Infusion of sodium nitroprusside induces platelet dysfunction in vitro.

The effect of sodium nitroprusside (SNP) infusion on platelet function was prospectively evaluated in 29 patients undergoing cardiac surgical procedures requiring cardiopulmonary bypass. Any patient receiving preoperative medication known to interfere with platelet function was excluded from this study. Platelet function was evaluated by measurement of platelet aggregation with both adenosine diphosphate (ADP) and epinephrine-induced aggregation tests. Ten patients served as a control population receiving fentanyl anesthesia and no SNP. Nineteen patients received SNP, as clinically indicated, following the induction of anesthesia (and prior to cardiopulmonary bypass) to maintain a mean blood pressure of 80 mmHg. The infusion rate and total dose of SNP delivered was recorded for each patient. Infusion rates of SNP greater than or equal to 3 micrograms.kg.-1 min-1 resulted in a dose-related decrease in platelet aggregation (P less than 0.05). This reduction in platelet function was accompanied by a concomitant increase in bleeding time from 5.8 +/- 0.6 to 9.3 +/- 0.4 min in the patients receiving SNP (P less than 0.05). In addition, with the administration of a total dose of SNP greater than or equal to 16 mg, a significant reduction in platelet aggregation (P less than 0.05) was observed. Platelet aggregation studies and bleeding time performed in the control group (following the administration of fentanyl (30 micrograms/kg) did not reveal any deviation from baseline values. The results from this in vivo study support previous in vitro data demonstrating a detrimental effect upon platelet function following SNP infusion.

Use of sodium nitroprusside in post-coronary bypass surgery. A plea for conservatism.

In 292 patients who underwent coronary artery bypass graft (CABG) surgery, seven patients developed sodium nitroprusside (SNP) toxicity in the postoperative period. Duration of infusion varied between 26 to 160 hrs and total SNP dose ranged from 1.8 to 12 mg/kg body weight. All patients were critically ill and required ventilatory support in the postoperative period. Tachyphylaxis to SNP requiring increase of SNP dose for control of hypertension, and loss of consciousness were the major signs of toxicity. Other commonly described signs of SNP toxicity were absent in those patients. Discontinuation of SNP therapy and treatment with sodium thiosulfate was followed by improvement in four patients. Three patients who failed to regain consciousness later died because of hemodynamic, pulmonary and/or renal complications. Our observation suggests that recommended doses of SNP may be toxic in unstable post-CABG patients. We recommend that the dose and duration of SNP infusion be minimized in critically ill patients.

[Microcirculation in the brain during controlled arterial hypotension. Experimental study of the effect of nipruton]. / Mikrotsirkuliatsiia v golovnom mozge pri upravliaemoi arterial'noi gipotonii. Eksperimental'noe issledovanie vozdeistviia niprutona.

The effect of nipruton (sodium nitroprusside)-induced controlled arterial hypotension on the intracerebral microcirculatory channel was studied on 4 rabbits with transplanted induced tumors (anaplastic astrocytomas) and 7 intact rabbits under general anesthesia. It was found that nipruton injected in doses necessary for marked reduction of arterial pressure (35-45 mm Hg) for a sufficient duration (30-55 minutes) causes no circulatory disorders in the brain. In animals with tachyphylaxis to nitropruton, in which the amount of the injected agent must be increased to 9-10 mg/kg, controlled arterial hypotension even of lesser depth (60-65 mm Hg) and lesser duration (20-25 minutes) can lead to partial obstruction of the intracerebral microcirculatory channel. i. e. to the no-reflow phenomenon.

Cyanide encephalopathy following therapy with sodium nitroprusside: report of a case.

Bilateral necrosis of the globus pallidus was observed in a 43-year-old man who had received treatment for malignant hypertension with sodium nitroprusside. Cyanide released from sodium nitroprusside may have caused the pallidal lesions in the presence of deranged liver function and episodes of hypoxia.

Cerebrospinal fluid cyanide after nitroprusside infusion in man.

Sodium nitroprusside (SNP) is frequently used as an hypotensive agent for clipping of intracranial aneurysms, repair of arteriovenous malformations and resection of vascular tumours. Cyanide (CN), which is its main metabolic product, has been recovered from the cerebrospinal fluid (CSF) of the rat after intravenous administration of CN, but recovery of CN from CSF after SNP has not been reported in man. Seven consenting adults were studied. Adequate premedication was provided with pentobarbitone 2 mg x kg-1 and atropine 0.4 mg one hour before operation. Anaesthesia was induced with thiopentone 8 mg x kg-1 and maintained with nitrous oxide 60 per cent with oxygen and supplemental fentanyl 0.05 mg and pancuronium 0.5-1 mg as needed. Lumbar subarachnoid, radial artery, central venous, and Foley urinary catheters were inserted. Arterial carbon dioxide tension (PaCO2) was maintained between 4.6-5.32 kPa (35-40 torr) with an Air Shields ventilator. Red cell, plasma and CSF cyanide were measured using a digital ionanalyzer before and at 30 minutes interval after infusing SNP at a rate sufficient to maintain the blood pressure at two thirds of the pre-operative level. Average total dose of SNP was 0.51 mg x kg-1. CN concentration in the red blood cells increased from 9.5 +/- 2.05 to 75.12 +/- 17.12. Plasma CN increased from 0.54 +/- 0.05 to 1.09 +/- 0.14 micrograms per cent. CSF CN increased from 0.11 +/- 0.04 to 0.72 +/- 0.07 micrograms per cent. Significant increase in red cell, plasma and CSF CN occurred five minutes after the start of SNP and returned to the preoperative level 19 hours later. Conclusion CN crosses the blood-brain barrier. Large doses of SNP in patients with neurovascular brain disorders warrants caution because cytotoxic cerebral oedema and CN encephalopathy have been described in rats after intravenous injection of sodium cyanide or exposure to hydrogen cyanide.

Cyanide toxicity following nitroprusside induced hypotension.

Several recently reported deaths following the use of sodium nitroprusside have been attributed to the accumulation of the nitroprusside metabolite, cyanide. In this study, brief nitroprusside infusions (mean = 36 minutes) were administered in currently recommended doses during intracranial surgery. The peak blood cyanide following the infusions was 65.2 +/- 17.5 microgram per cent (mean +/- SE) (n = 13). It occurred within 45 minutes after infusion. The highest cyanide level detected was 205 microgram per cent, which is within the range of reported lethal blood cyanide levels. Metabolic acidosis developed in the four patients with the highest blood cyanide levels (range 90-205 microgram per cent). This occurred between 45 and 180 minutes following the cyanide peak. Blood ATP levels were depressed in the same patients. These findings are indicative of disturbed aerobic metabolism. We conclude that there is evidence of cyanide toxicity when nitroprusside is infused into patients using currently recommended doses. We recommend that for short infusions the dose of sodium nitroprusside should not exceed 0.5 mg/kg.