title: Thiocyanate Accumulation in Critically Ill Patients Receiving Nitroprusside Infusions.
abstract: OBJECTIVE
  This study evaluated thiocyanate concentrations and factors associated with thiocyanate accumulation in intensive care unit patients receiving nitroprusside with and without sodium thiosulfate coadministration.
  
  
  METHODS
  This retrospective study evaluated critically ill adults who received nitroprusside infusions and had at least one thiocyanate concentration. Patients with thiocyanate accumulation (concentrations ≥30 µg/mL) were compared to patients without accumulation. Factors associated with accumulation were determined by Spearman correlation and multivariate regression.
  
  
  RESULTS
  Thiocyanate concentrations (n = 192) were obtained from 87 patients. Fourteen of the 87 (16%) patients experienced thiocyanate accumulation with a mean (SD) thiocyanate concentration of 44 ± 11 µg/mL. Patients with accumulation had received greater cumulative nitroprusside doses (28 vs 8.2 mg/kg, P < .01), greater cumulative sodium thiosulfate doses (16.8 vs 10.1 mg/kg, P < .01), and longer infusion durations (10.9 vs 6.0 days, P < .01), compared to patients without accumulation. Sodium thiosulfate coadministration resulted in greater thiocyanate concentrations (22.8 ± 16.7 vs 16.8 ± 14.9 μg/mL, P = .01), despite utilization of lower cumulative nitroprusside doses (10.2 vs 14.6 mg/kg, P = .03). Cumulative nitroprusside dose ( r2.44, P < .001) and cumulative sodium thiosulfate dose ( r2.32, P < .001) demonstrated a significant correlation with measured thiocyanate concentrations. Thiocyanate accumulation was independently associated with cumulative nitroprusside dose in mg/kg (regression coefficient 0.75, 95% CI 0.63-0.89; P < .01). No clinically significant adverse effects of cyanide or thiocyanate toxicity were observed.
  
  
  CONCLUSIONS
  Cumulative nitroprusside dose was independently associated with thiocyanate accumulation. Despite elevated thiocyanate levels in 16% of patients, there was no clinical evidence of cyanide or thiocyanate toxicity. Routine monitoring of thiocyanate concentrations appears most warranted in patients receiving higher cumulative doses of nitroprusside.
authors.affiliation: 1 Department of Pharmaceutical Services, University of California San Francisco Medical Center, San Francisco, CA, USA.
authors.forename: Amanda A
authors.initials: AA
authors.lastname: Morris
authors.affiliation: 2 Department of Clinical Pharmacy, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Aurora, CO, USA.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Page
authors.affiliation: 3 Department of Clinical Sciences, Touro University California College of Pharmacy, Vallejo, CA, USA.
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Baumgartner
authors.affiliation: 2 Department of Clinical Pharmacy, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Aurora, CO, USA.
authors.forename: Scott W
authors.initials: SW
authors.lastname: Mueller
authors.affiliation: 2 Department of Clinical Pharmacy, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Aurora, CO, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: MacLaren
authors.affiliation: 2 Department of Clinical Pharmacy, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Aurora, CO, USA.
authors.forename: Douglas N
authors.initials: DN
authors.lastname: Fish
authors.affiliation: 2 Department of Clinical Pharmacy, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Aurora, CO, USA.
authors.forename: Tyree H
authors.initials: TH
authors.lastname: Kiser
mesh_terms: D000328:Adult; D000368:Aged; D000931:Antidotes / Q000008:administration & dosage / Q000009:adverse effects*; D003422:Critical Care / Q000379:methods; D016638:Critical Illness / Q000628:therapy; D016903:Drug Monitoring; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007362:Intensive Care Units; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009599:Nitroprusside / Q000008:administration & dosage / Q000009:adverse effects*; D012044:Regression Analysis; D012189:Retrospective Studies; D018709:Statistics, Nonparametric; D013861:Thiocyanates / Q000097:blood*; D013885:Thiosulfates / Q000008:administration & dosage / Q000009:adverse effects*; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000009:adverse effects*
chemical_list: D000931:Antidotes; D013861:Thiocyanates; D013885:Thiosulfates; D014665:Vasodilator Agents; D009599:Nitroprusside; C017717:sodium thiosulfate; C031760:thiocyanate
keywords: critically ill; cyanide; nitroprusside; thiocyanate; thiosulfate; toxicology