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Modes of mechanical ventilation

Modes of mechanical ventilation refer to the various algorithms and patterns by which mechanical ventilators deliver positive pressure breaths to support or replace a patient's spontaneous respiration in cases of respiratory failure, such as hypoxemia or hypoventilation.^[1] These modes control key parameters including breath triggering, inspiratory flow, tidal volume or pressure limits, and cycle-off criteria, with the primary goals of maintaining adequate gas exchange, minimizing ventilator-induced lung injury, and facilitating patient-ventilator synchrony.^[1] They are essential in critical care settings for conditions like acute respiratory distress syndrome (ARDS), chronic obstructive pulmonary disease (COPD) exacerbations, or post-surgical recovery, where mechanical support is required to protect the airway and optimize oxygenation.^[1] Mechanical ventilation modes are broadly classified into volume-targeted and pressure-targeted categories, each with distinct advantages based on patient physiology and clinical needs.^[2] Volume-targeted modes, such as volume-assured or volume-limited assist-control (VAC), deliver a preset tidal volume (typically 4-8 mL/kg of ideal body weight) at a controlled respiratory rate (12-35 breaths per minute), ensuring consistent minute ventilation but potentially risking barotrauma if lung compliance decreases.^[1] In contrast, pressure-targeted modes, including pressure-limited assist-control (PAC), apply a fixed inspiratory pressure (usually 10-20 cm H₂O) to generate variable tidal volumes that adapt to changes in lung mechanics, offering better protection against overdistension but requiring monitoring to avoid inadequate ventilation.^[1] Additional common modes blend these principles or support weaning from ventilation. Synchronized intermittent mandatory ventilation (SIMV), often combined with pressure support ventilation (PSV at 5-15 cm H₂O), provides mandatory breaths synchronized with patient effort while allowing unsupported spontaneous breaths to promote respiratory muscle recovery.^[1] Pressure support alone assists patient-initiated breaths by augmenting inspiratory effort without mandatory timing, commonly used during weaning trials when patients meet criteria like PaO₂ ≥ 60 mmHg on FiO₂ ≤ 0.4.^[2] Advanced or nonconventional modes, such as airway pressure release ventilation (APRV), maintain sustained high airway pressure with brief releases to allow spontaneous breathing, reducing sedation needs and improving recruitment in ARDS.^[1] Mode selection involves interprofessional assessment of factors like underlying disease, airway resistance, and compliance, with ongoing adjustments to achieve lung-protective strategies and prevent complications like ventilator-associated pneumonia.^[1]

Fundamentals

Terminology

In mechanical ventilation, a ventilator breath refers to a mechanical breath delivered by the ventilator, which is characterized by the ventilator controlling the initiation, delivery, and termination of the breath based on preset parameters.^[3] These breaths are categorized into mandatory breaths, which are fully controlled by the ventilator without any patient effort, including both initiation and termination, as seen in fully controlled modes where the machine determines the timing and magnitude.^[3] In contrast, spontaneous breaths are initiated and controlled by the patient, with the ventilator providing supportive assistance such as pressure augmentation, allowing the patient to perform the work of breathing while receiving aid.^[3] The onset of a breath is determined by a trigger, which can be patient-initiated through detection of a pressure drop or flow change in the airway, or time-triggered by the ventilator's internal clock when no patient effort is sensed.^[3] The cycle marks the transition from inspiration to expiration, typically defined by criteria such as reaching a target volume, flow threshold, or time limit, ensuring the inspiratory phase ends appropriately to prevent overdistension or inadequate delivery.^[3] The control variable is the primary parameter regulated by the ventilator during breath delivery, most commonly volume (where a fixed tidal volume is delivered regardless of pressure changes) or pressure (where a set pressure is maintained, allowing volume to vary based on lung mechanics).^[3] Breath sequences describe the overall pattern of breath delivery, such as continuous mandatory ventilation (CMV), where all breaths are mandatory and ventilator-controlled without allowance for spontaneous efforts; intermittent mandatory ventilation (IMV), which intersperses mandatory breaths with opportunities for spontaneous breathing; and continuous spontaneous ventilation (CSV), where all breaths are patient-initiated with ventilator support.^[3] These sequences form the foundation for classifying ventilation modes but are elaborated further in dedicated sections on taxonomy. Inspiratory flow patterns dictate how gas is delivered during the breath, influencing pressure dynamics and alveolar recruitment. Constant flow (also known as square wave) maintains a steady rate throughout inspiration, which can lead to higher peak pressures but simpler volume control.^[4] Decelerating flow starts with high initial flow that tapers off toward zero at end-inspiration, promoting better gas distribution by allowing more time for peripheral alveoli to fill and reducing dead space ventilation, thereby improving oxygenation and CO2 elimination in heterogeneous lung conditions.^[5] Sinusoidal flow follows a smooth, wave-like pattern mimicking natural breathing, which may enhance comfort but has less pronounced effects on gas exchange compared to decelerating patterns in critically ill patients.^[6] Overall, decelerating patterns are associated with more uniform gas distribution across lung regions due to prolonged low-flow phases that facilitate collateral ventilation pathways.^[7] Mechanical ventilation is distinguished by its delivery interface: invasive ventilation requires an artificial airway, such as an endotracheal tube inserted through the mouth or nose into the trachea, or a tracheostomy tube directly into the windpipe, enabling direct control but increasing risks like infection and laryngeal injury.^[8] Non-invasive ventilation (NIV), conversely, provides support without tracheal intubation, using masks or nasal interfaces to deliver positive pressure, which preserves natural airway anatomy and reduces complications like ventilator-associated pneumonia, though it may be less effective in severe cases requiring full control.^[8]

Basic Principles

Mechanical ventilation involves the use of devices to assist or replace spontaneous breathing in patients with respiratory failure, evolving significantly since its inception in the early 20th century. The earliest forms, such as the iron lung—a negative-pressure ventilator developed in the 1920s and widely used during the 1952 polio epidemic—enclosed the patient's body to create pressure changes that facilitated respiration.^[9] By the mid-20th century, positive-pressure ventilators emerged, delivering air directly into the lungs via endotracheal tubes, marking a shift toward more invasive but controllable methods. Modern microprocessor-controlled ventilators, introduced in the 1970s and refined through the 21st century, incorporate advanced sensors, algorithms, and user interfaces to support precise delivery of breaths tailored to patient needs.^[9] Understanding mechanical ventilation requires foundational knowledge of respiratory mechanics, governed by the equation of motion for the respiratory system: P(t) = E \times V(t) + R \times \dot{V}(t) + P_{mus}(t), where P(t) is the pressure applied, E is elastance (the inverse of compliance), V(t) is volume, R is resistance, \dot{V}(t) is flow rate, and P_{mus}(t) accounts for respiratory muscle pressure.^[10] Compliance (C), which measures lung and chest wall elasticity, is derived as the change in volume per unit change in pressure: C = \frac{\Delta V}{\Delta P}; it quantifies how easily the lungs expand under pressure, with normal values around 50–100 mL/cm H₂O in adults.^[10] Resistance (R), representing opposition to airflow in airways, is calculated as the change in pressure per unit change in flow: R = \frac{\Delta P}{\Delta \dot{V}}; typical values range from 5–15 cm H₂O/L/s, reflecting frictional losses that increase with conditions like bronchospasm.^[10] These parameters underpin ventilator control, ensuring breaths align with physiological demands without excessive work of breathing. The operational principles of all mechanical ventilation modes are encapsulated in a taxonomy comprising 10 fundamental maxims, originally proposed in 2014.^[10] These maxims provide a systematic framework for classifying modes based on breath delivery mechanics:

The ventilatory cycle is defined by the flow-time curve, distinguishing inspiration (positive flow) from expiration (negative flow).^[10]
Assisted ventilation requires the ventilator to perform some or all of the work of breathing.^[10]
Control is achieved by either pressure (PC) or volume (VC), derived from the equation of motion.^[10]
Classification occurs by the variables that trigger (initiate) and cycle (terminate) inspiration.^[10]
Triggers and cycles can be initiated by the patient or the machine.^[10]
Cycles are categorized as spontaneous (both trigger and cycle patient-initiated) or mandatory (machine-initiated trigger, cycle, or both).^[10]
Breath sequences include continuous mandatory ventilation (CMV), intermittent mandatory ventilation (IMV), and continuous spontaneous ventilation (CSV).^[10]
Basic patterns encompass combinations like VC-CMV, reflecting control variable and sequence.^[10]
Seven targeting schemes—set-point, dual, bio-variable, servo, adaptive, optimal, and intelligent—differentiate mode types within patterns.^[10]
Full classification integrates the control variable, breath sequence, and targeting schemes.^[10]

This framework ensures consistent application across ventilators, emphasizing patient-ventilator synchrony and clinical efficacy.^[10]

Classification and Taxonomy

Classification Criteria

Mechanical ventilation modes are classified using a standardized taxonomy based on three primary axes: the control variable, the breath sequence, and the targeting scheme. This framework, originally proposed in 2014, enables precise description and comparison of modes by focusing on how the ventilator delivers breaths rather than proprietary trade names. The control variable represents the primary input manipulated by the ventilator to generate a breath, while the breath sequence defines the pattern of mandatory versus spontaneous breaths, and the targeting scheme outlines the method for achieving breath targets. The control variable is the foundational axis, distinguishing between volume-controlled (VC) and pressure-controlled (PC) modes. In VC modes, the ventilator delivers a fixed tidal volume, allowing airway pressure to vary based on patient lung compliance and resistance, which helps ensure consistent minute ventilation but may risk barotrauma if pressures rise excessively. Conversely, PC modes apply a fixed inspiratory pressure, resulting in variable tidal volumes that adapt to changes in lung mechanics, potentially reducing the risk of volutrauma but requiring monitoring to avoid hypoventilation. This dichotomy forms the basis for mode nomenclature, such as VC-CMV or PC-IMV. Breath sequences provide an overview of how breaths are initiated and terminated, categorized into three main types: continuous mandatory ventilation (CMV), intermittent mandatory ventilation (IMV), and continuous spontaneous ventilation (CSV). CMV involves all breaths being mandatory, either time-triggered or patient-triggered but always machine-cycled to ensure full ventilator support. IMV combines mandatory breaths (machine-timed or synchronized) with spontaneous breaths allowed between them, promoting partial patient effort while maintaining a minimum ventilation level. CSV, in contrast, consists entirely of patient-initiated and patient-cycled breaths, with the ventilator providing support only upon demand, suitable for weaning. Targeting schemes describe the algorithmic approach to meeting breath targets, encompassing seven categories denoted by letters for concise labeling: set point (s), dual (d), biovariable (b), servo (r), adaptive (a), optimal (o), and intelligent (i). Set point targeting maintains a single operator-defined variable at a constant level, such as fixed flow in VC modes. Dual control switches between pressure and volume targets dynamically, biovariable allows two variables to vary within limits, and servo uses proportional feedback for real-time adjustments. Adaptive schemes modify parameters based on patient-specific needs like auto-PEEP, optimal targeting minimizes physiological work (e.g., of breathing), and intelligent approaches incorporate predictive models or AI for decision-making. The 2025 taxonomy update refines this system by introducing a "variety" level to denote sub-variations, such as specific triggering mechanisms, exemplified by PC-CSVr[Flow] for flow-triggered pressure-controlled continuous spontaneous ventilation with servo targeting. This addition enhances granularity without altering the core axes, promoting global standardization particularly in multilingual clinical settings.

Breath Sequences

Breath sequences in mechanical ventilation classify the patterns by which mandatory (ventilator-delivered) and spontaneous (patient-initiated) breaths are timed and initiated, forming a core component of mode taxonomy alongside control variables like pressure or volume targeting. This classification distinguishes three primary sequences: continuous mandatory ventilation (CMV), intermittent mandatory ventilation (IMV), and continuous spontaneous ventilation (CSV). These sequences determine the level of ventilatory support, patient autonomy, and potential for synchrony, guiding clinical selection based on patient condition.^[10] In CMV, all breaths are mandatory, delivered consecutively without allowance for spontaneous breaths in between, ensuring total ventilator control over the respiratory cycle. Breaths are initiated either by a preset timer (time-triggered) or by the patient's inspiratory effort (patient-triggered), but the ventilator always cycles off the breath to prevent interruptions. This sequence is essential for full support in apneic patients or those with profound respiratory muscle weakness, as it guarantees a minimum respiratory rate and tidal volume regardless of patient effort. A subtype, CMV(1), denotes the fully controlled variant where breaths are exclusively time-triggered, eliminating any patient influence on timing for maximum precision in severe cases.^[10]^[11] IMV permits spontaneous breaths between periodic mandatory breaths, allowing partial patient control while maintaining a backup rate to ensure adequate ventilation. Mandatory breaths are typically time-triggered but can synchronize with patient efforts in advanced variants, with spontaneous breaths patient-triggered and cycled. Originally introduced in the 1970s, IMV has evolved significantly; by 2022, it was classified into four subtypes based on interaction between mandatory and spontaneous breathing, with further expansion to five types in 2025 classifications incorporating adaptive features. IMV(1) delivers mandatory breaths asynchronously at a fixed rate, regardless of patient activity, prioritizing reliability over synchrony. IMV(2) suppresses mandatory breaths if the patient's spontaneous rate exceeds the set backup, enhancing comfort during active breathing. IMV(3) adjusts based on minute ventilation, omitting mandatory breaths when patient output meets or exceeds targets. IMV(4) allows patient efforts to convert mandatory breaths into assisted spontaneous ones, improving synchrony. The 2025 expansion introduces IMV(5) as an adaptive subtype that dynamically modifies mandatory breath delivery using real-time physiological feedback, such as end-tidal CO2 or work of breathing, for optimized support. Clinically, IMV suits partial support scenarios, facilitating weaning by encouraging spontaneous efforts while preventing hypoventilation.^[11]^[12] CSV consists entirely of spontaneous breaths, with the ventilator providing no mandatory breaths; all cycles are patient-triggered and patient-cycled, often augmented by support like pressure assistance. This sequence relies on intact patient respiratory drive and is contraindicated in apneic states. It is primarily employed during weaning trials to assess readiness for liberation from mechanical ventilation, as it evaluates the patient's ability to maintain adequate ventilation independently.^[10] Overall, CMV offers comprehensive support for critical instability, IMV balances assistance with autonomy for transitioning patients, and CSV promotes independence in recovery phases, with selection influenced by factors like respiratory drive and synchrony needs.^[11]

Targeting Schemes

Targeting schemes in mechanical ventilation refer to the algorithms and control strategies employed by ventilators to achieve desired respiratory targets, such as tidal volume (V_T), pressure, or minute ventilation. These schemes form a key component of the taxonomic classification of ventilation modes, alongside control variables and breath sequences. The seven established targeting schemes—set point, dual, biovariable, servo, adaptive, optimal, and intelligent—provide a framework for how ventilators interact with patient physiology, ranging from fixed operator inputs to advanced automated adjustments. This classification, originally formalized in 2014 and updated in subsequent reviews including the 2025 taxonomy, ensures standardized terminology and facilitates clinical decision-making by matching schemes to patient needs, such as stability or variability in respiratory mechanics.^[10]^[13] The set point (s) scheme involves the operator manually setting fixed values for key parameters, such as constant tidal volume in volume-controlled modes or fixed inspiratory pressure in pressure-controlled modes. The ventilator uses basic feedback to deliver breaths that adhere strictly to these presets without automatic variation, ensuring predictable delivery in controlled environments. This scheme is widely applied in stable, sedated patients where consistency is prioritized over adaptability, as seen in volume-controlled continuous mandatory ventilation (VC-CMV), minimizing risks of over- or under-ventilation in postoperative care. Its simplicity stems from direct operator control, making it a foundational approach in most modern ventilators.^[10]^[13] In contrast, the dual (d) scheme controls two variables simultaneously within a breath, such as pressure and flow, by switching between control strategies to meet dual targets like limiting peak pressure while achieving a set tidal volume. The mechanism relies on the ventilator dynamically prioritizing one variable over the other based on real-time feedback, often starting with one control (e.g., pressure) and adjusting to another (e.g., volume) if limits are exceeded. Clinically, this is useful in patients with variable lung compliance, such as those with acute respiratory distress syndrome (ARDS), where it balances safety and efficacy; for example, it appears in hybrid modes on ventilators like the Dräger Evita series to prevent barotrauma while maintaining ventilation goals.^[10] The biovariable (b) scheme introduces variability by automatically adjusting two parameters, such as tidal volume and respiratory rate, based on patient feedback to mimic natural breathing patterns and avoid monotony. It operates by randomly varying outputs within physiological limits (e.g., 0-100% variability in pressure support), promoting better gas exchange and reducing ventilator-induced lung injury through enhanced recruitment. This approach is particularly beneficial during weaning from mechanical ventilation, where it supports spontaneous efforts in recovering patients, as implemented in variable pressure support modes on devices like the Maquet Servo-i, improving outcomes in prolonged ventilation scenarios.^[10]^[13] Servo (r) targeting employs a feedback control system where the ventilator output (e.g., pressure) automatically follows a varying input signal generated by the patient (e.g., inspiratory effort), using proportional adjustments. For example, in neurally adjusted ventilatory assist (NAVA), the mechanism is given by P(t) = \text{NAVA level} \times \text{EAdi}(t) where EAdi is the electrical activity of the diaphragm. This approach excels in dynamic conditions like proportional assist ventilation (PAV), where it amplifies patient effort to reduce imposed work of breathing, commonly used in weaning for patients with intact respiratory drive on ventilators such as the Puritan Bennett 840.^[10]^[14] The adaptive (a) scheme automatically adjusts targets in response to physiological changes, such as tuning inspiratory pressure to maintain a desired tidal volume despite variations in lung compliance or resistance. It functions by evaluating breath-to-breath feedback (e.g., delivered V_T) and incrementally modifying the primary control variable, often over several breaths, to achieve long-term goals like average minute ventilation. This is clinically advantageous in evolving conditions like ARDS or during transport, exemplified in pressure-regulated volume control (PRVC) modes on the Maquet Servo-i, where it provides consistent ventilation with reduced risk of volutrauma; studies highlight its role in minimizing clinician interventions in ICU settings.^[10]^[13] Optimal (o) targeting uses algorithms to minimize or maximize a performance criterion, such as work of breathing or oxygen consumption, by dynamically optimizing multiple parameters like tidal volume and rate. The mechanism involves iterative computations based on patient-specific data (e.g., compliance and effort metrics) to select the "best" ventilatory pattern from a range of options, often incorporating closed-loop control. It is applied in advanced support for passive or weaning patients, as in adaptive support ventilation (ASV) on Hamilton ventilators, where it automates adjustments to enhance efficiency and comfort, particularly in resource-limited ICUs as per high-impact reviews.^[10]^[14] Finally, the intelligent (i) scheme leverages artificial intelligence or machine learning for predictive adjustments, analyzing complex data patterns (e.g., waveforms, gas exchange) to proactively optimize ventilation beyond rule-based methods. Emerging prominently in 2025 ventilators, it employs techniques like fuzzy logic or neural networks to define a "zone of comfort" by integrating variables such as PCO_2, SpO_2, and patient effort, adapting in real-time to prevent desynchrony or deterioration. Clinical applications focus on high-acuity cases like sepsis-induced respiratory failure, with implementations in systems like Dräger's SmartCare/PS, showing promise in reducing ventilation duration through automated weaning protocols in recent trials.^[10]^[13]

Volume-Controlled Modes

Volume-Controlled Continuous Mandatory Ventilation (VC-CMV)

Volume-controlled continuous mandatory ventilation (VC-CMV) is a foundational mode of mechanical ventilation that provides full ventilatory support by delivering a predetermined tidal volume regardless of the patient's respiratory effort. In this mode, breaths are either patient-triggered or machine-triggered and time-cycled, ensuring a fixed tidal volume (VT) of 4-8 mL/kg ideal body weight is administered with a constant flow waveform.^[1]^[15] The constant inspiratory flow typically ranges from 40-60 L/min, resulting in a square wave pressure profile where peak inspiratory pressure (PIP) varies based on lung compliance and airway resistance.^[1] Key settings for VC-CMV include a respiratory rate (RR) of 12-20 breaths per minute and an inspiratory-to-expiratory (I:E) ratio of 1:2, which can be adjusted to optimize gas exchange while preventing auto-PEEP.^[1]^[15] PIP is not directly set but monitored, ideally kept below 35 cm H₂O to minimize injury, as it fluctuates with changes in pulmonary mechanics.^[15] This mode operates within a continuous mandatory ventilation sequence, delivering mandatory breaths that can be triggered by the patient or the machine, with synchronization to patient efforts when detected.^[1] VC-CMV is indicated for apneic patients or those with acute respiratory failure lacking spontaneous breathing efforts, such as in postoperative recovery or severe hypoventilation.^[1] It ensures reliable minute ventilation (VE), calculated as VE = VT × RR, derived from the product of the volume delivered per breath and the number of breaths per minute to maintain adequate alveolar ventilation.^[15]^[1] The primary advantage of VC-CMV is the guaranteed delivery of the set VT, providing consistent ventilation independent of patient or lung variability.^[1] However, it carries risks of barotrauma due to potentially high PIP in non-compliant lungs, necessitating close monitoring of plateau pressures and compliance.^[1]^[15]

Synchronized Intermittent Mandatory Ventilation (SIMV) with Volume Control

Synchronized intermittent mandatory ventilation (SIMV) with volume control is a partial ventilatory support mode that combines mandatory breaths delivered at a preset tidal volume with opportunities for spontaneous breathing, enhancing patient-ventilator synchrony during weaning. In this mode, the ventilator delivers a fixed number of mandatory breaths per minute, each with a clinician-set tidal volume, while permitting the patient to initiate additional spontaneous breaths between them. Unlike fully controlled modes, SIMV allows patients with intact respiratory drives to contribute to their ventilation, promoting gradual independence from mechanical support.^[16] The mechanism involves time-triggered mandatory breaths that can be patient-synchronized if an inspiratory effort is detected within a specific timing window, typically reducing the risk of breath stacking or asynchrony. If the patient does not trigger within the window, the ventilator delivers the mandatory breath asynchronously to maintain the set rate. Spontaneous breaths, detected by a drop in airway pressure, are not volume-guaranteed but can be augmented with pressure support to decrease the work of breathing. This hybrid approach ensures a baseline level of ventilation while accommodating variable patient effort.^[16]^[2] Typical settings for SIMV with volume control include a tidal volume of 6-8 mL/kg of ideal body weight for mandatory breaths to promote lung-protective ventilation, a mandatory respiratory rate of 8-12 breaths per minute during weaning phases, and optional pressure support of 5-10 cm H₂O for spontaneous breaths to improve comfort and efficiency. These parameters are adjusted based on patient response, arterial blood gases, and clinical goals, with the mandatory rate progressively reduced as tolerance improves.^[17]^[16]^[18] SIMV with volume control is indicated for weaning from mechanical ventilation in patients exhibiting partial respiratory drive, such as those recovering from acute respiratory failure, and for maintaining alveolar ventilation in scenarios where full control is unnecessary. It is particularly suitable for patients who can initiate breaths but require supplemental mandatory support to prevent fatigue or hypoventilation. In contemporary classifications, SIMV represents the IMV(1) subtype, emphasizing synchronization of mandatory breaths with patient efforts to optimize interaction.^[16]^[11] Key advantages include reduced patient-ventilator asynchrony compared to unsynchronized intermittent mandatory ventilation, improved comfort through breath synchronization, and facilitation of weaning by allowing progressive reduction in mandatory support while monitoring spontaneous contributions. The effective minute ventilation (VE) in this mode accounts for both components and is calculated as:

VE = (VT_{mand} \times RR_{mand}) + (VT_{spon} \times RR_{spon})

where VT_{mand} is the mandatory tidal volume, RR_{mand} is the mandatory respiratory rate, VT_{spon} is the average spontaneous tidal volume, and RR_{spon} is the spontaneous respiratory rate; this equation derives from summing the controlled ventilator-delivered volume and the patient's independent ventilatory effort to yield total alveolar ventilation per minute.^[16]^[2]

Volume Guarantee

Volume Guarantee (VG) is an adaptive, volume-targeted mode of mechanical ventilation primarily utilized in neonatal care to deliver a consistent tidal volume (VT) while limiting peak inspiratory pressure (PIP) to protect against lung injury. Developed for use in preterm and term infants, VG combines elements of pressure-limited and volume-controlled ventilation by automatically adjusting the inspiratory pressure on a breath-to-breath basis based on the measured expired VT from the previous breath. This ensures a target VT of 4-6 mL/kg ideal body weight, reducing variability in delivered volumes that can occur due to changing lung compliance or patient effort.^[19] The mechanism involves setting a maximum pressure limit, beyond which the ventilator does not exceed to prevent barotrauma, while the inspiratory pressure is dynamically adjusted to achieve the preset VT. In many implementations, such as on the Dräger Babylog or AVEA ventilators, the system measures expired VT using a flow sensor at the proximal airway and employs an algorithm to modulate PIP; some systems initiate this with test breaths to estimate initial lung compliance before ongoing adaptive adjustments. Compliance (C) is derived from prior breaths, allowing the ventilator to respond to changes in lung mechanics, such as improving compliance in recovering neonates. The adjustment follows the rearranged compliance formula:

\text{PIP} = \left( \frac{\text{Target } V_T}{C} \right) + \text{PEEP}

where this derives from the basic dynamic compliance equation C = \frac{V_T}{\text{PIP} - \text{PEEP}}. Key settings include the target VT (typically 4-5 mL/kg for respiratory distress syndrome), a maximum PIP limit (initially 25-30 cm H₂O, set 5-10 cm H₂O above expected working pressure), and a backup respiratory rate (usually <40 breaths/min to allow spontaneous breathing). The targeting scheme is adaptive (denoted as "a" in classifications), responding to real-time feedback without fixed set-points.^[19]^[20] VG is indicated for neonates with respiratory distress syndrome (RDS) and other forms of respiratory failure, where maintaining stable VT helps avoid inadvertent hyper- or hypoventilation. In taxonomies of mechanical ventilation modes, VG is classified as a pressure-controlled mode with adaptive volume targeting, such as PC-IMVa (pressure-controlled intermittent mandatory ventilation, adaptive), emphasizing its role in synchronized mandatory breath delivery with volume assurance. Advantages include protection against volutrauma by minimizing excessive VT excursions—studies show VG reduces VT variability by over 60% compared to pressure-limited modes—and facilitates automatic weaning as compliance improves, shortening ventilation duration without increasing hypocarbia risk. Systematic reviews confirm lower rates of bronchopulmonary dysplasia and intraventricular hemorrhage in preterm infants using VG versus traditional pressure-limited ventilation.^[19]

Pressure-Controlled Modes

Pressure-Controlled Continuous Mandatory Ventilation (PC-CMV)

Pressure-controlled continuous mandatory ventilation (PC-CMV) is a mode of mechanical ventilation in which the ventilator delivers mandatory breaths at a predetermined inspiratory pressure level, typically referred to as peak inspiratory pressure (PIP), while maintaining a constant airway pressure throughout inspiration. This is achieved through a decelerating flow waveform, where the initial flow is high and progressively decreases to sustain the set pressure until the inspiratory time ends, making the mode time-cycled. The resulting tidal volume (VT) is not fixed but varies inversely with changes in lung compliance and airway resistance; for instance, improved compliance leads to higher VT for the same PIP, promoting uniform alveolar distention and potentially better ventilation-perfusion matching.^[21]^[22]^[23] Key settings in PC-CMV include the PIP (commonly 15-30 cmH2O to achieve target VT of 6-8 mL/kg ideal body weight), respiratory rate (RR, typically 12-20 breaths per minute), and inspiratory-to-expiratory (I:E) ratio (often 1:2 to allow adequate expiratory time and prevent auto-PEEP). Positive end-expiratory pressure (PEEP) is also set to maintain alveolar recruitment, usually starting at 5-10 cmH2O and titrated based on oxygenation goals. The mode operates on a set-point targeting scheme, where the ventilator prioritizes maintaining the operator-defined pressure targets during inspiration, with breaths delivered at the set RR if not patient-triggered.^[21]^[24]^[25] PC-CMV is particularly indicated in patients with acute respiratory distress syndrome (ARDS) to limit barotrauma risk by capping inspiratory pressures and avoiding excessive VT delivery in non-compliant lungs. Its advantages include lower peak airway pressures compared to volume-targeted modes, which can reduce ventilator-induced lung injury, and improved patient-ventilator synchrony due to the pressure-limited delivery.^[21]^[26]^[27] Tidal volume in PC-CMV can be estimated using the relationship derived from respiratory system compliance, where the change in volume is proportional to the applied pressure difference across the system. The equation is:

V_T = C \times (PIP - PEEP)

Here, C represents static compliance (in mL/cmH₂O), PIP is the set peak inspiratory pressure, and PEEP is the positive end-expiratory pressure; this derivation stems from the basic definition of compliance as \Delta V / \Delta P, assuming negligible resistance effects during the plateau phase. Clinicians monitor exhaled VT to adjust PIP iteratively, ensuring protective ventilation targets are met.^[21]^[22]

Pressure-Regulated Volume Control (PRVC)

Pressure-Regulated Volume Control (PRVC) is an adaptive dual-control mode of mechanical ventilation that ensures delivery of a preset tidal volume (VT) while dynamically limiting peak inspiratory pressure (PIP) to protect against barotrauma. This hybrid approach integrates elements of both volume- and pressure-targeted ventilation, delivering breaths with a decelerating flow waveform similar to pressure-controlled modes but adjusting the pressure level breath by breath to meet the volume target. PRVC is classified under continuous mandatory ventilation schemes and is particularly valued for its ability to adapt to changes in patient lung mechanics without clinician intervention.^[28] The mechanism of PRVC initiates with a test breath, during which the ventilator delivers a low-pressure breath (typically at 5 cmH2O above PEEP) to estimate the patient's respiratory system compliance and determine the initial PIP required to achieve the target VT, usually set at 6-8 mL/kg of predicted body weight. Subsequent breaths are pressure-limited and time-cycled, with the ventilator monitoring the delivered VT from the previous breath (or an average of recent breaths, depending on the device) and incrementally adjusting the PIP upward or downward to correct any volume discrepancy. This adjustment employs an error-correction strategy based on estimated compliance (C), approximated by the relation ΔPIP = (Target VT - Delivered VT) / C, derived from the fundamental equation of motion VT ≈ C × (PIP - PEEP), enabling precise volume guarantee while capping PIP to avoid excessive pressure. Flow decelerates throughout inspiration to promote homogeneous gas distribution and reduce work of breathing.^[29]^[28] Clinically, PRVC requires settings for target VT, maximum PIP (typically 30-35 cmH2O), respiratory rate (RR), and inspiratory time (Ti), with breaths triggered by patient effort or time. In the 2025 updated taxonomy of mechanical ventilation modes, it is denoted as PC-CMVa, signifying pressure-controlled continuous mandatory ventilation with adaptive volume targeting. This mode is indicated for scenarios involving variable lung compliance, such as pulmonary edema or acute respiratory distress syndrome (ARDS), where traditional fixed-pressure modes might under- or over-deliver VT, risking hypoventilation or volutrauma. By combining the consistency of volume control with pressure limitation, PRVC enhances ventilator-patient synchrony, minimizes peak pressures, and supports lung-protective strategies, potentially reducing ventilator-induced lung injury in heterogeneous lung conditions.^[13]^[30]^[28] However, controversies surround the widespread adoption of adaptive modes like PRVC. While small studies suggest benefits in reducing peak pressures and improving synchrony, large randomized controlled trials are lacking, and evidence does not demonstrate clear superiority in outcomes like ventilation duration or survival. Critics note that PRVC may not guarantee constant VT in cases of patient effort or rapid compliance changes, as the ventilator cannot distinguish these, and warn against a "set it and forget it" approach, recommending vigilant monitoring rather than universal use.^[31]^[28]

Airway Pressure Release Ventilation (APRV)

Airway pressure release ventilation (APRV) is a time-cycled, pressure-targeted mode of mechanical ventilation that permits spontaneous breathing throughout the respiratory cycle while applying prolonged periods of high airway pressure interspersed with brief releases to a lower pressure level. This approach maintains continuous positive airway pressure (CPAP) at the higher level (P_high), typically set between 20 and 30 cmH₂O, to promote alveolar recruitment and stability, followed by short releases to P_low (usually 0 to 5 cmH₂O) for carbon dioxide elimination. Unlike mandatory ventilation modes that dictate breath timing, APRV allows unrestricted spontaneous breaths at any point, enhancing patient-ventilator synchrony and reducing the need for sedation. The mode originated from foundational work demonstrating its potential for simultaneous CPAP support and CO₂ removal in patients with acute lung injury.^[32] Key settings in APRV include P_high, P_low, T_high (duration at P_high, typically 4 to 6 seconds), and T_low (duration of release, 0.5 to 1 second), all adjusted as set points by the clinician to balance recruitment and ventilation. These parameters create an inverse inspiratory-to-expiratory ratio, with T_high comprising the majority of the cycle to sustain lung openness. In modern implementations, particularly as of 2025, APRV functions as a variant of pressure-controlled continuous spontaneous ventilation (PC-CSV), emphasizing pressure-limited delivery while supporting ongoing spontaneous efforts.^[32]^[33] APRV is primarily indicated for acute respiratory distress syndrome (ARDS) to facilitate lung recruitment and improve oxygenation through sustained high pressures that counteract alveolar collapse. By optimizing ventilation-perfusion matching and preserving spontaneous breathing, it reduces ventilator-induced lung injury compared to conventional modes. The mean airway pressure (MAP), which influences oxygenation, is approximated by the time-weighted average of the pressure levels:

\text{MAP} \approx \frac{T_{\text{high}} \cdot P_{\text{high}} + T_{\text{low}} \cdot P_{\text{low}}}{T_{\text{high}} + T_{\text{low}}}

This derivation reflects the proportional contribution of each phase to the overall cycle, with longer T_high elevating MAP to enhance oxygen delivery without excessive peak pressures.^[34]^[32] Despite these potential benefits, APRV remains controversial. Common misconceptions include claims that it causes barotrauma or volutrauma due to high pressures or tidal volumes, though evidence from randomized trials shows no increased risk when properly set. As of 2025, meta-analyses indicate possible improvements in oxygenation and ventilator days with early APRV use in ARDS, but results are heterogeneous, and no large multicenter RCTs confirm superiority over low tidal volume ventilation. Proper settings, such as the time-controlled adaptive ventilation (TCAV) approach, are emphasized to avoid adverse effects.^[35]^[36]

Spontaneous and Support Modes

Continuous Positive Airway Pressure (CPAP)

Continuous Positive Airway Pressure (CPAP) is a non-invasive mode of mechanical ventilation that provides a constant level of positive pressure to the airways throughout the entire respiratory cycle, supporting spontaneous breathing without delivering mandatory breaths.^[37] The patient determines their own respiratory rate and tidal volume (VT), while the ventilator maintains airway patency by counteracting collapse, particularly in the upper airways, and preventing atelectasis in the alveoli.^[37] This mechanism enhances oxygenation by recruiting collapsed lung units and improving ventilation-perfusion matching through stabilization of functional residual capacity.^[37] Typical CPAP settings involve a fixed positive end-expiratory pressure (PEEP) level ranging from 5 to 15 cmH₂O, titrated based on patient needs starting at 5 cmH₂O and increased in increments of 1-2 cmH₂O to achieve adequate oxygenation and ventilation.^[37] Additional parameters may include oxygen supplementation via a fraction of inspired oxygen (FiO₂) adjusted to maintain target saturation levels, and optional humidification to prevent mucosal drying.^[37] In some systems, automatic adjustments are available, such as in Auto-CPAP devices designed for specific conditions like obstructive sleep apnea (OSA), where pressure modulates in response to detected airflow limitations.^[37] CPAP is primarily indicated for obstructive sleep apnea (OSA), where it splints open the upper airway to eliminate apneic events and reduce associated cardiovascular risks.^[37] It is also used in acute cardiogenic pulmonary edema to alleviate respiratory distress by decreasing preload and afterload on the heart, thereby improving cardiac output and gas exchange.^[38] Key advantages include a significant reduction in the work of breathing compared to unassisted spontaneous ventilation, as the constant pressure offloads respiratory muscles and minimizes the effort required for inspiration.^[37] A notable variant is auto-positive airway pressure (APAP), which automatically titrates the pressure level within a preset range (typically 4-20 cmH₂O) based on real-time detection of respiratory events like apneas, hypopneas, or flow limitations using built-in algorithms and sensors.^[37] This adaptive approach contrasts with fixed CPAP by providing lower average pressures during stable breathing periods, potentially improving patient comfort and adherence without compromising efficacy in treating OSA.^[39]

Pressure Support Ventilation (PSV)

Pressure support ventilation (PSV), also known as pressure control-continuous spontaneous ventilation (PC-CSV), is a mode of mechanical ventilation that augments patient-initiated spontaneous breaths by delivering a preset level of positive pressure during inspiration. In this mode, all breaths are triggered by the patient's respiratory effort, typically via a flow or pressure trigger, distinguishing it from mandatory ventilation modes. Once triggered, the ventilator applies a constant pressure support level above the positive end-expiratory pressure (PEEP), limited to the set value, while inspiration is flow-cycled and terminates when the inspiratory flow decreases to a predetermined threshold, often around 25% of the peak inspiratory flow. This results in variable tidal volumes (VT) that depend on the patient's inspiratory effort, lung compliance, airway resistance, and the duration of inspiration, allowing for more natural breathing patterns compared to volume-targeted modes.^[40]^[41] Key settings in PSV include the pressure support level, typically ranging from 5 to 20 cmH₂O above PEEP to augment inspiration, with lower levels (under 5 cmH₂O) primarily overcoming endotracheal tube resistance and higher levels (around 10-12 cmH₂O) assuming much of the work of breathing to achieve VT of approximately 6-8 mL/kg ideal body weight. PEEP is set based on patient needs, often 5-10 cmH₂O, to maintain alveolar recruitment and prevent derecruitment, while a backup respiratory rate is configured to provide mandatory breaths if the patient's spontaneous rate falls below a threshold, ensuring safety during potential apneic episodes. Additional parameters include fraction of inspired oxygen (FiO₂, usually ≤40% during trials) and sensitivity thresholds for triggering, with the overall targeting focused on set points for pressure augmentation rather than fixed volumes or rates. In recent applications as of 2025, PC-CSV configurations in PSV emphasize optimized cycling criteria to enhance patient-ventilator interaction in acute settings.^[40]^[41]^[42] PSV is primarily indicated for weaning patients from mechanical ventilation, serving as the standard mode for spontaneous breathing trials (SBTs) where success is often assessed using the rapid shallow breathing index (RSBI = respiratory rate / VT in liters), with values below 105 predicting successful extubation. It is also used in managing chronic respiratory failure, such as in patients with chronic obstructive pulmonary disease (COPD) or neuromuscular weakness, and for post-extubation support in cases of hypercapnia or hypoxemia. In acute care scenarios, PSV supports patients transitioning from full ventilatory support, particularly in 2025 protocols incorporating PC-CSV for improved outcomes in prolonged weaning.^[40]^[41]^[43] A primary advantage of PSV is its enhancement of patient-ventilator synchrony by aligning ventilatory support directly with the patient's neural respiratory drive, reducing asynchrony events and improving comfort compared to intermittent mandatory ventilation modes. The fixed pressure augmentation, expressed as \Delta P = \text{PS level}, provides consistent inspiratory assistance regardless of breath-to-breath variability, which lowers the work of breathing, decreases respiratory rate, increases tidal volume, and reduces oxygen consumption during spontaneous efforts. This mode also facilitates reduced sedation requirements and better preservation of respiratory muscle function, contributing to successful weaning in a majority of eligible patients.^[40]^[41]

Bilevel Positive Airway Pressure (BiPAP)

Bilevel positive airway pressure (BiPAP) is a noninvasive mode of mechanical ventilation that delivers alternating levels of positive airway pressure to support spontaneous breathing, primarily through a tight-fitting face mask or nasal interface. It operates by providing a higher inspiratory positive airway pressure (IPAP) during inhalation to assist ventilation and a lower expiratory positive airway pressure (EPAP) during exhalation to maintain airway patency and improve oxygenation. Typical settings include IPAP ranging from 10 to 20 cmH₂O and EPAP from 4 to 10 cmH₂O, adjusted based on patient tolerance and clinical response. The mode cycles between these pressures either via flow-cycling, where the transition to expiration occurs when inspiratory flow decreases to a set percentage of peak flow (typically 25-50%), or time-cycling in spontaneous/timed variants, where a predetermined inspiratory time (usually 0.5-1.5 seconds) dictates the switch.^[44]^[45] Key adjustable parameters in BiPAP include IPAP and EPAP levels, backup respiratory rate (typically 12-16 breaths per minute to ensure ventilation during apnea), rise time (the duration to reach IPAP, often 100-600 ms for patient comfort), and inspiratory-to-expiratory ratio. The backup rate serves as a safety feature, delivering timed breaths if the patient's spontaneous rate falls below the set threshold, preventing hypoventilation in cases of central apnea. These settings are titrated to achieve adequate tidal volumes (6-8 mL/kg ideal body weight) and gas exchange while minimizing discomfort from air leaks or pressure intolerance.^[46]^[47]^[48] BiPAP is indicated for acute exacerbations of chronic obstructive pulmonary disease (COPD) with hypercapnic respiratory failure (e.g., pH <7.35 and PaCO₂ >45 mmHg) and for chronic or acute respiratory insufficiency in neuromuscular diseases such as amyotrophic lateral sclerosis or muscular dystrophy. In COPD, it serves as first-line therapy to unload respiratory muscles and correct acidosis. For neuromuscular conditions, it is a standard intervention to manage nocturnal hypoventilation and daytime hypercapnia, improving survival and quality of life.^[49]^[50]^[51] Among its advantages, BiPAP enhances alveolar ventilation by augmenting tidal volume and reducing work of breathing, leading to faster resolution of respiratory acidosis compared to standard oxygen therapy. Randomized trials in COPD exacerbations have demonstrated that it reduces the need for endotracheal intubation by 50-70% and lowers in-hospital mortality. The effective pressure support in BiPAP is derived from the difference between IPAP and EPAP, which provides the augmenting force for inspiration above the baseline expiratory pressure; this is expressed as:

\text{PS} = \text{IPAP} - \text{EPAP}

where PS represents the pressure support that directly influences minute ventilation by increasing inspiratory flow and tidal volume without requiring invasive airway access.^[49]^[52]^[53]

High-Frequency and Alternative Modes

High-Frequency Oscillatory Ventilation (HFOV)

High-frequency oscillatory ventilation (HFOV) is a specialized mode of mechanical ventilation that delivers rapid, small-volume breaths using sinusoidal pressure oscillations to facilitate gas exchange while minimizing lung injury. It operates at high respiratory rates of 300 to 900 breaths per minute, equivalent to frequencies of 5 to 15 Hz, producing tidal volumes of 1 to 3 mL/kg that are typically below anatomic dead space. Gas exchange occurs through mechanisms such as bulk convection, pendelluft, asymmetric velocity profiles, and Taylor dispersion, with carbon dioxide elimination enhanced by active expiration generated by a reciprocating piston or diaphragm in the ventilator circuit.^[54]^[55] Key settings in HFOV include mean airway pressure (MAP), which is maintained at 15 to 30 cmH₂O to optimize alveolar recruitment and oxygenation; amplitude (ΔP), set between 40 and 80 cmH₂O to control the pressure swing and thus tidal volume delivery; and frequency, adjustable from 5 to 15 Hz, where higher frequencies reduce tidal volume but increase the rate of oscillations. The MAP is adjusted to achieve adequate oxygenation, while amplitude and frequency are titrated to target normocapnia, with amplitude primarily influencing CO₂ clearance. In practice, initial settings are often derived from prior conventional ventilation parameters, with MAP starting 3 to 5 cmH₂O higher than previous levels.^[54]^[56] HFOV is primarily indicated for neonatal respiratory distress syndrome (RDS) associated with conditions like air leak syndromes or meconium aspiration. In adults, randomized trials such as the 2013 OSCILLATE study demonstrated increased mortality with HFOV compared to conventional ventilation in moderate to severe ARDS, leading current guidelines (ATS/ESICM/SCCM 2017, reaffirmed 2024) to strongly recommend against its use, even as rescue therapy.^[57]^[58] Its lung-protective advantages stem from the use of low tidal volumes and constant MAP, which reduce volutrauma, atelectrauma, and biotrauma compared to traditional modes. The oscillatory power driving ventilation and CO₂ clearance is proportional to frequency multiplied by amplitude squared, as derived from the principle that oscillation energy scales with the rate of cycles and the square of the pressure swing:

\text{Power} \propto f \times (\Delta P)^2

This relationship underscores how adjustments in frequency inversely affect tidal volume, while amplitude squared amplifies ventilatory efficacy.^[54]^[57]^[59]

Negative Pressure Ventilation

Negative pressure ventilation (NPV) is a noninvasive mechanical ventilation technique that uses external devices to apply subatmospheric pressure to the chest and abdomen, thereby expanding the thoracic cavity and facilitating inspiratory airflow into the lungs. This method mimics the physiology of spontaneous breathing by generating negative intrathoracic pressure without the need for an endotracheal tube or face mask. Historically, NPV gained prominence through the development of the iron lung, a large cylindrical chamber invented in the 1920s by Philip Drinker and Louis Shaw, which enclosed the patient's body (excluding the head) and cyclically reduced pressure during the 1950s polio epidemics to support thousands of patients with respiratory paralysis.^[60]^[61] The core mechanism of NPV involves a pump-driven system, such as a cuirass shell fitted over the thorax or a full-body enclosure, that creates subatmospheric pressure around the chest wall to lift the rib cage and displace the diaphragm caudally, increasing lung volume. Typical pressure levels range from -20 to -40 cmH₂O during inspiration, with the magnitude titrated based on patient tolerance and tidal volume requirements; expiration is passive, relying on the elastic recoil of the lungs and chest wall to return to baseline. Settings include adjustable pressure amplitude and cycle time, where inspiratory duration is often set to 1-2 seconds and respiratory rate to 12-20 breaths per minute, allowing synchronization with spontaneous efforts in assisted modes. Modern iterations, like the biphasic cuirass ventilator, may incorporate brief positive pressure phases during expiration to aid secretion clearance or enhance exhalation.^[61]^[60] NPV is primarily indicated for patients with neuromuscular diseases, such as Duchenne muscular dystrophy and amyotrophic lateral sclerosis, who develop chronic hypoventilation due to respiratory muscle weakness; it is particularly suited for nocturnal home ventilation to prevent CO₂ retention and reduce reliance on tracheostomy. In these settings, long-term use has been shown to improve survival and quality of life by unloading respiratory muscles without disrupting natural airway protection mechanisms. Advantages include preservation of hemodynamics, as the external negative pressure enhances venous return to the heart and maintains cardiac output, making it preferable in patients with cardiovascular instability compared to positive pressure methods.^[60]^[62]^[61] As of 2025, NPV remains rarely employed in invasive mechanical ventilation contexts due to the dominance of positive pressure systems but continues as a viable noninvasive option, especially in pediatric intensive care units for acute respiratory failure in conditions like bronchiolitis, where it has reduced intubation rates by up to 28% in observational studies. Its role in home settings for neuromuscular support persists, often as an adjunct to positive pressure ventilation for patients intolerant to masks or with excessive oral secretions, though adoption is limited by device bulkiness and availability.^[61]^[63]

Liquid Ventilation

Liquid ventilation involves the use of oxygenated perfluorocarbon (PFC) liquids to facilitate gas exchange in the lungs, serving as an experimental alternative to conventional gas-based mechanical ventilation. PFCs are inert, biocompatible liquids with high solubility for respiratory gases, allowing them to carry significantly more oxygen and carbon dioxide than air. This approach aims to protect lung tissue in conditions of severe respiratory failure by reducing surface tension and minimizing ventilator-induced injury.^[64] The mechanism of liquid ventilation relies on filling the lungs with PFC, which is pre-oxygenated and warmed to body temperature, to enable diffusion-based gas exchange across the alveolar-capillary membrane. Total liquid ventilation (TLCV) completely replaces pulmonary gas with liquid, using a specialized circuit to deliver and withdraw tidal volumes of PFC, typically at rates mimicking normal respiratory frequencies. In contrast, partial liquid ventilation (PLV) involves instilling PFC to functional residual capacity while maintaining conventional gas ventilation superimposed on the liquid-filled lungs, allowing for hybrid support. Both methods leverage the density and evaporative properties of PFCs, but require continuous monitoring to prevent complications such as overdistension or inadequate clearance.^[65]^[66] Key settings for liquid ventilation include precise control of liquid volume to match lung capacity (e.g., 10-15 mL/kg for TLCV), maintenance of PFC temperature at 37-39°C to optimize viscosity and gas solubility, and equilibration with high oxygen concentrations (FiO₂ up to 100%) prior to delivery. Oxygenation is achieved through direct dissolution in the liquid, with PFC capacity approximately 50 mL O₂ per 100 mL liquid at atmospheric pressure, compared to about 0.3 mL O₂ per 100 mL air, enabling superior oxygen delivery. Challenges in delivery systems stem from the high density of PFCs (1.8-2.0 g/mL), necessitating robust pumps, non-collapsible tubing, and strategies for continuous PFC replenishment due to evaporation losses of 1-2 mL/kg/hour during PLV.^[64]^[67]^[68] Liquid ventilation has been investigated primarily for acute respiratory distress syndrome (ARDS) in adults and respiratory distress in neonates, where it demonstrates potential to improve oxygenation and CO₂ clearance while recruiting collapsed alveoli. Advantages include enhanced CO₂ elimination (up to 140-210 mL CO₂ per 100 mL PFC), reduced barotrauma, and anti-inflammatory effects from PFC distribution to dependent lung regions. As of 2025, liquid ventilation remains investigational and is not part of routine clinical practice, with ongoing trials focusing on its role in severe ARDS and therapeutic hypothermia rather than widespread adoption.^[69]^[70]^[71]

Advanced Closed-Loop Modes

Adaptive Support Ventilation (ASV)

Adaptive Support Ventilation (ASV) is an advanced closed-loop mode of mechanical ventilation designed to automate the adjustment of respiratory parameters based on a clinician-determined target minute ventilation (VE), while promoting an optimal breathing pattern that minimizes the patient's work of breathing (WOB). Developed initially through clinical applications described in 1994, ASV integrates elements of pressure-controlled ventilation for mandatory breaths and pressure support for spontaneous efforts, allowing seamless transitions between controlled and supported breathing as patient condition improves. This mode continuously monitors expired VE and lung mechanics, such as compliance and resistance, to dynamically adapt the respiratory rate (RR) and tidal volume (VT) every few minutes, ensuring the target VE is maintained within safe limits.^[72]^[73] The core mechanism of ASV involves setting a percentage of the target VE (typically 80-100%) and automatically adjusting RR and VT to achieve it, blending mandatory breaths with spontaneous ones based on patient effort detection via flow and pressure signals. The algorithm employs an intelligent targeting scheme (denoted as "i" in some implementations) that calculates the optimal RR-VT combination using a model derived from physiological principles to minimize WOB. This is achieved through the equation for optimal respiratory rate:

RR_{opt} = \frac{VE_{target}}{VT_{opt}}

where VT_{opt} is selected to balance elastic and resistive components of WOB, with the derivation rooted in minimizing total respiratory work via a rib cage compliance model that accounts for anatomical dead space and frequency-dependent resistance. As spontaneous breathing increases, ASV reduces mandatory breath frequency, facilitating weaning by providing just enough support to meet the VE target without over-assistance.^[74]^[75] Key clinician-set parameters for ASV include the target VE (often 100-150 mL/kg ideal body weight per minute), an upper VT limit (typically 6-8 mL/kg to prevent volutrauma), PEEP, and FiO2; the mode then handles RR, VT, inspiratory time, and pressure support levels autonomously. ASV integrates pressure-controlled ventilation, pressure support ventilation, and synchronized intermittent mandatory ventilation to enhance adaptability in modern ventilators.^[74]^[72] ASV is particularly indicated for weaning patients in the intensive care unit (ICU), where it supports recovery across various lung pathologies, including acute respiratory distress syndrome, chronic obstructive pulmonary disease, and postoperative states, by promoting early spontaneous breathing and reducing ventilator-induced complications. Advantages include a significant reduction in the frequency of clinician interventions for parameter adjustments—up to 50% fewer in some evaluations—leading to shorter weaning durations and lower peak airway pressures compared to conventional modes like synchronized intermittent mandatory ventilation. Clinical studies have demonstrated its safety and efficacy in maintaining adequate ventilation while accelerating liberation from mechanical support.^[74]^[72]^[75]

Neurally Adjusted Ventilatory Assist (NAVA)

Neurally adjusted ventilatory assist (NAVA) is a proportional mode of mechanical ventilation that synchronizes support with the patient's neural respiratory drive by monitoring the electrical activity of the diaphragm (EAdi). Introduced conceptually in a seminal 1999 study demonstrating the feasibility of neural control to prevent overdistension and underinflation during mechanical ventilation, NAVA uses EAdi as both the trigger for breaths and the basis for delivering proportional pressure support. This approach contrasts with traditional modes that rely on airway pressure or flow signals, which can lead to delays in detection of patient effort.^[76]^[77] The mechanism of NAVA involves inserting a specialized nasogastric catheter equipped with an array of electrodes positioned in the distal esophagus near the diaphragm to capture the EAdi signal, which reflects the neural output from the respiratory centers in the brainstem. The ventilator processes this signal in real time and delivers positive airway pressure proportional to the patient's inspiratory effort, governed by the equation:

P_{\text{aw}} = \text{NAVA level} \times \text{EAdi}

where P_{\text{aw}} is the airway pressure support (in cmH₂O), the NAVA level is the clinician-set gain factor (in cmH₂O/μV), and EAdi is the peak electrical activity (in μV). This proportional control derives from a feedback system that amplifies the neural drive without overriding it, ensuring breath timing, cycling, and magnitude align with the patient's needs; for instance, increasing EAdi during higher demand automatically scales support to maintain synchrony. Backup modes, such as pressure support, activate if EAdi detection fails.^[77]^[78]^[79] Clinically, NAVA settings include the NAVA level (typically starting at 0.5–2.5 cmH₂O/μV and titrated to achieve EAdi peaks of 5–15 μV), positive end-expiratory pressure (PEEP, set to maintain oxygenation), fraction of inspired oxygen (FiO₂), and EAdi trigger threshold (often 0.5–2 μV). Targeting employs servo-i algorithms to adjust support dynamically, aiming for stable EAdi without excessive unloading, which is monitored via waveform displays for optimization. Indications focus on scenarios with high asynchrony risk, such as in pediatric patients with acute respiratory distress or weaning difficulties, and adults in intensive care with conditions like ARDS or post-extubation support; studies show reduced asynchrony indices (e.g., from 30–50% in pressure support to <10% in NAVA) in both groups, improving comfort and diaphragm function.^[77]^[80]^[81] Advantages of NAVA center on superior patient-ventilator synchrony, as EAdi-based triggering eliminates delays (e.g., 100–300 ms in flow-triggered modes) and ineffective efforts, fostering physiologic variability in breathing patterns and reducing over- or under-assistance. In pediatrics, it lowers peak inspiratory pressures and sedation needs while enhancing oxygenation; in adults, it shortens ventilation duration by up to 35% in select cohorts by promoting efficient weaning. This neural proportionality supports natural respiratory control, minimizing ventilator-induced diaphragm dysfunction compared to fixed-support modes.^[77]^[82]^[83]

Proportional Assist Ventilation (PAV)

Proportional assist ventilation (PAV) is a patient-initiated mode of mechanical ventilation that delivers inspiratory pressure support in direct proportion to the patient's instantaneous respiratory effort, thereby amplifying the patient's own breathing mechanics without imposing a fixed tidal volume or flow pattern. Developed by Magdy Younes in the early 1990s, PAV aims to unload the resistive and elastic components of the respiratory system, allowing the patient to retain full control over their ventilatory pattern, including tidal volume, respiratory rate, and inspiratory flow waveform. This approach contrasts with traditional modes by dynamically adjusting support based on real-time measurements of airflow and lung volume, promoting greater patient-ventilator synchrony and comfort during spontaneous breathing trials.^[84]^[85] The core mechanism of PAV relies on the equation of motion for the respiratory system, which states that the total pressure required for ventilation (P_total) equals the sum of resistive pressure (related to airflow) and elastic pressure (related to lung volume): P_total = (R × Flow) + (E × Volume), where R is airway resistance, E is respiratory system elastance (the inverse of compliance, C, so E = 1/C), Flow is instantaneous inspiratory flow rate, and Volume is inspired volume. In PAV, the ventilator generates an assist pressure (P_aw) proportional to these components: P_aw = (G_r × Flow) + (G_c × Volume), where G_r is the resistance gain factor (in cmH₂O/L/s) and G_c is the elastance gain factor (in cmH₂O/L). This formulation effectively offsets the patient's effort (P_mus) by amplifying it to counteract resistive and elastic loads, such that the total pressure becomes P_total = P_mus + P_aw, with the ventilator providing support tailored to the patient's mechanics. Modern implementations, such as PAV+, incorporate automated estimation of R and E through periodic end-inspiratory occlusions (every 8–15 breaths) to adjust gains dynamically, ensuring accurate unloading even as patient conditions change.^[86]^[87] Settings for PAV typically involve clinician-adjusted gains for resistance (G_r) and elastance (G_c), often set to provide 60–80% of the total respiratory workload, meaning the ventilator unloads that proportion of the effort while the patient contributes the remainder. These gains are calibrated based on measured or estimated respiratory mechanics, with G_r targeting resistive unloading (e.g., 5–20 cmH₂O/L/s in obstructive patients) and G_c addressing elastic recoil (e.g., 10–30 cmH₂O/L), avoiding over-assistance that could lead to instability. An adaptive variant, PAV with load-adjustable gain factors (PAV+), automates gain adjustments to maintain a target level of patient effort, such as an estimated P_mus of 5–10 cmH₂O, enhancing usability at the bedside.^[88] PAV is particularly indicated for weaning from mechanical ventilation in patients with obstructive lung diseases, such as chronic obstructive pulmonary disease (COPD), where high airway resistance and dynamic hyperinflation complicate spontaneous breathing. In these cases, PAV facilitates gradual reduction of support by matching the patient's variable demand, improving tolerance during trials and reducing the risk of failure compared to fixed-pressure modes. It is also used in acute respiratory failure to minimize work of breathing while preserving diaphragmatic function.^[89] The primary advantages of PAV stem from its ability to closely match ventilatory support to patient demand, resulting in superior patient-ventilator synchrony, reduced dyspnea, and lower risk of over- or under-ventilation. By proportionally amplifying effort to offset R and 1/C (where total P = patient-generated P_mus + ventilator P_aw), PAV minimizes imposed work and enhances efficiency, as demonstrated in early theoretical models showing decreased peak airway pressures and preserved reflex feedback loops. Clinical studies have reported shorter weaning durations and improved comfort in obstructive patients, with gains set at 60–80% unloading achieving optimal balance between support and patient autonomy.^[84]

Automatic Tube Compensation (ATC)

Automatic Tube Compensation (ATC) is a ventilatory support feature designed to counteract the resistance imposed by the endotracheal tube (ETT) or tracheostomy tube during spontaneous breathing in mechanically ventilated patients.^[90] It operates as a closed-loop system that dynamically adjusts airway pressure to offset the flow-dependent pressure drop across the artificial airway, thereby reducing the additional work of breathing attributable to tube resistance without providing full ventilatory support.^[90] Introduced in the late 1990s, ATC has become a standard adjunct in modern intensive care unit ventilators as of 2025, integrated into major ventilator platforms.^[91]^[92] The mechanism of ATC relies on real-time measurement of inspiratory and expiratory flow through the ETT, followed by instantaneous pressure compensation to maintain tracheal pressure equivalent to what would occur without the tube.^[90] Tube resistance typically ranges from 10 to 50 cmH₂O/L/s, depending on tube size, length, and flow rates, with higher values in smaller or longer tubes due to turbulent flow characteristics.^[93] This compensation is flow-dependent and nonlinear in precise implementations, but fundamentally follows an analog to Ohm's law for respiratory mechanics, where the compensatory pressure P_{\text{comp}} is calculated as:

P_{\text{comp}} = \dot{V} \cdot R_{\text{tube}}

Here, \dot{V} represents the measured airflow (L/s), and R_{\text{tube}} is the tube-specific resistance (cmH₂O/L/s), ensuring the pressure gradient across the tube is neutralized.^[90]^[94] The system continuously computes this during both inspiration and expiration, distinguishing ATC from static pressure supports by its adaptive, patient-triggered response.^[95] Settings for ATC include selection of the ETT inner diameter (typically 6.5–8.5 mm for adults) to estimate resistance, along with adjustable compensation levels (e.g., 80–100% of calculated resistance) and flow sensitivity thresholds to initiate compensation.^[91] It is commonly integrated as an add-on to modes like pressure support ventilation (PSV) or continuous positive airway pressure (CPAP), allowing seamless activation without altering primary ventilator parameters.^[90]^[95] ATC is indicated primarily for intubated patients undergoing spontaneous breathing trials or weaning, where it minimizes the imposed work of breathing due to ETT resistance, which can account for up to 20–30% of total respiratory effort in uncompensated scenarios.^[90]^[96] It is particularly beneficial in patients with acute lung injury or chronic obstructive pulmonary disease, as it unloads inspiratory muscles and enhances alveolar ventilation without compromising cardiorespiratory stability.^[90] Advantages of ATC include improved patient comfort through reduced dyspnea and preserved natural breathing patterns, better patient-ventilator synchrony by eliminating tube-related triggering delays, and more accurate prediction of extubation success during minimal support trials.^[90]^[95] Clinical studies demonstrate that ATC lowers the pressure-time product of respiratory muscles by approximately 20–50% compared to uncompensated spontaneous breathing, facilitating earlier weaning without increasing reintubation risk.^[96]^[91]

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