Postgraduate Medical Journal (September 1974) 50, 576-581.

Sodium nitroprusside: theory and practice

IAN R. VERNERM.B.Ch.B., F.F.A.R.C.S., D.A.

The Middlesex Hospital, London

SummarySodium nitroprusside, by a peripheral vasodilatoraction, is a powerful hypotensive drug. In contrast toestablished agents, its hypotensive action is accom-panied by an unchanged or augmented cardiac output.Intravenous administration of sodium nitroprussiderapidly produces a profound and controllable hypo-tension. Normotension is swiftly restored by ceasingto infuse the agent, and antidotes are unnecessary. Itsattributes make it especially suitable for neurosurgicalanaesthesia, and although free cyanide is liberatedduring biotransformation, side effects are virtuallyabsent provided that dosage is reasonable. Specialcontraindications to its use are hypothyroidism andaltered cobalamin metabolism.

SODIUM nitroprusside was discovered in 1893 byPlayfair, and by 1929 Johnson had outlined its basicpharmacology. By 1955 Page et al. had shown thatit could be used to treat hypertensive patients, andthat even with prolonged administration its toxiceffects were minimal. It was not until 1970 that thefirst definitive paper on its use to produce hypoten-sion during anaesthesia appeared (Taylor, Styles andLamming, 1970). During the following 3 yearsnumerous papers describing its use during anaes-thesia have appeared, all of which have testified tothe efficiency and lack of side effects of the agent.Sodium nitroprusside is now established as aneffective and malleable hypotensive agent, and isthe drug of choice in many centres. It is, however,still a relatively untried drug, and its potentialtoxicity should be constantly born in mind. Doubt-less its possible lethal effects delayed its adoption byanaesthetists, but experience so far has shown that,provided care is taken in the use of the drug, it isremarkably free from deleterious effects.

PharmacologySodium nitroprusside (Na2Fe++(CN)5NO.2H2O)

forms reddish-brown crystals which are soluble inwater. In solution it is relatively stable, resistingoxidation at a neutral or slightly acidic pH. Thestructural unit is the nitroprusside radical, whichconsists of one iron atom linked to one nitrosyl andfive cyanide groups. The basic units link together to

form a lattice which contains the sodium and watermolecules. The exact mode of action of the com-pound is unknown, but since many nitrites havevasodepressor actions, it is assumed that the iron-nitrosyl group is the active part of the molecule. Ithas been estimated that the nitrosyl group is be-tween 30 and 1000 times more powerful than nitrites(Johnson, 1929). The primary action of sodiumnitroprusside is smooth muscle relaxation; thisaction is direct and most readily seen in thevascular system (Johnson, 1929; Page et al., 1955).Intravenous sodium nitroprusside rapidly producesa profound hypotension which is readily reversibleand is not accompanied by tachyphylaxis. Recentcontrolled studies by Wildsmith et al. (1973) andStyles, Coleman and Leary (1973) have delineatedthe cardiovascular changes which accompanysodium nitroprusside-induced hypotension bothin anaesthetized and non-anaesthetized humans.Both investigations are in close agreement. Thelowered arterial pressure was accompanied by aprofound fall in both central venous pressure andperipheral resistance, the heart rate was slightlyelevated and the cardiac output was either un-changed or else rose slightly. Changes in strokevolume were neither consistent nor significant. It isimportant to note that the hypotension was notaccompanied by a reduction in cardiac output, forin this respect sodium nitroprusside differs fromother hypotensive agents such as halothane or gang-lion blocking agents. The pharmacodynamics ofsodium nitroprusside would seem to be such thatany improvement in operating conditions is achievednot by a reduction in tissue perfusion, but rather bya reduction in arterial pressure. Provided thatarterial oxygenation is satisfactory, combination ofan unchanged or enhanced cardiac output coupledwith a decreased peripheral resistance means thattissue oxygen availability will be adequate evenunder hypotensive conditions.

Heart rateEarly reports of sodium nitroprusside hypotension

indicated a variable cardiac response. Schiffmannand Fuchs (1966), Jones and Cole (1968) and Tayloret al. (1970) all stated that the heart rate could

copyright. on 28 M

ay 2018 by guest. Protected by

http://pmj.bm

j.com/

Postgrad M

ed J: first published as 10.1136/pgmj.50.587.576 on 1 S

eptember 1974. D

ownloaded from

Sodium nitroprusside

remain unchanged, slow or accelerate. The more

recent studies have shown that there is normally a

20%0 increase in heart rate during the hypotensivephase. The rarity of a markedly elevated pulse ratefollowing upon the use of sodium nitroprusside un-

doubtedly plays a part in the ease with which it canproduce satisfactory operating conditions. In a fewinstances a pronounced tachycardia will be seen

after sodium nitroprusside has been given. In suchcircumstances hypotension may be difficult toestablish, but the rate can be slowed by administer-ing 0-adrenergic blocking drugs.

Myocardial functionNo adverse effects of sodium nitroprusside upon

myocardial function have been reported. Franciosaet al. (1972) studied the effects of sodium nitro-prusside upon cardiac output and left ventricularfunction in a series of patients who had sufferedrecent myocardial infarction. They found that, witha mild degree of hypotension, left ventricular fillingpressure fell and cardiac output was enhanced.From these observations and the condition of theirpatients they concluded that the coronary circulationwas not embarrassed by the procedure.

Effects on other organs

Kidneys. Johnson (1929) observed dilatation in theisolated and perfused renal artery on exposure tosodium nitroprusside, which was accompanied byincreased renal perfusion. The renal haemodynamiceffects in both dogs and humans were studied byPage et al. (1955). In dogs they found that both renalperfusion pressures and renal vascular resistancewere lowered. Para-amino hippurate and creatinineclearance values were largely unchanged, as was thetubular reabsorptive capacity for glucose. In humanbeings similar results were obtained, and it was notedthat in both species the hypertensive were more

sensitive to the effects of sodium nitroprusside thanwere the normotensive. Clear evidence of a vaso-

dilator action upon the renal vasculature was ob-tained radiographically by Moraca et al. (1962).

Intestines and uterus. Johnson (1929) found thatsodium nitroprusside inhibited contractions ofisolated and perfused strips of muscle excised fromthe uterus and intestines. However, Page et al. (1955)found that nitroprusside did not relax the virgin or

pregnant uterus of rabbits or the duodenum of dogseven when given in markedly hypotensive dosage.

Bronchial musculature. It might be expected thatsodium nitroprusside would relax bronchial muscula-ture and Johnson (1929) suggested its use thera-peutically to relieve bronchoconstriction. Thereappear to be no studies of the actions of sodiumnitroprusside on the bronchial tree. Personal ex-

perience indicates that though sodium nitroprusside

can relieve bronchoconstriction occurring duringgeneral anaesthesia, objective improvement does notoccur until arterial tension is grossly depressed. Itwould therefore seem that, at least unaided, sodiumnitroprusside has little place in the therapy ofbronchoconstriction.

Combination with other drugsSince sodium nitroprusside acts directly upon the

smooth muscle of vessel walls, it is to be expectedthat agents which reduce the muscle tone will aug-ment the hypotensive effects of nitroprusside. Pageet al. (1955) observed that many ganglioplegic ando-adrenergic blocking drugs substantially augmentedthe hypotensive actions of sodium nitroprusside inanimals. A similar picture is seen in human beings.Patients who have received oc-adrenergic blockingagents are markedly sensitive to sodium nitro-prusside, and the administration of ganglion blockersbefore or after an infusion of sodium nitroprussidegreatly increases the response to the latter. Drugswhich reduce cardiac output (e.g. halothane or -

adrenergic blockers) also augment its hypotensiveaction. Conversely, the inhalation of 15-20% carbon-dioxide was shown to decrease the hypotension ofsodium nitroprusside (Page et al., 1955).

Metabolism and toxicityThe evanescent action of sodium nitroprusside

may be attributed to its rapid bio-transformation.The iron atom of the nitroprusside radical reactswith free sulphydryl groups found in erythrocytes,and releases cyanide radicals. This reaction is non-enzymatic, and its slow time course precludes therelease of cyanide from being the mechanism ofaction of nitroprusside. The free cyanide radicals arethen linked enzymatically to sulphydryl groups,forming thiocyanate. The enzyme, which is presentin human erythrocytes and liver, was discoveredand named rhodanese by Lang (1933). The ending'ese' indicates that the enzyme is responsible for anirreversible reaction. The observation that thechronic administration of thiocyanate to humanbeings was followed by a rise in the serum levels ofcyanide cast doubts upon the irreversibility of thereaction. Goldstein and Rieders (1953) found thatthe reaction was indeed irreversible but that the con-version of thiocyanate to cyanide was under thecontrol of yet another enzyme present in human redcells. This enzyme, thiocyanate oxidase, gives a yieldof about 1% cyanide from thiocyanate over a periodof 1 hr. Optimum conditions for its action are a pHof 7-4 and a temperature of 40'C. In essence, there-fore, cyanide radicals are converted to thiocyanatesunder the influence of rhodanese, and some thio-cyanate is reconverted to cyanide by thiocyanateoxidase. Such an interconversion was observed by

577

copyright. on 28 M

ay 2018 by guest. Protected by

http://pmj.bm

j.com/

Postgrad M

ed J: first published as 10.1136/pgmj.50.587.576 on 1 S

eptember 1974. D

ownloaded from

I. R. Verner

Boxer and Richards in 1952. It should be appreciatedthat the administration of either nitroprusside orthiocyanate to humans, especially if prolonged, maylead to an accumulation of cyanide in the body. Thepossibility of cyanide intoxication after nitroprussideor thiocyanate therapy has naturally received con-siderable attention. Page et al. (1955) administerednitroprusside orally to chronic hypertensive patientsfor periods of 6 weeks to 2 years. Thiocyanate levelsin the blood were found to rise, especially if renalfunction was impaired. Toxic symptoms includedfatigue, nausea, loss of appetite and weakness.Thiocyanate levels of between 8 and 12 mg/100 mlblood were found to be unaccompanied by toxiceffects. Both Goldstein and Rieders (1953) and Pinesand Crymble (1952) estimated blood cyanide levelsafter the acute and chronic administration of thio-cyanate. Cyanide levels were always considerablybelow the 034 mg/100 ml blood levels stated byGettler and Baine (1958) to be the minimum fatalconcentration. Anaesthetic literature reveals nooccasions on which excessive cyanide levels havebeen found to result from the acute administrationof sodium nitroprusside. Cole (personal communica-tion) has found blood cyanide levels often to beunrecordable after sodium nitroprusside hypo-tension, but has cautioned that present methods ofcyanide estimation may be inadequate. It is certainthat some fatalities have occurred following nitro-prusside administration. One factor is common toall the known cases, namely that large amounts ofnitroprusside have been infused. In common withother agents whose detoxification relies uponenzymatic action the possibility of deficient oratypical enzymes occurring in human beings shouldalways be borne in mind.A further toxic action of nitroprusside has been

described by Nourok et al. (1964). Thiocyanates areeffective antithyroid agents, and the symptoms ofthiocyanate poisoning resemble hypothyroidism inmany respects. Nourok and his associates describeda case of hypothyroidism occurring after prolongednitroprusside therapy, and gave evidence that nitro-prusside (as well as thiocyanate) may have an anti-thyroid action. Obviously, nitroprusside should beadministered to hypothyroid individuals withcaution.

It is reassuring to note that many investigatorshave commented upon the absence of side-effectsafter using nitroprusside to induce hypotension forbrief periods.

Preparation of solutionsPharmaceutical preparations of sodium nitro-

prusside are not currently available, and hospitalpharmacies must therefore prepare their own stocksolutions. Analytical grade crystals are dissolved in

distilled water with a pH of approximately 5*0, tomake a 10 mg/ml solution. Heat sterilization willdestroy the solution, which is cold sterilized bypassage through a membrane filter (0 22 ii) andstored in sterilized 5 ml ampoules. If stored at atemperature of 40C the shelf life of the solution willbe approximately 3 months. Oxidative decompositionof the solution is shown by a colour change fromlight reddish-brown to deep blue. On no accountshould any solution showing a colour change beused. The basic working solution of sodium nitro-prusside is obtained by adding 5 ml of stock solutionof 500 ml 5% dextrose, making a 0-01 % solution.Weaker (0 005% or 0-002 %) working solutions maybe employed for frail subjects, whilst more robustindividuals may require stronger working solutionsof 0-02% or even 0 04%.

Technique of inducing hypotension with sodiumnitroprusside

Before inducing hypotension a stable state ofgeneral anaesthesia should be established. The exactanaesthetic technique is largely immaterial, andventilation can be either spontaneous or controlled.It is helpful if the anaesthetic technique is 'selfmaintaining' in so far as is possible, for satisfactoryhypotension with nitroprusside demands continuousconcentration. For this reason, endo-tracheal intuba-tion is virtually mandatory and techniques involvingfrequent injections of anaesthetic agents are leastsuitable. As with other hypotensive procedures, areduction in the VD/VT ratio may be expected andit is therefore important to ensure an adequateconcentration (>40 %) of oxygen in the inspiredgases. The anaesthetic agents should bias towardsthe hypotensive state, for the dose of nitroprussidecan then be kept to a minimum. Basic anaesthesiawith nitrous oxide, oxygen and halothane hasproved to be a suitable technique.

It is essential to monitor the arterial blood pressure.Two methods have the necessary sensitivity andreliability, namely oscillotonometry and directarterial cannulation. The invasive technique shouldbe employed when first using nitroprusside, for acontinuous recording will give early warning ofchanges in arterial pressure. With experience,oscillotonometry becomes an acceptable substitute;it is quicker to set up, mechanically more reliableand obviates the morbidity associated with arterialpuncture. The blood pressure cuff should not beplaced around an arm which is receiving a nitro-prusside-containing drip, for inflation of the cuff willthen retard the rate of infusion. Even transient inter-ruptions offlow will lead to blood pressure variations.All patients receiving nitroprusside require twoseparate intravenous infusions. One, for fluids andblood, is set up once anaesthesia has been induced.

578

copyright. on 28 M

ay 2018 by guest. Protected by

http://pmj.bm

j.com/

Postgrad M

ed J: first published as 10.1136/pgmj.50.587.576 on 1 S

eptember 1974. D

ownloaded from

Sodium nitroprusside 579

A wide-bore (14 gauge) cannula should be used, forthis infusion may be required to elevate bloodpressure rapidly. The other, kept exclusively fornitroprusside, is placed in situ immediately it isrequired to hypotense the patient. When the requiredworking solution has been made up, an intravenousadministration set is inserted into the bottle and thegiving set filled with the working solution. The dripset should never be filled with intravenous infusionfluid and the stock solution then added to theintravenous bottle, for in this way a nitroprusside-free fluid 'dead space' will exist in the tubing. Inthese circumstances there will be uncertainty as towhen hypotension will commence.The required working solution is clearly labelled,

and then connected directly to a small bore intra-venous cannula. The practice of inserting a nitro-prusside infusion into a side arm of the main infusionshould be avoided. Sodium nitroprusside is anextremely potent agent, and even the small amountinside an intravenous cannula is capable of causinga precipitous fall of blood pressure. Hypotensioncan be conducted with more certainty and safety ifthe nitroprusside infusion is kept entirely separatefrom the normal infusion.

Precise control of the nitroprusside infusion isimportant, and several methods are possible. Anormal infusion set with a standard control has theadvantage that no special equipment is required.However, standard drip controls may be too insensi-tive, especially at slow drip rates. More preciseregulation can be effected leaving the drip controlset in one position and raising or lowering the bottlecontaining the infusion to alter administration rates.A further improvement is the substitution of an over-size drip control for that supplied with the drip set.A microdrip infusion system, such as is used forpaediatric fluid administration, will give very finecontrol of infusion rates. Suitable sets have a smalldrip needle in the infusion chamber, the small dropletsize allowing very slow rates of infusion. Lastly,electronic drip-counting mechanisms or infusionpumps have been used. Whilst these mechanismsallow a very steady infusion rate to be maintainedalmost indefinitely, they suffer from the disadvan-tages of expense, mechanical unreliability and mayhave too slow a response time. Once confidence hasbeen obtained in the use of the agent it will be foundthat the normal drip set with standard control issatisfactory. The advantages of ready availabilityand reliability will be obvious.To induce hypotension the nitroprusside infusion

is commenced at a rate of 15-30 drops/min. Bloodpressure should be monitored continuously. Arterialpressure will usually start falling immediately or atleast within 2 min of commencing the infusion, butin rare cases where hypotension is refractory, the

nitroprusside infusion should be progressivelyspeeded up until an effect is observed. Once hypo-tension develops the rate of fall of pressure shouldbe carefully noted. A gradual fall can be allowed tocontinue unchecked until the desired level of tensionis reached, when the drip rate is then slowed to thelevel required for maintenance. However, if there isa rapid and progressive fall in blood pressure, thedrip rate should be checked long before the desiredtension is reached. For the beginner using nitro-prusside, and before the potentialities of the agentare realized, too rapid a fall in blood pressure isfrequently produced. Slowing or ceasing the infusionthen results in an equally rapid rise which is counter-acted by restarting the infusion. This results in a'see-saw' pressure level, and it may be 5 to 10 minbefore a stable level of hypotension is reached. Thiscan usually be avoided by inducing hypotensionmore slowly from the beginning.

Should the blood pressure fall too low, normo-tension can be reinstated by stopping the infusion.In most cases recovery of arterial pressure com-mences within 15 sec. Recovery is rapid and pro-gressive, being substantially complete within 2-5min. It is in the extreme transience of its action thatthe safety of nitroprusside lies. Antidotes are notrequired, and to boost recovery it is merely necessaryto infuse rapidly some 200 ml of normal intravenousfluids. The importance of a separate hypotensiveinfusion is reiterated, for under conditions ofextremehypotension the infusion of even the small amountof nitroprusside contained within an intravenouscannula ahead of a bolus of normal intravenousfluid may be sufficient to cause a serious fall ofpressure. It should be appreciated that in mostpatients there is no lower limit to the hypotensionwhich may be achieved with nitroprusside. Usuallythe level of hypotension is directly proportional tothe rate of infusion, a fact which can be used toadvantage, for blood pressure can be taken down ina 'step-wise' fashion to the target level. The speed andease with which arterial pressure levels may bechanged during the course of an anaesthetic is themost attractive feature of this drug, and in thisrespect it outmatches any other hypotensive agent.

If meticulous attention is paid to infusion ratesand blood pressure levels, controlled and effectivehypotension can be produced in almost all patients.Two types of patient may present difficulties. In onethere may be an increased sensitivity to the drug.Patients in this category are commonly elderly orinfirm, and it is here that the weaker working solu-tions should be employed. In contrast, others willbe remarkably resistant. Almost invariably these arerobust young adults. With such patients satisfactoryhypotension may not be established even by infusingnormal strength solutions at rates of between 120 and

copyright. on 28 M

ay 2018 by guest. Protected by

http://pmj.bm

j.com/

Postgrad M

ed J: first published as 10.1136/pgmj.50.587.576 on 1 S

eptember 1974. D

ownloaded from

0I . Verner

180 drops/min. Such infusion rates carry with themthe danger of too great a fluid load being deliveredto the patient. Here, either the concentration shouldbe increased (which will diminish the fluid load), oragents which augment the vaso-depressor actions ofnitroprusside should be added (which will reducethe amount required). Hence, increasing the in-spired concentration of halothane or adding smallamounts of ganglion-blockers will enable a moresatisfactory hypotension to be achieved. After suchmeasures the recovery of normotension may beslightly prolonged. Though true resistance to nitro-prusside is extremely rare, there are great variationsin sensitivity to this agent. The total amountnecessary to effect profound hypotension for periodsof between 1 and 3 hr can range between 5 and 200mg, and infusion rates varying between 15 and onehundred and twenty drops/min may be required. Ifit becomes obvious that excessive amounts are beinginfused, potentiating agents should be added. Untilmore information is available about the enzymaticmetabolism of cyanide in man, large amounts ofsodium nitroprusside should not be administeredwith abandon.

Restoration of normotensionNormotension should normally return within 5

min of ceasing the infusion.This is to be expected even if hypotension has been

prolonged or the total dosage large. Should a slowerrestitution be required, it may be obtained by pro-gressively retarding the rate of infusion. Once nitro-prusside is discontinued, any delay in the return ofnormotension can be attributed to either the effectsof anaesthesia or a deficiency in blood volume, andthe appropriate remedial steps can be taken. Whenit is certain that further hypotension will not berequired, the nitroprusside infusion should besecurely clamped or removed from the patient toavoid the possibility of inadvertent hypotension.

Indications for useSodium nitroprusside is a suitable agent for use

in most cases where hypotension is required. Itsspecial features are potency, rapid action and ex-treme controllability, allowing minute by minutecontrol of blood pressure. Pre-eminently it is theagent of choice during neurosurgery, where bloodpressure may need to be altered rapidly to meetvarying surgical conditions. For example, the surgicalapproach to an intracranial aneurysm may be con-ducted under slight or moderate hypotension, andthe blood pressure then lowered profoundly forsurgery of the aneurysmal sac. Once definitivesurgery of the lesion is complete, the blood pressuremay be rapidly restored to normal levels and theadequacy of treatment assessed. Should further

surgery be necessary, the blood pressure may againbe lowered within minutes to a more useful level.

Siegel, Moraca and Green (1971) have commentedfavourably upon the use of nitroprusside for intra-cerebral surgery, finding an improvement in themorbidity and mortality of patients with Grade I orII aneurysmal lesions. The malleability of the drug isa great advantage should uncontrollable haemorrhagedevielop during this operation. Whilst under ganglionblocking agents a considerable delay ensues beforenormal tone returns to the cardiovascular system,with sodium nitroprusside normal tone returns soonafter the infusion has stopped, and the disastrouseffects of hypovolaemia with hypotension canthereby be avoided.The surgery of pheochromocytomata is also best

carried out under nitroprusside hypotension, Katzand Wolf (1971). Patients with these tumours willnormally have received treatment by a- and 1-adrenergic blocking drugs, and will often be remark-ably sensitive to the hypotensive effects of nitro-prusside. Hypertension resulting from manipulationof the tumour can be remarkably easily and swiftlyannulled. When the pheochromocytoma has beenexcised discontinuing the nitroprusside will lead toa restoration of vascular tone within minutes and ifhypertension does not return, then it may be assumedthat surgery has been successful.

Nitroprusside may, of course, be used in mostsituations where hypotension is indicated. In onlyone instance, namely when a more gradual return ofblood pressure is required, can other agents be usedto more advantage. It appears likely that increasingexperience with this agent will lead to its wider usebecause of the rapidity and certainty with whichblood pressure can be lowered. Its use need not belimited to anaesthesia for it is valuable in severehypertensive crises outside the operating theatre.Should vasodilation be thought to be helpful duringangiography, then it will rapidly and transiently pro-duce the desired conditions. The ephemeral actionof this drug is perhaps its most attractive feature.Once hypotension has been discontinued, there areno long-lasting sequelae (vasomotor or smoothmuscle paralysis) and it is the only drug which canproduce hypotension for exactly the period required.

ContraindicationsContraindications to hypotension are outside the

scope of this article, but they obviously apply equallyto nitroprusside and to other hypotensive agents. Acontraindication to nitroprusside is hypothyroidism.According to the severity of the disease this will beeither relative or absolute, but in any case prolongedexposure should never be permitted. The literaturepertaining to the use of nitroprusside is remarkablyfree of contraindications or reports of deleterious

580

copyright. on 28 M

ay 2018 by guest. Protected by

http://pmj.bm

j.com/

Postgrad M

ed J: first published as 10.1136/pgmj.50.587.576 on 1 S

eptember 1974. D

ownloaded from

Sodium nitroprusside 581

sequelae. Nevertheless it cannot be overstressed thatcaution should always be exercised when using arelatively new agent, and if the speed of administra-sion or the total amount given ever begins to causeanxiety it should be remembered that discretionshould always precede valour.

ReferencesBOXER, G.E. & RICHARDS, J.C. (1952) Studies on the meta-

bolism of the carbon of cyanide and thiocyanate. Archivesof Biochemistry, 39, 7.

FRANCIOSA, J.A., GUIHA, N.H., LIMAS, C.J., RODRIGUERA, E.& COHN, J.N. (1972) Improved left ventricular functionduring nitroprusside infusion in acute myocardial infarc-tion. Lancet, i, 650.

GETTLER, A.C. & BAINE, J.C. (1958) Toxicology of cyanide.American Journal of Medical Sciences, 195, 182.

GOLDSTEIN, F. & RIEDERS, F. (1953) Conversion of thio-cyanate to cyanide by an erythrocytic enzyme. AmericanJournal of Physiology, 173, 287.

JOHNSON, C.C. (1929) The actions and toxicity of sodiumnitroprusside. Archives of Internal Pharmacodynamics, 35,480.

JONES, G.O.M. & COLE, P. (1968) Sodium nitroprusside as ahypotensive agent. British Journal of Anaesthesia, 40, 804.

KATZ, R.L. & WOLF, C.E. (1971) Highlights of ClinicalAnaesthesiology, p. 56. Harper and Row: New York.

LANG, K. (1933) Die Rhodanbildung im Tierkorper. Bio-chemische Zeitschrift, 259, 243.

MORACA, P.P., ELMARS, M.B., HALE, D.E., WASMUTH, C.E.& POUTASSE, E.F. (1962) Clinical evaluation of sodiumnitroprusside as a hypotensive agent. Anesthesiology, 23,193.

NOUROK, D.S., GLASSOCK, R.J., SOLOMON, D.H. & MAX-WELL, M.H. (1964) Hypothyroidism following prolongedsodium nitroprusside therapy. American Journal ofMedical Sciences, 248, 129.

PAGE, I.H., CORCORAN, A.C., DUSTAN, H.P. & KOPPANYI, T.(1955) Cardiovascular actions of sodium nitroprusside inanimals and hypertensive patients. Circulation, 11, 188.

PINES, K.L. & CRYMBLE, M.M. (1952) In vitro conversion ofthiocyanate to cyanide in presence of erythrocytes.Proceedings of the Society for Experimental Biology andMedicine, 81, 160.

SCHIFFMANN, H. & FUCHS, P. (1968) Controlled hypotensioneffected by sodium nitroprusside. Acta anaesthesiologicaScandinavica, supp. 23, 704.

SIEGEL, P., MORACA, P.P. & GREEN, J.R. (1971) Sodiumnitroprusside in the surgical treatment of cerebralaneurysms and arteriovenous malformations. BritishJournal of Anaesthesia, 43, 790.

STYLES, M., COLEMAN, A.J. & LEARY, W.P. (1973) Somehaemodynamic effects of sodium nitroprusside. Anesthesio-logy, 38, 173.

TAYLOR, T.H., STYLES, M. & LAMMING, A.J. (1970) Sodiumnitroprusside as a hypotensive agent in general anaes-thesia. British Journal of Anaesthesia, 42, 859.

WILDSMITH, J.A.W., MARSHALL, R.L., JENKINSON, J.L.,MACRAE, W.R. & SCOTT, D.B. (1973) Haemodynamiceffects of sodium nitroprusside during nitrous oxide/halothane anaesthesia. British Journal of Anaesthesia, 45,71.

AddendumSince submission of this manuscript an important communication on the metabolism ofsodium nitroprusside

has been published [Vesey, C.J., Cole, P.V., Linnell, J.C. and Wilson, J. (1974) Some metabolic effects ofsodium nitroprusside in man. British Medical Journal, 2, 140.] The authors found a highly significant rise inplasma cyanide levels after sodium nitroprusside was infused during major orthopaedic surgery. Plasma vitaminB12 and methylcobalamin levels were simultaneously decreased. In one instance, after prolonged administra-tion of sodium nitroprusside, erythrocyte cyanide concentration rose, but was reduced by intravenouslyadministered hydroxocobalamin.Although no adverse effects on the patients are reported, the authors caution that sodium nitroprusside may

be contraindicated for patients with low plasma B12 levels, liver disease, or Leber's optic atrophy, and suggestthe prophylactic use of hydroxocobalamin whenever sodium nitroprusside is to be used.

copyright. on 28 M

ay 2018 by guest. Protected by

http://pmj.bm

j.com/

Postgrad M

ed J: first published as 10.1136/pgmj.50.587.576 on 1 S

eptember 1974. D

ownloaded from