Wittwer, Erica D.

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.

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.

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.

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, I 2 = 0%) and die (OR 1.62, 95% CI 1.19–2.21, p = 0.002, I 2 = 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, I 2 = 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.

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.

Background: Clozapine is an atypical antipsychotic with potent alpha-adrenergic blocking properties when administered at high dosages, resulting in vasodilatory shock in overdose settings. Case Summary: A 39-year-old man presented with profound catecholamine- and vasopressin-refractory vasodilatory shock following massive clozapine ingestion. Angiotensin II was initiated when the patient was requiring 2.2 µg/kg/min norepinephrine equivalents of vasopressor support, resulting in a prompt increase in the perfusion pressure. All vasopressors were liberated within 18 hours of angiotensin II initiation, and the patient was discharged with no deficits. Conclusions: Synthetic angiotensin II may represent a therapeutic option for refractory hypotension resulting from high dosages of clozapine or other potent alpha-adrenergic blocking medications.