Management of intracranial hypertension with and without invasive intracranial pressure monitoring

Table 3 Concepts that need to be considered for the interpretation of neutral and divergent results regarding intracranial pressure monitoring benefit

Concept	Interpretation
Selection bias	Some observational studies include participants that would be excluded in a clinical trial (e.g., non salvageable patients) of ICP monitoring. They are less likely to receive ICP monitoring in clinical practice and very much more likely to die or have unfavorable outcomes. Confounding adjustment is not enough to address selection bias when the proposed treatment (or monitoring device) would not have been received in a clinical trial
Confounding	While many studies address confounding at baseline, the use of ICP monitoring may lead to differential treatment intensities, which may vary from place to place. Therefore, modern causal inference methods that properly address time-dependent confounding with G-methods is necessary to address not only treatment thresholds, but the benefits or not of ICP monitoring
Dichotomania	Dichotomization of continuous variables leads to loss of information. While there are thresholds that are associated with increases in mortality, the relationship between high ICP levels and worse outcomes is not linear and certainly not a two-level (higher or lower than 20 or 22 mmHg) relationship. This dichotomization leads to riskier treatments being proposed for patients with intermediate (20-25 mmHg) ICP elevations that may not be as harmful as very high (> 30 mmHg) ICP elevations
Risk-guided management	In Medicine, in general, management is guided by different prognostic risk categories. Riskier therapies should be reserved for high risk scenarios where no other alternatives exist. Using tier 3 therapies (barbiturates, hypothermia, craniectomy) for intermediate risk patients based on dichotomania (ICP threshold) may therefore lead to more harm than benefit. Even among the very high risk patients, it may not be beneficial whatsoever, unless as a bridge to a definitive treatment
Prognostic association vs causal effect	Increased intracranial pressure is essentially the consequence of a severe acute brain injury, whether traumatic or not, and is a potential mediator of worse outcomes. Its prognostic association with worse outcomes is well documented. However, whether high ICP has a causal effect on increased mortality or disability is likely dependent on the non-linear relationship of high ICP with worse outcomes. At very high ICP levels (i.e., > 30 mmHg), this is very likely true and high ICP likely mediates this relationship. However, at intermediate high ICP levels (20-30 mmHg), it's likely that there is a complex interplay between treatment intensity, underlying cause of high ICP (diffuse axonal injury, cerebral edema, contusions, etc.), physiological compensation (e.g., maintenance or not of cerebral flow autoregulation) and ICU-acquired complications potentially caused by treatment intensity. Hence, we cannot assume that treatment escalation above proposed ICP thresholds is always beneficial with the current evidence base

ICP: Intracranial pressure; ICU: Intensive care unit.