Pharmacologic Strategies for Intraoperative Hypotension When Ephedrine Is Unavailable: An Evidence-Based Review

Background/Objectives: Intraoperative hypotension (IOHs) affects up to 87% of patients under general anesthesia and is consistently associated with acute kidney injury, myocardial damage, stroke, and mortality. The intermittent unavailability of ephedrine across healthcare systems underscores the need for evidence-based alternatives. This review critically evaluates pharmacological options for IOH when ephedrine is unavailable, focusing on receptor pharmacodynamics, population-specific evidence, and clinical consequences of inadequately managed hypotension. Methods: A narrative, evidence-based review was conducted examining mechanisms of action, dosing strategies, adverse effect profiles, and clinical applicability of key vasoactive agents: ephedrine, phenylephrine, norepinephrine, and epinephrine. Population-specific evidence across obstetric, pediatric, and elderly cohorts was synthesized from randomized controlled trials, meta-analyses, and observational studies. The clinical impact of IOH on neurological, cardiovascular, and renal outcomes was reviewed. Results: Each vasopressor exhibits a distinct receptor-selectivity profile that determines its hemodynamic effect and optimal clinical context. Norepinephrine's favorable α1/β1 balance tends to preserve cardiac output better than pure α1-agonists and has emerged as a promising alternative in obstetric and elderly populations, although the optimal agent ultimately depends on the underlying mechanism of hypotension and individual patient characteristics. Epinephrine provides combined vasopressor and inotropic support for hypotension with myocardial depression. IOH is associated with a greater than twofold increase in postoperative AKI and significantly elevated risks of myocardial infarction and stroke, with outcomes driven by cumulative hypotensive exposure rather than isolated pressure nadirs. Conclusions: Effective management of IOH requires individualized vasopressor selection guided by underlying pathophysiology, cardiovascular profile, and surgical context. A physiology-based strategy-rather than protocol-driven drug substitution-enables anesthesiologists to achieve precise hemodynamic control and preserve end-organ perfusion even when ephedrine is unavailable.