Renin-angiotensin system (RAS) inhibitors, such as angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs), are invaluable in the management of hypertension, heart failure, and chronic kidney disease. They have a well-established role in the chronic management of blood pressure and the reduction of further cardiovascular and renal damage (1). However, the physiological effects and molecular pathways of RAS inhibitors may also have implications for surgery and anesthesia management.
RAS inhibitors function by modulating the body’s renin-angiotensin-aldosterone system, which regulates blood pressure, fluid and electrolyte balance, and systemic vascular resistance. ACE inhibitors reduce the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, thereby lowering blood pressure and decreasing afterload on the heart. ARBs, on the other hand, block the angiotensin II receptor, directly attenuating the effects of angiotensin II. Although these mechanisms are beneficial for the long-term management of cardiovascular diseases, they also underpin the intraoperative hemodynamic instability—particularly hypotension—that can occur with RAS inhibitors when patients undergo surgery under general anesthesia (2).
The main concern with the use of RAS inhibitors during the perioperative period is the increased risk of refractory hypotension upon induction of anesthesia. This risk stems from a diminished ability for compensatory vasoconstriction, which is crucial for maintaining systemic vascular resistance in the face of the vasodilatory properties of anesthetic drugs. A study by Comfere et al. highlighted the association between preoperative use of ACE inhibitors or ARBs and increased intraoperative hypotension, emphasizing the need for vigilant hemodynamic monitoring and readiness to manage significant blood pressure drops during surgery (1). Another consideration is the potential for reduced renal perfusion in patients on RAS inhibitors undergoing surgery. The kidneys rely on the balancing ability of angiotensin II-mediated efferent arteriole constriction to maintain glomerular filtration pressure. In the context of surgery and anesthesia, especially in procedures associated with significant fluid shifts or blood loss, the inhibition of angiotensin II by RAS inhibitors can compromise renal autoregulation, leading to renal failure/insufficiency. Kheterpal et al. demonstrated that the preoperative use of ACE inhibitors or ARBs is associated with an increased risk of postoperative renal failure in patients undergoing major noncardiac surgery, underscoring the importance of renal function assessment and proper intraoperative fluid management in this patient population (2).
Given these considerations, healthcare providers should decide whether to continue or withhold RAS inhibitors in the perioperative period only after considering an individual patient’s cardiovascular and renal baseline function, the nature of the surgery and anesthesia regimen, and the expected hemodynamic changes. A systematic review by Roshanov et al. suggested that withholding ACE inhibitors or ARBs before surgery might reduce the incidence of intraoperative hypotension without increasing postoperative cardiovascular events, though the evidence remains inconclusive and further research is needed to establish definitive guidelines (3).
In summary, RAS inhibitors play a pivotal role in managing chronic cardiovascular and renal conditions but pose specific challenges in the perioperative setting due to their impact on hemodynamics and renal perfusion. To optimize perioperative care, anesthesiologists and surgeons must be aware of these considerations; they should tailor hemodynamic monitoring and management strategies to address the risk of hypotension and renal impairment in each patient. Ongoing research and clinical vigilance are essential to refining perioperative management protocols for patients on RAS inhibitors, ensuring safe and effective surgical outcomes.
References
- Comfere T, Sprung J, Kumar MM, et al. Angiotensin system inhibitors in a general surgical population. Anesth Analg. 2005;100(3):636-644.
- Kheterpal S, Tremper KK, Heung M, et al. Development and validation of an acute kidney injury risk index for patients undergoing general surgery: results from a national data set. Anesthesiology. 2009;110(3):505-515.
- Roshanov PS, Rochwerg B, Patel A, et al. Withholding versus continuing angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers before noncardiac surgery. Anesthesiology. 2017;126(1):16-27.
