Sodium nitroprusside is not associated with metabolic acidosis during intraoperative infusion in children

Abstract

Background: Sodium nitroprusside (SNP) is a potent vasodilator that has been used to induce deliberate hypotension in children during surgery involving significant blood loss, including craniofacial and spinal fusion procedures. SNP metabolism liberates cyanide, which may cause interference with cellular energy metabolism, leading to metabolic acidosis and central nervous system injury. We performed a retrospective, case-control study to determine whether the short-term intra-operative use of SNP for deliberate hypotension is associated with metabolic acidosis in children undergoing surgical procedures for craniofacial or spinal anomalies. Cyanide and thiocyanate concentrations were also recorded in patients who received SNP.

Methods: Data from 166 children undergoing craniofacial and spinal fusion surgery between 2005 and 2010 at Lucile Packard Children's Hospital (LPCH) at Stanford were analyzed. Records from 60 patients who received SNP (SNP group) as part of a multicenter, randomized, double-blind study were compared with records from 106 eligible patients who had blood pressure reduction using anesthetic agents and did not receive SNP (control group). Metabolic acidosis was defined as serum bicarbonate (HCO3) < 18.5 mEq/L. Whole blood CN, plasma thiocyanate and urinary thiocyanate concentrations were measured in patients in the SNP group. Differences in metabolic acidosis rates between the SNP and control groups were assessed through a test of noninferiority in the rate for the SNP group with a noninferiority threshold of 0.2. A z-test was used to test the null hypothesis. The alternative hypothesis was that the difference in these rates was less than 0.2. The same noninferiority threshold of 0.2 was also used to perform separate, secondary tests for noninferiority in the proportion of patients with HCO3 levels below 18.5 mEq/L and the proportion of patients who required HCO3 administration.

Results: Fewer patients in the SNP group experienced metabolic acidosis compared to the control group (31.7% vs. 36.8%, respectively; p < .001). No whole blood CN levels above the lower limit of quantification were detected in any of the 51 patients with validated CN data. Plasma and urinary thiocyanate levels were also low.

Conclusions: Our findings suggest that SNP, when used for short-term deliberate hypotension, does not cause an increased incidence of metabolic acidosis compared with the use of anesthetic agents alone.

Trial registration number: NCT00135668.

Figures

Figure 1

SNP metabolism. *SNP = sodium nitroprusside; CN- = cyanide; NO = nitric oxide; METHGB = methemoglobin; CYANOHGB = cyanohemoglobin; OXYHGB = oxyhemoglobin. *Modified with permission from Figure 1[2].

Figure 2

Plot of relationship between metabolic acidosis (MA) occurrence and both the duration of SNP administration and average SNP infusion rate until either MA was detected or the end of the study. Only patients in the SNP group are plotted. Patients with and without MA are plotted using a “+” and “o,” respectively.