Refractory Hypotension After Induction of Anesthesia in a Patient Chronically Treated with Angiotensin Receptor Antagonists

An increasing number of patients scheduled for surgery are chronically treated with angiotensin II receptor antagonists (ARA). These drugs interfere with the renin-angiotensin system by inhibiting the angiotensin II (AII) binding to its receptor, resulting in increased AII- and normal bradykinin blood levels (1). By contrast, AII synthesis inhibition by angiotensin-converting enzyme inhibitors (ACEI), results in increased bradykinin- and low AII blood levels (2). The arterial blood pressure response to induction documented in patients treated with ACEI (3,4) may not be similar in patients chronically treated with ARA. We report the management of a patient, chronically treated with an ACEI (enalapril) and thereafter with an ARA (irbesartan), who developed a severe hypotension refractory to ephedrine and phenylephrine in response to induction. Case Report A 75-yr-old man (weight, 95 kg) was scheduled for an endarterectomy, first of the right and some months later of the left internal carotid artery. He was treated for hypertension with nicardipine (50 mg daily) and enalapril (5 mg daily). Preoperatively arterial blood pressure was 160/90 mm Hg, and heart rate was 68 bpm and echocardiography revealed a normal left ventricular function but an asymmetric septal hypertrophy and a slightly dilated left atrium. The patient was premedicated with oral midazolam (5 mg) and nicardipine (50 mg), whereas enalapril was withdrawn the eve of surgery. Before induction of anesthesia, 900 mL of a lactated Ringer’s solution was infused. Invasive blood pressure, heart rate, 5-lead electrocardiogram and ST segment analysis were continuously monitored. Anesthesia was slowly induced with 25 μg sufentanil, 120 mg propofol and 50 mg atracurium and maintained with O2/N2O 50%. Blood samples were withdrawn when blood pressure decreased 4 min. after induction by more than 30% below the preoperative value (96 mm Hg). Plasma converting-enzyme activity was 69 U/l (normal range: 40–100 U/l), vasopressin concentration was 1.7 pg/mL (normal range: 1.3–3.9 pg/mL), norepinephrine concentration was 195 pg/mL (normal range: 200–300 pg/mL), and epinephrine concentration was 25 pg/mL (normal range: 25–55 pg/mL). Despite repeated IV ephedrine administration (up to 27 mg), blood pressure decreased to 88/46 mm Hg, heart rate was 46 bpm. Transesophageal echocardiography showed a left ventricular (LV) fractional area change (FAC) of 43%, a left ventricular end-diastolic cross-sectional area (EDA) of 14.6 cm and a LV end-systolic cross-sectional area (ESA) of 7.4 cm2 and an end-systolic meridional wall stress (ESWS) of 36.4 × 103dyne/cm2. A bolus of 1 mg terlipressin (Glypressine, Ferring, Malmö, Sweden) was administered IV 9 min after induction. Blood pressure increased to 118/53 mm Hg 1 min later and remained stable (between 126/57 and 148/82 mm Hg) during the anesthesia period. EDA increased to 22 cm2, ESA increased to 11 cm2, FAC slightly increased to 49% and ESWS increased to 59.4 × 103dyne/cm2. Heart rate decreased to 34 bpm, but increased to 56 bpm after IV administration of atropine, 1 mg. No cardiac neurological postoperative complications were noted. Two months later the patient was scheduled for an endarterectomy of the left internal carotid artery. Because he experienced a persistent cough, 18 days prior to surgery, enalapril was withdrawn and replaced by irbesartan (150 mg daily). Preoperative blood pressure was 150/70 mm Hg and heart rate was 56 bpm. The patient was premedicated with oral midazolam 5 mg. Three hours before surgery, irbesartan (150 mg), and nicardipine, (50 mg) were given. Before induction of anesthesia 900 mL of a lactated Ringer’s solution was administered. Anesthesia was slowly induced with 45 μg sufentanil, 140 mg propofol and 50 mg atracurium and maintained with O2/N2O 50%. Blood pressure decreased 3 min. after induction to 92/44 mm Hg. Despite repeated IV ephedrine administrations (up to 18 mg), blood pressure decreased on the 5th min. to 47/30 mm Hg. The blood pressure decrease was so severe and rapid that no blood samples for hormone levels were drawn and no transesophageal echocardiography was performed. BP increased after IV phenylephrine (200 μg) administration to 88/66 mm Hg but decreased again to 79/46 mm Hg despite the administration of IV ephedrine (6 mg). Twelve min after induction of anesthesia, terlipressin 1 mg bolus was administered. Blood pressure increased after 1 min. to 102/50 but decreased again to 78/52 mm Hg. Administrations of terlipressin, 1 mg were repeated on the 17th and on the 35th min after induction until blood pressure increased to 118/72 mm Hg and remained stable during the entire anesthesia period. No neurological nor cardiac postoperative complications occurred. Discussion We report refractory hypotension, after induction of anesthesia in a patient chronically treated with drugs inhibiting the renin-angiotensin system. Although irbesartan and enalapril produce comparable blood pressure reductions (2), the larger blood pressure decrease and increased terlipressin requirement in the second procedure may be explained by irbesartan administration on the morning of surgery. This suggests that ARB-therapy when continued up to the morning of surgery is a major factor influencing the manner in which anesthesia lowers blood pressure. We did not observe an increase in norepinephrine, epinephrine and vasopressin blood levels as expected during hypotension (5,6). This indicates that the sympathetic system and the vasopressin system were not activated by the severe blood pressure decrease (6). In both cases, the hypotensive episodes were refractory to classical vasoconstrictor therapy. Ephedrine administration was ineffective in restoring blood pressure, which is consistent with the decreased vasopressor effect of norepinephrine in ACEI-treated patients undergoing anesthesia (7). The lack of effect of sympathetic system-agonists to restore blood pressure led us to consider the use of an agonist of the vasopressin system to treat this refractory hypotension (8). Terlipressin, or triglycyl-lysine vasopressin, is a synthetic vasopressin analog, which is slowly converted to lysine vasopressin, resulting in a continuous release of small amounts of vasopressin (9). In accordance with the documented vasoconstrictor activity of vasopressin (10,11), echocardiographic measurements showed that terlipressin increased the cardiac filling without impairing LV function. Terlipressin administration was associated with a long lasting (>1h) effect on blood pressure associated with a slight decrease in heart rate. We conclude that both chronic ACEI-therapy and chronic ARA-therapy may lead to refractory hypotension after induction of anesthesia. Irbesartan administration on the morning of surgery appears to be an important factor influencing anesthesia-induced hypotension. Hypotensive episodes refractory to classical vasoconstrictor therapy were successfully treated with an agonist of the vasopressin system.