Association of Noninvasive Respiratory Support with Extubation Outcomes in Brain-injured Patients Receiving Mechanical Ventilation: A Secondary Analysis of the ENIO Prospective Observational Study.

Rationale: Noninvasive respiratory support using a high-flow nasal cannula (HFNC) or noninvasive positive pressure ventilation (NIPPV) can decrease the risk of reintubation in patients being liberated from mechanical ventilation, but effects in patients with acute brain injury (ABI) are unknown. Objectives: To evaluate the association between postextubation noninvasive respiratory support and reintubation in patients with ABI being liberated from mechanical ventilation. Methods: This was a secondary analysis of a prospective, observational study of mechanically ventilated patients with ABI (clinicaltrials.gov identifier NCT03400904). The primary endpoint was reintubation during ICU admission. We used mixed-effects logistic regression models with patient-level covariates and random intercepts for hospital and country to evaluate the association between prophylactic (i.e., planned) HFNC or NIPPV and reintubation. Measurements and Main Results: 1,115 patients were included from 62 hospitals and 19 countries, of whom 267 received HFNC or NIPPV following extubation (23.9%). Compared with conventional oxygen therapy, neither prophylactic HFNC nor NIPPV was associated with decreased odds of reintubation (respectively, odds ratios of 0.97 [95% confidence interval, 0.54-1.73] and 0.63 [0.30-1.32]). Findings remained consistent in sensitivity analyses accounting for alternate adjustment procedures, missing data, shorter time frames of the primary endpoint, and competing risks precluding reintubation. In a Bayesian analysis using skeptical and data-driven priors, the probabilities of reduced reintubation ranged from 17% to 34% for HFNC and from 46% to 74% for NIPPV. Conclusions: In a large cohort of brain-injured patients undergoing liberation from mechanical ventilation, prophylactic use of HFNC and NIPPV were not associated with reintubation. Prospective trials are needed to confirm treatment effects in this population. Primary study registered with www.clinicaltrials.gov (NCT03400904).

Crosstalk Between the Nervous System and Systemic Organs in Acute Brain Injury.

Organ crosstalk is a complex biological communication between distal organs mediated via cellular, soluble, and neurohormonal actions, based on a two-way pathway. The communication between the central nervous system and peripheral organs involves nerves, endocrine, and immunity systems as well as the emotional and cognitive centers of the brain. Particularly, acute brain injury is complicated by neuroinflammation and neurodegeneration causing multiorgan inflammation, microbial dysbiosis, gastrointestinal dysfunction and dysmotility, liver dysfunction, acute kidney injury, and cardiac dysfunction. Organ crosstalk has become increasingly popular, although the information is still limited. The present narrative review provides an update on the crosstalk between the nervous system and systemic organs after acute brain injury. Future research might help to target this pathophysiological process, preventing the progression toward multiorgan dysfunction in critically ill patients with brain injury.

A Comprehensive Perspective on Intracranial Pressure Monitoring and Individualized Management in Neurocritical Care: Results of a Survey with Global Experts.

BACKGROUND: Numerous trials have addressed intracranial pressure (ICP) management in neurocritical care. However, identifying its harmful thresholds and controlling ICP remain challenging in terms of improving outcomes. Evidence suggests that an individualized approach is necessary for establishing tolerance limits for ICP, incorporating factors such as ICP waveform (ICPW) or pulse morphology along with additional data provided by other invasive (e.g., brain oximetry) and noninvasive monitoring (NIM) methods (e.g., transcranial Doppler, optic nerve sheath diameter ultrasound, and pupillometry). This study aims to assess current ICP monitoring practices among experienced clinicians and explore whether guidelines should incorporate ancillary parameters from NIM and ICPW in future updates. METHODS: We conducted a survey among experienced professionals involved in researching and managing patients with severe injury across low-middle-income countries (LMICs) and high-income countries (HICs). We sought their insights on ICP monitoring, particularly focusing on the impact of NIM and ICPW in various clinical scenarios. RESULTS: From October to December 2023, 109 professionals from the Americas and Europe participated in the survey, evenly distributed between LMIC and HIC. When ICP ranged from 22 to 25 mm Hg, 62.3% of respondents were open to considering additional information, such as ICPW and other monitoring techniques, before adjusting therapy intensity levels. Moreover, 77% of respondents were inclined to reassess patients with ICP in the 18-22 mm Hg range, potentially escalating therapy intensity levels with the support of ICPW and NIM. Differences emerged between LMIC and HIC participants, with more LMIC respondents preferring arterial blood pressure transducer leveling at the heart and endorsing the use of NIM techniques and ICPW as ancillary information. CONCLUSIONS: Experienced clinicians tend to personalize ICP management, emphasizing the importance of considering various monitoring techniques. ICPW and noninvasive techniques, particularly in LMIC settings, warrant further exploration and could potentially enhance individualized patient care. The study suggests updating guidelines to include these additional components for a more personalized approach to ICP management.

Ten good reasons to consider gastrointestinal function after acute brain injury.

The brain-gut axis represents a bidirectional communication linking brain function with the gastrointestinal (GI) system. This interaction comprises a top-down communication from the brain to the gut, and a bottom-up communication from the gut to the brain, including neural, endocrine, immune, and humoral signaling. Acute brain injury (ABI) can lead to systemic complications including GI dysfunction. Techniques for monitoring GI function are currently few, neglected, and many under investigation. The use of ultrasound could provide a measure of gastric emptying, bowel peristalsis, bowel diameter, bowel wall thickness and tissue perfusion. Despite novel biomarkers represent a limitation in clinical practice, intra-abdominal pressure (IAP) is easy-to-use and measurable at bedside. Increased IAP can be both cause and consequence of GI dysfunction, and it can influence cerebral perfusion pressure and intracranial pressure via physiological mechanisms. Here, we address ten good reasons to consider GI function in patients with ABI, highlighting the importance of its assessment in neurocritical care.

Perfusion tomography in early follow-up of acute traumatic subdural hematoma: a case series.

Perfusion Computed Tomography (PCT) is an alternative tool to assess cerebral hemodynamics during trauma. As acute traumatic subdural hematomas (ASH) is a severe primary injury associated with poor outcomes, the aim of this study was to evaluate the cerebral hemodynamics in this context. Five adult patients with moderate and severe traumatic brain injury (TBI) and ASH were included. All individuals were indicated for surgical evacuation. Before and after surgery, PCT was performed and cerebral blood flow (CBF), cerebral blood volume (CBV) and mean transit time (MTT) were evaluated. These parameters were associated with the outcome at 6 months post-trauma with the extended Glasgow Outcome Scale (GOSE). Mean age of population was 46 years (SD: 8.1). Mean post-resuscitation Glasgow coma scale (GCS) was 10 (SD: 3.4). Mean preoperative midline brain shift was 10.1 mm (SD: 1.8). Preoperative CBF and MTT were 23.9 ml/100 g/min (SD: 6.1) and 7.3 s (1.3) respectively. After surgery, CBF increase to 30.7 ml/100 g/min (SD: 5.1), and MTT decrease to 5.8s (SD:1.0), however, both changes don't achieve statistically significance (p = 0.06). Additionally, CBV increase after surgery, from 2.34 (SD: 0.67) to 2.63 ml/100 g (SD: 1.10), (p = 0.31). Spearman correlation test of postoperative and preoperative CBF ratio with outcome at 6 months was 0.94 (p = 0.054). One patient died with the highest preoperative MTT (9.97 s) and CBV (4.51 ml/100 g). CBF seems to increase after surgery, especially when evaluated together with the MTT values. It is suggested that the improvement in postoperative brain hemodynamics correlates to favorable outcome.

The intracranial compartmental syndrome: a proposed model for acute brain injury monitoring and management.

For decades, one of the main targets in the management of severe acute brain injury (ABI) has been intracranial hypertension (IH) control. However, the determination of IH has suffered variations in its thresholds over time without clear evidence for it. Meanwhile, progress in the understanding of intracranial content (brain, blood and cerebrospinal fluid) dynamics and recent development in monitoring techniques suggest that targeting intracranial compliance (ICC) could be a more reliable approach rather than guiding actions by predetermined intracranial pressure values. It is known that ICC impairment forecasts IH, as intracranial volume may rapidly increase inside the skull, a closed bony box with derisory expansibility. Therefore, an intracranial compartmental syndrome (ICCS) can occur with deleterious brain effects, precipitating a reduction in brain perfusion, thereby inducing brain ischemia. The present perspective review aims to discuss the ICCS concept and suggest an integrative model for the combination of modern invasive and noninvasive techniques for IH and ICC assessment. The theory and logic suggest that the combination of multiple ancillary methods may enhance ICC impairment prediction, pointing proactive actions and improving patient outcomes.

"THE MANTLE" bundle for minimizing cerebral hypoxia in severe traumatic brain injury.

To ensure neuronal survival after severe traumatic brain injury, oxygen supply is essential. Cerebral tissue oxygenation represents the balance between oxygen supply and consumption, largely reflecting the adequacy of cerebral perfusion. Multiple physiological parameters determine the oxygen delivered to the brain, including blood pressure, hemoglobin level, systemic oxygenation, microcirculation and many factors are involved in the delivery of oxygen to its final recipient, through the respiratory chain. Brain tissue hypoxia occurs when the supply of oxygen is not adequate or when for some reasons it cannot be used at the cellular level. The causes of hypoxia are variable and can be analyzed pathophysiologically following "the oxygen route." The current trend is precision medicine, individualized and therapeutically directed to the pathophysiology of specific brain damage; however, this requires the availability of multimodal monitoring. For this purpose, we developed the acronym "THE MANTLE," a bundle of therapeutical interventions, which covers and protects the brain, optimizing the components of the oxygen transport system from ambient air to the mitochondria.

Tracheostomy timing and outcome in critically ill patients with stroke: a meta-analysis and meta-regression.

BACKGROUND: Stroke patients requiring mechanical ventilation often have a poor prognosis. The optimal timing of tracheostomy and its impact on mortality in stroke patients remains uncertain. We performed a systematic review and meta-analysis of tracheostomy timing and its association with reported all-cause overall mortality. Secondary outcomes were the effect of tracheostomy timing on neurological outcome (modified Rankin Scale, mRS), hospital length of stay (LOS), and intensive care unit (ICU) LOS. METHODS: We searched 5 databases for entries related to acute stroke and tracheostomy from inception to 25 November 2022. We adhered to PRISMA guidance for reporting systematic reviews and meta-analyses. Selected studies included (1) ICU-admitted patients who had stroke (either acute ischaemic stroke, AIS or intracerebral haemorrhage, ICH) and received a tracheostomy (with known timing) during their stay and (2) > 20 tracheotomised. Studies primarily reporting sub-arachnoid haemorrhage (SAH) were excluded. Where this was not possible, adjusted meta-analysis and meta-regression with study-level moderators were performed. Tracheostomy timing was analysed continuously and categorically, where early (< 5 days from initiation of mechanical ventilation to tracheostomy) and late (> 10 days) timing was defined per the protocol of SETPOINT2, the largest and most recent randomised controlled trial on tracheostomy timing in stroke patients. RESULTS: Thirteen studies involving 17,346 patients (mean age = 59.8 years, female 44%) met the inclusion criteria. ICH, AIS, and SAH comprised 83%, 12%, and 5% of known strokes, respectively. The mean time to tracheostomy was 9.7 days. Overall reported all-cause mortality (adjusted for follow-up) was 15.7%. One in five patients had good neurological outcome (mRS 0-3; median follow-up duration was 180 days). Overall, patients were ventilated for approximately 12 days and had an ICU LOS of 16 days and a hospital LOS of 28 days. A meta-regression analysis using tracheostomy time as a continuous variable showed no statistically significant association between tracheostomy timing and mortality (ß = - 0.3, 95% CI = - 2.3 to 1.74, p = 0.8). Early tracheostomy conferred no mortality benefit when compared to late tracheostomy (7.8% vs. 16.4%, p = 0.7). Tracheostomy timing was not associated with secondary outcomes (good neurological outcome, ICU LOS and hospital LOS). CONCLUSIONS: In this meta-analysis of over 17,000 critically ill stroke patients, the timing of tracheostomy was not associated with mortality, neurological outcomes, or ICU/hospital LOS. TRIAL REGISTRATION: PROSPERO-CRD42022351732 registered on 17th of August 2022.

Intracranial Pressure Monitoring in Moderate Traumatic Brain Injury: A Systematic Review and Meta-Analysis.

BACKGROUND: The principal aim of this study was to determine the prevalence of intracranial pressure (ICP) monitoring and intracranial hypertension (IHT) in patients treated for moderate traumatic brain injury (TBI). A secondary objective was to assess factors associated with ICP monitoring. METHODS: We conducted a systematic review of the literature to identify studies that assessed ICP monitoring in moderate TBI. The meta-analysis was performed by using a random-effects model. RESULTS: A total of 13 studies comprising 116,714 patients were pooled to estimate the overall prevalence of ICP monitoring and IHT (one episode or more of ICP > 20 mm Hg) after moderate TBI. The prevalence rate for ICP monitoring was 18.3% (95% confidence interval 8.1-36.1%), whereas the proportion of IHT was 44% (95% confidence interval 33.8-54.7%). Three studies were pooled to estimate the prevalence of ICP monitoring according to Glasgow Coma Scale (GCS) (≤ 10 vs. > 10). ICP monitoring was performed in 32.2% of patients with GCS ≤ 10 versus 15.2% of patients with GCS > 10 (p = 0.59). Both subgroups were highly heterogeneous. We found no other variables associated with ICP monitoring or IHT. CONCLUSIONS: The prevalence of ICP monitoring in moderate TBI is low, but the prevalence of IHT is high among patients undergoing ICP monitoring. Current literature is limited in size and quality and does not identify factors associated with ICP monitoring or IHT. Further research is needed to guide the optimal use of ICP monitoring in moderate TBI.

Acute Intracranial Hypertension During Pregnancy: Special Considerations and Management Adjustments.

Pregnancy is associated with a number of pathophysiological changes (including modification of vascular resistance, increased vascular permeability, and coagulative disorders) that can lead to specific (eclampsia, preeclampsia) or not specific (intracranial hemorrhage) neurological complications. In addition to these disorders, pregnancy can affect numerous preexisting neurologic conditions, including epilepsy, brain tumors, and intracerebral bleeding from cerebral aneurysm or arteriovenous malformations. Intracranial complications related to pregnancy can expose patients to a high risk of intracranial hypertension (IHT). Unfortunately, at present, the therapeutic measures that are generally adopted for the control of elevated intracranial pressure (ICP) in the general population have not been examined in pregnant patients, and their efficacy and safety for the mother and the fetus is still unknown. In addition, no specific guidelines for the application of the staircase approach, including escalating treatments with increasing intensity of level, for the management of IHT exist for this population. Although some of basic measures can be considered safe even in pregnant patients (management of stable hemodynamic and respiratory function, optimization of systemic physiology), some other interventions, such as hyperventilation, osmotic therapy, hypothermia, barbiturates, and decompressive craniectomy, can lead to specific concerns for the safety of both mother and fetus. The aim of this review is to summarize the neurological pathophysiological changes occurring during pregnancy and explore the effects of the possible therapeutic interventions applied to the general population for the management of IHT during pregnancy, taking into consideration ethical and clinical concerns as well as the decision for the timing of treatment and delivery.

Ketamine in acute phase of severe traumatic brain injury "an old drug for new uses?"

Maintaining an adequate level of sedation and analgesia plays a key role in the management of traumatic brain injury (TBI). To date, it is unclear which drug or combination of drugs is most effective in achieving these goals. Ketamine is an agent with attractive pharmacological and pharmacokinetics characteristics. Current evidence shows that ketamine does not increase and may instead decrease intracranial pressure, and its safety profile makes it a reliable tool in the prehospital environment. In this point of view, we discuss different aspects of the use of ketamine in the acute phase of TBI, with its potential benefits and pitfalls.

Management of severe traumatic brain injury in regions with limited resources.

IMPORTANCE: Severe traumatic brain injury (sTBI) is a critical health problem in regions of limited resources (RLRs). Younger populations are among the most impacted. The objective of this review is to analyze recent consensus-based algorithms, protocols and guidelines proposed for the care of patients with TBI in RLRs. OBSERVATIONS: The principal mechanisms for sTBI in RLRs are road traffic injuries (RTIs) and violence. Limitations of care include suboptimal or non-existent pre-hospital care, overburdened emergency services, lack of trained human resources, and surgical and intensive care. Low-cost neuromonitoring systems are currently in testing, and formal neurotrauma registries are forming to evaluate both long-term outcomes and best practices at every level of care from hospital transport to the emergency department (ED), to the operating room and intensive care unit (ICU). CONCLUSIONS AND RELEVANCE: The burden of sTBI is highest in RLRs. As working-age adults are the predominantly affected age-group, an increase in disability-adjusted life years (DALYs) generates a loss of economic growth in regions where economic growth is needed most. Four multi-institutional collaborations between high-income countries (HICs) and LMICs have developed evidence and consensus-based documents focused on capacity building for sTBI care as a means of addressing this substantial burden of disease.

Impact of Cervical Collars on Intracranial Pressure Values in Traumatic Brain Injury: A Systematic Review and Meta-Analysis of Prospective Studies.

BACKGROUND: Spinal cord injury (SCI) is present in around 2-4% of trauma victims. More than half of this injuries are located at the cervical region. Twenty percent of victims with cervical spinal trauma and 5% of patients with severe traumatic brain injury (TBI) will have an SCI. Cervical immobilization with rigid or semirigid collars is routinely used as prophylactic or definitive treatment intervention in general trauma care. An important adverse effect of cervical collars application is the increase in intracranial pressure (ICP) values. This systematic review and meta-analysis aim to estimate the overall magnitude of ICP changes after cervical collar application. METHODS: Major electronic databases (Ovid/Medline, Embase and Cochrane Library) were systematically searched for prospective studies that assessed ICP changes after cervical collar applications. Study level characteristics and ICP values before, during and after cervical collar application, were extracted. The meta-analysis was performed using random-effects model. RESULTS: Five studies comprising 86 patients were included in the systematic review and the quantitative synthesis. The overall increase in ICP after collar application was statistically significant (weighted mean difference [WMD] = 4.43; 95%CI 1.70, 7.17; P < 0.01), meaning an overall ICP increase of approximately 4.4 mmHg. The decrease in ICP values after collar removal reached statistical significance (WMD = - 2.99; 95%CI - 5.45, - 0.52; P = 0.02), meaning an overall ICP decrease of approximately 3 mmHg after collar removal. ICP values before and after cervical collar application were not statistically significant (WMD = 0.49; 95%CI - 1.61, 2.59; P = 0.65), meaning no ICP change. CONCLUSIONS: Heterogeneous studies of application of cervical collars as a partial motion restriction strategy after injuries have demonstrated increases in ICP in TBI patients. Increases in ICP can induce complications in TBI patients. Appropriate selection criteria for cervical motion restriction in TBI patients need to be considered.

Intracranial Hypertension After Spontaneous Intracerebral Hemorrhage: A Systematic Review and Meta-analysis of Prevalence and Mortality Rate.

The objective of this study was to determine the prevalence of intracranial hypertension (IHT) and the associated mortality rate in patients who suffered from primary intracerebral hemorrhage (ICH). A secondary objective was to assess predisposing factors to IHT development. We conducted a systematic literature search of major electronic databases (MEDLINE, EMBASE, and Cochrane Library), for studies that assessed intracranial pressure (ICP) monitoring in patients with acute ICH. Study level and outcome measures were extracted. The meta-analysis was performed using a random-effects model. A total of six studies comprising 381 patients were pooled to estimate the overall prevalence of any episode of IHT (ICP > 20 mmHg) after ICH. The pooled prevalence rate for any episode of IHT after ICH was 67% (95% CI 51-84%). Four studies comprising 239 patients were pooled in order to estimate the overall mortality rate associated with IHT. Pooled mortality rate was 50% (95% CI 24-76%). For both outcomes, heterogeneity was statistically significant, and risk of bias was nonsignificant. Reported variables correlated significantly with increased ICP were lower Glasgow Coma Scale score at admission, midline shift, hemorrhage volume, and hydrocephalus. The prevalence and mortality rates associated with IHT after ICH are high and may be underestimated. Predicting factors for the development of IHT reflect the magnitude of the primary injury. However, the results of present meta-analysis should be interpreted with caution due to methodological limitations such as selection bias of patients who had ICP monitoring, and lack of standardized IHT definition.

Cerebral Fat Embolism: Recognition, Complications, and Prognosis.

Fat embolism syndrome (FES) is a rare syndrome caused by embolization of fat particles into multiple organs including the brain. It typically manifests with petechial rash, deteriorating mental status, and progressive respiratory insufficiency, usually occurring within 24-48 h of trauma with long-bone fractures or an orthopedic surgery. The diagnosis of FES is based on clinical and imaging findings, but requires exclusion of alternative diagnoses. Although there is no specific treatment for FES, prompt recognition is important because it can avoid unnecessary interventions and clarify prognosis. Patients with severe FES can become critically ill, but even comatose patients with respiratory failure may recover favorably. Prophylactic measures, such as early stabilization of fractures and certain intraoperative techniques, may help decrease the incidence and severity of FES.