Pharmacology for Anaesthesia and Intensive Care

P1: PSB Printer: Yet To Come
9780521704632c15 CUFX213A/Peck 9780521618168 December 28, 2007 13:25

Section IIICardiovascular drugs

Red blood cell

Cyanocobalamine

Vitamin B 12

Sulphydryl groups

Rhodanase

CN

SCN

Kidney

Liver

OxyHb

MetHb

CyanoMetHb

NO

SNP

CN

Figure 15.1.Metabolism of sodium nitroprusside (SNP). CN–, cyanide; SCN, thiocyanate.

Toxicity

The major risk of toxicity comes from CN−,although SCN is also toxic. Free CN−can

bind cytochrome oxidase and impair aerobic metabolism. In doing so a metabolic

acidosis develops and the mixed venous oxygen saturation increases as tissues

become unable to utilize oxygen. Other signs include tachycardia, arrhythmias,

hyperventilation and sweating. Plasma CN−levels above 8μg.ml−^1 result in toxicity.

Itshould be suspected in those who are resistant to SNP despite an adequate dose

and in those who develop tachyphylaxis. It is more likely to occur in patients with

hypothermia, severe renal or hepatic failure and those with vitamin B 12 deficiency.

The management of CN−toxicity involves halting the SNP infusion and optimizing

oxygen delivery to tissues. Three treatments are useful:


Dicobalt edetate, which chelates CN−ions.


Sodium thiosulphate, which provides additional sulphydryl groups to facilitate the

conversion of CN−to SCN. This is sometime used as prophylaxis.


Nitrites – either sodium nitrite or amyl nitrite will convert oxyhaemoglobin to

methaemoglobin, which has a higher affinity for CN−than cytochrome oxidase.