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Vasoplegia, characterized by low systemic vascular resistance despite normal to high cardiac output, can result from various conditions, including cardiac surgery, and progress to vasoplegic shock if untreated. This case study involves a male in his 70s with multiple risk factors, including a left ventricular ejection fraction of 35%, who developed vasoplegia after taking lisinopril on the day of his elective coronary artery bypass graft (CABG) surgery. Despite initial management with vasopressors, the patient's condition necessitated postponing the CABG. The patient was stabilized in the ICU with a combination of vasopressin, epinephrine, norepinephrine, and hydrocortisone, and his vasoplegia was successfully treated with hydroxocobalamin, leading to significant clinical improvement. The patient later underwent a successful CABG without preoperative ACE inhibitor use. This case underscores the potential of hydroxocobalamin as an effective treatment for vasoplegia, particularly following ACE inhibitor use in cardiac surgery patients. [ABSTRACT FROM AUTHOR]

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]

Introduction: Severe metformin overdose can result in life-threatening conditions such as metabolic acidosis with hyperlactatemia and vasoplegic shock. Current treatment guidelines recommend hemodialysis and supportive care. However, this case report presents the use of methylene blue as an additional treatment for severe metformin overdose-induced vasoplegic shock, which is not commonly described in the literature or guidelines. Case report: A 55-year-old woman presented to the emergency department after ingesting 82.5 g of metformin, resulting in severe metabolic acidosis with hyperlactatemia and refractory vasoplegic shock. Despite continuous hemodialysis and high levels of noradrenalin and vasopressin, the shock persisted. Methylene blue was administered, leading to an immediate and persistent reduction in the noradrenalin dose and rapid shock resolution. Discussion: This case illustrates the potential use of methylene blue in the treatment of severe metformin overdose. The mechanism for metformin-induced vasoplegia is likely mediated by nitric oxide (NO). Methylene blue has been used to treat NO-mediated vasoplegia in other conditions, such as sepsis and poisoning with beta-blockers and calcium channel blockers, but it is rarely described in metformin toxicity. Methylene blue has a rapid onset of action, with only a few mild side effects. This case report emphasizes the need for clinicians to consider methylene blue as a potential treatment option in cases of refractory vasoplegic shock due to severe metformin overdose.

This article titled "Methylene Blue–Induced Serotonin Toxicity: Case Files of the Medical Toxicology Fellowship at the New York City Poison Control Center" discusses a case of serotonin toxicity caused by methylene blue. The article explores the use of naloxone in ACE-I toxicity and the mechanism of methylene blue as a vasopressor. It also discusses the mechanism of methylene blue-induced serotonin toxicity. The case study provides insights into the management of these conditions. The article also discusses the history of methylene blue-induced serotonin toxicity, dosage and timing of methylene blue administration, and its contribution to the risk of serotonin toxicity. It further examines the prevalence of vasoplegic shock versus cardiogenic shock in patients with amlodipine toxicity and the use of high-dose insulin therapy to treat CCB toxicity. The article also discusses the potential synergistic effect of dihydropyridine CCB toxicity combined with ACE-I toxicity in causing vasoplegic shock. Finally, the article addresses the question of whether methylene blue should be withheld in patients on therapeutic SRI therapy who develop acute methemoglobinemia. [Extracted from the article]

A dysregulated host response is a common feature in critically ill patients due to both infectious and non-infectious origins that can lead to life-threatening organ dysfunction, which is still the primary cause of death in intensive care units worldwide. In its course, pathologic, unregulated levels of inflammatory mediators are often released into the circulation, a phenomenon also referred to as a "cytokine storm". To date, there are no approved therapies to modulate the excessive immune response and limit hyperinflammation with the goal of preventing related organ failure and death. In this context, extracorporeal blood purification therapies aiming at the alteration of the host inflammatory response through broad-spectrum, non-selective removal of inflammatory mediators have come into focus. A novel hemoadsorption device (CytoSorb®, CytoSorbents Inc., Princeton, NJ, USA) has shown promising results in patients with hyperinflammation from various origins. Although a significant body of literature exists, there is ongoing research to address many important remaining questions, including the optimal selection of patient groups who might benefit the most, optimal timing for therapy initiation, optimal schedule for adsorber exchanges and therapy duration, as well as an investigation into the potential removal of concomitant antibiotics and other medications. In this review, we discuss the existing evidence and provide a consensus-based best practice guidance for CytoSorb® hemoadsorption therapy in patients with vasoplegic shock. [ABSTRACT FROM AUTHOR]

• Methylene blue and hydroxocobalamin were associated with reduction in vasopressor requirements in refractory vasoplegic shock (VS). • Methylene blue and hydroxocobalamin were associated with improved MAP in refractory VS. • Hydroxocobalamin was associated with a greater reduction in vasopressor requirements compared to methylene blue in refractory VS. To compare changes in vasopressor requirements and hemodynamic responses after hydroxocobalamin or methylene blue administration for vasoplegic shock (VS). Retrospective cohort analysis. Single-center, academic medical center. Cardiothoracic surgery adult patients. Hydroxocobalamin or methylene blue. The primary outcome was a change in vasopressor requirements over the first 24 hours (1, 3, 6, 12, and 24 hours) after hydroxocobalamin or methylene blue initiation. Secondary outcomes included changes in mean arterial pressure (MAP), systemic vascular resistance, and lactate. A total of 120 adult patients who received hydroxocobalamin (n = 77) or methylene blue (n = 43) were included. Vasopressor requirements at baseline were 0.34 µg/kg/min (95% CI 0.28-0.4) norepinephrine equivalent (NEE) in the hydroxocobalamin group, and 0.59 µg/kg/min (95% CI 0.52-0.66) NEE in the methylene blue group; p < 0.001. Vasopressor requirements decreased significantly at each time point within each group (hour 1 mean [95% CI] NEE, hydroxocobalamin 0.27 µg/kg/min [0.21-0.33]; methylene blue 0.44 µg/kg/min [0.38-0.51]; p < 0.001). The mean MAP at baseline was 65 mmHg (95% CI 63-67) in the hydroxocobalamin group, and 57 mmHg (95% CI 54-59) in the methylene blue group; p < 0.001. The mean MAP increased significantly from baseline at each time point within each group (hour 1 mean [95% CI] hydroxocobalamin 73 mmHg [71-75]; methylene blue 67 mmHg [65-70]; p < 0.001). After adjusting for baseline characteristics, a significantly greater reduction in vasopressor requirements and an increase in MAP were noted in the hydroxocobalamin group compared with the methylene blue group. Hydroxocobalamin was associated with a greater reduction in vasopressor requirements than methylene blue in treating VS associated with cardiopulmonary bypass. [ABSTRACT FROM AUTHOR]

IntroductionVenoarterial extracorporeal membrane oxygenation (ECMO) is a rescue therapy that can stabilize patients with hemodynamic compromise. Indications continue to evolve, including drug overdose. However, the indication merely for vasoplegic shock following drug overdose is controversial.Case summaryWe report a case of a 57-year-old male with high-risk idiopathic pulmonary arterial hypertension treated with upfront triple combination therapy (sildenafil, bosentan, and intravenous treprostinil infusion via subcutaneous abdominal implantable pump). In one of the refills of the drug reservoir, accidental administration of 1 months's supply of treprostinil (200 mg) into the subcutaneous tissue occurred, causing refractory vasoplegic shock. He required urgent VA-ECMO for 96 h, surviving to discharge 28 days later.DiscussionTreprostinil poisoning is rare due to its less frequent use but is life-threatening. ECMO may be considered in vasoplegic shock due to overdose of vasodilatory medication. It allows organ perfusion to be maintained, with the knowledge that recovery is as rapid as drug elimination.

Despite efforts to improve treatment outcomes, mortality in septic shock remains high. In some patients, despite the use of several adrenergic drugs, features of refractory vasoplegic shock with progressive multiorgan failure are observed. We present a case report of the successful reversal of vasoplegic shock following the use of methylene blue, a selective inhibitor of the inducible form of nitric oxide synthase, which prevents vasodilation in response to inflammatory cytokines. We also briefly review the literature. [ABSTRACT FROM AUTHOR]

To describe angiotensin II (ANGII) use in patients on mechanical circulatory support (MCS). To evaluate the efficacy and safety of ANGII in patients with shock on MCS. Retrospective cohort study. A single-center, quaternary care academic medical center. The study comprised critically ill patients on MCS. None. Fourteen patients were included in this retrospective analysis. The median age was 54 years (44.8, 68.3) and 78.6% were men. Six patients were receiving venoarterial extracorporeal membrane oxygenation support, 4 patients were receiving venovenous extracorporeal membrane oxygenation support, and 4 patients were on left ventricular assist devices. Five patients (36%) achieved hemodynamic response to ANGII at 3 hours, defined as a mean arterial pressure (MAP) of ≥65 mmHg or a 10-mmHg increase in MAP with a decrease or no change in total vasopressor dose. Overall, the median MAP increased from 61 mmHg (51, 73) at baseline to 66 mmHg (58, 71) at 3 hours, and the median norepinephrine dose decreased from 0.45 µg/kg/min (0.28, 0.6) at baseline to 0.2 µg/kg/min (0.18, 0.32) at 3 hours. The in-hospital mortality rate was 78.6%. Two patients experienced severe adverse drug events and 1 patient had a sentinel thrombotic event. This study suggested that ANGII may provide a salvage treatment option in patients on MCS with refractory vasodilatory shock. There are several safety considerations with the use of ANGII in these patients. Prospective randomized controlled trials are needed to evaluate the safety and efficacy of ANGII in patients on MCS. [ABSTRACT FROM AUTHOR]

Septic and vasoplegic shock are common types of vasodilatory shock (VS) with high mortality. After fluid resuscitation and the use of catecholamine-mediated vasopressors (CMV), vasopressin, angiotensin II, methylene blue (MB), and hydroxocobalamin can be added to maintain blood pressure. VS treatment utilizes a phased approach with secondary vasopressors added to vasopressor agents to maintain an acceptable mean arterial pressure (MAP). This review covers additional vasopressors and adjunctive therapies used when fluid and catecholamine-mediated vasopressors fail to maintain target MAP. Evidence supporting additional vasopressor agents in catecholamine-resistant VS is limited to case reports, series, and a few randomized control trials (RCTs) to guide recommendations. Vasopressin is the most common agent added next when MAPs are not adequately supported with CMV. VS patients failing fluids and vasopressors with cardiomyopathy may have cardiotonic agents such as dobutamine or milrinone added before or after vasopressin. Angiotensin II, another class of vasopressor, is used in VS to maintain adequate MAP. MB and/or hydroxocobalamin, vitamin C, thiamine, and corticosteroids are adjunctive therapies used in refractory VS. More RCTs are needed to confirm the utility of these drugs, at what doses, which combinations and in what order they should be given. [ABSTRACT FROM AUTHOR]

Indeed, systemic concentrations of pro-inflammatory cytokines in patients with severe COVID-19 are not as high as has been reported in patients with other causes of acute respiratory distress syndrome. On April 10, 2020, the U.S. Food and Drug Administration granted Emergency Use Authorization for CytoSorb use in critically ill COVID-19 patients with confirmed or imminent respiratory failure. Keywords: COVID-19; cytokine adsorber; organ failure; vasoplegic shock EN COVID-19 cytokine adsorber organ failure vasoplegic shock 1026 1029 4 05/27/22 20220601 NES 220601 "However beautiful the strategy, you should occasionally look at the results." is a famous saying by Sir Winston Churchill. In a prospective, randomized, open-label study, Supady et al ([11]) investigated 34 COVID-19 patients with ECMO therapy and showed that the median IL-6 drop over 72 hours occurred regardless of the use of CytoSorb ([11]). [Extracted from the article]

Objectives: To investigate the effect of extracorporeal cytokine reduction by CytoSorb (CytoSorbents, Monmouth Junction, NJ) on COVID-19-associated vasoplegic shock.Design: Prospective, randomized controlled pilot study.Setting: Eight ICUs at three sites of the tertiary-care university hospital Charité-Universitätsmedizin Berlin.Patients: COVID-19 patients with vasoplegic shock requiring norepinephrine greater than 0.2 µg/kg/min, C-reactive protein greater than 100 mg/L, and indication for hemodialysis.Interventions: Randomization of 1:1 to receive CytoSorb for 3-7 days or standard therapy. To account for inadvertent removal of antibiotics, patients in the treatment group received an additional dose at each adsorber change.Measurements and Main Results: The primary endpoint was time until resolution of vasoplegic shock, estimated by Cox-regression. Secondary endpoints included mortality, interleukin-6 concentrations, and catecholamine requirements. The study was registered in the German Registry of Clinical Trials (DRKS00021447). From November 2020 to March 2021, 50 patients were enrolled. Twenty-three patients were randomized to receive CytoSorb and 26 patients to receive standard of care. One patient randomized to cytokine adsorption was excluded due to withdrawal of informed consent. Resolution of vasoplegic shock was observed in 13 of 23 patients (56.5%) in the CytoSorb and 12 of 26 patients (46.2%) in the control group after a median of 5 days (interquartile range [IQR], 4-5 d) and 4 days (IQR, 3-5 d). The hazard ratio (HR) for the primary endpoint, adjusted for the predefined variables age, gender, extracorporeal membrane oxygenation-therapy, or time from shock onset to study inclusion was HR, 1.23 (95% CI, 0.54-2.79); p = 0.63. The mortality rate was 78% in the CytoSorb and 73% in the control group (unadjusted HR, 1.17 [95% CI, 0.61-2.23]; p = 0.64). The effects on inflammatory markers, catecholamine requirements, and the type and rates of adverse events were similar between the groups.Conclusions: In severely ill COVID-19 patients, CytoSorb did not improve resolution of vasoplegic shock or predefined secondary endpoints. [ABSTRACT FROM AUTHOR]

Up to one-third of all patients admitted to intensive care units carry a diagnosis of shock. The use of angiotensin II is becoming widespread in all forms of shock, including cardiogenic, after the U.S. Food and Drug Administration's (FDA's) initial approval for vasoplegic shock in 2017. Here, the authors review the literature on angiotensin II's mechanism of action, benefits, and future therapeutic opportunities. [ABSTRACT FROM AUTHOR]

Purpose: To determine whether intravenous vitamin C compared with placebo, reduces vasopressor requirements in patients with vasoplegic shock., Methods: Double-blinded, randomised clinical trial (RCT) conducted in two intensive care units in Perth, Australia. Vasopressor requirements at enrolment needed to be >10 μg/min noradrenaline after hypovolaemia was clinically excluded. Patients received either intravenous 1.5 g sodium ascorbate in 100 ml normal saline every 6 h for 5 days, or placebo (100 ml normal saline). The primary outcome was duration of vasopressor usage in hours. Secondary outcomes were ICU and hospital length of stay, and 28-day, ICU and hospital mortality., Results: Of the 71 patients randomised (35 vitamin C, 36 placebo group), the median vasopressor duration was 44 h [95% CI, 37-54 h] and 55 h [95% CI, 33-66 h]) in the vitamin C and placebo groups (p = 0.057). ICU and hospital length of stay, mortality outcomes were similar between groups., Conclusions: In this RCT of patients with vasoplegic shock of at least moderate severity, the use of IV vitamin C compared with placebo did not significantly reduce the duration of vasopressors., Trial Registration: Prospective registration - trial number ACTRN12617001392358., Competing Interests: Declaration of Competing Interest The authors have no competing interests to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)