Mechanical hyperinflation maneuver and intracranial compliance of critical neurological patients: protocol for a randomized controlled equivalence trial

The protocol complies with a randomized controlled equivalence trial, double-blinded, parallel (1:1 ratio), and exploratory approved by the Research Ethics Committee of the Hospital de Clínicas of the Universidade Federal do Parana (CAAE: 01,378,118.7.0000.0096). The individuals are allocated through simple randomization into two groups. All items in the Data Set of the Register of Tests by the WHO were recorded on the database of the Brazilian Clinical Trial Registry (RBR – 5qs9k2n). Any alteration in the protocol is informed to the above-mentioned bodies. When preparing this protocol, we used the SPIRIT reporting guidelines [17], and a table with the standard protocol items (SPIRIT) is presented in Table 1. The SPIRIT checklist is available as an additional file (Additional file 1).

Information and guidelines on this research (objectives, methodology, risks, and benefits) are given to critical neurological patients admitted to ICU at the Clinical Hospital Complex of the Federal University of Paraná and met the inclusion criteria. The term of consent will be obtained by one of the researchers of the group, before the admission of the participant in the research. Their inclusion in the study is effective by agreeing to participate and signing an Informed Consent (IC), according to Resolution 466/2012 by the National Health Council This researcher will make the initial contact with the person responsible for the participant, explaining in detail all the procedures that will be performed.

Individuals with acute stroke diagnosis are included in the study upon neuroimage exam confirmation, with symptoms dating back to 72 h, under MV through a tracheal tube, both male and female and over the age of 18, whose relatives signed the IC. Exclusion criteria included individuals who received contraindication for the enhancement of positive ITP (pneumothorax, hemothorax, and acute respiratory distress syndrome), presented peak pressure (Ppeak) > 40 cmH₂O in the MV, patients with Richmond Agitation-Sedation Scale (RASS) above -3 (asynchronicity in MV and difficulty in coupling to the ICP monitoring sensor), patients with hemodynamic instability according to higher concentrations of vasoactive amines over the last 12 h, and those who had been subjected decompressive craniectomy.

The following strategies will be carried out for achieving adequate participant: dissemination of the research among members of the multidisciplinary team, training of physiotherapists to screen potential patients for the study, and actively search for patients in intensive care units.

To control possible confusing factors regarding ICP increase, we will assess and monitor the level of carbon gas (CO₂) exhaled – end-tidal CO₂ (ETCO₂) and pain throughout the data collection. ETCO₂ assessment is performed using a capnograph (Dräger Vamos@ plus monitor), whose sensors are calibrated 2 h before the collection period and alarms, reference measures, and oxygen compensation adjusted [2]. Pain is assessed according to the Behavioral Pain Scale, and the evaluation tool focused on behavioral indicators of pain previously translated and adapted to Portuguese [18, 19]. All researchers were properly trained for data collection.

The participants are randomly allocated to two groups using a simple randomization procedure with computerized random numbers (Randomizer software program—Version 4.0). Participant allocation was conducted using sequentially numbered, opaque and sealed envelopes, opened only at the time of participant’s inclusion in the study. Randomization and allocation procedures were conducted by an independent physical therapist not involved with assessment or interventions, same for recruitment.

Prior to the beginning of the trial, study personnel will undergo training sessions on data collection and will be individually tested on data entry as well as outcome assessments. Study data will be collected on a paper form and transferred to an excel spreadsheet. To ensure the integrity of the data, regular quality checks will be performed to assess for missing data and invalid field entries.

All electronic study data will be stored on a secure terminal server at the Department of Prevention and Rehabilitation in Physical Therapy, Universidade Federal do Parana, being access limited only to authorized staff, encrypted and password-protected with limited access. All electronic information will be recorded using study identification numbers, rather than participant names.

All data and all source documents, as well as the consent forms, will be filed archived at in a cabinet with restricted access to members of the research group.

After the assessments, the selected patients are randomly allocated into two groups (Fig. 1): experimental group (EG)—composed of individuals who will be subjected to MHM + tracheal aspiration—and control group (CG)—only tracheal aspiration intervention. All individuals will be positioned on dorsal decubitus at the bedside at 30°; MV is adjusted on assisted ventilation mode, controlling volume, tidal volume (Vt) of 6 ml/Kg of predicted weight, positive expiratory-end pressure (PEEP) 8 cmH₂O, inspired oxygen fraction (FIO₂₎, peripheral oxygen saturation (SpO₂) of 94%, and respiratory rate (RR) and flow (V) adjusted to maintain ventilation synchrony and gasometric demands. We will use a number 14 closed aspiration system with verified cuff pressure and the occurrence of leaks. All participants will be subjected to tracheal aspiration, and only 2 h later, the data collection is initiated (Fig. 2). During these 2 h, patients will only be monitored and maintained on the initial position; no concomitant procedures or disconnection of MV circuit are conducted. In case it is not possible to maintain such conditions, the collection is suspended and started again at the appropriate moment. According to Robba et al. (2016), PEEP of 8 does not cause effects on ICP [20].

Assessments will range five stages: T0 (monitoring start), T1 (before ventilation maneuver for the intervention or control groups), T2 (end of ventilation maneuver our control), T3 (after tracheal aspiration), and T4/T5 (monitoring after 10 and 20 min of procedure). The five initial minutes are required for the initial collection of hemodynamic, ventilation, and neurological data. After the start of this period is T1 with a 10-min duration, followed by T2 and T3, with a 5-min duration each. The individuals in T1 who constituted the MHM group will have their ventilation parameters altered for 10 min according to the lung hyperinflation maneuver adopted, subsequently returning to the baseline values. During this period, the individuals in the control group will be only monitored. In T2, both groups will be subjected to tracheal aspiration; subsequently, data will be monitored for 5 min. Finally, the individuals of both groups were monitored at T4 and T5, 10 and 20 min after the procedure, respectively, to verify vital data stabilization (Fig. 2).

We will perform ventilation adjustments to proceed with the MHM. The patient will be maintained on dorsal decubitus at the bedside at 30°, on assisted ventilation mode, and controlled volume. Vt will be increased by 150% based on ideal tidal volume; square wave V; inspiratory time (Ti) equal to 1.5 s, adjusted to a peak of inspiratory flow (PIF) lower than the peak of expiratory flow (PEF); RR of 14 irpm, reduced in case of auto-PEEP; PEEP 8 cmH₂O; FIO₂ minimum of SpO₂ of at least 94%. These parameters will be preserved for 10 min. The MV alarms will be adjusted to allow the safety of the maneuver; in addition, in case of Ppeak above 40 cmH₂O or plateau pressure (Pplateau) above 30 cmH₂O, the maneuver is immediately interrupted and the previous parameters reestablished. The hyperinflation maneuver will not be associated with any other bronchial hygiene maneuver.

After 10 min, the recommendations of the American Association for Respiratory Care [21] (2010) will be applied in the aspiration procedure, suggesting that the patients are ventilated with FIO₂ at 100% for 30 s before and 60 s after the procedure to avoid hypoxemia. In this study, each patient will be subjected to tracheal aspiration for 15 s for three consecutive times through a closed aspiration system with catheter number 14. Subsequently, the ventilation parameters will be readjusted according to the initial parameters.

The CG will be positioned in dorsal decubitus at 30° and will undergo initial ventilatory adjustments and tracheal aspiration, the same procedures performed in the EG 2 h before the start of data collection. Between T1 and T2, they will only be monitored, not going through the MHM. In T3, they will be aspirated as well as EG. They will undergo non-invasive ICC monitoring at the same moments as the EG.

The vital signs (heart rate (HR), RR, MAP, and SpO₂) will be assessed continuously and registered during the assessment stages through a multiparameter monitor Mindray iMEC12, while capnography will be assessed through a monitor and sensor Dräger Vamos®. Criteria for interrupting the intervention are HR < 60 bpm, systolic blood pressure > 180 mmHg, and diastolic blood pressure < 50 mmHg. The ICP assessed in a non-invasive manner will also be monitored during all procedures and 20 min after the end of the collections. The MV alarms will be adjusted to allow to control the airway pressures.

An expert physiotherapist will be present throughout the collection, and in case of hemodynamic and/or neurological instability, as well as an increase in airway pressures above the allowed values, the collection will be suspended, and a physician of the ICU staff will join the procedure.

Primary outcomes will consist of the alterations in ICC indicated in the morphology analysis of the ICP wave due to the MHM since in critical neurological patients, it is crucial to control the secondary lesion and complications caused by the need for MV. Secondary outcomes will range from respiratory mechanics and hemodynamic stability.

During an extensive literature search, no randomized clinical trials were found that investigated the effect of MHM on CHF in post stroke patients. Thus, it was decided to use a study that investigated the effects of a physiotherapy technique on ICP for the sample calculation.

To obtain the sample size needed for this study, we used the combination of statistical software’s R and G-Power 3.1. First, we extracted the intracranial pressure with the techniques performed in the study bellow [28]. From this previous work, we detected that the median value of ICP for the control group was 16.9, and for the intervention group, it is 11.7. Then, we calculated the Cohen-D effect size from the medians using the package ‘rcompanion’ in R [29]. The final step using the GPower is where we estimate with a power of 95% and a confidence level of 95% the minimum sample size for a T-Student equivalence test [30]. The total number of subjects is 60, equally distributed in two groups of 30 patients.

The collected data will be organized on a spreadsheet and summarized using techniques of descriptive statistical analysis. The qualitative variables will be summarized by building frequency tables and the quantitative variables by calculating the descriptive measures (average, mean, standard deviation, and percentiles 25–75).

The evaluations’ primary outcome and secondary outcomes will be made in 5 different times; for that, the data will be analyzed by analysis of variance (ANOVA) two-way for repeated measures with the Tukey post-test for results that present normal distribution and homogeneity of variances, verified by the test of Shapiro–Wilk and Average in Levene, respectively.

Data will be analyzed on an intention-to-treat basis to include all participants based on the random allocation regardless of whether the intervention has been received or not. Adherence to intervention or withdrawal, which is recorded by our trained research assistants on a weekly basis, serves as a covariate and will be included in the data analysis.

Missing data will not be imputed for main primary and secondary analyses. As sensitivity analyses, these analyses will be repeated, using multiple imputation with chained equations for missing data.

The principal investigator and co-investigators will monitor the data collection and storage to ensure that the data is kept and used in accordance with the protocol. A statistician, who is independent and without competing interests, will be responsible to inspect clinical data collected during the study period.

Led by the study coordinator, regular trial conduct, procedural checks, and quality assurance checks will be completed by the study staff. They will verify that all documents containing protected health information are secured and align with the procedures outlined in the protocol.

We aim to publish results from the study in international peer-reviewed journals brain injury rehabilitation. The full protocol, participant-level dataset, and statistical code are granted public access. Authorship will be determined in line with the International Committee of Medical Journal Editors guidelines.

All data will only be accessed by the study researchers and kept strictly confidential. Patient data will be protected by locked cabinets, and use of passwords limited access storage of electronic data. Data will be collected on paper forms and scanned in sequence. As a way to avoid errors, they will be double-checked when they are scanned.