Acute traumatic coma awakening by right median nerve electrical stimulation: a randomised controlled trial.

PURPOSE: Severe traumatic brain injury (TBI) leads to acute coma and may result in prolonged disorder of consciousness (pDOC). We aimed to determine whether right median nerve electrical stimulation is a safe and effective treatment for accelerating emergence from coma after TBI. METHODS: This randomised controlled trial was performed in 22 centres in China. Participants with acute coma at 7-14 days after TBI were randomly assigned (1:1) to either routine therapy and right median nerve electrical stimulation (RMNS group) or routine treatment (control group). The RMNS group received 20 mA, 300 µs, 40 Hz stimulation pulses, lasting 20 s per minutes, 8 h per day, for 2 weeks. The primary outcome was the proportion of patients who regained consciousness 6 months post-injury. The secondary endpoints were Glasgow Coma Scale (GCS), Full Outline of Unresponsiveness scale (FOUR), Coma Recovery Scale-Revised (CRS-R), Disability Rating Scale (DRS) and Glasgow Outcome Scale Extended (GOSE) scores reported as medians on day 28, 3 months and 6 months after injury, and GCS and FOUR scores on day 1 and day 7 during stimulation. Primary analyses were based on the intention-to-treat set. RESULTS: Between March 26, 2016, and October 18, 2020, 329 participants were recruited, of whom 167 were randomised to the RMNS group and 162 to the control group. At 6 months post-injury, a higher proportion of patients in the RMNS group regained consciousness compared with the control group (72.5%, n = 121, 95% confidence interval (CI) 65.2-78.7% vs. 56.8%, n = 92, 95% CI 49.1-64.2%, p = 0.004). GOSE at 3 months and 6 months (5 [interquartile range (IQR) 3-7] vs. 4 [IQR 2-6], p = 0.002; 6 [IQR 3-7] vs. 4 [IQR 2-7], p = 0.0005) and FOUR at 28 days (15 [IQR 13-16] vs. 13 [interquartile range (IQR) 11-16], p = 0.002) were significantly increased in the RMNS group compared with the control group. Trajectory analysis showed that significantly more patients in the RMNS group had faster GCS, CRS-R and DRS improvement (p = 0.01, 0.004 and 0.04, respectively). Adverse events were similar in both groups. No serious adverse events were associated with the stimulation device. CONCLUSION: Right median nerve electrical stimulation is a possible effective treatment for patients with acute traumatic coma, that will require validation in a confirmatory trial.

Right median nerve electrical stimulation for acute traumatic coma (the Asia Coma Electrical Stimulation trial): study protocol for a randomised controlled trial.

BACKGROUND: Traumatic brain injury (TBI) has become the most common cause of death and disability in persons between 15 and 30 years of age, and about 10-15% of patients affected by TBI will end up in a coma. Coma caused by TBI presents a significant challenge to neuroscientists. Right median nerve electrical stimulation has been reported as a simple, inexpensive, non-invasive technique to speed recovery and improve outcomes for traumatic comatose patients. METHODS/DESIGN: This multicentre, prospective, randomised (1:1) controlled trial aims to demonstrate the efficacy and safety of electrical right median nerve stimulation (RMNS) in both accelerating emergence from coma and promoting long-term outcomes. This trial aims to enrol 380 TBI comatose patients to partake in either an electrical stimulation group or a non-stimulation group. Patients assigned to the stimulation group will receive RMNS in addition to standard treatment at an amplitude of 15-20 mA with a pulse width of 300 µs at 40 Hz ON for 20 s and OFF for 40 s. The electrical treatment will last for 8 h per day for 2 weeks. The primary endpoint will be the percentage of patients regaining consciousness 6 months after injury. The secondary endpoints will be Extended Glasgow Outcome Scale, Coma Recovery Scale-Revised and Disability Rating Scale scores at 28 days, 3 months and 6 months after injury; Glasgow Coma Scale, Glasgow Coma Scale Motor Part and Full Outline of Unresponsiveness scale scores on day 1 and day 7 after enrolment and 28 days, 3 months and 6 months after injury; duration of unconsciousness and mechanical ventilation; length of intensive care unit and hospital stays; and incidence of adverse events. DISCUSSION: Right median nerve electrical stimulation has been used as a safe, inexpensive, non-invasive therapy for neuroresuscitation of coma patients for more than two decades, yet no trial has robustly proven the efficacy and safety of this treatment. The Asia Coma Electrical Stimulation (ACES) trial has the following novel features compared with other major RMNS trials: (1) the ACES trial is an Asian multicentre randomised controlled trial; (2) RMNS therapy starts at an early stage 7-14 days after the injury; and (3) various assessment scales are used to evaluate the condition of patients. We hope the ACES trial will lead to optimal use of right median nerve electrical treatment. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02645578 . Registered on 23 December 2015.

Right Median Nerve Electrical Stimulation for Acute Traumatic Coma Patients.

The right median nerve as a peripheral portal to the central nervous system can be electrically stimulated to help coma arousal after traumatic brain injury (TBI). The present study set out to examine the efficacy and safety of right median nerve electrical stimulation (RMNS) in a cohort of 437 comatose patients after severe TBI from August 2005 to December 2011. The patients were enrolled 2 weeks after their injury and assigned to the RMNS group (n=221) receiving electrical stimulation for 2 weeks or the control group (n = 216) treated by standard management according to the date of birth in the month. The baseline data were similar. After the 2-week treatment, the RMNS-treated patients demonstrated a more rapid increase of the mean Glasgow Coma Score, although statistical significance was not reached (8.43 ± 4.98 vs. 7.47 ± 5.37, p = 0.0532). The follow-up data at 6-month post-injury showed a significantly higher proportion of patients who regained consciousness (59.8% vs. 46.2%, p = 0.0073). There was a lower proportion of vegetative persons in the RMNS group than in the control group (17.6% vs. 22.0%, p = 0.0012). For persons regaining consciousness, the functional independence measurement (FIM) score was higher among the RMNS group patients (91.45 ± 8.65 vs. 76.23 ± 11.02, p < 0.001). There were no unique complications associated with the RMNS treatment. The current study, although with some limitations, showed that RMNS may serve as an easy, effective, and noninvasive technique to promote the recovery of traumatic coma in the early phase.

Diverse effects of hypothermia therapy in patients with severe traumatic brain injury based on the computed tomography classification of the traumatic coma data bank.

A multicenter randomized controlled trial of patients with severe traumatic brain injury who received therapeutic hypothermia or fever control was performed from 2002 to 2008 in Japan (BHYPO). There was no difference in the therapeutic effect on traumatic brain injury between the two groups. The efficacy of hypothermia treatment and the objective of the treatment were reexamined based on a secondary analysis of the BHYPO trial in 135 patients (88 treated with therapeutic hypothermia and 47 with fever control). This analysis was performed to examine clinical outcomes according to the CT classification of the Traumatic Coma Data Bank on admission. Clinical outcomes were evaluated with the Glasgow Outcome Scale and mortality at 6 months after injury. Good recovery and moderate disability were defined as favorable outcomes. Favorable outcomes in young patients (≤50 years old) with evacuated mass lesions significantly increased from 33.3% with fever control to 77.8% with therapeutic hypothermia. Patients with diffuse injury III who were treated with therapeutic hypothermia, however, had significantly higher mortality than patients treated with fever control. It was difficult to control intracranial pressure with hypothermia for patients with diffuse injury III, but hypothermia was effective for young patients with an evacuated mass lesion.

[Recovery of consciousness by electrical dorsal column stimulation in brain injury patients].

Treatment with electrical dorsal column stimulation was performed in 7 cases of diffuse axonal injury, 2 cases of brain contusion and 1 case of hypoxic diffuse brain damage. After inadequate response to various treatment modalities, each patient was implanted with a spinal cord stimulation system. The effectiveness was assessed using a standard scoring system which consisted of state scale and reaction scale (the society for treatment of coma). Both state scale and reaction scale were considered to improve in 4 patients after dorsal column stimulation. In 5 patients, the effectiveness of dorsal column stimulation could not be distinguished from natural improvement. One patient of hypoxic brain damage showed slight deterioration after the dorsal column stimulation. Among the state scale, significant improvement was found in spontaneous movement of the oral cavity and pharynx, spontaneous changes of expression muscles, concern about circumstances, voluntary purposeful movement, and coherent verbalization 2 weeks after the operation. As dorsal column stimulation can cause consciousness recovery from the semicomatose state, it should be considered as the treatment choice for the consciousness disturbance.

Acute management of acquired brain injury Part III: an evidence-based review of interventions used to promote arousal from coma.

PRIMARY OBJECTIVE: To review the literature regarding techniques used to promote arousal from coma following an acquired brain injury. MAIN OUTCOMES: A literature search of multiple databases (CINAHL, EMBASE, MEDLINE and PsycINFO) and hand searched articles covering the years 1980-2008 was performed. Peer reviewed articles were assessed for methodological quality using the PEDro scoring system for randomized controlled trials and the Downs and Black tool for RCTs and non-randomized trials. Levels of evidence were assigned and recommendations were made. RESULTS: Research into coma arousal has generally focused on the stimulation of neural pathways responsible for arousal. These pathways have been targeted using pharmacological and non-pharmacological techniques. This review reports the evidence surrounding agents targeting dopamine pathways (amantadine, bromocriptine and levodopa), sensory stimulation, music therapy and median nerve electrical stimulation. Each of these interventions has shown some degree of benefit in improving consciousness, but further research is necessary. CONCLUSIONS: Despite numerous studies, strong evidence was only found for one intervention (Amantadine use in children) and this was based on a single study. However, each of the interventions showed promise in some aspect of arousal and warrant further study. More methodologically rigorous study is needed before any definitive conclusions can be drawn.

How does information influence hope in family members of traumatic coma patients in intensive care unit?

AIMS: To assess the interplay between hope and the information provided by health care professionals. BACKGROUND: Earlier research learned that hope is crucial for relatives of traumatic coma patients. Also it has been reported that the need for information is extremely important for relatives of critically ill patients. DESIGN: A qualitative approach according to the 'grounded theory' method with constant comparison was used. METHOD: We held 24 in-depth interviews with 22 family members of 16 patients with traumatic coma. Data processing and data analysis took place in a cyclic process wherein the induction of themes was alternated by confrontation with new material. RESULTS: Family members of traumatic coma patients want information that is as accurate as possible, provided by doctors and nurses in an understandable manner and leaving room for hope. At first, family members can do no more than passively absorb the information they receive. After some time, they actively start working with information and learn what to build their hope on. In this way, concrete hope evolves and seems to be strongly determined by information. Information that is more positive than warranted is not appreciated at all. It leads to false hope and once its real nature becomes apparent, to increased distress and loss of trust in the professionals. CONCLUSION: The process of hope is crucial in coping with traumatic coma and information can facilitate this process. RELEVANCE TO CLINICAL PRACTICE: If professionals, especially nurses, keep the process in mind that family members go through in handling information, they can not only facilitate this process but also help them to establish realistic hope.

Cell therapy of comatose states.

We demonstrated that liquor from adult humans can maintain proliferative activity of cells of immature nervous tissue in vitro. The paper presents the results of a retrospective clinical study of the efficiency of cell therapy in the treatment of II-III degree comatose patients with severe brain injury. Cell suspension consisting of cells derived from immature nervous and hemopoietic tissues was injected into the recipient subarachnoidal space through a cerebrospinal puncture. The mortality in the study group was 8% vs. 56% in the control group. The 1.5-year follow-up demonstrated significantly better quality of life in patients receiving cell therapy in comparison with patients of the control group. Cell therapy proved to be ineffective for patients in a comatose state caused by hypoxic encephalopathy. The study demonstrated the efficiency of cell therapy in patients with severe brain injury during the acute period of the disease.

[Cerebral circulatory autoregulation as a guide for controlling the parameters of assisted ventilation in acute severe brain injury].

The paper presents the results of cerebral circulation (CC) in 17 ventilated patients with severe brain injury in its acute phase. All the patients developed traumatic subarachnoidal hemorrhage, which was accompanied with angiospasm in the majority of cases. Doppler transcranial study (DTCS) was performed, by using the carotid compression test; the findings correlated with paCO2 and CV parameters. A dynamic study was performed every two days starting from their admission to an intensive care unit to the recovery from coma or normalization of CC parameters. The dilation and constriction components of the CC reserve were assessed from the results of this test and continued to be controlled during therapy. Thus, this paper shows the possibility of goal-oriented correction of CC autoregulation and optimization by selecting the parameters of assisted ventilation and by changing paCO2 under the guidance of Doppler transcranial study.

Effect of arousal methods for 175 cases of prolonged coma after severe traumatic brain injury and its related factors.

OBJECTIVE: To determine the effect of arousal methods for prolonged coma of 175 patients with severe traumatic brain injury and related factors. METHODS: There were 175 cases with persistent coma longer than 1 month after severe traumatic brain injury. Coma lasted 1-12 months. Arousal procedures included hyperbaric oxygen, physical therapy and arousal drugs. RESULTS: In the 175 prolonged coma patients 110 got recovery of consciousness; in 118 cases with coma of 1-3 months, 86 cases recovered consciousness (72.9%); in 42 cases with coma of 4-6 months, 20 cases recovered consciousness (47.6); and in 15 cases with coma of longer than 6 months, only 4 cases recovered consciousness (26.7%). The recovery of consciousness depended on patient's primary brain stem damage, cerebral hernia, GCS score, and age. CONCLUSIONS: Application of appropriate arousal procedures improves recovery of consciousness in patients with prolonged coma.

Rehabilitative management of patients with disorders of consciousness: grand rounds.

BACKGROUND: There are no standards of care to guide the selection of rehabilitation assessment and treatment procedures for patients with disorders of consciousness. Recently, consensus-based recommendations for management of patients in the vegetative and minimally conscious states have been developed and disseminated in neurology and neurorehabilitation. This is an important first step toward achieving evidence-based guidelines of care. OBJECTIVE: Using a "Grand Rounds" format, we illustrate the application of consensus-based diagnostic, prognostic, and treatment recommendations in a patient who sustained severe traumatic brain injury with prolonged alteration in consciousness. After discussing the salient features of the case, we summarize the basic tenets of clinical care for this population.

Electrical treatment of coma via the median nerve.

The median nerve is a portal to interact with the injured comatose brain. Peripheral nerve electrical stimulation has a central nervous system effect. Two to three weeks of right median nerve stimulation (RMNS) can hasten awakening from deep coma by increasing the dopamine levels. Three cases of electrically treated GCS-4 teenagers with acute diffuse brain injuries from motor vehicle crashes are presented by video. Pilot studies of RMNS for acute post-traumatic coma states have been done over the last ten years at East Carolina University and the University of Virginia. The neurophysiological effects of RMNS have been well documented at several neurosurgical centers in Japan using neuroimaging and spinal fluid assays. RMNS is a safe, inexpensive, non-invasive therapy for neuro-resuscitation of coma patients. When employed early in the coma, the time in the ICU may be shortened and the quality of the final outcome may be enhanced.

Notorious pitfalls in the care of multi-trauma patients.

In this review we elaborate on the more specific circumstances that are needed for adequate trauma care, such as the correct recognition and management of a tension pneumothorax, a tracheobronchial disruption, systemic air embolism and hypoventilation. Furthermore the trauma clinician must be aware of the different life threatening causes of haemorrhage and hypovolemia. Traumatic pericardial tamponade, myocardial contusion and a tension pneumothorax can all prove to be difficult diagnoses, but may all present with signs of hypotension with an increase in central venous pressure (CVP). In contrast, internal haemorrhage is most often accompanied by hypotension with a low CVP. Immediate evaluation and treatment of thoracic trauma, such as rupture of the aortal arch, is mandatory, as is the utilisation of the correct diagnostic strategy to evaluate the possibility of intra-abdominal and retroperitoneal injury. Both an unnecessary laparotomy and a delayed diagnosis must be avoided when dealing intra-abdominal injuries, such as kidney trauma. Furthermore, we stress the importance of the swift diagnosis and treatment of fractures of long bones and the pelvis, to prevent ongoing massive haemorrhage. Certain criteria should be met, in a hospital setting with sufficient day-to-day trauma experience, to be able to provide quality care for the multi-trauma patient. This will minimise the risk of errors and serious medical and judicial consequences.

Battlefield advanced trauma life support.

Prevent secondary injury by: Preventing hypoxia, hypercarbia and hypovolaemia. Giving oxygen if available and ensure a clear airway at all times. Treating fits with diazepam in appropriate doses. Establishing a working diagnosis. Searching for associated injuries. Constantly repeating the mini-neurological examination. Identifying and evacuating appropriate casualties to a neurosurgical unit.