A Novel Non-invasive Technique of Cerebral Compliance and Auto-regulation Assessment

Introduction Multimodal monitoring in neurocritical care is essential in current practice. It aims to early Identify treats occurring in the brain of comatose patients and implement targeted therapies to avoid further complications and poorer outcomes. Some of the methods used for monitoring require invasive procedures, such as the assessment of intracranial pressure (ICP) with intracranial catheter. However, these techniques can raise morbidity, are costly, and are not available or contraindicated1. In addition, the invasive ICP method is not perfectly accurate with cases in which, intracranial hypertension (ICH) may be present despite normal screen ICP values2. Transcranial Doppler (TCD) is a noninvasive bedside ultrasound technique which could be implemented in the monitoring of raised ICP3-4 and in the identification of impaired intracranial compliance by the compression of the internal jugular veins (IJVs)1. However, such application of the method has not been validate with large prospective studies. Validation of this technique would be of value for screening patients prior to suffer the consequences of ICH. Recently, a non-invasive cranial strain gauge sensor has been developed, able to provide the curves of cardiac beat by beat cranial dilation. The sensor registers have been demonstrated to be similar to those obtained by the invasive ICP catheters, although large series comparing both techniques are lacking. Objectives 1\) Evaluate the reliability of TCD during the IJVs compression in the assessment of intracranial compliance; 2) evaluate dynamic cerebral auto regulation (dCAR) during IJVs compression. 3) Evaluate the suitability of novel non-invasive intracranial compliance system. Methods This is a prospective observational study which will be performed at "Hospital das Clinicas" (São Paulo University School of Medicine). The sample desired is of 50 consecutive subjects, as a pilot study based in recommendations of the literature5. After ethics committee approval, neurological patients of any cause, gender or age, whose underwent ICP monitoring displaying both ICP curves and values will be included. The non-invasive system of intracranial compliance monitoring (Brain4Care Brasil, São Carlos, Brazil) will be used concomitantly. We will exclude patients without insonation window. The control group will be of healthy subjects, to evaluate PI and cerebral auto-regulation during IJVs compression. Initially, the study of dynamic cerebral auto regulation through the relationship of spontaneous fluctuations of cerebral blood flow velocity in the middle cerebral arteries (MCAs) and arterial blood pressure, will be done using TCD (DWL Doppler Box 2 MHz, Germany) for five minutes, plus the optic nerve sheath measure (Sonosite Micromaxx 13 MHz, USA), then, ultrasound guided (Sonosite Micromaxx 13 MHz, USA) IJVs compression will be performed for 60 seconds in the included patients, and the following variables will be registered prior and after intervention: blood pressure, mean arterial blood pressure, heart rate, breathing rate, hemoglobin, hematocrit, carbon dioxide pressure (pCO2), oxygen saturation, systolic flow velocity, diastolic flow velocity, mean velocity, pulsatility index, ICP values and changes in the ICP relation P1-P2 (waveform behavior). One researcher (SB) will perform TCD examinations and obtain patients data, while two blinded researchers (RN and MLO) the offline analysis. Data will be presented as mean ± standard error of the mean or median and interquartile ranges depending on the nature of the variable. The Chi-square test (χ2) will be used to assess the difference in sex distribution and etiology between groups. To evaluate the homogeneity of the sample we will use the Lèvene test. And, we will use the Kolmogorov-Smirnov test to evaluate the normality of distribution of each variable studied. According to the homogeneity and normality of distribution (Gaussian) of the studied variable will be used the appropriate statistical test (parametric or non-parametric) for each variable. In the homogeneous and Gaussian variables during rest, the analysis of variance (ANOVA) of a factor will be used to test the differences between the groups. In cases of significant F, the Scheffé post-hoc test will be performed for multiple comparisons. In non-homogeneous and / or non-Gaussian variables during rest, the Kruskal-Wallis test will be used, followed by the Dunn's test between the groups. On the other hand, in the homogeneous and Gaussian variables analyzed during the physiological maneuvers, the analysis of variance (ANOVA) of two factors will be used to test the differences between groups. In cases of significant F, the Scheffé post-hoc test will be performed for multiple comparisons. However, in non-homogeneous and / or non-Gaussian variables analyzed during physiological maneuvers, the Wilcoxon (paired data) and Mann-Whitney (unpaired data) tests, when appropriate, will be used. Will be considered as statistically significant to differences with P values \<0.05.