Genomics relevant to the neuroanaesthesiologist

INTRODUCTION

‘It is more important to know what sort of person has a disease, than to know what sort of disease a person has’. ~ Hippocrates (circa. 460–370 BC)

The essence of Hippocrates’ observation is coming to fruition 25 centuries later[1] in the understanding of genomics to explain inter-individual variability, and in response, application of the knowledge to improve clinical outcomes. Anaesthesia speciality has been the forerunner for many discoveries and applications in genomics from the infant stages of the field, for example, interactions of barbiturate in patients with porphyria (1937),[2] cholinesterase deficiency leading to succinylcholine-induced prolonged apnoea (1957)[3] and malignant hyperthermia (1962).[4] In the field of neurosurgery, reports of personalised therapy decisions based on genetic, epigenetic and molecular biomarkers have recently emerged – use of candidate molecular markers to complement diagnoses, aid prognosis and allow individualised treatment to patients with glioblastoma multiforme, thereby avoiding unnecessary therapy, reducing toxicity and associated costs.[5] While the decision to operate or not is being aided by genetics, the perioperative period is itself a model of stress and inflammation superimposed on complex disease and is associated with pain and haemodynamic/metabolic shifts[6] – all these elements have a genetic basis for individual response variability. As can be imagined, surgical trauma triggers an integrated neuroendocrine reaction, and the body mounts a counter-regulatory response. The balance between these pro-inflammatory pathways and the response is an individually determined process and affects patient outcomes. This makes it imperative that personalisation be the backbone of patient management during this period.

Moreover, the patient is exposed to multiple drugs in a short course of time perioperatively. We know that drug response variability is a major factor leading to perioperative adverse reactions, and genetic factors contribute to an estimated 50% of drug response variability.[7] This is because about 59% of drugs cited in adverse drug reactions are metabolised by at least one enzyme with a variant allele known to cause poor metabolism.[8] [9] Hence, genomics should play an important role in the practice of anaesthesia today. This is of futuristic importance given projections that by 2020, the number of surgeries will increase by 25%, associated costs by 50% and likelihood of atherosclerotic-related cardiac, cerebral and renal complications by 100%.[6] [10] [11] Personalised medicine may be the key to preventing these predictions from becoming true.

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