vitamin-b-12 and Shock--Septic

Vasodilatory shock, as observed in postoperative states and sepsis, is hallmarked by low systemic vascular resistance and low blood pressure compensated by increased cardiac output. Gasotransmitters, such as nitric oxide and hydrogen sulfide, are implicated in the development and perpetuation of vasodilatory shock. Established therapies do not target these physiologic drivers of vasodilation. Due to their nontoxic and pleotropic effects, micronutrients are being used as rescue therapy in postoperative vasoplegia and septic shock. Here, we outline the pathophysiology of vasodilatory shock, describe the rationale for vitamin B12 (hydroxocobalamin) in vasodilatory shock, and identify literature evaluating its use in vasoplegic states.

Topics: Humans; Shock, Septic; Vasoplegia; Vitamin B 12; Vitamin B Complex

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

Topics: Gases; Gasotransmitters; Humans; Running; Shock, Septic; Vitamin B 12; Vitamins

Introduction and objective: a study was made of the folic acid (Fol) and vitamin B12 (B12) serum concentrations in critical patients with septic shock upon admission and after three days of stay in the Intensive Care Unit (ICU), with an analysis of their association to inflammatory parameters and patient morbidity-mortality. Methods: a prospective analytical study was made of 30 critically ill patients with septic shock. Demographic data, comorbidities, clinical information and severity scores were recorded. Data collected included serum Fol and B12 levels using the DxI® Autoanalyzer (Beckman Coulter) based on a competitive electrochemoluminescence immunoassay. Results: mean serum Fol was within the reference range stipulated by the laboratory on the first day. Nevertheless, a total of 21.4 % of the patients had high Fol levels, with 14.2 % being Fol deficient. An association was observed between Fol (p ˂ 0.012) status and 28-day mortality, and the number of days of mechanical ventilation, fraction of inspired oxygen (FiO2) and fibrinogen increased in patients with higher Fol levels (p ˂ 0.05). In addition, 85.7 % of cases had B12 levels above the reference values, with a correlation being observed between B12 and Fol. Conclusions: this study proposes Fol as a novel morbidity-mortality biomarker in critical septic patients, and reinforces the usefulness of B12 as a morbidity biomarker. It is thus suggested that the measurement of Fol upon admission and over the first 72 hours of hospital stay could provide prognostic information about the clinical course and outcome of septic shock patients.. Introducción y objetivo: se realizó un estudio de las concentraciones séricas de ácido fólico (Fol) y vitamina B12 (B12) en pacientes críticos con shock séptico al ingreso y después de tres días de estancia en la Unidad de Cuidados Intensivos (UCI), con un análisis de su asociación con los parámetros inflamatorios y la morbimortalidad de los pacientes. Método: se realizó un estudio analítico prospectivo de 30 pacientes críticos con shock séptico. Se registraron datos demográficos, comorbilidades, información clínica y puntuaciones de gravedad. Los datos recopilados incluyeron los niveles séricos de Fol y B12 utilizando el autoanalizador DxI® (Beckman Coulter) basado en un inmunoensayo de electroquimioluminiscencia competitivo. Resultados: la media de Fol sérico estuvo dentro del rango de referencia estipulado por el laboratorio el primer día. Sin embargo, el 21,4 % de los pacientes presentaban niveles altos de Fol y el 14,2 % presentaban deficiencia de Fol. Se observó una asociación entre el estado de Fol (p ˂ 0,012) con la mortalidad a los 28 días, con el número de días de ventilación mecánica, con la fracción de oxígeno inspirado (FiO2) y con el fibrinógeno, que aumentaron en los pacientes con niveles de Fol más altos (p ˂ 0,05). Además, el 85,7 % de los casos tenían niveles de B12 por encima de los valores de referencia, observándose una correlación entre B12 y Fol. Conclusiones: este estudio propone al Fol como nuevo biomarcador de morbimortalidad en los pacientes críticos con sepsis y refuerza la utilidad de la B12 como biomarcador de morbilidad. Por tanto, se sugiere que la medición de Fol al ingreso y durante las primeras 72 horas de estancia hospitalaria podría proporcionar información pronóstica sobre el curso clínico y el resultado de los pacientes con shock séptico.

Topics: Biomarkers; Folic Acid; Humans; Intensive Care Units; Morbidity; Prospective Studies; Sepsis; Shock, Septic; Vitamin B 12

There is considerable evidence that elevated plasma homocysteine levels are associated with a prothrombotic milieu, whereas activation of the coagulation cascade is an important component of the pathogenesis of sepsis. The protein C pathway has been reported to play a central role both in the propagation of sepsis and a hyperhomocysteinemia-induced hypercoagulable state. Our primary aim was to measure plasma homocysteine levels in mechanically ventilated patients with severe sepsis/septic shock and to assess the association of these levels with relevant clinical outcomes.. The study cohort included 102 mechanically ventilated patients with severe sepsis or septic shock. Demographics, comorbidities, clinical data and severity scores were recorded. Plasma homocysteine, vitamin B12, folate, creatinine, and protein C levels were measured in all study subjects upon enrollment, and genotyping for the C677T and A1298C polymorphisisms of the methylenetetrahydrofolate reductase (MTHFR) gene and for factor V Leiden (FVL) mutations was performed as well. The primary outcomes were mortality at 28 and 90 days; secondary outcomes included the number of days without renal or cardiovascular failure and the ventilator-free days during the study period.. Homocysteine levels were not significantly associated with any primary or secondary outcomes in the multivariable analysis. In addition, a synergistic effect of homocysteine with protein C levels was not detected.. Our data suggest that plasma homocysteine levels may not inform the prognosis of mechanically ventilated patients with severe sepsis/septic shock.

Topics: Activated Protein C Resistance; Aged; Blood Coagulation Tests; Cohort Studies; Comorbidity; Factor V; Female; Folic Acid; Homocysteine; Homocystinuria; Hospital Mortality; Humans; Hyperhomocysteinemia; Male; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; Muscle Spasticity; Point Mutation; Protein C; Psychotic Disorders; Respiration, Artificial; Sepsis; Shock, Septic; Thrombophilia; Vitamin B 12

Cobalamin carrier proteins,the Transcobalamins (TCS), are elevated during trauma, infections and chronic inflammatory conditions. This remains un-explained. It is proposed that such TC elevations signal a need for cobalamin central to the resolution of inflammation. Thus Cobalamin may regulate the transcription factor, NFkappaB, activation or suppression of which determines the inflammatory response and its resolution. Such regulation may involve at least 5 separate mechanisms: (i) hormone-like regulation of TNFalpha, through reduction of excess NO by cobalamin, as well as through the selective inhibition, in tandem with glutathione, of inducible nitric oxide synthase; (ii) quenching of nitric oxide radicals and reactive oxygen species, enhanced by cobalamin's glutathione sparing effect; (iii) the promotion of acetylcholine synthesis, central to the neuro-immune cholinergic anti-inflammatory pathway; (iv) the promotion of oxidative phosphorylation; (v) and a bacteriostatic role of the TCS released by neutrophil secondary granules during phagocytosis, which also appears to modulate the inflammatory response. TC elevations are dependent on NFkappaB activation, through crosstalk between NFkappaB and Sp1, another member of the helix-loop-helix protein family, which directly mediates transcription of the TCII gene. Sp1 also has binding sites on the TNFalpha and EGF gene promoters. NFkappaB may thus ensure sufficient cobalamin to determine its own eventual suppression. Cobalamin's established regulation of EGF may additionally preserve normal function of macrophages and the coagulation cascade in wound healing. By regulating NFkappaB, Cobalamin may also be the as yet unidentified mediator needed to potentiate the anti-inflammatory action of eicosanoids derived from omega-3 essential fatty acids. Moreover, animal and human clinical data suggests that high dose cobalamin may prove a promising approach to SIRS/sepsis/septic and traumatic shock.

Topics: Acetylcholine; Glutathione; Humans; Inflammation; Models, Biological; NF-kappa B; Nitric Oxide; Nitric Oxide Synthase; Sepsis; Shock, Septic; Shock, Traumatic; Systemic Inflammatory Response Syndrome; Vitamin B 12