Sepsis: personalization v protocolization?

The founding tenet of evidence-based medicine is to combine best evidence with clinical expertise. As David Sackett opined ‘Without clinical expertise, practice risks becoming tyrannised by evidence’. Rigid protocols and mandates, based on an inconclusive and low-level evidence base, cannot suit the physiological, biochemical and biological heterogeneity displayed by the individual septic patient. Indeed, clear proof of outcome benefit through adoption of an inflexible management approach is lacking and will certainly be detrimental to some. Therapy thus needs to be tailored to meet the individual patient’s needs. The same principle should be applied to clinical trials; the continued disappointments of multiple investigational strategies trialled over three decades, despite (often) a sound biological rationale, suggest a repeated methodological failure that does not account for the marked heterogeneity within the septic patient’s biological phenotype and thus marked variation in their host response. The increasing availability of rapid point-of-care diagnostics and theranostics should facilitate better patient selection and titrated optimization of the therapeutic intervention.