The drug-induced, reversible coma of anaesthesia requires three clinical outcomes: unconsciousness, immobility, and the control of autonomic nervous system (ANS) responses to surgical stimulation.

Producing the anaesthetised state with a single anaesthetic agent, such as an inhaled vapour or propofol, is challenging, primarily because suppressing ANS responses requires very high anaesthetic concentrations, resulting in haemodynamic depression and prolonged recovery.

The antinociceptive effects of opioids (i.e. minimum alveolar concentration reduction) are thus central to the well-entrenched ‘balanced anaesthesia’ concept.

In recent years, the notion of ‘multimodal general anaesthesia’ has extended the concept of balanced anaesthesia to include more drugs that target different neuroanatomical circuits and multiple neurophysiologic mechanisms.

The opioid epidemic has provided some of the motivation to move away from opioids toward other adjunct drugs.