Agbeko 2012.

Methods	Design: RCT (cross‐over design) Unit of randomisation: participant Unit of analysis: the participant, while engaged in a study position Follow‐up: 28 days
Participants	Number of centres: 2 Setting: Paediatric ICU Country: UK and USA Number of participants: 9 Age (years; mean and SD): 10 (± 5) years; range 2–16 years for the 8 participants who completed the study (the age was not provided for the one participant who withdrew from the study) Gender: 7 male and 1 female (the gender was not provided for the one participant who withdrew from the study) Inclusion criteria: age < 18 years, with a diagnosis of severe TBI (GCS ≤ 8) necessitating ICP monitoring Method of recruitment: not reported Recruitment dates: 2004‐2006
Interventions	Intervention: the physiological challenge protocol was identical for both study sites. The degree of HBE was routinely maintained at 30°. From this baseline position, the degree of HBE was varied between 0° and 40° in 10° increments/decrements in a random order, with the axis of rotation at the foot of the bed. The angle of elevation was measured with a protractor. Midline position of the head relative to the neck and thorax was maintained. Including baseline and recovery recordings, a maximum daily total of 6 physiologic signal recording episodes during HBE changes were obtained, each of 10‐min duration. If an intraventricular ICP‐monitoring device was in place, then this remained closed during the HBE challenges. A set of physiological challenges, including 4 random changes in HBE were administered in random order each day to each participant as long as there was an ICP‐monitoring device in place and the participant was deemed clinically stable by the treating physician. Routine neurocritical care included supine position with the HBE at 30° (hips extended); intubation and ventilation to normocapnia; sedation/analgesia with morphine, fentanyl, or midazolam, or a combination of these; and norepinephrine or phenylephrine to increase mean arterial pressure to maintain CPP at 40–70 mmHg dependent on age. In addition, if treatment goals were not met, then barbiturate coma to burst suppression on electroencephalogram monitoring, muscle paralysis with a short‐acting paralytic, and drainage of cerebrospinal fluid via an intraventricular drain were used at the discretion of the attending physician.
Outcomes	ICP, both parenchymal and ventricular, was measured with the Physiologic Data Acquisition System ICP Camino® (Camino Laboratories, San Diego, CA) CPP was calculated: MAP minus ICP ABP was measured with the Physiologic Data Acquisition System ICP Camino®
Notes	Quote: The change in orthostatic pressure (ICP) attributable to a change in HBE angle is proportional to the change in vertical height between the subject’s jugular venous bulb and right atrium. This relationship was confounded by subject height in this paediatric cohort. Therefore, the relationship between ICP change and change in HBE position was normalised to the vertical distance change between the subject’s jugular bulb and right atrium. This was estimated by measuring the distance between the left tragus and ipsilateral nipple. A linear model was used based on the premise that hydrostatic mechanisms would account for most of the change in ICP changes. Ethical approval for the study was obtained from the "Great Ormond Street Hospital for Children National Health Serice Trust/Institute of Child Health Research Ethics Committee and Oregon Health and Science University Institutional Review Board. Parental or legal guardian informed consent was obtained at both sites according to the Declaration of Helsinki guidelines." p. e40 Funding source: "This work was undertaken at Great Ormond Street Hospital/UCL Institute of Child Health, which received a proportion of funding from the Department of Health's NIHR Biomedical Research Centre's funding scheme." p. e39
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	The order of the interventions was determined by pulling folded pieces of paper stating the angle degrees from an envelope by a member of the clinical staff not involved in the study.
Allocation concealment (selection bias)	Unclear risk	The paper reported the use of envelopes for the assignment of interventions, but it is uncertain whether the envelopes were opaque or not and if they were closed or sequentially numbered.
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Although the study seems to have had an open design (no blinding was mentioned in the paper), the short duration of the HBE challenges protocol (10 min) and the prespecified criteria (clinical status deterioration) to stop the protocol make a performance bias unlikely to have occurred.
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Although the study seems to have had an open design (no blinding was mentioned in the paper), the nature of the outcomes with an automated measure makes it unclear to what extent a detection bias may have occurred.
Incomplete outcome data (attrition bias) All outcomes	Low risk	8 participants were analysed from a total of 10 that had been initially recruited. Reasons for exclusion seem justified (1 participant was conscious at the beginning of the protocol and was not randomised into the study, and another participant was randomised but only received one change of HBE instead of 3). In addition, participants received a variable number of sessions of change in position (HBE "challenges"). Usable data were obtained from 8 participants during 18 sessions, resulting in a total of 66 HBE challenges. Number of sessions per participant ranged between 1 and 4.
Selective reporting (reporting bias)	Unclear risk	We did not have access to the study protocol. From the information published in the articles, all outcomes seemed to be reported. However, we cannot exclude a risk of selective reporting.
Other bias	Low risk	No other sources of bias were identified.