Terlipressin for refractory hypotension following angiotensin‐II receptor antagonist overdose

Abstract

A 54-year-old female presented to the Emergency Department following the ingestion of 32 tablets containing a combination of irbesartan 300 mg and hydrochlorothiazide 12.5 mg (CoAprovel, Bristol-Myers Squibb, Uxbridge, UK) and an unknown quantity of diazepam, paracetamol and alcohol. She had a past history of hypertension and alcohol dependency. On admission her arterial pressure was 95/50 mmHg and she had a sinus tachycardia (105 min−1). Seven hours after ingestion she became profoundly hypotensive and despite 2 litres of fluid her arterial pressure was 72/35 mmHg, with a central venous pressure of 13 mmHg. The patient developed 4 mm ST segment depression in leads V2-V5 but remained asymptomatic. She was administered ephedrine 30 mg with no response, and was transferred to ICU, where an infusion of phenylephrine 0.6 μg.kg−1.min−1 was started, with little improvement. The phenylephrine was stopped and norepinephrine and dobutamine were commenced, but despite increasing these to 0.25 μg.kg−1.min−1 and 10 μg.kg−1.min−1, respectively, she remained hypotensive. We decided to administer terlipressin 1 mg (Glypressin, Ferring, Malmö, Sweden) by slow intravenous bolus. Within 2 h her arterial pressure was within normal limits and she could be weaned off all vasopressors and inotropes. She remained normotensive, enabling transfer to the ward the following day, during which her observations were satisfactory. She was discharged home 2 days later after a psychiatric consultation. Patients who have been chronically treated with angiotensin receptor antagonists (AIIR1) have been shown to exhibit hypotension after induction of anaesthesia, which is often refractory to classical vasoconstrictor therapy [1]. As both the sympathetic and renin-angiotensin systems are blunted, the role of the vasopressin in restoring arterial pressure in these cases has been proposed [2]. Arginine-vasopressin, a postpituitary nine amino-acid peptide, stimulates vasopressin receptors – notably the vascular V1a receptors, to cause marked arterial constriction and has been used for septic and catecholamine resistant shock [3, 4]. It has also been shown to improve cerebral blood flow in resuscitation and is included in American Heart Association resuscitation guidelines [5, 6]. Terlipressin (triglycycl–lysine vasopressin) is a drug precursor slowly metabolised to lysine-vasopressin by plasma esterases. It has been reported to be effective in the treatment of vasodilatory shock secondary to calcium-channel blocker overdose and bupivacaine intoxication [7, 8]. Terlipressin was shown to be effective in rapidly restoring arterial pressure with no concomitant impairment in the left ventricular function in patients chronically treated with AIIR1 antagonists who presented with refractory hypotension after induction of anaesthesia [2]. Although our patient was not under general anaesthesia, the normal physiological mechanisms involved in maintaining blood pressure were blunted by the supranormal dose of AIIR1 antagonists. The resulting hypotension would have been caused by vasodilation and decrease in vascular adrenergic receptor sensitivity limiting the clinical effect of adrenergic drugs. Terlipressin results in limited postoperative hypertension and tachycardia [3]. A report of cardiac ischaemia following terlipressin used for treating intra-operative hypotension was associated with an acute increase in left ventricular afterload [9]. We feel that myocardial ischaemia on ECG in our patient was caused by a decrease in perfusion pressure in the coronary arteries. Following the administration of terlipressin there was resolution of the ST segment depression and a cardiac troponin assay was negative, indicating absence of significant myocardial ischaemic injury in this case. In conclusion, we suggest terlipressin may be used for the treatment of refractory hypotension secondary to angiotensin receptor antagonist overdose if conventional vasopressors have been unsuccessful.