Andrew J. Baker

Despite their potential interest for clinical management, measurements of respiratory mechanics in patients with acute respiratory distress syndrome (ARDS) are seldom performed in routine practice. We introduced a systematic assessment of respiratory mechanics in our clinical practice. After the first year of clinical use, we retrospectively assessed whether these measurements had any influence on clinical management and physiological parameters associated with clinical outcomes by comparing their value before and after performing the test. The respiratory mechanics assessment constituted a set of bedside measurements to determine passive lung and chest wall mechanics, response to positive end-expiratory pressure, and alveolar derecruitment. It was obtained early after ARDS diagnosis. The results were provided to the clinical team to be used at their own discretion. We compared ventilator settings and physiological variables before and after the test. The physiological endpoints were oxygenation index, dead space, and plateau and driving pressures. Sixty-one consecutive patients with ARDS were enrolled. Esophageal pressure was measured in 53 patients (86.9%). In 41 patients (67.2%), ventilator settings were changed after the measurements, often by reducing positive end-expiratory pressure or by switching pressure-targeted mode to volume-targeted mode. Following changes, the oxygenation index, airway plateau, and driving pressures were significantly improved, whereas the dead-space fraction remained unchanged. The oxygenation index continued to improve in the next 48 h. Implementing a systematic respiratory mechanics test leads to frequent individual adaptations of ventilator settings and allows improvement in oxygenation indexes and reduction of the risk of overdistention at the same time. The present study involves data from our ongoing registry for respiratory mechanics (ClinicalTrials.gov identifier: NCT02623192 . Registered 30 July 2015).

Death after withdrawal of mechanical ventilation frequently follows the sequence of progressive hypoxemia and hypotension leading to cardiac arrest. Accurate timing of the determination of death is fundamental to trust in controlled donation after circulatory death (cDCD) programs and is generally based on cessation of circulation (pulselessness), brain function (apnea), and the passage of time. If death is understood to be the unresuscitatable loss of brain function, the clinical determination that death following apnea and pulselessness has occurred is largely inferential. We sought to elucidate the relationship between the available clinical variables and the loss of brain function and its inability to be resuscitated.

Elevated catecholamine levels might be associated with unfavorable outcome after traumatic brain injury (TBI). We investigated the association between catecholamine levels in the first 24 h post-trauma and functional outcome in patients with isolated moderate-to-severe TBI. A cohort of 174 patients who sustained isolated blunt TBI was prospectively enrolled from three Level-1 Trauma Centers. Epinephrine (Epi) and norepinephrine (NE) concentrations were measured at admission (baseline), 6, 12 and 24 h post-injury. Outcome was assessed at 6 months by the extended Glasgow Outcome Scale (GOSE) score. Fractional polynomial plots and logistic regression models (fixed and random effects) were used to study the association between catecholamine levels and outcome. Effect size was reported as the odds ratio (OR) associated with one logarithmic change in catecholamine level. At 6 months, 109 patients (62.6%) had an unfavorable outcome (GOSE 5–8 vs. 1–4), including 51 deaths (29.3%). Higher admission levels of Epi were associated with a higher risk of unfavorable outcome (OR, 2.04, 95% CI: 1.31–3.18, p = 0.002) and mortality (OR, 2.86, 95% CI: 1.62–5.01, p = 0.001). Higher admission levels of NE were associated with higher risk of unfavorable outcome (OR, 1.59, 95% CI: 1.07–2.35, p = 0.022) but not mortality (OR, 1.45, 95% CI: 0.98–2.17, p = 0.07). There was no relationship between the changes in Epi levels over time and mortality or unfavorable outcome. Changes in NE levels with time were statistically associated with a higher risk of mortality, but the changes had no relation to unfavorable outcome. Elevated circulating catecholamines, especially Epi levels on hospital admission, are independently associated with functional outcome and mortality after isolated moderate-to-severe TBI.

Background There are a range of opinions on the benefits and thresholds for the transfusion of red blood cells in critically ill patients with traumatic brain injury (TBI) and an urgent need to understand the neurophysiologic effects. The aim of this study was to examine the influence of red blood cell transfusions on cerebral tissue oxygenation (SctO₂) in critically ill TBI patients. Methods This prospective observational study enrolled consecutive TBI patients with anemia requiring transfusion. Cerebral tissue oxygen saturation (SctO₂) was measured noninvasively with bilateral frontal scalp probes using near-infrared spectroscopy (NIRS) technology. Data were collected at baseline and for 24 h after transfusion. The primary outcome was the applicability of a four-wavelength near-infrared spectrometer to monitor SctO₂ changes during a transfusion. Secondary outcomes included the correlation of SctO₂ with other relevant physiological variables, the dependence of SctO₂ on baseline hemoglobin and transfusion, and the effect of red blood cell transfusion on fractional tissue oxygen extraction. Results We enrolled 24 patients with severe TBI, of which five patients (21 %) were excluded due to poor SctO₂ signal quality from large subdural hematomas and bifrontal decompressive craniectomies. Twenty transfusions were monitored in 19 patients. The mean pre- and post-transfusion hemoglobin concentrations were significantly different [74 g/L (SD 8 g/L) and 84 g/L (SD 9 g/L), respectively; p value 2 was not significantly greater than pre-transfusion SctO₂ [left-side pre-transfusion 69 % (SD 7) vs. post-transfusion 70 % (SD 10); p = 0.68, and right-side pre-transfusion 69 % (SD 5) vs. post-transfusion 71 % (SD 7); p = 0.11]. In a multivariable mixed linear analysis, mean arterial pressure was the only variable significantly associated with a change in SctO₂. Conclusions The bifrontal method of recording changes in NIRS signal was not able to detect a measurable impact on SctO₂ in this sample of patients receiving red blood cell transfusion therapy in a narrow but conventionally relevant, range of anemia.

Traumatic brain injury (TBI) elicits intense sympathetic nervous system (SNS) activation with profuse catecholamine secretion. The resultant hyperadrenergic state is linked to immunomodulation both within the brain and systemically. Dysregulated inflammation post-TBI exacerbates secondary brain injury and contributes to unfavorable patient outcomes including death. The aim of this study was to characterize the early dynamic profile of circulating inflammatory cytokines/chemokines in patients admitted for moderate-to-severe TBI, to examine interrelationships between these mediators and catecholamines, as well as clinical indices of injury severity and neurological outcome. Blood was sampled from 166 isolated TBI patients (aged 45 ± 20.3 years; 74.7 % male) on admission, 6-, 12-, and 24-h post-injury and from healthy controls (N = 21). Plasma cytokine [interleukin (IL)-1β, -2, -4, -5, -10, -12p70, -13, tumor necrosis factor (TNF)-α, interferon (IFN)-γ] and chemokine [IL-8, eotaxin, eotaxin-3, IFN-γ-induced protein (IP)-10, monocyte chemoattractant protein (MCP)-1, -4, macrophage-derived chemokine (MDC), macrophage inflammatory protein (MIP)-1β, thymus activation regulated chemokine (TARC)] concentrations were analyzed using high-sensitivity electrochemiluminescence multiplex immunoassays. Plasma catecholamines [epinephrine (Epi), norepinephrine (NE)] were measured by immunoassay. Neurological outcome at 6 months was assessed using the extended Glasgow outcome scale (GOSE) dichotomized as good (>4) or poor (≤4) outcomes. Patients showed altered levels of IL-10 and all chemokines assayed relative to controls. Significant differences in a number of markers were evident between moderate and severe TBI cohorts. Elevated IL-8, IL-10, and TNF-α, as well as alterations in 8 of 9 chemokines, were associated with poor outcome at 6 months. Notably, a positive association was found between Epi and IL-1β, IL-10, Eotaxin, IL-8, and MCP-1. NE was positively associated with IL-1β, IL-10, TNF-α, eotaxin, IL-8, IP-10, and MCP-1. Our results provide further evidence that exaggerated SNS activation acutely after isolated TBI in humans may contribute to harmful peripheral inflammatory cytokine/chemokine dysregulation. These findings are consistent with a potentially beneficial role for therapies aimed at modulating the inflammatory response and hyperadrenergic state acutely post-injury.

Traumatic Brain Injury (TBI) is a global health concern. The majority of TBI’s are mild, yet our ability to diagnose and treat mTBI is lacking. This deficiency results from a variety of issues including the difficulty in interpreting ambiguous clinically presented symptoms, and ineffective imaging techniques. Thus, researchers have begun to explore cellular and molecular based approaches to improve both diagnosis and prognosis. This has been met with a variety of challenges, including difficulty in relating biological markers to current clinical symptoms, and overcoming our lack of fundamental understanding of the pathophysiology of mTBI. However, recent adoption of high throughput technologies and a change in focus from the identification of single to multiple markers has given just optimism to mTBI research. The purpose of this review is to highlight a number of current experimental peripheral blood biomarkers of mTBI, as well as comment on the issues surrounding their clinical application and utility.