian cardiac anesthesiologists, clinical perfusionists, and cardiac surgeons; their practice may differ from that of clinicians globally. Second, despite our excellent response rate, 287/819 (35%) clinicians did not participate. Despite these limitations, our survey provides important information regarding the management of blood pressure during cardiac surgery, highlights the need for better evidence, and supports the feasibility of a trial evaluating a range of blood pressure targets during cardiac surgery.
The variability in practice described by respondents to our survey is consistent with the published, though arguably vague, professional Society guidelines for blood pressure management during cardiac surgery, which reflect the lack of robust evidence supporting a clear blood pressure threshold or management strategy. Observational evidence clearly suggests that intraoperative hypotension before, during, and after CPB is associated with adverse outcomes after cardiac surgery, including acute kidney injury,^11,14^ stroke,^11,13^ and mortality.^11,12^ However, this has not been borne out by a large and well-designed randomized controlled trial, which may be due to limitations in the evidence or the absence of a causal relationship between intraoperative blood pressure management and postoperative morbidity and mortality. Better evidence is required to guide practice. The responses to our survey support the clinical acceptability of a trial examining blood pressure target thresholds at the extreme ends of the range recommended by existing guidelines and the feasibility of maintaining blood pressure within a narrow target range.