The role of methadone in cardiac surgery for management of postoperative pain.

Background: This retrospective study evaluated the efficacy and safety of intraoperative methadone compared with short-acting opioids. Methods: Patients undergoing cardiac surgery with cardiopulmonary bypass (n=11 967) from 2018 to 2023 from a single health system were categorised into groups based on intraoperative opioid administration: no methadone (Group O), methadone plus other opioids (Group M+O), and methadone only (Group M). Results: Patients in Groups M and M+O had lower mean pain scores until postoperative day (POD) 7 compared with Group O after adjusting for covariates (P<0.01). Both Groups M and M+O had lower total opioid administered compared with Group O for all days POD0-POD6 (all P<0.001). The median number of hours until initial postoperative opioid after surgery was 2.55 (inter-quartile range [IQR]=1.07-5.12), 6.82 (IQR=3.52-12.98), and 7.0 (IQR=3.82-12.95) for Group O, Group M+O, and Group M, respectively. The incidence of postoperative complications did not differ between groups. Conclusions: Intraoperative administration of methadone was associated with better pain control without significant side-effects after cardiac surgery.

Intraoperative Versus Postoperative Hydroxocobalamin for Vasoplegic Shock in Cardiothoracic Surgery.

OBJECTIVES: Hydroxocobalamin inhibits nitric oxide pathways contributing to vasoplegic shock in patients undergoing cardiopulmonary bypass (CPB). The objective of this study was to evaluate the effect of intraoperative versus postoperative application of hydroxocobalamin for vasoplegic shock in patients undergoing CPB. DESIGN: This was a historic cohort study. SETTING: The study was conducted at a quaternary academic cardiovascular surgery program. PARTICIPANTS: Adults undergoing cardiac surgery using CPB were participants in the study. INTERVENTIONS: Hydroxocobalamin (5 g) intravenously over 15 minutes. MEASUREMENTS AND MAIN RESULTS: The treatment groups were assigned based on the receipt location of hydroxocobalamin (ie, intensive care unit [ICU] versus operating room [OR]). The primary outcome was vasopressor-free days in the first 14 days after CPB. Of the 112 patients included, 37 patients received hydroxocobalamin in the OR and 75 in the ICU. Patients in the OR group were younger than those in the ICU group (57.5 v 63.9 years, p = 0.007), with statistically similar American Society of Anesthesiologists scores. The mean CPB duration was 3.4 hours in the OR group and 2.9 hours in the ICU group (p = 0.09). In both groups, the norepinephrine-equivalent dose of vasopressors at hydroxocobalamin was 0.27 µg/kg/min. Days alive and free of vasopressors were not different between the OR and ICU groups (estimated difference 0.48 [95% CI -1.76-2.72], p = 0.67). The odds of postoperative renal failure, mesenteric ischemia, ICU, hospital length of stay, and in-hospital mortality were also similar between groups. CONCLUSIONS: A difference in vasopressor-free days after CPB was not found between patients who received hydroxocobalamin intraoperatively versus postoperatively for vasoplegic shock.

Impact of ketamine versus propofol for anesthetic induction on cognitive dysfunction, delirium, and acute kidney injury following cardiac surgery in elderly, high-risk patients.

Objective: Evaluate the effects of ketamine versus propofol when used for induction of anesthesia in elderly, high-risk cardiac surgical patients on postoperative complications including cognitive dysfunction, delirium, and acute kidney injury. Methods: Prospective, randomized study performed at a tertiary medical center. A total of 52 patients aged ≥70 and older presenting for complex cardiac surgery were randomized to receive either ketamine or propofol for induction of anesthesia. Patients underwent a battery of cognitive testing preoperatively and postoperatively and the incidence of delirium and acute kidney injury were measured. Norepinephrine (NEE) equivalents following induction were assessed for each group. Results: A total of 49 patients were included, 25 in the ketamine group and 24 in the propofol group with 3 patients excluded from the analysis. No difference was found between groups in either postoperative cognitive dysfunction or delirium incidence. Acute kidney injury occurred in 6 (24%) patients in the ketamine group in 12 (50%) patients in the propofol group, but the difference did not meet statistical significance (P = 0.08; Relative Risk = 2.1, 95% CI 0.9-4.7). NEE equivalents were lower in the ketamine group, 9.6 ± 22.2 versus 32.7 ± 46.0, P < 0.03. Conclusions: The use of ketamine versus propofol for induction of anesthesia did not impact the incidence of postoperative cognitive dysfunction or delirium. Twice as many patients in the propofol group developed acute kidney injury, although not reaching statistical significance and warranting further investigation. In elderly, high-risk patients, ketamine was associated with a significantly reduced need for vasopressor support following induction.

Hydroxocobalamin for Vasodilatory Hypotension in Shock: A Systematic Review With Meta-Analysis for Comparison to Methylene Blue.

Hydroxocobalamin inhibits nitric oxide-mediated vasodilation, and has been used in settings of refractory shock. However, its effectiveness and role in treating hypotension remain unclear. The authors systematically searched Ovid Medline, Embase, EBM Reviews, Scopus, and Web of Science Core Collection for clinical studies reporting on adult persons who received hydroxocobalamin for vasodilatory shock. A meta-analysis was performed with random-effects models comparing the hemodynamic effects of hydroxocobalamin to methylene blue. The Risk of Bias in Nonrandomized Studies of Interventions tool was used to assess the risk of bias. A total of 24 studies were identified and comprised mainly of case reports (n = 12), case series (n = 9), and 3 cohort studies. Hydroxocobalamin was applied mainly for cardiac surgery vasoplegia, but also was reported in the settings of liver transplantation, septic shock, drug-induced hypotension, and noncardiac postoperative vasoplegia. In the pooled analysis, hydroxocobalamin was associated with a higher mean arterial pressure (MAP) at 1 hour than methylene blue (mean difference 7.80, 95% CI 2.63-12.98). There were no significant differences in change in MAP (mean difference -4.57, 95% CI -16.05 to 6.91) or vasopressor dosage (mean difference -0.03, 95% CI -0.12 to 0.06) at 1 hour compared to baseline between hydroxocobalamin and methylene blue. Mortality was also similar (odds ratio 0.92, 95% CI 0.42-2.03). The evidence supporting the use of hydroxocobalamin for shock is limited to anecdotal reports and a few cohort studies. Hydroxocobalamin appears to positively affect hemodynamics in shock, albeit similar to methylene blue.

Tris-Hydroxymethyl Aminomethane in Critically Ill Adults: A Systematic Review.

Tris-hydroxymethyl aminomethane (THAM) is an amino alcohol used clinically to buffer acid loads and raise pH in acidotic conditions. Unlike sodium bicarbonate, which increases plasma sodium levels with use and produces carbon dioxide (CO 2 ) as part of the buffering process, THAM does neither. Although not widely used in modern critical care and unavailable for clinical use in 2016, THAM has been available in the United States since 2020. Clinical experience and existing literature suggest that THAM may have clinical utility in acid-base management in conditions such as liver transplantation where rising sodium levels during perioperative care may be dangerous, and in managing acid-base derangements during care of patients with acute respiratory distress syndrome (ARDS). To clarify the evidence base supporting the clinical use of THAM, we conducted a systematic review to assess the efficacy and safety of THAM as a buffering agent in critically ill adults using Ovid EBM Reviews, Ovid Embase, Ovid Medline, Scopus, and Web of Science Core Collection. Randomized-, crossover-, retrospective cohort-, parallel-designed clinical trials, case series, and case reports of adult patients who received THAM in the operative or critical care setting were included. Conference abstracts of qualifying study designs were also included. Two independent reviewers extracted the data regarding the study details, demographics, treatment, and outcomes data. A third reviewer adjudicated discrepancies. A total of 21 studies including 3 randomized controlled trials, 5 observational studies, 4 case series, and 9 case reports met inclusion criteria. Eight studies (38%) were abstracts published in conference proceedings. In total, 417 critically ill patients received THAM to treat acidosis in critically ill surgical and nonsurgical patients, during liver transplantation, and in ARDS. In general, THAM corrected acidosis with an efficacy equivalent to sodium bicarbonate and did so with less hypercarbia and hypernatremia. Adverse effects of THAM included hyperkalemia, hypoglycemia, ventilator depression, and tissue damage with extravasation. We conclude that THAM may have potential advantages in some critical care settings, but that clinical evidence is limited, and high-quality evaluations are necessary.

Single-Center Retrospective Comparison of Opioid-Based and Multimodal Analgesic Regimens in Adult Cardiac Surgery.

OBJECTIVES: To compare the outcomes of 2 multimodal analgesic regimens with an opioid-based one. DESIGN: A 2-stage, retrospective study. SETTING: A large tertiary-care facility. PARTICIPANTS: Adult cardiac surgical patients. INTERVENTIONS: Patients received one of three regimens: opioid-only or 2 multimodal regimens. The opioid regimen included intraoperative fentanyl and patient-controlled analgesia pumps. Multimodal regimen 1 included preoperative extended-release oxycodone, intraoperative ketamine infusion, and postoperative morphine suppository. Multimodal regimen 2 included intraoperative methadone and dexmedetomidine infusion. MEASUREMENTS AND MAIN RESULTS: Outcomes measured included opioid use, pain scores, time to tracheal extubation, postoperative antiemetic use as a surrogate marker for postoperative nausea and vomiting (PONV), age, sex, surgical procedure(s), body mass index, time to first bowel movement, intensive care unit length of stay (LOS), and hospital LOS. Intraoperative median oral morphine equivalents (OMEs) declined from 425 mg (314, 518) to 150 mg (75, 150) and 230 mg (160, 240), p < 0.001, in multimodal regimens 1 and 2, respectively, compared with the opioid-only regimen. Predischarge opioid use was reduced from a median OME of 7.5 mg (0, 22.5) to 5 mg (0, 22.5) and 0 mg (0, 15.0), p < 0.001, in multimodal regimens 1 and 2, respectively. Pain scores were reduced in the multimodal regimen 2 for hours 0 to 6 (estimated difference = -1.5, 95% CI -1.8 to -1.2, p < 0.001) compared with the opioid-only regimen. The PONV treatment was reduced in multimodal regimen 1 versus the opioid-based or multimodal regimen 2 (53% v 64% and 62%), and time to tracheal extubation was clinically equivalent across all regimens: 4.2 (2.8, 6.0), 3.6 (2.3, 5.7), and (3.0, 6.2) hours for the opioid and multimodal regimens 1 and 2, respectively. CONCLUSIONS: Multimodal analgesic regimens, particularly when incorporating methadone and dexmedetomidine, significantly reduced total and predischarge opioid use in cardiac surgical patients.

Procainamide pharmacokinetics during extracorporeal membrane oxygenation.

Procainamide is a useful agent for management of ventricular arrhythmia, however its disposition and appropriate dosing during extracorporeal membrane oxygenation (ECMO) is unknown. We report experience with continuous procainamide infusion in a critically ill adult requiring venoarterial ECMO for incessant ventricular tachycardia. Pharmacokinetic analysis of procainamide and its metabolite, N-acetylprocainamide (NAPA), was performed using serum and urine specimens. Kidney function was preserved, and sequencing of the N-acetyltransferase 2 gene revealed the patient was a phenotypic slow acetylator. Procainamide volume of distribution and half-life were calculated and found to be similar to healthy individuals. However, despite elevated serum procainamide concentrations, NAPA concentrations remained far lower in the serum and urine. The magnitude of procainamide and NAPA discordance suggested alternative contributors to the deranged pharmacokinetic profile, and we hypothesized NAPA sequestration by the ECMO circuit. Ultimately, the patient received orthotopic cardiac transplantation and was discharged home in stable condition. Procainamide should be used cautiously during ECMO, with close therapeutic drug monitoring of serum procainamide and NAPA concentrations. The achievement of therapeutic NAPA concentrations while maintaining safe serum procainamide concentrations during ECMO support may be challenging.

Does Minimally Invasive Mitral Valve Repair Mean Less Postoperative Pain?

BACKGROUND: Rapid recovery after minimally invasive mitral valve (MV) repair has been demonstrated in many studies, but the issue of postoperative pain has not been fully elucidated. We evaluated pain scores and medication use in patients undergoing MV repair by minimally invasive surgery (MIS) and open sternotomy (OS). METHODS: Between 2008 and 2019, 1332 patients underwent isolated MV repair by OS, and 913 underwent minimally invasive MV repair. After 1:1 propensity score matching, the study included 709 patients in each group. Opioid use was quantified as oral morphine equivalents in milligrams for each hospital day. The highest pain scores were collected from a visual analogue scale at 6-hour intervals. Predictive modeling was employed to compare pain medications and pain scores between the groups. RESULTS: The postoperative median length of stay was 3 (3-4) and 5 (4-5) days for the MIS and OS groups, respectively (P < .001). The predicted geometric mean oral morphine equivalents demonstrated lower opioid use for the MIS group compared with the OS group for the first 4 days. However, the predicted mean pain score was higher in the first 24 hours for the MIS group compared with the OS group (4.7 [4.5-4.8] vs 4.4 [4.3-4.5], respectively, on a visual analogue scale of 0 to 10). CONCLUSIONS: MV repair by MIS methods was associated with decreased opioid use but not with decreased postoperative pain scores. Possible explanations include the difference in incision site pain and subjective differences in postoperative pain expectations.

Heparin Versus Bivalirudin for Anticoagulation in Adult Extracorporeal Membrane Oxygenation: A Systematic Review and Meta-Analysis.

Extracorporeal membrane oxygenation (ECMO) poses unique thrombotic and hemorrhagic risks, and the optimal anticoagulant choice is unknown. We systematically searched Ovid EBM Reviews, Ovid Embase, Ovid Medline, Scopus, and Web of Science Core Collection for randomized-, crossover-, retrospective cohort-, or parallel-designed clinical studies of adult patients receiving ECMO that compared heparin recipients with bivalirudin recipients. Meta-analysis was performed with random-effects models. The ROBINS-I tool was used to assess the risk of bias. Six retrospective observational studies met the inclusion criteria for the qualitative summary. Five studies were suitable for meta-analysis. Those who received heparin were more likely to experience circuit-related thrombosis (odds ratio [OR] 2.05, 95% confidence interval [CI] 1.25-3.37, p = 0.005, I2 = 0%) and die (OR 1.62, 95% CI 1.19-2.21, p = 0.002, I2 = 0%) compared with those who received bivalirudin. There were no differences in major bleeding events between heparin and bivalirudin recipients (OR 1.83, 95% CI 0.55-6.09, p = 0.33, I2 = 82.7%). In retrospective settings compared with heparin anticoagulation, bivalirudin was associated with less circuit-related thrombotic events and greater survival in adults supported on ECMO, without contributing to more bleeding complications. Prospective controlled studies comparing heparin and bivalirudin in adult ECMO patients are warranted to corroborate these findings.

Angiotensin II for Vasodilatory Hypotension in Patients Requiring Mechanical Circulatory Support.

Background: Patients supported on mechanical circulatory support devices experience vasodilatory hypotension due to high surface area exposure to nonbiological and non-endothelialized surfaces. Angiotensin II has been studied in general settings of vasodilatory shock, however concerns exist regarding the use of this vasopressor in patients with pre-existing cardiac failure. The objective of this study was to assess the systemic and central hemodynamic effects of angiotensin II in patients with primary cardiac or respiratory failure requiring treatment with mechanical circulatory support devices. Methods: Multicenter retrospective observational study of adults supported on a mechanical circulatory support device who received angiotensin II for vasodilatory shock. The primary outcome was the intraindividual change from baseline in mean arterial pressure (MAP) and vasopressor dosage after angiotensin II. Results: Fifty patients were included with mechanical circulatory devices that were primarily used for cardiac failure (n = 41) or respiratory failure (n = 9). At angiotensin II initiation, the norepinephrine equivalent vasopressor dosage was 0.44 (0.34, 0.64) and 0.47 (0.33, 0.73) mcg/kg/min in the cardiac and respiratory groups, respectively. In the cardiac group, MAP increased from 60 to 70 mmHg (intraindividual P < .001) in the 1 h after angiotensin II initiation and the vasopressor dosage declined by 0.04 mcg/kg/min (intraindividual P < .001). By 12 h, the vasopressor dosage declined by 0.16 mcg/kg/min (P = .001). There were no significant changes in cardiac index or mean pulmonary artery pressure throughout the 12 h following angiotensin II. In the respiratory group, similar but nonsignificant effects at 1 h on MAP (61-81 mmHg, P = .26) and vasopressor dosage (decline by 0.13 mcg/kg/min, P = .06) were observed. Conclusions: In patients requiring mechanical circulatory support for cardiac failure, angiotensin II produced beneficial systemic hemodynamic effects without negatively impacting cardiac function or pulmonary pressures. The systemic hemodynamic effects in those with respiratory failure were nonsignificant due to limited sample size.

Cardiac tamponade in a patient supported by veno-arterial extracorporeal membrane oxygenation.

Cardiac tamponade occurring in a patient supported on central veno-arterial extracorporeal membrane oxygenation is depicted in a transesophageal echocardiography image and associated rendering. Prompt recognition of tamponade, which can be assisted with echocardiography, and emergent evacuation is critical to restoring cardiovascular stability.

Phenytoin Pharmacokinetics During Venoarterial Extracorporeal Membrane Oxygenation and Plasma Exchange.

Currently, there is minimal guidance to antiepileptic dose adjustment for a patient requiring either venoarterial (VA) extracorporeal membrane oxygenation (ECMO) or plasma exchange (PLEX) therapy, and to our knowledge, there are rare guidances for a patient requiring both. Given the dangers with non-therapeutic concentrations of phenytoin, it is critical for the intensive care unit (ICU) practitioner to understand how the pharmacokinetic parameters of phenytoin change in critically ill patients requiring extracorporeal support. This case study presents a 41-year-old female transferred to the cardiovascular ICU requiring VA ECMO and PLEX for the treatment of systemic lupus erythematosus (SLE)-induced catastrophic antiphospholipid syndrome (CAPS). Free phenytoin concentrations were measured to assess the removal of phenytoin. There was no significant decrease in the free phenytoin concentrations post-PLEX and while on ECMO. Free phenytoin concentrations are not influenced in the setting of PLEX and while on ECMO.

Angiotensin II Infusion for Shock: A Multicenter Study of Postmarketing Use.

BACKGROUND: Vasodilatory shock refractory to catecholamine vasopressors and arginine vasopressin is highly morbid and responsible for significant mortality. Synthetic angiotensin II is a potent vasoconstrictor that may be suitable for use in these patients. RESEARCH QUESTION: What is the safety and effectiveness of angiotensin II and what variables are associated with a favorable hemodynamic response? STUDY DESIGN AND METHODS: We performed a multicenter, retrospective study at five tertiary medical centers in the United States. The primary end point of hemodynamic responsiveness to angiotensin II was defined as attainment of mean arterial pressure (MAP) of ≥ 65 mm Hg with a stable or reduced total vasopressor dosage 3 h after drug initiation. RESULTS: Of 270 included patients, 181 (67%) demonstrated hemodynamic responsiveness to angiotensin II. Responders showed a greater increase in MAP (+10.3 mm Hg vs +1.6 mm Hg, P < .001) and reduction in vasopressor dosage (-0.20 µg/kg/min vs +0.04 µg/kg/min; P < .001) compared with nonresponders at 3 h. Variables associated with favorable hemodynamic response included lower lactate concentration (OR 1.11; 95% CI, 1.05-1.17, P < .001) and receipt of vasopressin (OR, 6.05; 95% CI, 1.98-18.6; P = .002). In severity-adjusted multivariate analysis, hemodynamic responsiveness to angiotensin II was associated with reduced likelihood of 30-day mortality (hazard ratio, 0.50; 95% CI, 0.35-0.71; P < .001). Arrhythmias occurred in 28 patients (10%) and VTE was identified in 4 patients. INTERPRETATION: In postmarketing use for vasopressor-refractory shock, 67% of angiotensin II recipients demonstrated a favorable hemodynamic response. Patients with lower lactate concentrations and those receiving vasopressin were more likely to respond to angiotensin II. Patients who responded to angiotensin II experienced reduced mortality.