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Optimizing PEEP in ARDS: A Narrative Review of Personalized Strategies,

Advancements, and Clinical Outcomes

Preprint · March 2024

DOI: 10.13140/RG.2.2.30555.37927

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Optimizing PEEP in ARDS:
A Narrative Review of
Personalized Strategies,
Advancements, and Clinical
Outcomes
Magdy Khames Aly
ICU department Zayed Military Hospital Abu Dhabi, UAE
Magdy.aly@msc.mil.ae
 Table of Contents
List of Abbreviations .......................................................................................................................................................................... 3
Chapter 1. Introduction ..................................................................................................................................................................... 4
a. Background: ............................................................................................................................................................................. 4
b. Rationale: ................................................................................................................................................................................. 5
c. Objectives: ................................................................................................................................................................................ 5
d. Research questions: ................................................................................................................................................................. 6
Chapter 2. Methodology: ................................................................................................................................................................... 7
Data Extraction ............................................................................................................................................................................ 7
The conceptual variables and their inter-relationships: .......................................................................................................... 7
1.Independent Variables: .......................................................................................................................................................... 7
2. Dependent Variable: ............................................................................................................................................................. 7
3. Control Variables: ................................................................................................................................................................. 8
4. Mediator Variables: .............................................................................................................................................................. 8
5. Moderator Variables: ............................................................................................................................................................ 9
6. Outcome Variables: .............................................................................................................................................................. 9
Table: Conceptual Variables ..................................................................................................................................................... 10
Conceptual Framework: ........................................................................................................................................................... 11
Relationships between variables: ............................................................................................................................................. 11
Figure 1: Conceptual Variables ................................................................................................................................................ 12
Figure 2: Suggestive Individualized PEEP Flowchart: .......................................................................................................... 13
Chapter 3. Literature reviews: ......................................................................................................................................................... 14
1.Observational studies on PEEP in ARDS patients .............................................................................................................. 14
1.1 Findings ............................................................................................................................................................................ 14
1.2 Research Gaps .................................................................................................................................................................. 15
1.3 Implications ...................................................................................................................................................................... 16
2.Personalized PEEP strategies ................................................................................................................................................ 17
2.1 Findings ............................................................................................................................................................................ 17
2.2 Research Gaps .................................................................................................................................................................. 20
3. Reviews and meta-analyses of PEEP trials.......................................................................................................................... 22
3.1 Findings ............................................................................................................................................................................ 22
3.2 Research Gaps .................................................................................................................................................................. 23
3.3 Implications ...................................................................................................................................................................... 24
4. Randomized controlled trials of PEEP strategies ............................................................................................................... 25
4.1 Findings ............................................................................................................................................................................ 25
4.2 Research Gaps .................................................................................................................................................................. 27
4.3 Implications ...................................................................................................................................................................... 28
Chapter 4. Discussion ...................................................................................................................................................................... 30
Chapter 5. Conclusion ..................................................................................................................................................................... 33
References ........................................................................................................................................................................................ 34
 List of Abbreviations

ARDS Acute Respiratory Distress Syndrome

BMI Body Mass Index
BPD BronchoPulmonary Dysplasia
CPAP Continuous Positive Airway Pressure
CPB CardioPulmonary Bypass
CRS Compliance of the Respiratory System
DP Driving Pressure
EELV End-Expiratory Lung Volume
EIT Electrical Impedance Tomography
H2O Water
HFOV High-Frequency Oscillatory Ventilation
LPV Lung Protective Ventilation
LTV Low Tidal Volume
NOV NO mechanical Ventilation
PEEP Positive End Expiratory Pressure
PEEPind Positive End Expiratory Pressure individualized
PPC Postoperative Pulmonary Complications
RCT Randomized Controlled Trials
RDS Respiratory Distress Syndrome
RM Recruitment Maneuver
SARS-CoV Severe-Acute-Respiratory-Syndrome-related CoronaVirus
VCV Volume Control Ventilation
VG Volume Guarantee
VILI Ventilator-Induced Lung Injury
 Optimizing PEEP in ARDS: A Narritive Review of
Personalized Strategies, Advancements, and Clinical
Outcomes

Chapter 1. Introduction
a. Background:
The management of acute respiratory distress syndrome (ARDS) has long been a
cornerstone in critical care medicine, requiring meticulous attention to ventilatory strategies
to optimize patient outcomes. Among these strategies, positive end-expiratory pressure
(PEEP) stands as a crucial intervention aimed at improving oxygenation and reducing
ventilator-induced lung injury. Given its critical role, recent literature has seen a surge in
studies exploring the nuances of PEEP application, including observational analyses.
personalized strategies, understanding pathophysiological mechanisms, and evaluating
outcomes through reviews and randomized controlled trials. This survey delves into the
breadth of current research, providing a comprehensive view of recent advancements and
ongoing debates surrounding PEEP in ARDS patients(Sklar & Munshi, 2022)

PEEP is a modality of mechanical ventilation that maintains a positive pressure within the
lungs at the end of expiration, aiming to keep alveoli open and improve gas exchange. Since
its inception, PEEP has been a subject of intense research, particularly in the context of
ARDS—a condition characterized by widespread inflammation and alveolar damage leading
to severe hypoxemia. The historical trajectory of PEEP research reflects a constant search
for the optimal balance between the beneficial effects on oxygenation and potential harm
due to overdistention and hemodynamic compromise.(Carpio & Mora, 2023; Chikhani et al.,
2016)

Focusing on recent advancements, this review delves into the personalized application of
PEEP, which has gained prominence due to the heterogeneity observed in ARDS patients.
Personalization is essential as a one-size-fits-all approach may not be suitable considering
the diverse etiologies, pathophysiology, and patient-specific characteristics like lung
mechanics and comorbidities. Current literature includes observational studies on PEEP in
ARDS, personalized PEEP strategies, the pathophysiological mechanisms of PEEP, reviews,
and meta-analyses of PEEP trials, and randomized controlled trials assessing different PEEP
strategies.(Cutuli et al., 2023; Sklar & Munshi, 2022)
 b. Rationale:
Justify the Review:
The rationale for this comprehensive literature review is underscored by the evolving nature
of ventilatory management in ARDS and the imperative need for evidence-based
approaches. The relevance of this review is particularly accentuated by the recent SARS-
CoV-2 pandemic, which has thrust ARDS and its management into the limelight. By
examining the array of recent studies, this review endeavors to contribute to the ongoing
discourse on the optimization of PEEP, ultimately aiming to inform clinical decision-making
and improve patient outcomes(Coleman & Aldrich, 2021; Mart & Ely, 2020; Schmidt et al.,
2020).

Outline the Scope:

The scope of this review encompasses literature published in recent years, focusing on
studies that examine the application of PEEP in ARDS patients across various clinical
settings. The review includes observational studies, personalized strategy formulations,
pathophysiological explorations, comprehensive reviews and meta-analyses, as well as
randomized controlled trials(Cutuli et al., 2023; Yamamoto et al., 2022).

Highlight the Contribution:

The contribution of this literature review lies in its ability to synthesize a coherent narrative
from a plethora of studies, encompassing theoretical underpinnings, practical
implementations, and clinical trials. Its goal is to elucidate the intricacies of PEEP strategy
in ARDS, propose a framework for personalized approaches, and offer insights that can steer
future research and clinical decision-making. By undertaking this effort, the review seeks to
enhance comprehension of ventilatory management in ARDS and facilitate the transition
towards more personalized, patient-centered care models.
c. Objectives:
This survey aims to synthesize the current literature on PEEP in ARDS, identifying salient
themes, research gaps, and implications for clinical practice. It seeks to evaluate the
effectiveness of personalized PEEP strategies based on patient-specific characteristics and
to assess the impact of these strategies on clinical outcomes.
d. Research questions:
1.What are the current approaches and strategies for PEEP titration in mechanical
ventilation?
2.What patient-specific characteristics have been taken into account in the formulation of
individualized PEEP strategies?
3. How have patient-specific characteristics influenced the choice and optimization of PEEP
levels in various patient cohorts, including adults and pediatric patients?
4.What is the impact of personalized PEEP strategies on clinical outcomes, such as
oxygenation, lung recruitment, and mortality?
5. What are the limitations and challenges associated with implementing personalized PEEP
strategies in clinical practice?
6.Are there specific patient subgroups or clinical conditions where personalized PEEP
strategies have shown greater efficacy or benefit?
7.What gaps exist in the current literature regarding the development and validation of
personalized PEEP strategies based on patient-specific characteristics?
8. What are the implications of the findings for clinical practice, and what recommendations
can be made for incorporating patient-specific characteristics into PEEP titration
protocols?

These research questions will guide the narrative review by addressing the current
knowledge gaps and exploring the relationship between patient-specific characteristics and
the development of personalized PEEP strategies.
 Chapter 2. Methodology:
a.inclusion Criteria: we will select relevant studies based on the publication date range, study
designs (e.g., randomized controlled trials, observational studies), and populations (e.g.,
adult patients, pediatric patients).
b. Databases: the electronic databases to be searched will include PubMed, Semantic scholar,
and Google scholar.
c. Search Terms: Provide a comprehensive list of keywords and Medical Subject Headings
(MeSH) terms to be used during the literature search.
d. Study Selection: studies discussing PEEP titration strategies and ventilatory protocols

Data Extraction
a. Data Items: Define the variables to be extracted from each included study, such as patient
demographics, PEEP titration methods, outcomes, and any patient-specific characteristics
considered in the PEEP strategy.
b. Data Extraction Process:

The conceptual variables and their inter-relationships:

1.Independent Variables:
1.1. Patient-specific characteristics:

These characteristics can impact the optimal PEEP level by influencing lung mechanics,
hemodynamics, and disease severity. For instance, individuals with higher lung compliance
might be able to withstand higher PEEP levels, whereas those with severe pulmonary
hypertension may necessitate lower PEEP levels to prevent hemodynamic compromise.

1.2. Optimal PEEP level:

This is the PEEP level that optimizes lung mechanics, hemodynamics, and gas exchange
for a given patient. The optimal PEEP level may vary depending on the patient's individual
characteristics.

2. Dependent Variable:
2.1 Optimal PEEP level:

Optimal PEEP can be considered as a dependent variable, as the optimal PEEP level may
vary depending on the individual characteristics of the patient.
 2.2 Outcome Variables:

Mortality

Ventilator-free days

ICU length of stay

3. Control Variables:
3.1 Ventilator settings (other than PEEP):

These settings may affect lung mechanics and gas exchange and, therefore, need to be
controlled for when determining the optimal PEEP level.

3.2 Sedation and analgesia:

These medications may affect respiratory drive and lung mechanics and, therefore, need to
be controlled for when determining the optimal PEEP level.

3.3 Fluid management:

Fluid overload can exacerbate pulmonary edema and elevate the likelihood of ventilator-
induced lung injury, underscoring the importance of its management in establishing the
optimal PEEP level.

3.4 Other medical interventions:

Other medical interventions, such as prone positioning and neuromuscular blockade, may
impact lung mechanics and gas exchange, and thus should be taken into account when
determining the optimal PEEP level.

4. Mediator Variables:
4.1 Lung mechanics:

PEEP can influence lung mechanics by augmenting lung volume and diminishing airway
resistance. These alterations in lung mechanics have the potential to enhance gas exchange
and mitigate the likelihood of ventilator-induced lung injury.

4.2 Hemodynamics:

PEEP can influence hemodynamics by elevating intrathoracic pressure and diminishing

venous return. These alterations in hemodynamics may result in hypotension and
compromised organ perfusion, particularly in patients with underlying cardiovascular
conditions.
 4.3 Gas exchange:

PEEP can enhance gas exchange by augmenting lung volume and diminishing airway
resistance. These alterations in lung mechanics have the potential to optimize the matching
of ventilation and perfusion, consequently improving oxygenation and decreasing carbon
dioxide retention.

5. Moderator Variables:
5.1 Patient age:

Age may impact lung mechanics, hemodynamics, and disease severity, thus potentially
moderating the relationship between patient-specific characteristics and the optimal PEEP
level.

5.2 Disease severity:

Disease severity may impact lung mechanics, hemodynamics, and gas exchange,
potentially moderating the relationship between patient-specific characteristics and the
optimal PEEP level.

6. Outcome Variables:
6.1 Mortality:

Optimal PEEP levels can impact mortality by decreasing the likelihood of ventilator-
induced lung injury and enhancing gas exchange.

6.2 Ventilator-free days:

PEEP may increase ventilator-free days by reducing the duration of mechanical

ventilation.

6.3 ICU length of stay:

PEEP may decrease ICU length of stay by enhancing clinical outcomes and mitigating
the risk of complications.
Table: Conceptual Variables

Variable
Description Role Relationship
Type

The factor that is

manipulated or controlled Influences the
by the researcher. In the Determines the outcome variable
Independent
context of PEEP strategies, treatment or (e.g., patient
Variable
this could be the level of intervention. outcomes, lung
PEEP applied during function).
mechanical ventilation.

The outcome or response

that is measured. In this Represents the
Dependent case, it could be patient effect of the Affected by the
Variable outcomes such as independent level of PEEP.
oxygenation, lung variable.
compliance, or mortality.

A variable that is held

constant to minimize its
impact on the relationship Ensures that
Helps isolate the
between the independent other factors do
Control effect of PEEP
and dependent variables. not confound
Variable on patient
For example, patient age, the
outcomes.
comorbidities, and relationship.
baseline lung function
could be controlled.

A variable that explains the

process through which the
independent variable affects Helps understand
the dependent variable. In Part of the why PEEP
Mediator
the context of PEEP causal influences
Variable
strategies, a potential pathway. patient
mediator could be lung outcomes.
compliance or
oxygenation.
 Variable
Description Role Relationship
Type

A variable that affects the

strength or direction of the
Determines
relationship between the
whether the
independent and dependent
Moderator Influences the effect of PEEP
variables. For instance,
Variable relationship. varies across
patient body mass index
different BMI
(BMI) might moderate the
levels.
impact of PEEP on
outcomes.

Conceptual Framework:
The conceptual framework of the study is based on the hypothesis that patient-specific
characteristics influence the optimal PEEP level in ARDS patients. We will investigate this
hypothesis by examining the relationships between the independent variables, dependent
variable, and outcome variables. The results of the study will be used to develop a
personalized PEEP strategy that takes into account patient-specific characteristics.
Relationships between variables:

1. Direct Effect (Independent Variable → Dependent Variable):

o Increasing PEEP levels may lead to improved oxygenation (dependent variable) in
patients.
2. Mediation (Independent Variable → Mediator → Dependent Variable):
o Higher PEEP levels improve lung compliance (mediator), which subsequently
enhances oxygenation (dependent variable).
3. Moderation (Independent Variable × Moderator → Dependent Variable):
o The impact of PEEP on outcomes (dependent variable) may vary depending on the
patient's BMI (moderator).
Figure 1: Conceptual Variables
Figure 2: Suggestive Individualized PEEP Flowchart:
 Chapter 3. Literature reviews:

1.Observational studies on PEEP in ARDS patients

1.1 Findings
Personalized Ventilatory Support Strategies
The concept of individualized ventilatory support is becoming increasingly important
in the management of ARDS patients. The current literature emphasizes the need for a
tailored approach to PEEP settings to optimize patient outcomes.

In the paper by(Radhi et al., 2023), the authors discuss the significance of personalized
PEEP in ARDS management. They emphasize that despite numerous large studies, no
superior strategy between high or low PEEP has been definitively established, indicating
that the optimal PEEP level may be specific to each patient. They examine the
physiological impacts of PEEP and the different approaches to identifying the ideal
PEEP at the bedside, offering potential guidance to clinicians in caring for mechanically
ventilated patients and opening up new paths for research.

Similarly,(Gordo et al., 2022) discusses the importance of personalized ventilatory

support, especially in the context of the SARS-CoV-2 pandemic. The paper highlights
the development of personalized ventilation concepts in response to the heightened
complexity of respiratory support for patients with SARS-CoV-2 pneumonia.

Protective Ventilation Strategies in Surgical and Non-ARDS Context

Although not directly focused on ARDS, the study by (Koritarova & Georgiev, 2022)
presents evidence in favor of employing protective ventilation strategies during
extended gynecological surgeries. They illustrate that intraoperative PEEP, in
conjunction with low tidal volume and recruitment maneuvers, can enhance
postoperative oxygenation and decrease atelectasis occurrence. This observational study
supportresearch reinforces the overarching idea that protective lung strategies, such as
utilizing PEEP, can yield benefits across different clinical contexts, beyond ARDS.

Synthesis and Conclusions

There is a consensus among the papers that personalized ventilation strategies,
including the application of PEEP, can lead to better patient outcomes. The literature
suggests moving away from a one-size-fits-all approach to PEEP in ARDS and supports
the need for individualized PEEP settings based on patient response. The application of
protective ventilation strategies with PEEP is also shown to be beneficial in non-ARDS
scenarios, such as during surgery, indicating the broad relevance of these approaches.
However, there remains a lack of definitive guidance on how to determine the optimal
PEEP for each patient, signaling the need for further research in this area.
1.2 Research Gaps
Research Gaps and Discrepancies
While the reviewed papers converge on the benefit of individualized and protective
ventilation strategies, several research gaps and discrepancies remain that warrant
further investigation.

Optimal PEEP Determination: (Radhi et al., 2023a) underscore the absence of a

definitive superior strategy for determining the optimal PEEP in ARDS patients. While
several methods have been suggested to evaluate the ideal PEEP level, there is still no
consensus on the most efficient approach. Future research endeavors could focus on
establishing standardized, evidence-based protocols for evaluating patient-specific
PEEP levels, taking into account variables like lung mechanics, disease severity, and
patient response to treatment.

Personalized Ventilation Beyond ARDS: (Gordo et al., 2022) focus on SARS-CoV-

2 pneumonia, while (Radhi et al., 2023a) concentrate on ARDS management. The
different contexts suggest that personalized ventilation strategies may need to be
adapted for various respiratory conditions. Comparative studies could explore the
effectiveness of personalized ventilation in different diseases, potentially leading to
tailored strategies for a range of respiratory illnesses.

Protective Ventilation in Surgery: The study conducted by (Koritarova & Georgiev,

2022) emphasizes the beneficial effects of protective ventilation in prolonged
gynecological surgeries. However, the generalizability of these results to various
surgical procedures and specialties, especially shorter surgeries, remains to be
elucidated. Further research is warranted to assess the wider applicability of protective
ventilation strategies in diverse surgical settings.

Methodological Differences: The studies reviewed vary in their methodologies,

from numerical simulations and experimental measurements in the paper by(Gattinoni
et al., 2006) to observational cohort studies as seen in (Koritarova & Georgiev, 2022)
These methodological differences may impact the generalizability and replicability of
the findings. Future research could aim to harmonize methodologies across studies or
conduct multicenter trials to validate and compare results.

Synthesis of Evidence: While individual studies contribute valuable insights, there

is a gap in the synthesis of evidence across different studies and contexts. Systematic
reviews and meta-analyses could integrate data from various sources to provide more
robust conclusions on personalized and protective ventilation strategies.

In conclusion, the current literature indicates a promising shift towards

personalized ventilation strategies for improved patient outcomes. However, there are
significant research gaps that need to be addressed to establish clear guidelines and best
practices. Addressing these gaps through rigorous and collaborative research efforts
could lead to significant advancements in the management of respiratory conditions and
 contribute to the development of innovative strategies in both clinical and non-clinical
settings.

1.3 Implications
Theoretical Implications:
The recent research outlined in the reviewed papers significantly enhances the
theoretical understanding of ventilation strategies in medical and public health contexts.
The concept of individualized PEEP, as discussed by(Radhi et al., 2023a), challenges
traditional one-size-fits-all theories of ventilatory support and emphasizes the intricacies
of human respiratory physiology. It raises doubts about the validity of standardized
ventilation protocols and advocates for the growing paradigm of precision medicine,
where treatment is customized to the unique physiological and pathological attributes of
each patient.

Furthermore, the findings from (Koritarova & Georgiev, 2022)contribute to the

theoretical basis for perioperative care, supporting theories that advocate for lung-
protective strategies to mitigate postoperative complications. This evidence suggests
that protective lung strategies may be beneficial across a spectrum of medical scenarios,
which could lead to a reexamination of current theories on the management of intubated
patients in various settings.

Practical Implications:
The practical implications of these findings are extensive. For clinicians, the
transition towards personalized PEEP strategies in ARDS management could result in
the creation of novel protocols and bedside tools to enhance mechanical ventilation
settings for individual patients. This has the potential to enhance patient outcomes and
reduce the occurrence of ventilator-associated complications.

For surgical practice, the evidence presented by (Koritarova & Georgiev, 2022) may
prompt modifications in intraoperative and postoperative care protocols, potentially
shortening hospital stays and enhancing the quality of recovery for surgical patients.

Finally, the research gaps and discrepancies identified suggest a need for future
research directions, such as multicenter trials to validate protective ventilation strategies
across different patient populations and clinical settings.

Overall, the recent research supports a shift towards more nuanced and patient-
centered approaches to ventilation, which could have significant implications for
clinical practice, public health policy, and the broader healthcare system.
2.Personalized PEEP strategies
2.1 Findings
The article titled (Radhi et al., 2023)" Positive end-expiratory pressure in acute
respiratory distress syndrome; where have we been, where are we going?" discusses the
application of positive end-expiratory pressure (PEEP) in patients with Acute
Respiratory Distress Syndrome (ARDS). ARDS is a complex condition associated with
high mortality and limited therapeutic options. PEEP is commonly used in ARDS
management as part of a protective lung ventilation strategy to optimize respiratory
system compliance and improve oxygenation.

However, the effectiveness of PEEP can vary significantly among patients, and
inappropriate levels of PEEP can potentially cause harm. Traditionally, clinical trials
have compared strategies employing low PEEP with those using higher PEEP levels.
Yet, no superior strategy has emerged, possibly due to the failure to stratify patients
based on their individual responses to different PEEP levels.

The article proposes the concept of personalized PEEP strategies, emphasizing the
importance of individualizing PEEP based on patient-specific factors. In the era of
personalized medicine, a one-size-fits-all approach may not be suitable for PEEP
management. Instead, the authors suggest tailoring PEEP levels to each patient's
physiology and response, considering factors such as lung compliance and oxygenation
status.

The manuscript reviews various physiological effects of PEEP and methods available
for determining optimal PEEP at the bedside. It provides guidance for physicians
managing mechanically ventilated patients and identifies new avenues for research in
this field.

Overall, the article advocates for a shift towards personalized PEEP strategies in
ARDS management, emphasizing the importance of individualized approaches to
optimize patient outcomes.

The article “Effects of different positive end-expiratory pressure titration strategies

during prone positioning in patients with acute respiratory distress syndrome: a
prospective interventional study “(Boesing et al., 2022)The article explores the impact
of personalized positive end-expiratory pressure (PEEP) strategies on patients with
moderate to severe acute respiratory distress syndrome (ARDS) undergoing prone
positioning. Here's a breakdown of the efficacy and research implications:

Efficacy and Impact of Personalized PEEP Strategies:

1. Primary Endpoint Analysis: The study primarily aimed to analyze the effect of
different PEEP titration strategies (PEEPARDSNetwork, PEEPEstat,RS, PEEPPtpexp)
on end-expiratory transpulmonary pressure (Ptpexp) during both supine and prone
positioning in patients with moderate to severe ARDS.
 2. Findings:
- Ptpexp increased progressively during prone positioning compared to supine
positioning.
- Ptpexp was higher with PEEPEstat,RS and PEEPPtpexp strategies compared to
PEEPARDSNetwork.
- PEEP levels were lower during prone positioning with personalized PEEP strategies.
- Mechanical power increased progressively with personalized PEEP strategies during
supine positioning but was attenuated during prone positioning.
- Prone positioning significantly improved oxygenation while maintaining stable
hemodynamics.

3. Conclusions:
- Prone positioning led to increased transpulmonary pressures while improving
oxygenation and hemodynamics when PEEP was titrated according to the lower PEEP
table recommended by the ARDS Network.
- Lower PEEP strategy (PEEPARDSNetwork) combined with prone positioning may
contribute to a lung-protective ventilation strategy in moderate to severe ARDS.

Research Gaps and Implications:

1. Interaction Between PEEP Strategies and Prone Positioning: The study highlights the
interaction between prone positioning and personalized PEEP strategies, suggesting a
potential optimization of lung-protective ventilation in ARDS patients. However,
further investigation is warranted to elucidate the precise mechanisms and long-term
outcomes associated with these strategies.

2. Optimal PEEP Titration: Despite advancements in understanding lung recruitability and

individualized PEEP titration, there remains controversy regarding the optimal strategy.
This study provides insights into the impact of different PEEP titration approaches on
lung mechanics, gas exchange, and hemodynamics, but additional research is needed to
validate these findings across diverse patient populations.

3. Long-term Clinical Outcomes: While the study evaluates immediate physiological

responses to personalized PEEP strategies and prone positioning, long-term clinical
outcomes such as ventilator-free days, mortality rates, and quality of life measures are
not addressed. Future research should focus on assessing the efficacy and safety of these
interventions on patient-centered outcomes.

4. Patient Selection and Generalizability: The study includes a specific cohort of patients
with moderate to severe ARDS, raising questions about the generalizability of findings
to broader ARDS populations. Further studies should explore the applicability of
personalized PEEP strategies and prone positioning across different ARDS severity
levels and etiologies.

5. Comparative Effectiveness: While the study compares different PEEP titration

strategies, it does not directly compare the efficacy of prone positioning with other
interventions or standard care protocols. Future research could investigate the
comparative effectiveness of personalized PEEP strategies against alternative
ventilation approaches or adjunctive therapies in ARDS management.

In summary, while the study sheds light on the potential benefits of personalized PEEP
strategies in conjunction with prone positioning for ARDS management, several research
gaps exist, emphasizing the need for further investigation to optimize ventilatory support
and improve patient outcomes in this population.

The article “How I set up Positive End-Expiratory Pressure: Evidence- And physiology-
based!”by Rezoagli et al. 2019(Rezoagli & Bellani, 2019) discusses the efficacy and
impact of personalized Positive End-Expiratory Pressure (PEEP) strategies in the
treatment of critically ill patients, particularly those suffering from Acute Respiratory
Distress Syndrome (ARDS). PEEP is highlighted as a crucial intervention in preventing
alveolar collapse, counteracting surfactant impairment, and reducing intrapulmonary
shunting. The authors emphasize the benefits of maintaining alveolar recruitment through
PEEP, which leads to higher end-expiratory lung volume (EELV) and improved
compliance of the respiratory system (CRS). Additionally, PEEP is recognized for its role
in reducing ventilation heterogeneity and protecting against atelectrauma and biotrauma.

The personalized PEEP strategy outlined in the article is based on physiological

considerations and closely monitoring individual responses. It involves targeting two
main objectives: driving pressure and oxygenation. The article advocates for increasing
PEEP levels while monitoring the response in driving pressure and oxygenation, with
adjustments made based on changes in compliance of the respiratory system (CRS). The
authors suggest using a moderate recruitment maneuver (RM) to assess lung recruitability
and adjust PEEP levels accordingly. Bedside electrical impedance tomography (EIT) is
proposed as a tool to aid in PEEP titration by providing regional information on lung
dynamics.

The article by Baedorf Kassis et al. 2018(Baedorf Kassis et al., 2018) discusses the
efficacy and impact of personalized positive end-expiratory pressure (PEEP) strategies in
managing patients with acute respiratory distress syndrome (ARDS). It emphasizes the
importance of PEEP in lung-protective ventilation strategies but acknowledges the lack
of standardized methods to set PEEP levels. The use of esophageal manometry is
highlighted as a valuable tool for personalizing and optimizing mechanical ventilation in
ARDS patients by estimating pleural pressures and differentiating between chest wall and
lung contributions to respiratory mechanics.

The article suggests that elevated pleural pressures may lead to negative transpulmonary
pressures at end expiration, resulting in lung collapse. By measuring esophageal pressures
and adjusting PEEP to maintain positive transpulmonary pressures, atelectasis,
derecruitment of the lung, and cyclical opening and closing of airways and alveoli can be
minimized, thus optimizing lung mechanics and oxygenation.
 Although acknowledging some limitations such as spatial and positional artifacts, the
article suggests that esophageal pressures provide valuable insights into a patient's unique
physiology, aiding in clinical decision-making at the bedside. It cites multiple studies
illustrating the benefits of using esophageal pressures to titrate PEEP in patients with
obesity and ARDS.

Overall, the article supports the use of personalized PEEP strategies based on
esophageal pressures to improve clinical outcomes in ARDS patients by optimizing lung
mechanics and oxygenation.

2.2 Research Gaps

Optimal PEEP Determination: (Radhi et al., 2023a) despite the comprehensive review
of personalized PEEP strategies, several research gaps and implications remain:
1. Clinical Validation of Personalized PEEP Strategies: While the article discusses various
methods for determining personalized PEEP, there is a need for further clinical validation
of these strategies. Large-scale prospective studies are necessary to assess the
effectiveness and impact of personalized PEEP approaches on patient outcomes.

2. Standardization of Assessment Methods: The article mentions different methods for

assessing optimal PEEP, including pressure-volume curves and esophageal pressure
monitoring. However, there is currently no standardized approach for selecting the most
appropriate method in clinical practice. Future research should focus on comparing these
methods and establishing guidelines for their use.

3. Identification of Biomarkers for PEEP Responsiveness: One key aspect of personalized

PEEP strategies is identifying biomarkers or physiological parameters that predict
individual responsiveness to PEEP. Research efforts should be directed toward
identifying such biomarkers, which could help tailor PEEP settings to each patient's
specific needs.

4. Long-Term Outcomes and Safety: While optimizing PEEP may improve short-term
outcomes such as oxygenation and lung compliance, the long-term effects and safety of
personalized PEEP strategies remain unclear. Future studies should investigate the impact
of personalized PEEP on long-term outcomes, including ventilator-free days, mortality,
and ventilator-induced lung injury. 5. Cost-Effectiveness Analysis: Personalized PEEP
strategies may involve additional resources and monitoring equipment. Therefore, it is
essential to conduct cost-effectiveness analyses to evaluate the economic implications of
implementing these strategies in clinical practice. In conclusion, while personalized PEEP
strategies hold promise for improving outcomes in ARDS patients, further research is
needed to address existing gaps and validate their clinical utility. This will require
collaboration between clinicians, researchers, and industry partners to advance
personalized medicine in critical care settings.
Several research gaps and implications are worth noting in (Rezoagli & Bellani, 2019)
1. Clinical Validation: The personalized PEEP strategy proposed in the article is largely
based on physiological principles and clinical experience. However, further validation
through well-designed clinical trials is necessary to assess its efficacy and impact on
patient outcomes, including mortality rates.

2. Comparison with Alternative Strategies: The article acknowledges that there is no

presumption of the superiority of the proposed PEEP strategy over other approaches.
Future research should compare personalized PEEP strategies with alternative methods
of PEEP titration to determine which approach yields the best outcomes for patients with
ARDS.

3. Optimal PEEP Levels: although higher PEEP levels have shown potential benefits in
enhancing survival among ARDS patients, the precise optimal PEEP level for each
individual patient remains unclear. Subsequent research endeavors should strive to
ascertain the most suitable PEEP level by considering patient-specific variables and the
severity of the underlying disease.

4. Long-Term Impact: The article emphasizes the short-term benefits of personalized PEEP
strategies, including enhanced oxygenation and compliance. Nevertheless, it is crucial to
also assess the long-term effects on lung function, ventilator-free days, and quality of life
in forthcoming studies.

5. Subphenotypes of ARDS: Recent studies have identified subphenotypes of ARDS with

distinct physiological characteristics and responses to treatment. It is imperative for future
research to explore whether personalized PEEP strategies are equally effective across
various subphenotypes of ARDS.

In conclusion, although personalized PEEP strategies show promise in optimizing

ventilator management for critically ill patients with ARDS, further research is needed to
validate their efficacy, compare them with alternative approaches, determine optimal
PEEP levels, assess long-term outcomes, and consider the influence of ARDS
subphenotypes.

Regarding research gaps and implications in study (Baedorf Kassis et al., 2018), the
article emphasizes the need for further investigation into the optimal methods for PEEP
titration in ARDS patients. While esophageal manometry shows promise as a tool for
personalized PEEP strategies, more research is needed to validate its effectiveness and
feasibility in different clinical settings. The article also stresses the importance of
addressing spatial and positional artifacts associated with esophageal pressure
measurements to ensure accurate and reliable results. Further studies should explore the
potential impact of personalized PEEP strategies on long-term outcomes, such as
mortality and ventilator-free days, to better understand their clinical significance.
Additionally, research should focus on identifying patient populations that may benefit
most from personalized PEEP strategies and developing standardized protocols for their
implementation in clinical practice.
3. Reviews and meta-analyses of PEEP trials
3.1 Findings
These documents summarizes key findings from several papers concerning the use of
Positive End-Expiratory Pressure (PEEP) in mechanical ventilation strategies across
various clinical settings. PEEP is a crucial component of ventilatory support, which has
been the subject of extensive research, particularly in its application in different patient
populations such as those with obesity, acute respiratory distress syndrome (ARDS), and
in the context of mechanical ventilation in general.

3.1.1 Optimized Ventilation Strategies for Specific Patient Populations

The first group of papers focuses on the optimization of mechanical ventilation
strategies for specific patient populations, such as those with obesity and ARDS.

In the study by (Wang et al., 2022) a network meta-analysis was conducted to determine
the most effective mechanical ventilation strategy for lung protection in patients with
obesity undergoing surgery. The paper concluded that volume-controlled ventilation with
individualized PEEP and a recruitment maneuver (VCV+PEEPind+RM) was the most
effective strategy for improving oxygenation and reducing pulmonary atelectasis. This
study suggests a tailored approach to mechanical ventilation for patients with obesity,
emphasizing individualization and the use of recruitment maneuvers.

On the contrary, (Yamamoto et al., 2022) conducted a systematic review and meta-
analysis to evaluate the effectiveness of higher PEEP in ARDS patients. The results did
not demonstrate a significant decrease in 28-day mortality with the implementation of
higher PEEP compared to lower PEEP. This indicates that the advantage of higher PEEP
might not apply universally to all ARDS patients and that additional factors, like the
utilization of low tidal volume strategies, could influence the efficacy of PEEP.

3.1.2 Driving Pressure-Guided Ventilation Strategy

The second group includes papers by (Yang et al., 2022)], which explore a ventilation
strategy guided by driving pressure (DP).

(Yang et al., 2022) presents an updated review of the driving pressure-guided

ventilation strategy, proposing that it could be more effective than traditional lung-
protective ventilation strategies in decreasing postoperative pulmonary complications.
This underscores a growing field of study that emphasizes driving pressure as a
potentially more crucial parameter than PEEP or tidal volume alone.

In a similar (LI et al., 2022) conducted a meta-analysis and found that the driving
pressure-guided ventilation strategy was associated with decreased mortality and
improved oxygenation index in mechanically ventilated patients. This aligns with Yang's
 review, reinforcing the potential clinical benefits of focusing on driving pressure during
mechanical ventilation.

The reviewed papers collectively enhance our understanding of the role of PEEP and
mechanical ventilation strategies in different clinical settings. While there is a consensus
on the importance of individualized approaches and the potential benefits of recruitment
maneuvers in patients with obesity, there is less agreement on the benefits of higher PEEP
in ARDS patients. Emerging evidence on driving pressure-guided ventilation strategies
suggests potential advantages over traditional parameters such as PEEP levels.

3.2 Research Gaps

Research Gaps and Discrepancies
Despite the valuable insights provided by the aforementioned studies, there remain
several research gaps and discrepancies that warrant further investigation to optimize
mechanical ventilation strategies across different patient populations and clinical
scenarios.

3.2.1 Lack of Consensus on PEEP Optimization in ARDS

The studies by (Wang et al., 2022) and (Yamamoto et al., 2022) illustrate a discrepancy
in the application of PEEP for different patient populations. While individualized PEEP
with a recruitment maneuver was found beneficial in patients with obesity, higher PEEP
did not significantly reduce 28-day mortality in ARDS patients. This lack of consensus
on the optimal PEEP strategy in ARDS highlights a need for further research, possibly
focusing on patient-specific factors or disease severity that could influence the response
to different PEEP levels.

3.2.2 Variability in Quality of Evidence

The studies reviewed often reported varying qualities of evidence, from very low to
moderate. This variability may stem from differences in study design, sample sizes, and
heterogeneity in patient populations. Future research should aim to conduct large-scale,
high-quality randomized controlled trials (RCTs) with standardized protocols to
strengthen the quality of evidence and provide more definitive guidance on mechanical
ventilation strategies.

3.2.3 Driving Pressure-Guided Ventilation Strategy Efficacy

While (Yang et al., 2022) suggest that driving pressure-guided ventilation may offer
advantages over traditional lung-protective strategies, it is essential to recognize that the
concept of driving pressure as a ventilation guide is still relatively new. Further large-
scale RCTs are necessary to validate these results and determine the optimal integration
of driving pressure into current mechanical ventilation protocols.
 3.2.4 Individualized Ventilation Approaches
The studies underscore the significance of personalized ventilation strategies,
especially concerning obesity. Nevertheless, there is a dearth of specific guidelines on
customizing parameters like PEEP and driving pressure. Further research is essential to
create and validate algorithms or decision-support tools that can assist clinicians in
adjusting ventilation settings based on individual patient physiology in real-time.

3.2.5 Impact of Ventilation on Long-Term Outcomes

Although the studies primarily focus on short-term outcomes such as oxygenation and
mortality, there is limited information available on the long-term outcomes of patients
exposed to various ventilation strategies. It is imperative for future research to investigate
the effects of mechanical ventilation strategies on long-term pulmonary function, quality
of life, and rehabilitation outcomes.

3.2.6 Integration of Ventilation Strategies with Other Therapies

The interaction between mechanical ventilation strategies and other therapeutic
interventions, such as prone positioning, sedation, and neuromuscular blockade, remains
an area with limited data. Research should aim to investigate how these therapies can be
optimized in conjunction with different ventilation strategies to improve patient
outcomes.

In conclusion, while the current body of research has significantly advanced our
understanding of mechanical ventilation strategies, these gaps and discrepancies
underscore the need for ongoing research efforts. Addressing these areas could lead to
more personalized, effective, and evidence-based mechanical ventilation practices that
improve patient outcomes across various clinical settings.

3.3 Implications
The practical implications of the findings from the reviewed themes are profound and
multifaceted, impacting clinical practice, policy formulation, and future research
directions in respiratory care and critical medicine.

From a clinical perspective, the identification of VCV+PEEPind+RM as an optimal

strategy for patients with obesity undergoing surgery provides anesthesiologists and
intensivists with a clear directive to enhance perioperative lung protection and
oxygenation in this high-risk group. This could result in the implementation of more
personalized ventilation protocols, taking into account patient-specific factors such as
body mass index (BMI), lung mechanics, and intraoperative positioning(Fernandez-
Bustamante et al., 2015).

In the context of ARDS, the lack of consensus on the benefits of higher PEEP
underscores the necessity for a more nuanced approach to managing these patients.
Clinicians may need to consider additional factors, such as lung recruitability and
individual patient response, rather than adhering to a one-size-fits-all PEEP strategy. This
 could inform the development of dynamic clinical guidelines that allow for more
personalized treatment plans.

The implications for policy are equally significant. The emerging evidence on the
efficacy of driving pressure-guided ventilation strategies may prompt healthcare
organizations and professional bodies to update their guidelines to include this parameter
as part of lung-protective ventilation protocols.

For future research directions, the gaps identified in the current body of literature
suggest that large-scale, multicenter RCTs are required to establish more definitive
evidence for the use of specific mechanical ventilation strategies. Researchers should also
explore the development of predictive tools using machine learning and artificial
intelligence to aid in the real-time adjustment of ventilation parameters for individual
patients.

On a theoretical level, the findings from these papers challenge and refine existing
theories regarding the pathophysiology of mechanically ventilated patients. The focus on
driving pressure, for example, shifts the theoretical emphasis from traditional parameters
such as PEEP and tidal volume to a more holistic view of lung mechanics during
ventilation. This could lead to the development of new theoretical frameworks that better
explain the complex interactions between different ventilation parameters and patient
outcomes.

In summary, the insights gleaned from the recent research on mechanical ventilation
strategies have significant implications for improving patient care, shaping healthcare
policies, and guiding future scientific inquiry. The emphasis on individualized care, the
potential shift towards driving pressure-guided ventilation, and the reaffirmed importance
of effective ventilation systems in public health highlight the dynamic and evolving
nature of respiratory care and its foundational theories.
4. Randomized controlled trials of PEEP strategies
4.1 Findings

These documents summarizes the key findings from various randomized controlled
trials that focus on the efficacy and outcomes of different Positive End-Expiratory
Pressure (PEEP) strategies in mechanical ventilation. The papers are grouped based on
the patient population and context in which the PEEP strategies were evaluated.

Pediatric Cardiac Surgery

A common theme in pediatric cardiac surgery is the exploration of ventilation strategies
during cardiopulmonary bypass (CPB) and their effects on postoperative outcomes. The
studies in this group focused on different approaches to ventilation during surgery to
determine whether they could improve oxygenation and reduce pulmonary complications.

In the study by (Elhaddad et al., 2022) the authors compared three different ventilation
strategies during CPB: no mechanical ventilation (NOV), continuous positive airway
 pressure (CPAP) of 5 cmH2O, and low tidal volume (LTV) pressure-controlled
ventilation. They found that maintaining ventilation during CPB, particularly with the
LTV strategy, was linked to improved post-bypass oxygenation. However, there was no
significant reduction in postoperative pulmonary complications (PPCs) among the
different strategies.

(Padalino et al., 2022) also examined a ‘protective’ low-tidal/low-frequency ventilation

strategy during CPB in children with congenital heart disease. Their study found that
while this approach was deemed safe and benign, it did not provide substantial benefits
compared to non-ventilated patients in terms of postoperative ventilation time.

Mechanical Ventilation in Various Patient Populations

This group encompasses studies that assessed PEEP strategies in various contexts, such
as adult patients undergoing mechanical ventilation and animal models of acute
respiratory distress syndrome (ARDS).

(LI et al., 2022) conducted a meta-analysis to assess the effects of a driving pressure-
guided ventilation strategy in adult patients undergoing mechanical ventilation. They
compared this approach to a lung protective ventilation (LPV) strategy and aimed to
collect evidence from different randomized controlled trials. The paper demonstrates a
focus on optimizing mechanical ventilation strategies, although specific outcomes are not
detailed in the abstract.

(Wang et al., 2022) investigated the impact of varying tidal volumes on extravascular
lung water in piglet models of ARDS induced by paraquat. Their findings indicated that
employing a lung-protective ventilation approach with lower tidal volumes led to a
reduction in extravascular lung water and enhanced oxygenation when contrasted with
the use of higher tidal volumes.

Premature Infants with Respiratory Distress Syndrome

In the context of neonatal care, particularly for premature infants with respiratory
distress syndrome (RDS), different ventilation strategies can have long-term impacts on
respiratory outcomes.

(Solís-García et al., 2021) implemented a high-frequency oscillatory ventilation

(HFOV) strategy with volume guarantee (VG) as an early rescue therapy for severe RDS.
They reported improved respiratory outcomes at two years in preterm infants, including
higher survival without bronchopulmonary dysplasia (BPD) and fewer respiratory
treatments and hospital admissions.

The studies reviewed here illustrate ongoing research into the optimization of PEEP
strategies across different patient populations and clinical scenarios. While there is a
general consensus on the potential benefits of tailored ventilation strategies, more
research is needed to establish best practices and guidelines that can be applied
universally.
4.2 Research Gaps
The reviewed studies provide valuable insights into the use of different mechanical
ventilation strategies across various patient populations. However, there are several
research gaps and discrepancies that warrant further investigation.

Optimal Ventilation Strategies during CPB in Pediatric Cardiac Surgery

While the studies by (Elhaddad et al., 2022) and (Padalino et al., 2022)] evaluate the
impact of ventilation strategies during CPB on postoperative outcomes, there remains a
lack of consensus on the optimal approach. The discrepancy in the findings—the former
suggesting improved oxygenation with LTV and the latter finding no significant
advantage with low-tidal/low-frequency ventilation—highlights the need for more
research. Future studies could focus on larger sample sizes, long-term outcomes, and the
interaction between ventilation strategies and specific types of congenital heart defects.

Driving Pressure-Guided Ventilation Strategy in Adults

The meta-analysis by (LI et al., 2022) indicates an interest in driving pressure-guided
strategies but does not provide detailed outcomes, making it difficult to compare with
other studies. Research gaps include the need for standardized definitions and protocols
for driving pressure-guided ventilation, as well as direct comparisons with traditional
lung-protective strategies. Further studies should aim to provide clarity on patient-
centered outcomes, such as mortality, length of stay in the ICU, and long-term pulmonary
function.

Lung Protective Strategies in Models of ARDS

The study by (Bastarache & Blackwell, 2009; Rissel et al., 2022) in piglet models of
ARDS offers support for lung protective strategies using lower tidal volumes.
Nonetheless, the translation of results from animal models to human patients presents
challenges. There remains a lack of clarity on the applicability of these findings to
different types of human ARDS, which can be affected by factors such as the underlying
cause, patient comorbidities, and concurrent therapies. Moreover, the optimal trade-off
between reducing ventilator-induced lung injury and maintaining sufficient gas exchange
warrants additional investigation.

Long-term Outcomes in Neonatal Care

(Solís-García et al., 2021) demonstrate that a lung protection strategy with HFOV-VG
may enhance long-term respiratory outcomes in preterm infants. However, a research gap
exists in comprehending the mechanisms underlying these improved outcomes and their
generalizability to diverse settings or varying populations of preterm infants.
Furthermore, there is a scarcity of data concerning the neurodevelopmental consequences
of HFOV-VG, necessitating longitudinal studies to evaluate cognitive and motor
outcomes.

Methodological Considerations and Standardization

Across the studies, there is a need for greater standardization of ventilation strategies,
definitions of pulmonary complications, and outcome measures. Methodological
differences, such as the design of ventilation protocols, patient selection criteria, and
 follow-up duration, may contribute to discrepancies in findings. Standardizing these
elements could enhance the comparability of studies and facilitate the development of
evidence-based guidelines.

Future Research Directions

Future research should address these gaps by:
1. Conducting multicenter trials to validate findings and improve generalizability.
2. Exploring individualized ventilation strategies that account for patient heterogeneity.
3. Investigating the long-term pulmonary and neurodevelopmental effects of different
ventilation strategies in neonates and children.
4. Developing predictive models to identify patients who may benefit most from specific
ventilation strategies.
5. Integrating advanced monitoring techniques to optimize ventilator settings in real-time.

By addressing these research gaps, the medical community can move towards more
personalized and effective mechanical ventilation strategies that optimize outcomes for
patients with diverse respiratory needs.

4.3 Implications
The implications of the findings from these studies are both theoretical and practical,
offering valuable insights that may shape future research, clinical practice, and policy in
the field of mechanical ventilation.

Theoretical Implications
From a theoretical perspective, the studies collectively contribute to the evolving
understanding of lung mechanics and the pathophysiology of ventilator-induced lung
injury (VILI). The nuanced exploration of different PEEP strategies, including low-tidal
volume and pressure-controlled ventilation, and their variable effects on oxygenation and
lung protection, highlights the complexity of pulmonary responses to mechanical
ventilation. These findings challenge the one-size-fits-all theory of mechanical ventilation
and support a more individualized approach to ventilatory support. The growing body of
evidence suggests that lung protective strategies may need to be tailored not only to the
patient's condition but also to the specific phase of illness or surgery.

Practical Implications
Practically, the implications of these studies are significant for clinical practice. For
instance, the use of low-tidal volume ventilation during cardiopulmonary bypass in
pediatric cardiac surgery could become a standard practice if further research confirms its
benefits in oxygenation without increasing PPCs. In neonatal care, the positive outcomes
associated with high-frequency oscillatory ventilation could influence guidelines on
managing severe respiratory distress syndrome in preterm babies, potentially reducing the
incidence and severity of bronchopulmonary dysplasia.
 For adult patients with ARDS, the findings concerning lung protective strategies and
the potential benefits of driving pressure-guided ventilation could influence critical care
protocols and mechanical ventilation settings, potentially leading to decreased morbidity
and enhanced outcomes for this patient cohort.

Policy-wise, these studies may prompt healthcare systems to adopt new protocols and
invest in training for healthcare providers to apply evidence-based ventilation strategies.
This is especially pertinent in the realm of pediatric and neonatal intensive care, where
the stakes are high, and the margin for error is small.

Future Research Directions

The research points to the need for future studies that are more extensive and that seek
to standardize intervention protocols to allow for better comparison across studies.
Multicenter trials with larger sample sizes and diverse patient populations could help to
validate the findings and generalize them to broader clinical practice. There is also a need
to explore long-term outcomes, particularly in neonatal care, to understand the full impact
of early respiratory interventions on long-term neurodevelopmental and respiratory
health.

Advanced monitoring techniques, such as electrical impedance tomography or

biomarkers of lung injury, may play a role in future research to refine ventilation
strategies further and personalize care. Developing predictive models using artificial
intelligence could also assist clinicians in real-time decision-making for optimal
ventilator settings.

In conclusion, the research surveyed illustrates a gradual shift towards personalized

mechanical ventilation strategies that consider patient-specific characteristics and
responses to therapy. The practical application of these findings could lead to significant
improvements in patient outcomes and a reduction in the incidence of VILI and other
complications associated with mechanical ventilation. It also lays the groundwork for a
more nuanced theoretical understanding of respiratory physiology and the mechanics of
artificial ventilation.
 Chapter 4. Discussion
Based on this narrative review you can address the following :
Several potential limitations and challenges have been identified in implementing
personalized PEEP strategies. These include:

1.Lack of Consensus: currently, there is no consensus on the optimal method for

personalizing PEEP strategies based on patient-specific characteristics. Different studies
and experts may advocate for different approaches, making it challenging to establish
standardized guidelines.

2.Difficulty in Identifying Relevant Patient-Specific Characteristics: Determining the

patient-specific characteristics that should guide PEEP titration can be complex. Factors
such as lung compliance, severity of lung injury, chest wall compliance, and underlying
comorbidities may all play a role, but their relative importance and optimal thresholds
remain uncertain.

3.Variability in Measurement Techniques: The accurate measurement of patient-specific

characteristics, such as lung compliance or driving pressure, can be challenging and may
vary depending on the measurement technique used. Inconsistent or inaccurate
measurements can impact the reliability and applicability of personalized PEEP
strategies.

4. Limited Availability of Monitoring Tools: Some patient-specific characteristics that could

guide PEEP titration may require specialized monitoring tools or techniques that may not
be readily available in all clinical settings. This limitation can hinder the widespread
implementation of personalized PEEP strategies.

5. Time and Resource Constraints: Implementing personalized PEEP strategies may require
additional time and resources for data collection, analysis, and decision-making. This can
pose challenges in busy clinical settings where healthcare professionals may already be
facing time constraints.

6. Lack of Robust Evidence: Despite the increasing interest in personalized PEEP strategies,
the evidence supporting their effectiveness and impact on patient outcomes remains
limited. Well-designed clinical trials and large-scale studies are required to establish more
robust evidence for the implementation of personalized PEEP strategies.

7. Potential for Harm: Individualizing PEEP based on patient-specific characteristics carries

the risk of over- or underestimating the optimal PEEP level, which could potentially result
in harm to the patient. Balancing the potential benefits with the risk of unintended
consequences is crucial in the implementation of personalized PEEP strategies.

8. Training and Education: Implementing personalized PEEP strategies requires healthcare

professionals to have a deep understanding of the underlying principles and the ability to
 interpret and apply patient-specific data. Adequate training and education are essential to
ensure the safe and effective implementation of personalized PEEP strategies.

It is crucial to address these limitations and challenges to improve the feasibility and
clinical utility of personalized PEEP strategies and to facilitate their effective
implementation in routine clinical practice.

To address the lack of consensus in personalized PEEP strategies, several potential

solutions can be considered:

1.Conduct Well-Designed Clinical Trials: Well-designed randomized controlled trials

(RCTs) comparing various personalized PEEP strategies can assist in producing high-
quality evidence and establishing consensus. These trials should encompass a diverse
range of patient populations and integrate relevant patient-specific characteristics in
PEEP titration protocols.

2.Collaboration and Consensus-Building Efforts: Researchers, clinicians, and experts in the

field should collaborate and engage in consensus-building efforts to identify the most
relevant patient-specific characteristics and develop standardized guidelines for
personalized PEEP strategies. This can involve expert panels, consensus conferences, or
professional society guidelines.

3.Systematic Reviews and Meta-Analyses: Conducting systematic reviews and meta-

analyses of existing studies on personalized PEEP strategies can help synthesize the
available evidence and identify commonalities or trends across studies. This can
contribute to establishing a more standardized approach or identifying areas of agreement.

4.Development of Clinical Decision Support Tools: Developing and implementing clinical

decision support tools, such as computerized algorithms or predictive models, can aid
clinicians in personalizing PEEP strategies based on patient-specific characteristics.
These tools can provide real-time guidance and facilitate consistent decision-making.

5.Education and Training: offering education and training programs for healthcare
professionals on personalized PEEP strategies can improve their comprehension of the
fundamental principles and provide them with the essential skills to implement these
strategies proficiently. This may involve workshops, online courses, or educational
materials.

6.Multidisciplinary Approach: Emphasizing a multidisciplinary approach involving

respiratory therapists, intensivists, pulmonologists, and other healthcare professionals can
foster collaboration and knowledge sharing. This approach can help integrate expertise
from different disciplines and facilitate a consensus on personalized PEEP strategies.

7.Continuous Quality Improvement Initiatives: Implementing quality improvement

initiatives, such as audit and feedback programs or clinical practice guidelines, can help
 monitor and improve the implementation of personalized PEEP strategies over time.
Regular evaluation and feedback can contribute to refining and optimizing these
strategies.

8.Knowledge Translation and Dissemination: Promoting the dissemination of research

findings and best practices related to personalized PEEP strategies through publications,
conferences, and educational platforms can increase awareness and facilitate knowledge
translation. This can help bridge the gap between research and clinical practice.

Addressing the lack of consensus in personalized PEEP strategies requires a

collaborative and evidence-based approach, involving research, education, and a
multidisciplinary effort to establish standardized guidelines and improve clinical
implementation.
 Chapter 5. Conclusion
In summary, the studies reviewed provide valuable insights into mechanical ventilation
strategies across different clinical contexts. While they demonstrate progress in
developing individualized, lung-protective protocols, several research gaps remain that
could be addressed to further optimize outcomes. Large, multicenter studies are still
needed to validate findings and establish best practices through rigorous evidence. Future
research directions should also explore personalization approaches leveraging advanced
monitoring, long-term impacts, and theoretical frameworks integrating physiological
complexity. Addressing these gaps through collaborative, interdisciplinary efforts can
help realize the full potential of mechanical ventilation to precisely support respiratory
health and improve patient experiences worldwide.

This narrative review underscores the significance of incorporating patient-specific

characteristics in crafting personalized PEEP strategies. It is crucial to recognize the
potential impact of personalized PEEP strategies on enhancing patient outcomes. Further
research in this field is imperative to advance our understanding and implementation of
tailored ventilation approaches, ultimately improving respiratory health and patient
experiences.
 References
Baedorf Kassis, E., Loring, S. H., & Talmor, D. (2018). Should we titrate peep based on end-
expiratory transpulmonary pressure?-yes. Annals of Translational Medicine, 6(19), 390–
390. https://doi.org/10.21037/ATM.2018.06.35
Bastarache, J. A., & Blackwell, T. S. (2009). Development of animal models for the acute
respiratory distress syndrome. Disease Models & Mechanisms, 2(5–6), 218.
https://doi.org/10.1242/DMM.001677
Boesing, C., Graf, P. T., Schmitt, F., Thiel, M., Pelosi, P., Rocco, P. R. M., Luecke, T., & Krebs,
J. (2022). Effects of different positive end-expiratory pressure titration strategies during
prone positioning in patients with acute respiratory distress syndrome: a prospective
interventional study. Critical Care, 26(1). https://doi.org/10.1186/S13054-022-03956-8
Carpio, A. L. M., & Mora, J. I. (2023). Positive End-Expiratory Pressure. StatPearls.
https://www.ncbi.nlm.nih.gov/books/NBK441904/
Chikhani, M., Das, A., Haque, M., Wang, W., Bates, D. G., & Hardman, J. G. (2016). High
PEEP in acute respiratory distress syndrome: quantitative evaluation between improved
arterial oxygenation and decreased oxygen delivery. BJA: British Journal of Anaesthesia,
117(5), 650. https://doi.org/10.1093/BJA/AEW314
Coleman, M. H., & Aldrich, J. M. (2021). Acute Respiratory Distress Syndrome: Ventilator
Management and Rescue Therapies. Critical Care Clinics, 37(4), 851.
https://doi.org/10.1016/J.CCC.2021.05.008
Cutuli, S. L., Grieco, D. L., Michi, T., Cesarano, M., Rosà, T., Pintaudi, G., Menga, L. S.,
Ruggiero, E., Giammatteo, V., Bello, G., De Pascale, G., & Antonelli, M. (2023).
Personalized Respiratory Support in ARDS: A Physiology-to-Bedside Review. Journal of
Clinical Medicine 2023, Vol. 12, Page 4176, 12(13), 4176.
https://doi.org/10.3390/JCM12134176
Elhaddad, A. M., Youssef, M. F., Ebad, A. A., Abdelsalam, M. S., & Kamel, M. M. (2022).
Effect of Ventilation Strategy During Cardiopulmonary Bypass on Arterial Oxygenation
and Postoperative Pulmonary Complications After Pediatric Cardiac Surgery: A
Randomized Controlled Study. Journal of Cardiothoracic and Vascular Anesthesia, 36(12),
4357–4363. https://doi.org/10.1053/J.JVCA.2022.08.023
Fernandez-Bustamante, A., Hashimoto, S., Neto, A. S., Moine, P., Melo, M. F. V., & Repine, J.
E. (2015). Perioperative lung protective ventilation in obese patients. BMC Anesthesiology,
15(1). https://doi.org/10.1186/S12871-015-0032-X
Gattinoni, L., Caironi, P., Cressoni, M., Chiumello, D., Ranieri, V. M., Quintel, M., Russo, S.,
Patroniti, N., Cornejo, R., & Bugedo, G. (2006). Lung recruitment in patients with the acute
respiratory distress syndrome. The New England Journal of Medicine, 354(17), 1775–1786.
https://doi.org/10.1056/NEJMOA052052
Gordo, F., Parro, L., & Mohamed, M. (2022). Ventilation support in SARS-CoV-2 pneumonia.
Strategy and indications. Revista Española de Quimioterapia, 35(Suppl 1), 50.
https://doi.org/10.37201/REQ/S01.12.2022
Koritarova, V., & Georgiev, S. (2022). The Impact of Protective Ventilation Strategy, Applied in
Patients During Prolonged Gynecological Surgery, on Postoperative Oxygenation.
Proceedings of the Bulgarian Academy of Sciences, 75(1), 129–135.
https://doi.org/10.7546/CRABS.2022.01.15
LI, Y., ZHANG, Q., LIU, N., TAN, X. Y., YUE, H., & FANG, M. X. (2022). The effect of
driving pressure-guided ventilation strategy on the patients with mechanical ventilation: a
meta-analysis of randomized controlled trials. European Review for Medical and
Pharmacological Sciences, 26(16), 5835–5843.
https://doi.org/10.26355/EURREV_202208_29523
Mart, M. F., & Ely, E. W. (2020). Coronavirus Disease 2019 Acute Respiratory Distress
Syndrome: Guideline-Driven Care Should Be Our Natural Reflex. Critical Care Medicine,
48(12), 1835–1837. https://doi.org/10.1097/CCM.0000000000004627
Padalino, M. A., Vedovelli, L., Simonato, M., Bandini, A., Paganini, G., Mezzalira, L.,
Faganello, N., Carollo, C., Gregori, D., Vida, V., & Cogo, P. (2022). Protective continuous
ventilation strategy during cardiopulmonary bypass in children undergoing surgery for
congenital heart disease: a prospective study. Interactive Cardiovascular and Thoracic
Surgery, 35(2). https://doi.org/10.1093/ICVTS/IVAC084
Radhi, S. S., Freebairn, R. C., Chiew, Y. S., Chase, J. G., & Cove, M. E. (2023). Positive end-
expiratory pressure in acute respiratory distress syndrome; where have we been, where are
we going? Clinical Critical Care, 31(1), 2023:e0011-2023:e0011.
https://doi.org/10.54205/CCC.V31.262904
Rezoagli, E., & Bellani, G. (2019). How i set up positive end-expiratory pressure: Evidence- A
nd physiology-based! Critical Care, 23(1), 1–3. https://doi.org/10.1186/S13054-019-2695-
Z/FIGURES/1
Rissel, R., Renz, M., Mohnke, K., Riedel, J., Ritter, K., Ziebart, A., Ruemmler, R., Hartmann, E.
K., & Kamuf, J. (2022). Comparison of two porcine acute lung injury models: a post-hoc
analysis. Intensive Care Medicine Experimental, 10(1). https://doi.org/10.1186/S40635-
022-00466-3
Schmidt, M., Hajage, D., Lebreton, G., Monsel, A., Voiriot, G., Levy, D., Baron, E., Beurton, A.,
Chommeloux, J., Meng, P., Nemlaghi, S., Bay, P., Leprince, P., Demoule, A., Guidet, B.,
Constantin, J. M., Fartoukh, M., Dres, M., Combes, A., … Morawiec, E. (2020).
Extracorporeal membrane oxygenation for severe acute respiratory distress syndrome
associated with COVID-19: a retrospective cohort study. The Lancet Respiratory Medicine,
8(11), 1121–1131. https://doi.org/10.1016/S2213-2600(20)30328-3
Sklar, M. C., & Munshi, L. (2022). Advances in Ventilator Management for Patients with Acute
Respiratory Distress Syndrome. Clinics in Chest Medicine, 43(3), 499.
https://doi.org/10.1016/J.CCM.2022.05.002
Solís-García, G., González-Pacheco, N., Ramos-Navarro, C., Rodríguez Sánchez de la Blanca,
A., & Sánchez-Luna, M. (2021). Target volume-guarantee in high-frequency oscillatory
ventilation for preterm respiratory distress syndrome: Low volumes and high frequencies
lead to adequate ventilation. Pediatric Pulmonology, 56(8), 2597–2603.
https://doi.org/10.1002/PPUL.25529
Wang, J., Zeng, J., Zhang, C., Zheng, W., Huang, X., Zhao, N., Duan, G., & Yu, C. (2022).
Optimized ventilation strategy for surgery on patients with obesity from the perspective of
lung protection: A network meta-analysis. Frontiers in Immunology, 13, 1032783.
https://doi.org/10.3389/FIMMU.2022.1032783/FULL
Yamamoto, R., Sugimura, S., Kikuyama, K., Takayama, C., Fujimoto, J., Yamashita, K.,
Norisue, Y., & Narita, C. (2022). Efficacy of Higher Positive End-Expiratory Pressure
Ventilation Strategy in Patients With Acute Respiratory Distress Syndrome: A Systematic
Review and Meta-Analysis. Cureus, 14(7). https://doi.org/10.7759/CUREUS.26957
 Yang, G., Hu, C., & Sun, Z. (2022). An Updated Review of Driving-Pressure Guided Ventilation
Strategy and Its Clinical Application. BioMed Research International, 2022.
https://doi.org/10.1155/2022/6236438

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