Admixture of anesthetic drugs in the era of precision monitoring: a dangerous convenience

Pharmacologic complexity and the fallacy of drug mixingDespite these advances, the practice of mixing anesthetic drugs within a single syringe persists.Common combinations include propofol with ketamine, dexmedetomidine, or opioids, as well as more complex multi-drug admixtures [8][9][10].These mixtures may be delivered via continuous infusion or manual boluses, often justified by convenience.However, this practice is increasingly difficult to reconcile with contemporary pharmacologic principles.Multiple authors have cautioned against drug admixture, [11, 12, 13, 14, 15,16] emphasizing that it fundamentally compromises the clinician's ability to interpret pharmacodynamic responses.Hypnotic agents such as propofol primarily modulate cortical activity and level of consciousness, whereas analgesics, particularly opioids and adjuncts like ketamine, act on nociceptive pathways and autonomic responses.When administered as a mixture, their effects become inseparably intertwined.Overlapping side-effect profiles, including respiratory depression, hypotension, and bradycardia, further obscure attribution of clinical responses to a specific agent.Critically, pharmacodynamic interactions between these drugs are not simply additive but often synergistic and non-linear.As a result, the clinician loses the ability to predict, interpret, or adjust drug effects with precision. Loss of independent titrationMixing hypnotic and analgesic agents into a single syringe or infusion inevitably results in fixed ratios of drugs, representing a departure from the core principle of balanced anesthesia: the independent and physiologically guided titration of distinct drug classes.These fixed proportions cannot adapt to dynamic changes in surgical stimulus, patient sensitivity, or pharmacokinetic variability.In practice, this creates a scenario in which adjusting one pharmacologic domain In contemporary anesthetic practice, balanced multimodal general anesthesia relies on the precise titration of hypnotic and analgesic agents that act through distinct mechanisms across central and peripheral neural pathways.This approach aims to achieve unconsciousness, amnesia, antinociception, and akinesia while minimizing hemodynamic instability, drug toxicity, delayed emergence, and postoperative complications [1].Accordingly, modern anesthesia increasingly depends on multimodal monitoring.Electroencephalogram (EEG) provides a real-time assessment of consciousness and hypnotic level, [2, 3] while emerging technologies seek to quantify the nociception-antinociception balance [4].Together, these tools support individualized, physiologyguided titration of anesthetic drugs to maintain an appropriate balance between unconsciousness, unresponsiveness, and analgesia [5][6][7].