How We Die: The Impact of Nonneurologic Organ Dysfunction after Severe Traumatic Brain Injury

Abstract

Although nonneurologic organ dysfunction (NNOD) has been shown to significantly affect mortality in subarachnoid hemorrhage, the contribution of NNOD to mortality after severe traumatic brain injury (TBI) has yet to be defined. We hypothesized that NNOD has a significant impact on mortality after severe TBI. The trauma registry was queried for all patients admitted between January 2004 and December 2004 who died during their initial hospitalization after severe TBI (head Abbreviated Injury Score 3 or greater). Cause of death and contributing factors to mortality were determined by an attending trauma surgeon from the medical record. The data were analyzed using both Fisher's exact and Wilcoxon rank sum. One hundred thirty-five patients met inclusion criteria. Sixty-seven per cent were males, 83 per cent were white, and the mean age was 38.5 years. Mean length of stay was 2.9 days. Fifty-four patients (40%) had isolated TBI (chest Abbreviated Injury Score = 0, abdominal Abbreviated Injury Score = 0). Of the 81 deaths attributed to a single cause, 48 (60%) patients died from nonsurvivable TBI or brain death, whereas 33 (40%) died of a nonneurologic cause. Cardiovascular and respiratory dysfunction (excluding pneumonia) contributed to mortality in 51.1 per cent and 34.1 per cent of patients, respectively. NNOD contributes to approximately two-thirds of all deaths after severe TBI. These complications occur early and are seen even among those with isolated head injuries. These findings demonstrate the impact of the extracranial manifestations of severe TBI on overall mortality and highlight potential areas for future intervention and research.

Non- Neurological Complications after Traumatic Brain Injury: A Prospective Observational Study

“…[ 7 16 17 18 ] Few studies showed that acute lung injury resulted in doubling of mortality after TBI[ 14 19 ] and moderate and severe respiratory failure were the poor prognostic factors. [ 14 19 20 ] Other similar studies did not find any association with mortality. [ 7 21 ] Very few of our patients had severe respiratory failure which could be life-threatening.…”

Estradiol to Androstenedione Ratios Moderate the Relationship between Neurological Injury Severity and Mortality Risk after Severe Traumatic Brain Injury

“…Complications associated with NNOD include arrhythmias, myocardial ischemia, neurogenic pulmonary edema, congestive heart failure, sepsis, and acute kidney injury (AKI). 3,4,51 These complications occur early and even among those with isolated head injuries, 4 supporting the importance of the acute autonomic SNS response as a contributor to the systemic response to TBI. 8,52,53 As noted earlier, E2 production may have reciprocal effects on SNS-mediated inflammation, by blocking adrenergic reuptake 8,47 and through estrogen receptor-dependent processes, [49][50][51] suggesting the need to characterize the pathway of E2 production after injury as potentially explaining effects on outcome and mortality prediction.…”

“…In severe TBI, aromatization pathway biomarkers likely reflect a complex interplay between amplified aromatization, the peripheral inflammatory response, and their subsequent effects on peripheral vascular vasodilatation that accompanies systemic hypotension, the development of NNOD, and progression to multi-system organ failure. Approximately 40% of single cause acute mortality associated with TBI is because of NNOD, and 85% of TBI-related mortality is in part because of non-neurological conditions/complications, 4 suggesting the systemic response to TBI may be just as important to consider as neurological injury when prognosticating mortality or poor global outcome. Patients with TBI are susceptible to sepsis, which may contribute to an exacerbated inflammatory response and lead to NNOD.…”

“…A high percentage of TBI associated mortality due to nonneurological organ dysfunction (NNOD), 3,4 much of which arises from systemic nervous system (SNS) overactivity and dysfunction. [3][4][5] Aseptic peripheral inflammation occurs, in part, from the acute hepatic response after TBI, 6 a phenomenon resulting from the autonomic SNS in response to TBI. 6,7 Also, overactivity of SNS-innervated peripheral lymphoid tissue stimulates the systemic inflammatory response to TBI, including ongoing tumor necrosis factor (TNF)a and other cytokine production.…”

Mitochondria in traumatic brain injury and mitochondrial‐targeted multipotential therapeutic strategies

“…A systemic inflammatory response syndrome is a persistent pathological process that worsens patient outcome (Kemp et al ., 2008). Activation of the sympathetic nervous system is critical in CNS‐induced immunodepression and organ inflammation.…”