Mastering the brain in critical conditions: an update.

Acute brain injuries, such as traumatic brain injury and ischemic and hemorragic stroke, are a leading cause of death and disability worldwide. While characterized by clearly distict primary events-vascular damage in strokes and biomechanical damage in traumatic brain injuries-they share common secondary injury mechanisms influencing long-term outcomes. Growing evidence suggests that a more personalized approach to optimize energy substrate delivery to the injured brain and prognosticate towards families could be beneficial. In this context, continuous invasive and/or non-invasive neuromonitoring, together with clinical evaluation and neuroimaging to support strategies that optimize cerebral blood flow and metabolic delivery, as well as approaches to neuroprognostication are gaining interest. Recently, the European Society of Intensive Care Medicine organized a 2-day course focused on a practical case-based clinical approach of acute brain-injured patients in different scenarios and on future perspectives to advance the management of this population. The aim of this manuscript is to update clinicians dealing with acute brain injured patients in the intensive care unit, describing current knowledge and clinical practice based on the insights presented during this course.

Neurological Pupil Index for the Early Prediction of Outcome in Severe Acute Brain Injury Patients.

In this study, we examined the early value of automated quantitative pupillary examination, using the Neurological Pupil index (NPi), to predict the long-term outcome of acute brain injured (ABI) patients. We performed a single-centre retrospective study (October 2016−March 2019) in ABI patients who underwent NPi measurement during the first 3 days following brain insult. We examined the performance of NPi­alone or in combination with other baseline demographic (age) and radiologic (CT midline shift) predictors­to prognosticate unfavourable 6-month outcome (Glasgow Outcome Scale 1−3). A total of 145 severely brain-injured subjects (65 traumatic brain injury, TBI; 80 non-TBI) were studied. At each time point tested, NPi <3 was highly predictive of unfavourable outcome, with highest specificity (100% (90−100)) at day 3 (sensitivity 24% (15−35), negative predictive value 36% (34−39)). The addition of NPi, from day 1 following ABI to age and cerebral CT scan, provided the best prognostic performance (AUROC curve 0.85 vs. 0.78 without NPi, p = 0.008; DeLong test) for 6-month neurological outcome prediction. NPi, assessed at the early post-injury phase, has a superior ability to predict unfavourable long-term neurological outcomes in severely brain-injured patients. The added prognostic value of NPi was most significant when complemented with baseline demographic and radiologic information.

Factors Associated With Brain Tissue Oxygenation Changes After RBC Transfusion in Acute Brain Injury Patients.

OBJECTIVES: Anemia is common after acute brain injury and can be associated with brain tissue hypoxia. RBC transfusion (RBCT) can improve brain oxygenation; however, predictors of such improvement remain unknown. We aimed to identify the factors associated with PbtO2 increase (greater than 20% from baseline value) after RBCT, using a generalized mixed model. DESIGN: This is a multicentric retrospective cohort study (2012-2020). SETTING: This study was conducted in three European ICUs of University Hospitals located in Belgium, Switzerland, and Austria. PATIENTS: All patients with acute brain injury who were monitored with brain tissue oxygenation (PbtO2) catheters and received at least one RBCT. INTERVENTION: Patients received at least one RBCT. PbtO2 was recorded before, 1 hour, and 2 hours after RBCT. MEASUREMENTS AND MAIN RESULTS: We included 69 patients receiving a total of 109 RBCTs after a median of 9 days (5-13 d) after injury. Baseline hemoglobin (Hb) and PbtO2 were 7.9 g/dL [7.3-8.7 g/dL] and 21 mm Hg (16-26 mm Hg), respectively; 2 hours after RBCT, the median absolute Hb and PbtO2 increases from baseline were 1.2 g/dL [0.8-1.8 g/dL] (p = 0.001) and 3 mm Hg (0-6 mm Hg) (p = 0.001). A 20% increase in PbtO2 after RBCT was observed in 45 transfusions (41%). High heart rate (HR) and low PbtO2 at baseline were independently associated with a 20% increase in PbtO2 after RBCT. Baseline PbtO2 had an area under receiver operator characteristic of 0.73 (95% CI, 0.64-0.83) to predict PbtO2 increase; a PbtO2 of 20 mm Hg had a sensitivity of 58% and a specificity of 73% to predict PbtO2 increase after RBCT. CONCLUSIONS: Lower PbtO2 values and high HR at baseline could predict a significant increase in brain oxygenation after RBCT.

Hypertonic lactate for the treatment of intracranial hypertension in patients with acute brain injury.

Hypertonic lactate (HL) is emerging as alternative treatment of intracranial hypertension following acute brain injury (ABI), but comparative studies are limited. Here, we examined the effectiveness of HL on main cerebral and systemic physiologic variables, and further compared it to that of standard hypertonic saline (HS). Retrospective cohort analysis of ABI subjects who received sequential osmotherapy with 7.5% HS followed by HL-given at equi-osmolar (2400 mOsmol/L) and isovolumic (1.5 mL/kg) bolus doses-to reduce sustained elevations of ICP (> 20 mmHg). The effect of HL on brain (intracranial pressure [ICP], brain tissue PO2 [PbtO2], cerebral microdialysis [CMD] glucose and lactate/pyruvate ratio [LPR]) and blood (chloride, pH) variables was examined at different time-points (30, 60, 90, 120 min vs. baseline), and compared to that of HS. A total of 34 treatments among 17 consecutive subjects (13 traumatic brain injury [TBI], 4 non-TBI) were studied. Both agents significantly reduced ICP (p < 0.001, at all time-points tested): when comparing treatment effectiveness, absolute ICP decrease in mmHg and the duration of treatment effect (median time with ICP < 20 mmHg following osmotherapy 183 [108-257] vs. 150 [111-419] min) did not differ significantly between HL and HS (all p > 0.2). None of the treatment had statistically significant effects on PbtO2 and CMD biomarkers. Treatment with HL did not cause hyperchloremia and resulted in a more favourable systemic chloride balance than HS (Δ blood chloride - 1 ± 2.5 vs. + 4 ± 3 mmol/L; p < 0.001). This is the first clinical study showing that HL has comparative effectiveness than HS for the treatment of intracranial hypertension, while at the same time avoiding hyperchloremic acidosis. Both agents had no significant effect on cerebral oxygenation and metabolism.

Electroencephalography of mechanically ventilated patients at high risk of delirium.

OBJECTIVE: Neurophysiological exploration of ICU delirium is limited. Here, we examined EEG characteristics of medical-surgical critically ill patients with new-onset altered consciousness state at high risk for ICU delirium. MATERIALS AND METHODS: Pre-planned analysis of non-neurological mechanically ventilated medical-surgical ICU subjects, who underwent a prospective multicenter randomized, controlled EEG study (NCT03129438, April 2017-November 2018). EEG characteristics, according to the 2012 ACNS nomenclature, included background activity, rhythmic periodic patterns/epileptic activity, amplitude, frequency, stimulus-induced discharges, triphasic waves, reactivity, and NREM sleep. We explored EEG findings in delirious versus non-delirious patients, specifically focusing on the presence of burst-suppression and rhythmic periodic patterns (ictal-interictal continuum), and ictal activity. RESULTS: We analyzed 91 patients (median age, 66 years) who underwent EEG because of new-onset altered consciousness state at a median 5 days from admission; 42 patients developed delirium (46%). Burst-suppression (10 vs 0%, p = .02), rhythmic/periodic patterns (43% vs 22%, p = .03) and epileptiform activity (7 vs 0%, p = .05) were more frequent in delirious versus non-delirious patients. The presence of at least one of these abnormal EEG findings (32/91 patients; 35%) was associated with a significant increase in the likelihood of delirium (42 vs 15%, p = .006). Cumulative dose of sedatives and analgesics, as well as all other EEG characteristics, did not differ significantly between the two groups. CONCLUSION: In mechanically ventilated non-neurological critically ill patients with new-onset alteration of consciousness, EEG showing burst-suppression, rhythmic or periodic patterns, or seizures/status epilepticus indicate an increased risk of ICU delirium.

Acute Distress Respiratory Syndrome After Subarachnoid Hemorrhage: Incidence and Impact on the Outcome in a Large Multicenter, Retrospective Cohort.

BACKGROUND: Respiratory complications are frequently reported after aneurismal subarachnoid hemorrhage (aSAH), even if their association with outcome remains controversial. Acute respiratory distress syndrome (ARDS) is one of the most severe pulmonary complications after aSAH, with a reported incidence ranging from 11 to 50%. This study aims to assess in a large cohort of aSAH patients, during the first week after an intensive care unit (ICU) admission, the incidence of ARDS defined according to the Berlin criteria and its effect on outcome. METHODS: This is a multicentric, retrospective cohort study in 3 European intensive care units. We collected data between January 2009 and December 2017. We included adult patients (≥ 18 years) with a diagnosis of aSAH admitted to the ICU. RESULTS: A total of 855 patients fulfilled the inclusion criteria. ARDS was assessable in 851 patients. The cumulative incidence of ARDS was 2.2% on the first day since ICU admission, 3.2% on day three, and 3.6% on day seven. At the univariate analysis, ARDS was associated with a poor outcome (p = 0.005) at ICU discharge, and at the multivariable analysis, patients with ARDS showed a worse neurological outcome (Odds ratio = 3.00, 95% confidence interval 1.16-7.72; p = 0.023). CONCLUSIONS: ARDS has a low incidence in the first 7 days of ICU stay after aSAH, but it is associated with worse outcome.

Acute Kidney Injury in Traumatic Brain Injury Patients: Results From the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury Study.

OBJECTIVES: Acute kidney injury is frequent in polytrauma patients, and it is associated with increased mortality and extended hospital length of stay. However, the specific prevalence of acute kidney injury after traumatic brain injury is less recognized. The present study aims to describe the occurrence rate, risk factors, timing, and association with outcome of acute kidney injury in a large cohort of traumatic brain injury patients. DESIGN: The Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury is a multicenter, prospective observational, longitudinal, cohort study. SETTING: Sixty-five ICUs across Europe. PATIENTS: For the present study, we selected 4,509 traumatic brain injury patients with an ICU length of stay greater than 72 hours and with at least two serum creatinine values during the first 7 days of ICU stay. MEASUREMENTS AND MAIN RESULTS: We classified acute kidney injury in three stages according to the Kidney Disease Improving Global Outcome criteria: acute kidney injury stage 1 equals to serum creatinine × 1.5-1.9 times from baseline or an increase greater than or equal to 0.3 mg/dL in 48 hours; acute kidney injury stage 2 equals to serum creatinine × 2-2.9 times baseline; acute kidney injury stage 3 equals to serum creatinine × three times baseline or greater than or equal to 4 mg/dL or need for renal replacement therapy. Standard reporting techniques were used to report incidences. A multivariable Cox regression analysis was performed to model the cause-specific hazard of acute kidney injury and its association with the long-term outcome. We included a total of 1,262 patients. The occurrence rate of acute kidney injury during the first week was as follows: acute kidney injury stage 1 equals to 8% (n = 100), acute kidney injury stage 2 equals to 1% (n = 14), and acute kidney injury stage 3 equals to 3% (n = 36). Acute kidney injury occurred early after ICU admission, with a median of 2 days (interquartile range 1-4 d). Renal history (hazard ratio = 2.48; 95% CI, 1.39-4.43; p = 0.002), insulin-dependent diabetes (hazard ratio = 2.52; 95% CI, 1.22-5.197; p = 0.012), hypernatremia (hazard ratio = 1.88; 95% CI, 1.31-2.71; p = 0.001), and osmotic therapy administration (hazard ratio = 2.08; 95% CI, 1.45-2.99; p < 0.001) were significantly associated with the risk of developing acute kidney injury. Acute kidney injury was also associated with an increased ICU length of stay and with a higher probability of 6 months unfavorable Extended Glasgow Outcome Scale and mortality. CONCLUSIONS: Acute kidney injury after traumatic brain injury is an early phenomenon, affecting about one in 10 patients. Its occurrence negatively impacts mortality and neurologic outcome at 6 months. Osmotic therapy use during ICU stay could be a modifiable risk factor.

Tracheostomy practice and timing in traumatic brain-injured patients: a CENTER-TBI study.

PURPOSE: Indications and optimal timing for tracheostomy in traumatic brain-injured (TBI) patients are uncertain. This study aims to describe the patients' characteristics, timing, and factors related to the decision to perform a tracheostomy and differences in strategies among different countries and assess the effect of the timing of tracheostomy on patients' outcomes. METHODS: We selected TBI patients from CENTER-TBI, a prospective observational longitudinal cohort study, with an intensive care unit stay ≥ 72 h. Tracheostomy was defined as early (≤ 7 days from admission) or late (> 7 days). We used a Cox regression model to identify critical factors that affected the timing of tracheostomy. The outcome was assessed at 6 months using the extended Glasgow Outcome Score. RESULTS: Of the 1358 included patients, 433 (31.8%) had a tracheostomy. Age (hazard rate, HR = 1.04, 95% CI = 1.01-1.07, p = 0.003), Glasgow coma scale ≤ 8 (HR = 1.70, 95% CI = 1.22-2.36 at 7; p < 0.001), thoracic trauma (HR = 1.24, 95% CI = 1.01-1.52, p = 0.020), hypoxemia (HR = 1.37, 95% CI = 1.05-1.79, p = 0.048), unreactive pupil (HR = 1.76, 95% CI = 1.27-2.45 at 7; p < 0.001) were predictors for tracheostomy. Considerable heterogeneity among countries was found in tracheostomy frequency (7.9-50.2%) and timing (early 0-17.6%). Patients with a late tracheostomy were more likely to have a worse neurological outcome, i.e., mortality and poor neurological sequels (OR = 1.69, 95% CI = 1.07-2.67, p = 0.018), and longer length of stay (LOS) (38.5 vs. 49.4 days, p = 0.003). CONCLUSIONS: Tracheostomy after TBI is routinely performed in severe neurological damaged patients. Early tracheostomy is associated with a better neurological outcome and reduced LOS, but the causality of this relationship remains unproven.

Noninvasive Intracranial Pressure Estimation With Transcranial Doppler: A Prospective Observational Study.

BACKGROUND: Transcranial Doppler (TCD) ultrasonography has been described for the noninvasive assessment of intracranial pressure (ICP). This study investigates the relationship between standard, invasive intracranial pressure monitoring (ICPi) and noninvasive ICP assessment using a simple formula based on TCD-derived flow velocity (FV) and mean arterial blood pressure values (ICPTCD). MATERIAL AND METHODS: We performed a prospective observational study on 100 consecutive traumatic brain injury patients requiring invasive ICP monitoring, admitted to the Neurosciences and Trauma Critical Care Unit of Addenbrooke's Hospital, Cambridge, UK. ICPi was compared with ICPTCD using a method based on the "diastolic velocity-derived estimator" (FVd), which was initially described for the noninvasive estimation of cerebral perfusion pressure but subsequently utilized for ICP assessment. RESULTS: Median ICPi was 13 mm Hg (interquartile range: 10, 17.25 mm Hg). There was no correlation between ICPi and ICPTCD (R=-0.17; 95% confidence interval [CI]: -0.35, 0.03; P=0.097). Bland-Altman analysis demonstrated wide 95% limits of agreement between ICPi and ICPTCD (-27.58, 30.10; SD, 14.42). ICPTCD was not able to detect intracranial hypertension (ICPi >20 mm Hg); the area under the receiver operating characteristic curve for prediction was 34.5% (95% CI, 23.1%-45.9%) with 0% sensitivity and 74.4% specificity for ICPTCD to detect ICPi>20 mm Hg. CONCLUSIONS: Using a formula based on diastolic FV, TCD is an insufficiently accurate method for the noninvasive assessment of ICP. Further studies are warranted to confirm these results in a broader patient cohort.

Death by neurologic criteria: pathophysiology, definition, diagnostic criteria and tests.

Death by neurologic criteria is an irreversible sequence of events culminating in permanent cessation of cerebral functions. In this context, there are no responses arising from the brain, no cranial nerve reflexes nor motor responses to pain stimuli, and no respiratory drive. The diagnosis of death by neurologic criteria implies that there is clinical evidence of the complete and irreversible cessation of brainstem and cerebral functions. The diagnosis, confirmation, and certification of death are core skills for medical practitioners. The aim of this review is to discuss the pathophysiology and definition of death by neurological criteria, describing the clinical assessment, and the use of ancillary tests for the diagnosis of brainstem death.