hydroxocobalamin and Hypotension

Hydroxocobalamin inhibits nitric oxide-mediated vasodilation, and has been used in settings of refractory shock. However, its effectiveness and role in treating hypotension remain unclear. The authors systematically searched Ovid Medline, Embase, EBM Reviews, Scopus, and Web of Science Core Collection for clinical studies reporting on adult persons who received hydroxocobalamin for vasodilatory shock. A meta-analysis was performed with random-effects models comparing the hemodynamic effects of hydroxocobalamin to methylene blue. The Risk of Bias in Nonrandomized Studies of Interventions tool was used to assess the risk of bias. A total of 24 studies were identified and comprised mainly of case reports (n = 12), case series (n = 9), and 3 cohort studies. Hydroxocobalamin was applied mainly for cardiac surgery vasoplegia, but also was reported in the settings of liver transplantation, septic shock, drug-induced hypotension, and noncardiac postoperative vasoplegia. In the pooled analysis, hydroxocobalamin was associated with a higher mean arterial pressure (MAP) at 1 hour than methylene blue (mean difference 7.80, 95% CI 2.63-12.98). There were no significant differences in change in MAP (mean difference -4.57, 95% CI -16.05 to 6.91) or vasopressor dosage (mean difference -0.03, 95% CI -0.12 to 0.06) at 1 hour compared to baseline between hydroxocobalamin and methylene blue. Mortality was also similar (odds ratio 0.92, 95% CI 0.42-2.03). The evidence supporting the use of hydroxocobalamin for shock is limited to anecdotal reports and a few cohort studies. Hydroxocobalamin appears to positively affect hemodynamics in shock, albeit similar to methylene blue.

Topics: Adult; Humans; Hydroxocobalamin; Hypotension; Methylene Blue; Shock; Vasodilation; Vasoplegia

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: Humans; Hydroxocobalamin; Hypotension; Shock; Vasoconstrictor Agents; Vasodilation

Hydroxocobalamin has been observed to cause transient hypertension in healthy subjects, but rigorous studies examining its efficacy are lacking.. Adults in shock who received hydroxocobalamin from 2017 to 2021 were analyzed retrospectively. Hourly hemodynamics from 24 h before and after treatment were collected, and the difference and hourly change of mean arterial pressure (MAP), systolic blood pressure (SBP), diastolic blood pressure (DBP), and norepinephrine-equivalent dose (NED) were examined in mixed-effects models.. This study included 3992 hemodynamic data points from 35 patients and is the largest case series to date. In the mixed effects model, there was no difference in MAP 24-h after hydroxocobalamin administration (estimated fixed effect [EFE] -0.2 mmHg, p = 0.89). A two-piecewise mixed model found that the hourly change in MAP was not different from zero in either the pre-administration (EFE 0.0 mmHg/h, p = 0.80) or post-administration segments (EFE 0.0 mmHg/h, p = 0.55). Analysis of the SBP, DBP, and NED also found similar insignificant results.. Although hydroxocobalamin has been observed to cause hypertension in healthy subjects, our results suggest that in patients with shock, hydroxocobalamin may not be effective in improving hemodynamics at 24 h after administration.

Topics: Adult; Blood Pressure; Hemodynamics; Humans; Hydroxocobalamin; Hypotension; Retrospective Studies

Topics: Hemodynamics; Humans; Hydroxocobalamin; Hypotension; Shock; Vasodilation

BACKGROUND Cardiac vasoplegic syndrome is a form of vasodilatory shock characterized by profound vasodilation and low systemic vascular resistance, which results in significant hypotension despite high cardiac output and appropriate fluid resuscitation. In up to 45% of patients, cardiopulmonary bypass (CPB) can precipitate vasoplegic syndrome. Vasoplegic syndrome after CPB that is refractory to other vasopressors, such as catecholamine and vasopressin, has been successfully treated with inhibitors of the nitric oxide (NO) system, such as methylene blue and hydroxocobalamin. Methylene blue has been the treatment of choice because of its effectiveness for both prevention and rescue therapy. Hydroxocobalamin has demonstrated efficacy in combination with methylene blue, and also on its own when vasoplegic syndrome is refractory to methylene blue. CASE REPORT We present 2 cases that expand upon the existing evidence supporting the efficacy of hydroxocobalamin as a first-line option for inhibiting the NO system in vasoplegic syndrome that is refractory to other vasopressors. Specifically, we demonstrate the appropriate and successful use of hydroxocobalamin alone to treat refractory vasoplegic syndrome after CPB. CONCLUSIONS Refractory vasoplegic syndrome that occurs after CPB has been successfully treated with inhibitors of the NO system, such as methylene blue and hydroxocobalamin. The present cases expand upon the scant existing evidence of the efficacy of hydroxocobalamin as an appropriate option for refractory vasoplegic syndrome.

Topics: Cardiopulmonary Bypass; Humans; Hydroxocobalamin; Hypotension; Methylene Blue; Vasoplegia

Topics: Humans; Hydroxocobalamin; Hypotension; Shock

Hydroxocobalamin (vitamin B12a) is an emerging treatment for vasoplegic syndrome (VS) associated with cardiopulmonary bypass (CPB). Given its cost and scarcity, an institutional guideline for its use as a rescue treatment in cases of suspected VS was developed. Hemodynamic variables and vasopressor requirements were reviewed for a series of 24 post-CPB patients who received B12a. Favorable changes in hemodynamic parameters and vasopressor requirements were seen after B12a administration although guideline criteria for VS were inconsistently met. These findings support the continued study of B12a in patients with CPB-associated VS.

Topics: Aged; Cardiopulmonary Bypass; Female; Hemodynamics; Humans; Hydroxocobalamin; Hypotension; Male; Middle Aged; Retrospective Studies; Treatment Outcome; Vasoconstrictor Agents; Vasoplegia; Vitamin B Complex

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

The objective was to compare systolic blood pressure (sBP) over time in swine that have had 30% of their blood volume removed (Class III shock) and treated with intravenous (IV) whole blood or IV hydroxocobalamin, compared to nontreated control animals.. Thirty swine (45 to 55 kg) were anesthetized, intubated, and instrumented with continuous femoral and pulmonary artery pressure monitoring. Animals were hemorrhaged a total of 20 mL/kg over a 20-minute period. Five minutes after hemorrhage, animals were randomly assigned to receive 150 mg/kg IV hydroxocobalamin solubilized in 180 mL of saline, 500 mL of whole blood, or no treatment. Animals were monitored for 60 minutes thereafter. A sample size of 10 animals per group was determined based on a power of 80% and an alpha of 0.05 to detect an effect size of at least a 0.25 difference (>1 standard deviation) in mean sBP between groups. sBP values were analyzed using repeated-measures analysis of variance (RANOVA). Secondary outcome data were analyzed using repeated-measures multivariate analysis of variance (RMANOVA).. There were no significant differences between hemodynamic parameters of IV hydroxocobalamin versus whole blood versus control group at baseline (MANOVA; Wilks' lambda; p = 0.868) or immediately posthemorrhage (mean sBP = 47 mm Hg vs. 41 mm Hg vs. 37 mm Hg; mean arterial pressure = 39 mm Hg vs. 28 mm Hg vs. 34 mm Hg; mean serum lactate = 1.2 mmol/L vs. 1.4 mmol/L vs. 1.4 mmol/L; MANOVA; Wilks' lambda; p = 0.348). The outcome RANOVA model detected a significant difference by time between groups (p < 0.001). Specifically, 10 minutes after treatment, treated animals showed a significant increase in mean sBP compared to nontreated animals (mean sBP = 76.3 mm Hg vs. 85.7 mm Hg vs. 51.1 mm Hg; p < 0.001). RMANOVA modeling of the secondary data detected a significant difference in mean arterial pressure, heart rate, and serum lactate (p < 0.001). Similar to sBP, 10 minutes after treatment, treated animals showed a significant increase in mean arterial pressure compared to nontreated animals (mean arterial pressure = 67.7 mm Hg vs. 61.4 mm Hg vs. 40.5 mm Hg). By 10 minutes, mean heart rate was significantly slower in treated animals compared to nontreated animals (mean heart rate = 97.3 beats/min vs. 95.2 beats/min vs. 129.5 beats/min; p < 0.05). Serum lactate, an early predictor of shock, continued to rise in the control group, whereas it did not in treated animals. Thirty minutes after treatment, serum lactate values of treated animals were significantly lower compared to nontreated animals (p < 0.05). This trend continued throughout the 60-minute observation period such that 60-minute values for lactate were 1.4 mmol/L versus 1.1 mmol/L versus 3.8 mmol/L. IV hydroxocobalamin produced a statistically significant increase in systemic vascular resistance compared to control, but not whole blood, with a concomitant decrease in cardiac output.. Intravenous hydroxocobalamin was more effective than no treatment and as effective as whole blood transfusion, in reversing hypotension and inhibiting rises in serum lactate in this prehospital, controlled, Class III swine hemorrhage model.

Topics: Animals; Blood Pressure; Blood Transfusion; Disease Models, Animal; Female; Hemodynamics; Hydroxocobalamin; Hypotension; Injections, Intravenous; Monitoring, Physiologic; Prospective Studies; Random Allocation; Resuscitation; Shock, Hemorrhagic; Swine; Vascular Resistance

Topics: Color; Dialysis Solutions; Humans; Hydroxocobalamin; Hypotension; Liver Transplantation; Male; Middle Aged; Renal Dialysis

The search for new nitric oxide donors is warranted by the limitations of organic nitrates currently used in cardiology. The new organic nitrate 2-nitrate-1,3-dibuthoxypropan (NDBP) exhibited promising cardiovascular activities in previous studies. The aim of this study was to investigate the cardiorespiratory responses evoked by NDBP and to compare them to the clinically used organic nitrate nitroglycerine (NTG). Arterial pressure, heart rate and respiration were recorded in conscious adult male Wistar rats. Bolus i.v. injection of NDBP (1 to 15mg/kg; n=8) and NTG (0.1 to 5mg/kg; n=8) produced hypotension. NDBP induced bradycardia at all doses, while NTG induced tachycardia at three lower doses but bradycardia at higher doses. Hydroxocobalamin (20mg/kg; HDX), a NO scavenger, blunted hypotension induced by NDBP (15mg/kg), and its bradycardic effect (n=6). In addition, HDX blunted both hypotension and bradycardia induced by a single dose of NTG (2.5mg/kg; n=6). Both NDBP and NTG altered respiratory rate, inducing a biphasic effect with a bradypnea followed by a tachypnea; HDX attenuated these responses. Our data indicate that NDBP and NTG induce hypotension, bradycardia and bradypnea, which are mediated by nitric oxide release.

Topics: Animals; Arterial Pressure; Bradycardia; Cardiovascular Agents; Consciousness; Dose-Response Relationship, Drug; Heart Rate; Hydroxocobalamin; Hypotension; Male; Nitrates; Nitric Oxide; Nitroglycerin; Propane; Rats; Rats, Wistar; Respiration; Tachypnea; Vasodilator Agents

Easily administrated cyanide antidotes are needed for first responders, military troops, and emergency department staff after cyanide exposure in mass casualty incidents or due to smoke inhalation during fires involving many victims. Hydroxocobalamin has proven to be an effective antidote, but cannot be given intramuscularly because the volume of diluent needed is too large. Thus, intraosseous (IO) infusion may be an alternative, as it is simple and has been recommended for the administration of other resuscitation drugs. The primary objective of this study was to compare the efficacy of IO delivery of hydroxocobalamin to intravenous (IV) injection for the management of acute cyanide toxicity in a well-described porcine model.. Twenty-four swine (45 to 55 kg) were anesthetized, intubated, and instrumented with continuous mean arterial pressure (MAP) and cardiac output monitoring. Cyanide was continuously infused until severe hypotension (50% of baseline MAP), followed by IO or IV hydroxocobalamin treatment. Animals were randomly assigned to receive IV (150 mg/kg) or IO (150 mg/kg) hydroxocobalamin and monitored for 60 minutes after start of antidotal infusion. The primary outcome measure was the change in MAP after antidotal treatment from onset of hypotension (time zero) to 60 minutes. A sample size of 12 animals per group was determined by group size analysis based on power of 80% to detect a one standard deviation of the mean MAP between the groups with an alpha of 0.05. Whole blood cyanide, lactate, pH, nitrotyrosine (nitric oxide marker) levels, cerebral and renal near infrared spectrometry (NIRS) oxygenation, and inflammatory markers were also measured. Repeated-measures analysis of variance was used to determine statistically significant changes between groups over time.. At baseline and at the point of hypotension, physiologic parameters were similar between groups. At the conclusion of the study, 10 out of 12 animals in the IV group and 10 out of 12 in IO group survived (p = 1.0). Both groups demonstrated a similar return to baseline MAP (p = 0.997). Cardiac output, oxygen saturation, and systemic vascular resistance were also found to be similar between groups (p > 0.4), and no difference was detected between bicarbonate, pH, and lactate levels (p > 0.8). Cyanide levels were undetectable after the hydroxocobalamin infusion throughout the study in both groups (p = 1.0). Cerebral and renal NIRS oxygenation decreased in parallel to MAP during cyanide infusion and increased after antidote infusion in both groups. Serum nitrotyrosine increased during cyanide infusion in all animals and then decreased in both study arms after hydroxocobalamin infusion (p > 0.5). Serum cytokines increased starting at cyanide infusion and no difference was detected between groups (tumor necrosis factor-α, interleukin [IL]-1β, IL-6, and IL-10).. The authors found no difference in the efficacy of IV versus IO hydroxocobalamin in the treatment of severe cyanide toxicity in a validated porcine model.

Topics: Animals; Blood Pressure; Cyanides; Disease Models, Animal; Female; Hydroxocobalamin; Hypotension; Infusions, Intraosseous; Infusions, Intravenous; Male; Monitoring, Physiologic; Severity of Illness Index; Swine; Vascular Resistance; Vitamin B Complex

Topics: Animals; Female; Hydroxocobalamin; Hypotension; Male

Cyanide can cause severe hypotension with acute toxicity. To our knowledge, no study has directly compared hydroxocobalamin and sodium nitrite with sodium thiosulfate in an acute cyanide toxicity model. Our objective is to compare the return to baseline of mean arterial blood pressure between 2 groups of swine with acute cyanide toxicity and treated with hydroxocobalamin with sodium thiosulfate or sodium nitrite with sodium thiosulfate.. Twenty-four swine were intubated, anesthetized, and instrumented (continuous arterial and cardiac output monitoring) and then intoxicated with a continuous cyanide infusion until severe hypotension. The animals were divided into 2 arms of 12 each and then randomly assigned to intravenous hydroxocobalamin (150 mg/kg)+sodium thiosulfate (413 mg/kg) or sodium nitrite (10 mg/kg)+sodium thiosulfate (413 mg/kg) and monitored for 40 minutes after start of antidotal infusion. Twenty animals were needed for 80% power to detect a significant difference in outcomes (alpha 0.05). Repeated measures of analysis of covariance and post hoc t test were used for determining significance.. Baseline mean weights, time to hypotension (31 minutes 3 seconds versus 28 minutes 6 seconds), and cyanide dose at hypotension (5.6 versus 5.9 mg/kg) were similar. One animal in the hydroxocobalamin group and 2 animals in the sodium nitrite group died during antidote infusion and were excluded from analysis. Hydroxocobalamin resulted in a faster return to baseline mean arterial pressure, with improvement beginning at 5 minutes and lasting through the conclusion of the study (P<.05). No statistically significant difference was detected between groups for cardiac output, pulse rate, systemic vascular resistance, or mortality at 40 minutes post intoxication. Mean cyanide blood levels (4.03 versus 4.05 microg/mL) and lactate levels (peak 7.9 versus 8.1 mmol/L) at hypotension were similar. Lactate levels (5.1 versus 4.48 mmol/L), pH (7.40 versus 7.37), and base excess (-0.75 versus 1.27) at 40 minutes were also similar.. Hydroxocobalamin with sodium thiosulfate led to a faster return to baseline mean arterial pressure compared with sodium nitrite with sodium thiosulfate; however, there was no difference between the antidote combinations in mortality, serum acidosis, or serum lactate.

Topics: Acidosis; Animals; Antidotes; Blood Pressure; Cyanides; Disease Models, Animal; Drug Therapy, Combination; Female; Hydroxocobalamin; Hypotension; Lactates; Male; Monitoring, Physiologic; Sodium Nitrite; Sus scrofa; Thiosulfates; Time Factors

The cobalt atom of hydroxocobalamin (OHC) binds cyanide and nitric oxide (NO) and OHC attenuates vascular responses to NO in vitro. NO mediates the hypotension of endotoxemia. Thus, we tested the postulate that OHC may attenuate the acute phase hypotension and toxicity associated with administration of Escherichia coli endotoxin (LPS). Rats were given OHC (20 mg/kg i.v.) or phosphate-buffered saline (PBS, 1 ml/kg i.v.) 30 min before or 15 min after giving LPS (0.8 mg/kg i.v.). Administration of OHC to PBS-treated control rats did not affect mean arterial pressure (MAP), heart rate or the plasma or urine content of the reactive nitrogen intermediates nitrate and nitrite (RNI). LPS decreased MAP by 50 mm Hg in PBS-treated rats and increased the plasma and urinary content of RNI. Administration of OHC to PBS-treated rats did not affect MAP or RNI. However, treatment with OHC before or after giving LPS attenuated LPS-induced hypotension and increases in plasma RNI and enhanced LPS-induced urinary excretion of RNI. OHC (20 mg/kg i.p.) or cyanocobalamin (10 mg/kg i.p.) given to Swiss-Webster mice 30 min before giving LPS (16 mg/kg i.p.) decreased the 24-hr mortality of LPS from 80 to 50% and the 36- and 96-hr mortality from 100 to 60% (OHC) or 70% (cyanocobalamin). Urine obtained from conscious rats given LPS (5 mg/kg i.p.) and OHC (20 mg/kg i.p.) exhibited a UV-visible absorbance spectrum with absorbance peaks characteristic of that formed after coincubation of NO and OHC.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Blood Pressure; Hydroxocobalamin; Hypotension; Lipopolysaccharides; Male; Mice; Mortality; Nitric Oxide; Rats; Rats, Sprague-Dawley; Spectrophotometry; Vitamin B 12

Topics: Acidosis; Adult; Cyanides; Cyanosis; Gastric Lavage; Gastrointestinal Hemorrhage; Humans; Hydrogen Cyanide; Hydrogen-Ion Concentration; Hydroxocobalamin; Hypotension; Liver; Middle Aged; Poisoning; Suicide; Time Factors; Vitamin B 12

The infusion of sodium nitroprusside during surgical operations produced plasma levels of cyanide of up to four times the control value. Plasma thiocyanate showed little change except during prolonged infusion of the drug, but total plasma B(12) tended to fall, as did methylcobalamin. Other cobalamins showed little change after nitroprusside infusion for short periods. During longer infusions the ratio of methylcobalamin to adenosyl + hydroxocobalamin fell and cyanocobalamin concentrations were high.

Topics: Anesthesia, General; Child; Cyanides; Female; Ferricyanides; Humans; Hydroxocobalamin; Hypotension; Hypotension, Controlled; Infusions, Parenteral; Middle Aged; Thiocyanates; Vitamin B 12