I. Disorders of Consciousness

One in eight patients with severe closed head injury has been reported to suffer from prolonged coma and vegetative state as a consequence of the head injury. Research suggests that the responsiveness and environmental awareness of people in vegetative state (VS) or minimally conscious state (MCS) is often underestimated by clinicians. The mainstay of diagnosis is clinical evaluation for evidence of localizing or discriminating behaviours indicating awareness of self or the environment. The Glasgow Coma Scale (GCS) is widely used in acute settings to evaluate the level of consciousness. Clinicians must be aware that although the GCS is very useful for some aspects of traumatic brain injury (TBI) care, it is not a valid diagnostic tool for prolonged disorders of consciousness (PDOC), and more sensitive and refined assessment is required to categorize prolonged disorders of consciousness (PDOC). This is important as treatment and prognosis is highly dependent on accurate differentiation of the type of disorders of consciousness (DOC).

The prognosis is not always poor. 50% of vegetative survivors of severe brain injuries are able to regain consciousness within one year of injury and up to 40% subsequently improve to a higher level of the GCS. Sensory stimulation in particular has been promoted as a means to facilitate recovery and counter the negative impact of sensory deprivation often present in institutional care. Multi-modal stimulation may improve outcomes but too much stimuli may be more than the injured brain can handle. Close observation of responses to controlled stimuli allows for monitoring of progress. Carefully and gradually mobilizing these patients helps reduce the potential adverse effects associated with immobilization. Families can frequently play an important role.

For patients who are in a state of post-traumatic amnesia (PTA), it is necessary to document their progression to identify patterns of recovery and also to plan for when patients may be ready to progress to active sub-acute rehabilitation. Formal evaluation with validated tools is necessary given the fluctuating course of recovery associated with poor awareness typical at this level of recovery. Further, clinical care should focus on an orienting, structured, less stimulating environment with efforts focussed on minimizing use of restraints and sedating medications.

Patients with disorders of consciousness, in particular coma or a minimally conscious state, require ongoing access to interdisciplinary and specialized care. As such, not all centres may be able to provide this level of specialized care, even with adequate resources to monitor and rehabilitate these challenging patients. There must be frequent reassessment using standardized assessments. The degree of stimulation and mobilization needs to be monitored as the optimal balance of stimulation and rest is not known.

The team may need to do prolonged observations and multiple trials to determine true responsiveness of those in prolonged VS. The use of a tilt table or other mechanical device will likely be required and should be available in any centre that cares for patients with low levels of consciousness (LCFS 1-2). For patients with LCFS scores of 3 to 5 who are in a PTA state, the care environment must be able to provide a low stimulation environment with structure and consistency of care including consistent staffing as well as orienting information and materials for patients.

Indicators examples

• Number and proportion of patients with whom restraints are used.
• Frequency of the use of restraints / week.
• Average duration of the use of restraints.
• Presence of low stimulation rooms (LSR).
• Average length of LSR use (days).
• Proportion of individuals with a severe disorder of consciousness who are assessed monthly during the first year post injury.

The following are suggestions of tools and resources that can be used to support the implementation of the recommendations in this section. Healthcare professionals must respect the legal and normative regulations of the regulatory bodies, in particular with regards to scopes of practice and restricted/protected activities, as these may differ provincially

All individuals with TBI, who have a disorder of consciousness, require close and ongoing assessment and observation. Family members may play a productive role in the early stages of care, especially with regaining consciousness.

Post-traumatic amnesia

The recommendation regarding post-traumatic amnesia assessment in individuals with traumatic brain injury were adapted from the INCOG2022 guideline, which synthesized evidence from multiple studies, including by Ponsford al.2021; a prospective longitudinal study Spiteri et al. (2021) and Hennessy et al. (2020).

The recommendations regarding using various environmental interventions, such as auditory or multimodal stimulation, light therapy and sleep hygiene in management of post traumatic amnesia with the aim to reduce agitation were adapted from the INCOG 2022 guideline, informed by a number of studies, including reviews by Carrier et al. (2021) and Block et al. (2021); an RCT by Makley et al. (2020) a randomized crossover trial by Park et al. (2016) and a systematic review by Carrier et al. (2022).

Non-pharmacological Interventions 

Multimodal Sensory Stimulation. Abbasi et al. (2009) conducted a well-designed randomized controlled trial (RCT) to evaluate the effects of sensory stimulation through structured family visits on consciousness as assessed by the Glasgow Coma Scale (GCS). Families received training about coma; how to provide appropriate stimulation and how to remain calm. Patients receiving family visits showed significantly greater GCS scores on each day of the intervention and attained a mean GCS that was 2 points higher than that of the control group. Although no long-term outcomes were evaluated and no follow-up was reported, these results suggest that family-provided stimulation may be an effective intervention for stimulating recovery from a coma. (Abbasi et al., 2009). 

A number of small studies of sensory stimulation including auditory, olfactory and tactile stimulation alone or in combination with other modalities provide early evidence for their use in care. The literature includes studies by Moattari et al. (2016), Heine et al. (2017), Cheng et al. (2018), Luaute et al. (2018), Deshpande et al. (2019). Due to smaller sample sizes and variations in methodology, concrete recommendations on stimulus dosage and schedule cannot be made at this point. Caution should be used to avoid overstimulation.

Johnson et al. (1993) randomly assigned patients to a group that received multimodal sensory stimulation or to a group that received no purposeful sensory stimulation at all. The primary outcome in this study was changes in the GCS post treatment. However, Johnson et al. (1993) did not report any data on this measure and only presented data on biochemical and physiological parameters of questionable clinical importance. The strength of the study findings has been questioned due to the “poor” methodological score (PEDro = 3); conclusions, were not based upon the study’s findings. Overall, the studies identified in this area generally show greater improvements in a variety of measures following multimodal sensory stimulation. Some studies aimed to investigate if the duration of coma could be reduced using sensory stimulation as their only objective. For example, Mitchell et al. (1990) reported that patients subjected to multimodal sensory stimulation experienced significant reductions in the duration of coma compared with controls. Again, duration of coma was their only outcome and in the absence of other measures of clinical importance, such as functional indicators (i.e., Glasgow Outcome Scale or Disability Rating Scale), such results fall short in demonstrating any clinical functional benefit of sensory stimulation. A 2002 Cochrane review showed similar results stating that there was insufficient evidence to refute or support the use of multisensory programs for patients in coma or  unresponsive wakefulness syndrome (Lombardi et al., 2002).

Auditory Stimulation. PTA duration is often used as an indicator of injury severity and as a predictor of outcome; therefore, it has been recommended that a validated PTA assessment tool be performed regularly until PTA has resolved (J. Ponsford & Sinclair, 2014). Numerous studies have examined potential assessment tools (Frey, Rojas, Anderson, & Arciniegas, 2007; Jackson, Novack, & Dowler, 1998; Shores, 1995; Tate et al., 2006; Tate, Pfaff, & Jurjevic, 2000). Recommendations regarding the management of individuals with PTA have been made mainly on clinical experience and little research is available to support these guidelines (Ponsford & Sinclair, 2014; Ponsford, Tweedly, Lee, & Taffe, 2012; Snow & Ponsford, 2012). 

A small RCT by Gorji et al. (2014) looked at the impact of an auditory stimulus (MP3 recording of a familiar voice twice daily for 15 minutes) vs. no additional stimulation on consciousness level in 13 patients with traumatic coma. Glasgow Coma Scale was applied to evaluate patients’ level of consciousness. The study found that the experimental group achieved a GCS score of 15 sooner than the control group, suggesting that familiar auditory stimulation could have positive effects for patients with traumatic coma in the ICU. Additional smaller studies examined physiologic effects of auditory stimulation by familiar voices (Pape et al., 2015, Parveen et al., 2015, Moghaddam et al., 2016) or music (Sun et al., 2015).

Insufficient evidence (non-pharmacological interventions). Multiple studies assessing the utility of various pharmaceutical and non-pharmaceutical interventions were reviewed, but the evidence they provided is not sufficient to make recommendations at this stage due to methodological limitations, small sample sizes, mixed intervention modalities, lack of replication and early stages of research.

A crossover RCT by Matsumoto-Miyazaki et al. (2016) and a cross-over Pragmatic Clinical Trial (PCT) by Matsumoto-Miyazaki et al. (2016) examined effects of acupuncture alone or in combination with Transcranial magnetic stimulation.

Hyperbaric oxygen therapy (HBO) was studied in a case control by Liu et al. (2022) provided indirect evidence of the potential benefit of HBO. Additional research is needed to gather more direct evidence of HBO utility (Lu et al., 2021). 

Several recent studies have provided indirect support for the potential benefit of Repetitive Transcranial Magnetic Stimulation (rTMS) including a Case Controlled study by Liu et al. (2022), an RCT by Bender Pape et al. (2020), and an RCT by He et al. (2018). It is important to note that most of the studies reviewed combined the treatment with another modality, making it difficult to isolate the potential effects of rTMS. More research is needed to establish more direct evidence of the utility of rTMS. 

Transcranial extracorporeal shockwave therapy was evaluated in a pre-post study by Lohse-Busch et al. (2014) in 5 patients with unresponsive wakefulness syndrome. The limitations of this trial include its small sample size and lack of replication. 

Transcranial direct current stimulation (tDCS) was evaluated in several studies, including a Pre-Post study by Straudi et al. (2019), an RCT by Thibaut et al. (2017) and a Pre-Post study by Angelakis et al. (2014).This research provides some emerging evidence, but it is lacking breadth of evidence across replication to determine if it should be a clinical practice guideline recommendation at this stage. 

Transcutaneous nerve stimulation was assessed in a Pre-Post study by Hakon et al. (2020), an RCT by Nekkanti et al. (2016), and a PCT by Lei et al. (2015) presenting another area of ongoing research and emerging evidence.

Pharmacological Interventions

Melatonin. A small PCT by Guaraldi et al. (2014) studied the nocturnal melatonin levels and light-induced melatonin suppression in 6 patients, suggesting benefits of melatonin supplementation.

Zoloidem. Two retrospective chart review studies by Oommen et al. (2019) and Zhang et al. (2021) looked at the effects of zoloidem in to investigate the effects of the medication to improve wakefulness in individuals with disorders of consciousness post TBI. A pre-post study by Du et al. (2014) explored the efficacy and indications of 10 mg of zolpidem delivered via a nasogastric tube in a group of 165 patients with unresponsive wakefulness syndrome  due to traumatic and acquired brain injuries. The study showed positive effects on restoring brain function in patients with injuries in non-brain stem areas.

Amantadine. Amantadine has been studied alone or in combination with other pharmaceutical and non-pharmaceutical interventions in numerous trials including Hintze et al. (2022), Hadgu et al. (2021), Bender Pape et al. (2020), Abbasivah et al. (2019), Oommen et al. (2019), Ghalaenovi et al. (2018) and Salyhoglu & Sahyn (2019). An earlier placebo-controlled RCT by Giacino (2012) provides level A evidence that amantadine may promote recovery of consciousness in subacute phase post TBI. 

Insufficient evidence (pharmacological interventions). Multiple studies assessing the utility of various pharmaceutical interventions were reviewed, but the evidence they provided is not sufficient to make recommendations at this stage due to methodological limitations, small sample sizes, mixed intervention modalities, lack of replication and early stages of research.

At this stage insufficient evidence exists in literature to either endorse or advise against the following pharmaceutical treatments for individuals with moderate to severe TBI and disorders of consciousness:

• Atorvastatin - Soltani et al. (2021) 
• Citicoline - Shokouhi et al. (2014)
• Intrathecal baclofen - Margetis et al. (2014)
• Lorazepam Retrospective Chart Review - Zhang et al. (2021) 
• Methylphenidate - Kamali et al. (2021) and Oommen et al. (2019) 
• Modafinil - Hintze et al. (2022), Oommen et al. (2019) and Dhamapurkar et al. (2017) 
• Selenium - Moghaddam et al. (2017) 
• Vitamin D - Sharma et al. (2020), literature review by Choudhary et al. (2021)