Perioperative use of Perioperative use of RAAS Antagonists: RAAS Antagonists: Evidence and Controversy Evidence and Controversy Moises Auron MD, FAAP Moises Auron MD, FAAP Department of Hospital Department of Hospital Medicine Medicine Cleveland Clinic Cleveland Clinic
A review of the existing evidence that supports the current practice in perioperative medicine regarding Renin-angiotensin-aldosterone system antagonists, mainly ACE inhibitors and Angiotensin type 1 receptor blockers (ARB's). Presented as the Cleveland Clinic Hospital Medicine Grand Rounds on April 1, 2009. CME AMA Category 1 - 1 hour.
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Perioperative use of RAAS Perioperative use of RAAS Antagonists: Evidence and Antagonists: Evidence and
ControversyControversy
Moises Auron MD, FAAPMoises Auron MD, FAAP
Department of Hospital MedicineDepartment of Hospital Medicine
• Appraise the evidence supporting the current perioperative management of Renin-Angiotensin-Aldosterone system (RAAS) antagonists in non-cardiac surgery.
• Appraise the existence of newer RAAS antagonists such as Aliskiren (direct renin inhibitor) and its management in the perioperative setting.
• Current practice: discontinue both ACEI and ARB on the morning of surgery.
• Based on several small, controlled, randomized studies which found an increased frequency of refractory hypotension requiring intensive intravenous fluids and vasopressors after the induction of anesthesia when RAAS-antagonists were not discontinued preoperatively.
Brabant• Hemodynamic response to induction between
ARB, beta-blockers (BB), Ca channel blockers (CB) and ACEI.
• ↓BP : SBP ↓ of > 30% from the preoperative value or an absolute SBP < 90 mm Hg. – ARB (12 of 12)– BB/CB-treated patients (27 of 45)– ACEI (18 of 27) (P< 0.05).
• ARB group – increased refractory to adrenergic agents (4 of 12) vs. BB/CB group (0 of 45) vs. ACEI (1 of 27).
• Patients on chronic anti-HTN treatment with ACEI/ARB (N = 267)
• Incidence of ↓BP during the first 30 minutes after induction of anesthesia was more frequent in patients whose most recent ACEI/ARB was taken < 10 h. (60% vs. 46%, O.R. 1.74 (95% C.I. 1.03 to 2.93, P = 0.04)
• Heropoulos– Assessment of hemodynamic and hormonal responses to:
• ETI• Incision• Limb-tourniquet inflation
– RCT; N = 30 patients undergoing limb surgery – Enalaprilat vs. placebo.
• - 1.25 mg IV 20 min prior to induction vs. 0.625 mg IV at the onset of tourniquet-associated hypertension.
– Venous blood samples for PRA and catecholamine (pre-intubation, 3 min post-intubation, 3 min post-incision, at onset of tourniquet hypertension, 3 min post-extubation and 1 hr postoperatively)
• No significant differences in catecholamine levels.
• Pre-operative enalapril in balanced hypotensive anesthesia for cerebrovascular surgery.
• Controlled ↓BP - minimize intraoperative bleeding. RCT vs. placebo.
• Enalapril ↓ HTN response to ETI, ↓ postoperative vasodilators, more stable BP control.
• “Preoperative fasting may be the contributor to peri-operative ↓BP - improper fluid balance and Na2+ depletion - prevented by ensuring proper intravascular volume status”
• Effect of pre-op ACEI on AKI (↓GFR > 50%) – CABG.
• Preop ACEI (N = 281) - ↓ post-op AKI (O.R. 0.48; 95% CI, 0.23 to 0.77; P < 0.04)
• Incidence of AKI requiring dialysis:– 2.4% in ACEI group vs. 6.3% in controls (P =
0.03). (44)
Ann Thorac Surg. 2008 Oct;86(4):1160-5.
Cittanova
• Prospective study (N = 249) - aortic surgery
• Chronic treatment with ACEI (withheld in AM) - only factor associated with significative postoperative renal impairment (O.R. 2.01 95% C.I. 1.05 to 3.83)
Anesth Analg. 2001 Nov;93(5):1111-5.
Kincaid
• Retrospective (N= 1209) – CABG
• Preop ACEI along with intra-op aprotinin – ARF (OR 2.9, 95% CI 1.4 to 5.8, P < 0.0001).
• Hohne– Assessment of the initial (first 20 minutes)
hemodynamic effect of ACEI in spinal anesthesia for lower body procedures.
– RCT (21 on chronic ACEI vs. 21 control)– Decrease in BP was similar.– Plasma vasopressin and norepinephrine
levels increased.
Acta Anaesthesiol Scand. 2003 Aug;47(7):891-6.
Aliskiren
• Direct renin inhibitor
• Long half life (30 - 40h)
• Increased renal vasodilatory effect vs. ACEI and ARB. (59)
• Low oral bioavailability– Terminal half life is 24 hrs.
• Weak antihypertensive (second-line agent)
J Am Coll Cardiol. 2008 Feb 5;51(5):519-28.Circulation. 2008 Aug 12;118(7):773-84.Am J Health Syst Pharm. 2008 Jul 15;65(14):1323-32.
Conclusions
• RAAS-antagonists - associated with a variable incidence of hypotension during the initial 30 minutes after induction of anesthesia in non-cardiac surgery
• These hypotensive episodes have not been linked to any significant postoperative complications.
• The ACEI/ARB should be held at least 10 hours or for one dose before the induction of anesthesia.
Conclusions (cont.)
• Careful hemodynamic monitoring
• Prevention of hypovolemia
• When to continue RAAS-antagonists?– Complicated hypertensive patient– Chronic heart failure of ischemic heart
disease– Cardiac surgery– Requires discussion with anesthesiologist