Severe traumatic brain injury treatment

Severe traumatic brain injury treatment

There are currently no established treatments for the underlying pathophysiology in TBI and while neuro-rehabilitation efforts are promising, there are currently is a lack of consensus regarding rehabilitation following TBI of any severity 1).

see Severe traumatic brain injury guidelines.

see also Pediatric traumatic brain injury guidelines.

Severe traumatic brain injury (TBI) is currently managed in the intensive care unit with a combined medical-surgical approach. Treatment aims to prevent additional brain damage and to optimise conditions for brain recovery. TBI is typically considered and treated as one pathological entity, although in fact it is a syndrome comprising a range of lesions that can require different therapies and physiological goals. Owing to advances in monitoring and imaging, there is now the potential to identify specific mechanisms of brain damage and to better target treatment to individuals or subsets of patients. Targeted treatment is especially relevant for elderly people-who now represent an increasing proportion of patients with TBI-as preinjury comorbidities and their therapies demand tailored management strategies. Progress in monitoring and in understanding pathophysiological mechanisms of TBI could change current management in the intensive care unit, enabling targeted interventions that could ultimately improve outcomes 2).

Monitoring

see Intracranial pressure monitoring for severe traumatic brain injury.

Hormonal replacement

Hormonal analysis should be considered in patients with moderate-to-severe traumatic brain injury, so that appropriate hormonal replacement can be done to optimize the clinical outcome 3).

Case series

Data from 729 severe traumatic brain injury patients admitted between 1996 and 2016 were used. Treatment was guided by controlling intracranial pressure and cerebral perfusion pressure according to a local protocol.

Cerebral perfusion pressurepressure reactivity index curves were fitted automatically using a previously published curve-fitting heuristic from the relationship between pressure reactivity index and cerebral perfusion pressure. The cerebral perfusion pressure values at which this “U-shaped curve” crossed the fixed threshold from intact to impaired pressure reactivity (pressure reactivity index = 0.3) were denoted automatically the “lower” and “upper” cerebral perfusion pressure limits of reactivity, respectively. The percentage of time with cerebral perfusion pressure below (%cerebral perfusion pressure < lower limit of reactivity), above (%cerebral perfusion pressure > upper limit of reactivity), or within these reactivity limits (%cerebral perfusion pressure within limits of reactivity) was calculated for each patient and compared across dichotomized Glasgow Outcome Scores. After adjusting for age, initial Glasgow Coma Scale, and mean intracranial pressure, percentage of time with cerebral perfusion pressure less than lower limit of reactivity was associated with unfavorable outcome (odds ratio %cerebral perfusion pressure < lower limit of reactivity, 1.04; 95% CI, 1.02-1.06; p < 0.001) and mortality (odds ratio, 1.06; 95% CI, 1.04-1.08; p < 0.001).

Individualized autoregulation-guided cerebral perfusion pressure management may be a plausible alternative to fixed cerebral perfusion pressure threshold management in severe traumatic brain injury patients. Prospective randomized research will help define which autoregulation-guided method is beneficial, safe, and most practical 4).

Medicaments

Despite the incidence of these injuries and their substantial socioeconomic implications, no specific pharmacological intervention is available for clinical use.

see Progesterone for acute traumatic brain injury.

see 21-aminosteroids for severe traumatic brain injury.

Neuroprotection

see Neuroprotection in traumatic Brain Injury

see Decompressive craniectomy for severe traumatic brain injury.

Cell-based therapies

Cell-based therapies are currently being investigated in treating neurotrauma due to their ability to secrete neurotrophic factors and anti-inflammatory cytokines that can regulate the hostile milieu associated with chronic neuroinflammation found in TBI. In tandem, the stimulation and mobilization of endogenous stem/progenitor cells from the bone marrow through granulocyte colony stimulating factor (G-CSF) poses as an attractive therapeutic intervention for chronic TBI.

The potential of a combined therapy of human umbilical cord blood cells (hUCB) and G-CSF at the acute stage of TBI to counteract the progressive secondary effects of chronic TBI using the controlled cortical impact model.

Four different groups of adult Sprague Dawley rats were treated with saline alone, G-CSF+saline, hUCB+saline or hUCB+G-CSF, 7-days post CCI moderate TBI. Eight weeks after TBI, brains were harvested to analyze hippocampal cell loss, neuroinflammatory response, and neurogenesis by using immunohistochemical techniques. Results revealed that the rats exposed to TBI treated with saline exhibited widespread neuroinflammation, impaired endogenous neurogenesis in DG and SVZ, and severe hippocampal cell loss. hUCB monotherapy suppressed neuroinflammation, nearly normalized the neurogenesis, and reduced hippocampal cell loss compared to saline alone. G-CSF monotherapy produced partial and short-lived benefits characterized by low levels of neuroinflammation in striatum, DG, SVZ, and corpus callosum and fornix, a modest neurogenesis, and a moderate reduction of hippocampal cells loss. On the other hand, combined therapy of hUCB+G-CSF displayed synergistic effects that robustly dampened neuroinflammation, while enhancing endogenous neurogenesis and reducing hippocampal cell loss. Vigorous and long-lasting recovery of motor function accompanied the combined therapy, which was either moderately or short-lived in the monotherapy conditions. These results suggest that combined treatment rather than monotherapy appears optimal for abrogating histophalogical and motor impairments in chronic TBI 5).

Research

Research in traumatic brain injury (TBI) is challenging for several reasons; in particular, the heterogeneity between patients regarding causes, pathophysiology, treatment, and outcome. Advances in basic science have failed to translate into successful clinical treatments, and the evidence underpinning guideline recommendations is weak. Because clinical research has been hampered by non-standardised data collection, restricted multidisciplinary collaboration, and the lack of sensitivity of classification and efficacy analyses, multidisciplinary collaborations are now being fostered. Approaches to deal with heterogeneity have been developed by the IMPACT study group. These approaches can increase statistical power in clinical trials by up to 50% and are also relevant to other heterogeneous neurological diseases, such as stroke and subarachnoid haemorrhage. Rather than trying to limit heterogeneity, we might also be able to exploit it by analysing differences in treatment and outcome between countries and centres in comparative effectiveness research. This approach has great potential to advance care in patients with TBI 6).

Anticoagulation Resumption after traumatic brain injury

Anticoagulation Resumption after traumatic brain injury.

Thromboprophylaxis

The early administration of venous thromboembolism (VTE) chemoprophylaxis within 24 h after admission in patients with severe TBI did not increase the risk of intracranial bleeding progression 7).

Transcutaneous Vagus Nerve Stimulation for Severe Traumatic Brain Injury

see Transcutaneous Vagus Nerve Stimulation for Severe Traumatic Brain Injury.

References

1)

Marklund N, Bellander BM, Godbolt A, Levin H, McCrory P, Thelin EP. Treatments and rehabilitation in the acute and chronic state of traumatic brain injury. J Intern Med. 2019 Mar 18. doi: 10.1111/joim.12900. [Epub ahead of print] PubMed PMID: 30883980.
2)

Stocchetti N, Carbonara M, Citerio G, Ercole A, Skrifvars MB, Smielewski P, Zoerle T, Menon DK. Severe traumatic brain injury: targeted management in the intensive care unit. Lancet Neurol. 2017 Jun;16(6):452-464. doi: 10.1016/S1474-4422(17)30118-7. Review. PubMed PMID: 28504109.
3)

Prasanna KL, Mittal RS, Gandhi A. Neuroendocrine dysfunction in acute phase of moderate-to-severe traumatic brain injury: A prospective study. Brain Inj. 2015;29(3):336-342. PubMed PMID: 25671810.
4)

Donnelly J, Czosnyka M, Adams H, Robba C, Steiner LA, Cardim D, Cabella B, Liu X, Ercole A, Hutchinson PJ, Menon DK, Aries MJH, Smielewski P. Individualizing Thresholds of Cerebral Perfusion Pressure Using Estimated Limits of Autoregulation. Crit Care Med. 2017 Sep;45(9):1464-1471. doi: 10.1097/CCM.0000000000002575. PubMed PMID: 28816837.
5)

Acosta SA, Tajiri N, Shinozuka K, Ishikawa H, Sanberg PR, Sanchez-Ramos J, Song S, Kaneko Y, Borlongan CV. Combination therapy of human umbilical cord blood cells and granulocyte colony stimulating factor reduces histopathological and motor impairments in an experimental model of chronic traumatic brain injury. PLoS One. 2014 Mar 12;9(3):e90953. doi: 10.1371/journal.pone.0090953. eCollection 2014. PubMed PMID: 24621603.
6)

Maas AI, Murray GD, Roozenbeek B, Lingsma HF, Butcher I, McHugh GS, Weir J, Lu J, Steyerberg EW; International Mission on Prognosis Analysis of Clinical Trials in Traumatic Brain Injury (IMPACT) Study Group. Advancing care for traumatic brain injury: findings from the IMPACT studies and perspectives on future research. Lancet Neurol. 2013 Dec;12(12):1200-10. doi: 10.1016/S1474-4422(13)70234-5. Epub 2013 Oct 17. PubMed PMID: 24139680; PubMed Central PMCID: PMC3895622.
7)

Störmann P, Osinloye W, Freiman TM, Seifert V, Marzi I, Lustenberger T. Early Chemical Thromboprophylaxis Does not Increase the Risk of Intracranial Hematoma Progression in Patients with Isolated Severe Traumatic Brain Injury. World J Surg. 2019 Jul 2. doi: 10.1007/s00268-019-05072-1. [Epub ahead of print] PubMed PMID: 31267142.

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