Assessment of Cerebral Compliance and Hemodynamics in Severe COVID-19

The gravity of the disease caused by the new coronavirus 2019 (COVID-19) is predominantly harbored in severe acute respiratory syndrome (SARS), often requiring ventilatory support. However, in some cases it has been observed that the involvement of this entity is not restrict to the respiratory tract, but also to the central nervous system (CNS), heart, kidneys, intestines and testicles, or even the cross-response of the immune system with potential for Guillain-Barre and Miller-Fisher syndromes. It is not yet clear whether acute respiratory failure in patients with COVID-19 is due exclusively to pulmonary invasion or because of concurrent CNS disorders, however, as many of these patients have neurological symptoms such as headache, anosmia, paresthesia, nausea, vomiting and consciousness level alterations during the early stages of the disease, the hypothesis of this entity in promoting cerebral compliance (CC) impairment directly (i.e. encephalitis, edema or focal ischemia) or indirectly (i.e. hypoxic distress and linkage to angiotensin-converting enzyme) becomes suitable.

Intracranial pressure (ICP) monitoring is relevant in several CNS diseases with risk for critical intracranial hypertension (ICH)(10). Still, this parameter is considered in specific situations, limiting its use in neurocritical settings, especially because of the invasive nature of the monitoring techniques available. ICH has potential to compromise CC and, consequently, promote brain tissue damage. Regarding COVID-19, unless a mass effect structural damage documented by encephalic imaging is evident, there is no justification to perform a trepanation to implant an ICP monitor, hence, noninvasive techniques such as transcranial Doppler by means of cerebral hemodynamics evaluation and the novel cranial pulse detector (B4C), by means of the quantitative evaluation of the ICP curves, may play a role in this scenario.

The purpose of the present study was to evaluate CC in a set of COVID-19 patients, since implementation until withdrawal of respiratory support in ICU, to evaluate the potential persistence of CC impairment in this population. Prolonged CC impairment observation may aid decision making and targeted therapy in this population. Study design A single center, observational and prospective research was conducted including consecutive subjects in intensive care units (ICU) of the Hospital das Clínicas, São Paulo University, Brazil, with approval of local ethics committee. Our inclusion criteria regarded patients with SARS for COVID-19, under ventilatory support of any age and gender. Exclusion criteria comprehended the absence of legally authorized responsible (LAR) consent, patients without temporal acoustic window for TCD assessment, patients unable to undergo monitoring with the NICC sensor due to lesions and/or skin infections in the sensor application region, patients with head circumference smaller than 47 cm. The study protocol followed the Standards for Reporting of Diagnostic Accuracy Studies (STARD) statement.

Eligible subjects are selected by the ICU team (SF, BT, EB and LMSM) during the first three days of orotracheal intubation for CC monitoring with B4C and TCD hemodynamics evaluation once, marking the beginning of SARS. The same evaluations are repeated once again during the first three days after extubating, as a sign of recovery stage. Clinical parameters were controlled to avoid assessment bias, as systemic arterial pressure, hydric balance, presence of CNS depressors with influence on cerebrovascular hemodynamics, laboratorial partial O2 and CO2 pressures and hemoglobin, and temperature. One operator is performing TCD and B4C evaluations. Overall sample clinical condition was quantified using the simplified acute physiologic score (SAPS 3).

CC monitoring techniques Cerebral compliance was evaluated noninvasively by the cranial deformation method developed by brain4care (B4C). The B4C sensor consists of a support for a sensor bar for the detection of local cranial bone deformations adapted with deformation sensors. The detection of these deformations is obtained by a cantilever bar modeled by finite element calculations. For this bar, voltage meters are attached for deformation detection. Noninvasive contact with the skull is obtained by adequate pressure directly into the scalp by means of a pin. Variations in ICP cause deformations in the cranial bone detected by the sensor bar. The device filters, amplifies, and scans the sensor signal and sends the data to a mobile device. The method is completely non-invasive and painless. In addition, it does not interfere with any routine monitoring.