Sodium Nitroprusside

Source: UK SPC (eMC) for Sodium Nitroprusside 50 mg/2 mL Concentrate For Solution For Infusion, §4.2 (https://www.medicines.org.uk/emc/product/100870/smpc). Infusions generally have to be started with low doses; the hypotensive effect is immediate and baseline values are rapidly achieved after the end of the infusion. In the titration phase, exact titration with blood pressure measurements every one to two minutes is required; towards the end of the infusion the rate is gradually reduced. §4.4 requires continuous ECG monitoring and, where relevant, monitoring of the most important haemodynamic parameters during infusion; under surgical conditions blood pressure is best measured directly via an arterial cannula, while for infusions over several days non-invasive blood pressure measurement is sufficient. PREVENTION OF CYANIDE TOXICITY: it is strongly recommended always to give the sodium nitroprusside infusion with a simultaneous continuous infusion of sodium thiosulfate solution via a SEPARATE venous access at a ratio of approx. 1:10 (sodium nitroprusside dihydrate : sodium thiosulfate) based on the weights of the active substances; practically, draw sodium thiosulfate solution 100 mg/mL into a second Perfusor syringe and infuse at a volume ratio of approx. 12:1 via a separate venous access (SPC Table 2); when using an Infusomat for the nitroprusside the volume ratio should be 60:1 or 120:1. §4.8 states cyanide intoxication is completely avoidable by simultaneously administering a thiosulfate infusion at a molar ratio of 5:1 (thiosulfate : sodium nitroprusside), and that signs of toxicity can occur if the dose of 0.05 mg CN-/kg/min (the detoxification capacity of the human body) is exceeded without simultaneous thiosulfate. As an antidote for suspected or observed cyanide toxicity (e.g. when no thiosulfate is available for co-administration), hydroxocobalamin and/or methaemoglobin-forming agents might be required. THIOCYANATE TOXICITY: if infused over several days (with high doses already within 24 hours), thiocyanate levels must be monitored, especially in renally impaired patients, and must not exceed 6 mg/100 mL; concentrations above 6 mg/100 mL lead to toxic symptoms such as weakness, vomiting, dizziness and tinnitus; in thiocyanate intoxication stop the infusion and, if necessary, remove thiocyanate by dialysis. ELDERLY: elderly patients frequently require lower doses. HEPATIC IMPAIRMENT: cyanide released from sodium nitroprusside is mainly metabolised by hepatic enzymes and may accumulate in severe hepatic impairment — use with caution, titrate carefully, monitor more closely for cyanide toxicity, and reduce or discontinue gradually if necessary. PAEDIATRIC: the UK SPC states safety and efficacy in children and adolescents have not been demonstrated so far, no data are available, and therefore Sodium Nitroprusside should NOT be administered to children and adolescents — hence no paediatric per-kg dose is given here. (For cross-reference only, the US label in this bundle quotes an average effective rate of about 3 mcg/kg/min in adult and paediatric patients, a starting rate of 0.3 mcg/kg/min and a maximum of 10 mcg/kg/min — US labelling differs from the UK SPC and the UK SPC position above takes precedence.) HANDLING: protect from light (coloured syringes and tubing); the solution is clear colourless to faint brownish — strongly coloured solutions must not be used; no additional drugs may be added to the ready-to-use infusion solution. Some sections of the product information we used were incomplete — check the full SPC.