Effects of positive end-expiratory pressure on intracranial pressure, cerebral perfusion pressure, and brain oxygenation in acute brain injury: Friend or foe? A scoping review

Abstract

Background: Patients with acute brain injury (ABI) are a peculiar population because ABI does not only affect the brain but also other organs such as the lungs, as theorized in brain-lung crosstalk models. ABI patients often require mechanical ventilation (MV) to avoid the complications of impaired respiratory function that can follow ABI; MV should be settled with meticulousness owing to its effects on the intracranial compartment, especially regarding positive end-expiratory pressure (PEEP). This scoping review aimed to (1) describe the physiological basis and mechanisms related to the effects of PEEP in ABI; (2) examine how clinical research is conducted on this topic; (3) identify methods for setting PEEP in ABI; and (4) investigate the impact of the application of PEEP in ABI on the outcome.

Methods: The five-stage paradigm devised by Peters et al. and expanded by Arksey and O'Malley, Levac et al., and the Joanna Briggs Institute was used for methodology. We also adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) extension criteria. Inclusion criteria: we compiled all scientific data from peer-reviewed journals and studies that discussed the application of PEEP and its impact on intracranial pressure, cerebral perfusion pressure, and brain oxygenation in adult patients with ABI. Exclusion criteria: studies that only examined a pediatric patient group (those under the age of 18), experiments conducted solely on animals; studies without intracranial pressure and/or cerebral perfusion pressure determinations, and studies with incomplete information. Two authors searched and screened for inclusion in papers published up to July 2023 using the PubMed-indexed online database. Data were presented in narrative and tubular form.

Results: The initial search yielded 330 references on the application of PEEP in ABI, of which 36 met our inclusion criteria. PEEP has recognized beneficial effects on gas exchange, but it produces hemodynamic changes that should be predicted to avoid undesired consequences on cerebral blood flow and intracranial pressure. Moreover, the elastic properties of the lungs influence the transmission of the forces applied by MV over the brain so they should be taken into consideration. Currently, there are no specific tools that can predict the effect of PEEP on the brain, but there is an established need for a comprehensive monitoring approach for these patients, acknowledging the etiology of ABI and the measurable variables to personalize MV.

Conclusion: PEEP can be safely used in patients with ABI to improve gas exchange keeping in mind its potentially harmful effects, which can be predicted with adequate monitoring supported by bedside non-invasive neuromonitoring tools.

Keywords: Acute brain injury; Brain–lung crosstalk; Intracranial pressure; Mechanical ventilation; Multimodal monitoring; Positive end-expiratory pressure.

Figure 1

PRISMA 2020 flow diagram for new systematic reviews, which included searches of databases and registers only. PRISMA: Preferred Reporting Items for Systematic Reviews and Meta-Analyses.

Figure 2

Advantages (green) and Disadvantages (red) of PEEP on different organs. Brain Advantages: improve cerebral oxygenation (as consequence of lung recruitment and improved gas exchange); Disadvantages: increase ICP and CBV (by reducing the venous outflow), reduction of CPP, and reduction of CBF and cerebral compliance (especially when PEEP impaired hemodynamics). Heart Advantages: decreased afterload (by the reduction of left ventricular transmural pressure); Disadvantages: decreased preload, stroke volume, CO, MAP (by hindering venous return), increase of PVR (as a reflex response, to improve venous return and preload). Abdomen Advantages: increase venous return (squeezing the splanchnic vessels); Disadvantages: venous compression; splanchnic, renal, and liver hypoperfusion (when PEEP overcomes the venous pressure); increased ITP and IAP. Lung Advantages: improves PaO₂, V/Q ratio, reduces shunt, and alveolar collapse, when it produces alveolar recruitment. Disadvantages: increase PaCO₂ and dead space, lung hyperinflation with barotrauma and biotrauma. CBF: Cerebral blood flow; CBV: Cerebral blood volume; CO: Cardiac output; CPP: Cerebral perfusion pressure; IAP: Intra-abdominal pressure; ICP: Intracranial pressure; ITP: Intrathoracic pressure; MAP: Mean arterial pressure; PaCO₂: Arterial partial pressure of carbon dioxide; PaO₂: Arterial partial pressure of oxygen; PEEP: Positive end-expiratory pressure; PVR: Peripheric vascular resistance; V/Q: Ratio between ventilation and perfusion of the lungs.

Figure 3

The DEPARTMENT acronym. Damage: as a general rule, supported by clinical and experimental studies, the greater the lung damage, the lower the transmission of pressures from the thoracic cavity to the intracranial compartment.^[1,49] Euvolemia: is fundamental to ensure euvolemia before PEEP titration^[44] to avoid the hemodynamic harmful consequence of PEEP, especially when high PEEP (>15 cmH₂O) is necessary.^[45] The PEEP-test of Lai et al.^[46] could help with predicting volume responsiveness. PEEP lower than ICP: PEEP should be kept under the baseline ICP value^[53] (0 cmH₂O PEEP should be avoided).^[2] Arterial blood gasses: PEEP as part of the management of ABI patients has the goal to reach and maintain safe blood gas levels of O₂ (PaO₂ target: 80–120 mmHg) and CO₂ (PaCO₂ target: 35–45 mmHg).^[34] Relationship: PEEP could impact other organs and their equilibrium, thus the relationship between PEEP and ICP, ITP, and IAP should always be considered to prevent undesirable consequences.^[[39], [40], [41]^,43] Titration: PEEP should be a personalized ventilatory parameter^[32]; in ABI patients, close attention should be given to baseline ICP and its change during PEEP setting as well as systemic and cerebral hemodynamic parameters. Avoid 0 cmH₂O PEEP^[2] and start from 5 cmH₂O PEEP and increase the level to improve oxygenation (pay attention to plateau and driving pressure).^[88] Monitoring: PEEP should always be used under close systemic and multimodal neuromonitoring. Even if invasive ICP remains the gold standard, non-invasive tools like TCD,^[[50], [51], [52], [53]^]ONDS,^[[63], [64], [65]^] and LUS^[75] are gaining reliability when invasive ICP is not available. Methods to monitor cerebral oxygenation (NIRS, PtiO₂, SvjO₂) should be implemented in clinical practice.^[90] Evaluate: PEEP is not contraindicated in ABI and its use is safe under close multimodal monitoring^[3,34]and comprehensive monitoring of the elastic properties of the respiratory system.^[48,49,80] Normal systemic hemodynamics: ensuring hemodynamic stability as part of a good general approach^[89,90] is fundamental in ABI patients; preventing the decrease of CBF and CPP following PEEP and ensuring the stability of MAP is pivotal,^[1] thus when properly settled, PEEP could support CO and peripheric circulation.^[43] Tapered gradually: PEEP should be decreased gradually. The lung has a viscoelastic property, meaning that the applied stress is not constant during a sustained strain. The deformation of the tissue is expressed as strain, which is the ratio between the applied tidal volume and the end-expiratory lung volume. Increased lung damage has been found with sustained inflation followed by abrupt deflation of PEEP levels, which led to hemodynamic impairment and increased lung microvascular pressure.^[96] In a recent animal study, Rocha et al.^[97] demonstrated that an abrupt versus gradual release of PEEP associated with standard or high fluid volume status causes epithelial cell damage and increased pulmonary arterial pressure. Detrimental effects of an abrupt increase of PEEP were also assumed to affect the brain.^[98] ABI: Acute brain injury; CBF: Cerebral blood flow; CO: Cardiac output; CPP: Cerebral perfusion pressure; IAP: Intra-abdominal pressure; ICP: Intracranial pressure; ITP: Intrathoracic pressure; LUS: Lung ultrasound; MAP: Mean arterial pressure; NIRS: Near infrared spectroscopy; ONDS: Optic nerve sheath diameter; PaO₂: Arterial partial pressure of oxygen; PEEP: Positive end-expiratory pressure; PtiO₂: Brain tissue oxygen tension; SvjO₂: Venous jugular saturation of oxygen; TCD: Transcranial doppler.

Figure 4

Safety goals during PEEP titration. The figurative circular diagram stresses the importance of continuous monitoring in support of organ (and systemic) stability. CO: Cardiac output; CPP: Cerebral perfusion pressure; C_RS: Compliance of the respiratory system; IAP: Intra-abdominal pressure; ICP: Intracranial pressure; MAP: Mean arterial pressure; PaCO₂: Arterial partial pressure of carbon dioxide; PaO₂: Arterial partial pressure of oxygen; PEEP: Positive end-expiratory pressure; PtiO₂: Brain tissue oxygenation; SaO₂: Saturation of oxygen; SvjO₂: Venous jugular oxygen saturation.