Continuous Right Ventricular Pressure Monitoring in Cardiac Surgery.

OBJECTIVE: Right ventricular (RV) dysfunction in cardiac surgery can lead to RV failure, which is associated with increased morbidity and mortality. Abnormal RV function can be identified using RV pressure monitoring. The primary objective of the study is to determine the proportion of patients with abnormal RV early to end-diastole diastolic pressure gradient (RVDPG) and abnormal RV end-diastolic pressure (RVEDP) before initiation and after cardiopulmonary bypass (CPB) separation. The secondary objective is to evaluate if RVDPG before CPB initiation is associated with difficult and complex separation from CPB, RV dysfunction, and failure at the end of cardiac surgery. DESIGN: Prospective study. SETTING: Tertiary care cardiac institute. PARTICIPANTS: Cardiac surgical patients. INTERVENTION: Cardiac surgery. MEASUREMENTS AND MAIN RESULTS: Automated electronic quantification of RVDPG and RVEDP were obtained. Hemodynamic measurements were correlated with cardiac and extracardiac parameters from transesophageal echocardiography and postoperative complications. Abnormal RVDPG was present in 80% of the patients (n = 105) at baseline, with a mean RVEDP of 14.2 ± 3.9 mmHg. Patients experienced an RVDPG > 4 mmHg for a median duration of 50.2% of the intraoperative period before CPB initiation and 60.6% after CPB separation. A total of 46 (43.8%) patients had difficult/complex separation from CPB, 18 (38.3%) patients had RV dysfunction, and 8 (17%) had RV failure. Abnormal RVDPG before CPB was not associated with postoperative outcome. CONCLUSION: Elevated RVDPG and RVEDP are common in cardiac surgery. RVDPG and RVEDP before CPB initiation are not associated with RV dysfunction and failure but can be used to diagnose them.

Early Detection and Correction of Cerebral Desaturation With Noninvasive Oxy-Hemoglobin, Deoxy-Hemoglobin, and Total Hemoglobin in Cardiac Surgery: A Case Series.

Regional cerebral oxygen saturation (rS o2 ) obtained from near-infrared spectroscopy (NIRS) provides valuable information during cardiac surgery. The rS o2 is calculated from the proportion of oxygenated to total hemoglobin in the cerebral vasculature. Root O3 cerebral oximetry (Masimo) allows for individual identification of changes in total (ΔcHbi), oxygenated (Δ o2 Hbi), and deoxygenated (ΔHHbi) hemoglobin spectral absorptions. Variations in these parameters from baseline help identify the underlying mechanisms of cerebral desaturation. This case series represents the first preliminary description of Δ o2 Hbi, ΔHHbi, and ΔcHbi variations in 10 cardiac surgical settings. Hemoglobin spectral absorption changes can be classified according to 3 distinct variations of cerebral desaturation. Reduced cerebral oxygen content or increased cerebral metabolism without major blood flow changes is reflected by decreased Δ o2 Hbi, unchanged ΔcHbi, and increased ΔHHbi Reduced cerebral arterial blood flow is suggested by decreased Δ o2 Hbi and ΔcHbi, with variable ΔHHbi. Finally, acute cerebral congestion may be suspected with increased ΔHHbi and ΔcHbi with unchanged Δ o2 Hbi. Cerebral desaturation can also result from mixed mechanisms reflected by variable combination of those 3 patterns. Normal cerebral saturation can occur, where reduced cerebral oxygen content such as anemia is balanced by a reduction in cerebral oxygen consumption such as during hypothermia. A summative algorithm using rS o2 , Δ o2 Hbi, ΔHHbi, and ΔcHbi is proposed. Further explorations involving more patients should be performed to establish the potential role and limitations of monitoring hemoglobin spectral absorption signals.

In Vivo Protamine Titration Using Activated Coagulation Time to Neutralize Heparin Anticoagulation in Cardiac Surgery: Proof of Concept.

OBJECTIVE: In vivo protamine titration (IVPT) is based on the observation of a plateau on the decay curve of the celite activated clotting times (ACTs) during protamine infusion for heparin reversal. The aim of the present study was to determine the optimal protamine/heparin ratio to reverse anticoagulation using IVPT curves. DESIGN: Prospective, randomized study. SETTING: Tertiary care university hospital. PARTICIPANTS: The study comprised 138 patients undergoing elective cardiac surgery requiring cardiopulmonary bypass. INTERVENTIONS: The control group was given a protamine infusion of 1.3 mg per 1 mg (100 U) of heparin over 21 minutes. ACT was measured every 3 minutes. In the test group, the protamine dose was prepared using the same ratio as for the control group, and ACT values were measured every 3 minutes until a plateau was reached (2 consecutive ACT values <160 s), at which time the protamine infusion was stopped. The protamine/heparin ratio, blood losses, transfusions, and heparin concentrations were recorded. RESULTS: The protamine dose was lower in the test group (456.00 ± 105.66 mg [control group] v 295.25 ± 100.60 mg [test group]; p < 0.0001). The mean protamine/heparin ratios were 1.30 ± 0.10 (control group) and 0.81 ± 0.22 (test group) (p < 0.0001). Heparin concentrations were greater in the test group 15 minutes (0.10 [0-0.2] U/mL v 0 [0-0.1] U/mL; p = < 0.0001) and 3 hours (0 [0-0.1] U/mL v 0 [0-0] U/mL; p = 0.0002) after protamine infusion. There was no difference in the blood losses and transfusion requirements. CONCLUSIONS: IVPT is safe and efficient in this low-risk population.

Preliminary Experience Using Diastolic Right Ventricular Pressure Gradient Monitoring in Cardiac Surgery.

OBJECTIVES: Right ventricular (RV) dysfunction in cardiac surgery is associated with increased mortality and morbidity and difficult separation from cardiopulmonary bypass (DSB). The primary objective of the present study was to describe the prevalence and characteristics of patients with abnormal RV diastolic pressure gradient (PG). The secondary objective was to explore the association among abnormal diastolic PG and DSB, postoperative complications, high central venous pressure (CVP), and high RV end-diastolic pressure (RVEDP). DESIGN: Retrospective and prospective validation study. SETTING: Tertiary care cardiac institute. PARTICIPANTS: Cardiac surgical patients (n=374) from a retrospective analysis (n=259) and a prospective validation group (n=115). INTERVENTION: RV pressure waveforms were obtained using a pulmonary artery catheter with a pacing port opened at 19 cm distal to the tip of the catheter. Abnormal RV diastolic PG was defined as >4 mmHg. Both elevated RVEDP and high CVP were defined as >16 mmHg. MEASUREMENTS AND MAIN RESULTS: From the retrospective and validation cohorts, 42.5% and 48% of the patients had abnormal RV diastolic PG before cardiac surgery, respectively. Abnormal RV diastolic PG before cardiac surgery was associated with higher EuroSCORE II (odds ratio 2.29 [1.10-4.80] v 1.62 [1.10-3.04]; p = 0.041), abnormal hepatic venous flow (45% v 29%; p = 0.038), higher body mass index (28.9 [25.5-32.5] v 27.0 [24.9-30.5]; p = 0.022), pulmonary hypertension (48% v 37%; p = 0.005), and more frequent DSB (32% v 19%; p = 0.023). However, RV diastolic PG was not an independent predictor of DSB, whereas RVEDP (odds ratio 1.67 [1.09-2.55]; p = 0.018) was independently associated with DSB. In addition, RV pressure monitoring indices were superior to CVP in predicting DSB. CONCLUSION: Abnormal RV diastolic PG is common before cardiac surgery and is associated with a higher proportion of known preoperative risk factors. However, an abnormal RV diastolic PG gradient is not an independent predictor of DSB in contrast to RVEDP.

Effect of methylprednisolone on acute kidney injury in patients undergoing cardiac surgery with a cardiopulmonary bypass pump: a randomized controlled trial.

BACKGROUND: Perioperative corticosteroid use may reduce acute kidney injury. We sought to test whether methylprednisolone reduces the risk of acute kidney injury after cardiac surgery. METHODS: We conducted a prespecified substudy of a randomized controlled trial involving patients undergoing cardiac surgery with cardiopulmonary bypass (2007-2014); patients were recruited from 79 centres in 18 countries. Eligibility criteria included a moderate-to-high risk of perioperative death based on a preoperative score of 6 or greater on the European System for Cardiac Operative Risk Evaluation I. Patients (n = 7286) were randomly assigned (1:1) to receive intravenous methylprednisolone (250 mg at anesthetic induction and 250 mg at initiation of cardiopulmonary bypass) or placebo. Patients, caregivers, data collectors and outcome adjudicators were unaware of the assigned intervention. The primary outcome was postoperative acute kidney injury, defined as an increase in the serum creatinine concentration (from the preoperative value) of 0.3 mg/dL or greater (≥ 26.5 µmol/L) or 50% or greater in the 14-day period after surgery, or use of dialysis within 30 days after surgery. RESULTS: Acute kidney injury occurred in 1479/3647 patients (40.6%) in the methylprednisolone group and in 1426/3639 patients (39.2%) in the placebo group (adjusted relative risk 1.04, 95% confidence interval 0.96 to 1.11). Results were consistent across several definitions of acute kidney injury and in patients with preoperative chronic kidney disease. INTERPRETATION: Intraoperative corticosteroid use did not reduce the risk of acute kidney injury in patients with a moderate-to-high risk of perioperative death who had cardiac surgery with cardiopulmonary bypass. Our results do not support the prophylactic use of steroids during cardiopulmonary bypass surgery. Trial registration: ClinicalTrials.gov, no. NCT00427388.

Delirium After Cardiac Surgery and Cumulative Fluid Balance: A Case-Control Cohort Study.

OBJECTIVE: To assess a novel hypothesis to explain delirium after cardiac surgery through the relationship between cumulative fluid balance and delirium. This hypothesis involved an inflammatory process combined with a hypervolemic state, which could lead to venous congestion reaching the brain. DESIGN: Retrospective case-control (1:1) cohort study. SETTING: University-affiliated tertiary cardiology center. PARTICIPANTS: Cardiac surgery intensive care unit (ICU) patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Cumulative fluid balance was evaluated at 3 times: (1) upon arrival at the ICU after surgery, (2) 24 hours post-ICU arrival, and (3) 48 hours post-ICU arrival. A generalized estimated equation was used to model the association between cumulative fluid balance and delirium occurrence 24 hours later. Covariates were selected based on the statistical differences between cases and controls on delirium risk factors and clinical characteristics. The cohort included 346 patients, of which 39 (11%), 104 (30%), and 142 patients (41%) presented delirium at 24, 48, and 72 hours post-ICU arrival, respectively. The effect of time had an odds ratio (OR) of 2.14, 95% confidence interval (CI) 1.603 to 2.851, and a p value < 0.001. The cumulative fluid balance was associated with delirium occurrence (OR 1.20, 95% CI: 1.066-1.355, p = .003). History of neurological disorder, having both hearing and visual impairment, type of procedure, perioperative cerebral oximetry, mean pulmonary artery pressure pre-cardiopulmonary bypass (CPB), and mean arterial pressure post-CPB also contributed to delirium in the model. CONCLUSION: Delirium is associated with a cumulative fluid balance, but the extent through which this plays an etiologic role remains to be determined.

Myocardial Protection in Minimally Invasive Mitral Valve Surgery: Retrograde Cardioplegia Alone Using Endovascular Coronary Sinus Catheter Compared With Combined Antegrade and Retrograde Cardioplegia.

OBJECTIVE: To compare myocardial protection with retrograde cardioplegia alone with antegrade and retrograde cardioplegia in minimally invasive mitral valve surgery (MIMS). DESIGN: Retrospective study. SETTING: Tertiary care university hospital. PARTICIPANTS: The authors studied 97 MIMS patients using retrograde cardioplegia alone and 118 MIMS patients using antegrade and retrograde cardioplegia. INTERVENTIONS: The data from patients admitted for MIMS using retrograde cardioplegia (MIMS retro) between 2009 to 2012 were compared with the data from patients undergoing MIMS with antegrade and retrograde cardioplegia (MIMS ante-retro) between 2006 and 2010 (control group). Cardioplegia in the MIMS retro group was delivered solely through an endovascular coronary sinus (CS) catheter positioned under echographic and fluoroscopic guidance. Antegrade and retrograde cardioplegia was used in the MIMS ante-retro group. Data regarding myocardial infarction (MI; creatine kinase Mb, troponin T, electrocardiogram), myocardial function, and hemodynamic stability were collected for comparison. MEASUREMENTS AND MAIN RESULTS: Adequate cardioplegia administration (CS pressure >30 mmHg and asystole) was attained in 74.2% of the patients with retrograde cardioplegia alone. In 23.7% of the patients, the addition of an antegrade cardioplegia was necessary. No difference was observed in the incidence of MI (0 MIMS retro v 1 for MIMS ante-retro, p = 0.3623), difficult separation from cardiopulmonary bypass, and postoperative malignant arrhythmia. No difference was found for maximal creatine kinase Mb (39.1 [28.0-49.1] v 37.9 [28.6-50.9]; p = 0.8299) and for maximal troponin T levels (0.39 [0.27-0.70] v 0.47 [0.32-0.79]; p = 0.1231) for MIMS retro and MIMS ante-retro, respectively. However, lactate levels in the MIMS retro group were significantly lower than in the MIMS ante-retro group (2.1 [1.4-3.05] v 2.4 [1.8-3.3], respectively; p = 0.0453). No difference was observed in duration of intensive care unit stay and death. MIMS retro patients had a shorter hospital stay (7.0 [6.0-8.0] v 8.0 [7.0-9.0] days; p = 0.0003). CONCLUSION: Retrograde cardioplegia administration alone provided comparable myocardial protection to antegrade and retrograde cardioplegia during MIMS, but was not sufficient to achieve asystole in one-fifth of patients.

Perioperative Right Ventricular Pressure Monitoring in Cardiac Surgery.

Right ventricular (RV) dysfunction is a cause of increased morbidity and mortality in both cardiac surgery and noncardiac surgery and in the intensive care unit. Early diagnosis of this condition still poses a challenge. The diagnosis of RV dysfunction traditionally is based on a combination of echocardiography, hemodynamic measurements, and clinical symptoms. This review describes the method of using RV pressure waveform analysis to diagnose and grade the severity of RV dysfunction. The authors describe the technique, optimal use, and pitfalls of this method, which has been used at the Montreal Heart Institute since 2002, and review the current literature on this method. The RV pressure waveform is obtained using a pulmonary artery catheter with the capability of measuring RV pressure by connecting a pressure transducer to the pacemaker port. The authors describe how RV pressure waveform analysis can facilitate the diagnosis of systolic and diastolic RV dysfunction, the evaluation of RV-arterial coupling, and help diagnose RV outflow tract obstruction. RV pressure waveform analysis also can be used to guide pharmacologic treatment and fluid resuscitation strategies for RV dysfunction.

Acute Right Ventricular Failure in Cardiac Surgery During Cardiopulmonary Bypass Separation: A Retrospective Case Series of 12 Years' Experience With Intratracheal Milrinone Administration.

OBJECTIVE: To report the authors' 12 years of experience with intratracheal milrinone administration and to assess the efficacy and limitations of intratracheal milrinone bolus administration for the treatment of unexpected acute right ventricular (RV) failure in patients undergoing cardiac surgery. DESIGN: Retrospective analysis. SETTING: Single-center university hospital. PARTICIPANTS: One hundred seventy-six patients (4.6%) undergoing on-pump cardiac surgery. INTERVENTIONS: Endotracheal tube administration of milrinone (5-mg bolus) after unexpected acute RV failure during separation from cardiopulmonary bypass (CPB) weaning. RV failure was defined as the simultaneous presence of all of the following criteria: (1) hemodynamic instability or difficult separation from CPB with associated elevated central venous pressure or abnormal RV pressure waveform, (2) >20% reduction of RV fractional area change from baseline evaluated by transesophageal echocardiography, and (3) anatomical visualization of impaired or absent RV wall motion by direct intraoperative visual inspection. MEASUREMENTS AND MAIN RESULTS: Intratracheal milrinone administration was found to improve RV failure in 109 patients (61.9%) whereas RV failure persisted in 67 patients (38.1%). Using a multiple logistic regression model, severely decreased left ventricular ejection fraction (<35% v >50%) (adjusted odds ratio [OR] 3.72; 95% confidence interval [CI] 1.2-11.3; p = 0.012), longer CPB time (adjusted OR 1.014; CI 1.01-1.02; p = 0.001) and elevated postoperative fluid balance (adjusted OR 1.39; CI 1.1-1.8; p = 0.02) were found to be significant predictors of persistent RV failure. CONCLUSION: Intratracheal instillation of milrinone was associated with clinical improvement of RV failure occurring during separation from CPB in almost two-thirds of patients. Factors limiting its therapeutic efficacy include severe left ventricular dysfunction, increased fluid balance, and long CPB time.

Effect of Fibrinogen Concentrate vs Cryoprecipitate on Blood Component Transfusion After Cardiac Surgery: The FIBRES Randomized Clinical Trial.

IMPORTANCE: Excessive bleeding is a common complication of cardiac surgery. An important cause of bleeding is acquired hypofibrinogenemia (fibrinogen level <1.5-2.0 g/L), for which guidelines recommend fibrinogen replacement with cryoprecipitate or fibrinogen concentrate. The 2 products have important differences, but comparative clinical data are lacking. OBJECTIVE: To determine if fibrinogen concentrate is noninferior to cryoprecipitate for treatment of bleeding related to hypofibrinogenemia after cardiac surgery. DESIGN, SETTING, AND PARTICIPANTS: Randomized clinical trial at 11 Canadian hospitals enrolling adult patients experiencing clinically significant bleeding and hypofibrinogenemia after cardiac surgery (from February 10, 2017, to November 1, 2018). Final 28-day follow-up visit was completed on November 28, 2018. INTERVENTIONS: Fibrinogen concentrate (4 g; n = 415) or cryoprecipitate (10 units; n = 412) for each ordered dose within 24 hours after cardiopulmonary bypass. MAIN OUTCOMES AND MEASURES: Primary outcome was blood components (red blood cells, platelets, plasma) administered during 24 hours post bypass. A 2-sample, 1-sided test for the ratio of the mean number of units was conducted to evaluate noninferiority (threshold for noninferiority ratio, <1.2). RESULTS: Of 827 randomized patients, 735 (372 fibrinogen concentrate, 363 cryoprecipitate) were treated and included in the primary analysis (median age, 64 [interquartile range, 53-72] years; 30% women; 72% underwent complex operations; 95% moderate to severe bleeding; and pretreatment fibrinogen level, 1.6 [interquartile range, 1.3-1.9] g/L). The trial met the a priori stopping criterion for noninferiority at the interim analysis after 827 of planned 1200 patients were randomized. Mean 24-hour postbypass allogeneic transfusions were 16.3 (95% CI, 14.9 to 17.8) units in the fibrinogen concentrate group and 17.0 (95% CI, 15.6 to 18.6) units in the cryoprecipitate group (ratio, 0.96 [1-sided 97.5% CI, -∞ to 1.09; P < .001 for noninferiority] [2-sided 95% CI, 0.84 to 1.09; P = .50 for superiority]). Thromboembolic events occurred in 26 patients (7.0%) in the fibrinogen concentrate group and 35 patients (9.6%) in the cryoprecipitate group. CONCLUSIONS AND RELEVANCE: In patients undergoing cardiac surgery who develop clinically significant bleeding and hypofibrinogenemia after cardiopulmonary bypass, fibrinogen concentrate is noninferior to cryoprecipitate with regard to number of blood components transfused in a 24-hour period post bypass. Use of fibrinogen concentrate may be considered for management of bleeding in patients with acquired hypofibrinogenemia in cardiac surgery. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03037424.

Myocardial Protection in Mitral Valve Surgery: Comparison Between Minimally Invasive Approach and Standard Sternotomy.

OBJECTIVE: To compare antegrade and retrograde cardioplegia administration in minimally invasive mitral valve surgery (MIMS) and open mitral valve surgery (OMS) for myocardial protection. DESIGN: Retrospective study. SETTING: Tertiary care university hospital. PARTICIPANTS: The study comprised 118 patients undergoing MIMS and 118 patients undergoing OMS. INTERVENTIONS: The data of patients admitted for MIMS from 2006 to 2010 were reviewed. Patients undergoing isolated elective OMS from 2004 to 2006 were used as a control group. Cardioplegia in the MIMS group was delivered via the distal port of the endoaortic clamp and an endovascular coronary sinus catheter positioned using echographic and fluoroscopic guidance. Antegrade and retrograde cardioplegia were used in OMS. Data regarding myocardial infarction (MI) (creatine kinase [CK]-MB, troponin T, electrocardiography); myocardial function; and hemodynamic stability were collected. MEASUREMENTS AND MAIN RESULTS: There was no difference in the perioperative MI incidence between both groups (1 in each group, p = 0.96). No statistically significant difference was found for maximal CK-MB (35.9 µg/L [25.1-50.1] v 37.9 µg/L [28.6-50.9]; p = 0.31) or the number of patients with CK-MB levels >50 µg/L (29 v 33; p = 0.55) or CK-MB >100 µg/L (3 v 4; p = 0.70) between the OMS and MIMS groups. However, maximum troponin T levels in the MIMS group were significantly lower (0.47 µg/L [0.32-0.79] v 0.65 µg/L [0.45-0.94]; p = 0.0007). No difference in the incidence of difficult weaning from bypass and intra-aortic balloon pump use between the MIMS and OMS groups was found. CONCLUSIONS: Antegrade and retrograde cardioplegia administration during MIMS and OMS provided comparable myocardial protection.

Low-Dose Versus High-Dose Tranexamic Acid Reduces the Risk of Nonischemic Seizures After Cardiac Surgery With Cardiopulmonary Bypass.

OBJECTIVE: The incidence of postoperative nonischemic seizures associated with the use of tranexamic acid (TXA) and the possibility of prevention with a low-dose regimen of TXA were evaluated. DESIGN: Retrospective study. SETTING: Tertiary care university hospital. PARTICIPANTS: A total of 12,195 patients who underwent cardiac surgical procedures under cardiopulmonary bypass (CPB) were evaluated. INTERVENTIONS: The files of every clinical seizure case diagnosed in the surgical intensive care unit between April 2006 and April 2014 were reviewed. Patients who experienced a postoperative seizure underwent a cerebral computed tomography scan to exclude an ischemic lesion. Dosage and type of antifibrinolytic used and surgery characteristics were retrieved from perfusion files. Low-dose TXA was defined as 1,000-mg bolus, 400-mg/h infusion, and 500 mg in CPB priming. High-dose TXA was defined as 30-mg/kg bolus, 15 mg/kg/h, and 2 mg/kg in CPB priming. RESULTS: No seizure was observed in the 886 patients who did not receive antifibrinolytics. A total of 98 clinical seizures (0.8%) were recorded in the intensive care unit, and ischemic cause was excluded in the majority of them after computed tomography scan results were reviewed (91 patients [93%]). Low-dose TXA was associated with fewer seizures than was high-dose TXA (46 of 7,452 cases [0.70%] v 34 of 2,190 cases [1.55%], respectively; p < 0.0001). Open-chamber cardiac surgery also was linked to a higher incidence of seizures compared with revascularization (80 of 6,662 [1.20%] and 11 of 5,533 [0.20%], respectively; p < 0.0001). CONCLUSIONS: Lower doses of TXA were associated with a lower incidence of nonischemic seizures compared with higher doses of the drug.

Methylprednisolone Does Not Reduce Persistent Pain after Cardiac Surgery.

BACKGROUND: Persistent incisional pain is common after cardiac surgery and is believed to be in part related to inflammation and poorly controlled acute pain. Methylprednisolone is a corticosteroid with substantial antiinflammatory and analgesic properties and is thus likely to ameliorate persistent surgical pain. Therefore, the authors tested the primary hypothesis that patients randomized to methylprednisolone have less persistent incisional pain than those given placebo. METHODS: One thousand forty-three patients having cardiopulmonary bypass for cardiac surgery via a median sternotomy were included in this substudy of Steroids in Cardiac Surgery (SIRS) trial. Patients were randomized to 500 mg intraoperative methylprednisolone or placebo. Incisional pain was assessed at 30 days and 6 months after surgery, and the potential risk factors were also evaluated. RESULTS: Methylprednisolone administration did not reduce pain at 30 days or persistent incisional pain at 6 months, which occurred in 78 of 520 patients (15.7%) in the methylprednisolone group and in 88 of 523 patients (17.8%) in the placebo group. The odds ratio for methylprednisolone was 0.93 (95% CI, 0.79 to 1.09, P = 0.37). Furthermore, there was no difference in worst pain and average pain in the last 24 h, pain interference with daily life, or use of pain medicine at 6 months. Younger age, female sex, and surgical infections were associated with the development of persistent incisional pain. CONCLUSIONS: Intraoperative methylprednisolone administration does not reduce persistent incisional pain at 6 months in patients recovering from cardiac surgery.

Interrelationship of preoperative anemia, intraoperative anemia, and red blood cell transfusion as potentially modifiable risk factors for acute kidney injury in cardiac surgery: a historical multicentre cohort study.

PURPOSE: Acute kidney injury (AKI) is a potentially serious complication of cardiac surgery. Anemia and red blood cell (RBC) transfusion have individually been identified as potentially modifiable risk factors, but their interrelationship with AKI has not been clearly defined. The purpose of this study was to explore the interrelationship of preoperative anemia, intraoperative anemia, and RBC transfusion on the day of surgery with AKI in cardiac surgery. METHODS: This historical cohort study included 16 hospitals, each contributing data on approximately 100 consecutive patients who underwent cardiac surgery with cardiopulmonary bypass. Acute kidney injury was defined as a > 50% increase in creatinine levels during the first postoperative week. Multivariable regression was used to identify the interrelationship between preoperative anemia (hemoglobin < 130 g·L(-1) in males and < 120 g·L(-1) in females), intraoperative anemia (hemoglobin < 80 g·L(-1) during cardiopulmonary bypass), RBC transfusion on the day of surgery, and their interaction terms, after adjusting for site and baseline AKI risk. RESULTS: Of the 1,444 patients included in the study, 541 (37%) had preoperative anemia, 501 (35%) developed intraoperative anemia, 619 (43%) received RBC transfusions, and 238 (16%) developed AKI. After risk-adjustment, an individual with the combination of these three risk factors had a 2.6-fold (95% confidence interval 2.0 to 3.3) increase in the relative risk of AKI over an individual with none of these risk factors. CONCLUSIONS: Preoperative anemia, intraoperative anemia, and RBC transfusion on the day of surgery are interrelated risk factors for AKI after cardiac surgery. Targeting these risk factors may reduce the burden of AKI.

Off-label use of recombinant activated factor VII in surgical and non-surgical patients at 16 Canadian hospitals from 2007 to 2010 (Canadian Registry Report).

PURPOSE: Recombinant activated factor VII (rFVIIa) is a pro-hemostatic drug that is approved for treatment of bleeding in hemophilia patients, but it is frequently used off-label in non-hemophiliacs. The purpose of this study was to determine if the off-label use of rFVIIa is expanding and whether this poses a net harm to patients. METHODS: For this historical cohort study, data were collected on all non-hemophilia patients who received rFVIIa from 2007 to 2010 at 16 Canadian centres, and the pattern of use was examined. Logistic regression was used to determine the prognostic importance of severity of bleeding and the presence of an rFVIIa dose-effect relationship with major adverse events. RESULTS: One thousand three hundred seventy-eight patients received rFVIIa off-label, and 987 (72%) of these patients underwent cardiac surgery. The median [interquartile range] dose was 57 [36-85] µg·kg(-1). Usage increased from 2007 to 2008 (n = 341 and 380, respectively) but decreased in 2009 and 2010 (n = 350 and 307, respectively). Dose of rFVIIa and bleeding severity were associated with measured adverse events (P < 0.05). After adjusting for bleeding severity, dose was not associated with any of the adverse events. CONCLUSIONS: The off-label use of rFVIIa in Canada remains stable. Since severity of bleeding is prognostically important, the benefits of rapidly gaining control of bleeding that is non-responsive to conventional therapies may at times warrant the use of potent hemostatic drugs with established risk profiles, such as rFVIIa.

Evaluation of autonomic reserves in cardiac surgery patients.

OBJECTIVE: Autonomic nervous system dysfunction is a well-recognized but rarely evaluated risk factor for patients undergoing cardiac surgery. By measuring autonomic reserves in patients scheduled for cardiac surgery, the authors aimed to identify those with autonomic dysfunction and to evaluate their risk of perioperative complications. DESIGN: This was a prospective, observational study. SETTING: The study was conducted in a single academic center. PARTICIPANTS: Sixty-seven patients completed the study. INTERVENTIONS: Autonomic reserves were evaluated using analysis of heart rate variability (HRV) and blood pressure variability (BPV) after a Valsalva maneuver. MEASUREMENTS AND MAIN RESULTS: The patients were divided into 2 groups depending on their response to the autonomic challenge, a group with autonomic reserves (AR, n = 38) and a group with negligible autonomic reserves (NAR, n = 29). The groups were compared for baseline psychologic distress, demographic and medical profiles, autonomic response to morphine premedication and the induction of anesthesia, hemodynamic instability, the occurrence of decreases in cerebral oxygen saturation, and postoperative complications. Patients in the NAR group had significantly higher psychologic distress scores (p < 0.001), a higher baseline parasympathetic tone (p = 0.003), were unable to increase parasympathetic tone with morphine premedication, had more severe hypotension at the induction of anesthesia (p < 0.001), more episodes of decreases in cerebral saturation (p = 0.0485), and a higher overall complication rate (p = 0.0388) independent of other variables studied. CONCLUSIONS: Patients with diminished autonomic reserves can be identified before cardiac surgery using analysis of HRV and BPV of the response to the Valsalva maneuver, and some evidence suggests that they may be at increased risk of perioperative complications.

Reversal of decreases in cerebral saturation in high-risk cardiac surgery.

OBJECTIVES: To measure the incidence of cerebral desaturation during high-risk cardiac surgery and to evaluate strategies to reverse cerebral desaturation. DESIGN: Prospective observational study followed by a randomized controlled study with 1 intervention group and 1 control group. SETTING: Tertiary care center specialized in cardiac surgery. PARTICIPANTS: All patients were scheduled for high-risk cardiac surgery, 279 consecutive patients in the prospective study and 48 patients in the randomized study. INTERVENTIONS: An algorithmic approach of strategies to reverse cerebral desaturation. In the control group, no attempts were made to reverse cerebral desaturation. MEASUREMENTS AND MAIN RESULTS: Cerebral saturation was measured using near-infrared reflectance spectroscopy. A decrease of 20% from baseline for 15 seconds defined cerebral desaturation. The success or failure of the interventions was noted. Demographic data were collected. Models for predicting the probability and the reversal of cerebral desaturation were based on multiple logistic regressions. In the randomized study, 12 hours of measurements were continued in the intensive care unit without interventions. Differences in desaturation load (% desaturation × time) were compared between groups. Half of the high-risk patients had cerebral desaturation that could be reversed 88% of the time. Interventions resulted in smaller desaturation loads in the operating room and in the intensive care unit. CONCLUSIONS: Cerebral desaturation in high-risk cardiac surgery is frequent but can be reversed most of the time resulting in a smaller desaturation load. A large randomized study will be needed to measure the impact of reversing cerebral desaturation on patient's outcome.

Methemoglobin as a marker of acute anemic stress in cardiac surgery.

Biological evidence supports plasma methemoglobin as a biomarker for anemia-induced tissue hypoxia. In this translational planned substudy of the multinational randomized controlled transfusion thresholds in cardiac surgery (TRICS-III) trial, which included adults undergoing cardiac surgery requiring cardiopulmonary bypass with a moderate-to-high risk of death, we investigated the relationship between perioperative hemoglobin concentration (Hb) and methemoglobin; and evaluated its association with postoperative outcomes. The primary endpoint was a composite of death, myocardial infarction, stroke, and severe acute kidney injury at 28 days. We observe weak non-linear associations between decreasing Hb and increasing methemoglobin, which were strongest in magnitude at the post-surgical time point. Increased levels of post-surgical methemoglobin were associated with a trend toward an elevated risk for stroke and exploratory neurological outcomes. Our generalizable study demonstrates post-surgical methemoglobin may be a marker of anemia-induced organ injury/dysfunction, and may have utility for guiding personalized approaches to anemia management. Clinicaltrials.gov registration NCT02042898.