PERSONALIZED ANESTHESIA: THE ROLE OF PHARMACOGENETICS IN THE SELECTION OF ANESTHETIC AND ANALGESIC AGENTS

Abstract

Interindividual variability in responses to anesthetic and analgesic agents remains a major challenge in perioperative medicine and cannot be fully explained by conventional clinical factors alone. Pharmacogenetics offers a scientific framework for understanding genetic determinants of drug metabolism and pharmacodynamic responses, thereby supporting the development of personalized anesthesia strategies. This study aimed to analyze current scientific evidence on the role of pharmacogenetic factors in variability of response to anesthetic and analgesic agents and to evaluate the potential of pharmacogenetics for improving drug selection, patient safety, and clinical outcomes in perioperative care. A narrative literature review was conducted using PubMed, Scopus, and Web of Science databases. Peer-reviewed clinical studies, cohort studies, randomized controlled trials, and systematic reviews published in English over the past 15 years were analyzed. Studies investigating associations between genetic polymorphisms and clinical outcomes related to anesthetic and analgesic drug response were included. Due to heterogeneity of study designs and outcome measures, qualitative thematic synthesis was applied. The strongest and most consistent pharmacogenetic associations were identified for opioid analgesics, particularly involving CYP2D6 polymorphisms affecting metabolism of codeine and tramadol. Clinically actionable genetic markers were also observed for malignant hyperthermia susceptibility linked to RYR1 mutations, directly influencing anesthetic drug selection. Evidence for pharmacogenetic effects on general anesthetics, sedatives, and neuromuscular blockers remains limited and inconsistent. Pharmacogenetic influences on postoperative pain and ICU sedation show potential but currently lack sufficient validation for routine clinical implementation. Pharmacogenetic information can improve anesthetic and analgesic drug selection in selected high-risk clinical contexts, particularly for opioid prescribing and prevention of genetically mediated anesthetic complications. However, current evidence does not support universal genotype-guided anesthesia protocols. Pharmacogenetics should presently be applied as a targeted precision-medicine tool, with broader implementation dependent on further prospective clinical trials, standardized clinical algorithms, and integration into perioperative decision-support systems.