hydroxocobalamin and Shock--Septic

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.

Topics: Angiotensin II; Ascorbic Acid; Cardiotonic Agents; Catecholamines; Cytomegalovirus Infections; Dobutamine; Humans; Hydroxocobalamin; Methylene Blue; Milrinone; Shock; Shock, Septic; Thiamine; Vasoconstrictor Agents; Vasopressins

Elevated hydrogen sulfide (H. In adults with septic shock, is comparing high-dose IV hydroxocobalamin with placebo feasible?. We conducted a phase 2 single-center, double-blind, allocation-concealed, placebo-controlled, parallel-group pilot randomized controlled trial comparing high-dose IV hydroxocobalamin with placebo in critically ill adults with septic shock. Patients meeting Sepsis 3 criteria were randomized 1:1 to receive a single 5-g dose of high-dose IV hydroxocobalamin or equivalent volume 0.9% saline solution as placebo. The primary outcome was study feasibility (enrollment rate, clinical and laboratory compliance rate, and contamination rate). Secondary outcomes included between-group differences in plasma H. Twenty patients were enrolled over 19 months, establishing an enrollment rate of 1.05 patients per month. Protocol adherence rates were 100% with zero contamination. In the high-dose IV hydroxocobalamin group, compared to placebo, there was a greater reduction in vasopressor dose between randomization and postinfusion (-36% vs 4%, P < .001) and randomization and 3-h postinfusion (-28% vs 10%, P = .019). In the high-dose IV hydroxocobalamin group, the plasma H. This pilot trial established favorable feasibility metrics. Consistent with the proposed mechanism of benefit, high-dose IV hydroxocobalamin compared with placebo was associated with reduced vasopressor dose and H. ClinicalTrials.gov; No.: NCT03783091; URL: www.. gov.

Topics: Adult; Double-Blind Method; Humans; Hydroxocobalamin; Hypotension; Pilot Projects; Shock, Septic; Vasoconstrictor Agents; Vitamin B 12

Methemoglobinemia is a rare disorder of the blood in which there is an increase in methemoglobin, which occurs when hemoglobin is present in the oxidized form. Methemoglobin impairs hemoglobin's ability to transport oxygen, produces functional anemia, and leads to tissue hypoxia. We report the successful management of a case of refractory hypoxia due to acutely acquired methemoglobinemia in a patient undergoing treatment for coronavirus disease 2019 (COVID-19) pneumonia. The cause of methemoglobinemia in this patient remains unknown. Hypoxia and methemoglobinemia did not respond to methylene blue and required administration of packed red blood cell transfusions.

Topics: Acute Kidney Injury; Aged; Antibodies, Monoclonal, Humanized; Antioxidants; Ascorbic Acid; Betacoronavirus; Coronavirus Infections; Corynebacterium; Corynebacterium Infections; COVID-19; Cytokine Release Syndrome; Enzyme Inhibitors; Erythrocyte Transfusion; Hematinics; Humans; Hydroxocobalamin; Hydroxychloroquine; Hypoxia; Male; Methemoglobinemia; Methylene Blue; Pandemics; Pneumonia, Bacterial; Pneumonia, Viral; Renal Replacement Therapy; Respiratory Insufficiency; SARS-CoV-2; Shock, Septic

In this case report, we describe 2 patients with septic shock requiring high-dose vasopressors for hemodynamic support despite aggressive fluid resuscitation. After the administration of high-dose hydroxocobalamin for presumed septic vasoplegic syndrome, both patients had an immediate response to hydroxocobalamin with a rapid and lasting improvement of blood pressure that significantly reduced the need for vasopressor support.

Topics: Blood Pressure; Humans; Hydroxocobalamin; Male; Middle Aged; Shock, Septic; Treatment Outcome; Vasoplegia

Early, non-clinical studies support the use of hydroxocobalamin to treat sepsis-induced hypotension, but there is no translational, large animal model. The objective of this study was to compare survival in a sepsis model where large swine had endotoxaemia induced with lipopolysaccharide (LPS) and were treated with intravenous hydroxocobalamin (HOC), noradrenaline (NA), or saline. Thirty swine (45-55 kg) were anaesthetized, intubated, and instrumented with continuous femoral and pulmonary artery pressure monitoring. Hypotension, predefined as 50% of baseline, was induced with LPS. Animals then received HOC, NA, or saline and monitored for 3 hours. The main outcome was survival to the conclusion of the study. Using a power of 80% and an alpha of 0.05, 10 animals were used per group. Secondary outcomes included: mean arterial pressure (MAP), systemic vascular resistance (SVR) and cardiac output (CO) along with several markers of sepsis. No differences were detected between groups at baseline or after hypotension. The survival distributions of the three groups were significantly different with more HOC animals surviving (10/10) compared with NA (8/10) or Saline (5/10) (log-rank P < 0.03). MAP was found to be higher in both the HOC and NA groups and HOC achieved the highest SVR. In this large animal, translational study of an endotoxaemic model of sepsis, hydroxocobalamin improved survival when compared with saline.

Topics: Administration, Intravenous; Animals; Biomarkers; Disease Models, Animal; Female; Gases; Hemodynamics; Hydroxocobalamin; Hypotension; Lipopolysaccharides; Norepinephrine; Saline Solution; Shock, Septic; Swine

Topics: Humans; Hydroxocobalamin; Nervous System; Pyridoxine; Research; Shock; Shock, Septic; Thiamine