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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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Angiotensin II is a peptide hormone vasopressor that activates angiotensin type 1 (AT1) receptors leading to vasoconstriction, the augmentation of arterial blood pressure (ABP), and organ perfusion. Angiotensin II was found to increase the ABP in catecholamine-refractory vasodilatory shock. Whether this effect improves the chances of survival or not remains inconclusive. Therefore, we conducted a systematic review and meta-analysis to evaluate the efficacy and safety of angiotensin II in vasoplegic shock. Objectives: To evaluate the clinical significance of angiotensin II effects in vasoplegic shock concerning the hemodynamic impact, mortality outcomes, and side effects. Methods: Following PRISMA guidelines, we searched PubMed and EMBASE for experimental and observational studies published in English exploring the clinical outcomes of angiotensin II use in vasodilatory shock till 1 July 2024. Two independent authors assessed the quality and risk of bias of the included studies. A random effect model (Mantel–Haenszel) was used to combine data. The primary outcome was in-hospital mortality associated with angiotensin II use in comparison to standard therapy, while the secondary outcomes were mean arterial pressure (MAP) change, multi-organ failure (MOF), and the incidence of atrial fibrillation (AF). The Q test and I2 were used to examine heterogeneity, with I2 > 50% indicating marked heterogeneity. Results: A total of eight studies (n = 974) comparing angiotensin II to standard therapy in vasoplegic shock were included in the systematic review, with three studies comprising 461 patients included in the final analysis of the primary outcome. Only one study evaluated the use of angiotensin II as a primary vasopressor, while the rest reported angiotensin II use in catecholamine-refractory vasodilatory shock. Overall, angiotensin II use was associated with similar in-hospital mortality compared to standard therapy (risk ratio [RR] = 0.83; 95% CI, 0.68–1.02, I2 = 0%). Likewise, there was no difference in MOF and AF (MOF: RR = 1.01; 95% CI, 0.61–1.65, I2 = 0%; AF: RR = 1.27; 95% CI, 0.38–4.23, I2 = 5%). However, angiotensin II use demonstrated a significant MAP increase (mean difference = −9.60; 95% CI, −9.71, −9.49, I2 = 0%). Conclusions: In vasodilatory shock, angiotensin II use demonstrated comparable in-hospital mortality compared to standard therapy. Nevertheless, it resulted in significant MAP change, which may encourage clinicians to use it in cases of profound hypotension. [ABSTRACT FROM AUTHOR]

Angiotensin II is a recently introduced vasopressor, which has been available since 2017. The novelty and the relatively high cost of angiotensin II currently limit its broader application. It induces vasoconstriction by activating the renin–angiotensin–aldosterone system and is currently the sole vasopressor functioning through this pathway. Beyond vasoconstriction, angiotensin II also affects various other physiological processes. Current evidence supports its use in managing vasoplegic and cardiogenic shock in patients who are unresponsive to catecholamines and vasopressin. However, due to limited data, the optimal timing for initiating therapy with angiotensin II, strategies for combining it with other vasopressors, and strategies for its discontinuation remain unclear. Ongoing and planned studies aim to address some of these uncertainties. This article reviews the physiological and pathophysiological effects of angiotensin II, describes its pharmacology, and provides a narrative review of the current literature. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. 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. 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. 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. [ABSTRACT FROM AUTHOR]

Background Systemic inflammation due to cardiogenic shock is associated with vasoplegia leading to organ hypoperfusion, right heart failure, and poor clinical outcome. Extracorporeal cytokine hemoadsorption emerged to attenuate excessive levels of inflammatory cytokines, potentially improving patient outcomes. Nevertheless, its prognostic impact during high-risk left ventricular assist device (LVAD) implantation remains unknown. Methods In total, 40 consecutive patients with advanced heart failure underwent continuous-flow LVAD implantation at our institution between 2018 and 2020. Out of 25 high-risk patients in cardiogenic shock (Interagency Registry for Mechanically Assisted Circulatory Support profile 1 and 2), 9 patients (CytoSorb group) underwent LVAD implantation with and 16 patients (control group) without simultaneous cytokine hemoadsorption during cardiopulmonary bypass. Besides preoperative patient characteristics, postoperative lactate clearance, vasopressor administration and mean arterial pressure, perioperative complication, and 30-day mortality rates were retrospectively analyzed. Results Apart from an increased rate of reoperations within the CytoSorb group, baseline characteristics including the severity of ventricular dysfunction and consecutive signs of end-organ failure were similar in both groups. Preoperative short-term mechanical circulatory support bridging was comparable (66.7 vs. 75%; p = 0.66) prior to LVAD implantation. Procedural characteristics including intraoperative volume management and postoperative vasopressor administration were similar in both groups. There was no difference regarding postoperative lactate clearance, although postoperative mean arterial pressure was significantly higher in the control group (71.3 vs. 57.4 mm Hg; p < 0.01). Furthermore, the 30-day mortality rate was significantly higher in the CytoSorb group (33.3 vs. 0.0%; p = 0.01). Conclusion Extracorporeal cytokine hemoadsorption during high-risk LVAD implantation was not associated with a decrease of postoperative vasopressor support, improved hemodynamics, or an accelerated lactate clearance. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Casein kinase II (CK2) has recently emerged as a pivotal mediator in the propagation of inflammation across various diseases. Nevertheless, its role in the pathogenesis of sepsis remains unexplored. Here, we investigated the involvement of CK2 in sepsis progression and the potential beneficial effects of silmitasertib, a selective and potent CK2α inhibitor, currently under clinical trials for COVID-19 and cancer. Sepsis was induced by caecal ligation and puncture (CLP) in four-month-old C57BL/6OlaHsd mice. One hour after the CLP/Sham procedure, animals were assigned to receive silmitasertib (50 mg/kg/i.v.) or vehicle. Plasma/organs were collected at 24 h for analysis. A second set of experiments was performed for survival rate over 120 h. Septic mice developed multiorgan failure, including renal dysfunction due to hypoperfusion (reduced renal blood flow) and increased plasma levels of creatinine. Renal derangements were associated with local overactivation of CK2, and downstream activation of the NF-ĸB-iNOS-NO axis, paralleled by a systemic cytokine storm. Interestingly, all markers of injury/inflammation were mitigated following silmitasertib administration. Additionally, when compared to sham-operated mice, sepsis led to vascular hyporesponsiveness due to an aberrant systemic and local release of NO. Silmitasertib restored sepsis-induced vascular abnormalities. Overall, these pharmacological effects of silmitasertib significantly reduced sepsis mortality. Our findings reveal, for the first time, the potential benefits of a selective and potent CK2 inhibitor to counteract sepsis-induced hyperinflammatory storm, vasoplegia, and ultimately prolonging the survival of septic mice, thus suggesting a pivotal role of CK2 in sepsis and silmitasertib as a novel powerful pharmacological tool for drug repurposing in sepsis.

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Study design: Retrospective cohort study Objectives: Vasoplegia is a life-threatening form of distributive or vasodilatory shock that is characterized by reduced systemic vascular resistance with resultant hypotension and normal to elevated cardiac output affecting morbidity and mortality. Vasoplegia in the context of Spine Surgery has not been described previously. The purpose of this case series is to determine incidence, risk factors, complications and postoperative outcome in patients with vasoplegia after complex multi-level thoraco-lumbar spine surgery. Methods: A retrospective review of the electronic medical records at our institution was conducted between January 2014 and June 2018. All patients undergoing multi-level spine surgery (>6 levels) were screened for intraoperative hypotension. Patient demographics, surgical characteristics, neurological status, blood loss, risk factors, medical treatment, complications, hospital course and mortality were collected. All patients included in this study had a minimum follow-up period of 3 months. Results: Out of 8521 surgically treated patients, 994 patients with multi-level thoraco-lumbar spine surgery were identified. A total of 41 patients had intraoperative hypotensive events. Of those, 5 patients with vasoplegia could be identified after elimination of all other potential contributing factors. Vasoplegia did not influence the neurological outcome. One major and three minor complications occurred. All patients showed full recovery. The risk factors identified for vasoplegia include prolonged surgery with osteotomies. Conclusions: Vasoplegia is a rare condition with an incidence of.6%. Patients experiencing vasoplegia did not appear to experience worse surgical outcomes. The use of special intraoperative hemodynamic monitoring should be considered in selected cases. [ABSTRACT FROM AUTHOR]

Angiotensin II is a recently introduced vasopressor, which has been available since 2017. The novelty and the relatively high cost of angiotensin II currently limit its broader application. It induces vasoconstriction by activating the renin–angiotensin–aldosterone system and is currently the sole vasopressor functioning through this pathway. Beyond vasoconstriction, angiotensin II also affects various other physiological processes. Current evidence supports its use in managing vasoplegic and cardiogenic shock in patients who are unresponsive to catecholamines and vasopressin. However, due to limited data, the optimal timing for initiating therapy with angiotensin II, strategies for combining it with other vasopressors, and strategies for its discontinuation remain unclear. Ongoing and planned studies aim to address some of these uncertainties. This article reviews the physiological and pathophysiological effects of angiotensin II, describes its pharmacology, and provides a narrative review of the current literature.

Objective: Vasoplegic shock, sometimes referred to as distributive shock, is a life-threatening clinical syndrome involving systemic vasodilation and is associated with significant morbidity and mortality in intensive care unit (ICU) patients. The most common etiology is sepsis; others include post-cardiac bypass vasoplegia and various toxidromes. Key components of management include fluid resuscitation and vasopressors to restore vascular tone. Methylene blue selectively targets inducible nitric oxide synthase, a key component of early vasodilation in response to inflammation. We investigated whether the timing of administration of methylene blue influences clinical response, as measured by subsequent vasopressor requirements, fluid resuscitation, organ system function, and mortality. Design: This study was a retrospective case series including 33 cases. Data were collected for each case, including timing of administration, vasopressor and fluid requirements, Sequential Organ Failure Assessment (SOFA) scores, and inhospital mortality. A Spearman's rank correlation was performed to assess the correlation between the timing of administration of methylene blue and improvement in relevant clinical parameters. Setting: A large metropolitan Intensive Care Unit (47 beds). Patients and participants: Included in this study were adult patients who received methylene blue in the participating ICU between 2020 and 2022 for managing vasoplegic shock. Interventions: Administration of intravenous methylene blue. Measurements and results: No correlation between the timing of administration and reduction in vasopressor requirements was observed. Administration of methylene blue within 8 hours of the onset of shock refractory to 5 mcg/min of noradrenaline was found to weakly correlate with reduced total SOFA score on Day 1 (Rs=0.39, p=0.04), and patients who received methylene blue within eight hours had a lower mortality (60.0% vs 78.2%). Conclusions: These findings suggest that a prolonged period of vasoplegic shock before consideration of methylene blue should not discourage its use. A prospective randomized control study will be a valuable direction for future research. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. This was a historic cohort study. The study was conducted at a quaternary academic cardiovascular surgery program. Adults undergoing cardiac surgery using CPB were participants in the study. Hydroxocobalamin (5 g) intravenously over 15 minutes. 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. A difference in vasopressor-free days after CPB was not found between patients who received hydroxocobalamin intraoperatively versus postoperatively for vasoplegic shock. [ABSTRACT FROM AUTHOR]

• Vasoplegia is a common phenomenon during and after cardiac surgery. • There are few studies on the occurrence of intraoperative vasoplegia in lung transplant. • In this study, vasoplegia incidence in lung transplant is comparable to cardiac surgery. • Male sex and cystic fibrosis are risk factors for vasoplegia in lung transplant. 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. Retrospective study of single and bilateral lung transplants from April 2013 to September 2021. The study was conducted at an academic hospital. Patients ≥18 years of age who underwent lung transplantation. None. 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. 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. [ABSTRACT FROM AUTHOR]

Metformin overdose may result in vasodilatory shock, lactic acidosis and death. Hemodialysis is an effective means of extracorporeal elimination, but may be insufficient in the shock setting. We present a case of a 39 yo male who presented with hypotension, coma, hypoglycemia, and lactate of 6.5 mmol/L after ingesting an unknown medication. Metformin overdose was suspected, and he was started on hemodialysis. He developed profound vasoplegia refractory to high doses of norepinephrine, vasopressin, epinephrine and phenylephrine. Venoarterial extracorporeal membrane oxygenation (VA ECMO) was initiated and he had full recovery. Serum analysis with high resolution liquid chromatography mass spectrometry revealed a metformin level of 678 μg/mL and trazodone level of 2.1 μg/mL. This case is one of only a handful of reported cases of metformin overdose requiring ECMO support, and we report the highest serum metformin levels in the literature to date. We recommend early aggressive hemodialysis and vasopressor support in all suspected cases of metformin toxicity as well as VA ECMO if refractory to these therapies.ObjectiveWe present a case of vasodilatory shock secondary to metformin overdose requiring venoarterial extracorporeal membrane oxygenation (VA ECMO) support. This case is one of only a handful of reported cases of metformin overdose requiring ECMO support, and we report the highest serum metformin levels in the literature to date.Data sourcesUniversity of San Francisco, Fresno.Study designCase report.Data extractionClinical records and high resolution liquid chromatography mass spectroscopy analysis.Data synthesisNone.ConclusionsVenoarterial ECMO provided an effective means of hemodynamic support for a patient with severe metformin toxicity.

Background: Angiotensin II is a peptide hormone vasopressor that activates angiotensin type 1 (AT1) receptors leading to vasoconstriction, the augmentation of arterial blood pressure (ABP), and organ perfusion. Angiotensin II was found to increase the ABP in catecholamine-refractory vasodilatory shock. Whether this effect improves the chances of survival or not remains inconclusive. Therefore, we conducted a systematic review and meta-analysis to evaluate the efficacy and safety of angiotensin II in vasoplegic shock. Objectives: To evaluate the clinical significance of angiotensin II effects in vasoplegic shock concerning the hemodynamic impact, mortality outcomes, and side effects. Methods: Following PRISMA guidelines, we searched PubMed and EMBASE for experimental and observational studies published in English exploring the clinical outcomes of angiotensin II use in vasodilatory shock till 1 July 2024. Two independent authors assessed the quality and risk of bias of the included studies. A random effect model (Mantel–Haenszel) was used to combine data. The primary outcome was in-hospital mortality associated with angiotensin II use in comparison to standard therapy, while the secondary outcomes were mean arterial pressure (MAP) change, multi-organ failure (MOF), and the incidence of atrial fibrillation (AF). The Q test and I2 were used to examine heterogeneity, with I2 > 50% indicating marked heterogeneity. Results: A total of eight studies (n = 974) comparing angiotensin II to standard therapy in vasoplegic shock were included in the systematic review, with three studies comprising 461 patients included in the final analysis of the primary outcome. Only one study evaluated the use of angiotensin II as a primary vasopressor, while the rest reported angiotensin II use in catecholamine-refractory vasodilatory shock. Overall, angiotensin II use was associated with similar in-hospital mortality compared to standard therapy (risk ratio [RR] = 0.83; 95% CI, 0.68–1.02, I2 = 0%). Likewise, there was no difference in MOF and AF (MOF: RR = 1.01; 95% CI, 0.61–1.65, I2 = 0%; AF: RR = 1.27; 95% CI, 0.38–4.23, I2 = 5%). However, angiotensin II use demonstrated a significant MAP increase (mean difference = −9.60; 95% CI, −9.71, −9.49, I2 = 0%). Conclusions: In vasodilatory shock, angiotensin II use demonstrated comparable in-hospital mortality compared to standard therapy. Nevertheless, it resulted in significant MAP change, which may encourage clinicians to use it in cases of profound hypotension.

Abstract Background Norepinephrine is a commonly used drug for treating vasoplegic acute circulatory failure in ICU. The prediction of norepinephrine macro- and micro-circulatory response is complicated by its uneven receptors’ distribution between the arterial and the venous structures, and by the presence of a physiological vascular waterfall (VW) that disconnects the arterial and the venous circulation in two pressure systems. The objectives of this study were to describe the VW in patients with arterial hypotension due to vasodilatory circulatory shock, and its behavior according to its response to norepinephrine infusion. Methods A prospective, observational, bi-centric study has included adult patients, for whom the physician decided to initiate norepinephrine during the six first hours following admission to the ICU after cardiac surgery, and unresponsive to a fluid challenge. The mean systemic pressure (MSP) and the critical closing pressure (CCP) were measured at inclusion and after norepinephrine infusion. Results Thirty patients were included. Norepinephrine increased arterial pressure and total peripheral resistances in all cohort. The cohort was dichotomized as VW responders (patients with a change of VW over the least significant change (≥ 93% increase in VW)), and as VW non-responders. In 19 (63%) of the 30 patients, VW increased from 3.47 [− 14.43;7.71] mmHg to 43.6 [25.8;48.1] mmHg, p

Pulmonary edema has been considered a rare complication that can occur in the early phase of circulatory compensation in dihydropyridine overdose. Here, we present the case of a previously healthy adolescent with distributive shock secondary to supratherapeutic ingestion of amlodipine, enalapril, and atorvastatin. Twelve hours after ingestion, she developed refractory vasoplegia despite conventional vasopressor management. The patient received methylene blue and single-pass albumin dialysis as additional therapeutic measures. Improvement in the hemodynamic pattern began two hours after the initiation of this therapy and coincided with the onset of dyspnea, crackles, and hypoxemia consistent with pulmonary edema. The treatment of this complication was performed with positive pressure, and on the tenth day, she was discharged without complications. With this case report, we aim to highlight that pulmonary edema can be a potentially life-threatening complication, often underdiagnosed in calcium channel blocker intoxication.

ABSTRACT Purpose: Vasoplegia, or vasoplegic shock, is a syndrome whose main characteristic is reducing blood pressure in the presence of a standard or high cardiac output. For the treatment, vasopressors are recommended, and the most used is norepinephrine. However, new drugs have been evaluated, and conflicting results exist in the literature. Methods: This is a systematic review of the literature with meta-analysis, written according to the recommendations of the PRISMA report. The SCOPUS, PubMed, and ScienceDirect databases were used to select the scientific articles included in the study. Searches were conducted in December 2022 using the terms “vasopressin,” “norepinephrine,” “vasoplegic shock,” “postoperative,” and “surgery.” Meta-analysis was performed using Review Manager (RevMan) 5.4. The endpoint associated with the study was efficiency in treating vasoplegic shock and reduced risk of death. Results: In total, 2,090 articles were retrieved; after applying the inclusion and exclusion criteria, ten studies were selected to compose the present review. We found no significant difference when assessing the outcome mortality comparing vasopressin versus norepinephrine (odds ratio = 1.60; confidence interval 0.47–5.50), nor when comparing studies on vasopressin versus placebo. When we analyzed the length of hospital stay compared to the use of vasopressin and norepinephrine, we identified a shorter length of hospital stay in cases that used vasopressin; however, the meta-analysis did not demonstrate statistical significance. Conclusions: Considering the outcomes included in our study, it is worth noting that most studies showed that using vasopressin was safe and can be considered in managing postoperative vasoplegic shock.

This review of the use of vasopressin aims to be comprehensive and highly practical, based on the available scientific evidence and our extensive clinical experience with the drug. It summarizes controversies about vasopressin use in septic shock and other vasodilatory states. Vasopressin is a natural hormone with powerful vasoconstrictive effects and is responsible for the regulation of plasma osmolality by maintaining fluid homeostasis. Septic shock is defined by the need for vasopressors to correct hypotension and lactic acidosis secondary to infection, with a high mortality rate. The Surviving Sepsis Campaign guidelines recommend vasopressin as a second-line vasopressor, added to norepinephrine. However, these guidelines do not address specific debates surrounding the use of vasopressin in real-world clinical practice. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. 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. 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. 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. Australian and New Zealand Clinical Trials Registry—ACTRN12621000195853 23/02/2021. [ABSTRACT FROM AUTHOR]

Introduction: Refractory shock, which fails to respond to conventional vasopressor therapy, is a common complication of sepsis. Methylene blue has emerged as a potential adjunctive treatment option for reversing refractory shock in sepsis. The aim of this study was to evaluate the impact of intravenous methylene blue infusion on hemodynamic improvement and mortality in patients with refractory shock. Methodology: This was an observational prospective study for the duration of six months conducted at intensive care a medical college and teaching hospital including 76 patients with a diagnosis of septic shock requiring vasopressor therapy. Intravenous (IV) methylene blue was infused as bolus dose with 2 mg/kg dose in 20 minutes and its response to mean arterial blood pressure, decrease in vasopressor therapy, lactate level, and urine output was recorded in next 2 hours. Patients with improvement in mean arterial pressure (MAP) by 10% or decrease in vasopressor therapy in next 2 hours were leveled as responder. The length of intensive care unit (ICU) stay, duration of mechanical ventilation, incidence of acute kidney injury (AKI), and mortality were compared between responder and non-responder. Results: A total of 76 patients with refractory shock were included in the study. With the use of IV methylene blue, 41 (53.9%) patients showed significant improvement in MAP within 2 hours (70.17 ± 8.30 vs 64.28 ± 11.84, p = 0.005). Responders were 4.019 times more likely to have vasopressor-free time within 24 hours (18.4% vs 5.3%, p = 0.020, odds ratio 4.019, 95% confidence interval, 1.180-13.682). However, there was no significant difference in terms of mortality, length of ICU stay, ventilator free days, and incidence of AKI. In the responder group, there was a significant increase in the MAP and decrease in vasopressor requirement pre- and post-infusion of methylene blue (p < 0.05). Responder had shorter vasopressor-free days as compared with non-responder (5.34 vs 6.79, p = 0.008) while the mean survival time was longer with responders (21.97 vs 15.93 days, p = 0.024). Conclusion: The use of IV methylene blue in refractory shock as an adjuvant therapy significantly improved the mean arterial blood pressure and decreased the requirement of vasopressor therapy as well as improvement in the survival time. However, there was no change in the mortality, length of ICU stay, ventilator-free days, or incidence of AKI in the patients [ABSTRACT FROM AUTHOR]