ACE Inhibitors and Hypotension

Description

Significant hypotension has been reported after the induction of general anesthesia in patients on angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARBs).
At this time, guidelines have not been established regarding preoperative management (withdrawal or continuation) of ACEI or ARBs. Large randomized controlled studies are lacking and most information stems from retrospective studies:
- Elective, noncardiac surgical patients who have taken ACEI or ARBs on the morning of surgery appear to have an increased risk of moderate hypotension (systolic blood pressure [SBP] <85 mm Hg) (1) and vasopressor requirement (2).
- Vascular surgical patients who have taken ACEI or ARBs on the morning of surgery appear to have an increased incidence of hypotension and level of severity (3).
- Cardiac surgical patients who withhold ACE inhibitors before surgery appear to maintain a greater MAP and require less vasopressors while on bypass. Additionally, they may require more vasodilator therapy post-bypass and do not incur hypotension at the time of anesthesia induction (4).

Epidemiology

Incidence

ACEI/ARBs are frequently prescribed for antihypertensive therapy with particular advantages in:
- Renal protection in diabetes mellitus (DM) and hypertension (HTN)
- Prevention of cardiac remodeling after myocardial infarction (MI)
Lower risk of cerebrovascular accident (CVA) and MI (4)

Prevalence

Approximately 50 million individuals in the US (and 1 billion worldwide) have HTN.

Morbidity

In addition to causing hypotension, ACEI/ARBs can also cause renal impairment and hyperkalemia. They are contraindicated in renal artery stenosis and should be used with caution in hypovolemia.

Etiology/Risk Factors

Concurrent use of diuretics with ACEI/ARBs has been associated with a higher risk of hypotension during anesthesia (2).

Physiology/Pathophysiology

The physiology of the renin-angiotensin-aldosterone system (RAAS) plays an essential role in the short-term regulation of blood pressure and long-term regulation of intravascular volume.
- Angiotensinogen is an inactive glycoprotein produced in the liver.
- Renin is secreted by the kidneys into the bloodstream when pressure receptors sense low blood volume. Renin is highly specific in cleaving angiotensinogen to angiotensin I.
- Angiotensin converting enzyme (ACE) is a nonspecific enzyme in the vascular endothelium which converts angiotensin I to angiotensin II. ACE also inactivates bradykinin, a potent vasodilator.
- Angiotensin II can cause immediate vasoconstriction of arterial and venous vessels, with a resultant increase in the systemic vascular resistance (SVR) and venous return. It constricts renal efferent arterioles during moderate decreases in perfusion pressure in order to preserve the glomerular filtration rate (GFR). Small amounts are also produced independently of ACE.
- Aldosterone is produced by the adrenal glands in response to angiotensin II and hyperkalemia. It plays a role in sodium retention and increasing the blood volume; it has a slower response and longer duration (5).
Blood pressure regulation is also maintained by other systems.
- The sympathetic nervous system maintains vascular tone, heart rate, and contractility; however, induction of anesthesia results in a reduction of sympathetic tone in both the arterial and venous vessels. This results in a lower SVR as well as decreases in effective blood volume and preload.
- Vasopressin (antidiuretic hormone) is an important compensatory mechanism in hypovolemia.
Refractory hypotension: ACEI and ARBs impair the RAAS; general anesthesia impairs the sympathetic nervous system. Thus, the combination leaves the vasopressin system as the main mechanism of maintaining blood pressure.
Other:
- Genetics may influence which patients are susceptible to hypotension following induction.
- Neuraxial blocks: Whether ACEI or ARBs cause refractory hypotension in patients receiving an epidural or spinal is unclear.

Prevantative Measures

Patients may be asked to withhold their ACEI/ARB on the day of surgery.
If they are not withheld, cancellation of surgery is not necessarily warranted. Consider volume administration, the use of an induction agent other than propofol (or lower doses), and having vasopressors including vasopressin available.

Despite intraoperative hypotension being an independent predictor of mortality in the first year after surgery (12), no standard definition exists.

A common practical approach is to establish the patient's baseline from several readings and attempt to stay within 20% (6).
However, the lowest "safe" blood pressure will vary with an individual's comorbidities such as aortic stenosis or cerebrovascular insufficiency.
Adequate cerebral perfusion has been cited as a MAP >70 mm Hg (7), with higher MAPs often necessary in chronic HTN. MAPs <70 mm Hg may be tolerated for a short time in hypertensive patients. Cerebral ischemia resulting in stroke was not noted in these studies.

Differential Diagnosis

Hypotension, in general, may be seen in ~9% of patients in the first 10 minutes following the induction of anesthesia (8). The following predictors were found:

ASA III-V
Age >50
Baseline MAP <70 mm Hg
Use of propofol for induction
Increased doses of fentanyl
Chronic HTN
Hypovolemia

Volume infusion
Sympathomimetics such as ephedrine or phenylephrine as first-line treatment. One study showed that doses of ephedrine and phenylephrine did not usually exceed 20–25 mg and 200 mcg, respectively (3).
Vasopressin may be helpful in refractory cases. It is usually administered as an infusion for vasodilatory shock; bolus therapy is off label. It may have a more sustained effect than other pressors.
Terlipressin, an AVP analog, may also be useful (9).
Methylene blue has been reported in the treatment of refractory hypotension. The mechanism of action is an in inhibition of cGMP in the endothelium.

Comfere T , Spring J , Kumar M , et al. Angiotensin system inhibitors in a general surgical population. Anesth Analg. 2005;100:636–644.
Pigott DW , Nagle C , Allman K , et al. Effect of omitting regular ACE inhibitor medication before cardiac surgery on haemodynamic variables and vasoactive drug requirement. Br J Anesth. 1999;83:715–720.
Bertrand M , Gilles G , Meersschaert K , et al. Should the angiotensin II antagonists be discontinued before surgery. Anesth Analg. 2001;92:26–30.
White W. Angiotensin-converting enzyme inhibitors in the treatment of hypertension: An update. J Clin Hypertens. 2007;9:876–882.
Colson P , Ryckwaert F , Coriat P. Renin angiotensin system antagonists and anesthesia. Anesth Analg. 1999;89:1143–1155.
Howell SJ , Sear JW , Foex P. Hypertension, hypertensive heart disease, and perioperative cardiac risk. Br J Anaesth. 2004;92:570–583.
Drummond JC. The lower limit of autoregulation: Time to revise our thinking?Anesthesiology. 1997;86:1431–1433.
Reich D , Hossain S , Baez B , et al. Predictors of hypotension after induction of general anesthesia. Anesth Analg. 2005;101:622–628.
Meersschaert K , Brun L , Gourdin M , et al. 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;94:835–840.
Hohne C , Meier L , Boemke W , et al. ACE inhibition does not exaggerate the blood pressure decrease in the early phase of spinal anaesthesia. Acta Anaesthesiol Scand. 2003;47:891–896.
Kheterpal S , Khodaparast O , Shanks A , et al. Chronic angiotensin-converting enzyme inhibitor or angiotension receptor blocker therapy combined with diuretic therapy as associated with increased episodes of hypotension in noncardiac surgery. J Cardiothoracic Vasc Anesth. 2008;22:180–186.
Monk TG , Saini V , Weldon BC. Anesthetic management and one-year mortality after noncardiac surgery. Anes Analg. 2005;100:4–10.

Augoustides J. Angiotensin blockade and general anesthesia: So little known, so far to go. J Cardiothoracic Vasc Anesth. 2008;22:177–179.
Smith I , Jackson I. Beta-blockers, calcium channel blockers, angiotensin receptor blockers: Should they be stopped or not before ambulatory anaesthesia. Curr Opin Anesth. 2010;23:687–690.

See Also (Topic, Algorithm, Electronic Media Element)

Angiotensin
Hypotension
Renin

ICD9

458.8 Other specified hypotension

ICD10

I95.2 Hypotension due to drugs

Hypertensive patients often demonstrate very labile blood pressures. Excessive drops in MAP cause concern for a possible increase in morbidity and possibly mortality.
Following induction of anesthesia in association with use of ACEI/ARBs, there appears to be an increased incidence of hypotension due to a reduction in vascular tone, especially on the venous return. The angiotensin II system is unable to compensate for the hypotension; therefore, these patients are more volume sensitive to maintain preload.
Arguments against discontinuing ARBs and ACEI include: Neuroprotection, as well as improved hemodynamic stability, decreased ischemia–reperfusion injury, and renal protection.

John B. Carter , MD

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