Adverse renal effects associated with cardiopulmonary bypass.

Cardiac surgery on cardiopulmonary bypass (CPB) is associated with postoperative renal dysfunction, one of the most common complications of this surgical cohort. Acute kidney injury (AKI) is associated with increased short-term morbidity and mortality and has been the focus of much research. There is increasing recognition of the role of AKI as the key pathophysiological state leading to the disease entities acute and chronic kidney disease (AKD and CKD). In this narrative review, we will consider the epidemiology of renal dysfunction after cardiac surgery on CPB and the clinical manifestations across the spectrum of disease. We will discuss the transition between different states of injury and dysfunction, and, importantly, the relevance to clinicians. The specific facets of kidney injury on extracorporeal circulation will be described and the current evidence evaluated for the use of perfusion-based techniques to reduce the incidence and mitigate the complications of renal dysfunction after cardiac surgery.

Neurologic complications after cardiopulmonary bypass - A narrative review.

Neurologic complications, associated with cardiac surgery and cardiopulmonary bypass (CPB) in adults, are common and can be devastating in some cases. This comprehensive review will not only consider the broad categories of stroke and neurocognitive dysfunction, but it also summarises other neurological complications associated with CPB, and it provides an update about risks, prevention and treatment. Where appropriate, we consider the impact of off-pump techniques upon our understanding of the contribution of CPB to adverse outcomes.

Frailty and perioperative patient-reported disability in patients undergoing cardiac surgery: a pilot study.

BACKGROUND: Preoperative frailty may predispose patients to poorer outcomes in cardiac surgery; however, there are limited data concerning how preoperative frailty predicts patient-centred outcomes, such as patient-reported disability. Our objective was to evaluate the association between preoperative frailty and postoperative disability. METHODS: Patients were prospectively evaluated using the Comprehensive Assessment of Frailty score, separating patients into frail and non-frail cohorts. Disability levels were quantified using the WHO Disability Assessment Schedule (WHODAS) 2.0 in percentage of the maximum disability score, with disability defined as a value ≥25%. RESULTS: Frail patients had increased median [inter-quartile range] disability scores of 31 [16-45]% preoperatively, 29 [9-54]% at 1 month, and 15 [3-31]% at 3 months postoperatively, compared with disability scores in non-frail patients of 10 [5-17]%, 17 [6-29]%, and 2.1 [0-12.0]%, respectively. Preoperative frailty was associated with a reduced likelihood of patients being free of disability and alive at 3 months; adjusted odds ratio 0.51 (for age, European System for Cardiac Operative Risk Evaluation II, and WHODAS 2.0: 12-Part Questionnaire score); P=0.045. The trajectory of disability scores, assessed in percentage change from the preoperative baseline, showed non-frail patients had increased disability burden at 1 month, whereas frail patients had reduced disability burden (+4.2% vs -2.1%; P=0.04). Although the disability burden decreased for both groups at 3 months, this was most marked for frail patients (-6.3% vs -10.4%; P=0.02). CONCLUSIONS: Disability burden in frail patients improves continuously postoperatively, whereas in non-frail patients, it worsens at 1 month before improving at 3 months postoperatively. This positive trajectory of patient-centred outcomes in frail patients should be considered in preoperative decision-making.

Perioperative Management of the Patient at High-Risk for Cardiac Surgery-Associated Acute Kidney Injury.

Acute kidney injury (AKI) is one of the most common major complications of cardiac surgery, and is associated with increased morbidity and mortality. Cardiac surgery-associated AKI has a complex, multifactorial etiology, including numerous factors such as primary cardiac dysfunction, hemodynamic derangements of cardiac surgery and cardiopulmonary bypass, and the possibility of a large volume of blood transfusion. There are no truly effective pharmacologic therapies for the management of AKI, and, therefore, anesthesiologists, intensivists, and cardiac surgeons must remain vigilant and attempt to minimize the risk of developing renal dysfunction. This narrative review describes the current state of the scientific literature concerning the specific aspects of cardiac surgery-associated AKI, and presents it in a chronological fashion to aid the perioperative clinician in their approach to this high-risk patient group. The evidence was considered for risk prediction models, preoperative optimization, and the intraoperative and postoperative management of cardiac surgery patients to improve renal outcomes.

Neuromonitoring and Neurocognitive Outcomes in Cardiac Surgery: A Narrative Review.

Neurocognitive dysfunction after cardiac surgery can present with diverse clinical phenotypes, which include postoperative delirium, postoperative cognitive dysfunction, and stroke, and it presents a significant healthcare burden for both patients and providers. Neurologic monitoring during cardiac surgery includes several modalities assessing cerebral perfusion and oxygenation (near-infrared spectroscopy, transcranial Doppler and jugular venous bulb saturation monitoring) and those that measure cerebral function (processed and unprocessed electroencephalogram), reflecting an absence of a single, definitive neuromonitor. This narrative review briefly describes the technologic basis of these neuromonitoring modalities, before exploring their use in clinical practice, both as tools to predict neurocognitive dysfunction, and with a bundle of interventions designed to optimize cerebral oxygen supply, with the aim of reducing postoperative delirium and cognitive dysfunction following cardiac surgery.

Role of Hypothermia in Adult Cardiac Surgery Patients: A Systematic Review and Meta-analysis.

OBJECTIVE: To review studies that assessed systemic hypothermia as an organ protection strategy in adults undergoing cardiac surgery with cardiopulmonary bypass. DESIGN: A systematic review and meta-analysis. SETTING AND PARTICIPANTS: Randomized controlled trials, irrespective of blinding, language, publication status, and date of publication, were identified by searching the Cochrane Central register of Controlled Trials, MEDLINE, and Embase until November 2020. Risk of bias assessment was performed according to Cochrane methodology. Treatment effects were expressed as risk ratios and 95% confidence intervals. Heterogeneity was expressed as I2. INTERVENTIONS: Systemic hypothermia. MEASUREMENTS AND MAIN RESULTS: Forty-eight trials enrolling 6,690 patients were included in the analysis. Methodologic quality of the studies included was low, mostly due to insufficient allocation concealment or blinding. Random-effects meta-analysis did not resolve uncertainty as to the risks and benefits for hypothermia versus normothermia for key primary and secondary outcomes, including mortality (1.21, 0.94 to 1.56, I2 = 0%) and brain injury (0.87, 0.67 to 1.14, I2 = 0%). Sensitivity analyses restricted to trials at low risk of important bias demonstrated higher mortality with hypothermia (1.70, 1.05 to 2.75, I2 = 0%), with little or no treatment effect on brain injury (1.01, 0.69 to 1.49, I2 = 0%). There was no interaction between cardioplegia temperature and the effects of cardiopulmonary bypass temperature on outcomes. There was insufficient evidence to assess the effects of hypothermia in noncoronary artery bypass graft surgery. CONCLUSION: The existing evidence for an organ-protective effect of hypothermia in adult cardiac surgery is of low quality and inconsistent.

Prevention of Cardiac Surgery-Associated Acute Kidney Injury by Implementing the KDIGO Guidelines in High-Risk Patients Identified by Biomarkers: The PrevAKI-Multicenter Randomized Controlled Trial.

BACKGROUND: Prospective, single-center trials have shown that the implementation of the Kidney Disease: Improving Global Outcomes (KDIGO) recommendations in high-risk patients significantly reduced the development of acute kidney injury (AKI) after surgery. We sought to evaluate the feasibility of implementing a bundle of supportive measures based on the KDIGO guideline in high-risk patients undergoing cardiac surgery in a multicenter setting in preparation for a large definitive trial. METHODS: In this multicenter, multinational, randomized controlled trial, we examined the adherence to the KDIGO bundle consisting of optimization of volume status and hemodynamics, functional hemodynamic monitoring, avoidance of nephrotoxic drugs, and prevention of hyperglycemia in high-risk patients identified by the urinary biomarkers tissue inhibitor of metalloproteinases-2 [TIMP-2] and insulin growth factor-binding protein 7 [IGFBP7] after cardiac surgery. The primary end point was the adherence to the bundle protocol and was evaluated by the percentage of compliant patients with a 95% confidence interval (CI) according to Clopper-Pearson. Secondary end points included the development and severity of AKI. RESULTS: In total, 278 patients were included in the final analysis. In the intervention group, 65.4% of patients received the complete bundle as compared to 4.2% in the control group (absolute risk reduction [ARR] 61.2 [95% CI, 52.6-69.9]; P < .001). AKI rates were statistically not different in both groups (46.3% intervention versus 41.5% control group; ARR -4.8% [95% CI, -16.4 to 6.9]; P = .423). However, the occurrence of moderate and severe AKI was significantly lower in the intervention group as compared to the control group (14.0% vs 23.9%; ARR 10.0% [95% CI, 0.9-19.1]; P = .034). There were no significant effects on other specified secondary outcomes. CONCLUSIONS: Implementation of a KDIGO-derived treatment bundle is feasible in a multinational setting. Furthermore, moderate to severe AKI was significantly reduced in the intervention group.

Multicenter International Survey on Cardiopulmonary Bypass Perfusion Practices in Adult Cardiac Surgery.

OBJECTIVES: To assess current practice in adult cardiac surgery during cardiopulmonary bypass (CPB) across European and non-European countries. DESIGN: International, multicenter, web-based survey including 28 multiple choice questions addressing hemodynamic and tissue oxygenation parameters, organ protection measures, and the monitoring and usage of anesthetic drugs as part of the anesthetic and perfusion practice during CPB. SETTING: Online survey endorsed by the European Association of Cardiothoracic Anesthesiologists. PARTICIPANTS: Representatives of anesthesiology departments in European and non-European adult cardiac surgical centers. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The survey was distributed via e-mail to European Association of Cardiothoracic Anesthesiologists members (n = 797) and kept open for 1 month. The response rate was 34% (n = 271). After exclusion of responses from the same centers and of incomplete answers, data from 202 cardiac centers in 56 countries, of which 67% of centers were university hospitals, were analyzed. Optimization of pump flows and tissue oxygenation parameters during CPB were applied by the majority of centers, with target flow rates of >2.2 L/min/m2 in 93% (n = 187) of centers and mean arterial blood pressures between 51 and 90 mmHg in 85% (n = 172). Hemoglobin transfusion triggers were either individualized or between 7 and 8 g/dL in 92% (n = 186) of centers. Mixed venous oxyhemoglobin saturations were assessed routinely in 59% (n = 120) and lactate in 88% (n = 178) of cardiac surgery units. Noninvasive cerebral saturation monitoring was used in a subgroup of patients or routinely in 84% (n = 169) of sites, and depth-of-anesthesia monitoring was used routinely in 53% (n = 106). Transesophageal echocardiography and pulmonary artery catheters were used routinely or in subgroups of patients in 97% (n = 195) and 71% (n = 153) of centers, respectively. The preferred site for temperature monitoring was the nasopharynx in 66% (n = 134) of centers. Anesthetic techniques were variable, with 26% of centers (n = 52) using low-tidal-volume ventilation and 28% (n = 57) using continuous positive airway pressure during CPB. Volatile agents were used routinely as the only agent during CPB in 36% sites (n = 73) and propofol in 47% (n = 95). Other drugs routinely administered included magnesium in 45% (n = 91), steroids in 18% (n = 37), tranexamic acid in 88% (n = 177), and aprotinin in 15% (n = 30) of the centers. CONCLUSION: This international CPB survey revealed that techniques for optimization of pump flow and oxygenation during CPB usually were applied. Furthermore, cerebral and hemodynamic monitoring devices were frequently used during CPB. However, most CPB-related anesthetic techniques and medications were more variable. More high-quality randomized controlled trials are needed to assess anesthetic techniques and organ protection.

A Multinational Observational Study Exploring Adherence With the Kidney Disease: Improving Global Outcomes Recommendations for Prevention of Acute Kidney Injury After Cardiac Surgery.

BACKGROUND: The Kidney Disease: Improving Global Outcomes (KDIGO) guidelines recommend a bundle of different measures for patients at increased risk of acute kidney injury (AKI). Prospective, single-center, randomized controlled trials (RCTs) have shown that management in accordance with the KDIGO recommendations was associated with a significant reduction in the incidence of postoperative AKI in high-risk patients. However, compliance with the KDIGO bundle in routine clinical practice is unknown. METHODS: This observational prevalence study was performed in conjunction with a prospective RCT investigating the role of the KDIGO bundle in high-risk patients undergoing cardiac surgery. A 2-day observational prevalence study was performed in all participating centers before the RCT to explore routine clinical practice. The participating hospitals provided the following data: demographics and surgical characteristics, AKI rates, and compliance rates with the individual components of the bundle. RESULTS: Ninety-five patients were enrolled in 12 participating hospitals. The incidence of AKI within 72 hours after cardiac surgery was 24.2%. In 5.3% of all patients, clinical management was fully compliant with all 6 components of the bundle. Nephrotoxic drugs were discontinued in 52.6% of patients, volume optimization was performed in 70.5%, 52.6% of the patients underwent functional hemodynamic monitoring, close monitoring of serum creatinine and urine output was undertaken in 24.2% of patients, hyperglycemia was avoided in 41.1% of patients, and no patient received radiocontrast agents. The patients received on average 3.4 (standard deviation [SD] ±1.1) of 6 supportive measures as recommended by the KDIGO guidelines. There was no significant difference in the number of applied measures between AKI and non-AKI patients (3.2 [SD ±1.1] vs 3.5 [SD ±1.1]; P = .347). CONCLUSIONS: In patients after cardiac surgery, compliance with the KDIGO recommendations was low in routine clinical practice.

Intraoperative Optimization of Both Depth of Anesthesia and Cerebral Oxygenation in Elderly Patients Undergoing Coronary Artery Bypass Graft Surgery-A Randomized Controlled Pilot Trial.

OBJECTIVES: Does intraoperative optimization of both depth of anesthesia and regional cerebral tissue oxygenation (rScO2) in elderly patients reduce postoperative cognitive decline (primary outcome) or delirium (secondary outcome)? DESIGN: Prospective randomized controlled single blind trial. SETTING: A single major urban teaching and university hospital and tertiary referral center. PARTICIPANTS: Patients, 65 years of age and older, undergoing elective coronary artery bypass graft surgery on cardiopulmonary bypass. INTERVENTIONS: Intraoperative depth of anesthesia bispectral index (BIS) values were targeted at 50 ± 10. Regional cerebral tissue desaturations of more than 15% of the pre-induction value, or below 50%, were avoided. MEASUREMENTS AND MAIN RESULTS: Eighty-two patients were included, and mean depth of anesthesia values using BIS were significantly higher during surgery in the intervention group with 40.6 (7.3) versus 35.4 (6.7) in the control group, mean (standard deviation), p = 0.004. The cognitive function was similar between the treatment and control groups at 6 weeks postoperatively with a Mini Mental State Examination (MMSE) of 27 (26,29) in the intervention group and an MMSE of 29 (27,29) in the control group, median (interquartile range), with p = 0.12. The authors observed a reduction in the incidence of delirium, occurring in 2.4% (n = 1) of patients in the intervention group and in 20% (n = 8) in the control group (p = 0.01). CONCLUSIONS: This pilot trial demonstrates that noninvasive target-controlled depth of anesthesia monitoring is feasible. Cognitive function at 6 weeks showed no difference between the treatment and control groups; however, postoperative delirium was reduced in the intervention group.

Current Practice of Calcium Use During Cardiopulmonary Bypass Weaning: Results of an International Survey.

OBJECTIVES: To describe international practices on the use of calcium salts during cardiopulmonary bypass (CPB) weaning in adult cardiac surgery patients. DESIGN: Multiple-choice survey on current practice of CPB weaning. SETTING: Online survey using the SurveyMonkey platform. PARTICIPANTS: Departments of cardiac anesthesiology worldwide. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Out of 112 surveys sent, 100 centers from 32 countries replied. The majority of centers (88 of 100 = 88%) administer calcium salts intraoperatively: 71 of 100 (71%) are using these drugs for CPB weaning and 78 of 100 (78%) for correction of hypocalcemia. Among the 88 centers that use calcium salts intraoperatively, 66% (58 of 88) of respondents use calcium chloride, 22% (19 of 88) use calcium gluconate, and 12% (11 of 88) use both drugs. Calcium salts are routinely used during normal (47 of 71 centers = 66%) and difficult (59 of 71 centers = 83%) weaning from CPB. Doses of 5 to 15 mg/kg during termination of CPB were used by 55 of 71 centers (77%) either by bolus (39 of 71, 55%) or over a time period longer than 1 minute (32 of 71 = 45%). Norepinephrine is the most commonly used first line vasopressor or inotropic agent used to support hemodynamics during termination of CPB in 32 out of 100 centers (32%), and calcium is the second one, used by 23 out of 100 centers (23%). CONCLUSION: This survey demonstrates that the majority of cardiac centers use calcium in adult patients undergoing cardiac surgery, especially during weaning from CPB. There is variability on the type of drug, dose, and modality of drug administration.

Remote Ischemic Preconditioning and Outcomes of Cardiac Surgery.

BACKGROUND: Whether remote ischemic preconditioning (transient ischemia and reperfusion of the arm) can improve clinical outcomes in patients undergoing coronary-artery bypass graft (CABG) surgery is not known. We investigated this question in a randomized trial. METHODS: We conducted a multicenter, sham-controlled trial involving adults at increased surgical risk who were undergoing on-pump CABG (with or without valve surgery) with blood cardioplegia. After anesthesia induction and before surgical incision, patients were randomly assigned to remote ischemic preconditioning (four 5-minute inflations and deflations of a standard blood-pressure cuff on the upper arm) or sham conditioning (control group). Anesthetic management and perioperative care were not standardized. The combined primary end point was death from cardiovascular causes, nonfatal myocardial infarction, coronary revascularization, or stroke, assessed 12 months after randomization. RESULTS: We enrolled a total of 1612 patients (811 in the control group and 801 in the ischemic-preconditioning group) at 30 cardiac surgery centers in the United Kingdom. There was no significant difference in the cumulative incidence of the primary end point at 12 months between the patients in the remote ischemic preconditioning group and those in the control group (212 patients [26.5%] and 225 patients [27.7%], respectively; hazard ratio with ischemic preconditioning, 0.95; 95% confidence interval, 0.79 to 1.15; P=0.58). Furthermore, there were no significant between-group differences in either adverse events or the secondary end points of perioperative myocardial injury (assessed on the basis of the area under the curve for the high-sensitivity assay of serum troponin T at 72 hours), inotrope score (calculated from the maximum dose of the individual inotropic agents administered in the first 3 days after surgery), acute kidney injury, duration of stay in the intensive care unit and hospital, distance on the 6-minute walk test, and quality of life. CONCLUSIONS: Remote ischemic preconditioning did not improve clinical outcomes in patients undergoing elective on-pump CABG with or without valve surgery. (Funded by the Efficacy and Mechanism Evaluation Program [a Medical Research Council and National Institute of Health Research partnership] and the British Heart Foundation; ERICCA ClinicalTrials.gov number, NCT01247545.).

Aggregation of Marginal Gains in Cardiac Surgery: Feasibility of a Perioperative Care Bundle for Enhanced Recovery in Cardiac Surgical Patients.

OBJECTIVES: The aim of this pilot study was to assess the feasibility of a perioperative care bundle for enhanced recovery after cardiac surgery (ERACS). DESIGN: A prospective, observational study. SETTING: A major urban teaching and university hospital and tertiary referral center. PARTICIPANTS: The study included 53 patients undergoing cardiac surgery before implementation of an ERACS protocol (pre-ERACS group) and 52 patients undergoing cardiac surgery after implementation of an ERACS protocol (ERACS group). INTERVENTIONS: Based on recommendations from a consensus review in colorectal surgery, the following enhanced recovery perioperative care bundle was applied: detailed preoperative information, avoidance of prolonged fasting periods preoperatively, preoperative carbohydrate beverages, optimization of analgesia with avoidance of long-acting opioids, prevention of postoperative nausea and vomiting, early enteral nutrition postoperatively, and early mobilization. MEASUREMENTS AND MAIN RESULTS: The authors hypothesized that length of hospital stay would be reduced with ERACS. Secondary outcome variables included a composite of postoperative complications and pain scores. Whereas the length of stay in the group of patients receiving the bundle of enhanced recovery interventions remained unchanged compared with the non-ERACS group, there was a statistically significant reduction in the number of patients in the ERACS group presenting with one or more postoperative complications (including hospital-acquired infections, acute kidney injury, atrial fibrillation, respiratory failure, postoperative myocardial infarction, and death). In addition, postoperative pain scores were improved significantly in the ERACS group. CONCLUSIONS: This pilot study demonstrated that ERACS is feasible and has the potential for improved postoperative morbidity after cardiac surgery. A larger multicenter quality improvement study implementing perioperative care bundles would be the next step to further assess outcomes in ERACS patients.

Cardiac myosin-binding protein C: a potential early biomarker of myocardial injury.

Cardiac troponins are released and cleared slowly after myocardial injury, complicating the diagnosis of early, and recurrent, acute myocardial infarction. Cardiac myosin-binding protein C (cMyC) is a similarly cardiac-restricted protein that may have different release/clearance kinetics. Using novel antibodies raised against the cardiac-specific N-terminus of cMyC, we used confocal microscopy, immunoblotting and immunoassay to document its location and release. In rodents, we demonstrate rapid release of cMyC using in vitro and in vivo models of acute myocardial infarction. In patients, with ST elevation myocardial infarction (STEMI, n = 20), undergoing therapeutic ablation of septal hypertrophy (TASH, n = 20) or having coronary artery bypass surgery (CABG, n = 20), serum was collected prospectively and frequently. cMyC appears in the serum as full-length and fragmented protein. Compared to cTnT measured using a contemporary high-sensitivity commercial assay, cMyC peaks earlier (STEMI, 9.3 ± 3.1 vs 11.8 ± 3.4 h, P < 0.007; TASH, 9.7 ± 1.4 vs 21.6 ± 1.4 h, P < 0.0001), accumulates more rapidly (during first 4 h after TASH, 25.8 ± 1.9 vs 4.0 ± 0.4 ng/L/min, P < 0.0001) and disappears more rapidly (post-CABG, decay half-time 5.5 ± 0.8 vs 22 ± 5 h, P < 0.0001). Our results demonstrate that following defined myocardial injury, the rise and fall in the serum of cMyC is more rapid than that of cTnT. We speculate that these characteristics could enable earlier diagnosis of myocardial infarction and reinfarction in suspected non-STEMI, a population not included in this early translational study.

Comparison between propofol and total inhalational anaesthesia on cardiovascular outcomes following on-pump cardiac surgery in higher-risk patients: a randomised controlled pilot and feasibility study.

OBJECTIVES: Myocardial revascularisation and cardiopulmonary bypass (CPB) can cause ischaemia-reperfusion injury, leading to myocardial and other end-organ damage. Volatile anaesthetics protect the myocardium in experimental studies. However, there is uncertainty about whether this translates into clinical benefits because of the coadministration of propofol and its detrimental effects, restricting myocardial protective processes. METHODS: In this single-blinded, parallel-group randomised controlled feasibility trial, higher-risk patients undergoing elective coronary artery bypass graft (CABG) surgery with an additive European System for Cardiac Operative Risk Evaluation ≥5 were randomised to receive either propofol or total inhalational anaesthesia as single agents for maintenance of anaesthesia. The primary outcome was the feasibility of recruiting and randomising 50 patients across two cardiac surgical centres, and secondary outcomes included the feasibility of collecting the planned perioperative data, clinically relevant outcomes and assessments of effective patient identification, screening and recruitment. RESULTS: All 50 patients were recruited within 11 months in two centres, allowing for a 13-month hiatus in recruitment due to the COVID-19 pandemic. Overall, 50/108 (46%) of eligible patients were recruited. One patient withdrew before surgery and one patient did not undergo surgery. All but one completed in-hospital and 30-day follow-up. CONCLUSIONS: It is feasible to recruit and randomise higher-risk patients undergoing CABG surgery to a study comparing total inhalational and propofol anaesthesia in a timely manner and with high acceptance and completion rates. TRIAL REGISTRATION NUMBER: NCT04039854.