Francis Bernard

Mortality associated with withdrawal of life-sustaining therapy for patients with severe traumatic brain injury: a Canadian multicentre cohort study

Background: Severe traumatic brain injury often leads to death from withdrawal of life-sustaining therapy, although prognosis is difficult to determine. Methods: To evaluate variation in mortality following the withdrawal of life-sustaining therapy and hospital mortality in patients with critical illness and severe traumatic brain injury, we conducted a two-year multicentre retrospective cohort study in six Canadian level-one trauma centres. The effect of centre on hospital mortality and withdrawal of life-sustaining therapy was evaluated using multivariable logistic regression adjusted for baseline patient-level covariates (sex, age, pupillary reactivity and score on the Glasgow coma scale). Results: We randomly selected 720 patients with traumatic brain injury for our study. The overall hospital mortality among these patients was 228/720 (31.7%, 95% confidence interval [CI] 28.4%–35.2%) and ranged from 10.8% to 44.2% across centres (χ2 test for overall difference, p < 0.001). Most deaths (70.2% [160/228], 95% CI 63.9%–75.7%) were associated with withdrawal of life-sustaining therapy, ranging from 45.0% (18/40) to 86.8% (46/53) (χ2 test for overall difference, p < 0.001) across centres. Adjusted odd ratios (ORs) for the effect of centre on hospital mortality ranged from 0.61 to 1.55 (p < 0.001). The incidence of withdrawal of life-sustaining therapy varied by centre, with ORs ranging from 0.42 to 2.40 (p = 0.001). About one half of deaths that occurred following the withdrawal of life-sustaining therapies happened within the first three days of care. Interpretation: We observed significant variation in mortality across centres. This may be explained in part by regional variations in physician, family or community approaches to the withdrawal of life-sustaining therapy. Considering the high proportion of early deaths associated with the withdrawal of life-sustaining therapy and the limited accuracy of current prognostic indicators, caution should be used regarding early withdrawal of life-sustaining therapy following severe traumatic brain injury.

Efficacy and safety of dopamine agonists in traumatic brain injury: a systematic review of randomized controlled trials.

In the intensive care unit, dopamine agonists (DA) have been used in traumatic brain injury (TBI) patients to augment or accelerate cognitive recovery and rehabilitation. However, the efficacy and safety of DA in this population is not well established. We conducted a systematic review of randomized controlled trials (RCTs) examining the clinical efficacy and safety of DA in patients with TBI. We searched MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials, comparing DA to either placebo, standard treatment, or another active comparator. There was no restriction for age, date, or language of publication. Sensitivity analyses were planned to evaluate the potential effect of timing of TBI, age, drugs, and year of publication on efficacy. Among the 790 citations identified, 20 RCTs evaluating methylphenidate, amantadine, and bromocriptine were eligible. Significant clinical heterogeneity was observed between and within studies, which precluded any pooling of data. Efficacy outcomes included mainly neuropsychological measures of cognitive functioning. A total of 76 different neuropsychological tests were used, but most of them (59%) only once. Only 5 studies systematically assessed safety. No trend could be drawn from the analysis of efficacy and safety. Important sources of bias in the studies were of major concern. Considering the absence of consensus regarding clinical outcome, the lack of safety assessment, and the high risk of bias in the included trials, more research is warranted before DA can be recommended in critically ill TBI patients.

Rest-activity cycle disturbances in the acute phase of moderate to severe traumatic brain injury

Background. Sleep-wake disturbances are among the most persistent sequelae after traumatic brain injury (TBI) and probably arise during the hospital stay following TBI. These disturbances are characterized by difficulties sleeping at night and staying awake during the day. Objective. The aim of the present study was to document rest-activity cycle consolidation in acute moderate/severe TBI using actigraphy and to assess its association with injury severity and outcome. Methods. In all, 16 hospitalized patients (27.1 ± 11.3 years) with moderate/severe TBI wore actigraphs for 10 days, starting in the intensive care unit (ICU) when continuous sedation was discontinued and patients had reached medical stability. Activity counts were summed for daytime (7:00-21:59 hours) and nighttime periods (22:00-6:59 hours). The ratio of daytime period activity to total 24-hour activity was used to quantify rest-activity cycle consolidation. An analysis of variance was carried out to characterize the evolution of the daytime activity ratio over the recording period. Results. Rest-activity cycle was consolidated only 46.6% of all days; however, a significant linear trend of improvement was observed over time. Greater TBI severity and longer ICU and hospital lengths of stay were associated with poorer rest-activity cycle consolidation and evolution. Patients with more rapid return to consolidated rest-activity cycle were more likely to have cleared posttraumatic amnesia and have lower disability at hospital discharge. Conclusions. Patients with acute moderate/severe TBI had an altered rest-activity cycle, probably reflecting severe fragmentation of sleep and wake episodes, which globally improved over time. A faster return to rest-activity cycle consolidation may predict enhanced brain recovery.

Serum albumin level as a predictor of outcome in traumatic brain injury: potential for treatment.

BACKGROUND Serum albumin level is correlated with outcome in various clinical situations. Albumin has multiple physiologic properties that could be beneficial in brain injury. The Lund therapy for elevated intracranial pressure uses albumin as part of its protocol and demonstrates favorable outcome. We sought to find out if albumin is associated with outcome after traumatic brain injury to justify conducting a randomized trial. METHODS A retrospective study of traumatic brain injury patients was conducted. Characteristics known to influence outcome were included in a multiple logistic regression model to analyze predictors of poor outcome at 6 months. RESULTS Data were available for 138 patients. The majority of patients (65%) had a severe injury (Glasgow Coma Scale score <9). Seventy percent of patients had a favorable outcome. Albumin levels decrease considerably from normal values in the first few days after injury irrespective of outcome. Albumin remained <25 g/L for a longer period of time in patient with an unfavorable outcome (6 days vs. 3 days, p = 0.012). Multiple logistic regression analysis identified albumin levels, age, Glasgow Coma Scale score at admission, and Injury Severity Score as predictors of poor outcome. CONCLUSION Serum albumin level seems to be an independent predictor of poor outcome. The model also identified classic predictors of poor outcome that tends to strengthen its adequacy. Because albumin level is the only modifiable factor influencing outcome, it seems justified to carry out a randomized trial of the use of albumin in the treatment of brain injury.

Clinical outcomes, predictors, and prevalence of anterior pituitary disorders following traumatic brain injury: a systematic review.

Objectives:To assess the clinical outcomes, predictors, and prevalence of anterior pituitary disorders following traumatic brain injury. Data Sources:We searched Medline, Embase, Cochrane Registry, BIOSIS, and Trip Database up to February 2012 and consulted bibliographies of narrative reviews and selected articles. Study Selection:We included cohort, case-control, cross-sectional studies and randomized trials enrolling at least five adults with blunt traumatic brain injury in whom at least one anterior pituitary axis was assessed. We excluded case series and studies in which other neurological conditions were indistinguishable from traumatic brain injury. Data Extraction:Two independent reviewers selected citations, extracted data, and assessed the risk of bias using a standardized form. Data Synthesis:We performed meta-analyses using random effect models and assessed heterogeneity using the I2 index. Results:We included 66 studies (5,386 patients) evaluating prevalence, 14 evaluating clinical outcomes, and 27 evaluating predictors. Thirty studies were at low risk of bias. Anterior pituitary disorders were associated with a trend toward increased ICU mortality (risk ratio, 1.79; 95% CI, 0.99–3.21; four studies) and no difference in Glasgow Outcome Scale score (mean difference, –0.45; 95% CI, –1.10 to 0.20; three studies). Age (mean difference, 3.19; 95% CI, 0.31–6.08; 19 studies), traumatic brain injury severity (risk ratio, 2.15; 95% CI, 1.20–3.86 for patients with severe vs nonsevere traumatic brain injury; seven studies), and skull fractures (risk ratio, 1.73; 95% CI, 1.03–2.91; six studies) predicted anterior pituitary disorders. Over the long term, 31.6% (95% CI, 23.6–40.1%; 27 studies) of patients had at least one anterior pituitary disorder. We observed significant heterogeneity that was not solely explained by the risk of bias or traumatic brain injury severity. Conclusions:Approximately one third of traumatic brain injury patients have persistent anterior pituitary disorder. Older age, traumatic brain injury severity, and skull fractures predict anterior pituitary disorders, which in turn may be associated with higher ICU mortality. Further high-quality studies are warranted to better define the burden of anterior pituitary disorders and to identify high-risk patients.

Fulminant Legionellosis in Two Patients Treated with Infliximab for Crohn’s Disease: Case Series and Literature Review

Two cases of fulminant pulmonary legionellosis, complicated by prolonged intensive care unit stays and acute respiratory distress syndrome, and who were recently treated with infliximab for Crohns disease, are described. A review of the literature revealed three additional cases in patients with inflammatory bowel disease, and a total of 22 cases of Legionella pneumophila pneumonia in the context of treatment with antitumour necrosis (TNF)-alpha medications. The median age of the patients was 49 years, and men and women were affected equally. The case fatality rate was 14% (three of 22). Early recognition and treatment of this anti-TNF-alpha-related complication would likely result in reduced mortality and morbidity. Physicians prescribing anti-TNF-alpha drugs should be aware of this association.

Best evidence in critical care medicine Daily interruption of sedative infusions in critically ill patients undergoing mechanical ventilation

Structured abstractQuestionDoes daily interruption of sedative infusions in critically ill patients receiving mechanical ventilation decrease the duration of mechanical ventilation and length of stay in the intensive care unit (ICU) and hospital?PopulationThis study investigated intubated patients in the medical ICU of the University of Chicago Hospital. The study coordinators enrolled 150 patients who required sedation for agitation or discomfort according to the treating ICU team. Amongst the 150 patients enrolled, the 128 patients who were ultimately included in the study were those who were still alive and intubated after the initial 48 hr in the ICU. The study excluded patients who were pregnant, already receiving sedatives upon transfer to the ICU, or who were post-cardiac arrest.InterventionPatients were randomly assigned to receive one of two sedation infusion strategies. The treatment group had sedation medications stopped daily. A study nurse then observed these patients until they awoke. A study physician was then summoned to restart the sedative medications at half their previous dose and then retitrate to the desired effect (Ramsay level 3–4 on a 1–6 scale). The control group received “routine care” of the rounding ICU team. Both of these treatment groups had their patients either assigned to midazolam or propofol as the sedative agent, making a total of four different treatment groups.Outcomes of interestThe primary outcomes were the lengths of time with mechanical ventilation, in the ICU and in the hospital. Secondary outcomes included adverse events (e.g., premature self-extubation, reintubation, long-term ventilation, withdrawal of care and death).For the daily interruption group, the number of days intubated and in the ICU was significantly lower, and there was a trend toward fewer hospital days (Figure). Furthermore, there were fewer diagnostic studies done for the intervention group to determine the cause of a change in mental status. Other secondary outcomes did not differ between the groups. No important differences were seen with regards to which sedative agent was used.ConclusionIntubated medical ICU patients who receive daily interruption of sedative infusions have shorter times on the ventilator and in the ICU.

Sleep in the Acute Phase of Severe Traumatic Brain Injury: A Snapshot of Polysomnography.

Background and Objectives. The onset of pervasive sleep-wake disturbances associated with traumatic brain injury (TBI) is poorly understood. This study aimed to (a) determine the feasibility of using polysomnography in patients in the acute, hospitalized stage of severe TBI and (b) explore sleep quality and sleep architecture during this stage of recovery, compared to patients with other traumatic injuries. Methods. A cross-sectional case-control design was used. We examined the sleep of 7 patients with severe TBI (17-47 years; 20.3 ± 15.0 days postinjury) and 6 patients with orthopedic and/or spinal cord injuries (OSCI; 19-58 years; 16.9 ± 4.9 days postinjury). One night of ambulatory polysomnography was performed at bedside. Results. Compared to OSCI patients, TBI patients showed a significantly longer duration of nocturnal sleep and earlier nighttime sleep onset. Sleep efficiency was low and comparable in both groups. All sleep stages were observed in both groups with normal proportions according to age. Conclusion. Patients in the acute stage of severe TBI exhibit increased sleep duration and earlier sleep onset, suggesting that the injured brain enhances sleep need and/or decreases the ability to maintain wakefulness. As poor sleep efficiency could compromise brain recovery, further studies should investigate whether strategies known to optimize sleep in healthy individuals are efficacious in acute TBI. While there are several inherent challenges, polysomnography is a useful means of examining sleep in the early stage of recovery in patients with severe TBI.

Parallel recovery of consciousness and sleep in acute traumatic brain injury

Objective: To investigate whether the progressive recuperation of consciousness was associated with the reconsolidation of sleep and wake states in hospitalized patients with acute traumatic brain injury (TBI). Methods: This study comprised 30 hospitalized patients (age 29.1 ± 13.5 years) in the acute phase of moderate or severe TBI. Testing started 21.0 ± 13.7 days postinjury. Consciousness level and cognitive functioning were assessed daily with the Rancho Los Amigos scale of cognitive functioning (RLA). Sleep and wake cycle characteristics were estimated with continuous wrist actigraphy. Mixed model analyses were performed on 233 days with the RLA (fixed effect) and sleep-wake variables (random effects). Linear contrast analyses were performed in order to verify if consolidation of the sleep and wake states improved linearly with increasing RLA score. Results: Associations were found between scores on the consciousness/cognitive functioning scale and measures of sleep-wake cycle consolidation (p < 0.001), nighttime sleep duration (p = 0.018), and nighttime fragmentation index (p < 0.001). These associations showed strong linear relationships (p < 0.01 for all), revealing that consciousness and cognition improved in parallel with sleep-wake quality. Consolidated 24-hour sleep-wake cycle occurred when patients were able to give context-appropriate, goal-directed responses. Conclusions: Our results showed that when the brain has not sufficiently recovered a certain level of consciousness, it is also unable to generate a 24-hour sleep-wake cycle and consolidated nighttime sleep. This study contributes to elucidating the pathophysiology of severe sleep-wake cycle alterations in the acute phase of moderate to severe TBI.

Skin microcirculation and vasopressin infusion: a laser Doppler study

Use of arginine vasopressin in the management of refractory vasodilatory shock has been associated with development of ischaemic skin lesions. Because of the increasing popularity of arginine vasopressin, it is important to evaluate its effects on microcirculatory blood flow. Such studies are crucial if we are to appreciate the microcirculatory consequences of our various resuscitation strategies. However, methodological issues must always be considered because they can significantly influence interpretation of the results. Some aspects of use of laser Doppler to evaluate the microcirculation are reviewed within the context of recent findings presented by Luckner and coworkers in this issue of Critical Care.