Patients with severe acquired brain injury show increased arousal in tilt-table training

¨Brain injury is common and may require long periods of rehabilitation. In Denmark, almost 1,800 patients with acquired brain injury (ABI) have severe physical disabilities, are in a state of coma (i.e. vegetative state (VS) or a minimally conscious state (MCS)) and require rehabilitation for more than 28 days [1]. VS is defined as ”complete unawareness of the self and the environment; it is accompanied by sleep-wake cycles with either complete or partial preservation of hypothalamic and brainstem autonomic functions” [2]. The MCS is characterised by inconsistent, but clearly discernible behavioural evidence of consciousness [3].

Most physical rehabilitation efforts directed at these patients aim to facilitate postural control and arousal [4]. Rehabilitation on a tilt-table is furthermore believed to improve circulation, prevent contractures and increase pulmonary ventilation [5-8].

Evidence supports the idea that early and intensive mobilisation is beneficial for regaining function [9, 10]. One way to mobilise patients in a low state of consciousness or severe paralysis is by use of a tilt-table [5].

Complications such as a rapid orthostatic drop in blood pressure, tachycardia or tachypnoea due to sympathetic dysfunction or the absence of an active venous pump in the paralysed muscles of the lower extremities can occur and can result in a decrease in the intensity of mobilisation which may influence the final rehabilitation outcome [11, 12]. Such complications may be avoided through the use of an integrated tilt-table stepping device. Indeed, one previous study have reported that eight out of nine patients had no drop in blood pressure or increase in heart rate or breathing frequency when using a tilt-table with an integrated robotic stepping device [12]. Nevertheless, these tilt-tables are expensive and therefore often not available in the relevant departments in Danish health-care settings. Thus, this study was conducted to investigate if using a normal tilt-table without an integrated robotic stepping device was feasible for mobilising patients with severe ABI. Additionally, we wanted to investigate if tilt-table training facilitated increased arousal assessed as the time patients had their eyes open.

The primary aim of this study was to investigate if patients with severe ABI could tolerate 20 min. of mobilisation without experiencing orthostatic reactions such as hypotension, tachycardia or tachypnoea more than three times when mobilised on a tilt-table. Secondly, we wanted to investigate if the patients showed increased signs of arousel (i.e. increased eyes-open time during tilt-table training compared with a control period) and thirdly, if mobilisation on a tilt-table had any effect on muscle tone.

MATERIAL AND METHODS

Subjects and design

The patients admitted to the ward from August 2010 to April 2011 were included consecutively. The inclusion criteria were lack of consciousness (VS or MCS) or severe paralysis, at least 18 years of age and injury within three months. The exclusion criteria were fractures, wounds or deep venous thrombosis of the lower extremities making mobilisation on a tilt-table contraindicated.

Procedure

Before inclusion, all patients received standard rehabilitation in the department, which may include mobilisation on a tilt-table. All treatment sessions were conducted in the patient’s own room to avoid unexpected study-related stimulation. 30 min. prior to treatment, the patient was placed in a lying position and no other physical interventions were performed. During this period, a camera recorded the patient to establish the amount of time the patient had open eyes (i.e. as a measure of arousal). The patient was then moved to the tilt-table where baseline blood pressure, heart rate and breathing frequency were measured. This procedure was necessary to ensure the patient’s comfort. Next, the patient was tilted head-up to 30° and the first measurements of blood pressure, heart rate and breathing frequency were performed. After 1 min., the patient was further tilted to 60°, measurements were repeated and followed by the last tilt to 80° (Figure 1). Our clinical practice stipulates 80° as the maximum angle mobilisation in most patients in order to maintain a comfortable position. If orthostatic hypotension, tachycardia, or tachypnoea occurred, the patient was instantly returned to the supine position. This procedure was repeated three times or until 20 measurements had been performed (approximately 20 min.). We adopoted this approach to avoid terminating the treatment due to trivial accidental reactions such as coughing or yawning.

Outcome measures

The primary outcome of the study was time to interruption or termination of treatment due to signs of orthostatic intolerance. Orthostatic hypotension was defined as a drop in systolic or diastolic blood pressure of 20 or 10 mmHg, respectively. Tachycardia was defined as an increase of > 30 beats/min. [13]. Tachypnoea was defined as an increase of breathing frequency of more than 30% from baseline or more than 35 respiratory cycles/min. [12]. For recordings, we used an electronic non-invasive blood pressure monitor (Propaq CS242 BP Monitor, Welch Allyn, New York, USA), which also recorded heart rate and oxygen saturation. Breathing frequency was measured manually each minute by counting the number of breaths for 15 sec. and multiplying by four. We also monitored the effective tilt time before the first, second and third interruption.

Arousal was measured as the proportion of the intervention period that patients kept their eyes open. For comparison, the time with eyes open was also measured during the 30 min. prior to the intervention (i.e. comparing the proportion of eyes open time). Spasticity or hypertonia were recorded at elbows and ankle joints using the Modified Ashworth Scale (MAS) (6-point ordinal scale) before and after the tilt session [14, 15].

Data analysis

All data were analysed using SPSS version 19 (SPSS inc. Chicago, Illinois). The number of patients experiencing symptoms of orthostatic intolerance was expressed as a frequency. Paired sample t-test was used to test for differences in time elapsed before symptoms were detected and for the differences in the proportion of time the patient had open eyes before and during the intervention. Finally, we used the χ2-test to analyse differences between pre and post testing in MAS. A two-sided significance level of 0.05 was used.

Ethics and funding

This study followed the Helsinki Declaration and was approved by the local ethics committee. Written informed consent was obtained from a legal proxy before participation in the study.

Trial registration: not relevant.

RESULTS

A total of 56 patients were admitted to the department during the inclusion period. In all, 20 participants were found to be eligible for the study. After inclusion, two patients improved their function so that tilt-table training was no longer relevant, and two patients were unable to cooperate to consecutive blood pressure measurements due to severe dystonia. Therefore, a total of 16 patients were enrolled. All patients had received standard rehabilitation during their stay in the department according to their capabilities which may have included mobilisation.

Patient characteristics are given in Table 1. Fifteen of the patients were receiving medication that could directly or indirectly (side effects) affect the postural regulation of heart rate and blood pressure.

Orthostatic reactions

Fifteen of the 16 patients were unable to complete 20 min. of training as symptoms were observed at three occasions when mobilised to a standing position on a tilt-table (Table 2). Only one patient had just one interruption due to an orthostatic reaction and thus completed the 20 min. of training. The average time before the occurrence of symptoms during the first, second, and third tilt-test was 244 ± 234, 277 ± 257 and 155 ± 67 sec., respectively (all values are means ± standard deviation). There were no significant differences in these periods between the three recordings (Table 2). Only 19% of the orthostatic reactions occurred at 30° tilt, 37% at 60° and 44% at 80%.

Arousal and muscle tone

There was a significant difference between the mean proportion of time that patients had open eyes in the control period and during the intervention. The proportion of time before the intervention was 22.1% of the 30-min. period corresponding to 7 min. (range: 0-77%). During treatment, the average period that the patients had their eyes open was 9.5 min. The average total intervention time was approximately 15 min., meaning that patients maintained their eyse open for an average 66% (range: 0-100%; p < 0.01) of the intervention period (Table 3).

The modus scores of MAS did not differ before and after the treatment (Table 3).

DISCUSSION

This study illustrates the challenge of mobilising patients with severe sub-acute ABI using a tilt-table without an integrated stepping device. The majority of the patients experienced orthostatic reactions during the intervention and were unable to complete the 20 min. of mobilisation. A novel finding was that despite their failure to remain in the upright position for longer periods, patients had their eyes open for significantly longer periods in the upright tilted position than in the supine position, which indicates that the patients were more aroused in this position. No changes in muscle tone were observed following the tilt training.

Only one patient managed to remain in the head-up tilted position for 20 min. Our study therefore confirms the results of Luther et al who also found problems with orthostatic intolerance in nine patients who were very similar to the ones participating in our study There was a minor difference in orthostatic intolerance (7 min. in the study by Luther et al versus 4 min. 30 sec. in ours) [12].

The time to signs of orthostatic intolerance is of interest. The question of whether or not the mean intervention period sufficed as an effective treatment for the patient remains unanswered. If the purpose of tilt-table training is to prevent contractures, one study has indicated that 30 min. of daily standing is sufficient [7]. Luther’s study [12] and the present results support the notion that this intensity is difficult to reach as patients experience orthostatic intolerance. On the other hand, a study by Chang et al found that 5 min. of standing significantly increased pulmonary ventilation [6]. This is very close to that observed in the present study (4 min. 30 sec.).

A significant difference in eyes open time (i.e. arousal) was observed as a direct result of the mobilisation on a tilt-table. We propose that the increase in eyes open time is of clinical importance. A study by Elliot et al supports this notion, as they observed 12 patients in VS or MCS for 20 min. while standing on a tilt-table for reactions associated with awareness. Eight of the patients showed positive reactions including “eyes open” [16]. Therefore, a higher intensity of standing (i.e. longer duration) may be beneficial.

In patients with severe ABI, the orthostatic reactions may be due to either damage to the brain stem or to long duration of imobilisation. It is well known that head-up tilt activates three of the mechanisms responsible for cardiovascular adaptation to the upright posture. Suppression of the release of vasopressin and the renin-angiotensin-aldosterone system as well as stimulation of the release of atrial natriuretic peptide have been associated with orthostatic intolerance due to inactivity, such as prolonged head down bed rest [17-19]. Verheyden et al managed to improve the orthostatic intolerance in patients with neurally mediated syncope by tilt-table training [20]. It could therefore be hypothesised that a treatment protocol with repeated head-up tilt training would improve the orthostatic tolerance through these mechanisms even in a patient with severe ABI.

We observed no change in muscle tone. Most patients scored “0” before treatment and an insignificant trend in our results shows a lower score after mobilisation in those patients who scored more than “0”. Results may have been different in a group of patients with higher scores.

We compared an average baseline measurement with a single reading during tilting. We found this necessary because we had to respond to the patient’s reactions in terms of blood pressure, since we had no recording of the actual cerebral perfusion, which is the truly important clinical value.

In the present study, the proportion of time that the patient had open eyes was used as a simple measure for the level of arousal. Alternative methods for investigation of arousal would have been preferred, but where not possible in the setup of the present study. Even so, our results indicate that in the future it may be of interest to compare this to other tests measuring arousal or awareness.

Only three patients were on drugs that directly affected blood pressure including the one patient who completed the protocol. Since we were unable to discontinue the patients’ medication, this was a potential bias.

CONCLUSION

Patients with severe ABI admitted for subacute rehabilitation showed reactions of orthostatic intolerance when mobilised on a tilt-table without an integrated stepping device, which resulted in a low mobilisation intensity. Despite the short period, patients showed a significant increase in arousal when mobilised (measured as percentage of time with eyes open) .

Future studies should include measurements of neuroendocrine changes associated with handling of sodium and water, and an estimate of changes in intravascular volume in response to tilt in order to better understand the mechanism behind orthostatic hypotension in severely brain-injured patients. The necessary dose of tilt-table training compared with tilt-table training using an integrated stepping device with a view to restoring the orthostatic tolerance should be investigated.

Correspondence: Christian G. Riberholt, Afdeling for Højt Specialiseret Neurorehabilitering/Traumatisk Hjerneskade, Hvidovre Hospital, Kettegård Allé 30, 2650 Hvidovre, Denmark. E-mail: christian.riberholt@regionh.dk

Accepted: 25 September 2013

Conflicts of interest:Disclosure forms provided by the authors are available with the full text of this article at www.danmedj.dk

Acknowledgement: We wish to extend our gratitude to Tina Jørgensen, Department of Physical Therapy, Hvidovre Hospital, and Julie W. Hansen, Department of Neurorehabilitation, Traumatic Brain Injury Unit, Glostrup University Hospital, for acquisition of data.