NITROPRUSSIDE

I. Pharmacokinetics

  1. Short t-1/2 (1-2min), rapid onset of action
  2. Dose: 0.25-10 ug/kg/min IV x 10min max

II. Used to reduce BP, decrease afterload

III. Adverse effects:

  1. Cyanide poisoning
  1. Metabolism of nitroprusside and cyanide:
  1. Photodegradation releases cyanide from nitroprusside, as does normal in vivo metabolism
  2. Cyanide combines with endogenous thiosulfate to form thiocyanate, which is excreted in urine
  3. Endogenous thiosulfate, required for elimination of cyanide from the body, is normally present in small concentrations, enough to metabolize the cyanide from about 50mg of nitroprusside; thiosulfate stores are reduced in chronic illness
  4. Thiocyanate is itself toxic and has a t-1/2 of 2.7d; longer in renal failure
  1. Effects of cyanide-inhibits oxidative phosphorylation, causing
  1. CNS effects-decreased mental status, agitation, lethargy, sz, coma, death
  2. CV effect-initially tachycardia and hypertension (which can lead to increased doses of nitroprusside), then shock, arrhythmias
  3. Metabolic acidosis
  1. Thiocyanate toxicity
  1. Accumulates to toxic level when nitroprusside given over 7-14d (3-6d in severe renal failure)
  2. Occurs sooner if co-administer thiosulfate with nitroprusside
  3. Causes rash, abd. pain, tinnitus, n/v, weakness, CNS disturbance (delusions, agitation, tremor, sz, coma, death)
  4. Dx by clinical and thiocyanate levels (nl < 4mg/l, <8mg/l if smoker; toxic when >100mg/l)
  5. Tx-stop drug, hemodialysis
  1. Cyanide levels
  1. Usual RBC levels < 1.9 uMol/l (50ug/l)
  2. Toxicity starts at about 40uMol/l (1mg/l)
  3. >200uMol/l almost always causes serious toxicity
  1. Safe dose of nitroprusside is unlimited if add sodium thiosulfate (add 1g to each 100mg nitroprusside)
  2. Without thiosulfate, recommended dose of up to 10ug/kg/min can cause toxicity in <2h; differs from pt to pt but >1-2ug/kg/min can eventually result in toxicity
  3. Treatment of cyanide toxicity
  1. Stop drug!
  2. 100% O2
  3. Sodium Thiosulfate
  4. Sodium nitrite-produces low-grade methemoglobinemia which traps cynide; skip this if already severely anemic and not severely cyanide toxic
  1. Diagnosis of cyanide toxicity
  1. Levels (see above)-take too long, must use clinical picture (see above)
  2. Causes decreased O2 consumption, so increases venous pO2 (unless cardiac output is decreased, in which case can be cyanotic), so get PINK SKIN AND BRIGHT RED VENOUS BLOOD
  1. Decreased pO2 due to altered pulmonary hemodynamics
  2. Increased ICP (rare)
  3. Nausea, vomiting
  4. Caution in pts w/known renal failure

(Source: Crit. Care Clin. 7:555, 1991)