Transcript Journal Club

Journal Club
Britni Fabacher Hebert, PGY 4
Angiotensin Blockade in the
Perioperative Period
 Case Presentation
 Brief Review of Angiotensin Blockage
 Medications implicated
 Is there increased risk of hypotension perioperatively?
 When would we hold which agents and in whom?
 What are the possible downfalls of missed doses
preoperatively
 Discussion
Case Presentation
 55 yo F with HTN and degenerative joint disease of the
spine is scheduled for elective cervical fusion. She is on
losartan 75 mg daily. Within minutes of induction, her
systolic blood pressure drops below 70 mmHg. IV fluids,
ephedrine, norepinephrine and epinephrine are
unsuccessful. After 30 minutes, systolic blood pressure
normalizes.
 Should her losartan have been held prior to surgery?
Brief Review of Angiotensin
Effects and Blockade
Is there increased risk for
hypotension?
Background
 Early 1990s
 Established that blood pressure control intraoperatively is
beneficial
 Established that beta blockers and calcium channel
blockers safely stabilize blood pressure during induction
 Case reports question safety of ACEI/ARBs at induction
 Reports of severe refractory hypotension
Coriat et al, 1994
 Randomized, control, non-blinded trial
 Inclusion criteria:

Scheduled for peripheral vascular surgery lasting < 2hours

chronic enalapril or captopril prior to peripheral vascular surgery

Admitted at least 3 days prior to surgery
 Exclusion Criteria

Treatment with ACEI for diagnosis other than HTN

SBP > 170 at enrollment

Beta blocker or clonidine use

Recent myocardial infarction, unstable angina or IHD on nitrates
Design
 Randomized to one of two groups
 Continuation of ACEI through the morning of the
surgery
 Discontinuation of ACEI the day prior to surgery
 Induction Sequence was protocoled
 Blood pressure, heart rate monitored by radial arterial line
 Free of surgical stimulation for 10 minutes after induction
 Protocol to administer fluids and ephedrine for SBP < 90
Coriat et al, 1994
Parameters
 Blood Pressure
 Heart Rate
 At 3-5 days preoperatively & Preinduction:
 ACEI plasma levels
 Plasma renin activity
 Plasma converting-enzyme activity
 Catecholamine levels were assessed at pre- &
postinduction, 2 minutes after ventilation and during any
hypotensive episodes
Coriat et al, 1994
Results
Coriat et al, 1994
Results
Coriat et al, 1994
Results
Coriat et al, 1994
Results
Coriat et al, 1994
Discussion
 Not blinded
 Single center study
 Very low patient numbers
 Not powered to detect potentially large outcomes, including
clinically significant hypertensive episodes
 Did not assess longer term outcomes of concern: neurologic
sequelae, renal insufficiency, myocardial infarction
 Did not show the refractory nature of said hypotension
discussed in the literature (all episodes responded to ephedrine)
Coriat et al, 1994
Rosenman et al
 Meta- Analysis by the Mayo Clinic in 2008
 Searched 7 major databases for articles from 1981 – 2006
 Inclusion Criteria:
 Prospective cohort or controlled trials
 Enrolling adults > 18 years old for nonemergent surgery
 Chronic use of ACEI or ARB
 Clinically significant outcomes asessed
 Random effects model used and I2 calculated
Results
Rosenman et al
Results
Rosenman et al
Results
Rosenman et al
Results
Rosenman et al
Limitations
 Significant variability between studies
 I2 59%
 Possibility of publication bias is very real
 Very small numbers preclude assessment of clinically
important outcomes
 Though reported, the studies were not designed to assess
MI as outcome
Schirmer & Schurmann, 2007
 Excluded by dates from the Meta-analysis
 Article in German, only reviews available in English
 Randomized, Double Blinded, Control study of 100
patients on chronic ACEI
Results
Schirmer & Schurmann, 2007
Results
Schirmer & Schurmann, 2007
Auron et al
 In depth review of the available evidence in noncardiac surgery
 Notable Study findings
 Bertrand et al & Comfere et al: A cutoff of 10 hours for ARB
withdrawal seemed significant
 Bertrand et al: ARB use has similar, if not more
profound/frequent episodes of hypotension at induction
compared to ACEI
 Rosenman et al: Studied ACEI/ARB in combination with
other antihypertensive agents. Only the group with
ACEI/ARB + diuretics showed significant hypotension
Downfalls of Withdrawal?
 Neuroprotective Effect of RAAS Antagonism
 Decrease in POAF
 Renoprotective?
Conclusion
 Data quality is moderate at best
 There does seem to be increased risk of hypotension, possibly
refractory, with continuation of ACEI/ARBs prior to
noncardiac surgery
 Effect on clinically relevant outcomes is unclear
 Target populations : + dehydration and/or use of diuretics
 Continue in those with systolic heart failure as indication for
ACEI
 Cessation of drug at least one half life prior to induction is goal
Discussion
& Questions
Resources

Auron M, Harte B, Kumar A, et al. Renin angiotensin system antagonists in the perioperative setting: clinical consequences and
recommendations for practice. Postgrad Med J (2011). doi:10.1136/pgmj.2010.112987

Brabant SM, Bertrand M, Eyraud D, et al. The hemodynamic effects of anesthetic induction in vascular surgical patients
chronically treated with angiotensin II receptor antagonists. Anesth Analg 1999;89:1388e92.

Bertrand M, Godet G, Meersschaert K, et al. Should the angiotensin II antagonists be discontinued before surgery? Anesth
Analg 2001;92:26e30.

Coriat P, Richer C, Douraki T, et al. Influence of chronic angiotensin-converting enzyme inhibition on anesthetic induction.
Anesthesiology 1994;81:299e307.

Kheterpal S, Khodaparast O, Shanks A, et al. Chronic angiotensin-converting enzyme inhibitor or angiotensin receptor blocker
therapy combined with diuretic therapy is associated with increased episodes of hypotension in noncardiac surgery. J
Cardiothorac Vasc Anesth 2008;22:180e6.

McCarthy GJ, Hainsworth M, Lindsay K, et al. Pressor responses to tracheal intubation after sublingual captopril. A pilot
study. Anaesthesia 1990;45:243e5.

Rosenman DJ, McDonald FS, Ebbert JO, et al. Clinical consequences of withholding versus administering renin-angiotensinaldosterone system antagonists in the preoperative period. J Hosp Med 2008;3:319e25.

Schirmer U, Schurmann W. Preoperative administration of angiotensin-converting enzyme inhibitors. Anaesthesist
2007;56:557e61.