perioperative use of raas antagonists
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DESCRIPTIONA 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.
- 1. Perioperative use of RAAS Antagonists: Evidence and Controversy Moises Auron MD, FAAP Department of Hospital Medicine Cleveland Clinic
- 2. Objectives
- 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.
- 3. Introduction
- The renin-angiotensin-aldosterone system (RAAS) antagonists (RAAS-antagonists) include:
- Angiotensin-converting enzyme inhibitors (ACEI)
- Angiotensin II receptor subtype 1 blockers (ARB)
- Direct renin inhibitors (Aliskiren)
- Aldosterone antagonists (Spironolactone, Eplerenone)
- 4. RAAS antagonists: indications
- Congestive heart failure
- Coronary artery disease
- Diabetic nephropathy
- Prevention of progression of chronic renal failure
- 5. RAAS antagonists and surgery
- Intra-operative hypotension after induction of anesthesia
- Post-operative acute renal failure
- Not associated with increased mortality
- All based on small studies
- 6. J Intern Med. 2008 Sep;264(3):224-36.
- 7. J Intern Med. 2008 Sep;264(3):224-36.
- 8. Pharmacology of RAAS antagonists: perioperative implications
- Sympathetic blockade
- Increase in the bioavailability of the vasodilatory agents:
- Nitric oxide
- Inhibition of the vasoconstrictor effects of angiotensin II
- Reduction in the secretion of aldosterone and ADH
- Decrease in renal salt and water reabsorption.
- Pleiotropic effects
- inhibition of the different angiotensin peptides as well as both renin and pro-renin receptors
- 9. Effects of anesthesia on the BP
- Increased venous pooling of blood
- Decreased cardiac output
- Arterial hypotension.
- 10. Intra-operative BP
- Maintained by:
- Sympathetic nervous system
- Arginine-vasopressine (AVP)
- Secretion stimulated as well by Angiotensin II
- 11. Intra-operative BP
- Multilevel effect for maintenance of intra-operative BP
- Adequate hydration
- AVP agonists (terlipressin)
- 12. Pharmacogenomics of RAAS
- Genetic susceptibility to the RAAS-antagonists affected by single nucleotide polymorphism (SNP) mutations in:
- Angiotensin receptor 1
- Angiotensin receptor 2.
- Affects intraoperative hemodynamic response to RAAS-antagonists.
- 13. ACEI Am J Health Syst Pharm. 2004 May 1;61(9):899-912.
- 14. ARB Circulation 2001;103;904-912.
- EVIDENCE AGAINST
- 16. Cleveland Clinic: IMPACT
- 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.
- Sublingual captopril (12.5 mg and 25 mg) vs. placebo 25 minutes before ETI
- N = 40
- Captopril - increased BP (P frequent hypotensive episodes.
Anesth Analg. 2001 Jan;92(1):26-30. 21. Comfere
- 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)
Anesth Analg. 2005 Mar;100(3):636-44. 22. Shirmer
- Patients on chronic antiHTN with ACEI (N = 100) RCT.
- 50 received ACEI in AM of surgery vs. 50 who didnt.
- BP and HR were significantly lower in the ACEI group requiring supportive adrenergic agonists
- 17 of 50 in the ACEI vs. 5 of 50 in the withdrawal group.
Anaesthesist. 2007 Jun;56(6):557-61. 23. Licker
- Pts with CAD undergoing non-cardiac surgery
- N = 32; 16 receiving chronic ACEI and 16 didnt.
- Induction-related BP: 9 (ACEI) vs. 2 (control).
- Diminished response to phenylephrine in the ACEI group.
- Decreased -adrenergic vasoconstrictive response?
Can J Anaesth. 2000 May;47(5):433-40. 24. Kheterpal
- Prospective observational study: N= 12,381
- Diuretics + ACEI/ARB increased BP and requirement for vasopressors vs. ACEI alone or when combination with Ca-vs.
- Propensity score matching and ROC curve analysis was done to control for comorbidities that may acquaint for hemodynamic variations between groups.
J Cardiothorac Vasc Anesth. 2008 Apr;22(2):180-6. 25. Rosenman
- Systematic review
- Random-effects meta-analysis (incorporates within-study and between-study variability)
- 5 studies; N = 434
- Preoperative RAAS-antagonists on the day of surgery increased likelihood of BP requiring vasopressors after induction ( RR 1.50 , 95% CI 1.15 to 1.96).
- No difference noted in incidence of peri-operative MI between groups (RR 0.41, 95% CI 0.07 to 2.53).
J Hosp Med. 2008 Jul;3(4):319-25. 26. Metaanalysis: Hypotension J Hosp Med. 2008;3:319325 27. Metaanalysis: AMI J Hosp Med. 2008;3:319325 28. EVIDENCE SUPPORTING RAAS-ANTAGONISTS 29.
- None of the studies showed any significant difference in postoperative complications.
- No proof of association between BP and:
- Major CV complications
- Renal failure
- ICU LOS
- Increased mortality
- Assessment of hemodynamic and hormonal responses to: