The effect of early exercise on intracranial pressure in neurocritical patients: a systematic review

Background: Neurocritical patients commonly present with increased intracranial pressure and are regularly treated with physiotherapy through exercise early after admission to the intensive care unit. However, the effect of exercise on intracranial pressure is minimally investigated, and there appears to be no systematic reviews or meta-analyses addressing this topic in the published literature. This study aimed to determine the effect of exercise on the intracranial pressure of neurocritical patients. Methods: Through a systematic review, literature searches on PubMed, PEDro, and CENTRAL were conducted in January 2020. The keywords used were: “physical therapy”, “physiotherapy”, “exercise”, “range of motion”, “intracranial pressure”, and “ICP”, combined using Boolean operators “OR” and “AND”. Only studies published in the English and Indonesian language were considered. Results: A total of five studies involving 193 patients (mean age 41-56 years old) were included in this review. Most included studies reported that intracranial pressure did not change significantly after passive range of motion exercise, and some studies found that intracranial pressure actually decreased significantly during and after passive range of motion and active exercise. An additional finding was that isometric exercise significantly increased mean intracranial pressure in patients with normal intracranial pressure. All studies reported that exercise could be used safely in patients. Conclusion: Exercise, in particular passive range of motion, does not increase the intracranial pressure of neurocritical patients and does not lead to any adverse effects, as long as isometric or Valsalva-like maneuvers are avoided.


Introduction
Patients with severe cerebral diseases or injuries, such as cerebral infarction, intracerebral/cerebral hemorrhage, and traumatic brain injury (TBI), commonly present with increased intracranial pressure (ICP) that can affect patient outcome. 1 Increased ICP can result in decreased cerebral perfusion pressure (CPP) causing cerebral ischemia, 2 or cause herniation of the brainstem or other vital structures, which may lead to deleterious neurological damage or even brain death in severe cases. 3,4 Consequently, monitoring and controlling ICP is essential in neurocritical care.
Neurosurgical patients are prone to a wide variety of complications that could occur as a result of immobilization, such as contractures, deep vein thrombosis, 5 muscle wasting, 6 and pulmonary complications. 7 Thus, patients are regularly treated with physiotherapy early after admission to the ICU, as recommended by the European Respiratory Society and European Society of Intensive Care Medicine Task Force on Physiotherapy for Critically Ill Patients. 8 Physiotherapy interventions provided can include passive and active exercises, and respiratory/chest physiotherapy such as postural drainage, tapping, vibrocompression, vibration, increased expiratory flow rate (IEF) and endotracheal aspiration (ETA) techniques.
A systematic review 9 concluded that respiratory physiotherapy (maneuvers that included airway clearance and ETA techniques) lead to increased ICP in critically ill patients admitted to the ICU. However, although standard physiotherapy through passive and active exercise is often provided in the ICU, there is limited research regarding exercise in patients in the acute phase of cerebral diseases or injuries. There is still a common fear of harming critically ill patients with elevated ICP, which often results in "minimal handling" of patients. 10,11 Hence, it is important to know whether exercise is safe to conduct without any detrimental effects on ICP in this category of patients to relieve the fear of harming the patient.
Currently, there are no systematic reviews or meta-analyses in the published literature addressing the effect of exercise on ICP in neurocritical patients. Therefore, this systematic review aimed to examine the effect of exercise on ICP in neurocritical patients.

Method
This systematic review was carried out according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. 12

Eligibility Criteria
The inclusion criteria of this review were: 1) study participants were neurological-neurosurgical patients with ICP monitoring; 2) the intervention provided was exercise, where exercise interventions were defined as passive range of motion (PROM) or passive exercise and active exercise. PROM or passive exercise was defined as repeated movements of a joint within the range of that joint performed by the physiotherapist, while active exercise was defined as repeated movements of a joint within the range of that joint performed by the patient; 3) the outcome was ICP value; and 4) studies published in English or Indonesian. Dissertations, thesis, literature reviews, case reports, letters, abstracts, studies using animal models, and studies published in other languages were excluded.

Information Sources and Search Strategy
The literature search was conducted using the keywords: "physical therapy", "physiotherapy", "exercise", "range of motion", "intracranial pressure", and "ICP", which were combined using Boolean operators "OR" and "AND" in PubMed, Physiotherapy Evidence Database (PEDro), and Cochrane Central Register of Controlled Trials (CENTRAL) from database inception to January 2020. An example of the search strategy for use in CENTRAL can be seen in Table 1.

Data Collection Process and Data Items
Data of study population, intervention, and outcome were extracted using the Joanna Briggs Institute (JBI) Data Extraction Form for Experimental/Observational Studies.

Data Synthesis
The findings of the included studies were summarized and a narrative synthesis approach was undertaken.

Assessment of Methodological Quality
Relevant studies were retrieved in full and were critically appraised for methodological quality by two reviewers (SAPT and PEM) using the JBI Critical Appraisal Checklist for Quasi-Experimental Studies (non-randomized experimental studies), which consists of nine questions to evaluate the study's research design and validity of results. 13 The included articles were classified as "high quality" if they achieved a total score of ≥5 or as "low quality" if they 43 Published by: Indoscholar Publishing Services (www.indoscholar.com) scored ≤4. The total score was used to indicate the methodological quality of the articles and was not used as an inclusion or exclusion criteria. No disagreements occurred among review authors. Figure 1 shows the number of records identified, included and excluded. A total of 284 articles were identified, with 210 remaining after duplicates were removed. Following the screening of these articles, a total of five articles appeared to be relevant to this review and were retrieved in full-text.  Table 2 shows the critical appraisal results of the included studies. All studies were clear regarding the "cause" (exercise) and "effect" (ICP) explored, compared the results of measurement before and after the intervention/treatment, had complete follow-up of participants, used reliable outcome measures, and used appropriate statistical analyses. All but one study 14 included participants that were similar in terms of characteristics. One study involved a control group of healthy individuals for the purpose of comparing the results. As this study 14 involved a healthy control group, there were differences in the characteristics of participants and treatment/care provided in the compared groups, and outcomes in the control group were measured differently compared to the patient group. The remaining studies compared the results between periods (before, during, and after the intervention). Four studies achieved a score of 8/9 and one study obtained a score of 6/9, meaning that all studies were classified as "high quality" quasi-experimental studies. The details of study characteristics are provided in Table 3. The five studies included a total of 193 participants between the mean age of 41 and 56 years. Individual sample sizes of these studies ranged from 12 to 84. All studies involved patients of both genders with neurological-neurosurgical disease treated in the neuro-ICU. The majority of studies provided exercise in the form of PROM, 5,10,14,15 while one also provided active exercise, 15 and another study 16 provided bedside cycle exercise using a bedside cycle ergometer for both passive and active exercise.

Result
Besides ICP, other haemodynamic variables such as CPP, mean arterial pressure (MAP), blood pressure (BP), heart rate (HR), and systemic arterial pressure (SAP) were also considered as outcomes in the studies included in this review. However, this review specifically focused on presenting the results of the effects of exercise on ICP.
Two of the five studies showed significant decreases in ICP during PROM when compared to before PROM. 10,14 Two studies 14,15 found significant decreases in ICP after PROM when compared to before PROM; more specifically, Brimioulle et al., 15 reported that in JBI Checklist Criteria Koch et al. 5 Brimioulle et al. 15 Thelandersson et al. 14 Roth et al. 10 Thelandersson et al. 16 1

Conclusion
In