Ultrasound assessment of gastric contents in children before general anaesthesia for acute appendicitis.

There is increasing evidence that a minority of adults with acute appendicitis have gastric contents, posing an increased risk of pulmonary aspiration. This study aimed to evaluate the proportion of children with acute appendicitis who have gastric contents considered to pose a higher risk of pulmonary aspiration. We analysed point-of-care gastric ultrasound data routinely collected in children before emergency appendicectomy in a specialist paediatric hospital over a 30-month period. Based on qualitative and quantitative antral assessment in the supine and right lateral decubitus positions, gastric contents were classified as 'higher-risk' (clear liquid with calculated gastric fluid volume > 0.8 ml.kg-1 , thick liquid or solid) or 'lower-risk' of pulmonary aspiration. The 115 children studied had a mean (SD) age of 11 (3) years; 37 (32%; 95%CI: 24-42%) presented with higher-risk gastric contents, including 15 (13%; 95%CI: 8-21%) with solid/thick liquid contents. Gastric contents could not be determined in 13 children as ultrasound examination was not feasible in the right lateral decubitus position. No cases of pulmonary aspiration occurred. This study shows that gastric ultrasound is feasible in children before emergency appendicectomy. This technique showed a range of gastric content measurements, which could contribute towards defining the risk of pulmonary aspiration.

French recommendations for the management of patients with spinal cord injury or at risk of spinal cord injury.

OBJECTIVES: To update the French guidelines on the management of trauma patients with spinal cord injury or suspected spinal cord injury. DESIGN: A consensus committee of 27 experts was formed. A formal conflict-of-interest (COI) policy was developed at the outset of the process and enforced throughout. The entire guidelines process was conducted independently of any industrial funding (i.e. pharmaceutical, medical devices). The authors were advised to follow the rules of the Grading of Recommendations Assessment, Development and Evaluation (GRADE®) system to guide assessment of quality of evidence. The potential drawbacks of making strong recommendations in the presence of low-quality evidence were emphasised. METHODS: The committee studied twelve questions: (1) What are the indications and arrangements for spinal immobilisation? (2) What are the arrangements for pre-hospital orotracheal intubation? (3) What are the objectives of haemodynamic resuscitation during the lesion assessment, and during the first few days in hospital? (4) What is the best way to manage these patients to improve their long-term prognosis? (5) What is the place of corticosteroid therapy in the initial phase? (6) What are the indications for magnetic resonance imaging in the lesion assessment phase? (7) What is the optimal time for surgical management? (8) What are the best arrangements for orotracheal intubation in the hospital environment? (9) What are the specific conditions for weaning these patients from mechanical ventilation for? (10) What are the procedures for analgesic treatment of these patients? (11) What are the specific arrangements for installing and mobilising these patients? (12) What is the place of early intermittent bladder sampling in these patients? Each question was formulated in a PICO (Patients, Intervention, Comparison, Outcome) format and the evidence profiles were produced. The literature review and recommendations were made according to the GRADE® Methodology. RESULTS: The experts' work synthesis and the application of the GRADE method resulted in 19 recommendations. Among the recommendations formalised, 2 have a high level of evidence (GRADE 1+/-) and 12 have a low level of evidence (GRADE 2+/-). For 5 recommendations, the GRADE method could not be applied, resulting in expert advice. After two rounds of scoring and one amendment, strong agreement was reached on all the recommendations. CONCLUSIONS: There was significant agreement among experts on strong recommendations to improve practices for the management of patients with spinal cord injury.

Integrating a pharmacist into an anaesthesiology and critical care department: Is this worthwhile?

Background Operating rooms and Intensive Care Units are places where an optimal management of drugs and medical devices is required. Objective To evaluate the impact of a dedicated pharmacist in an academic Anaesthesiology and Critical Care Department. Setting This study was conducted in the Anaesthesiology and Critical Care Department of Grenoble University Hospital. Method Between November 2013 and June 2017, the drug-related problems occurring in three Intensive Care Units and their corrections by a full-time clinical pharmacist were analyzed using a structured order review instrument. Pharmaceutical costs in the Anaesthesiology and Critical Care Department were analyzed over a 7 year period (2010-2016), during which automated dispensing systems and recurrent meetings to review indications of medications and medical devices were implemented in the department. Main outcome measure Analysis of two issues: correcting drug-related problems and containing pharmaceutical costs. Results A total of 324 drug-related problems were identified. The most frequent problem concerned anti-infective agents (45%), and this was mainly due to the over-dosage of drugs (30%). Dosage adjustments were the most frequent interventions performed by the pharmacist (43%). Over the 7 year period, pharmaceutical costs decreased by 9% (€365,469), while the care activity of the department increased by 55% (+ 12,022 surgical procedures and + 1424 admissions in the ICU). Conclusion Integrating a pharmacist into the Anaesthesiology and Critical Care Department was associated with interventions to correct drug-related problems and containing pharmaceutical costs. Pharmacists should play a central role in such medical environments, to optimize the use of drugs and medical devices.

An elevated respiratory quotient predicts complications after cardiac surgery under extracorporeal circulation: an observational pilot study.

Following cardiac surgery, hyperlactatemia due to anaerobic metabolism is associated with an increase in both morbidity and mortality. We previously found that an elevated respiratory quotient (RQ) predicts anaerobic metabolism. In the present study we aimed to demonstrate that it is also associated with poor outcome following cardiac surgery. This single institution, prospective, observational study includes all those patients that were consecutively admitted to the intensive care unit (ICU) after cardiac surgery with cardiopulmonary bypass, that had also been monitored using pulmonary artery catheter. Data were recorded at admission (H0) and after one hour (H1) including: oxygen consumption ([Formula: see text]), carbon dioxide production ([Formula: see text]), RQ ([Formula: see text]), lactate levels and mixed venous oxygen saturation ([Formula: see text]). The primary endpoint was defined as mortality at 30 days. Comparison of the area under the curve (AUC) for receiver operating characteristic curves was used to analyze the prognostic predictive value of RQ, lactate levels and [Formula: see text], in terms of patient outcome. We studied 151 patients admitted to the ICU between May 2015 and February 2016. Seventy eight patients experienced a worse than expected outcome in the post-operative period, and among those seven died. RQ at H1 in non-survivors ([Formula: see text]) was higher than in survivors ([Formula: see text]; p = 0.02). The AUC for RQ to predict mortality was 0.77 (IC95% [0.70-0.84]), with a threshold value of 0.76 (sensitivity 64%, specificity 100%). By comparison, the AUC for lactate levels was significantly superior (AUClact 0.89, IC95% [0.83-0.93], p = 0.02). In this study, elevated RQ appeared to be predictive of mortality after cardiac surgery with CPB.

Hypertonic sodium lactate reverses brain oxygenation and metabolism dysfunction after traumatic brain injury.

BACKGROUND: The mechanisms by which hypertonic sodium lactate (HSL) solution act in injured brain are unclear. We investigated the effects of HSL on brain metabolism, oxygenation, and perfusion in a rodent model of diffuse traumatic brain injury (TBI). METHODS: Thirty minutes after trauma, anaesthetised adult rats were randomly assigned to receive a 3 h infusion of either a saline solution (TBI-saline group) or HSL (TBI-HSL group). The sham-saline and sham-HSL groups received no insult. Three series of experiments were conducted up to 4 h after TBI (or equivalent) to investigate: 1) brain oedema using diffusion-weighted magnetic resonance imaging and brain metabolism using localized 1H-magnetic resonance spectroscopy (n = 10 rats per group). The respiratory control ratio was then determined using oxygraphic analysis of extracted mitochondria, 2) brain oxygenation and perfusion using quantitative blood-oxygenation-level-dependent magnetic resonance approach (n = 10 rats per group), and 3) mitochondrial ultrastructural changes (n = 1 rat per group). RESULTS: Compared with the TBI-saline group, the TBI-HSL and the sham-operated groups had reduced brain oedema. Concomitantly, the TBI-HSL group had lower intracellular lactate/creatine ratio [0.049 (0.047-0.098) vs 0.097 (0.079-0.157); P < 0.05], higher mitochondrial respiratory control ratio, higher tissue oxygen saturation [77% (71-79) vs 66% (55-73); P < 0.05], and reduced mitochondrial cristae thickness in astrocytes [27.5 (22.5-38.4) nm vs 38.4 (31.0-47.5) nm; P < 0.01] compared with the TBI-saline group. Serum sodium and lactate concentrations and serum osmolality were higher in the TBI-HSL than in the TBI-saline group. CONCLUSIONS: These findings indicate that the hypertonic sodium lactate solution can reverse brain oxygenation and metabolism dysfunction after traumatic brain injury through vasodilatory, mitochondrial, and anti-oedema effects.

Reduced mortality by meeting guideline criteria before using recombinant activated factor VII in severe trauma patients with massive bleeding.

BACKGROUND: Management of trauma patients with severe bleeding has led to criteria before considering use of recombinant activated factor VII (rFVIIa), including haemoglobin >8 g dl-1, serum fibrinogen ≥1.0 g l-1, platelets >50,000 x 109 l-1, arterial pH ≥ 7.20, and body temperature ≥34 °C. We hypothesized that meeting these criteria is associated with improved outcomes. METHODS: In this prospective cohort study of 26 French trauma centres, subjects were included if they received rFVIIa for persistent massive bleeding despite appropriate care after severe blunt and/or penetrating trauma. RESULTS: After surgery and/or embolization as haemostatic interventions, 112 subjects received a first dose of 103 µg kg-1 rFVIIa (82-200) (median, 25th-75th percentile) at 420 min (285-647) post-trauma. Of these, 71 (63%) "responders" were still alive at 24h post-trauma and had their transfusion requirements reduced by > 2 packed red blood cell units after rFVIIa treatment. Mortality was 54% on day 30 post-trauma. There were 21%, 44% and 35% subjects who fulfilled 0-1, 2-3 or 4-5, respectively, of the guidelines before receiving rFVIIa. Survival at day 30 was 13%, 49% and 64% and the proportion of responders was 39%, 64% and 82%, when subjects fulfilled 0-1, 2-3 or 4-5 conditions, respectively (both P <0.01). CONCLUSIONS: In actively bleeding trauma patients, meeting guideline criteria before considering rFVIIa was associated with lower mortality and a higher proportion of responders to the rFVIIa.

Which pelvic ring fractures are potentially lethal?

PURPOSE: Global mortality of polytraumatised patients presenting pelvic ring fractures remains high (330%), despite improvements in treatment algorithms in Level I Trauma Centers. Many classifications have been developed in order to identify and analyse these pelvic ring lesions. However, it remains difficult to predict intra-pelvic haemorrhage. The aim of this study was to identify pelvic ring anatomical lesions associated with significant blood loss, susceptible to lead to life-threatening haemorrhage. MATERIAL AND METHOD: This study focused on a retrospective analysis of patients' medical files, all of whom were admitted to one of the shock rooms of Grenoble University Hospital, France, between January 2004 and December 2008. Treatment was given according to the institutional algorithm of the Alps Trauma Center and Emergency North Alpine Network Trauma System (TRENAU). Different hemodynamical parameters at arrival were measured, and the fractures were classified according to Young and Burgess, Tile, Letournel and Denis. One hundred and ninety seven patients were analysed. They were subdivided into two groups, embolised (Group E) and non-embolised (Group NE). RESULTS: Group NE included 171 patients with a mean age of 40.2 ± 8.7 years (15-90). Group E included 26 patients with a mean age of 41.6 ± 5.3 years (18-67). Twenty-six patients died during the initial treatment phase. Eleven belonged to Group E and 15 to Group NE. Mortality was significantly higher in Group E (42.3% vs 8.8% in Group NE) (p < 0.05). There were significantly many more Tile C unstable fractures in Group E (p = 0.0014), and anterior lesions, according to Letournel, with pubic symphysis disruption were significantly more likely to lead to active bleeding treated by selective embolisation (p = 0.0014). Posterior pelvic ring lesions with iliac wing fracture and transforaminal sacral fractures (Denis 2) were also more frequently associated with bleeding treated by embolisation (p = 0.0088 and p = 0.0369 respectively). DISCUSSION/CONCLUSION: It appears that in our series the primary identification and classification of osteo-ligamentous lesions (according to Letournel and Denis' classifications) allows to anticipate the importance of bleeding and to adapt the management of patients accordingly, in order to quickly organise angiography with embolisation.

Prone position affects stroke volume variation performance in predicting fluid responsiveness in neurosurgical patients.

BACKGROUND: Stroke volume variation (SVV) during mechanical ventilation predicts preload responsiveness. We hypothesized that the prone position would alter the performance of this dynamic indicator. METHODS: Two parallel groups of ventilated neurosurgical patients with low tidal volume (6-8 ml.kg-1) were studied before surgical incision. SVV was measured at T0, T15 and T30 min during a fluid volume expansion (250 mL hetastarch 6% over 30 min) with patients in either the supine (N.=29; Supine group) or prone position (N.=23; Prone group). Fluid responsiveness was defined as an increase in the stroke volume index (SVI) of ≥20% at T30. Receiver-operating characteristics (ROC) curves were generated for SVV. RESULTS: Prone positioning significantly increased SVV. Volume expansion in the Prone group increased SVI but led to a decline in SVV from 16% (12-22; median, 25-75th percentile) at T0 to 9% (8-13%) at T30. These effects on SVI and SVV were more pronounced compared to those obtained in the Supine group (P ≤0.05). Fluid responsiveness was predicted by SVV >12% at T0 (sensitivity 88%, specificity 62%) in the Supine group. In the Prone group, the area under the ROC curve of SVV (0.53; 95% confidence interval 0.27-0.79) did not allow the determination of a threshold SVV value. CONCLUSION: In ventilated patients with low tidal volume, a prone position may have a direct effect on the heart that alters the performance of SVV in predicting fluid responsiveness. External factor such as prone position renders difficult the interpretation of SVV as a dynamic indicator of cardiac preload.

[Hypernatremia in head-injured patients: friend or foe?]. / Hypernatrémie chez le patient cérébrolésé: utile ou dangereux?

Hypernatremia is defined by a serum sodium concentration of more than 145 mmol/L and reflects a disturbance of the regulation between water and sodium. The high incidence of hypernatremia in patients with severe brain injury is due various causes including poor thirst, diabetes insipidus, iatrogenic sodium administration, and primary hyperaldosteronism. Hypernatremia in the intensive care unit is independently associated with increased mortality and complications rates. Because of the rapid brain adaptation to extracellular hypertonicity, sustained hypernatremia exposes the patient to an exacerbation of brain edema during attempt to normalize natremia. Like serum glucose, serum sodium concentration must be tightly monitored in the intensive care unit.

[Impact of a trauma network on mortality in patients with severe pelvic trauma]. / Impact de la mise en place d'un réseau de soins en traumatologie sur la mortalité des patients traumatisés graves du bassin.

AIM: To evaluate the impact of a regional trauma network on intra-hospital mortality rates of patients admitted with severe pelvic trauma. STUDY: Retrospective observational study. PATIENTS: Sixty-five trauma patients with serious pelvic fracture (pelvic abbreviated injury scale [AIS] score of 3 or more). METHODS: Demographic, physiologic and biological parameters were recorded. Observed mortality rates were compared to predicted mortality according to the Trauma Revised Injury Severity Score methodology adjusted by a case mix variation model. RESULTS: Twenty-nine patients were admitted in a level I trauma centre (reference centre) and 36 in level II trauma centres (centres with interventional radiology facility and/or neurosurgery). Patients from the level I trauma centre were more severely injured than those who were admitted at the level II trauma centres (Injury Severity Score [ISS]: 30 [13-75] vs 22 [9-59]; P<0.01). Time from trauma to hospital admission was also longer in level I trauma centre (115 [50-290] min vs 90 [28-240] min, P <0.01). Observed mortality rates (14%; 95% confidence interval, 95% CI, [1-26%]) were lower than the predicted mortality (29%; 95% CI [13-44%]) in the level I trauma centre. No difference in mortality rates was found in the level II trauma centres. CONCLUSION: The regional trauma network could screen the most severely injured patients with pelvic trauma to admit them at a level I trauma centre. The observed mortality of these patients was lower than the predicted mortality despite increased time from trauma to admission.

[Therapeutic hypothermia for severe traumatic brain injury]. / Hypothermie thérapeutique en traumatologie crânienne grave.

Therapeutic hypothermia (TH) is considered a standard of care in the post-resuscitation phase of cardiac arrest. In experimental models of traumatic brain injury (TBI), TH was found to have neuroprotective properties. However, TH failed to demonstrate beneficial effects on neurological outcome in patients with TBI. The absence of benefits of TH uniformly applied in TBI patients should not question the use of TH as a second-tier therapy to treat elevated intracranial pressure. The management of all the practical aspects of TH is a key factor to avoid side effects and to optimize the potential benefit of TH in the treatment of intracranial hypertension. Induction of TH can be achieved with external surface cooling or with intra-vascular devices. The therapeutic target should be set at a 35°C using brain temperature as reference, and should be maintained at least during 48 hours and ideally over the entire period of elevated intracranial pressure. The control of the rewarming phase is crucial to avoid temperature overshooting and should not exceed 1°C/day. Besides its use in the management of intracranial hypertension, therapeutic cooling is also essential to treat hyperthermia in brain-injured patients. In this review, we will discuss the benefit-risk balance and practical aspects of therapeutic temperature management in TBI patients.

[Organization of mechanical ventilation in French Intensive care units]. / Organisation de la ventilation artificielle dans les unités de réanimation en France.

OBJECTIVES: To clarify the procedures related to mechanical ventilation in the intensive care unit setting: allocation of ventilators, team education, maintenance and reference documents. STUDY DESIGN: Declarative survey. METHODS: Between September and December 2010, we assessed the assignment and types of ventilators (ICU ventilators, temporary repair ventilators, non-invasive ventilators [NIV], and transportation ventilators), medical and nurse education, maintenance of the ventilators, presence of reference documents. Results are expressed in median/range and proportions. RESULTS: Among the 62 participating ICUs, a median of 15 ventilators/ICU (range 1-50) was reported with more than one trademark in 47 (76%) units. Specific ventilators were used for NIV in 22 (35%) units, temporary repair in 49 (79%) and transportation in all the units. Nurse education courses were given by ICU physicians in 54 (87%) units or by a company in 29 (47%) units. Medical education courses were made by ICU senior physicians in 55 (89%) units or by a company in 21 (34%) units. These courses were organized occasionally in 24 (39%) ICU and bi-annually in 16 (26%) units. Maintenance procedures were made by the ICU staff in 39 (63%) units, dedicated staff (17 [27%]) or bioengineering technicians (14 [23%] ICU). Reference documents were written for maintenance procedures in 48 (77%) units, ventilator setup in 22 (35%) units and ventilator dysfunction in 20 (32%) ICU. CONCLUSIONS: This first survey shows disparate distribution of ventilators and practices among French ICU. Education and understanding of the proper use of ventilators are key issues for security improvement.

Trauma network for severely injured patients.

Survival after severe trauma may depend on a structured chain of care from the management at the scene of trauma to hospital care and rehabilitation. In the USA, the trauma system is organized according to a pre-hospital triage by paramedics to facilitate the admission of patients to tertiary trauma centres. In France, trauma patients are transported to the most suitable facility, according to the on-scene triage by an emergency physician. Because French hospital's resources become scarce and expensive, the access to all techniques of resuscitation after severe trauma is restricted to tertiary trauma centres, at the expense of prolonged duration of transfer to these centres with a possible impact on mortality. The Northern French Alps Emergency Network created a regional trauma network system in 2008. This organization was based upon the interplay between the resources of each hospital participating to the network and the categorization of trauma severity at the scene. A regional registry allows the assessment of trauma system, which has included 3,690 severe trauma patients within the past 3 years. Bystanders, medical call dispatch centres, and interdisciplinary trauma team should form a structured and continuous chain of care to allocate each severe trauma patient to the best place of treatment.

[Early rehabilitation for neurologic patients]. / Intérêt d'une rééducation précoce pour les patients neurologiques.

Rehabilitation improves the functional prognosis of patients after a neurologic lesion, and tendency is to begin rehabilitation as soon as possible. This review focuses on the interest and the feasibility of very early rehabilitation, initiated from critical care units. It is necessary to precisely assess patients' impairments and disabilities in order to define rehabilitation objectives. Valid and simple tools must support this evaluation. Rehabilitation will be directed to preventing decubitus complications and active rehabilitation. The sooner rehabilitation is started; the better functional prognosis seems to be.

[Assessment of an educational maze for major trauma care teaching]. / Évaluation d'un labyrinthe pédagogique pour l'enseignement de la traumatologie grave.

BACKGROUND: Assess efficacy, satisfaction and usefulness of an educational maze based on posters and audioguide for major trauma care teaching to medical students. The educational maze consists of posters with audio comments recorded in an audioguide. This tool was part of a larger educational program including medical simulation. STUDY DESIGN: Prospective, interventional, observational, monocentric study. STUDENT: Medical student of Grenoble University Hospital, in the four last years of medical school, following a training course in anesthesia, emergency medical services and intensive care units. METHOD: Forty essentials key messages for major trauma management were included in 10 posters and audioguides. A first assessment with short opened answers was handed to the students at the end of the educational maze to assess their memorization. A second assessment with simple choice answers regarding satisfaction and usefulness of this new educational tool was realized at the end of the entire program. RESULT: One hundred and eighty-four medical students attending the major trauma program were included in this study. On the first test, 75% of essential knowledge on major trauma management was memorized by more than 50% of the medical students. On the second test, 94% of medical students had a high satisfaction level of this educational maze. CONCLUSION: An educational maze based on posters and audioguides seems to be an efficient, useful tool for teaching essential knowledge on major trauma management to medical students.

[Pupillometry in anesthesia and critical care]. / La pupillométrie en anesthésie-réanimation.

Pupil size reflects the balance between sympathetic and parasympathetic systems. Due to technological advances, accurate and repeated pupil size measurements are possible using infrared, video-recorded pupillometers. Two pupil size reflexes are assessed: the pupillary reflex dilation during noxious stimulation, and the pupil light reflex when the pupil is exposed to the light. The pupillary reflex dilation estimates the level of analgesia in response to a painful procedure or to a calibrated noxious stimulus, i.e., tetanic stimulus, in nonverbal patients. This might be of particular interest in optimizing the management of opioids in anaesthetized patients and in assessing pain levels in the intensive care unit. The pupil light reflex measurement is part of the routine monitoring for severely head-injured patients. The impact of pupillometry in this condition remains to be determined.

[Near infrared spectroscopy monitoring in the neurointensive care]. / Monitorage par spectroscopie de proche infrarouge en neuroréanimation.

Near infrared spectroscopy (NIRS) can noninvasively measure cerebral saturation in oxygen, that permits to estimate brain oxygenation and metabolism. This technique could be incorporated into a multimodal monitoring for severely brain-injured patients. This review presents the principles of NIRS, its limits, the main results from clinical studies and its perspectives. More clinical studies are needed before recommending the routine use of NIRS in the ICU.

A beat-by-beat, on-line, cardiovascular index, CARDEAN, to assess circulatory responses to surgery: a randomized clinical trial during spine surgery.

Automated assessment of circulatory response to surgical stimuli is unsolved. Would detection of cardiac baroreflex inhibition assess adequacy of intra-operative anti-nociception upon incision, as performed on-line on a beat-by-beat basis by a cardiovascular index, CARDEAN™? 18 ASA I-II patients undergoing spinal disc repair were studied, in a prospective randomized single-blinded trial (observational study). During infusion of propofol to maintain bispectral index between 40 and 60, patients were allocated to receive an effect site target-controlled infusion of remifentanil at Ce = 2 or 4 ng ml(-1). Upon incision and during surgery, circulatory response was assessed using beat-by-beat measurements of minor hypertension and tachycardia to give a cardiovascular index, CARDEAN, scaled between 0 and 100. Upon skin incision, CARDEAN increased in the remifentanil Ce = 2 ng ml(-1) group (n = 7, P < 0.05), while it did not increase in the remifentanil Ce = 4 ng ml(-1) group (n = 7, P = 0.18). During surgery, retrospectively, CARDEAN > 60 was associated with tachycardia and hypertension (P (k) = 0.81 ± 0.10). Changes in CARDEAN appeared linked to adequacy of anti-nociception.

[Normobaric hyperoxia therapy for patients with traumatic brain injury]. / Hyperoxie normobarique chez le patient traumatisé crânien.

Cerebral ischaemia plays a major role in the outcome of brain-injured patients. Because brain oxygenation can be assessed at bedside using intra-parenchymal devices, there has been a growing interest about whether therapeutic hyperoxia could be beneficial for severely head-injured patients. Normobaric hyperoxia increases brain oxygenation and may improve glucose-lactate metabolism in brain regions at risk for ischaemia. However, benefits of normobaric hyperoxia on neurological outcome are not established yet, that hinders the systematic use of therapeutic hyperoxia in head-injured patients. This therapeutic option might be proposed when brain ischemia persists despite the optimization of cerebral blood flow and arterial oxygen blood content.