Frisvold 

et al. Critical Care (2023) 27:247 Critical Care

https://doi.org/10.1186/s13054-023-04532-4

REVIEW Open Access

Respiratory challenges and ventilatory

management in different types of acute
brain‑injured patients
S. Frisvold1,2, S. Coppola3,4,5, S. Ehrmann6,7, D. Chiumello3,4,5 and Claude Guérin8* 

Abstract 
Acute brain injury (ABI) covers various clinical entities that may require invasive mechanical ventilation (MV) in the
intensive care unit (ICU). The goal of MV, which is to protect the lung and the brain from further injury, may be difficult
to achieve in the most severe forms of lung or brain injury. This narrative review aims to address the respiratory issues
and ventilator management, specific to ABI patients in the ICU.
Keywords  Acute brain injury, Mechanical ventilation, Lung protective ventilation, Cerebral autoregulation,
Neurogenic pulmonary edema, Acute respiratory distress syndrome

Introduction often able to breathe spontaneously [1–3]. Better under-

In patients with acute brain injury (ABI) the delivery of standing the complex relationship between brain and res-
mechanical ventilation (MV) in the intensive care unit piration/ventilation and providing judicious respiratory
(ICU) involves adequate timing for intubation, lung pro- support are critical issues.
tective ventilation (LPV), brain protection, and weaning.
Unlike non-neurocritical patients, ABI patients usually Respiratory challenges in patients with ABI
have no primary respiratory indication for ventilator sup- Severe ABI refers to a sudden event that results in brain
port, but often require prolonged MV, although they are damage and reduced perfusion leading to reduced alert-
ness. ABI is heterogeneous and covers different sub-
types, notably traumatic brain injury (TBI), subarachnoid
*Correspondence: hemorrhage (SAH), intracranial bleeding and hypoxic
Claude Guérin ischemic brain injury. Since the brain is surrounded by
[email protected]
1
Department of Anesthesia and Intensive Care, University Hospital the inextensible skull, any change affecting brain volume
of North Norway, Tromso, Norway would result in an increase in intracranial pressure (ICP)
2
Department of Clinical Medicine, UiT the Arctic University of Norway, and impairment of cerebral blood flow upon depletion of
Tromso, Norway
3
Department of Anesthesia and Intensive Care, ASST Santi Paolo e Carlo, the compensatory reserve. Therefore, perfusion is tightly
San Paolo University Hospital, Milan, Italy regulated by cerebral autoregulation (CA) to preserve
4
Department of Health Sciences, University of Milan, Milan, Italy cerebral blood flow facing variations in systemic pressure
5
Coordinated Research Center On Respiratory Failure, University of Milan,
Milan, Italy and metabolism. CA is a potent modulator of cerebral
6
CHRU Tours, Médecine Intensive Réanimation, CIC INSERM 1415, CRICS- vasoreactivity [4].  Changes in P ­ aCO2 alters CA:  both
TriggerSep F-CRIN Research Network, Tours, France hypo and hypercapnia can induce cerebral ischemia from
7
INSERM, Centre d’étude Des Pathologies Respiratoires, U1100, Université
de Tours, Tours, France the reduction of perfusion through vasoconstriction or
8
Faculté de Médecine Lyon Est, Université Claude Bernard Lyon 1, 8 vasodilatation, respectively, the latter also promoting
Avenue Rockefeller, 69008 Lyon, France higher ICP.

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Frisvold et al. Critical Care (2023) 27:247 Page 2 of 11

Respiratory dysfunction is common in ABI and can Acute lung injury

result from either dysregulation of the breathing patterns Apart from a damaged or dysregulated respiratory center,
or acute lung injury. ABI is commonly associated with acute lung injury, such
as neurogenic pulmonary edema (NPE), lung inflamma-
Dysregulated respiratory centers function tion, acute respiratory distress syndrome (ARDS), aspira-
The brainstem contains the respiratory centers responsi- tion pneumonia, ventilator-associated pneumonia (VAP)
ble for regulating breathing. In ABI, the respiratory cent- and lung contusion [10–12].
ers can be dysregulated either through direct damage to The most common ABIs associated with NPE are SAH,
the brainstem or indirectly through an increase in ICP aneurysm rupture and TBI. NPE is typically character-
and mass effects due to cerebral hemorrhage or edema. ized by the presence of respiratory distress, hypoxemia
Damage to the respiratory center leads to impaired res- and bilateral alveolar opacities with diffuse infiltrates
piratory drive [5]. in both lungs in the absence of any other cause of res-
They regulate the respiratory response to stabilize C
­ O2, piratory failure [13, 14]. Thus, NPE is like the most
e.g., after an increase in ­PaCO2 and low pH in the cere- severe form of acute hypoxemic respiratory failure,  e.g.
brospinal fluid or brain tissue [6]. The peripheral chemo- the ARDS, but with a different pathophysiology (Fig. 1).
receptors located in the carotid body and the lungs affect Typically, in the presence of increased ICP, a massive
drive by modifying the sensitivity and threshold of cen- neural sympathetic discharge from anatomical regions
tral chemoreceptors, providing faster and more intense such as the hypothalamus, the basal portion of the pre-
response to changes in hypoxemia, P ­ aCO2 and pH [7]. optic nucleus and periventricular system can occur [15].
In addition, the lung mechanoreceptors are stretch This central sympathetic discharge likely induces pul-
receptors activated by lung inflation and inhibit central monary and systemic vasoconstriction or impairment in
chemoreceptors that terminate inspiration during the vascular permeability, promoting pulmonary edema [16].
Hering–Breuer inhibitory reflex [8]. The respiratory drive In addition to the catecholamines storm that leads to
pathway can be compromised not only because of respir- NPE, a massive release of cytokines from the injured
atory biochemical input (respiratory acidosis or hypox- brain can contribute to cytokine-induced inflammation
emia) and/or a mechanical input such as atelectasis, but leading to ARDS [17–19]. The mechanisms of neuro-
also from the primary brain injury [9]. immunomodulation and ARDS have been recently
reviewed [20]. Lung contusion due to multiple trauma

Fig. 1  Pathways of acute lung injury directly related to acute brain injury. High intracranial pressure (ICP) can promote two different sequences of
events that end up into neurogenic pulmonary edema or acute respiratory distress syndrome (ARDS). Both of them may coexist in a given patient.
SVR: systemic vascular resistance, PVR: pulmonary vascular resistance, LV: left ventricle, DAMP: damage-associated molecules pattern
 Frisvold et al. Critical Care (2023) 27:247 Page 3 of 11

that TBI patients frequently experience represents an upper safety P­ aO2 target in all-comer critically ill patients
additional risk factor for ARDS [21]. [34]. Cerebral oxygen supply by the use of microdialysis
The reduced consciousness also makes the ABI patients or brain tissue oxygen monitoring may serve as a marker
more susceptible for aspiration pneumonia, impaired for impending cerebral hypoxia [35]. Oxygen targeted
mucus clearance and VAP than ICU patients without ABI by continuous monitoring of brain tissue oxygen will be
[19, 22, 23]. In a recent large European cohort of about addressed in an ongoing study [36]. To conclude, the role
thousand patients with TBI, one out of five developed of excessive hyperoxemia is uncertain and avoiding it
VAP after a median interval of 5 days (interquartile range seems to be a reasonable strategy.
3–7 days, indicating that 75% of episodes occurred in the Hypocapnia is used to control acute bursts of high
first week of MV) [24]. Systematic performance of bron- ICP. Recently, a retrospective analysis found that mild
choalveolar lavage within 24 h after intubation of trauma hypocapnia (30–34 mmHg) might be associated to better
patients showed that 80% of samples grew some micro- cerebrovascular reactivity and did not worsen cerebral
organisms and 30% are suspect of early pneumonia [22]. energy metabolism [37]. Guidelines suggest that ­PaCO2
In summary, ABI can affect the respiratory system should be maintained in the normal or low normal ref-
through different mechanisms and may interfere with erence range when ICP is high [3, 38]. The increased
evaluation of cerebral recovery and further delay the cerebral blood flow that follows hypercapnia might have
initiation of the weaning process. The respiratory sup- a role in delayed cerebral ischemia (DCI), if ICP is con-
port should simultaneously  accomodate  the inter- trolled with external ventricular drainage [39]. Since
play between ICP, P ­ aCO2 and cerebral perfusion, and patients with ABI are a heterogeneous group, future
deliver the lung protective ventilation, e.g. protecting the studies should identify those patients who may benefit
brain and the lung simultaneoulsy, which are potential from higher P­ aCO2 targets.
contradictory goals. While invasive MV represents the standard manage-
ment strategy to achieve above mentioned physiological
Ventilatory management of patients with ABI goals for ABI patients, non-invasive methods could be an
Figure 2 summarizes the brain–lung interactions during option in some circumstances.
mechanical ventilation, the role of ­PaCO2 and the CA.
High‑flow oxygen and non‑invasive ventilation
Oxygen and carbon dioxide targets There is limited evidence for use of high-flow oxygen
The safety range of oxygenation targets in ABI patients is and non-invasive ventilation (NIV) in ABI patients, at
uncertain. Traditionally, the goal of oxygen supplemen- variance of  acute hypoxemic respiratory failure in other
tation in patients with ABI has been to avoid hypoxia patient populations [40, 41]. Coma is a contraindication
[25]. Recent research supports the need to consider for NIV unless it is due to acute hypercapnia in patients
an upper limit of oxygen supplementation [26, 27]. The with chronic obstructive pulmonary disease [42]. Skull
CENTER-TBI, which is a large European, multicenter base fracture is a relative contradiction for use of high
observational study, showed that the median highest flow and NIV. Chest trauma might also complicate
arterial oxygen partial pressure (­PaO2) level during the the use of  NIV although some studies showed it feasi-
first week after ICU admission was 134 mmHg [26]. The ble in case of isolated chest trauma [43]. To our knowl-
maximal and mean P ­ aO2 were independently associated edge, there are no published RCTs on the use of NIV in
with an unfavorable functional neurologic outcome or patients with TBI. Clinicians need to consider the indi-
death at 6 months. However, a cut-off for upper limit of vidual patient´s clinical status and coexisting respiratory
­PaO2 related to worse outcome was not defined [2]. By abnormalities when making decisions about the use of
contrast, no difference in outcome based on P ­ aO2 lev- NIV. However, most often, ABI compromises the air-
els ranging from 60 to > 300  mmHg was found by oth- way, warranting early intubation, sometimes after a brief
ers [28, 29]. A post hoc analysis of a randomized trial, attempt of NIV.
identified ­PaO2 thresholds of 150 and 200  mmHg asso-
ciated with better functional neurological outcome [30]. Invasive mechanical ventilation
This is supported by a meta-analysis of observational Indications for endotracheal intubation are to provide
studies on adult ABI patients where hyperoxemia ­(PaO2 airway protection, treat hypoxemia and inadequate ven-
cut-off point > 200  mmHg) was associated with poor tilation, management of brain edema with tight P ­ aCO2
neurological outcome [31]. Among randomized clinical targets and reduction of cerebral metabolism.
trials (RCTs) performed in the ICU setting, the adverse Table  1 provides an overview of the ventilation man-
effects of hyperoxemia has not been confirmed [32, 33]. agement, fluid strategies, and indication for steroid use
Recent meta-analysis of RCTs did not support to set an
Frisvold et al. Critical Care (2023) 27:247 Page 4 of 11

Fig. 2  Schematic representation of the lung–brain interactions. During positive pressure mechanical ventilation, cerebral blood flow (CBF) can be
reduced from different sources. The transmission of airway pressure to the cardiovascular structures depends on the pleural pressure and thus on
the transpulmonary pressure ­(PL) and lung compliance. With normal lung compliance, the higher the airway pressure, the higher the right atrial
pressure, which can lead to a reduction in venous return (orange flash). Increase in abdominal pressure counteracts this effect in normal conditions.
Increased tidal volume increases pulmonary venous pressure (Pv). These changes result in lower right ventricular ejection volume, and thus, cardiac
output (CO) will decrease. CO reduction is limited by the fact that the increased intrathoracic pressure will decrease the left ventricle afterload.
Despite changes in CO and arterial pressure, cerebral autoregulation maintains CBF and intracranial pressure (ICP) within a certain range of arterial
pressure. However, ICP is highly dependent on venous outflow from the cranial cavity. Positive pressure ventilation with increased right atrial
pressure can reduce venous outflow from the cranial cavity and thereby increase ICP. In patients with impaired pulmonary compliance (i.e., severe
acute respiratory distress syndrome), the effects of positive pressure mechanical ventilation on alveolar pressure (PA) and P ­ L are often attenuated.
Hypoxemia (low ­PaO2) and hypercapnia (high ­PaCO2) both increase pulmonary artery pressure (Pa) and pulmonary vascular resistance, thereby
increasing right ventricular afterload. Alterations in ­PaCO2, ­PaO2 and hydrogen ion also trigger chemoreceptors (yellow circles) to send signals to
the respiratory center to regulate respiratory drive. At the level of cerebral circulation, hypercapnia increases CBF and hypocapnia has the opposite
effect. The interaction between low brain compliance, cerebral autoregulation and different levels of C ­ O2 has not been studied. Ao aorta, ­PaCO2
partial pressure of carbon dioxide, ­PaO2 partial pressure of oxygen, Ca carotid artery, cardiac output (CO), CBF cerebral blood flow, CPP cerebral
perfusion pressure, CVR cerebral vascular resistance, ICP intracranial pressure, IVC inferior vena cava, MAP mean arterial pressure, Pa pulmonary
artery pressure, PA alveolar pressure, Pv pulmonary venous pressure, ­PaO2 partial pressure of oxygen, ­PL transpulmonary pressure, SVC superior vena
cava
 Frisvold et al. Critical Care

Table 1  Respiratory management of intubated ABI patients with and without intracranial hypertension and/or ARDS
Respiratory management Normal lung Normal lung ARDS ARDS
(references) Normal ICP High ICP Normal ICP High ICP
(2023) 27:247

VT [44–46] 7–9 ml/kg PBW 7–9 ml/kg PBW 6–8 ml/kg PBW 6–8 ml/kg PBW

PEEP [47, 47–50] 5 ­cmH2O 5 ­cmH2O. If higher PEEP, surveil- At least 5 ­cmH2O, higher PEEP in At least 5 ­cmH2O, higher PEEP in more
lance of ICP/CPP/multimodal brain more severe ARDS, titration based on severe ARDS, titration based on plateau
monitoring plateau pressure, driving pressure, pressure, driving pressure, oxygenation
oxygenation and hemodynamic and hemodynamic response to higher
response to higher PEEP PEEP
ICP/CPP/multimodal brain monitoring
PaO2 target (mmHg) [25, 26, 51] Avoid hyperoxemia ­(PaO2 > 200) PaO2 80–200 PaO2 80–120, depending of ARDS PaO2 80–200
severity
PaCO2 target (mmHg) [38] PaCO2 35–45 PaCO2 32–38 Permissive hypercapnia (< 60), Permissive hypercapnia contraindi-
depending on pH (> 7, 25) cated. Adjunctive therapy earlier
ICP/CPP/multimodal brain monitoring
Prone position [52] Not recommended Not recommended PaO2/FIO2 < 150 mmHg with PEEP ≥ 5 PaO2/FIO2 < 150 mmHg
­cmH2O Case-by-case basis
ICP/CPP/multimodal brain monitoring
Lung recruitment [53] Systematic use, not recommended Systematic use, not recommended Systematic use, not recommended Systematic use, not recommended
Fluid restriction strategy [54, 55] Not recommended unless specific Avoid positive fluid balance and tar- Yes Avoid positive fluid balance and target
indication get euvolemia for CPP management euvolemia for CPP management
Avoid hypotonic fluids Avoid hypotonic fluids
ICP/CPP/multimodal brain monitoring
Steroids [56, 57] No indication except for specific Higher mortality in TBI with high dose Dexamethasone may be indicated If TBI severity is the main problem
indication of methylprednisolone steroids may be avoided. Steroids may
be beneficial if ARDS is the dominant
problem
Page 5 of 11
Frisvold et al. Critical Care (2023) 27:247 Page 6 of 11

in patients with ABI with and without high ICP and/or contradictory results about the response related to
ARDS based on the studies included in this review. brain and lung compliance [66–68]. Measurement of
transpulmonary pressure could not clarify which ABI
Specific types of ABI patients and ventilatory management patients had adverse effect on high PEEP [44]. PEEP
The management of ABI in the acute phase is mainly adjustment is therefore recommended only during
driven by the goal to ensure adequate cerebral perfusion, rigorous ICP monitoring and curve analysis if brain
by cerebral perfusion pressure or ICP-oriented targets compliance is suspected to be low [44]. The role of res-
[38, 58]. piratory mechanics variables other than PEEP and VT
The different forms of severe ABI have disease-specific has been explored in recent observational studies. A
characteristics that can influence ventilation manage- sub-analysis of the Target Temperature Management-2
ment. Patients with severe TBI are most treated with ICP trial found that respiratory rate, driving pressure, and
monitoring, which serves as a guide to ICU management mechanical power were independently associated with
[38, 59]. Strict low-range P­ aCO2 and PEEP targets are 6-month mortality in post-cardiac arrest survivors [69].
used for ICP control. Recently, CA as part of ICP man- Mechanical power  (MP) might also be associated with
agement and the interaction of PEEP and LPV with CA mortality in patients with ABI from other causes [70,
has been evaluated [44, 47]. 71]. A recent observational study found that the  MP
ICU management of patients with SAH targets pre- during the first week of MV was associated with poor
vention of rebleeding, intraventricular hemorrhage, outcome independently on oxygenation [71]. MP might
and later-stage DCI [60]. In contrast to  TBI, general- also be related to PEEP-induced high ICP [44].
ized contusion and cytotoxic edema are not the primary
pathophysiological problem. Since these patients com-
monly have external ventricular drainage, strict P ­ aCO2 Ventilatory management of ABI patients with concurrent
targets for ICP monitoring are not required as often as ARDS
in patients with TBI. In the DCI phase, microdialysis or As detailed earlier in the ventilator management of
brain tissue oxygen is sometimes used to detect local patients with ABI some conflicting physiological goals
cerebral hypoxia and set ­PaO2 targets [61, 62]. An assess- may arise when aiming at protecting both the lung
ment of neurological function and reduced sedation is and the brain [72]. Typical, permissive hypercapnia
required to diagnose DCI. Spontaneous ventilation with as part of LPV may have cerebral side effects leading
the following broader ­ PaCO2 target is therefore used to a complex if not impossible evaluation of the ben-
more liberally than in TBI patients. efit-risk ratio. While in patients without lung injury
Most patients with severe intracerebral hemorrhage the value of strict LPV remains debated and cerebral
have systemic  hypertension. Lowering blood pressure, physiology may predominantly drive patient manage-
rather than measures to lower ICP, has been the focus of ment, the situation is more complex in case of estab-
general management in the ICU [63]. Treatment in the lished ARDS [11, 73]. Permissive hypercapnia might
stroke unit is associated with a better outcome, but this be feasible if ICP is controlled with external ventricu-
does not necessarily improve when the patient is admit- lar drainage. Another option is to increase respiratory
ted to the ICU [64]. The indication for the use of ICP rate up to the limit of Auto-PEEP or plateau pressure.
monitoring and targets is unclear and is often derived Since respiratory rate contributes to  MP, compensat-
from the TBI literature. ing for low VT by increasing respiratory rate might not
be the solution for regulating P­ aCO2 in ABI. RCTs are
Ventilatory settings for ABI patients with no lung injury required to assess the interplay between inflammatory
In non-ARDS patients, no difference in patient out- and mechanical stress of the lungs in this population,
come was found in two large multicenter RCTs as well as potential interventions and their impact on
between low (6 ml/kg predicted body weight) vs. inter- long-term outcomes on both cerebral and pulmonary
mediate (10  ml/kg) tidal volume (VT) [45] and low (5 recovery (weaning of MV).
­cmH2O) vs. high (8 ­cmH2O) PEEP [48]. As these trials Prone position in patients with moderate to severe
were not dedicated to ABI patients, a small propor- ARDS is a cornerstone treatment that might be con-
tion of the patients had ABI. Limiting VT with con- sidered in patients with co-existing ABI. Since prone
comitant permissive hypercapnia is difficult to carry position might affect ­PaCO2 and venous return from
out with a simultaneous ICP control. Dead space the brain, ICP monitoring is strongly advised in acute,
reduction by replacing heat-moisture exchangers with severe ABI [3, 74]. High ICP was a non-inclusion crite-
heated-humidifiers is feasible and can set low VT rion in Proseva trial [52]. The role of alveolar recruit-
without increasing P
­ aCO2 [65]. High PEEP has shown ment maneuvers to improve oxygenation in ARDS is
 Frisvold et al. Critical Care (2023) 27:247 Page 7 of 11

uncertain [53]. In patients with acute, severe ABI, the as compared to the liberal fluid strategy, was similar in
role of the recruitment maneuver with cardiopulmo- terms of patient mortality but was associated with less
nary interaction, should lead to caution when using this days spent under invasive MV [54]. In ABI patients, in
maneuver. addition to careful adjustment of the ventilator pres-
Asynchronies between patient to ventilator  might be sures, ensuring that patients are euvolemic might protect
the clinical consequences of the alterations in the respira- against the adverse effects of higher ventilator pressures
tory drive or prolonged MV. and fluctuations in P­ aCO2. Fluid management must con-
During assisted mechanical ventilation, the critical sider administrating fluids vs the risk of cerebral edema
determinant of respiratory drive and work of breathing due to disruption of the blood brain barrier and cell
is the set peak flow. An insufficient peak flow is associ- damage.
ated with higher drive and work of breathing. Low peak In ABI patients with or without ARDS, the restrictive
flow leads to air hunger and excessive peak flow leads to fluid strategy is therefore recommended to prevent any
excessively short inspiratory time associated with asyn- further brain edema. However, it is important to take
chrony and breath stacking. Highest peak flows increase care to avoid hypovolemia in order to achieve the  cere-
respiratory rates because of shortened inspiratory time. bral perfusion pressure goal [55, 75].
In fact, a shorter inspiratory time decreases the negative Steroids. In patients with ARDS, steroids may play a
feedback derived from lung inflation, resulting in a higher beneficial role in the acute phase [56]. In TBI, the MRC-
ventilatory frequency. Physiologically, high volume or CRASH trial found that mortality was higher with meth-
lung inflation reduces the respiratory drive and the peak ylprednisolone than with placebo; therefore, steroid use
flow becomes less relevant. Flow dyssynchrony is typical is not recommended [57]. In general, steroid use is not
in situations of high drive or of activation of respiratory recommended in any form of ABI patients with acute
muscles after time-initiated ventilator cycles during con- cerebral swelling due to a lack of evidence [76].
trolled MV called “respiratory entrainment” secondary
to a sustained activation of the Hering–Breuer reflex and Weaning
C3, C5 spinal reflex leading to reverse triggering [77]. Luo Prolonged MV may further delay rehabilitation and ICU
et  al. investigated the patient–ventilator asynchrony in discharge, increasing the risk of long-term sequelae and
mechanically ventilated brain-injured patients and found complications with physical, psychological and psychi-
that the prevalence of asynchrony was 38% higher than in atric as well as cognitive symptoms as part of the post-
patients without brain injury [78], while the most preva- intensive care syndrome which does also affect patients’
lent type of asynchrony was ineffective triggering, char- relatives [80]. Also, in patients with ABI, there has been
acterized by a lower drive in terms of P0.1 values. The increased focus on weaning practices and early rehabili-
asynchrony index was similar after stroke, craniotomy for tation [81, 82].
brain tumor or TBI, and significantly lower during pres- Uncertainty persists about the best approach to suc-
sure control/assisted ventilation than during other venti- cessful weaning of ABI patients and involves sedation
lation modes and higher during combined use of opioids practices, weaning criteria, and timing for tracheotomy.
and sedatives. Similarly, to non-neurological patients, Traditionally, critically ill patients have been treated with
asynchrony is a sign of uncoupling between the neuronal deep sedation and immobilization, which prolong time
input and muscular efficiency and is associated with pro- to extubation [83]. This practice is in particularly com-
longed MV [78]. Recently, in patients with ABI, patient- mon in patients with ABI, where deep sedation has been
ventilator asynchrony was monitored with esophageal used to reduce cerebral metabolism, prevent intracranial
pressure monitoring [78]. It was demonstrated that asyn- hypertension and for fever control. Recently, ABCDEF
chrony, in particular ineffective trigging is common and bundle (Assess, prevent, and manage pain; Both sponta-
associated with combination of analgesia and sedation neous awakening and breathing trials: Choice of Analge-
strategy. The prevalence of ventilator-induced diaphragm sia and Sedation; Delirium assess, prevent, and manage;
dysfunction in brain-injured patients is likely to play an Early Mobility and Exercise; Family engagement/ empow-
important role but remains to be investigated [79]. erment) received acknowledgement within intensive care
medicine [84]. Among ABI patients, data are lacking to
Additional management precisely decipher the relative contributions of sequelae
Two additional strategies relevant for the ventilatory of the initial cerebral insult and intensive care acquired
management will be briefly discussed in this part: fluid long-term neurological, muscular and cognitive symp-
balance and steroids. toms. Patients with ABI have higher extubation failure
Fluid management in ABI. The FACCT trial in ARDS than patients without [85, 86].
patients (with no ABI) found that a restrictive strategy,
Frisvold et al. Critical Care (2023) 27:247 Page 8 of 11

Several factors may contribute to extend the dura- combination of neuro- and respiratory monitoring and
tion of MV, some are non-modifiable such as the brain large multicenter trials in ABI patients advances our
injury itself, recovery of consciousness being one key knowledge in terms of optimized treatment and out-
factor for weaning readiness; others, like  management- comes. The future will offer the opportunity to combine
related factors may be modified such as deep and pro- physiological studies and the use of big data analysis to
longed sedation and screening practice for weaning identify predictors and optimize ventilation strategies for
readiness [87, 88]. Once extubated, patients with ABI are patients with severe ABI.
at high risk of re-intubation, mainly because of respira-
tory and airway failure due to dysphagia, lack of muscle
Abbreviations
strength and poor cough. In a large international obser- ABI Acute brain injury
vational study, that evaluated 1512 patients with ABI who ARDS Acute respiratory distress syndrome
were ventilated more than 24  h with an initial Glasgow CA Cerebral autoregulation
DCI Delayed cerebral ischemia
coma scale (GCS) ≤ 12, 19% of patients were reintubated GCS Glasgow coma scale
within 5  days of extubation. Authors identified predic- ICP Intracranial pressure
tors of extubation failure at day 5 which were combined ICU Intensive care unit
LPV Lung protective ventilation
in a score which may be easy to use at the bedside and MP Mechanical power
comprising the following variables associated with extu- MV Mechanical ventilation
bation success: TBI, vigorous cough, gag reflex, swallow- NPE Neurogenic pulmonary edema
NIV Non-invasive ventilation
ing attempts, endotracheal suctioning less than twice per PaCO2 Arterial carbon dioxide partial pressure
hour, GCS motor component at 6, body temperature nor- PaO2 Arterial oxygen partial pressure
mal or low. The score area under the receiver operating PEEP Positive end-expiratory pressure
RCT​ Randomized controlled trial
characteristics curve was 0.65 (95% confidence interval, SAH Subarachnoid hemorrhage
0.53–0.76) in the validation cohort, clinical evaluation of TBI Traumatic brain injury
cut-offs with high or low positive predictive value may be VT Tidal volume
VAP Ventilator associated pneumonia
warranted to decipher potential clinical use of this score.
Of note, 21% of the patients of this large international Acknowledgements
cohort did not undergo usual weaning toward extubation Not applicable.
but underwent direct tracheostomy. The optimal tim- Author contributions
ing of eventual tracheostomy of ICU patients has been Each author has made substantial contributions to the conception of the work
the matter of long-lasting debates, with a current lack of and substantively revised it; approved the submitted version; agreed both to
be personally accountable for the author’s own contributions and to ensure
firm benefit of early tracheostomy. A recent large scale that questions related to the accuracy or integrity of any part of the work,
retrospective study including 1538 patients, specifically even ones in which the author was not personally involved, are appropriately
evaluated timing of tracheostomy among the subgroup investigated, resolved, and the resolution documented in the literature.
of 498 patients with a GCS below 8 at ICU admission Funding
and showed a lack of significant link between tracheos- Shirin K. Frisvold was funded by Northern Norway Regional Health Authority
tomy timing and patient outcome [89]. An observational (Grant no. 181021).
study on 1358 patients with TBI showed an association Availability of data and materials
between late tracheostomy and poor neurological out- Data sharing is not applicable to this article as no datasets were generated or
come [90]. However, this finding was not confirmed by analyzed during the current study.
the SETPOINT2 RCT on patients with stroke [91]. Cur-
rent guidelines recommend considering tracheostomy Declarations
in patients who failed an extubation or have persistent Ethics approval and consent to participate
reduced level of consciousness with no recommenda- Not applicable.
tion on optimal timing of tracheostomy [3]. Focusing on
Consent for publication
measures to reduce sedation/analgesia with early wean- Not applicable.
ing of patients with severe ABI  are the target of future
studies (NCT04291235, NCT04080440). Competing interests
The authors declare that they have no competing interests.

Conclusions Received: 29 April 2023 Accepted: 15 June 2023

Neurologically ill patients have specific  challenging res-
piratory problems and lung–brain interactions. Opti-
mal delivery of  MV  has not been studied extensively in
this setting  and RCTs are scarce. Recent interest in the
 Frisvold et al. Critical Care (2023) 27:247 Page 9 of 11

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