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.

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.

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.

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.

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.

Predicting the Response of Hydroxocobalamin in Postoperative Vasoplegia in Recipients of Cardiopulmonary Bypass.

OBJECTIVE: The primary aim of this study was to identify predictors of response to hydroxocobalamin. DESIGN: A retrospective cohort study. SETTING: A single large academic medical center within the cardiovascular surgery intensive care unit. PARTICIPANTS: Postoperative cardiovascular surgery patients within 96 hours of cardiopulmonary bypass separation between May 7, 2018, and August 1, 2020. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of the 66 administrations, 43 administrations yielded hemodynamic improvements (65.2%). Comparing responders to nonresponders, nonresponders had a greater median cardiopulmonary bypass duration (223 v 131 minutes; p < 0.001) and a prolonged median cross-clamp time (153 v 77 minutes; p = 0.014). Multivariate modeling demonstrated a reduction in the odds of being a responder by 57% for every 60 minutes of cardiopulmonary bypass duration (odds ratio, 0.43; 95% confidence interval, 0.28-0.68; p < 0.001), but there was no significant difference based on time from intensive care unit admission to hydroxocobalamin administration (odds ratio, 0.95; 95% confidence interval, 0.88-1.03; p = 0.20). CONCLUSION: Shorter total bypass duration and more rapid utilization after bypass of hydroxocobalamin were associated with a higher likelihood of response to refractory vasoplegic shock.

Stellate Ganglion Blockade for Refractory Ventricular Arrhythmias: Implications of Ultrasound-Guided Technique and Review of the Evidence.

Refractory ventricular arrhythmias (VAs) carry high mortality rates despite electrical and pharmacologic therapy utilization. These patients often require aggressive hemodynamic support, including mechanical circulatory devices such as extracorporeal membrane oxygenation because of progressive hemodynamic and metabolic deterioration. Sympathetic nervous system stimulation and neuronal remodeling after myocardial insults have been implicated as drivers of refractory VAs. This understanding has led to interest in and a growing body of experience with percutaneous blockade of the stellate ganglion as a means of interrupting the vicious cycle of refractory VAs. A number of techniques have been described for stellate ganglion blockade, including landmark-driven approaches, fluoroscopy-assisted blockade, and ultrasound guidance. Herein, the literature is evaluated and the authors' experience with stellate ganglion blockade using ultrasound guidance for refractory VAs is described.

Postoperative Nausea and Vomiting and Pain After Robotic-Assisted Mitral Valve Repair.

OBJECTIVE: To determine the rate and clinical factors associated with postoperative nausea and vomiting (PONV) and severe pain after robotic-assisted mitral valve repair. DESIGN: Retrospective chart review. SETTING: Major quaternary academic medical center. PARTICIPANTS: Adult patients undergoing robotic-assisted mitral valve repair from May 5, 2018 through September 13, 2019. INTERVENTIONS: Participant electronic medical records were abstracted for clinical characteristics, PONV within the first 72 postoperative hours, episodes of severe pain (defined as pain score ≥7 using an 11-point numerical pain rating scale), and opioid use within the first 24 postoperative hours. Multivariate analyses were performed. MEASUREMENTS AND MAIN RESULTS: Of 124 participants, PONV was noted in 83 (67%; 95% confidence interval [CI] 58%-75%) patients and severe pain in 96 (77%, 95% CI 69%-84%) patients. The median (interquartile range) time to PONV was 6.1 (3.7-14.7) hours. After adjusting for age, sex, and duration of surgery, pre-incisional use of methadone was associated with reduced risk for severe pain (odds ratio 0.40 [95% CI 0.16-0.99]; p = 0.048) and a lower 24-postoperative hour opioid requirement (estimate -29.0 mg intravenous morphine equivalents [95% CI -46.7 to -11.3]; p = 0.006). However, methadone was not associated with a reduction of the cumulative opioid dose (intraoperative and 24-hour postoperative opioid dose; p = 0.248). Both severe pain and PONV were associated with longer hospital stay. CONCLUSION: PONV and severe pain are common after robotic-assisted mitral valve repair. Peri-incisional methadone is associated with a modest decrease in the severe pain rate but without a reduction in opioid dose or hospital stay.

Electrophysiologic effects and outcomes of sympatholysis in patients with recurrent ventricular arrhythmia and structural heart disease.

INTRODUCTION: Autonomic modulation has been used as a therapy to control recurrent ventricular arrhythmia (VA). This study was to explore stellate ganglion block (SGB) effect on cardiac electrophysiologic properties and evaluate the long-term outcome of cardiac sympathetic denervation (CSD) for patients with recurrent VA and structural heart disease (SHD). MATERIALS AND METHODS: Patients who had recurrent VA due to SHD were enrolled prospectively. Electrophysiologic study and ventricular tachycardia (VT) induction were performed before and after left and right SGB. VA burden and long-term outcomes were assessed for a separate patient group who underwent left or bilateral CSD for drug-refractory VA due to SHD. RESULTS: Electrophysiologic study of nine patients showed that baseline mean (SD) corrected sinus node recovery time (cSNRT) increased from 320.4 (73.3) ms to 402.9 (114.2) ms after left and 482.4 (95.7) ms after bilateral SGB (P = .03). SGB did not significantly change P-R, QRS, and Q-T intervals and ventricular effective refractory period, nor did the inducibility of VA. Nineteen patients underwent left (n = 14) or bilateral (n = 5) CSD. CSD reduced VA burden and appropriate ICD therapies from a median (interquartile range) of 2.5 (0.4-11.6) episodes weekly to 0.1 (0.0-2.4) episodes weekly at 6-month follow-up (P = .002). Three-year freedom from orthotopic heart transplant (OHT) and death was 52.6%. New York Heart Association functional class III/IV and VT rate less than 160 beats per minute were predictors of recurrent VA, OHT, and death. CONCLUSION: SGB increased cSNRT without changing heart rate. CSD was more beneficial for patients with mild-to-moderate heart failure and faster VA.

Use of Hydroxocobalamin (Vitamin B12a) in Patients With Vasopressor Refractory Hypotension After Cardiopulmonary Bypass: A Case Series.

Hydroxocobalamin (vitamin B12a) is an emerging treatment for vasoplegic syndrome (VS) associated with cardiopulmonary bypass (CPB). Given its cost and scarcity, an institutional guideline for its use as a rescue treatment in cases of suspected VS was developed. Hemodynamic variables and vasopressor requirements were reviewed for a series of 24 post-CPB patients who received B12a. Favorable changes in hemodynamic parameters and vasopressor requirements were seen after B12a administration although guideline criteria for VS were inconsistently met. These findings support the continued study of B12a in patients with CPB-associated VS.

Urgent Ultrasound-Guided Bilateral Stellate Ganglion Blocks in a Patient With Medically Refractory Ventricular Arrhythmias.

OBJECTIVES: To describe the successful treatment of medically refractory ventricular arrhythmias in the ICU with ultrasound-guided bilateral stellate ganglion blocks. DATA SOURCES: The data were gathered from the medical record. STUDY SELECTION: This case was selected as it describes the use of ultrasound in the successful termination of a recurrent, malignant arrhythmia, rather than fluoroscopy, to perform bilateral stellate ganglion blocks at the patient's bedside in the ICU. DATA EXTRACTION: The data were extracted from the medical record. DATA SYNTHESIS: The data were synthesized from the patient's medical record. CONCLUSIONS: Performance of stellate ganglion blocks at the bedside in the ICU is feasible for patients who are suffering from refractory ventricular arrhythmias. This potentially life-saving block can be performed using ultrasound guidance, sparing the patient transport to a fluoroscopy suite.