hold the acei and arbs? what is the evidence?tsa.org/handouts/hold_the_ace_or_arb.pdflv j, perkovic...
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Hold the ACEi and ARBs? What is the evidence?
Davide Cattano, MD, PhD, FASA, CMQ Professor, Department of Anesthesiology
McGovern Medical School
The University of Texas Medical School at Houston
Medical Director, Preoperative Anesthesia Clinic
Anesthesia Service Chief Head and Neck Surgery
Memorial Hermann Hospital
Between Myth and Reality
Evidences and Doubts
TSA 2018, Lost Pines Sept 6th-9th
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I did not receive any honoraria, don’t
own any royalties, or gained other
benefits for this presentation.
I do not hold significant “interest”
that needs to be disclosed, related to
the presentation.
Disclosures
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Learning Objectives
• 1. Define physiology of blood pressure control by Angiotensin, identify current pharmacology strategies to control hypertension and compare anesthesiology preoperative guidelines.
• 2. Analyze the risk factors for intraoperative hypotension (IOH) and identify current mortality and morbidity related to IOH.
• 3. Discuss optimal perioperative clinical strategies based on evidence based medicine.
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Lv J, Perkovic V, Foote CV, Craig ME, Craig JC, Strippoli GF.
Antihypertensive agents for preventing diabetic kidney disease. Cochrane Database Syst
Rev. 2012 Dec 12;12:CD004136. doi: 10.1002/14651858.CD004136.pub3.
ACEIs were found to prevent new onset DKD and death in normo-albuminuric people with diabetes, and could therefore be used in this population.
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Xue H, Lu Z, Tang WL, Pang LW, Wang GM, Wong GW, Wright JM.
First-line drugs inhibiting the renin angiotensin system versus other first-line
antihypertensive drug classes for hypertension. Cochrane Database Syst Rev. 2015 Jan
11;1:CD008170. doi: 10.1002/14651858.CD008170.pub2.
• First-line thiazides caused less HF and stroke than
first-line RAS inhibitors.
• Compared with first-line CCBs, first-line RAS inhibitors
reduced HF but increased stroke. The magnitude of the
reduction in HF exceeded the increase in stroke.
We found predominantly moderate quality evidence that all-cause mortality is similar when first-line RAS inhibitors are compared to
other first-line antihypertensive agents.
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1. What are the current guidelines regarding ACEI/ARBs use in the perioperative period?
2. What are the dangers to using them during this period?
3. What do we know about these dangers?
4. Are the current “practice” guidelines appropriately addressing these matters? Is there enough evidence to justify them?
Clinical Questions and Dilemmas
• IOH (Intraoperative hypotension)
• AKI (Acute Kidney Injury)
• MINS (Myocardial Injury after Non cardiac Surgery)
• Others? (Stroke, IscOptNeu, “POCD/Delirium”)
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Fleisher, LA, Fleischmann, KE, Auerbach, AD, Barnason, SA, Beckman, JA, Bozkurt, B, Davila-
Roman, VG, Gerhard-Herman, MD, Holly, TA, Kane, GC, Marine, JE, Nelson, MT, Spencer, CC,
Thompson, A, Ting, HH, Uretsky, BF, Wijeysundera, DN
2014 ACC/AHA guideline on perioperative cardiovascular evaluation and management of
patients undergoing noncardiac surgery: Executive summary: A report of the American
College of Cardiology/American Heart Association Task Force on Practice Guidelines.
Circulation. (2014). 130 2215–45
ACEIs or ARBs
• Continuation of ACEIs or ARBs is reasonable perioperatively.
IIa, B
• If ACEIs or ARBs are held before surgery, it is reasonable to restart it PO as soon as clinically feasible.
IIa, C
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We recommend withholding ACEI/ARB starting 24 hours before noncardiac surgery in patients
treated chronically with an ACEI/ARB (Strong Recommendation; Low-Quality Evidence).
• Substantial increase in the risk of IOH associated with perioperative continuation of ACEI/ARB therapy.
• Because the risk of hypotension is greatest within 24 hours of surgery, physicians should consider
restarting ACEI/ARB on day 2 after surgery in patients receiving chronic ACEI/ARB therapy, if the
patient is hemodynamically stable.
Emmanuelle Duceppe, MD,a,b,c Joel Parlow, MD, MSc (Co-chair),d Paul MacDonald, MD,e Kristin Lyons, MDCM,f Michael McMullen, MD,d Sadeesh Srinathan,MD, MSc,g Michelle Graham, MD,h Vikas Tandon,MD,I Kim Styles,MD,j Amal Bessissow,MD,MSc,k Daniell. Sessler, MD,l Gregory Bryson,MD,MSc,m,n and P.J. Devereaux, MD, PhD (Co-chair)b,c,i. Canadian Cardiovascular Society Guidelines on Perioperative Cardiac Risk Assessment and Management for Patients Who Undergo Noncardiac Surgery. http://www.onlinecjc.ca/article/S0828-282X(16)30980-1/pdf
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Roshanov, PS, Rochwerg, B, Patel, A, Salehian, O, Duceppe, E, Belley-Côté, EP, Guyatt, GH, Sessler, DI, Le
Manach, Y, Borges, FK, Tandon, V, Worster, A, Thompson, A, Koshy, M, Devereaux, B, Spencer, FA,
Sanders, RD, Sloan, EN, Morley, EE, Paul, J, Raymer, KE, Punthakee, Z, Devereaux, PJ.
Withholding versus Continuing Angiotensin-converting Enzyme Inhibitors or Angiotensin II Receptor
Blockers before Noncardiac Surgery: An Analysis of the Vascular events In noncardiac Surgery
patients cohort evaluation Prospective Cohort. Anesthesiology. 2017 Jan;126(1):16-27.
Recommendation: consider withholding ACEI/ARBs
24 h before surgery.
A large randomized trial is needed to confirm this finding.
• Patients who withheld their ACEI/ARB in the 24 h before surgery were
less likely to suffer of all-cause death, stroke, or myocardial injury
after noncardiac surgery at 30 days compared to the ones who did not.
(150/1,245 [12.0%] vs. 459/3,557 [12.9%]; adjusted relative risk, 0.82; 95% CI, 0.70 to 0.96; P =
0.01); Adjusted relative risk, 0.80; 95% CI, 0.72 to 0.93; P < 0.001; respectively).
• The risk of PO hypotension was similar between the two groups.
(adjusted relative risk, 0.92; 95% CI, 0.77 to 1.10; P = 0.36). Results were consistent across the
range of preoperative blood pressures.
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Botto F1, Alonso-Coello P, Chan MT, Villar JC, Xavier D, Srinathan S, Guyatt G, Cruz P, Graham M, Wang CY, Berwanger O, Pearse RM, Biccard BM,
Abraham V, Malaga G, Hillis GS, Rodseth RN, Cook D, Polanczyk CA, Szczeklik W, Sessler DI, Sheth T, Ackland GL, Leuwer M, Garg AX, Lemanach Y,
Pettit S, Heels-Ansdell D, Luratibuse G, Walsh M, Sapsford R, Schünemann HJ, Kurz A, Thomas S, Mrkobrada M, Thabane L, Gerstein H, Paniagua P,
Nagele P, Raina P, Yusuf S, Devereaux PJ, Devereaux PJ, Sessler DI, Walsh M, Guyatt G, McQueen MJ, Bhandari M, Cook D, Bosch J, Buckley N, Yusuf
S, Chow CK, Hillis GS, Halliwell R, Li S, Lee VW, Mooney J, Polanczyk CA, Furtado MV, Berwanger O, Suzumura E, Santucci E, Leite K, Santo JA,
Jardim CA, Cavalcanti AB, Guimaraes HP, Jacka MJ, Graham M, McAlister F, McMurtry S, Townsend D, Pannu N, Bagshaw S, Bessissow A, Bhandari M,
Duceppe E, Eikelboom J, Ganame J, Hankinson J, Hill S, Jolly S, Lamy A, Ling E, Magloire P, Pare G, Reddy D, Szalay D, Tittley J, Weitz J, Whitlock R,
Darvish-Kazim S, Debeer J, Kavsak P, Kearon C, Mizera R, O'Donnell M, McQueen M, Pinthus J, Ribas S, Simunovic M, Tandon V, Vanhelder T,
Winemaker M, Gerstein H, McDonald S, O'Bryne P, Patel A, Paul J, Punthakee Z, Raymer K, Salehian O, Spencer F, Walter S, Worster A, Adili A, Clase
C, Cook D, Crowther M, Douketis J, Gangji A, Jackson P, Lim W, Lovrics P, Mazzadi S, Orovan W, Rudkowski J, Soth M, Tiboni M, Acedillo R, Garg A,
Hildebrand A, Lam N, Macneil D, Mrkobrada M, Roshanov PS, Srinathan SK, Ramsey C, John PS, Thorlacius L, Siddiqui FS, Grocott HP, McKay A, Lee
TW, Amadeo R, Funk D, McDonald H, Zacharias J, Villar JC, Cortés OL, Chaparro MS, Vásquez S, Castañeda A, Ferreira S, Coriat P, Monneret D,
Goarin JP, Esteve CI, Royer C, Daas G, Chan MT, Choi GY, Gin T, Lit LC, Xavier D, Sigamani A, Faruqui A, Dhanpal R, Almeida S, Cherian J, Furruqh S,
Abraham V, Afzal L, George P, Mala S, Schünemann H, Muti P, Vizza E, Wang CY, Ong GS, Mansor M, Tan AS, Shariffuddin II, Vasanthan V, Hashim
NH, Undok AW, Ki U, Lai HY, Ahmad WA, Razack AH, Malaga G, Valderrama-Victoria V, Loza-Herrera JD, De Los Angeles Lazo M, Rotta-Rotta A,
Szczeklik W, Sokolowska B, Musial J, Gorka J, Iwaszczuk P, Kozka M, Chwala M, Raczek M, Mrowiecki T, Kaczmarek B, Biccard B, Cassimjee H,
Gopalan D, Kisten T, Mugabi A, Naidoo P, Naidoo R, Rodseth R, Skinner D, Torborg A, Paniagua P, Urrutia G, Maestre ML, Santaló M, Gonzalez R, Font
A, Martínez C, Pelaez X, De Antonio M, Villamor JM, García JA, Ferré MJ, Popova E, Alonso-Coello P, Garutti I, Cruz P, Fernández C, Palencia M, Díaz
S, Del Castillo T, Varela A, de Miguel A, Muñoz M, Piñeiro P, Cusati G, Del Barrio M, Membrillo MJ, Orozco D, Reyes F, Sapsford RJ, Barth J, Scott J,
Hall A, Howell S, Lobley M, Woods J, Howard S, Fletcher J, Dewhirst N, Williams C, Rushton A, Welters I, Leuwer M, Pearse R, Ackland G, Khan A,
Niebrzegowska E, Benton S, Wragg A, Archbold A, Smith A, McAlees E, Ramballi C, Macdonald N, Januszewska M, Stephens R, Reyes A, Paredes LG,
Sultan P, Cain D, Whittle J, Del Arroyo AG, Sessler DI, Kurz A, Sun Z, Finnegan PS, Egan C, Honar H, Shahinyan A, Panjasawatwong K, Fu AY, Wang S,
Reineks E, Nagele P, Blood J, Kalin M, Gibson D, Wildes T; Vascular events In noncardiac Surgery patIents cOhort evaluatioN (VISION) Writing Group, on
behalf of The Vascular events In noncardiac Surgery patIents cOhort evaluatioN (VISION) Investigators; Appendix 1. The Vascular events In noncardiac
Surgery patIents cOhort evaluatioN (VISION) Study Investigators Writing Group; Appendix 2. The Vascular events In noncardiac Surgery patIents cOhort
evaluatioN Operations Committee; Vascular events In noncardiac Surgery patIents cOhort evaluatioN VISION Study Investigators.
Myocardial injury after noncardiac surgery: a large, international, prospective cohort study establishing diagnostic
criteria, characteristics, predictors, and 30-day outcomes. Anesthesiology. 2014 Mar;120(3):564-78.
Among adults undergoing noncardiac surgery, MINS
is common and associated with substantial mortality.
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• The VISION study, given its large sample size and complex multinational logistics, it was not
designed to capture extensive physiologic data. Because of this, the hypotension variables
were limited to a categorical response (yes/no) although the total duration of the episodes
was captured. Unfortunately, neither medication use after surgery nor renal outcomes were
systematically captured.
• Although ACEI/ARB use was associated with intraoperative hypotension and was
correlated with progressively longer total duration, it was not associated with the primary
outcome. Postoperative hypotension was associated with the primary outcome but not with
ACEI/ARB use.
• An acute elevation of creatinine can be precipitated by hypovolemia, sepsis, hemodynamic
instability due to new or worsening dysrhythmias, and so forth. Thus, it is tempting to
speculate that patients with deteriorating renal function were given their ACEIs/ARBs
inappropriately, leading to higher risk of adverse perioperative outcomes associated with
either chronic preoperative or acute perioperative renal injury.
London MJ.
Preoperative Administration of Angiotensin-converting Enzyme Inhibitors or Angiotensin II Receptor
Blockers: Do We Have Enough "VISION" to Stop It? . Anesthesiology. 2017 Jan;126(1):1-3.
There is contradicting information here
?
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In patients with moderate renal insufficiency undergoing cardiac catheterization, withholding ACEI/ARB resulted in a non-significant reduction in contrast-induced
AKI and a significant reduction in post-procedural rise of creatinine.
Bainey KR1, Rahim S2, Etherington K2, Rokoss ML2, Natarajan MK2, Velianou JL2, Brons S2, Mehta SR3;
Captain investigators.
Effects of withdrawing vs continuing renin-angiotensin blockers on incidence of acute kidney injury in
patients with renal insufficiency undergoing cardiac catheterization: Results from the Angiotensin
Converting Enzyme Inhibitor/Angiotensin Receptor Blocker and Contrast Induced Nephropathy in
Patients Receiving Cardiac Catheterization (CAPTAIN) trial. Am Heart J. 2015 Jul;170(1):110-6.
Coca SG, Garg AX, Swaminathan M, Garwood S, Hong K, Thiessen-Philbrook H, Passik C, Koyner JL, Parikh
CR; TRIBE-AKI Consortium.
Preoperative angiotensin-converting enzyme inhibitors and angiotensin receptor blocker use and
acute kidney injury in patients undergoing cardiac surgery. Nephrol Dial Transplant. 2013
Nov;28(11):2787-99. doi: 10.1093/ndt/gft405. Epub 2013 Sep 29.
• Preoperative ACEI/ARB usage was associated with functional but not structural acute kidney injury.
• As AKI from ACEI/ARB in this setting is unclear. ?
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• Many different definitions of IOH were found and resulted in different
IOH incidences.
• Any episode of SBP < 80 mmHg was found in 41% of the patients,
whereas 93% of the patients had at least one episode of SBP > 20%
below baseline. Both definitions are frequently used in the literature.
There is no widely accepted definition of
IOH.
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Salmasi V, Maheshwari K, Yang D, Mascha EJ, Singh A, Sessler DI, Kurz A.
Relationship between Intraoperative Hypotension, Defined by Either Reduction from Baseline or
Absolute Thresholds, and Acute Kidney and Myocardial Injury after Noncardiac Surgery: A
Retrospective Cohort Analysis. Anesthesiology. 2017 Jan;126(1):47-65.
Anesthetic management can thus be based on IO pressures without regard to preoperative pressure.
• MAP below absolute thresholds of 65 mmHg or relative thresholds
of 20% were progressively related to both myocardial and kidney
injury. They both had comparable ability to detect these outcomes.
• At any given threshold, prolonged exposure was associated with
increased odds.
• Preoperative BP did not have important interactions with the
outcomes studied at MAP < 65 mmHg
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Walsh M, Devereaux PJ, Garg AX, Kurz A, Turan A, Rodseth RN, Cywinski J, Thabane L, Sessler DI.
Relationship between intraoperative mean arterial pressure and clinical outcomes after noncardiac surgery: toward an
empirical definition of hypotension. Anesthesiology. 2013 Sep;119(3):507-15. doi: 10.1097/ALN.0b013e3182a10e26.
• The MAP threshold where the risk for AKI or Myocardial injury
increased was < 55 mmHg.
• Compared with never developing a MAP < 55 mmHg, those with a
MAP < 55 mmHg for 1-5, 6-10, 11-20, and >20 min had graded
increases in their risk of the two outcomes. (AKI: 1.18 [95% CI, 1.06-1.31],
1.19 [1.03-1.39], 1.32 [1.11-1.56], and 1.51 [1.24-1.84], respectively; myocardial injury 1.30
[1.06-1.5], 1.47 [1.13-1.93], 1.79 [1.33-2.39], and 1.82 [1.31-2.55], respectively].
Even short durations of an IO MAP < 55 mmHg are associated with
AKI and myocardial injury.
Randomized trials are required to determine whether outcomes improve with
interventions that maintain an IO MAP of at least 55 mmHg.
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Sessler DI, Meyhoff CS, Zimmerman NM, Mao G, Leslie K, Vásquez SM, Balaji P, Alvarez-Garcia J,
Cavalcanti AB, Parlow JL, Rahate PV, Seeberger MD, Gossetti B, Walker SA, Premchand RK, Dahl RM,
Duceppe E, Rodseth R, Botto F, Devereaux PJ.
Period-dependent Associations between Hypotension during and for Four Days after Noncardiac
Surgery and a Composite of Myocardial Infarction and Death: A Substudy of the POISE-2 Trial.
Anesthesiology. 2018 Feb;128(2):317-327.
• Clinically important hypotension was defined as SBP < 90 mmHg
requiring treatment.
• IO, the estimated average relative effect across MI and mortality per 10-
min increase in hypotension duration was 1.08 (98.3% CI, 1.03, 1.12; P < 0.001).
• For the remaining day of surgery, the OR per 10-min increase in
hypotension duration was 1.03 (98.3% CI, 1.01, 1.05; P < 0.001).
• The average relative effect OR in patients with hypotension during the
subsequent 4 days of hospitalization was 2.83 (98.3% CI, 1.26, 6.35; P = 0.002).
Clinically important hypotension was significantly associated with a
composite of MI and death during each of the perioperative periods
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van Waes JA, van Klei WA, Wijeysundera DN, van Wolfswinkel L, Lindsay TF, Beattie WS.
Association between Intraoperative Hypotension and Myocardial Injury after Vascular
Surgery. Anesthesiology. 2016 Jan;124(1):35-44.
• Depending on the definition, IOH occurred in 12-81% of the patients.
• 40% decrease from the pre-induction MAP with a cumulative duration
> 30 min was associated with PO myocardial injury. (relative risk, 1.8; 99% CI, 1.2 to 2.6, P < 0.001).
• PO MI and death within 30 days occurred in 26 (6%) and 17 (4%)
patients with IOH as defined by a < 60 mmHg, compared with 12 (3%;
P = 0.08) and 15 (3%; P = 0.77) patients without IOH, respectively.
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Gu WJ, Hou BL, Kwong JSW, Tian X, Qian Y, Cui Y, Hao J, Li JC, Ma ZL, Gu XP.
Association between intraoperative hypotension and 30-day mortality, major adverse cardiac events,
and acute kidney injury after non-cardiac surgery: A meta-analysis of cohort studies. Int J Cardiol.
2018 Feb 2. pii: S0167-5273(17)35125-2.
• Meta-analysis of 14 cohort studies that were heterogeneous in terms
of definition of IOH.
• IOH alone was associated with increased risk of 30-day mortality,
MACEs, especially myocardial injury, and AKI. (OR 1.29 [95% CI, 1.19-
1.41]), (OR 1.59 [95% CI, 1.23-2.05]), (OR 1.67 [95% CI, 1.31-2.13]), (OR 1.39 [95%
CI, 1.09-1.77]); respectively.
• Triple low (IOH coincident with low bispectral index and low MAC) also
predicts increased risk of 30-day mortality (OR 1.32 [95% CI, 1.03-1.68]).
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ACEIs/ARBs can be
continued perioperatively
if hemodynamically stable,
good renal function and
normal electrolytes.
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Steely AM1, Callas PW1, Bertges DJ2; Vascular Study Group of New England.
Renin-angiotensin-aldosterone-system inhibition is safe in the preoperative period
surrounding carotid endarterectomy. J Vasc Surg. 2016 Mar;63(3):715-21.
• Preoperative ACEI/ARB use was associated with marginally
increased use of IV BP med for HTN but not for hypotension,
and was not associated with increased MACE, stroke, or death.
• The use of preoperative ACEI/ARB appears safe before CEA.
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Vijay A, Grover A, Coulson TG, Myles PS
Perioperative management of patients treated with angiotensin-converting enzyme inhibitors and
angiotensin II receptor blockers: a quality improvement audit. Anaesth Intensive Care. 2016
May;44(3):346-52.
Problems:
• Possibility of confounding
• Possibility of Insufficient
sample size.
Future prospective randomized
clinical trials are required
No significant differences in measured outcomes between the
continued or withheld ACEI/ARB groups were found.
There was no statistically significant difference between the continued or
withheld groups in:
• Vasopressor or IV fluid administration ((metaraminol use 3.5 [1.5-8.3] mg Vs. 3.5
[1.5-8.5] mg, P=0.67) (1000 ml [800-1500] ml Vs. 1000 [800-1500] ml, P=0.096) respectively).
• Rates of PO AKI or AFib ((13% vs 18%, P=0.25)(15% versus 18%, P=0.71) respectively).
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Seshadri C. Mudumbai, MD, MS , Steven Takemoto, PhD, Brian A. Cason, MD, Selwyn Au, MS, Anjali Upadhyay, MS, Arthur W. Wallace, MD, PhD Thirty‐day mortality risk associated with the postoperative non-resumption of angiotensin‐converting enzyme inhibitors: A retrospective study of the veterans affairs healthcare system. J. Hosp. Med. 2014 May;9(5):289-296.
Restarting of an ACE‐I within PO day 0 to 14 is associated with
a decreased 30‐day mortality.
• Patients were classified into groups based upon the timing of PO
resumption of an ACEIs (PO days 0 to 14 and 15 to 30).
• Nonresumption of an ACEI in PO days 0 to 14 was independently
associated with increased 30‐day mortality compared to the restart
group. (hazard ratio: 3.44; 95% CI: 3.30‐3.60; P < 0.001) Sensitivity analyses
maintained this relationship.
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• ACEIs and ARBs are safe to use preoperatively.
• Withholding them for the IO period and restarting them as soon as clinically possible, might be the best course of action to prevent intra and postoperative hypotension and based on current evidences, HYPOTHETICALLY reduce adverse outcomes.
• Large scale randomized trials are still needed to find the right answer.
Conclusions