Toward individualized sedation in patients with acute brain damage.

Sedation/analgesia in patients with acute brain damage, either traumatic or non-traumatic, is paramount to prevent alterations in brain perfusion secondary to the injury. Despite reviews on sedative and analgesic drugs, adequate sedation is an overlooked therapy in the prevention and treatment of intracranial hypertension. When to indicate continued sedation? How to guide the level of sedation? How to terminate sedation? This narrative review provides a practical approach to the individualized use of sedative/analgesic drugs in patients with acute brain damage.

Using Pupillary Pain Index to Assess Nociception in Sedated Critically Ill Patients.

BACKGROUND: Pupillary reflex dilation is a reliable indicator of response to noxious stimulation. In a proof of concept study, we investigated the performance of pupillary pain index, a new score derived from pupillary reflex dilation measurements, to predict nociceptive response to endotracheal suctioning in sedated critically ill patients. METHODS: Twenty brain-injured and 20 non-brain-injured patients were studied within 48 hours of admission (T1) in the intensive care unit and at 48-72 hours later (T2). Video-based pupillometer was used to determine pupillary reflex dilation during tetanic stimulation. The tetanic stimulation (100 Hz) was applied to the skin area innervated by the ulnar nerve and was stepwise increased from 10 to 60 mA until pupil size had increased by 13% compared to baseline. The maximum intensity value allowed the determination of a pupillary pain index score ranging from 1 (no nociception) to 9 (high nociception). The Behavioral Pain Scale response to endotracheal suctioning was measured thereafter. RESULTS: Behavioral Pain Scale responses to endotracheal suctioning and pupillary pain index scores were positively correlated at T1 and T2 (both P < .01). After adjustments for repeated measurements and group of patients, the area under the receiver operating characteristic curve of pupillary pain index to predict Behavioral Pain Scale response to endotracheal suctioning was of 0.862 (95% CI, 0.714-0.954). In the combined set of patients, a pupillary pain index score of ≤4 could predict no nociceptive response to endotracheal suctioning with a sensitivity of 88% (95% CI, 68%-97%) and a specificity of 79% (95% CI, 66%-88%). By contrast with endotracheal suctioning, tetanic stimulation had no effect on intracranial pressure in the brain-injured group. CONCLUSIONS: These results are a proof of concept. The nociceptive response to endotracheal suctioning could be accurately predicted using the determination of pupillary pain index score in sedated critically ill patients whether they have brain injury or not.

Modeling the Influence of Age on Neurological Outcome and Quality of Life One Year after Traumatic Brain Injury: A Prospective Multi-Center Cohort Study.

After traumatic brain injury (TBI), the relationship between age and outcome at 1 year, including quality of life, has been poorly explored. The aim of our study was to describe this relationship in a cohort of TBI patients in a regional trauma system. Consecutive TBI patients with severe lesions on initial brain computed tomography (CT) scan were included from July 2014 to July 2016 in two French level-1 trauma centers. The primary outcome was the mortality at 1 year and secondary outcomes were Glasgow Outcome Scale-Extended (GOS-E) and quality of life using the Short Form Health Survey (SF-12). The relationship between age and outcome was modeled using the generalized linear model (GLM). Within the study period, 427 patients with TBI and type 3 Abbreviated Injury Scale (AIS) lesions were included. Finally, 380 patients were assessed for mortality. Ninety-six (25%) patients died at 1 year. The detailed neurological status was available for 317 patients. One year after the trauma, 141 (44%) patients had a favorable outcome (GOS-E 7 and 8), whereas 53 (17%) patients had a moderate disability (GOS-E 5-6), 27 (9%) patients had a severe disability or were in a vegetative state (GOS-E 2-4), and 96 (30%) patients had died (GOS-E 1). After 70 years of age, a dramatic increase in the odds of death and poor neurological outcome was found using GLM. No difference according to age was found for the quality of life. After TBI, the mortality at 1 year dramatically increased with age after 70 years. For elderly survivors, impairment of quality of life was not different from younger patients.

Dynamics of clinical recovery during the early phase of rehabilitation in patients with severe traumatic and non-traumatic brain injury.

PURPOSE: Our aim was to describe the changes in the functional outcome at the early phase of rehabilitation following severe brain injury and to identify the factors associated with faster recovery. METHODS: This retrospective analysis included 182 patients who were transferred from the intensive care unit (ICU) to a post-ICU neurorehabilitation unit following traumatic brain injury (TBI) (n = 82) or cerebrovascular accident (CVA) (n = 100). Admission, discharge and changes in scores were calculated for the Functional Independent Measurement (FIM) and the Wessex Head Injury Matrix (WHIM). Patients with high dynamics of clinical recovery were defined by delta FIM scores ≥22. RESULTS: Upon admission to the neurorehabilitation unit, 97% of patients had a FIM score <50 and 41% a WHIM score <32. Patients showed significantly improved FIM (+17 points; 7-37) and WHIM (+11 points; 3-19) scores with an over 22-day stay (14-38). Those with faster recovery (45%) were more likely those with high FIM and WHIM scores at admission. The nature and severity of the brain insult were not associated with the dynamics of recovery. CONCLUSIONS: Within a 2-6 week stay in a post-ICU neurorehabilitation unit, patients with severe disability could achieve partial functional independence and showed cognitive improvements.

Capillary lactate concentration on admission of normotensive trauma patients: a prospective study.

BACKGROUND: Elevated serum blood lactate is an indicator of on-going bleeding in severe trauma patients. Point-of-care (POC) capillary lactate measurement devices may be useful to rapidly assess lactate concentration at the bedside. The aim of this study was to test the diagnostic performance of capillary lactate to predict significant transfusion in normotensive trauma patients. METHODS: We conducted a prospective observational study in one level-I trauma centre. From August 2011 to February 2013, 120 consecutive adult patients with systolic blood pressure (SBP) higher than 90 mmHg were included. Capillary lactate was measured on admission in the trauma bay. The primary outcome was defined as a significant transfusion within the first 48 h. Diagnostic performance was determined using receiver operating characteristic (ROC) curve analysis. We also tested the agreement between capillary lactate and blood lactate concentrations using Bland and Altman analysis. RESULTS: Of the 120 normotensive trauma patients, 30 (25 %) required at least one unit of packed red blood cells (RBC) and 12 (10 %) patients received at least four RBC within the first 48 h. All patients with significant RBC transfusion had capillary lactate higher than 3.5 mmol/l. The area under the ROC curve of capillary lactate on admission to predict transfusion of at least 4 RBC units was 0.68 [95 % CI 0.58 - 0.78]. The average bias between capillary and blood lactate measurements was 2.4 mmol/l with a standard deviation of 3.0 mmol/l (n = 60 patients). CONCLUSIONS: Although a significant association was found between POC lactate concentration and transfusion requirements, the diagnostic performance of capillary lactate measurements was poor. Due to large disagreement between capillary lactate and blood lactate, capillary lactate cannot be considered in the clinical setting. TRIAL REGISTRATION: ClinicalTrials.gov, No. NCT01793428 .

A major trauma course based on posters, audio-guides and simulation improves the management skills of medical students: Evaluation via medical simulator.

BACKGROUND: Medical competence requires the acquisition of theoretical knowledge and technical skills. Severe trauma management teaching is poorly developed during internship. Nevertheless, the basics of major trauma management should be acquired by every future physician. For this reason, the major trauma course (MTC), an educational course in major traumatology, has been developed for medical students. Our objective was to evaluate, via a high fidelity medical simulator, the impact of the MTC on medical student skills concerning major trauma management. METHODS: The MTC contains 3 teaching modalities: posters with associated audio-guides, a procedural workshop on airway management and a teaching session using a medical simulator. Skills evaluation was performed 1 month before (step 1) and 1 month after (step 3) the MTC (step 2). Nineteen students were individually evaluated on 2 different major trauma scenarios. The primary endpoint was the difference between steps 1 and 3, in a combined score evaluating: admission, equipment, monitoring and safety (skill set 1) and systematic clinical examinations (skill set 2). RESULTS: After the course, the combined primary outcome score improved by 47% (P<0.01). Scenario choice or the order of use had no significant influence on the skill set evaluations. CONCLUSION: This study shows improvement in student skills for major trauma management, which we attribute mainly to the major trauma course developed in our institution.

Mannitol Improves Brain Tissue Oxygenation in a Model of Diffuse Traumatic Brain Injury.

OBJECTIVES: Based on evidence supporting a potential relation between posttraumatic brain hypoxia and microcirculatory derangements with cell edema, we investigated the effects of the antiedematous agent mannitol on brain tissue oxygenation in a model of diffuse traumatic brain injury. DESIGN: Experimental study. SETTING: Neurosciences and physiology laboratories. SUBJECTS: Adult male Wistar rats. INTERVENTIONS: Thirty minutes after diffuse traumatic brain injury (impact-acceleration model), rats were IV administered with either a saline solution (traumatic brain injury-saline group) or 20% mannitol (1 g/kg) (traumatic brain injury-mannitol group). Sham-saline and sham-mannitol groups received no insult. MEASUREMENTS AND MAIN RESULTS: Two series of experiments were conducted 2 hours after traumatic brain injury (or equivalent) to investigate 1) the effect of mannitol on brain edema and oxygenation, using a multiparametric magnetic resonance-based approach (n = 10 rats per group) to measure the apparent diffusion coefficient, tissue oxygen saturation, mean transit time, and blood volume fraction in the cortex and caudoputamen; 2) the effect of mannitol on brain tissue PO2 and on venous oxygen saturation of the superior sagittal sinus (n = 5 rats per group); and 3) the cortical ultrastructural changes after treatment (n = 1 per group, taken from the first experiment). Compared with the sham-saline group, the traumatic brain injury-saline group had significantly lower tissue oxygen saturation, brain tissue PO2, and venous oxygen saturation of the superior sagittal sinus values concomitant with diffuse brain edema. These effects were associated with microcirculatory collapse due to astrocyte swelling. Treatment with mannitol after traumatic brain injury reversed all these effects. In the absence of traumatic brain injury, mannitol had no effect on brain oxygenation. Mean transit time and blood volume fraction were comparable between the four groups of rats. CONCLUSION: The development of posttraumatic brain edema can limit the oxygen utilization by brain tissue without evidence of brain ischemia. Our findings indicate that an antiedematous agent such as mannitol can improve brain tissue oxygenation, possibly by limiting astrocyte swelling and restoring capillary perfusion.