The recommendations contained in this document are intended as guidance to clinicians managing patients admitted to the ICU with ABI. These recommendations were generated via a rigorous methodology that included a comprehensive systematic review and grading of available evidence, the engagement of a multidisciplinary, international expert panel, and the iterative refinement of consensus statements using the modified Delphi method. The principal limitation encountered was the paucity or lack of robust scientific evidence on many of the clinical questions posed, which means that several of the recommendations are based on the collective expert opinions of the panel [14,15,16,17,18,19]. As a corollary of this limitation, several knowledge gaps were identified, which have helped to establish an agenda for research (Table 2).
The decision to intubate a patient with isolated ABI in the absence of intrinsic respiratory failure is very common in emergency and intensive care medicine, yet scientific evidence is lacking to support specific approaches. Intubation is lifesaving in severe ABI patients and not beneficial in milder forms of ABI, yet the role of intubation in intermediate severity ABI remains unclear . Intubation commits patients to a course of mechanical ventilation and sedation, which significantly curtails the ability to clinically assess neurological function at the bedside. Studies are needed to explore strategies (including timing) regarding endotracheal intubation in the ABI population. These studies should be stratified according to ABI etiology (TBI, SAH, ICH, AIS) and consider the relative importance of clinical factors such as neurological severity (e.g., GCS), presence of airway protective reflexes, agitation or combativeness, ICP elevation, predicted clinical trajectory (e.g., likelihood and time-course of neurological worsening, the need for surgery or interventional management), and non-neurological injury or organ failure.
Invasive ventilation is used in patients with severe ABI to counter dysregulated breathing patterns and to maintain PaO2 and PaCO2 within physiological ranges . This enables effective and reliable oxygen delivery to the brain and provides a mechanism to indirectly control cerebral perfusion via adjustment of minute ventilation and PaCO2. Yet, these principles, well-established in neurointensive care, seem at variance with lung protective strategies which aim to reduce ventilator-induced lung injury (VILI) via settings in which relative hypercapnia and hypoxemia may be permitted. Lung protective ventilation has been associated with significantly higher survival in clinical trials of patients with ARDS [20,21,22,23,24] and with improved outcomes in mechanically ventilated ICU and surgical populations who do not have ARDS [25, 26]. Although patients with ABI have consistently been excluded from these trials, the Consensus recommended that patients with ABI who do not have ICP elevation should receive lung protective ventilation and PEEP as other mechanically ventilated patients would. Clinical trials are needed to determine the safety and efficacy of different lung protective ventilation strategies in ABI patients, both with and without ARDS. These trials should be stratified by ABI etiology and neurological severity and consider a range of different endpoints both proximal (neurophysiological impact, biomarkers of VILI) and more distal (mortality, neurological outcome, duration of mechanical ventilation and stay in the hospital).
Regarding arterial blood gases, the consensus recommended avoidance of hyperoxia and hypoxia, both associated with poor outcome after ABI. The panel recommended maintaining PaO2 80–120 mmHg, higher compared to the range commonly targeted in the general ICU population (55–80 mmHg). Overall, research is warranted to identify optimal PaO2 targets in this population. One approach will be to leverage large-scale multi-site observational studies using multivariable modeling, to precisely determine associations between specific PaO2 thresholds or target ranges and clinically significant outcomes in stratified ABI populations.
The panel recommended normocapnia in ABI patients without ICP elevation. It also recommended short-term hyperventilation in patients with cerebral herniation. However, there was a lack of agreement on the use of short-term mild hyperventilation (PaCO2 target 30–35 mmHg) to treat elevations in ICP. Although it is part of the staircase approach for the management of ICP, hyperventilation causes cerebral vasoconstriction and has been associated with poor outcome in the Lung Safe cohort , perhaps due to an increase in mechanical power . While early studies have explored this issue , contemporary trials are needed to investigate the effect of short courses of hyperventilation, in conjunction with other measures, on physiological endpoints and clinical outcomes in patients who have intracranial hypertension.
Little is known about how ventilator liberation should be accomplished in the setting of ABI . Available evidence and clinical experience suggest that decisions on ventilator weaning and tracheal extubation must integrate neurological features with other systemic variables, and this is the approach recommended by the panel. Mechanical ventilation may be prolonged unnecessarily, or tracheostomy performed prematurely, in a subset of patients who could have been successfully extubated. Studies are needed to investigate more precise approaches for ventilator weaning and extubation in the target population. Multivariable models should be tested and validated to individualize management based on patient-specific clinical and physiological features. Clinical trials should evaluate the effectiveness and efficacy of different liberation strategies. These trials could be designed to integrate tracheostomy either as a treatment arm or as an outcome variable.
Timely tracheotomy represents a means of effectively weaning sedation and discontinuing mechanical ventilation in patients who require an artificial airway but are otherwise able to breathe independently. Yet studies indicate that the selection of ABI patients for tracheostomy is highly variable, often dependent on regional or institutional factors [31, 32]. Our panel recommended consideration of this procedure in mechanically ventilated ABI patients who are persistently unconscious (but with an expected acceptable quality of life) or when one or several trials of extubation have failed; however, there was no consensus on the optimal timing of tracheostomy. Carefully designed studies would be needed to validate tracheostomy decision algorithms for patients with ABI, and to determine the optimal timing of this procedure based on patient-specific factors. Trials should consider stratification by ABI etiology, severity and predicted natural history.
The management of patients with concurrent ABI and acute respiratory failure is a specific scenario which merits further discussion. In the general ICU population, there is extensive evidence supporting non-invasive strategies, such as BiPAP and high-flow nasal canula oxygen, for patients who have acute respiratory failure and an underlying cause that can be effectively treated in a relatively short time frame . Randomized trials in carefully selected respiratory failure patients show that when compared to invasive ventilation, non-invasive techniques can significantly improve outcomes including survival . Importantly, preserved consciousness and airway protective reflexes are generally viewed as prerequisites for the successful use of these methods. The consensus panel found very limited evidence on the use of non-invasive respiratory support in patients who have acute respiratory failure in the setting of ABI; however, it did recommend consideration of high-flow oxygen therapy in selected patients with hypoxemia. These results are likely a reflection of clinical observations among members of the panel that high-flow nasal cannula oxygen therapy might be beneficial and is associated with a low risk of adverse effects. Studies are needed to determine the indications, safety, and efficacy of non-invasive strategies in selected ABI patients.
One additional clinical scenario which needs special consideration is that of patients who have ARDS in the setting of neurological injury. It has been reported that up to one-third of mechanically ventilated patients with ABI can develop ARDS . Several interventions have been validated as effective rescue therapies to increase survivability in patients with ARDS refractory hypoxemia [5, 22]. These interventions, which include alveolar recruitment maneuvers, prone positioning, neuromuscular blocking agents, and ECMO, are increasingly used as part of a stepwise algorithm for patients in the severe ARDS stratum; however, their feasibility and safety in ABI patients with ARDS are undetermined. A significant subset of ABI patients have concurrent spinal injuries and prone positioning might be unsafe in this group. ECMO generally requires systemic anticoagulation which could have catastrophic consequences in patients with recent ABI [35, 36]. The consensus panel recommended consideration of prone positioning and neuromuscular blocking drug infusions, but it was unable to provide a recommendation on the use of alveolar recruitment or ECMO. Studies are needed to guide clinicians in selecting patients with concurrent ABI and ARDS who are most likely to benefit, and least likely to be harmed, by these therapies.
In summary, this consensus statement proposes guidance for clinicians on mechanical ventilation and respiratory support in critically ill ABI patients. As with all guidelines, the recommendations provided here must be implemented in a treatment plan that is individualized and considers not only physiological parameters but also patient co-morbidities and clinical trajectory. The panel found deficiencies in the scientific evidence across the domains studied, underscoring an urgent need for innovative and high-quality research to improve the care and outcomes in this population. Well-designed randomized controlled trials are needed to explore the role of different ventilator strategies and physiologic targets in this specific population. A promising direction is the possibility of personalizing therapy based on patient-specific clinical and physiological features, for example, data from multimodal neuromonitoring techniques.