Hemodialysis Complications of Hydroxocobalamin: A Case Report

Hydroxocobalamin is a new antidote approved by the FDA for the treatment of cyanide poisoning. Our report describes a patient with cyanide poisoning who survived after treatment with hydroxocobalamin and complications we encountered with hemodialysis. A 34-year-old female presented to the emergency department after a syncopal event and seizures. Her systolic blood pressure was 75 mmHg, her QRS complex progressively widened, and pulses were lost. She was intubated and resuscitated with fluids, sodium bicarbonate for her QRS widening and vasopressors. Venous blood gas demonstrated a pH of 6.36 with an O2 saturation of 99%. Due to the acidemia with a normal pulse oximetry, simultaneous venous and arterial blood gases were obtained. Venous gas demonstrated a pH of 6.80 with a PO2 of 222 mmHg, an O2 saturation of 99%. The arterial blood gas showed a pH of 6.82, a PO2 518 mmHg, an O2 saturation of 100%. Cyanide was suspected and hydroxocobalamin and sodium thiosulfate were given. Within 40 min of hydroxocobalamin administration, vasopressors were discontinued. Initially, nephrology attempted dialysis for metabolic acidosis; however, the dialysis machine repeatedly shut down due to a “blood leak”. This was an unforeseen effect attributed to hydroxocobalamin. Cyanide level, drawn 20 min after the antidote was completed, was elevated at 22 mcg/dL. Her urinary thiocyanate level could not be analyzed due to an “interfering substance”. Hydroxocobalamin is an effective antidote. However, clinicians must be aware of its effects on hemodialysis machines which could delay the initiation of this important treatment modality in the severely acidemic patient

Cardiovascular Efficacy and Safety of Bococizumab in High-Risk Patients

Bococizumab is a humanized monoclonal antibody that inhibits proprotein convertase subtilisin- kexin type 9 (PCSK9) and reduces levels of low-density lipoprotein (LDL) cholesterol. We sought to evaluate the efficacy of bococizumab in patients at high cardiovascular risk. METHODS In two parallel, multinational trials with different entry criteria for LDL cholesterol levels, we randomly assigned the 27,438 patients in the combined trials to receive bococizumab (at a dose of 150 mg) subcutaneously every 2 weeks or placebo. The primary end point was nonfatal myocardial infarction, nonfatal stroke, hospitalization for unstable angina requiring urgent revascularization, or cardiovascular death; 93% of the patients were receiving statin therapy at baseline. The trials were stopped early after the sponsor elected to discontinue the development of bococizumab owing in part to the development of high rates of antidrug antibodies, as seen in data from other studies in the program. The median follow-up was 10 months. RESULTS At 14 weeks, patients in the combined trials had a mean change from baseline in LDL cholesterol levels of -56.0% in the bococizumab group and +2.9% in the placebo group, for a between-group difference of -59.0 percentage points (P<0.001) and a median reduction from baseline of 64.2% (P<0.001). In the lower-risk, shorter-duration trial (in which the patients had a baseline LDL cholesterol level of ≥70 mg per deciliter [1.8 mmol per liter] and the median follow-up was 7 months), major cardiovascular events occurred in 173 patients each in the bococizumab group and the placebo group (hazard ratio, 0.99; 95% confidence interval [CI], 0.80 to 1.22; P = 0.94). In the higher-risk, longer-duration trial (in which the patients had a baseline LDL cholesterol level of ≥100 mg per deciliter [2.6 mmol per liter] and the median follow-up was 12 months), major cardiovascular events occurred in 179 and 224 patients, respectively (hazard ratio, 0.79; 95% CI, 0.65 to 0.97; P = 0.02). The hazard ratio for the primary end point in the combined trials was 0.88 (95% CI, 0.76 to 1.02; P = 0.08). Injection-site reactions were more common in the bococizumab group than in the placebo group (10.4% vs. 1.3%, P<0.001). CONCLUSIONS In two randomized trials comparing the PCSK9 inhibitor bococizumab with placebo, bococizumab had no benefit with respect to major adverse cardiovascular events in the trial involving lower-risk patients but did have a significant benefit in the trial involving higher-risk patients