Why the Same Anesthetic Fails Sometimes

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Anesthetics remain safe, but they are not universally effective. Sex, genetics, body composition, and brain function influence how anesthetics are metabolized and tolerated, so the challenge lies in tailoring those drugs to each patient's biology.

Why it matters

Historically, anesthetic practice has relied on relatively stable models to predict drug response. However, recent research shows that this response results from a complex interaction of pharmacokinetics, pharmacodynamics, genetics, pathophysiology, preexisting brain state, and even psychosocial factors — all of which are variable and dynamic.

The details

Factors like advanced age, cardiovascular, liver, or kidney disease, and nutritional status affect the volume of distribution, metabolism, and elimination of anesthetics. Sex and sex hormones also influence individual sensitivity to anesthetics. Body composition, liver or kidney comorbidities, and genetic polymorphisms in metabolizing enzymes can all contribute to why the same patient may respond differently to the same anesthetic regimen on different occasions. The brain's response is also highly heterogeneous and is modulated by neurocognitive factors, surgery-induced neuroinflammation, and psychological variables like anxiety levels.

• In October 1846, William T.G. Morton publicly demonstrated the use of ether as an anesthetic, marking the birth of modern anesthesia.
• Today, general anesthetics make more than 300 million surgeries a year worldwide possible.

What’s next

To reduce variability in anesthetic response, anesthesiology is moving toward increasingly personalized clinical practice models supported by biomarkers, advanced monitoring, and analysis of large data sets.