Acta anaesth. scand. 1979, 23, 404-410
Sodium Nitroprusside as a Hypotensive Agent in Intracranial Aneurysm Surgery A. RUDEHILL, E. GORDON and M. LAGERKRANSER Departmrnt of Anaesthesia, Karolinska Hospital, k'ac k, Stockholm, Swcden
Sodium nitroprusside (SNP) was used to induce hypotension during iiitratraniat aneurysm surgery in 67 patients. The effects of SNP infusion (0.1 mg/ml) on blood pressure were rapid and it was easy to adjust blood pressure to desired levels in most patients. When SNP was stopped, the blood pressure returned instantly to the initial level. In eight patients an increase to about 25% or more above preliypotensive level was seen, counteracted in two patients by administration of small doses of halothane. There was a mean increase of 36%) in heart rate. Total doses of SNP were 0.05-120 mg (mean: 10.8), corresponding to 0.08-6.8 pg/kg/min (mean: 1.9). No metabolic acidosis indicating cyanide intoxication was observed. Tachyphylaxis was seen in three patients, and SNP had to be discontinued in one. It is concluded that SNP gives a rapid and effective hypotension but tachyphylaxis and subsequent danger of cyanide intoxication exist. Therefore, in some cases SNP has to be replaced by or combined with some other hypotensive agent to achieve the desired effect. As thrre is a risk of impairment of cerebral autoregulation after the use of SNP, it is important to avoid sudden and prolonged blood pressure fluctuations, and to continue with controlled hypcrvcntilation in the postoperative period to reduce thr risk of brain oedema and high intracranial pressure.
Received 30 Nouember 1978, accejted for publicotiorr 3 Jariziary 1979
Many neurosurgeons consider controlled sodium nitroprusside (SNP) (MORACA et al. hypotension necessary to obtain the best 1962, SCHIFFMANN & FUCHS1966, JONES & operative results when treating intracranial COLE1968, TAYLOR et al. 1970, SIECEL et al. aneurysms (DRAKE1971, SIEGELet al. 1971, 1971, CORKILL & HODGSON 1973, S T Y L Eal. S~~ CORKILL& HODGSON 1973, AITKEN & 1973, WILDSMITH et al. 1973, DRAKE1974, DRAKE1974, YASHON et al. 1975, SIQUEIRA DAVIESet al. 1975a, LAWSON et al. 1976a, C(L REHNIA 1976). Halothane and ganglionAITKEN& HUSE 1977). SNP is a complex blocking agents, such as trimetaphan, have cyanide compound, which has the advantages been the most used hypotensive drugs during of a quick onset and a rapidly evanescent reccnt years. However, none of these agents action, and has been used for a long time to is ideal : halothane, besides its myocardial treat severe hypertensive crisis (PAGEet al. depressant effect (PRYS-ROBERTS et al. 1974), 1955). The purpose of the present study was increases cerebral blood flow and intracranial to assess SNP as a n agent for inducing hypopressure (GORDON 1968) ; trimetaphan liber- tension during the surgical treatment of ates histamine and often produces a pro- intracranial arterial aneurysms. nounced tachyphylaxis, which sometimes makes repeated reduction of blood pressure 1964). difficult ( LARSON MATERIAL AND METHODS An agent increasingly used during recent Sixty-seven patients (37 females and 30 males) wit years to produce controlled hypotension is cerebral arterial aneurysms were included in the stud. 0001-.517~/79/0~O404-07 $02.50/0
0 1979 The Scandinavian Society of Anarsthesiologist\
405
SODIUM NITROPRUSSIDE IN ANEURYSM SURGERY
in which SNP was used for controlled hypotension. The mean age was 45 years (range 18-65 ycars). Fourteen patients had a history of essential hypertension, while the rest were healthy prior to bleeding from their aneurysm. The patients’ conscious level before surgery was unaffected in 41 cases, whilst in 26 cases there was a decreased level of ronscionsness and/or other neurological defirits.
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Methods About l + hours before operation, the patients were premedicated with diazepam (10-15 mg) per rectum. Atropine 0.5 mg and droperidol 0.1 mg/kg body weight (b.w.) were given intravenously before induction. Anaesthesia was induced with tliiopentone (200500 mg), followed by phenoperidine (1-2 mg). Panccironium bromide 0.1 mg/kg b.w. was given before intubation. Anaesthesia was maintained with incremental doses of phenoperidine, pancuronium and a mixture of 60% N 2 0 and 40% 0 2 . Controlled hyperventilation was employed to achieve PacO, values between 3.5 and 4.0 kPa. Hypertonic mannitol (1.0-1.5 g/kg b.w.) infusion was given routinely to produce a further reduction of intracranial pressure and brain volume. After testing for sufficient collateral circulation to (he hand, a cannula was inserted percutaneously into the radial artery, from which blood samples for bloodgas analyses could be obtained at regular intervals. Systolic (BP), diastolic, mean arterial blood pressures (MABP), ECG and heart rate were continuously rrcorded on a Grass 8-channel polygraph. SNP (0.01%), 50 mg dissolved in 500 ml 5.5% glucose, was given by continuous infusion. As the exact effect of SNP in each individual case was difficult to predict, the infusion was always started at about 10-30 ml/h (0.016-0.05 mg/min). BP started to fall within 1-2 min in all cases. The rate of infusion was then adjusted to achieve the desired level of BP. Immediately after the ligation of the aneurysm, SNP infusion was stopped to allow the BP to return to the initial level. I n cases of a more pronounced overshoot of the BP, a low concentration of halothane was added to the gas mixture until BP returned to more normal levels. Postoperatively, 35 patients remained intubated and hyperventilated for periods varying from a few hours to several days, depending on their pre- and postoperative condition, the length of the operation, and any difficulties or complications arising during anaesthesia and operation. Thirty-two patients wcre extubated at the end of operation. The radial artery rannula was kept br situ to facilitate postoperative blood-gas analyses for 1-2 days.
RESULTS T h e mean value of MARP was 94 mmHg
BO
70
60
50 a
b
C
Fig. 1. Mean arterial blood pressure (O----.) and heart rate (x - - - x) changes with sodium nitroprusside. Mean values of 67 patients before (a), during (b) and after (c) hypotension. I = s.e. mean.
(12.5 kPa) before the start of SNP infusion and 66 mmHg (8.8 kPa) during hypotension (Fig. 1). The lowest value of MABP recorded in this series in one patient was 25 mmHg (3.3 kPa), which lasted 2 minutes. The BP increased within a few minutes on discontinuing the SNP infusion, in many cases to levels markedly higher than the initial BP. I n six patients, the MABP rose to approximately 2576 above the prehypotensive level and returned to the initial level after 10-120 min. Two patients whose MABP rose to about 50% above the initial value were given halothane for a short period to reduce BP and to maintain it at an acceptable level. Heart rate increased during hypotension ; the mean value prior to hypotension was 58 beatslmin and during hypotension 79 beats/
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no
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Fig. 2. Histogram showing number of patients grouped according to the duration of hypotension.
min. It returned to the initial level after the SNP infusion was stopped (see Fig. 1). One patient developed a severe tachycardia immediately after commencing the SNP infusion. It was necessary to discontinue SNP, and to change to halothane for the induction of hypotension. Two other patients developed a milder degree of tachyphylaxis during relatively longer periods of hypotension (239 and 111 min, respectively) and required increasing doses of SNP to maintain their RP at a steady level, although hypotension could be maintained using SNP as the sole agent throughout the operation. In 13 patients, supraventricular arrhythmias were observed during or after the hypotension. In one case of nodal arrhythmia, it took a considerable time for the BP to reach the prehypotensive level. The other arrhythmias observed were of no haemodynamic importance. Metabolic acidosis which could be related to the SNP infusion was not observed during operation or in the postoperative period. T h e duration of hypotension varied widely hetween 2 and 322 min (Fig. 2). Total doses
no
20.
15.
10.
5
n
Fig. 3. Histogram showing number ofpatients grouped according to total dose of sodium nitroprusside.
SODIUM NITROPRUSSIDE IN ANEURYSM SURGERY
40 7
method are well balanced; and, secondly, to choose the technique of inducing hypotension which is most easily managed with a minimal impact on vital organ function, both during operation and in t h e postoperative period. During recent years SNP has been a valuable alternative to previous drugs in achieving hypotension during surgery. One of the main problems with trimetaphan was the early development of tachyphylaxis (LARSON1964). This phenomenon, although less frequent, can also occur during the use of SNP, but some authors (STYLES et al. 1973, HUSE1977) have not given any report of its occurrence. Three of our patients developed tachyphylaxis soon after the start of SNP administration ; they had received relatively small doses. I n one of these cases we had to discontinue the SNP infusion because of a n alarmingly severe tachycardia. The cause of the development of tachyphylaxis is not well understood. I t could be a physiological sympathetic response attempt'-3 3-4 4 - 5 5 - 6 6 - 7 Pg/kg/min. ing to counteract a failing perfiision in vital organs (LAWSON et al. 1976b). POSNER et al. Fig. 4. Histogram showing number of patients grouped ( 1976a) postulated that tachyphylaxis trigaccording to dose of sodium nitroprusside in pg/kg/min. gered by SNP depends on a cyanide accumulation, initiating cyanide intoxication and consequent hypoxia. GRAYLING et al. (1978) of SNP varied between 0.05 and 120 mg demonstrated in uitro on isolated smooth (mean: 10.8) (Fig. 3 ), corresponding to a muscle a n antagonizing effect of cyanide to dose of 0.08-6.8 pg/kg/min (mean: 1.9) (Fig. SNP, indicating that serum cyanide forma4). The rather wide range of doses depended tion may be responsible for the development primarily on the duration of hypotension, but of tachyphylaxis. Cyanide intoxication - although extremely rare after small doses of also on individual sensitivity to the drug. SNP - may depend on a failure in the normal chains of metabolism where cyanide is conI)I SCUSSION verted to thiocyanate by the enzyme rhodanApart from factors beyond the control of the ase and endogenous thiosulfate. Hence many et al. 1974, POSNER anaesthesiologist (such as the general status authors (VESEY e t al. et al. 1976) recommend the of the patient and the intracranial condition 1976a, b, GREISS after the subarachnoid bleeding), the method prophylactic use of hydroxocobolamine as a n of anaesthesia and the technique used for antidote to cyanide whereby such early toxic controlled hypotension have a marked influ- effects can possibly be avoided. Another explanation of both thr tachyence on both systemic and cerebral haemodynamics. It is therefore imperative that, phylaxis and the overshoot reaction of the firstly, the indications for induced hypoten- BP seen after SNP infusion has been given by sion to a certain level should be very clear so MILLERet al. (1977). From experimental that the risks and possible advantages of the studies in rats they found that SNP-induced
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A . RUDEHILL F.?’ A L .
hypotension resulted in elevations of the plasma renin activity. These results were confirmed by LIENHAKT et al. (1978) in clinical studies where thcy found resistance to SNP together with particularly high levels of plasma renin activity. Prom these studies it is not quite clear whether the increased plasma renin activity is due to a specific efl’ect of SNP, or if it is a result of induced hypotension itself. However, HOFBAUER et al. (1976) have shown in experimental work that renin release varied inversely with renal perfusion pressure, and MITCH & WALKER(1977) demonstrated significantly raised plasma renin activity both in hypotensive, oliguric patients in shock and in patients during halothane- and trimetaphan-induced hypotension. It therefore seems probable that activation of the sympathetic nervous system contributes to renin release during anaesthesia (PETT~NGER et al. 1979). Moreover, the different anaesthetic agents and drugs used for inducing hypotension appear to influence renin rclease in diKerent ways, and the initial renin level also plays a role in determining changes in renin release (MILLERet al. 1978). These differences might explain why tachyphylaxis occurs in some patients and not in others. However, many more specific and detailed studies are needed to clarify further the role of renin in the development of tachyphylaxis during induced hypotension. Reports in the literature of a fatal outcome (MERRIFIELI) & BLUNIIELL 1974, .JACK 1974, DAVIESet al. 1975b) after the use of very high doses of SNP show that the use of this agent is not without risks. However, although exact dose limits cannot generally be given, it is important that when signs of tachyphylaxis develop (i.e. when increasing doses of SNP have to be administered in order to induce hypotension or to maintain blood pressure at a desired level), abandoning the SNP infusion has to be seriously considered. I n the present series the highest total dose of SNP required by one patient was 120 mg, which corresponds to a dose of 6.3 pg/kg/min. I n the majority of other cases we could
achieve the desired level of hypotension with much smaller total doses, thereby considerably minimizing the risks of intoxication. A crucial point when using SNP during intracranial surgery is its specific effect on cerebral blood flow (CRF) and intracranial pressure (ICP). Data from experimental studies (IVANKOVICH et al. 1976) suggest that SNP increases CBF in the presence of unchanged blood pressure. If hypotension is induced by SNP, when cerebral autoregulation is lost, any subsequent sudden increases in blood pressure can lead to brain damage. The impairment of cerebral autoregulation has also been confirmed by BROWNet a1 (1977) in conscious patients undergoing carotid angiography. They demonstrated that during the administration of SNP very slight reductions in blood pressure result in a significant reduction in the CBF. TURNER et al. (1977) have shown that the administration of SNP induced a significant increase in ICP if hypotension resulted in less than 30‘>:, reduction of base-line blood pressure. Only after a reduction of blood pressure below this level did I C P start to decrease; this could also be enhanced by hypocapnia. These experimental and clinical data suggest that at certain times during controlled hypotension, either during the phase of induction or immediately after hypotension, SNP can still have a vasodilatory effect on the cerebral vessels. At these times rapid fluctuations in blood pressure can outstrip the ability of the cerebral circulation to regulate its flow. In many patients of the present series, blood pressure rose to very high levels after the SNP infusion had been stopped, and it remained, in a few cases, at this high level for a considerable time. The risk of increased cerebral blood volume and vasogenic brain oedema with high I C P is evidently great under such circumstances, and therefore we consider it important to maintain controlled hyperventilation during the early part of the postoperative period. It can therefore be concluded that SNP seems to be a useful hypotensive drug since,
S 0 I ) I U M NITROPRUSSIDE IN ANEURYSM SURGERY
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of angiotensin. Studies in the isolated perfused rat kidney. Clin. exp. Pharmacol. Physiol. 3, 73. HUSE,K. (1977) Die kontrollierte Hypotension mit Nitroprussidnatrium in der Neuroanaesthesie, Aiiaeslhesiologie und Wiederbelebung. Springer-Verlag, Berlin, Heidelberg, New York, p. 107. ~ V A N K O V I C H ,A . D., MILETICH, D. J., ALBRECIIT, R. F. & ZAEIED,B. (1976) Sodium nitroprusside and cerebral blood flow in the anesthetizrd and unanesthetized goat. AiiesthesioloLu44, 2 1. ,JACK,R. D. (1974) Toxicity of sodium nitroprusside. &it. 3.Armesth. 46, 952. JONES, G. 0. M. & COLE, P. (1968) Sodium nitroprusside as a hypotensive agent. Brit. 3. Anaesth. 40, 804. LARSON, A. G. (1964) Deliberate hypotension. Anesthesiology 25, 682. LAWSON, N. W., THOMPSON, D. S., NELSON,C. L., FLACKE, J. W. & NORTH,E. R. (1976a) Sodium nitroprusside-induced hypotension for supine total hip replacement. Anesth. Analg. 55, 654. LAWSON, N. W., THOMPSON, D. S., NELSON,C. L., FLACKE, J. W. & SEIFEN,A. B. (1976b) A dosage nomogram for sodium nitroprusside-induced liypoREFERENCES tension under anesthesia. Anesth. Analg. 55, 574. AITKEN,R. K. & DRAKB,C. G. (1974) A technique of J., DE LIENIIART,A., PEROL, M., ANTREASSIAN, anesthesia with induced hypotension for surgical VICTOR,D., PERTUISET,B. & VIARS, P. (1978) correction of intracranial aneurysms. Clin. Neurosiq. Variations in plasma renin activity in the course of 10, 107. deep hypotension induced by sodium nitroprusside. BROWN,F. D., HANLON,K., CROCKARD, H. A. & Vth European Congress of Anaesthesiology, Paris, MIJLLAN, S. (1977) Effect ofsodiirm nitroprusside on France, Sept. 4-9, 1978. Excerpta Medica, International Congress Series No. 452. cerebral blood flow in conscious human beings. Svrg. .Neural. 7, 67. MERRIFIELD, A. J. & BLUNDELL, M. D. (1974) Toxicity CORKILL, G. & HODGSON, J. (1973) Hypotension with of sodium nitroprusside. Brit.3. Anaesth. 46, 324. J. A. & PEACII,M. J. sodium nitroprusside in the surgery of cerebral MILLER,JR., E. D., ACKERLY, aneurysms. AnaestheJia 28, 191. (1978) Blood pressure support during general DAVIES, D. I%',, GREISS,L. & STEWARD, D. J. (1975a) anesthesia in a renin-dependent state in the rat. Anesthesiology 48, 404. Sodium nitropriisside in children: Observations on metabolism during normal and abnormal responses. MILLER,JR. E. D., ACKERLY, J. A., VAUGIIAN, JK. Canad. Annestti. Sac. 3. 22, 553. E. D., PEACH, M.J. & EPSTEIN,R. M. (1977) The renin-angiotensin system during controlled hypotenDAVIES, D. W., KADAR,D., STEWARD, D. J. & MUNRO, sion with sodium nitroprusside Anesthesiology 47,257. I . R. (1975b) A sudden death associated with the use MITCH,W. E. & WALKER, of sodium nitroprusside for induction of hypotension W. G. (1977) Plasma renin during anaesthesia. Canad. Anaesth. Sac. 3. 22, 547. angiotensin I1 in acute renal failure. Laiicet ii, 328. P. P., BITTE,E. M., HALE,D. E., WASMUTfI, DRAKE, C. C. (1971) Ruptured intracranial aneurysms. MORACA, Proc. roy. Sac. Med. 64, 477. C . E. & POUTASSE, E. F. (1962) Clinical evaluation of sodium nitroprusside as a hypotensive agent. GOKDON, E. (1968) The action of drugs on the intraAnesthesiology 23, 193. cranial contents. Proceedings of the ZVth World Congress PAGE, I. H., CORCORAN, A. C., DUSTAN, H. P. & of Anaesthesiologists, ed. T . B. BOULTON. Excepta KAPPANYI,T. (1955) Cardiovascular actions of Medica, London, Amsterdam, New York, p. 60. sodium nitroprusside in animals and hypertensive GRAYLING, G. W., MILLEK,.]R.E. D. & PEACH,M. J. patients. Circulation 11, 188. (1978) Sodium cyanide antagonism of the vasoW. A., GRAHAM, R. M. & KEETON,T. K. dilator action of sodium nitroprusside in the isolated PETTINGER, (1979) T h e role of beta-adrenoreceptors in mediarabbit aortic strip. Anesthesiology 49, 2 I . tion of renin release. Excerpt. Med. In press. GREISS,L., TREMBLAY, N. A. G. & DAVIES,D. M.'. (1976) The toxicity of sodium nitroprusside. Cnnad. POSNER, M. A ,, RODKEY, F. L. & TOBEY, R. E. (1976a) Nitroprusside-induced cyanide poisoning. Antidotal Anaesth. Sac. 3. 23, 480. effect of hydroxocobolamin. Anesthesiology 44, 330. HOFBAUER, K. G., ZSCHIEDKICH, H. & GROSS, Y. (1976) H. (1976b) Regulation of renin release and intrarenal formation POSNER, M. A,, TOBEY,R. E. & MCELROY,
in most cases, it can be readily adjusted to give a precise and rapid control of blood pressure. However, some patients are highly resistant to this agent and react with more or less severe cardiovascular symptoms, such as extreme tachycardia and arrhythmias. I n such cases a trial can be made to combine SNP with some other hypotensive agent, but if an immediately favourable response is not attained, the administration of SNP should be abandoned. Furthermore, it is evident that the risks of immediate postoperative disturbances of cerebral autoregulation after SNP-hypotension are sufficiently great to warrant continued controlled hyperventilation in this period to avoid or minimize brain oedema and high ICP.
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Hydroxocobolamin therapy of cyanide intoxication in guinea pigs. Anesthesiology 44, 157. PRYS-ROBERTS, C., LLOYD,.I. W., FISHER, A., KEKR, .J. H. & PATTERSON, T. J. S. (1974) Deliberate profound hypotension induced with halothane: Studies of haemodynamics and pulmonary gas exchange. Brit. 3. Auaesth. 46, 105. SCIIIFFMANN, H. & FtJClIS, P. (1966) Controlled hypotension effected by sodium nitroprusside. Acta nnnesth. scnird. Suppl. 23, 704. SIEGEL, P., MOKACA, P. P. & GREEN,J. R . (1971) Sodium nitroprusside in the surgical treatment of cerebral aneurysms and arteriovenous malformations. Brit. 3. Anaesth. 43, 790. SlQtJEIRA, E. B. & BEHNIA,R. (1976) Prolonged, profound hypotension produced safely with sodium nitroprusside. Surf. ,Veifrol. 6 , 169. STYLES, M., COLEMAN, A. J. (L LEARY,W. P. (1973) Some hemodynamic effects of sodium nitroprusside. Anesthesiology 38, 173. 'rAYLOR, T. H., STYLES, M. & LAMMING, A. J. (1970) Sodium nitroprusside as a hypotensive agent in general anaesthesia. Brit. 3.Anaesth. 42, 859. TURNER, .J. M., POWELL,D., GIBSON,R . M. &
MCDOWALL, D. G. (1977) Intracranial pressurr changes in neurosurgical patients during hypotension induced with sodium nitroprnssidr or trinictaphan. Brit. 3. Annesth. 49, 419. VESEY,C . J . ,COLE,P. V., I J N N E L I . , . ~C:. . & M'II.soN,,J. (1974) Some metabolic effccts o l sodium nitroprusside in man. Brit. med. 3. 2 , 140. CtrlLDSMITH, .J. A. W., MARSHALL, l
Sodium Nitroprusside as a Hypotensive Agent in Intracranial Aneurysm Surgery A. RUDEHILL, E. GORDON and M. LAGERKRANSER Departmrnt of Anaesthesia, Karolinska Hospital, k'ac k, Stockholm, Swcden
Sodium nitroprusside (SNP) was used to induce hypotension during iiitratraniat aneurysm surgery in 67 patients. The effects of SNP infusion (0.1 mg/ml) on blood pressure were rapid and it was easy to adjust blood pressure to desired levels in most patients. When SNP was stopped, the blood pressure returned instantly to the initial level. In eight patients an increase to about 25% or more above preliypotensive level was seen, counteracted in two patients by administration of small doses of halothane. There was a mean increase of 36%) in heart rate. Total doses of SNP were 0.05-120 mg (mean: 10.8), corresponding to 0.08-6.8 pg/kg/min (mean: 1.9). No metabolic acidosis indicating cyanide intoxication was observed. Tachyphylaxis was seen in three patients, and SNP had to be discontinued in one. It is concluded that SNP gives a rapid and effective hypotension but tachyphylaxis and subsequent danger of cyanide intoxication exist. Therefore, in some cases SNP has to be replaced by or combined with some other hypotensive agent to achieve the desired effect. As thrre is a risk of impairment of cerebral autoregulation after the use of SNP, it is important to avoid sudden and prolonged blood pressure fluctuations, and to continue with controlled hypcrvcntilation in the postoperative period to reduce thr risk of brain oedema and high intracranial pressure.
Received 30 Nouember 1978, accejted for publicotiorr 3 Jariziary 1979
Many neurosurgeons consider controlled sodium nitroprusside (SNP) (MORACA et al. hypotension necessary to obtain the best 1962, SCHIFFMANN & FUCHS1966, JONES & operative results when treating intracranial COLE1968, TAYLOR et al. 1970, SIECEL et al. aneurysms (DRAKE1971, SIEGELet al. 1971, 1971, CORKILL & HODGSON 1973, S T Y L Eal. S~~ CORKILL& HODGSON 1973, AITKEN & 1973, WILDSMITH et al. 1973, DRAKE1974, DRAKE1974, YASHON et al. 1975, SIQUEIRA DAVIESet al. 1975a, LAWSON et al. 1976a, C(L REHNIA 1976). Halothane and ganglionAITKEN& HUSE 1977). SNP is a complex blocking agents, such as trimetaphan, have cyanide compound, which has the advantages been the most used hypotensive drugs during of a quick onset and a rapidly evanescent reccnt years. However, none of these agents action, and has been used for a long time to is ideal : halothane, besides its myocardial treat severe hypertensive crisis (PAGEet al. depressant effect (PRYS-ROBERTS et al. 1974), 1955). The purpose of the present study was increases cerebral blood flow and intracranial to assess SNP as a n agent for inducing hypopressure (GORDON 1968) ; trimetaphan liber- tension during the surgical treatment of ates histamine and often produces a pro- intracranial arterial aneurysms. nounced tachyphylaxis, which sometimes makes repeated reduction of blood pressure 1964). difficult ( LARSON MATERIAL AND METHODS An agent increasingly used during recent Sixty-seven patients (37 females and 30 males) wit years to produce controlled hypotension is cerebral arterial aneurysms were included in the stud. 0001-.517~/79/0~O404-07 $02.50/0
0 1979 The Scandinavian Society of Anarsthesiologist\
405
SODIUM NITROPRUSSIDE IN ANEURYSM SURGERY
in which SNP was used for controlled hypotension. The mean age was 45 years (range 18-65 ycars). Fourteen patients had a history of essential hypertension, while the rest were healthy prior to bleeding from their aneurysm. The patients’ conscious level before surgery was unaffected in 41 cases, whilst in 26 cases there was a decreased level of ronscionsness and/or other neurological defirits.
i/rnin
I
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90
Methods About l + hours before operation, the patients were premedicated with diazepam (10-15 mg) per rectum. Atropine 0.5 mg and droperidol 0.1 mg/kg body weight (b.w.) were given intravenously before induction. Anaesthesia was induced with tliiopentone (200500 mg), followed by phenoperidine (1-2 mg). Panccironium bromide 0.1 mg/kg b.w. was given before intubation. Anaesthesia was maintained with incremental doses of phenoperidine, pancuronium and a mixture of 60% N 2 0 and 40% 0 2 . Controlled hyperventilation was employed to achieve PacO, values between 3.5 and 4.0 kPa. Hypertonic mannitol (1.0-1.5 g/kg b.w.) infusion was given routinely to produce a further reduction of intracranial pressure and brain volume. After testing for sufficient collateral circulation to (he hand, a cannula was inserted percutaneously into the radial artery, from which blood samples for bloodgas analyses could be obtained at regular intervals. Systolic (BP), diastolic, mean arterial blood pressures (MABP), ECG and heart rate were continuously rrcorded on a Grass 8-channel polygraph. SNP (0.01%), 50 mg dissolved in 500 ml 5.5% glucose, was given by continuous infusion. As the exact effect of SNP in each individual case was difficult to predict, the infusion was always started at about 10-30 ml/h (0.016-0.05 mg/min). BP started to fall within 1-2 min in all cases. The rate of infusion was then adjusted to achieve the desired level of BP. Immediately after the ligation of the aneurysm, SNP infusion was stopped to allow the BP to return to the initial level. I n cases of a more pronounced overshoot of the BP, a low concentration of halothane was added to the gas mixture until BP returned to more normal levels. Postoperatively, 35 patients remained intubated and hyperventilated for periods varying from a few hours to several days, depending on their pre- and postoperative condition, the length of the operation, and any difficulties or complications arising during anaesthesia and operation. Thirty-two patients wcre extubated at the end of operation. The radial artery rannula was kept br situ to facilitate postoperative blood-gas analyses for 1-2 days.
RESULTS T h e mean value of MARP was 94 mmHg
BO
70
60
50 a
b
C
Fig. 1. Mean arterial blood pressure (O----.) and heart rate (x - - - x) changes with sodium nitroprusside. Mean values of 67 patients before (a), during (b) and after (c) hypotension. I = s.e. mean.
(12.5 kPa) before the start of SNP infusion and 66 mmHg (8.8 kPa) during hypotension (Fig. 1). The lowest value of MABP recorded in this series in one patient was 25 mmHg (3.3 kPa), which lasted 2 minutes. The BP increased within a few minutes on discontinuing the SNP infusion, in many cases to levels markedly higher than the initial BP. I n six patients, the MABP rose to approximately 2576 above the prehypotensive level and returned to the initial level after 10-120 min. Two patients whose MABP rose to about 50% above the initial value were given halothane for a short period to reduce BP and to maintain it at an acceptable level. Heart rate increased during hypotension ; the mean value prior to hypotension was 58 beatslmin and during hypotension 79 beats/
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A . RU1)EHII.L ET AL.
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Fig. 2. Histogram showing number of patients grouped according to the duration of hypotension.
min. It returned to the initial level after the SNP infusion was stopped (see Fig. 1). One patient developed a severe tachycardia immediately after commencing the SNP infusion. It was necessary to discontinue SNP, and to change to halothane for the induction of hypotension. Two other patients developed a milder degree of tachyphylaxis during relatively longer periods of hypotension (239 and 111 min, respectively) and required increasing doses of SNP to maintain their RP at a steady level, although hypotension could be maintained using SNP as the sole agent throughout the operation. In 13 patients, supraventricular arrhythmias were observed during or after the hypotension. In one case of nodal arrhythmia, it took a considerable time for the BP to reach the prehypotensive level. The other arrhythmias observed were of no haemodynamic importance. Metabolic acidosis which could be related to the SNP infusion was not observed during operation or in the postoperative period. T h e duration of hypotension varied widely hetween 2 and 322 min (Fig. 2). Total doses
no
20.
15.
10.
5
n
Fig. 3. Histogram showing number ofpatients grouped according to total dose of sodium nitroprusside.
SODIUM NITROPRUSSIDE IN ANEURYSM SURGERY
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method are well balanced; and, secondly, to choose the technique of inducing hypotension which is most easily managed with a minimal impact on vital organ function, both during operation and in t h e postoperative period. During recent years SNP has been a valuable alternative to previous drugs in achieving hypotension during surgery. One of the main problems with trimetaphan was the early development of tachyphylaxis (LARSON1964). This phenomenon, although less frequent, can also occur during the use of SNP, but some authors (STYLES et al. 1973, HUSE1977) have not given any report of its occurrence. Three of our patients developed tachyphylaxis soon after the start of SNP administration ; they had received relatively small doses. I n one of these cases we had to discontinue the SNP infusion because of a n alarmingly severe tachycardia. The cause of the development of tachyphylaxis is not well understood. I t could be a physiological sympathetic response attempt'-3 3-4 4 - 5 5 - 6 6 - 7 Pg/kg/min. ing to counteract a failing perfiision in vital organs (LAWSON et al. 1976b). POSNER et al. Fig. 4. Histogram showing number of patients grouped ( 1976a) postulated that tachyphylaxis trigaccording to dose of sodium nitroprusside in pg/kg/min. gered by SNP depends on a cyanide accumulation, initiating cyanide intoxication and consequent hypoxia. GRAYLING et al. (1978) of SNP varied between 0.05 and 120 mg demonstrated in uitro on isolated smooth (mean: 10.8) (Fig. 3 ), corresponding to a muscle a n antagonizing effect of cyanide to dose of 0.08-6.8 pg/kg/min (mean: 1.9) (Fig. SNP, indicating that serum cyanide forma4). The rather wide range of doses depended tion may be responsible for the development primarily on the duration of hypotension, but of tachyphylaxis. Cyanide intoxication - although extremely rare after small doses of also on individual sensitivity to the drug. SNP - may depend on a failure in the normal chains of metabolism where cyanide is conI)I SCUSSION verted to thiocyanate by the enzyme rhodanApart from factors beyond the control of the ase and endogenous thiosulfate. Hence many et al. 1974, POSNER anaesthesiologist (such as the general status authors (VESEY e t al. et al. 1976) recommend the of the patient and the intracranial condition 1976a, b, GREISS after the subarachnoid bleeding), the method prophylactic use of hydroxocobolamine as a n of anaesthesia and the technique used for antidote to cyanide whereby such early toxic controlled hypotension have a marked influ- effects can possibly be avoided. Another explanation of both thr tachyence on both systemic and cerebral haemodynamics. It is therefore imperative that, phylaxis and the overshoot reaction of the firstly, the indications for induced hypoten- BP seen after SNP infusion has been given by sion to a certain level should be very clear so MILLERet al. (1977). From experimental that the risks and possible advantages of the studies in rats they found that SNP-induced
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hypotension resulted in elevations of the plasma renin activity. These results were confirmed by LIENHAKT et al. (1978) in clinical studies where thcy found resistance to SNP together with particularly high levels of plasma renin activity. Prom these studies it is not quite clear whether the increased plasma renin activity is due to a specific efl’ect of SNP, or if it is a result of induced hypotension itself. However, HOFBAUER et al. (1976) have shown in experimental work that renin release varied inversely with renal perfusion pressure, and MITCH & WALKER(1977) demonstrated significantly raised plasma renin activity both in hypotensive, oliguric patients in shock and in patients during halothane- and trimetaphan-induced hypotension. It therefore seems probable that activation of the sympathetic nervous system contributes to renin release during anaesthesia (PETT~NGER et al. 1979). Moreover, the different anaesthetic agents and drugs used for inducing hypotension appear to influence renin rclease in diKerent ways, and the initial renin level also plays a role in determining changes in renin release (MILLERet al. 1978). These differences might explain why tachyphylaxis occurs in some patients and not in others. However, many more specific and detailed studies are needed to clarify further the role of renin in the development of tachyphylaxis during induced hypotension. Reports in the literature of a fatal outcome (MERRIFIELI) & BLUNIIELL 1974, .JACK 1974, DAVIESet al. 1975b) after the use of very high doses of SNP show that the use of this agent is not without risks. However, although exact dose limits cannot generally be given, it is important that when signs of tachyphylaxis develop (i.e. when increasing doses of SNP have to be administered in order to induce hypotension or to maintain blood pressure at a desired level), abandoning the SNP infusion has to be seriously considered. I n the present series the highest total dose of SNP required by one patient was 120 mg, which corresponds to a dose of 6.3 pg/kg/min. I n the majority of other cases we could
achieve the desired level of hypotension with much smaller total doses, thereby considerably minimizing the risks of intoxication. A crucial point when using SNP during intracranial surgery is its specific effect on cerebral blood flow (CRF) and intracranial pressure (ICP). Data from experimental studies (IVANKOVICH et al. 1976) suggest that SNP increases CBF in the presence of unchanged blood pressure. If hypotension is induced by SNP, when cerebral autoregulation is lost, any subsequent sudden increases in blood pressure can lead to brain damage. The impairment of cerebral autoregulation has also been confirmed by BROWNet a1 (1977) in conscious patients undergoing carotid angiography. They demonstrated that during the administration of SNP very slight reductions in blood pressure result in a significant reduction in the CBF. TURNER et al. (1977) have shown that the administration of SNP induced a significant increase in ICP if hypotension resulted in less than 30‘>:, reduction of base-line blood pressure. Only after a reduction of blood pressure below this level did I C P start to decrease; this could also be enhanced by hypocapnia. These experimental and clinical data suggest that at certain times during controlled hypotension, either during the phase of induction or immediately after hypotension, SNP can still have a vasodilatory effect on the cerebral vessels. At these times rapid fluctuations in blood pressure can outstrip the ability of the cerebral circulation to regulate its flow. In many patients of the present series, blood pressure rose to very high levels after the SNP infusion had been stopped, and it remained, in a few cases, at this high level for a considerable time. The risk of increased cerebral blood volume and vasogenic brain oedema with high I C P is evidently great under such circumstances, and therefore we consider it important to maintain controlled hyperventilation during the early part of the postoperative period. It can therefore be concluded that SNP seems to be a useful hypotensive drug since,
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of angiotensin. Studies in the isolated perfused rat kidney. Clin. exp. Pharmacol. Physiol. 3, 73. HUSE,K. (1977) Die kontrollierte Hypotension mit Nitroprussidnatrium in der Neuroanaesthesie, Aiiaeslhesiologie und Wiederbelebung. Springer-Verlag, Berlin, Heidelberg, New York, p. 107. ~ V A N K O V I C H ,A . D., MILETICH, D. J., ALBRECIIT, R. F. & ZAEIED,B. (1976) Sodium nitroprusside and cerebral blood flow in the anesthetizrd and unanesthetized goat. AiiesthesioloLu44, 2 1. ,JACK,R. D. (1974) Toxicity of sodium nitroprusside. &it. 3.Armesth. 46, 952. JONES, G. 0. M. & COLE, P. (1968) Sodium nitroprusside as a hypotensive agent. Brit. 3. Anaesth. 40, 804. LARSON, A. G. (1964) Deliberate hypotension. Anesthesiology 25, 682. LAWSON, N. W., THOMPSON, D. S., NELSON,C. L., FLACKE, J. W. & NORTH,E. R. (1976a) Sodium nitroprusside-induced hypotension for supine total hip replacement. Anesth. Analg. 55, 654. LAWSON, N. W., THOMPSON, D. S., NELSON,C. L., FLACKE, J. W. & SEIFEN,A. B. (1976b) A dosage nomogram for sodium nitroprusside-induced liypoREFERENCES tension under anesthesia. Anesth. Analg. 55, 574. AITKEN,R. K. & DRAKB,C. G. (1974) A technique of J., DE LIENIIART,A., PEROL, M., ANTREASSIAN, anesthesia with induced hypotension for surgical VICTOR,D., PERTUISET,B. & VIARS, P. (1978) correction of intracranial aneurysms. Clin. Neurosiq. Variations in plasma renin activity in the course of 10, 107. deep hypotension induced by sodium nitroprusside. BROWN,F. D., HANLON,K., CROCKARD, H. A. & Vth European Congress of Anaesthesiology, Paris, MIJLLAN, S. (1977) Effect ofsodiirm nitroprusside on France, Sept. 4-9, 1978. Excerpta Medica, International Congress Series No. 452. cerebral blood flow in conscious human beings. Svrg. .Neural. 7, 67. MERRIFIELD, A. J. & BLUNDELL, M. D. (1974) Toxicity CORKILL, G. & HODGSON, J. (1973) Hypotension with of sodium nitroprusside. Brit.3. Anaesth. 46, 324. J. A. & PEACII,M. J. sodium nitroprusside in the surgery of cerebral MILLER,JR., E. D., ACKERLY, aneurysms. AnaestheJia 28, 191. (1978) Blood pressure support during general DAVIES, D. I%',, GREISS,L. & STEWARD, D. J. (1975a) anesthesia in a renin-dependent state in the rat. Anesthesiology 48, 404. Sodium nitropriisside in children: Observations on metabolism during normal and abnormal responses. MILLER,JR. E. D., ACKERLY, J. A., VAUGIIAN, JK. Canad. Annestti. Sac. 3. 22, 553. E. D., PEACH, M.J. & EPSTEIN,R. M. (1977) The renin-angiotensin system during controlled hypotenDAVIES, D. W., KADAR,D., STEWARD, D. J. & MUNRO, sion with sodium nitroprusside Anesthesiology 47,257. I . R. (1975b) A sudden death associated with the use MITCH,W. E. & WALKER, of sodium nitroprusside for induction of hypotension W. G. (1977) Plasma renin during anaesthesia. Canad. Anaesth. Sac. 3. 22, 547. angiotensin I1 in acute renal failure. Laiicet ii, 328. P. P., BITTE,E. M., HALE,D. E., WASMUTfI, DRAKE, C. C. (1971) Ruptured intracranial aneurysms. MORACA, Proc. roy. Sac. Med. 64, 477. C . E. & POUTASSE, E. F. (1962) Clinical evaluation of sodium nitroprusside as a hypotensive agent. GOKDON, E. (1968) The action of drugs on the intraAnesthesiology 23, 193. cranial contents. Proceedings of the ZVth World Congress PAGE, I. H., CORCORAN, A. C., DUSTAN, H. P. & of Anaesthesiologists, ed. T . B. BOULTON. Excepta KAPPANYI,T. (1955) Cardiovascular actions of Medica, London, Amsterdam, New York, p. 60. sodium nitroprusside in animals and hypertensive GRAYLING, G. W., MILLEK,.]R.E. D. & PEACH,M. J. patients. Circulation 11, 188. (1978) Sodium cyanide antagonism of the vasoW. A., GRAHAM, R. M. & KEETON,T. K. dilator action of sodium nitroprusside in the isolated PETTINGER, (1979) T h e role of beta-adrenoreceptors in mediarabbit aortic strip. Anesthesiology 49, 2 I . tion of renin release. Excerpt. Med. In press. GREISS,L., TREMBLAY, N. A. G. & DAVIES,D. M.'. (1976) The toxicity of sodium nitroprusside. Cnnad. POSNER, M. A ,, RODKEY, F. L. & TOBEY, R. E. (1976a) Nitroprusside-induced cyanide poisoning. Antidotal Anaesth. Sac. 3. 23, 480. effect of hydroxocobolamin. Anesthesiology 44, 330. HOFBAUER, K. G., ZSCHIEDKICH, H. & GROSS, Y. (1976) H. (1976b) Regulation of renin release and intrarenal formation POSNER, M. A,, TOBEY,R. E. & MCELROY,
in most cases, it can be readily adjusted to give a precise and rapid control of blood pressure. However, some patients are highly resistant to this agent and react with more or less severe cardiovascular symptoms, such as extreme tachycardia and arrhythmias. I n such cases a trial can be made to combine SNP with some other hypotensive agent, but if an immediately favourable response is not attained, the administration of SNP should be abandoned. Furthermore, it is evident that the risks of immediate postoperative disturbances of cerebral autoregulation after SNP-hypotension are sufficiently great to warrant continued controlled hyperventilation in this period to avoid or minimize brain oedema and high ICP.
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MCDOWALL, D. G. (1977) Intracranial pressurr changes in neurosurgical patients during hypotension induced with sodium nitroprnssidr or trinictaphan. Brit. 3. Annesth. 49, 419. VESEY,C . J . ,COLE,P. V., I J N N E L I . , . ~C:. . & M'II.soN,,J. (1974) Some metabolic effccts o l sodium nitroprusside in man. Brit. med. 3. 2 , 140. CtrlLDSMITH, .J. A. W., MARSHALL, l
