Hydroxocobalamin for the treatment of cardiac surgery-associated vasoplegia: a case series.

PURPOSE: Vasoplegia is a clinical syndrome marked by severe arteriolar vasodilatation, hypotension, and low systemic vascular resistance refractory to multiple vasopressor treatment. We report our experience with hydroxocobalamin (B12) infusion as a potential rescue adjunct for refractory vasoplegia during cardiopulmonary bypass (CPB). METHODS: We performed a retrospective chart review of 33 patients undergoing cardiac surgery between 1 January 2013 and 31 December 2015, who were given intravenous B12 for refractory hypotension during, or immediately following, CPB. We assessed mean arterial pressure (MAP) responses using semi-parametric group-based models (trajectory analysis). Vasopressor use was evaluated by norepinephrine-equivalent rates calculated five minutes prior, and up to 60 min following, B12 administration. RESULTS: Patients were mostly male (82%), had a mean (SD) age of 53 (13) yr, and median (IQR) EuroSCORE mortality index of 9 [4-40]. Four patterns of MAP responses to B12 were identified. In Group 1 ("poor responders") nine of 33 patients (27%) had the highest median [IQR] mortality risk (EuroSCORE 40 [4-52]), lowest mean pre-B12 MAP (50 mmHg), and minimal hemodynamic response in spite of continued vasopressor support. In contrast, Group 2 "responders" (8/33, 24%) showed a brisk MAP response (> 15 mmHg) to B12, sustained for > 60 min post-infusion, with 50% vasopressor reduction. Groups 3 and 4 had the lowest median mortality risk (EuroSCORE 8) and highest pre-B12 MAP (72 mmHg). Although Group 3 patients ("sustainers"; 9/33, 27%) showed a sustained MAP improvement, those in Group 4 ("rebounders"; 7/33, 21%) were characterized by hypertensive overshoot followed by a decrease in MAP. CONCLUSION: These data indicate considerable heterogeneity in patient response to B12, potentially dependent on both patient preoperative condition and non-standardized time of administration. B12 may provide a useful alternative therapy for refractory hypotension and vasoplegia, but controlled clinical trials to assess efficacy are needed.

A Comparison of a New Ultrasound-Based Whole Blood Viscoelastic Test (SEER Sonorheometry) Versus Thromboelastography in Cardiac Surgery.

BACKGROUND: Viscoelastic thromboelastography tests such as TEG™ are now routine for assessing the coagulation status of cardiac surgery patients. We compared TEG™ with a new technology, sonic estimation of elasticity via resonance (SEER) sonorheometry, to compare measures of coagulation dynamics of whole blood and assess its potential for rapid, near-point-of-care monitoring of hemostasis during cardiac surgery. METHODS: Whole blood coagulation assessment of a prospective cohort of 50 cardiac surgery patients was performed using SEER sonorheometry and blood samples collected at 4 time points during cardiac surgery: baseline before anesthetic induction, during cardiopulmonary bypass on rewarming, 10 minutes after heparin reversal by protamine, and on patient transfer to the intensive care unit. Clot strength trajectories (G, measured by TEG™; and clot stiffness measured by SEER sonorheometry) and clot times were assessed by repeated-measures mixed models. Strength of association between the 2 methods (clot stiffness and clot times) was assessed using a modified Bland-Altman method for repeated measures; Deming (orthogonal) regression was used to quantify method concordance (constant and proportional bias). RESULTS: Clot strength/stiffness and clot time measures for both techniques showed similar tracking of trajectories. Strength of association between methods was acceptable (correlations, 0.8-0.9); however, Deming regression detected substantial deviation (bias) between techniques. SEER clot stiffness values averaged approximately 10 hPa higher than corresponding G at all time points. Reaction time (TEG™) was 1 to 2.5 minutes longer than corresponding clot times (SEER). Laboratory times (from sample drop-off to results) were substantially less for SEER sonorheometry (median time, 11-17 minutes) compared with nonautomated kaolin TEG™ (median time, 42 minutes). CONCLUSIONS: Currently, no viscoelastic hemostatic analyzer system can be considered the "gold standard"; therefore, differences observed between TEG™ and SEER are of importance only because they show that the methods are not perfectly substitutable. Measurements of clot stiffness determined by the 2 methods were correlated but not interchangeable. Reasons for discrepancies include the substantial difference in the physical methods of inducing coagulation activation in samples and the mathematical assumptions underlying calculations of G. Future studies will be required to evaluate SEER sonorheometry's abilities to identify bleeding diatheses (sensitivity/specificity) or to develop treatment algorithms based on the new tests.

Developing a blood conservation program in cardiac surgery.

The beneficial effects of blood transfusions have been described and widely accepted. Multiple factors, including shortages, costs, infectious risks, immunologic risks, and the risk/benefit ratio to the patient, have made the medical community reassess the guidelines for transfusion. Cardiac surgery presents a unique subset of patients, because intervention at multiple stages in the care of these patients is possible to decrease the need for transfusion. An algorithm for a cardiac surgery program was developed and a reassessment performed. Once it was seen that no detrimental effect on patient care occurred, the program was expanded, was enhanced, and subsequently has been offered to the rest of the health care system. This program has resulted in a decrease in cost while maintaining patient outcomes. The success of the program is believed to be a result of the multidisciplinary approach taken, with a commitment from all members of the blood reduction team being the key component of this success.

Use of bivalirudin as an anticoagulant during cardiopulmonary bypass.

Bivalirudin is a short-acting direct thrombin inhibitor that has been used in cardiac surgical patients with heparin-induced thrombocytopenia (HIT) or suspected HIT. Although no direct thrombin inhibitor is indicated for anticoagulation during cardiac surgery in patients with heparin-induced thrombocytopenia (HIT) or suspected HIT, use of heparin-alternatives are increasing as the awareness of HIT increases. Reports of anticoagulation with bivalirudin are sporadic, however, with variable dosing and management strategies. In this report, we describe our management techniques for cardiopulmonary bypass with bivalirudin based upon our personal experience. Although the reported clinical experience with bivalirudin in cardiac surgery is reviewed, operative techniques for the perfusionist/surgeon team are discussed in detail. We recognize that the use of bivalirudin during cardiopulmonary bypass is evolving and modifications of technique will undoubtedly occur as further data and experience accumulate.

Transapical arterial cannulation for salvage cardiopulmonary bypass in transcatheter aortic valve replacement.

Hemodynamic instability during transcatheter aortic valve replacement procedures may require transient cardiopulmonary bypass for support. In patients with severe atherosclerosis, peripheral cannulation may not be possible. This method of direct left ventricle cannulation during transapical TAVR is a facile means to provide arterial inflow.

Bivalirudin during cardiopulmonary bypass in patients with previous or acute heparin-induced thrombocytopenia and heparin antibodies: results of the CHOOSE-ON trial.

BACKGROUND: The coronary artery bypass grafting (CABG) heparin-induced thrombocytopenia thrombosis syndrome (HITTS) on- and off-pump safety and efficacy (CHOOSE-ON) trial was designed as a safety and efficacy trial of bivalirudin for use in anticoagulation during cardiopulmonary bypass (CPB) in patients with confirmed or suspected HIT and (or) antiplatelet factor 4/heparin (anti-PF4/H) antibodies. METHODS: In an open-label, multicenter trial, 50 patients were enrolled prospectively. The primary study endpoint was in-hospital acute procedural success, defined as the absence of death, Q-wave myocardial infarction (MI), repeat operation for coronary revascularization, and stroke at day seven after surgery or hospital discharge, whichever occurred first. The secondary study endpoints were procedural success, defined as the absence of death, Q-wave MI, repeat operation for coronary revascularization, and stroke, at 30 days and 12 weeks after surgery. Perioperative blood loss, transfusions, and the incidence of major bleeding events were also captured. RESULTS: There were 49 patients treated with bivalirudin of which 43 had acute HIT and thrombosis syndrome (HITTS) with antibodies at time of surgery. Procedural success in-hospital or at 7 days was achieved in 46 (94%) patients. At day 30 procedural success was achieved in 42 (86%) patients, and after 12 weeks in 40 (82%) patients. Mean intraoperative blood loss was 575 +/- 524 mL, and mean 24-hour postoperative blood loss was 998 +/- 595 mL. Forty-one (84%) patients received transfusions before day 7 or discharge with a mean of 5.6 +/- 3.8 units of red blood cells, 8.6 +/- 7.2 units of platelets, and 6.0 +/- 4.7 units of fresh frozen plasma. No differences in outcome among bivalirudin-treated patients were observed between those in the overall group and those with moderately impaired renal function (n = 10). CONCLUSIONS: The current investigation expands the experience of safe and effective anticoagulation with bivalirudin during CPB to patients with confirmed or suspected HIT and anti-PF4/H antibodies, including in the setting of impaired renal function.

Bivalirudin anticoagulation for a patient with hypercoagulable immune syndromes undergoing mitral valve surgery.

Unfractionated heparin has been a near universal anticoagulant for cardiac surgery; however it is contraindicated in heparin-induced thrombocytopenia type II. Alternative anticoagulants such as bivalirudin (a direct thrombin inhibitor) are being utilized. Bivalirudin was successfully used in an immunologically complex patient (diagnoses of heparin-induced thrombocytopenia type II, systemic lupus erythematosus, antiphospholipid syndrome, and dialysis-dependent renal failure) requiring cardiopulmonary bypass. Thrombotic events are common in antiphospholipid syndrome patients undergoing cardiac surgery utilizing high-dose heparin. This may represent unrecognized heparin-induced thrombocytopenia type II. Our patient did not experience perioperative thrombotic or bleeding complications. The possible cross-reactivity between heparin induced thrombocytopenia type II and antiphospholipid syndrome has not been investigated.

A comparison of bivalirudin to heparin with protamine reversal in patients undergoing cardiac surgery with cardiopulmonary bypass: the EVOLUTION-ON study.

OBJECTIVES: Unfractionated heparin and its antidote, protamine sulfate, allow for rapid and reversible anticoagulation during cardiac surgery with cardiopulmonary bypass, yet limitations exist, including a variable dose-response, dependence on a cofactor for anticoagulant effect, and antigenic potential. This trial was performed to evaluate the safety and efficacy of bivalirudin as an alternative to heparin with protamine reversal in on-pump cardiac surgery. METHODS: We conducted a randomized, open-label, multicenter trial comparing heparin with protamine reversal to bivalirudin in patients undergoing cardiac surgery with cardiopulmonary bypass. The primary objective was to demonstrate comparable rates of in-hospital procedural success defined as freedom from death, Q-wave myocardial infarction, stroke, or repeat revascularization. Twenty-one institutions enrolled 101 patients randomized to bivalirudin and 49 patients to heparin treatment. RESULTS: The primary end point of procedural success was not significantly different between the bivalirudin arm and the heparin/protamine arms at 7 days, 30 days, or 12 weeks' follow-up. Adequate anticoagulation was achieved in all patients. Secondary end points including mortality, 24-hour blood loss, overall incidence of transfusions, and duration of surgery were similar between the two arms. CONCLUSIONS: Bivalirudin is a safe and effective anticoagulant for patients undergoing a wide range of cardiac surgical procedures with cardiopulmonary bypass. Procedural success rates with bivalirudin were similar to rates in patients receiving heparin anticoagulation, with no difference in mortality. Avoidance of blood stasis and attention to the intraoperative medical management of patients is critical for successful use of bivalirudin during cardiopulmonary bypass.

Anticoagulation with bivalirudin for off-pump coronary artery bypass grafting: the results of the EVOLUTION-OFF study.

OBJECTIVES: Unfractionated heparin has many shortcomings, including indirect and partial inhibition of thrombin, antibody formation, and platelet activation. Bivalirudin, a short-acting direct thrombin inhibitor, avoids these limitations and has superior outcomes during percutaneous revascularization. This trial was performed to evaluate the safety and efficacy of bivalirudin in off-pump coronary artery bypass grafting. METHODS: An open-label, multicenter randomized trial compared heparin with protamine reversal to bivalirudin in patients undergoing off-pump coronary artery bypass. The primary objective was safety as demonstrated by similar rates of procedural success defined as freedom from a composite of death, myocardial infarction, stroke, and repeat revascularization. Twenty-one institutions randomized 105 patients to receive bivalirudin and 52 patients to receive heparin. RESULTS: The mean age was 65 years for both groups. The bivalirudin group had more grafts: 3.0 +/- 1 versus 2.5 +/- 1. Procedural success rates at 30 days were identical in bivalirudin- and heparin-treated patients (93%). Operative times, total blood loss, reoperations for bleeding, and major adverse events were not significantly different. Strokes were more frequent in the heparin group: 5.5% versus 0; P = .05. Mortality was 2% in each group. Repeat revascularization was required in 3% of bivalirudin- and 2% of the heparin-treated patients. CONCLUSIONS: For patients undergoing off-pump coronary artery bypass grafting, bivalirudin was an effective anticoagulant, without excessive bleeding and with a safety profile similar to that of heparin. Further trials are warranted to assess whether anticoagulation with bivalirudin improves clinical outcomes.