Division of Critical Care Medicine, London Health Sciences Centre University Campus, University of Western Ontario, London, Ontario, Canada N6A 5A5. Present Address: Department of Anesthesia & Critical Care, King Abdulaziz University Hospital, King Abdulaziz University, PO Box 31648, Jeddah 21418, Saudi Arabia
Accepted for publication: August 17, 2000
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Abstract |
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Br J Anaesth 2001; 86: 13841
Keywords: sympathetic nervous system, phenylephrine; receptors, adrenergic; complications, tachyphylaxis
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Introduction |
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Case history |
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Despite the maintenance of adequate hydration (CVP and PAOP 12 mm Hg) and the presence of normal cardiac function (cardiac index
4.0 litre min1 m2), the phenylephrine dose had to be increased 3 days after starting the vasopressor therapy to maintain the same initial target SBP of 170190 mm Hg. There was no clinical or laboratory evidence of infection, renal dysfunction or acidbase disturbance at any time. The patient continued to have clinical evidence of cerebral vasospasm as her conscious state consistently deteriorated and then rapidly returned to normal whenever her SBP decreased below 170 mm Hg and was then restored. These transient episodes of relative hypotension occurred in relation to medication bag replacement and after nimodipine administration. The nimodipine dose was halved and then discontinued because hypotension occurred after each dose of nimodipine. On day 14 after SAH, a morning serum cortisol sample was taken and hydrocortisone 100 mg i.v. every 8 h was started, with a consequent reduction in phenylephrine infusion rate from a maximum of 2000 µg min1 to 800 µg min1. This decrease in vasopressor requirement occurred after three doses of hydrocortisone and without changing the target SBP (Fig. 1). The serum cortisol concentration was 566 nmol litre1 (normal range 119618 nmol litre1) and the patient maintained normal acidbase and renal function. Phenylephrine dose requirement continued to decline to 50100 µg min1, to give an SBP of 170190 mm Hg. After five doses, hydrocortisone was discontinued without any increase in phenylephrine dose requirement or any change in the target SBP. On day 17 after the SAH, the phenylephrine infusion rate was gradually decreased and then stopped. The SBP returned to 140 mm Hg without any change in the patients condition. On day 18 after the SAH, the patient was discharged from the ICU, with persistent left hemiparesis.
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Discussion |
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Although receptor reappearance has been described after stopping the adrenoceptor agonist,13 withholding phenylephrine was not possible in this patient because of persistent cerebral vasospasm, shown by the reproducible deterioration in the patients level of consciousness whenever her SBP decreased below 170 mm Hg, during medication bag replacement and after nimodipine administration. Halving the dose of nimodipine did not affect the decrease in SBP, with a concomitant deterioration in the patients level of consciousness after the administration of each dose of the drug. Corticosteroids prevent homologous down-regulation of ß2 receptors14 and up-regulate lymphocyte ß receptors.15 16 In addition, Aziz et al.17 have reported that inhaled budesonide resensitizes the cardiac ß2 receptor response to salbutamol in patients treated with long-acting ß2 agonists. Bollaert et al.18 described an improvement in the haemodynamic profile of patients with late septic shock who were treated with hydrocortisone in the absence of adrenal insufficiency. In this case report, vasopressor requirements were reduced by 50% within 12 h of hydrocortisone administration (Fig. 1), with no change in the patients CVP, PAOP or cardiac index, and with no clinical or laboratory evidence of adrenal insufficiency, acidbase disorder or renal dysfunction. On the basis of the study of Bollaert et al.18 and because the phenylephrine dose requirement decreased to a reasonable level of 50100 µg min1, hydrocortisone was stopped after five doses of the drug.
Although steroid-induced up-regulation of the adrenoceptors is one possible explanation for the decrease in phenylephrine requirement, another potentially plausible explanation is steroid-induced inhibition of nitric oxide synthase (NOS). Inhibition of this enzyme decreases endogenous production of nitric oxide (NO), a potent vasodilator that has been implicated in vascular hyporeactivity. This potential mechanism is supported by the findings of Szabo et al.,19 who found that NO-induced vascular hyporeactivity was reduced after dexamethasone, an NOS inhibitor. Similar findings were observed by Thiemermann and colleagues in rats with haemorrhagic shock.20 Whether the administration of large doses of phenylephrine induces the enzyme NOS is an intriguing question, but steroid-induced NOS inhibition has been shown only in animals. Future human studies are needed.
In conclusion, this case report demonstrated that short-term i.v. hydrocortisone decreased the escalating phenylephrine dose requirements in a patient with SAH who was being treated with induced hypertension to counteract cerebral vasospasm. Although adrenoceptor up-regulation in response to steroid therapy is a plausible explanation, the exact mechanism of the steroid-induced reduction in vasopressor requirement remains undetermined. Studies on the effect of steroids on vascular hyporeactivity in response to prolonged administration of an adrenoceptor agonist are warranted.
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References |
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