Blog with interesting cases and/or problems related to anesthesia with discussion based on best evidence in the literature.

July 11, 2008

chronic ACE inhibitor therapy, anesthesia and hypotension: should there be routine prohibition of ACE inhibitors on day of surgery?

2 cases of hypotension with patients taking chronic ACE inhibitors.

Case 1:

Rotator Cuff repair in a 47 y/o M. The patient's PMH was significant for DM and HTN. He was taking glyburide and an ACE inhibitor for medications. He was in other wise good health. He had taken his ACE inhibitor that morning. On induction of anesthesia he suffered significant hypotension with means in the 50 mmHg range. The surgical repair was performed in the beach chair position. Because of the loss of baroreceptor reflexes, maintaining reasonable blood pressure is known to be challenging in this position. However, blood pressures initially dropped to 60 mmHg systolic. Immediately phenylephrine was given. Response was sub optimal (the next cuff pressure read in the 80's mmHg systolic). Significant amounts of phenylephrine (300 mcg to 400 mcg) every few minutes was required to maintain SBP in the high 90's to low 100's mmHg. An infusion was started, and SBP gradually increased to high 100's and low teens for the remainder of the case which was aproximately three hours in duration. Maintaining adequate blood pressure in shoulder surgery performed in the sitting position is paramount. Several case reports have appeared describing catastrophic neurologic disasters (i.e. persistent vegetative state, brain death, stroke) after apparently unremarkable shoulder surgery [1,2,3]. It is recommended that an adjustment be made to accomodate the lower level of the arm compared to the brain when BP measurements are taken in the arm of a sitting patient, especially under GA. In this case, the patient emmerged without sequelae from his significant hypotension. Other than chronic ACE inhibitor therapy, there were no other obvious factors that would contribute to this man's significant hypotension.

Case 2:

A laparoscopic assisted Vaginal hysterectomy with combined pubvaginal sling was performed in a 58 y/o F. PMH was significant for HTN. Medications included Lisinopril and HCTZ. She had taken her lisinopril on the day of surgery. Preoperative BP was 137/61. On induction, SBP was reduced to mid 80's. Small amounts of phenylephrine were used to maintain SBPs in the 100 to 120's. The patient remained stable during the case with desflurane in 100% oxygen. The case lasted 3 hrs and 40 minutes, during which time the patient received 250 mcg fentanyl, 2.4 L ringers lactate. EBL was 300 mL with a UO of 200 mL for the case. In the PACU, the patient had decreased SBP (mid 80's). A one liter bolus of LR was given and blood pressure increased to low 90's, but then began to taper off. At this point, the patient developed episodes of paroxysmal sinus tachycardia (see figure). Electrolytes and a hemoglobin were checked along with a 12 lead EKG. All were within normal limits, with the exception of the Hgb, which had drifted from 13.1 g/dL preop to 11.1 g/dL in the PACU. It was decided to place her on a small amount of phenylephrine titrated to mean arterial BP of 60 to 65 mmHg and to give 500 mL hespan. As it was getting late, and she had been in the PACU for aproximately 3 hours, it was decided to consult internal medicine. IM decided to put her in the ICU for monitoring over night. That night at 8:30pm, 8 hrs after surgery, she was alert and oriented and feeling fine, sitting up in bed. She was still receiving a small amount of phenylephrine to maintain her mean bp in the 60's. Her maintenance fluid was NS at 150 mL/hr.

While it is certainly difficult to pin hypotension in any particular case on one single drug, like an ACE inhibitor, there is evidence to support chronic ACE inhibitor therapy as the cause. ACE inhibitors are being used more and more frequently to treat hypertension, CHF, and in diabetics with albuminuria to prevent diabetic nephropathy. Consequently, a large number of patients are coming to the OR who are treated with these medications. It is important to understand their impact on the course of anesthesia and to have a rational policy to deal with this class of medications. Certainly, Beta blockers have received a large deal of attention in the perioperative period. It is considered prudent by most clinicians to continue beta blockers throughout the perioperative period in an effort to reduce cardiac morbidity and prevent a rebound tachycardia from withdrawal. Alpha 1 agonists, if withdrawn suddenly, may also result in a rebound effect leading to exagerated hypertension.

ACE inhibitors inhibit the production of Angiontensin II from Angiontensin I. Angiontensin II is a critical component of the body's natural defense against hypotension in the face of various assaults (hemorrhage, hypovolemia, vasodilatory states). ACE inhibitors can also lead to elevated levels of bradykinin which also results in vasodilation. Furthermore, elevated bradykinin may result in increased conversion of arachidonic acid to prostaglandins, thus increasing prostacyclin and prostaglandin E2 (vasodilators).

Angiontensin II is a potent vasoconstrictor, but plays additional roles in maintaining SVR. It activates prejuntional receptors that potentiate stimulation-evoked norepinephrine release from sympathetic nerves [4]stimulates the adrenal medulla to release catecholamines [5], as well as inhibiting the reuptake of norepinephrine[6]. Therefore, the end result is a reduction of responsiveness of the vasculature to norepinephrine[7]. In controlled experimental situations where the Renin-Angiontensin system (RAS) is known to be critical, (hemorrhage), the supression of angiotensin II has been shown to result in severe shock which is refractory to resuscitation [8]. Although the physiological evidence that angiotensin II is important in maintaining normal blood pressure especially in critical states such as hypovolemia and hemorrhage, clinical studies to date have not proven this with hard end points (death, significant morbidity). But, just as important, there are no studies which demonstrate negative consequences from withholding ACE inhibitors in the perioperative period.

Nevertheless, prompted by several reports of hypotension in patients treated with ACE inhibitors upon induction of anesthesia [9,10,11 &12], Coriat et al. performed a prospective RCT to compare the incidence of hypotension upon induction in those on chronic ACE inhibitor thereapy vs. controls (ACE inhibitors witheld for 5 days)[13]. Those patients who took there ACE inhibitor on the morning of surgery (either enalipril or captopril) required ephedrine more frequently than those who did not (100% vs. 18%). These results were significant only for enalipril (longer acting medication), but not captopril (64% required ephedrine for hypotension vs. 21% in the captopril withdrawn group). The authors also noted that in patients who had held their ACE inhibitor therapy on the morning of surgery there was no increased incidence of tachycardia or hypertension in response to laryngoscopy or surgery. A year after this study, Tuman K et al. published a study looking at the effects of chronic ACE inhibitor use on patients undergoing CPB surgery[14]. They showed that those receiving chronic ACE inhibitors had a greater chance of requiring at least two vasoconstrictor infusions for low perfusion pressure after CPB (7.7%) compared to those not receiving ACE inhibitors (4.0%). They also found using logisitic regression analysis that ACE inhibitor use was an independent risk factor for requiring at least two vasoconstictor infusions after CPB. The authors found that low values of SVR were responsible for the above results. They found that the odds ratio for moderate hypotension after induction of anesthesia for general surgical cases in patients who received an ACE inhibitor within ten hours of surgery to be 1.74. Also importantly, there was no difference in complications between the groups in the postoperative period. This study also included patients taking ARBs.
Recently, Comfere also looked at ACE inhibitors[17]. In a retrospective review of 267 hypertensive patients receiving chronic ACEI/ARB therapy. Moderate hypotension was found (SBP < 85 mmHg) in patients who had their last ACEI/ARB dose <10 hrs from surgical incision (60% vs. 46% P=0.02).

Although there have been a few studies that demonstated no real difference between groups; most accept that patients taking ACE inhibitors are more likely to develop hypotension. Nevertheless, the significance of this clinically is controversial and consequently, some advocate continueing ACE inhibitors therapy through the morning of surgery. Nevertheless, based on many case reports, the above sited studies of large groups of patients and my own experience, I feel it prudent to advocate a policy requiring patients to hold their ACE inihibitor/ARB dose on the morning of surgery.

[1] Bhatti TM and EWnneking FK. Visual loss and ophthalmoplegia after Shoulder Surgery. Anesth Analg 2003; 96:899-902.
[2] Pohl A, Cullen DJ. Cerebral ischemia during shoulder surgery in the upright position: a case series. J Clin Anesth 2005;17:463-469.
[3] Cullen DJ and Kirby RR. Beach Chair position May Decrease Cerebral Perfusion: Catastrophic Outcomes Have Occurred. 2007 APSF newsletter; 22(2): circulation 81,489 (summer).
[4] Toda N, Inoue s, Okunishi H. Prejunctional alpha adrenoreceptor and angiotensin receptor function in isolated human, mokey and dog arteries. J Pharmacol exp Ther 1988;246:662-6.
[5] Peach MJ, Cline WH, Watts DT. Release of adrenal catecholamines by angiotensin II. Circ Res 1966;19:571-5.
[6] Khairallah PA. Action of angiotensin on adrenergic nerve endings: inhibition of norepinephrine reuptake. Fed Proc 1972;31:1351-07.
[7] richer C, Doussau MP, Giudicelli JF. Effects of captopril and enalapril on regional vascular resistance and reactivity in spontaneously hypertensive rats. Hypertension 1983;5:312-20.
[8] Zerbe RL, Feuerstein G, Kopin IJ: Effect of captopril on cardiovascular, sympathetic and vasopressin responses to hemorrhage. Eur J Pharmacol 1981; 72:391-5.
[9] Selby DG, Richards JD, Marshman JM: ACE inhibitors. 1989 Anaesth Intensive Care 17:110-11.
[10] Yates AP, Hunter DN: Anaesthesia and angiotensin-converting enzyme inhibitors: the effect of enalapril on perioperative cardiovascular stability. 1988 Anaesthesia 43:935-38.
[11] McConachi I, Healy TFJ: ACe inhibitors and anesthesia. 1988 Postgrad med J 65:273-274.
[12] Colson P, saussinc M, Seguin Jr, CDuchet D, Captal PA, roquefeuil B: Hemodynamic effectgs of anesthesia in patientschronically treated with angiotensin converting enzyme inhibitors. 1992 Anesth Analg 74:805-8.
[13] Coriat P, Richer C, couraki T, Gomez C et al. Influence of chronic angiotensin-converting enzyme inhibition on anesthetic induction. 1994 Anesthesiology 81:299-307.
[14] Tuman K, McCarthy RJ, O'connor CJ, Holm WE and Ivankovich AD. Angiotensin-Converting Enzyme Inhibitors Increase Vasoconstrictor Requirements After Cardiopulmonary Bypass. Anesth Analg 1995;80:473-9.
[15] Meersschaert K, Brun L, Gourdin M, Mouren S, Bertrand M, Riou B, Coriat P. Terlipressin-Ephedrine versus Ephedrine to treat hypotension at the induction of anesthesia in patients chronically treated with angiotensin converting enzyme inhibitors: a prospective, randomized, double-blinded, crossover study. Anesth Analg 2002;94:835-40.
[16] Comfere T, Sprung J, Kumar MM, Draper M, Wilson DP, Williams BA, Danielson DR, Liedl L, Warner DO. Angiotensin system inhibitors in a general surgical population. Anesth analg 2005;100:636-44.
[17]Comfere T, et al. Angiotensin system inhibitors in a general surgical population. Anesth Analg 2005; 100(3):636-44.

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