Biomarkers in Anesthesiology

Biomarkers are objectively measurable characteristics that indicate normal or pathogenic biological processes, or responses to pharmacological interventions. In anesthesiology, they extend beyond traditional vital signs and laboratory tests, providing molecular insights into real-time patient physiology.

Types of Biomarkers in Anesthesia

• Diagnostic
• Identify the presence of a disease or condition.
• Example: Troponin I for myocardial infarction.
• Predictive
• Forecast likely response to therapy.
• Example: CYP2D6 genotype predicts response to codeine.
• Prognostic
• Provide information about the likely course of a disease.
• Example: BNP for predicting heart failure outcomes.
• Pharmacodynamic/Response
• Reflect biological response to a drug.
• Example: BIS index for sedation depth.

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Why Biomarkers Matter in Anesthesia

Risk Stratification

• BNP/NT-proBNP: Indicators of myocardial strain, predict cardiac complications.
• HbA1c: Reflects long-term glycemic control, informs perioperative glucose strategies.
• CRP and IL-6: Markers of systemic inflammation, predict poor surgical outcomes.

Personalized Pharmacotherapy

• CYP450 polymorphisms: Influence anesthetic and opioid metabolism.
• OPRM1 and SLCO1B1: Affect opioid sensitivity and drug handling.

Monitoring Organ Function

• NGAL: Early biomarker for acute kidney injury.
• Troponin I: Specific for myocardial injury.
• S100B: Marker of CNS damage from blood-brain barrier disruption.

Anticipating Immune Response

• Procalcitonin and IL-6: Differentiate bacterial sepsis from sterile inflammation.

• Rodseth RN, Biccard BM. B-type natriuretic peptide for risk stratification in noncardiac surgery: a systematic review and meta-analysis. Anesthesiology. 2013;119(2):314–325.
• Kheterpal S, et al. Development and validation of a novel biomarker-based risk model for postoperative acute kidney injury. Anesthesiology. 2016;124(3):519–531.

Basic Science Foundations of Biomarkers

Molecular Biology and Biochemistry

• Troponin I/T: Released during myocardial necrosis.
• NGAL: Renal tubular stress protein, binds bacterial siderophores.
• Procalcitonin: Thyroid precursor protein, rises in bacterial sepsis.

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• Becker KL, et al. Procalcitonin in sepsis and systemic inflammation. Br J Pharmacol. 2010;159(2):253–264.

Physiology

• BNP: Released by stretched ventricles, promotes vasodilation and natriuresis.
• Cerebral Oximetry (NIRS): Uses near-infrared spectroscopy to assess brain oxygenation.
• TOF Ratio: Measures neuromuscular transmission for relaxant depth.

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Pharmacology

• CYP2D6: Affects metabolism of codeine and beta-blockers.
• Pseudocholinesterase: Breaks down succinylcholine, deficiency prolongs paralysis.
• BIS: EEG-derived index for anesthetic depth.

• Crews KR, et al. CPIC guidelines for codeine therapy based on CYP2D6 genotype. Clin Pharmacol Ther. 2012;91(2):321–326.
• Lien CA, et al. In: Miller's Anesthesia. 9th ed. Elsevier; 2020.

Pathology

• S100B: Astrocyte-derived protein indicating CNS damage.
• CRP and IL-6: Acute-phase proteins elevated in tissue injury and infection.
• Lactate: Marker of anaerobic metabolism and hypoperfusion.

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Immunology

• Procalcitonin: Elevated in bacterial but suppressed in viral infections.
• IL-6, IL-8: Key proinflammatory cytokines.
• CRP: Synthesized in the liver under IL-6 regulation.

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Genetics and Genomics

• RYR1/CACNA1S: Mutations linked to malignant hyperthermia.
• OPRM1: Alters mu-opioid receptor function, affecting analgesic response.
• SLCO1B1: Modulates hepatic drug transport.

• Rosenberg H, et al. Malignant hyperthermia susceptibility. Anesthesiology. 2007;107(1):124–132.
• Lotsch J, et al. Impact of genetic variation on opioid analgesia. Drug Discov Today. 2005;10(9):601–608.

Clinical Applications Across Perioperative Phases

Preoperative

• BNP: Detects subclinical cardiac dysfunction.
• HbA1c: Assesses glycemic risk.
• Genetic screening: Identifies malignant hyperthermia susceptibility.

Intraoperative

• TOF and BIS: Guide depth of anesthesia and neuromuscular blockade.
• NIRS: Monitors cerebral oxygenation.

Postoperative

• NGAL and creatinine: Detect renal injury.
• Troponin I/T: Detect perioperative myocardial infarction.
• CRP and IL-6: Identify infection or systemic inflammation.

Challenges and Ethical Considerations

• Complexity in interpretation: Nonspecific elevations may mislead decisions.
• Cost and accessibility: Advanced assays may not be widely available.
• Ethical issues: Genetic testing raises concerns about privacy and consent.

Conclusion

Biomarkers provide anesthesiologists with a deeper understanding of patient physiology, pathology, and pharmacologic response in real time. By integrating molecular biology, physiology, pharmacology, pathology, immunology, and genetics, perioperative care can be personalized—reducing complications and improving outcomes.