Vasoplegic syndrome during heart transplantation: A systematic review and meta-analysis.

BACKGROUND: Vasoplegic syndrome (VS) is a common occurrence during heart transplantation (HT). It currently lacks a uniform definition between transplant centers, and its pathophysiology and treatment remain enigmatic. This systematic review summarizes the available published clinical data regarding VS during HT. METHODS: We searched databases for all published reports on VS during HT. Data collected included the incidence of VS in the HT population, patient and intraoperative characteristics, and postoperative outcomes. RESULTS: Twenty-two publications were included in this review. The prevalence of VS during HT was 28.72% (95% confidence interval: 27.37%, 30.10%). Factors associated with VS included male sex, higher body mass index, hypothyroidism, pre-HT left ventricular assist device or venoarterial extracorporeal membrane oxygenation (VA-ECMO), pre-HT calcium channel blocker or amiodarone usage, longer cardiopulmonary bypass time, and higher blood product transfusion requirement. Patients who developed VS were more likely to require postoperative VA-ECMO support, renal replacement therapy, reoperation for bleeding, longer mechanical ventilation, and a greater 30-day and 1-year mortality. CONCLUSIONS: The results of our systematic review are an initial step for providing clinicians with data that can help identify high-risk patients and avenues for potential risk mitigation. Establishing guidelines that officially define VS will aid in the precise diagnosis of these patients during HT and guide treatment. Future studies of treatment strategies for refractory VS are needed in this high-risk patient population.

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.

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.

A norepinephrine weaning strategy using dynamic arterial elastance is associated with reduction of acute kidney injury in patients with vasoplegia after cardiac surgery: A post-hoc analysis of the randomized SNEAD study.

STUDY OBJECTIVE: To evaluate the impact of a dynamic arterial elastance guided norepinephrine weaning strategy on the occurrence of acute kidney injury (AKI) in patients with vasoplegia after cardiac surgery. DESIGN: A post-hoc analysis of a monocentric randomized controlled trial. SETTING: A tertiary care hospital in France. PARTICIPANTS: Vasoplegic cardiac surgical patients treated with norepinephrine. INTERVENTION: Patients were randomized to an algorithm-based norepinephrine weaning intervention (dynamic arterial elastance) group or a control group. MEASUREMENTS: The primary endpoint was the number of patients with AKI defined according to Kidney Disease Improving Global Outcomes (KDIGO) criteria. The secondary endpoint were major adverse cardiac post-operative events (new onset of atrial fibrillation or flutter, low cardiac output syndrome, and in-hospital death). End points were evaluated during the first seven post-operative days. RESULTS: 118 patients were analyzed. In the overall study population, the mean age was 70 (62-76) years, 65% were male and the median EuroSCORE was 7 (5-10). Overall, 46 (39%) patients developed AKI (30 KDIGO 1, 8 KDIGO 2, 8 KDIGO 3), and 6 patients required renal replacement therapy. The incidence of AKI was significantly lower in the intervention group than in the control group (16 patients (27%) vs 30 patients (51%), p = 0.12). Higher dose and longer duration of norepinephrine were associated with AKI severity. CONCLUSION: Decreasing norepinephrine exposure by using a dynamic arterial elastance guided norepinephrine weaning strategy was associated with a reduced incidence of acute kidney injury in patients with vasoplegia after cardiac surgery. Further prospective multicentric studies are needed to confirm these results.

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.

Vasoplegia Following Orthotopic Heart Transplantation: Prevalence, Predictors and Clinical Outcomes.

BACKGROUND: Patients undergoing heart transplant are at high risk for postoperative vasoplegia. Despite its frequency and association with poor clinical outcomes, there remains no consensus definition for vasoplegia, and the predisposing risk factors for vasoplegia remain unclear. Accordingly, the aim of this study was to evaluate the prevalence, predictors, and clinical outcomes associated with vasoplegia in a contemporary cohort of patients undergoing heart transplantation. METHODS: This was a retrospective cohort study of patients undergoing heart transplantation from January 2015 to December 2019. A binary definition of vasoplegia of a cardiac index of 2.5 L/min/m2 or greater and requirement for norepinephrine (≥5 µg/min), epinephrine (≥4 µg/min), or vasopressin (≥1 unit/h) to maintain a mean arterial blood pressure of 65 mm Hg, for 6 consecutive hours during the first 48 hours postoperatively, was used in determining prevalence. Given the relatively low threshold for the binary definition of vasoplegia, patients were divided into tertiles based on their cumulative vasopressor requirement in the 48 hours following transplant. Outcomes included all-cause mortality, intubation time, intensive care unit length of stay, and length of total hospitalization. RESULTS: After exclusion of patients with primary cardiogenic shock, major bleeding, or overt sepsis, data were collected on 95 eligible patients. By binary definition, vasoplegia incidence was 66.3%. We separately stratified by actual vasopressor requirement tertile (high, intermediate, low). Stratified by tertile, patients with vasoplegia were older (52.7 ± 10.2 vs 46.8 ± 12.7 vs 44.4 ± 11.3 years, P = .02), with higher rates of chronic kidney disease (18.8% vs 32.3% vs 3.1%, P = .01) and were more likely to have been transplanted from left ventricular assist device support (n = 42) (62.5% vs 32.3% vs 37.5%, P = .03). Cardiopulmonary bypass time was prolonged in those that developed vasoplegia (155 min [interquartile range 135-193] vs 131 min [interquartile range 117-152] vs 116 min [interquartile range 102-155], P = .003). Intubation time and length of intensive care unit and hospital stay were significantly increased in those that developed vasoplegia; however, this difference did not translate to a significant increase in all-cause mortality at 30 days or 1 year. CONCLUSIONS: Vasoplegia occurs at a high rate after heart transplantation. Older age, chronic kidney disease, mechanical circulatory support, and prolonged bypass time are all associated with vasoplegia; however, this study did not demonstrate an associated increase in all-cause mortality LAY SUMMARY: Patients undergoing heart transplantation are at high risk of vasoplegia, a condition defined by low blood pressure despite normal heart function. We found that vasoplegia was common after heart transplant, occurring in 60%-70% of patients after heart transplant after excluding those with other causes for low blood pressure. Factors implicated included age, poor kidney function, prolonged cardiopulmonary bypass time and preoperative left ventricular assist device support. We found no increased risk of death in patients with vasoplegia despite longer lengths of stay in intensive care and in hospital.

The Use of Angiotensin II for the Treatment of Post-cardiopulmonary Bypass Vasoplegia.

PURPOSE: Vasoplegia is a common complication after cardiac surgery and is related to the use of cardiopulmonary bypass (CPB). Despite its association with increased morbidity and mortality, no consensus exists in terms of its treatment. In December 2017, angiotensin II (AII) was approved by the Food and Drug Administration (FDA) for use in vasodilatory shock; however, except for the ATHOS-3 trial, its use in vasoplegic patients that underwent cardiac surgery on CPB has mainly been reported in case reports. Thus, the aim of this review is to collect all the clinically relevant data and describe the pharmacologic mechanism, efficacy, and safety of this novel pharmacologic agent for the treatment of refractory vasoplegia in this population. METHODS: Two independent reviewers performed a systematic search in PubMed, Embase, Web of Science, and Cochrane Library using relevant MeSH terms (Angiotensin II, Vasoplegia, Cardiopulmonary Bypass, Cardiac Surgical Procedures). RESULTS: The literature search yielded 820 unique articles. In total, 9 studies were included. Of those, 2 were randomized clinical trials (RCTs) and 6 were case reports and 1 was a retrospective cohort study. CONCLUSIONS: AII appears to be a promising means of treatment for patients with post-operative vasoplegia. It is demonstrated to be effective in raising blood pressure, while no major adverse events have been reported. It remains uncertain whether this agent will be broadly available and whether it will be more advantageous in the clinical management of vasoplegia compared to other available vasopressors. For that reason, we should contain our eagerness and enthusiasm regarding its use until supplementary knowledge becomes available.

Relation of Left Ventricular Assist Device Infections With Cardiac Transplant Outcomes.

Left ventricular assist device (LVAD)-specific infections (LSIs) are common in patients on LVAD support awaiting heart transplant (HT), yet their impact on post-HT outcomes is not completely understood. We hypothesized that LSIs would result in vasoplegia and negatively affect post-HT 30-day and 1-year outcomes. LSI was defined as driveline, pump, or pocket infection. The short-term outcome was a composite of acute renal failure, allograft rejection, and mortality at 30 days after HT. The long-term outcome was a composite of allograft rejection and death within 1 year after HT. We performed a retrospective analysis of 111 HT recipients bridged with durable LVAD support at our institution from May 2012 to August 2019. Of these, 63 patients had LSIs, with 94% of the infections being driveline infections. Vasoplegia was more prevalent in the LSI group but not significantly (7 vs 2 persons, p = 0.3). There was no difference in the composite end point of acute renal failure, rejection, or death at 30 days (30% vs 25%, p = 0.55) or 1-year end point of rejection and death (38% vs 40%, p = 0.87) in patients with LSI versus those without LSI. In conclusion, LSIs were common in patients on LVAD who underwent HT in our single-center contemporary cohort. However, LSI was not associated with adverse outcomes at 30 days or at 1 year after HT.

Risk factors for vasoplegia after coronary artery bypass and valve surgery.

INTRODUCTION: Vasoplegia denotes a state of low tissue perfusion characterized by hypotension, tachycardia, and low systemic vascular resistance. This state results in increased mortality and morbidity following cardiac surgery. A better understanding of the associated risk factors will guide the surgical team in patient management. The aim of this study is to determine which risk factors are involved in its emergence. METHODS: This prospective observational study included adult cardiac surgery patients between February - September 2018 at a single cardiothoracic surgery center. Patients were evaluated for cardiac contractility, surgical drainage, inotrope, and vasopressor requirement perioperatively. The groups were compared for demographic, echocardiographic, and operative variables. Variables significant in univariate analysis were carried on to binary logistic regression for risk factor analysis. RESULTS: A total of 31 patients were vasoplegic among a total of 487 included patients, resulting in a 6.37% incidence. In the vasoplegia group, chronic kidney failure, use of angiotensin-converting enzyme (ACE) inhibitors, use of angiotensin receptor blockers, and use of diuretics were more frequent, cardiopulmonary bypass (CPB) and aortic cross-clamp durations were longer, and mean Euroscore II was higher. Vasoplegia was more frequent in valve surgery and resternotomy patients. CPB duration, use of ACE inhibitors, use of angiotensin receptor blockers, and chronic renal failure were independent risk factors. CONCLUSION: Patients with long CPB duration, preoperative use of ACE inhibitors or Angiotensin receptor blockers, and a history of renal failure requiring dialysis are under increased risk of vasoplegia. Vasoplegia necessitates large-scale studies for a better understanding of its risk factors.

Incidence of vasoplegic syndrome after cardiac transplantation in patients treated with sacubitril/valsartan.

Vasoplegic syndrome (VS) is associated with poor outcomes after heart transplantation (HT). Our aim was to determine whether SAC/VALS is associated with VS after HT. We retrospectively analyzed all consecutive HT performed in three centers between January 2017 and August 2018. VS was defined as vasopressor need (norepinephrine or epinephrine >.5 mcg/kg/min or vasopressin) for more than 24 hours to maintain a mean arterial pressure >70 mm Hg. Ninety-six recipients underwent HT in the study period: 60 elective HT with no LVAD, 5 elective HT on long term LVAD, and 31 emergent HT: 3 on long-term LVAD and 28 on temporary mechanical circulatory support. Fourteen patients were on SAC/VALS treatment at the time of transplant, and 82 were not. The global incidence of VS was 15.6%, with no significant differences between the groups (7.14% in with SAC/VALS vs 17.07% in no-SAC/VALS). In conclusion, in our small cohort SAC/VALS was not associated with VS development.

Painful gynecologic and obstetric complications of female genital mutilation/cutting: A systematic review and meta-analysis.

BACKGROUND: The health complications experienced by women having undergone female genital mutilation/cutting (FGM/C) are a source of growing concern to healthcare workers globally as forced displacement and migration from countries with high rates of this practice increases. In this systematic review and meta-analysis, we investigate the association between FGM/C and painful gynecologic and obstetric complications in women affected by the practice. METHODS AND FINDINGS: We performed a comprehensive literature search from inception to December 19, 2019 of Ovid MEDLINE, Ovid EMBASE, The Cochrane Library (Wiley), and POPLINE (prior to its retirement) for studies mentioning FGM/C. Two reviewers independently screened studies reporting prevalences of painful gynecologic and obstetric sequelae resulting from FGM/C. Random effects models were used to estimate pooled odds ratios (ORs) for outcomes obtained from cross-sectional, cohort, and case-control designs. Subgroup analysis was performed to assess and control for effect differences introduced by study design. Validated appraisal tools were utilized to assess quality and risk of bias. Our study was registered with PROSPERO. Two reviewers independently screened 6,666 abstracts. Of 559 full-text studies assessed for eligibility, 116 met eligibility criteria, which included studies describing the incidence or prevalence of painful sequelae associated with FGM/C. Pooled analyses after adjustment for study design found that FGM/C was associated with dyspareunia (6,283 FGM/C and 3,382 non-FGM/C participants; pooled OR: 2.47; 95% confidence interval [CI]: 1.45-4.21; I2: 79%; p-value < 0.01), perineal tears (4,898 FGM/C and 4,229 non-FGM/C participants; pooled OR: 2.63; 95% CI: 1.35-5.11; I2: 67%; p-value = 0.01), dysuria (3,686 FGM/C and 3,482 non-FGM/C participants; pooled OR: 1.43; 95% CI: 1.17-1.75; I2: 0%; p-value = 0.01), episiotomy (29,341 FGM/C and 39,260 non-FGM/C participants; pooled OR: 1.89; 95% CI: 1.26-2.82; I2: 96%; p-value < 0.01), and prolonged labor (7,516 FGM/C and 8,060 non-FGM/C participants; pooled OR: 2.04; 95% CI: 1.27-3.28; I2: 90%; p-value < 0.01). There was insufficient evidence to conclude that there was an association between FGM/C and dysmenorrhea (7,349 FGM/C and 4,411 non-FGM/C participants; pooled OR: 1.66; 95% CI: 0.97-2.84; I2: 86%; p-value = 0.06), urinary tract infection (4,493 FGM/C and 3,776 non-FGM/C participants; pooled OR: 2.11; 95% CI: 0.80-5.54; I2: 90%; p-value = 0.10), instrumental delivery (5,176 FGM/C and 31,923 non-FGM/C participants; pooled OR: 1.18; 95% CI: 0.78-1.79; I2: 63%; p-value = 0.40), or cesarean delivery (34,693 FGM/C and 46,013 non-FGM/C participants; pooled OR: 1.51; 95% CI: 0.99-2.30; I2: 96%; p-value = 0.05). Studies generally met quality assurance criteria. Limitations of this study include the largely suboptimal quality of studies. CONCLUSIONS: In this study, we observed that specific painful outcomes are significantly more common in participants with FGM/C. Women who underwent FGM/C were around twice as likely as non-FGM/C women to experience dyspareunia, perineal tears, prolonged labor, and episiotomy. These data indicate that providers must familiarize themselves with the unique health consequences of FGM/C, including accurate diagnosis, pain management, and obstetric planning. REVIEW PROTOCOL REGISTRATION: The review protocol registration in PROSPERO is CRD42018115848.

Longer term hemodialysis-dependent chronic renal failure increases the risk of post-cardiac surgery vasoplegic syndrome.

PURPOSE: We evaluated whether longer term hemodialysis (HD) is associated with a higher incidence of vasoplegic syndrome (VS) after cardiac surgery. METHODS: This retrospective, single-center cohort study included 562 consecutive patients who underwent cardiac surgery in a tertiary hospital from January 2015 to December 2016. We assessed VS occurrence and its relationship with HD duration and other risk factors. To assess the effect of the HD duration on VS occurrence, we constructed ordinal variables: HD = 0 (non-HD), 0 < HD ≤ 5 (HD ≤ 5 years), 5 < HD ≤ 10, and 10 < HD. RESULTS: The overall mean (± standard deviation) age of patients was (73 ± 11) years, and there were 60.9% men. Forty-one patients (7.3%) were HD dependent. Cardiac surgeries included all coronary artery bypass graft procedures, all valvular procedures, and aortic surgery involving cardiopulmonary bypass (CPB). Sixty-six patients (10%) developed VS. Most preoperative patient characteristics were comparable between the VS and no-VS groups; a chronic HD status and a total CPB time of > 180 min were significantly more common in the VS group (P < 0.0001 and P = 0.02, respectively). Longer term HD significantly correlated with VS incidence (P < 0.0001). Ordinal variables for the HD duration and age and known risk factors for VS (preoperative use of angiotensin-converting enzyme inhibitors and beta-blockers, low left-ventricular ejection fraction, and CPB time > 180 min) were subjected to multivariate regression analysis. Long-term HD was identified as an independent predictor of VS (odds ratio, 2.29, 95% confidence interval, 1.66-3.18). CONCLUSIONS: Longer term HD may be associated with a higher VS incidence after cardiac surgery. VS should be given attention after cardiac surgery in chronic HD-dependent patients.

Vasoplegia After Cardiac Surgery Is Associated With Endothelial Glycocalyx Alterations.

OBJECTIVE: To assess endothelial glycocalyx (EG) alteration in vasoplegic syndrome after cardiac surgery with cardiopulmonary bypass. DESIGN: Prospective analysis SETTING: Single university hospitals. PARTICIPANTS: Patients undergoing elective cardiac surgery under cardiopulmonary bypass. INTERVENTIONS: Observational study METHODS: Heparan sulfate and syndecan-1 levels were assessed in plasma before surgery, on intensive care unit admission, and on the first postoperative day. The primary outcome was comparisons of heparan sulfate and syndecan-1 levels in patients with and without vasoplegic syndrome. RESULTS: A total of 46 patients were analyzed. Only syndecan-1 was modified by cardiac surgery (p < 0.05). Plasma syndecan-1 levels were lower in patients with vasoplegic syndrome at the 3 time-points and were associated with the cumulative norepinephrine dose. Baseline plasma syndecan-1 predicted the development of vasoplegic syndrome with an area under the curve of 0.7 (confidence interval 95%: 0.51-0.85, p = 0.045). Heparan sulfate levels were not modified by cardiac surgery. CONCLUSION: Patients with vasoplegic syndrome after cardiac surgery present a different pattern of EG components. Lower syndecan-1 levels were associated with vasoplegic syndrome. These preliminary results suggest a specific phenotype that may reflect endothelial activation leading to alteration of the EG.

Predictors and Clinical Outcomes of Vasoplegia in Patients Bridged to Heart Transplantation With Continuous-Flow Left Ventricular Assist Devices.

Background The presence of a durable left ventricular assist device (LVAD) is associated with increased risk of vasoplegia in the early postoperative period following heart transplantation (HT). However, preoperative predictors of vasoplegia and its impact on survival after HT are unknown. We sought to examine predictors and outcomes of patients who develop vasoplegia after HT following bridging therapy with an LVAD. Methods and Results We identified 94 patients who underwent HT after bridging with continuous-flow LVAD from 2008 to 2018 at a single institution. Vasoplegia was defined as persistent low vascular resistance requiring ≥2 intravenous vasopressors within 48 hours after HT for >24 hours to maintain mean arterial pressure >70 mm Hg. Overall, 44 patients (46.8%) developed vasoplegia after HT. Patients with and without vasoplegia had similar preoperative LVAD, echocardiographic, and hemodynamic parameters. Patients with vasoplegia were significantly older; had longer LVAD support, higher preoperative creatinine, longer cardiopulmonary bypass time, and higher Charlson comorbidity index; and more often underwent combined organ transplantation. In a multivariate logistic regression model, older age (odds ratio: 1.08 per year; P=0.010), longer LVAD support (odds ratio: 1.06 per month; P=0.007), higher creatinine (odds ratio: 3.9 per 1 mg/dL; P=0.039), and longer cardiopulmonary bypass time (odds ratio: 1.83 per hour; P=0.044) were independent predictors of vasoplegia. After mean follow-up of 4.0 years after HT, vasoplegia was associated with increased risk of all-cause mortality (hazard ratio: 5.20; 95% CI, 1.71-19.28; P=0.003). Conclusions Older age, longer LVAD support, impaired renal function, and prolonged intraoperative CPB time are independent predictors of vasoplegia in patients undergoing HT after LVAD bridging. Vasoplegia is associated with worse prognosis; therefore, detailed assessment of these predictors can be clinically important.

Vasoplegia After Restrictive Mitral Annuloplasty for Functional Mitral Regurgitation in Patients With Heart Failure.

OBJECTIVES: Patients undergoing heart failure surgery are at risk for developing postoperative vasoplegia. The aim of this study was to determine the incidence, survival, and predictors of vasoplegia in heart failure patients undergoing mitral valve repair for functional mitral regurgitation and to evaluate the effect of ischemic versus non-ischemic etiology. DESIGN: Retrospective. SETTING: University medical center, single institutional. PARTICIPANTS: Heart failure patients with functional mitral regurgitation who underwent restrictive mitral annuloplasty (2006-2015). MEASUREMENTS AND MAIN RESULTS: One hundred twenty-two patients were included (48% ischemic etiology). The incidence of vasoplegia was 19% and was not influenced by mitral regurgitation etiology. Ninety-day survival rate was decreased in vasoplegic compared with non-vasoplegic patients (65% v 93%, p < 0.001). After adjusting for age, gender, and heart failure etiology, prior hypertension (odds ratio [OR] 0.28; 95% confidence interval [CI] 0.08-0.91; p = 0.034), higher creatinine clearance (OR 0.97; 95% CI 0.95-0.99; p = 0.009), and beta-blocker use (OR 0.25; 95% CI 0.09-0.73; p = 0.011) decreased the risk of vasoplegia. Anemia (OR 3.00; 95% CI 1.10-8.20; p = 0.032) and longer cross clamp (OR 1.03; 95% CI 1.01-1.04; p = 0.001), cardiopulmonary bypass (OR 1.01; 95% CI 1.00-1.02; p = 0.003), and procedure times (OR 1.01; 95% CI 1.00-1.02, p = 0.002) increased the risk of vasoplegia. CONCLUSIONS: Vasoplegia occurs in 19% of heart failure patients undergoing mitral valve repair for functional mitral regurgitation. It is associated with a poor early outcome. Prior hypertension, a higher creatinine clearance, and beta-blocker use were associated with a decreased risk of vasoplegia, whereas anemia and longer procedure times were associated with an increased risk of vasoplegia, independent of heart failure etiology.

Intraoperative vasoplegic syndrome in patients with fulminant myocarditis on ventricular assist device placement.

PURPOSE: Fulminant myocarditis is uncommon, but life-threatening, and some patients need mechanical circulatory support. This study was performed to evaluate how different types of mechanical circulatory support-biventricular assist device (BiVAD) or left ventricular assist device (LVAD) placement-affect intraoperative hemodynamic status. METHODS: From January 2013 to September 2016, the patients who underwent BiVAD or LVAD placement for fulminant myocarditis were analyzed. The mean arterial pressure (MAP), mean pulmonary arterial pressure, central venous pressure (CVP), vasoactive score, and inotropic score were recorded at five time points: after the induction of anesthesia; at weaning, 30 min after weaning, and 60 min after weaning from cardiopulmonary bypass (CPB); and at the end of surgery. The vasoactive and inotropic scores were calculated as follows: vasoactive score = norepinephrine (µg/kg/min) × 100 + milrinone (µg/kg/min) × 10 + olprinone (µg/kg/min) × 25: inotropic score = dopamine (µg/kg/min) × 1 + dobutamine (µg/kg/min) × 1 + epinephrine (µg/kg/min) × 100. RESULTS: We enrolled 16 patients of fulminant myocarditis. Ten of them underwent BiVAD placement, and the other underwent LVAD placement. After weaning from CPB, the BiVAD group had a significantly lower MAP but no difference in CVP. The vasoactive score was significantly higher in the BiVAD group at weaning of CPB (p = 0.015), 30 min after weaning (p = 0.004), 60 min after weaning (p = 0.005), and at the end of surgery (p < 0.016). CONCLUSION: Patients with BiVAD placement required more vasoactive support to maintain optimal hemodynamic status compared with those with LVAD placement. This result indicates that BiVAD placement was more associated with vasoplegic syndrome.

Risk factors for vasoplegia after cardiac surgery: a meta-analysis.

OBJECTIVES: Postoperative vasoplegia (PV) is a common haemodynamic disorder after cardiac surgery and is associated with high operative mortality. Preventive and potent therapeutic measures are critical to improve the outcome. Identification of risk factors for PV may increase awareness and prompt therapeutic action. Our objective was to pool the available evidence on the risk factors for PV in cardiac surgery and to perform a meta-analysis. METHODS: PubMed, Embase, Ovid and Google Scholar databases were searched for studies published between 1965 and 2017. Three investigators independently screened the studies and extracted the data. Pooled estimates were obtained by a random effects model. Preoperative and operative patient data were gathered to determine their association with PV. RESULTS: The search yielded 109 potential studies for inclusion. Of these, 10 articles were analysed and their data extracted. The total number of patients included was 30 035 patients (1524 with vasoplegia and 28 511 without vasoplegia). The only preoperative variable that was significantly associated with PV was renal failure [odds ratio (OR) 1.47; 95% confidence interval (CI) 1.17-1.86]. Patients with isolated coronary artery bypass grafting had a lower risk for PV (OR 0.36; 95% CI 0.22-0.59), whereas previous cardiac surgery (OR 2.03; 95% CI 1.27-3.26) and combined procedures increased its incidence (OR 2.12; 95% CI 1.82-2.47). PV increased with higher use of red blood cells (OR 2.12; 95% CI 1.82-2.47), longer aortic cross-clamp (mean difference 8.15 min; 95% CI 8.79-27.50 min) and cardiopulmonary bypass (mean difference 25.72 min; 95% CI 12.75-38.69 min) duration. CONCLUSIONS: Patients with renal failure, higher use of red blood cell, longer and combined cardiac surgery procedures are at a higher risk for PV. Measures to promptly identify and treat PV in these patients should be considered.

Vasoplegia after implantation of a continuous flow left ventricular assist device: incidence, outcomes and predictors.

BACKGROUND: Vasoplegia after routine cardiac surgery is associated with severe postoperative complications and increased mortality. It is also prevalent in patients undergoing implantation of pulsatile flow left ventricular assist devices (LVAD). However, less is known regarding vasoplegia after implantation of newer generations of continuous flow LVADs (cfLVAD). We aim to report the incidence, impact on outcome and predictors of vasoplegia in these patients. METHODS: Adult patients scheduled for primary cfLVAD implantation were enrolled into a derivation cohort (n = 118, 2006-2013) and a temporal validation cohort (n = 73, 2014-2016). Vasoplegia was defined taking into consideration low mean arterial pressure and/or low systemic vascular resistance, preserved cardiac index and high vasopressor support. Vasoplegia was considered after bypass and the first 48 h of ICU stay lasting at least three consecutive hours. This concept of vasoplegia was compared to older definitions reported in the literature in terms of the incidence of postoperative vasoplegia and its association with adverse outcomes. Logistic regression was used to identify independent predictors. Their ability to discriminate patients with vasoplegia was quantified by the area under the receiver operating characteristic curve (AUC). RESULTS: The incidence of vasoplegia was 33.1% using the unified definition of vasoplegia. Vasoplegia was associated with increased ICU length-of-stay (10.5 [6.9-20.8] vs 6.1 [4.6-10.4] p = 0.002), increased ICU-mortality (OR 5.8, 95% CI 1.9-18.2) and one-year-mortality (OR 3.9, 95% CI 1.5-10.2), and a higher incidence of renal failure (OR 4.3, 95% CI 1.8-10.4). Multivariable analysis identified previous cardiothoracic surgery, preoperative dopamine administration, preoperative bilirubin levels and preoperative creatinine clearance as independent preoperative predictors of vasoplegia. The resultant prediction model exhibited a good discriminative ability (AUC 0.80, 95% CI 0.71-0.89, p <  0.01). Temporal validation resulted in an AUC of 0.74 (95% CI 0.61-0.87, p <  0.01). CONCLUSIONS: In the era of the new generation of cfLVADs, vasoplegia remains a prevalent (33%) and critical condition with worse short-term outcomes and survival. We identified previous cardiothoracic surgery, preoperative treatment with dopamine, preoperative bilirubin levels and preoperative creatinine clearance as independent predictors.

Vitamin D and Postoperative Vasopressor Use in Cardiopulmonary Bypass.

The use of cardiopulmonary bypass (CPB) in cardiac surgery often leads to a systemic inflammatory response. Up to 25% of patients undergoing CPB for cardiac surgery are reported to develop vasoplegic syndrome in the acute postoperative period, in which the patients are refractory to vasopressors. The purpose of this study is to assess vitamin D deficiency as a risk factor for vasoplegia after using CPB. We performed a retrospective review of 1322 patients undergoing adult cardiac surgery requiring CPB. Forty-six patients with previously recorded 25-hydroxy vitamin D (25(OH)D) levels within 6 months of surgery met the conditions of this study. The mean level of 25(OH)D was 32.7 ng/mL (standard deviation [SD] = 15.1). The mean age of patients was 67 (SD = 10.1) years old, most were male (63%) and white (78%). Average CPB time was 140 ± 44 minutes. Postoperative vasopressor use was compared to individual preoperative 25(OH)D levels. As a secondary end point, postoperative vasopressor use and vasoplegia were analyzed between 3 groups: Vitamin D deficient defined as 25(OH)D ≤20 ng/mL (n = 7), vitamin D insufficient defined as 25(OH)D between 20 and 29 ng/mL (n = 15), and vitamin D sufficient defined as 25(OH)D ≥30 ng/mL (n = 24). There was no correlation between vitamin D levels and postoperative vasopressor use. The mean doses of postoperative vasopressor use were 0.088 µg/kg/min (standard error of the mean [SEM] = 0.032), 0.085 µg/kg/min (SEM = 0.037), and 0.072 µg/kg/min (SEM = 0.024) of norepinephrine equivalents for the vitamin D deficient, insufficient, and sufficient groups, respectively. Incidence of vasoplegia for each group was the following: 0.143 for vitamin D deficient, 0.067 for vitamin D insufficient, and 0.125 for vitamin D sufficient. In this pilot study, there does not appear to be a relationship between vitamin D and vasopressor use following cardiac surgery utilizing CPB; however, there appears to be a trend toward an increased vasopressor usage in patients with decreased vitamin D levels. A larger sample size and a prospective analysis are warranted to further assess the significance of the relationship between vasoplegia and vitamin D deficiency. With further investigation, vitamin D has the potential to become a low-cost, low-risk therapeutic for improving outcomes in CPB surgery.

Postoperative Vasoplegic Syndrome Is Associated With Impaired Endothelial Vasomotor Response in Cardiac Surgery: A Prospective, Observational Study.

OBJECTIVES: Vasoplegic syndrome (VS) affects up to 30% of cardiac surgery patients. Onset of VS may be associated with overproduction of nitric oxide (NO). The response of the brachial artery to NO can be assessed using flow-mediated vasodilation (FMD). The aim of this study was to assess brachial artery diameter and FMD response immediately after cardiac surgery. DESIGN: Prospective, observational study. SETTING: Single-center study in a tertiary teaching hospital. PATIENTS: Patients older than 18 years undergoing elective cardiac surgery with cardiopulmonary bypass who provided informed consent. INTERVENTIONS: Brachial artery diameter and FMD response were measured before cardiac surgery and just after surgery on admission to the intensive care unit. Patients were screened for VS for the following 48 hours. RESULTS: Eleven (39%) of the 28 patients included in the study developed VS. Brachial artery diameter and FMD differed between VS and non-VS patients. On intensive care unit admission, mean (± standard deviation) brachial artery diameter was greater in VS patients than in non-VS patients (3.9 ± 0.7 mm v 3.0 ± 0.8 mm, respectively; p = 0.002). Similarly, the FMD response after surgery was greater in VS patients than in non-VS patients (42% ± 8% v 31% ± 1%, respectively; p = 0.014). Brachial artery diameter and FMD response after surgery were both predictive of VS, with an area under the curve (95% confidence interval) of 0.850 (0.705-0.995) (p = 0.002) and 0.755 (0.56-0.95) (p = 0.047), respectively. CONCLUSION: Cardiac surgery with cardiopulmonary bypass appears to alter the NO-mediated endothelial vasomotor response.