Use of hydroxocobalamin to treat intraoperative vasoplegic syndrome refractory to vasopressors and methylene blue during liver transplantation.

INTRODUCTION: For patients with catecholamine-resistant vasoplegic syndrome (VS) during liver transplantation (LT), treatment with methylene blue (MB) and/or hydroxocobalamin (B12) has been an acceptable therapy. However, data on the effectiveness of B12 is limited to case reports and case series. METHODS: We retrospectively reviewed records of patients undergoing LT from January 2016 through March 2022. We identified patients with VS treated with vasopressors and MB, and abstracted hemodynamic parameters, vasopressor requirements, and B12 administration from the records. The primary aim was to describe the treatment efficacy of B12 for VS refractory to vasopressors and MB, measured as no vasopressor requirement at the conclusion of the surgery. RESULTS: One hundred one patients received intraoperative VS treatment. For the 35 (34.7%) patients with successful VS treatment, 14 received MB only and 21 received both MB and B12. Of the 21 patients with VS resolution after receiving both MB and B12, 17 (89.5%) showed immediate, but transient, hemodynamic improvements at the time of MB administration and later showed sustained response to B12. CONCLUSION: Immediate but transient hemodynamic response to MB in VS patients during LT supports the diagnosis of VS and should prompt B12 administration for sustained treatment response.

Mortality and morbidity after combined heart and liver transplantation in the failing Fontan: An updated dual center retrospective study.

INTRODUCTION: As the adult Fontan population with Fontan associated liver disease continues to increase, more patients are being referred for transplantation, including combined heart and liver transplantation. METHODS: We report updated mortality and morbidity outcomes after combined heart and liver transplant in a retrospective cohort series of 40 patients (age 14 to 49 years) with Fontan circulation across two centers from 2006-2022. RESULTS: The 30-day, 1-year, 5-year and 10-year survival rate was 90%, 80%, 73% and 73% respectively. Sixty percent of patients met a composite comorbidity of needing either post-transplant mechanical circulatory support, renal replacement therapy or tracheostomy. Cardiopulmonary bypass time > 283 min (4.7 h) and meeting the composite comorbidity were associated with mortality by Kaplan Meier analysis. CONCLUSION: Further study to mitigate early mortality and the above comorbidities as well as the high risk of bleeding and vasoplegia in this patient population is warranted.

Vascular Reactivity Index as an Effective Predictor of Mortality in Patients With Septic Shock: A Retrospective Study.

BACKGROUND: Sepsis is a serious complication that occurs after trauma, burns, and infections, and it is an important cause of death in intensive care unit (ICU) patients. Despite many new measures being proposed for sepsis treatment, its mortality rate remains high; sepsis has become a serious threat to human health, and there is an urgent need to carry out in-depth clinical research related to sepsis. In recent years, it has been found that septic shock-induced vasoplegia is a result of vascular hyporesponsiveness to vasopressors. Therefore, this study intended to establish an objective formula related to vasoplegia that can be used to assess the prognosis of patients and guide clinical treatment. MATERIALS AND METHODS: A retrospective cohort study was conducted using data from 106 septic shock patients admitted to the ICU of Jining No. 1 People's Hospital from January 2020 to December 2022. The patients were divided into mortality and survival groups based on 28-day survival, and hemodynamics were monitored by the pulse index continuous cardiac output system. The dose and duration of vasopressors, major hemodynamic parameters, lactic acid (Lac) levels, and Sequential Organ Failure Assessment scores were recorded within 48 h of hospital admission. Multifactorial logistic regression was used to analyze the independent risk factors affecting the prognosis of patients, and the predictive value of the vascular response index (VRI) was analyzed by the receiver operating characteristic (ROC) curve. RESULTS: The differences between the survival and mortality groups in terms of age, sex ratio, body weight, ICU length of stay, distribution of infection sites, underlying disease conditions, baseline Lac levels, and some hemodynamic parameters were not statistically significant (P > .05). The results of multifactorial logistic regression showed that the admission Acute Physiology and Chronic Health Evaluation II score, Lac level at 24 h of treatment, maximal vasoactive inotropic score at 24 h (VISmax24), maximal vasoactive inotropic score at 48 h (VISmax48), and VRI were independent risk factors affecting 28-day mortality. Within 48 h of receiving vasopressor therapy, the VRI was lower in the mortality group than in the survival group. The area under the ROC curve for the VRI was 0.86, and the best cutoff value of the VRI for predicting 28-day mortality was 32.50 (YI = 0.80), with a sensitivity of 0.90, a specificity of 0.90, and a better prediction of mortality than the other indicators. CONCLUSIONS: The VRI is a good predictor of mortality in patients with septic shock, and a lower VRI indicates more severe vasoplegia, poorer prognosis, and higher mortality in patients with septic shock.

Droxidopa for Vasopressor Weaning in Critically Ill Patients with Persistent Hypotension: A Multicenter, Retrospective, Single-Arm Observational Study.

BACKGROUND: Persistent vasopressor requirements are a common reason for delayed liberation from the intensive care unit (ICU) and adjunct oral agents are sometimes used to hasten time to vasopressor discontinuation. We sought to describe the use of droxidopa for vasopressor weaning in critically ill patients with prolonged hypotension. MATERIALS AND METHODS: This retrospective, single-arm, observational study included adult patients admitted to an ICU at two academic centers between 06/2016-07/2023 who received droxidopa for vasopressor weaning. Patients who received droxidopa prior to admission or for another indication were excluded. The primary outcome was time to vasopressor discontinuation, defined as when vasopressors were stopped and remained off for at least 24 h. Secondary outcomes included rates of tachycardia and hypotension post-initiation, norepinephrine equivalents pre- and post-initiation, concomitant oral agent use, and dosing. A subgroup analysis was conducted in patients receiving droxidopa via feeding tubes. RESULTS: A total of 30 patients met inclusion criteria. Median age was 62 years old, 12 (40%) were female, and 73% were in a cardiac/cardiac surgical ICU. Patients were on vasopressors for a median of 16 days prior to droxidopa initiation. Median (IQR) time to vasopressor discontinuation was 70 h (23-192) and norepinephrine equivalents decreased immediately after initiation (0.08 vs 0.02 mcg/kg/min, p < 0.001). MAP increased after droxidopa initiation (68.8 vs 66.5 mm Hg, p = 0.008) while heart rates were unchanged (86 vs 84 BPM, p = 0.37) after initiation. Patients who weaned from vasopressors within 72 h versus longer than 72 h after droxidopa initiation were more likely to be on lower norepinephrine equivalents prior to initiation (0.05 vs 0.12 mcg/kg/min, p = 0.013). Feeding tube administration did not impact time to vasopressor discontinuation (p = 0.93). CONCLUSIONS: Droxidopa may be considered an adjunct therapy for vasopressor weaning. Effects were similar when analyzing patients receiving droxidopa via feeding tube.

Diagnosis and Management of Vasoplegia in Temporary Mechanical Circulatory Support: A Narrative Review.

Refractory vasodilatory shock, or vasoplegia, is a pathophysiologic state observed in the intensive care unit and operating room in patients with a variety of primary diagnoses. Definitions of vasoplegia vary by source but are qualitatively defined clinically as a normal or high cardiac index and low systemic vascular resistance causing hypotension despite high-dose vasopressors in the setting of euvolemia. This definition can be difficult to apply to patients undergoing mechanical circulatory support (MCS). A large body of mostly retrospective literature exists on vasoplegia in the non-MCS population, but the increased use of temporary MCS justifies an examination of vasoplegia in this population. MCS, particularly extracorporeal membrane oxygenation, adds complexity to the diagnosis and management of vasoplegia due to challenges in determining cardiac output (or total blood flow), lack of clarity on appropriate dosing of noncatecholamine interventions, increased thrombosis risk, the difficulty in determining the endpoints of adequate volume resuscitation, and the unclear effects of rescue agents (methylene blue, hydroxocobalamin, and angiotensin II) on MCS device monitoring and function. Care teams must combine data from invasive and noninvasive sources to diagnose vasoplegia in this population. In this narrative review, the available literature is surveyed to provide guidance on the diagnosis and management of vasoplegia in the temporary MCS population, with a focus on noncatecholamine treatments and special considerations for patients supported by extracorporeal membrane oxygenation, transvalvular heart pumps, and other ventricular assist devices.

Methylene Blue Reduces Mortality in Critically Ill and Perioperative Patients: A Meta-Analysis of Randomized Trials.

Vasodilatory hypotension is common in critically ill and perioperative patients, and is associated with adverse outcomes. As a nitric oxide production inhibitor, methylene blue (MB) exerts its vasoconstrictor property and is an adjuvant for catecholamine-refractory vasodilatory shock. However, the effects of MB on clinically relevant outcomes remain unclear. Therefore, the authors performed a meta-analysis of randomized trials on MB in critically ill and perioperative patients. The authors searched through databases for randomized trials on MB in critically ill and perioperative patients, which yielded 11 studies consisting of 556 patients. The primary outcome was mortality at the longest follow-up. Secondary outcomes included hemodynamic parameters and organ dysfunction (PROSPERO: CRD42023409243). Nine out of the 11 included randomized trials reported mortality, which was significantly lower in the MB group (risk ratio, 0.60 [95% CI 0.43-0.84] p = 0.003), with findings confirmed in septic shock and cardiac surgery subgroups. The authors found reduced lengths of stay in the intensive care unit (mean difference [MD], -0.9 days [95% CI -1.06 to -0.77] p < 0.001) and in the hospital (MD, -2.2 days [95% CI, -2.68 to -1.70] p < 0.001) in the MB group. MB was associated with increased mean arterial pressure (MD, 8.4 mmHg [95% CI 5.01-11.75] p < 0.001) and systemic vascular resistance (MD, 94.5 dyn/s/cm5 [95% CI 17.73-171.15] p = 0.02), with no difference in cardiac output (standardized MD, 0.16 [95% CI, -0.25 to 0.57] p = 0.45). This meta-analysis showed that MB reverses vasodilation in critically ill and perioperative patients and might improve survival. Further adequately powered randomized trials are needed to confirm these findings.

Perioperative Management of Pediatric Combined Heart and Liver Transplantation: A 17 year single center experience.

BACKGROUND: An increasing number of centers are undertaking combined heart and liver transplantation in adult and pediatric patients with congenital heart disease. AIM: The primary aim of this study was to describe the perioperative management of a single center cohort, identifying challenges and potential solutions. METHODS: We conducted a retrospective review of all patients undergoing combined heart and liver transplantation at Stanford Children's Hospital from 2006 to 2022. Preoperative information included cardiac diagnosis, hemodynamics, and severity of liver disease. Intraoperative data included length of surgery, cardiopulmonary bypass time, and blood products transfused. Postoperative data included blood products transfused in the intensive care unit, time to extubation, length of intensive care unit stay, survival outcomes and 30-day adverse events. RESULTS: Eighteen patients underwent en bloc combined heart and liver transplantation at Stanford Children's Hospital from 2006 to 2022, and the majority 15 (83%) were transplanted for failing Fontan circulation with Fontan Associated Liver Disease. Median surgical procedure time was 13.4 [11.5, 14.5] h with a cardiopulmonary bypass time of 4.3 [3.9, 5.8] h. Median total blood products transfused in the operating room post cardiopulmonary bypass was 89.4 [63.9, 127.0] mLs/kg. Nine patients (50%) had vasoplegia during cardiopulmonary bypass. Activated prothrombin complex concentrates were used post cardiopulmonary bypass in 15 (83%) patients with a 30-day thromboembolism rate of 22%. Median time to extubation was 4.0 [2.8, 6.5] days, median intensive care unit length of stay 20.0 [7.8, 48.3] days and median hospital length of stay 54.0 [30.5, 68.3] days. Incidence of renal replacement therapy was 11%; however, none required renal replacement therapy by the time of hospital discharge. Neurological events within 30 days were 17% and the 30 day and 1 year survival was 89%. CONCLUSIONS: Perioperative challenges include major perioperative bleeding, unstable hemodynamics, and end organ injury including acute kidney injury and neurological events. Successful outcomes for en bloc combined heart and liver transplantation are possible with careful multidisciplinary planning, communication, patient selection, and integrated peri-operative management.

HFSA Expert Consensus Statement on the Medical Management of Patients on Durable Mechanical Circulatory Support.

The medical management of patients supported with durable continuous flow left ventricular assist device (LVAD) support encompasses pharmacological therapies administered in the preoperative, intraoperative, postoperative, and chronic LVAD support stages. As patients live longer on LVAD support, the risks of LVAD-related complications and progression of cardiovascular and other diseases increase. Using existing data from cohort studies, registries, randomized trials, and expert opinion, this Heart Failure Society of America Consensus Document on the Medical Management of Patients on Durable Mechanical Circulatory Support offers best practices on the management of patients on durable mechanical circulatory support, focusing on pharmacological therapies administered to patients on continuous flow LVADs. Although quality data in the LVAD population are few, the use of guideline-directed heart failure medical therapies and the importance of blood pressure management, right ventricular preload and afterload optimization, and antiplatelet and anticoagulation regimens are discussed. Recommended pharmacological regimens used to mitigate or treat common complications encountered during LVAD support, including arrhythmias, vasoplegia, mucocutaneous bleeding, and infectious complications, are addressed. Finally, this document touches on important potential pharmacological interactions from antidepressants and herbal and nutritional supplements of relevance to providers of patients on LVAD support.

Evaluation of the Addition of Angiotensin II in Patients With Shock After Cardiac Surgery at a Veterans Affairs Medical Center.

BACKGROUND: Vasoplegic shock occurs in up to 37% of cardiac surgery patients. We investigated the use of angiotensin II for treating vasoplegic shock in these patients. OBJECTIVES: We assessed clinical outcomes and mortality in patients undergoing cardiac surgery at our center between March 1, 2018 and October 31, 2020 who developed vasoplegic shock, comparing those who received angiotensin II with those who did not. METHODS: This was a retrospective chart review. Response to angiotensin II was defined as increase in or maintenance of mean arterial pressure (MAP) and decrease in background vasopressor dosage. RESULTS: Angiotensin II was administered to 7 patients (postoperatively in 4 patients [57.1%]) with vasoplegic shock and baseline norepinephrine equivalent (NEE) of 0.49 ± 0.08 µg/kg/min; 12 patients with vasoplegic shock did not receive angiotensin II. Within 3 hours of angiotensin II administration, NEE decreased by 38.0 ± 33.1%. Angiotensin patients were more likely to newly require renal replacement therapy (66.7% vs 9.1%, P = 0.03) and had a longer, although not statistically significant, postoperative stay (23.1 vs 14.0 days, P = 0.16). Despite higher NEE requirements at baseline (0.49 vs 0.30, P = 0.03) and over the next 48 hours in the angiotensin group, no between-group differences in 7-day mortality (14.3% vs 0.0%, P = 0.37) or 30-day mortality (28.6% vs 8.3%, P = 0.52) were noted. CONCLUSION AND RELEVANCE: In patients who developed vasoplegic shock after cardiac surgery, angiotensin II administration allowed immediate dosage reductions of other vasopressors while maintaining MAP. Despite its small sample size, this study adds to the paucity of data in these patients and highlights future research needs.

Postoperative vasoplegia in lung transplantation: incidence and relation to outcome in a single-centre retrospective study.

BACKGROUND: The incidence and clinical importance of vasoplegia after lung transplantation remains poorly studied. We describe the incidence of vasoplegia and its association with complications after lung transplantation. METHODS: Perioperative data of 279 lung transplant recipients operated on from 2015 to 2020 in a UK hospital were analysed retrospectively. RESULTS: Vasoplegia occurred in 41.6% of patients after lung transplantation (mild, 31.0%; moderate, 55.2%; severe, 13.8%). Compared with non-vasoplegic patients, vasoplegic patients had a higher incidence of any acute kidney injury, defined by Kidney Disease Improving Global Outcomes (KDIGO) criteria (78.5% vs 65%, P=0.015), renal replacement therapy (47.4% vs 24.5%, P<0.001), and delayed chest closure (18.4% vs 9.2%, P=0.025); were ventilated longer (70 [32-368] vs 34 [19-105] h, P<0.001); and stayed longer in the ICU (12.9 [5-30] vs 6.8 [3-20] days, P<0.001). Mortality at 30 days and 1 yr was higher in patients with vasoplegia (11.2% vs 5.5% and 20.7% vs 11.7%, P=0.039, respectively). Severe vasoplegia represented a predictor of longer-term mortality (hazard ratio=1.65, P=0.008). Underlying infectious disease, increased BMI, higher preoperative pulmonary artery systolic pressure and bilirubin levels, lower glomerular filtration rate, and increased fresh frozen plasma transfusion were predictors of vasoplegia severity. Neutrophilia, leucocytosis, and increased C-reactive protein were associated with vasoplegia, but release of the neutrophil activation markers myeloperoxidase and heparin-binding protein was similar between groups. CONCLUSIONS: Influenced by preoperative status as well as procedural factors and inflammatory response, vasoplegia is a common and critical condition after lung transplantation with worse short-term outcomes and long-term survival.

Renin-angiotensin-aldosterone system dynamics after targeted blood pressure control using angiotensin II or norepinephrine in cardiac surgery: mechanistic randomised controlled trial.

BACKGROUND: The role of the renin-angiotensin-aldosterone axis in vasoplegia after cardiac surgery remains unclear. We tested the hypothesis that, compared with norepinephrine, infusion of angiotensin II titrated to achieve similar mean arterial pressure (MAP) would suppress plasma renin concentration (PRC) while maintaining aldosterone levels. METHODS: In a double-blind, randomised controlled trial, subjects received either an infusion of angiotensin II or norepinephrine to maintain MAP 70-80 mm Hg from induction of anaesthesia. We compared PRC, aldosterone, dipeptidyl peptidase-3, and angiotensin-converting enzyme 2 activity between treatment groups, before surgery, on ICU admission, and 24 h after surgery. RESULTS: In 60 patients (11.7% female; mean age 68 yr [11 yr]), norepinephrine increased median PRC at ICU admission (median difference [MD] 46 [inter-quartile range, IQR, 3-88] µU ml-1; P<0.001) but angiotensin II did not (MD -3 [IQR -62 to 35] µU ml-1; P=0.36). Aldosterone levels increased with both. The aldosterone:PRC ratio did not change with norepinephrine (MD -0.01 [IQR -0.14 to 0.03] µU ml-1 per ng dl-1, P=0.76) but increased with angiotensin II (MD 0.05 [IQR 0.004-0.26] µU ml-1 per ng dl-1, P<0.001). The upper quartile of PRC before surgery was associated with higher vasopressor requirements when norepinephrine was used to maintain MAP, but not angiotensin II. Dipeptidyl peptidase-3 levels and angiotensin-converting enzyme 2 activities were similar at all time points. CONCLUSIONS: Angiotensin II suppressed renin release while maintaining aldosterone levels compared with norepinephrine. Higher plasma renin concentration before surgery was associated with greater vasopressor requirement for norepinephrine, but not angiotensin II. CLINICAL TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry-ACTRN12621000195853 23/02/2021.

The haemodynamic effects of phenylephrine after cardiac surgery.

BACKGROUND: Phenylephrine increases systemic- and pulmonary resistances and therefore may increase blood pressures at the expense of blood flow. Cardio-pulmonary bypass alters vasoreactivity and many patients exhibit chronotropic insufficiency after cardiac surgery. We aimed to describe the haemodynamic effects of phenylephrine infusion after cardiac surgery. METHODS: Patients in steady state after low-risk cardiac surgery received incremental infusion rates of phenylephrine up to 1.0 µg/kg/min with the aim of increasing systemic mean arterial blood pressure 20 mmHg. Invasive haemodynamic parameters, including pulmonary wedge pressures, were captured along with echocardiographic measures of biventricular function before, during phenylephrine infusion at target systemic blood pressure, and 20 min after phenylephrine discontinuation. RESULTS: Thirty patients were included. Phenylephrine increased mean arterial pressure increased from 78 (±9) mmHg to 98 (±10) mmHg with phenylephrine infusion. Also, pulmonary blood pressure as well as systemic- and pulmonary resistances increased. The ratio between systemic- and pulmonary artery resistances did not change statistically significantly (p = .59). Median cardiac output was 4.35 (interquartile range [IQR] 3.6-5.4) L/min at baseline and increased significantly with phenylephrine infusion (median Δcardiac output was 0.25 [IQR 0.1-0.6] L/min) (p = .012). Pulmonary artery wedge pressure increased from 10.2 (±3.0) mmHg to 11.9 (±3.4) mmHg (p < .001). This was accompanied by significant increases in central venous pressure. Phenylephrine infusion increased left ventricular end-diastolic volume from 105 (±46) mL to 119 (±44) mL (p < .001). All results of phenylephrine infusion were reversed with discontinuation. CONCLUSION: In haemodynamically stable patients after cardiac surgery, phenylephrine increased PVR and SVR, but did not change the PVR/SVR ratio. Phenylephrine increased biventricular filling pressures and left ventricular end-diastolic area. Consequently, CO increased as ejection fraction was maintained. These findings do not discourage the use of phenylephrine after low-risk cardiac surgery. REGISTRATION: clinicaltrial.gov (identifier NCT04419662).

Efficacy and safety of angiotensin II in cardiogenic shock: A systematic review.

BACKGROUND: Cardiogenic shock (CS) is associated with high morbidity and mortality. In recent times, there is increasing interest in the role of angiotensin II in CS. We sought to systematically review the current literature on the use of angiotensin II in CS. METHODS: PubMed, EMBASE, Medline, Web of Science, PubMed Central, and CINAHL databases were systematically searched for studies that evaluated the efficacy of angiotensin II in patients with CS during 01/01/2010-07/07/2022. Outcomes of interest included change in mean arterial pressure (MAP), vasoactive medication requirements (percent change in norepinephrine equivalent [NEE] dose), all-cause mortality, and adverse events. RESULTS: Of the total 2,402 search results, 15 studies comprising 195 patients were included of which 156 (80%) received angiotensin II. Eleven patients (84.6%) in case reports and case series with reported MAP data at hour 12 noted an increase in MAP. Two studies noted a positive hemodynamic response (defined a priori) in eight (88.9%) and five (35.7%) patients. Eight studies reported a reduction in NEE dose at hour 12 after angiotensin II administration and one study noted a 100% reduction in NEE dose. Out of 47 patients with documented information, 13 patients had adverse outcomes which included hepatic injury (2), digital ischemia (1), ischemic optic neuropathy (1), ischemic colitis (2), agitated delirium (1), and thrombotic events (2). CONCLUSIONS: In this first systematic review of angiotensin II in CS, we note the early clinical experience. Angiotensin II was associated with improvements in MAP, decrease in vasopressor requirements, and minimal reported adverse events.

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.

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.

Plasma Renin Activity Increases With Cardiopulmonary Bypass and is Associated With Vasoplegia After Cardiac Surgery.

OBJECTIVES: To describe the trend in plasma renin activity over time in patients undergoing cardiac surgery on cardiopulmonary bypass, and to investigate if increased plasma renin activity is associated with postcardiopulmonary bypass vasoplegia. DESIGN: A prospective cohort study. SETTING: Patients were enrolled from June 2020 to May 2021 at a tertiary cardiac surgical institution. PATIENTS: A cohort of 100 adult patients undergoing cardiac surgery on cardiopulmonary bypass. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Plasma renin activity was measured at 5 time points: baseline, postoperatively, and at midnight on postoperative days 1, 2, and 3. Plasma renin activity and delta plasma renin activity were correlated with the incidence of vasoplegia and clinical outcomes. The median plasma renin activity increased approximately 3 times from baseline immediately after cardiac surgery, remained elevated on postoperative days 0, 1, and 2, and began to downtrend on postoperative day 3. Plasma renin activity was approximately 3 times higher at all measured time points in patients who developed vasoplegia versus those who did not. CONCLUSIONS: In patients undergoing cardiac surgery on cardiopulmonary bypass, plasma renin activity increased postoperatively and remained elevated through postoperative day 2. Additionally, patients with vasoplegic syndrome after cardiac surgery on cardiopulmonary bypass had more robust elevations in plasma renin activity than nonvasoplegic patients. These findings support the need for randomized controlled trials to determine if patients undergoing cardiac surgery with high plasma renin activity may benefit from targeted treatment with therapies such as synthetic angiotensin II.

Review of Postoperative Care for Heart Transplant Recipients.

The early postoperative management strategies after heart transplantation include optimizing the function of the denervated heart, correcting the causes of hemodynamic instability, and initiating and maintaining immunosuppressive therapy, allograft rejection surveillance, and prophylaxis against infections caused by immunosuppression. The course of postoperative support is influenced by the quality of allograft myocardial protection prior to implantation and reperfusion, donor-recipient heart size matching, surgical technique of orthotopic heart transplantation, and patient factors (eg, preoperative condition, immunologic compatibility, postoperative vasomotor tone, severity and reversibility of pulmonary vascular hypertension, pulmonary function, mediastinal blood loss, and end-organ perfusion). This review provides an overview of the early postoperative care of recipients and includes a brief description of the surgical techniques for orthotopic heart transplantation.

Incidence of Intraoperative Vasoplegic Syndrome in Lung Transplantation.

OBJECTIVES: Severe hypotension and low systemic vascular resistance in the setting of adequate cardiac output, known as "vasoplegic syndrome" (VS), is a physiologic disturbance reported in 9% to 44% of cardiac surgery patients. Although this phenomenon is well-documented in cardiac surgery, there are few studies on its occurrence in lung transplantation. The goal of this study was to characterize the incidence of VS in lung transplantation, as well as identify associated risk factors and outcomes. DESIGN: Retrospective study of single and bilateral lung transplants from April 2013 to September 2021. SETTING: The study was conducted at an academic hospital. PARTICIPANTS: Patients ≥18 years of age who underwent lung transplantation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The authors defined VS as mean arterial pressure <65 mmHg, cardiac index ≥2.2 L/min/m2, and ≥30 minutes of vasopressor administration after organ reperfusion. The association between VS and risk factors or outcomes was assessed using t tests, Mann-Whitney U, and chi-square tests. The authors ran multivariate logistic regression models to determine factors independently associated with VS. The incidence of VS was 13.9% (CI 10.4%-18.4%). In the multivariate model, male sex (odds ratio 2.85, CI 1.07-7.58, p = 0.04) and cystic fibrosis (odds ratio 5.76, CI 1.43-23.09, p = 0.01) were associated with VS. CONCLUSIONS: The incidence of VS in lung transplantation is comparable to that of cardiac surgery. Interestingly, male sex and cystic fibrosis are strong risk factors. Identifying lung transplant recipients at increased risk of VS may be crucial to anticipating intraoperative complications.

Effects of norepinephrine infusion during cardiopulmonary bypass on perioperative changes in lactic acid level (Norcal).

INTRODUCTION: Hyperlactatemia, a problem reported in up to 30% of cardiac surgery patients, results from excessive production of or decreased clearance of lactate. It is typically a symptom of tissue hypoperfusion and may be associated with the prevalence of postoperative acute mesenteric ischemia and renal failure, or prolonged intensive care unit (ICU) and hospital stay, and increased 30-day mortality. METHODS AND MEASUREMENTS: Eighty cardiac surgery patients using cardiopulmonary bypass (CPB) were randomly assigned into either a placebo (n = 39) or norepinephrine 0.05-0.2 µg/kg/min (n = 41) as well as norepinephrine boluses during CPB to maintain mean arterial blood pressure (MAP) at 65 to 80 mm Hg. Patient assignments were done after receiving ethical approval to proceed. The primary result was the perioperative changes in lactic acid level. Secondary findings were also recorded, including hemodynamic variables, the incidence of vasoplegia, intraoperative hypotension, myocardial ischemia, the need for vasopressor support, postoperative complications, and mortality. RESULTS: The peak levels and perioperative changes in blood lactate during the first 24 postoperative hours, the number of patients who experienced early hyperlactatemia on admission to the ICU (Placebo: 46.2%, Norepinephrine: 51.2%, p = .650), vasoplegia, hemodynamic changes, incidences of intraoperative hypotension, myocardial ischemia, postoperative complications, and mortality rates were similar in the two groups. Patients in the norepinephrine group received lower intraoperative rescue norepinephrine boluses to maintain the target MAP (p = .039) and had higher MAP values during the CPB and intraoperative blood loss [mean difference [95% confidence interval]; 177 [20.9-334.3] ml, p = .027]. CONCLUSION: norepinephrine and placebo infusions during the CPB with the maintenance of MAP from 65 to 80 mmHg had comparative effects on the changes in blood lactate and incidence of vasoplegia after cardiac surgery. Norepinephrine infusion maintained higher MAP values during the CPB.

Angiotensin-II for vasoplegia following cardiac surgery.

INTRODUCTION: The objective of this study was to describe the implementation and outcomes of a protocol outlining angiotensin-II utilization for vasoplegia following cardiac surgery. METHODS: This was a retrospective chart review at a single-center university hospital. Included patients received angiotensin-II for vasoplegia refractory to standard interventions, including norepinephrine 20 mcg/min and vasopressin 0.04 units/min, following cardiac surgery between April 2021 and April 2022. RESULTS: 30 patients received angiotensin-II for refractory vasoplegia. Adjunctive agents at angiotensin-II initiation included corticosteroids (26 patients; 87%), epinephrine (26 patients; 87%), dobutamine (17 patients; 57%), dopamine (9 patients; 30%), milrinone (2 patients; 7%), and hydroxocobalamin (4 patients; 13%). At 3 hours, the median mean arterial pressure increased from baseline (70 vs 61.5 mmHg, p = .0006). Median norepinephrine doses at angiotensin-II initiation, 1 hour, 3 hours, and angiotensin-II discontinuation were 0.22, 0.16 (p = .0023), 0.10 (p < .0001), and 0.07 (p < .0001) mcg/kg/min. Median dobutamine doses decreased throughout angiotensin-II infusion from eight to six mcg/kg/min (p = .0313). Other vasoactive medication doses were unchanged. Three patients (10%) subsequently received hydroxocobalamin. Thirteen (43.3%) and five (16.7%) patients experienced mortality by day 28 and venous or arterial thrombosis events, respectively. CONCLUSIONS: The administration of angiotensin-II to vasoplegic patients following cardiac surgery was associated with increased mean arterial pressure, reduced norepinephrine dosages, and reduced dobutamine dosages.