In this study, mICP values were significantly correlated with P2/P1 derived from NICPW analysis in a heterogeneous population of brain-injured patients. Moreover, P2/P1 values had, as for elevated mICP, prognostic value for early mortality. The predictive values of BCI and mICP were similar. The presence of DC did not influence overall results.
The classic studies of Marmarou et al.  and Langfitt et al. , by means of invasive ICP measurement, observed the relation between intracranial volume and ICP variations , whereas Nucci et al.  confirmed that changes in ICPW followed ICP variations; in particular, elevation of the second ICP peak was related to impaired ICC, although quantitative relations between ICPW peaks were not demonstrated in that study. Kazimierska et al.  performed intracranial elastance assessment by means of infusion test in normal pressure hydrocephalus patients and compared three techniques, including changes in P1 and P2 amplitudes, indicating that the ratio obtained from these peaks has good correlation with the intracranial volumetric manipulation.
ICPW is a well-known parameter for intensivists and neurosurgeons; however, clinical applicability of ICPW remains difficult because invasive systems do not routinely analyze P2/P1, being a clear recognition of the two peaks is not always possible. Therefore, isolated ICP values are currently recommended in the trigger for specific therapies of IHT . The expansion of multimodal neuromonitoring could help to further understand how ICP values should be optimized in clinical practice. In particular, as the combination of ICP values with brain oxygenation [26, 27], there is potential to combine information from ICP invasive measurement and the NICPW analysis to better understand intracranial compliance after an acute brain injury.
In experimental and clinical settings, the non-invasive P2/P1 ratio has been well correlated with ICP or applied as additional information to predict outcomes and assess shunting malfunctioning in children with hydrocephalus [28, 29] and idiopathic intracranial hypertension . In COVID-19 patients, the combination of P2/P1 with TCD allowed to identify disturbances in cerebral hemodynamics (CH) and predict early poor outcome . Moreover, the application of this system in previously unexplored health conditions has suggested interesting alterations in brain compliance among patients with end-stage renal disease under hemodialysis  and robotic prostatectomy surgery because of Trendelenburg positioning .
The clinical interest of P2/P1 should be in the understanding of the brain tolerance to different ICP values; as an example, if a patient with an ICP of 18 mmHg could be considered as having ICP values within acceptable ranges, the concomitant presence of P2/P1 > 1.2 might suggest poor intracranial compliance, potentially requiring additional investigations and interventions. On the opposite, an ICP of 23 mmHg, which should deserve prompt therapy according to guidelines, could be further evaluated in its pathogenesis (i.e., hyperthermia, awakening, fever) if P2/P1 ratio remains within normal ranges. A prospective study including additional neuromonitoring tools to better understand cerebral physiology during ICP surges is required to respond to this hypothesis.
This study has several limitations to acknowledge. First, a single-center study cohort might influence patients’ management and early outcome, so that generalizability of overall results could be biased. Second, the association of P2/P1 with early mortality does not imply that altered brain compliance could be the only explanation for death, rather, this could be explained by the neurological damage itself even considering that our three groups disclosed no overall severity admission differences Third, data acquisition was a single and short length recording in the early acute phase after admission with no additional information on the ICP behavior posteriorly. In fact, a cohort design is proper to outcome assessment and justifies further investigation and register more IHT events than the few occasions reported in the present study. Fourth, our results need for external validation. Although DC did not appear to significantly influence the applicability of NICPW analysis, some cautious should be considered in such patients, who will require dedicated investigations with such monitoring tools.