The pressure–time and flow-time curves seen during APRV are shown in Figure 2. P_High denotes the pressure inflating the lung, with lung volume changing with respiratory system compliance (C_RS) and the duration (T_High) of the applied pressure (P_High). These together define the continuous positive airway pressure (CPAP) phase of APRV (Figure 2).

To our knowledge, only two translational animal studies have investigated the APRV mode, examining how variations in P_High affect lung injury and inflammation (40, 41). Both studies used a heterogeneous porcine lung injury model of surfactant deactivation, which included both normal lung areas and areas with surfactant deactivation simulating ARDS. This setup allowed for assessing the pathological impact of lung overdistension (OD) and recruitment-derecruitment (RD) in both normal and surfactant-depleted tissues.

Four groups of animals were studied, with mechanical breaths set in the APRV mode to induce lung overdistension (OD) (OD↑; P_High = 40 cmH₂O) or not (OD↓; P_High = 28 cmH₂O), and lung recruitment-derecruitment (RD) or not. The RD was caused (RD↑) or prevented (RD↓) by controlling the end-expiratory flow termination (F_EE) point, by altering the expiratory time (T_Low). The exact expiratory time was determined using the peak expiratory flow (F_PE) equation: [F_PE x 25% (RD↑) or 75% (RD↓)] = F_EE. A higher percentage (75%) resulted in a shorter expiratory time. The expiratory time (T_Low) was set sufficiently brief to prevent alveolar collapse (RD↓), according to the equation, F PE × 75 % = F EE (1) which resulted in a very brief expiratory duration. The (T_Low) was set sufficiently long to cause alveolar collapse (RD↑) using the equation (41). F PE × 25 % = F EE (2)

This study did not evaluate efficacy or outcomes but aimed to identify the roles of the two main mechanisms of VILI, specifically OD and RD, on inflammation and pathophysiology. A P_High of 40 cmH₂O, with or without RD, was found not to cause pulmonary edema in normal tissue and only induced edema in surfactant deactivation tissue when OD was combined with RD. A similar porcine ARDS model confirmed that P_High 40 cmH₂O does not damage normal lung tissue and becomes problematic only when combined with RD (40).

A similar porcine ARDS model confirmed that a P_High of 40 cmH₂O does not damage normal lung tissue and only becomes problematic when combined with alveolar instability (RD) (40). This supports the conclusion that overdistending normal tissue (i.e., the Baby Lung) is not the primary cause of VILI (41–45). This is because the Baby Lung in the ARDS patient is not normal tissue, similar to that in the animal studies described. Instead, it has heterogeneously distributed lesions of unstable, collapsed, or edema-filled alveoli that standard clinical imaging methods cannot detect. These lesions have been called “Hidden Microatelectasis” and function as stress multipliers that correlate with VILI. Maintaining P_High below 30 cmH₂O during normal chest wall compliance (C_CW) reduces lung tissue damage in areas of surfactant deactivation when a brief expiratory duration prevents alveolar collapse (RD). These studies thus demonstrate that normal lung tissue is highly resistant to damage from high airway pressures, provided cyclic collapse and reopening are avoided.

P_High should be sustained during the steep portion of the pressure-volume curve between functional residual capacity (FRC) and total lung capacity (TLC). Therefore, P_High should be set equal to plateau pressure (P_Plat) when switching from volume control (VC) mode, to the peak inspiratory pressure (PIP) when switching from pressure control (PC) or dual targeted (DT) mode such as pressure regulated pressure control (PRVC) or mean airway pressure (Paw) plus 2–4 cmH₂O when using the high frequency oscillatory ventilation (HFOV) mode. When using APRV as the initial mode, P_High recommendations are Mild ARDS (20–24 cmH₂O), Moderate ARDS (25–29 cmH₂O), and Severe ARDS (26–30 cmH₂O), with the possibility of exceeding 30 cmH₂O with low C_RS.

Although tidal volume (V_T) is not targeted, it is important to note that V_T is generally <6 mL/kg in a severely injured lung (Figure 3B), as described in detail under the T_Low setting section. With decreased C_RS / increased E_RS, the V_T may be <4 mL/kg. In this instance, the P_High may be increased in 2 cmH₂O increments to achieve a minimum V_T of 5–6 mL/kg.

Before transitioning to APRV, it is advisable to evaluate the patient’s intravascular status to assess preload dependency, for example, with the passive leg raise maneuver (46). Data show that patients with positive preload dependency respond effectively to a fluid bolus without developing pulmonary edema (47).

Because lung recruitment can occur rapidly, monitor lung volume on chest radiograph. Check the diaphragm’s shape, which should typically reach its maximum at the mid-clavicular line, crossing the fifth anterior rib. If the diaphragms start to flatten—that is, if the peak curvature moves medially from the mid-clavicular line—reduce P_High by 2–3 cmH₂O. Then, adjust T_Low as needed to keep the fraction of F_EE at 75% of the F_PE (Equation 1) (See T_Low adjustment below).

The above recommendations align with those for standard mechanical ventilation, namely maintaining P_High ≤ 30 cmH₂O with normal C_CW. This approach is consistent with all ventilation mode guidelines and should not cause lung injury, as with other modes. Raising P_High above 30 cmH₂O may be necessary for patients with low C_CW, such as those with significant central obesity, ascites, or abdominal distension (48).

A practical method is to gradually increase P_High in 2 cmH₂O steps while monitoring changes in C_RS and driving pressure (ΔP) (ΔP = V_T/C_RS). It is essential to recognize that positive changes in C_RS and P may take considerable time to manifest if lung reopening occurs gradually, suggesting prolonged opening time constants. In these cases, APRV gradually opens the lung (49).

Future research opportunities include further studies on using esophageal manometry to estimate pleural pressure (P_PL). This method would allow P_High to be set above 30 cmH₂O in patients with low C_CW, reducing concerns about overdistension by providing a direct measurement of transpulmonary pressure (P_TP). The ARDSNet protocol was found to be less lung protective than the APRV mode set by the time-controlled adaptive ventilation (TCAV) method and guided by P_TP in a clinically relevant porcine model of sepsis and gut ischemia/reperfusion (50).

During conventional mechanical ventilation, the positive end-expiratory pressure (PEEP) applied by the ventilator is the end-expiratory pressure during each breath cycle. Setting P_Low to 0 cmH₂O with APRV using T_Low calculated as a fraction of F_EE at 75% of F_PE (Equation 1) does not create a PEEP of 0 cmH₂O because expiration is too brief for the expiratory flow to cease and the lungs to depressurize fully. This results in a time-controlled PEEP (TC-PEEP) (Figure 2, red dashed line). In a translational large-animal model, a P_Low of 0 cmH₂O yielded a significant TC-PEEP, slightly more than half the P_High (50).

A brief expiratory duration, rather than a fixed pressure (PEEP), stabilizes alveoli because the expiratory time is shorter than the lung’s fastest time constant of closure. Therefore, setting P_Low above 0 cmH₂O is unnecessary and may be harmful, as it can increase PaCO₂ levels and hinder clearance of secretions by slowing expiratory gas flow (51). Unlike PEEP in traditional ventilation, T_Low dynamically adjusts EELV (14), providing a physiologically responsive method that better adapts to changes in lung mechanics than compliance-based adjustments, arbitrary scales, or oxygenation targets, which have limited predictive value for patient outcomes (52).

Setting a P_Low above 0 cmH₂O creates expiratory resistance, reducing gas flow and causing two major issues:

Reduced expiratory flow limits CO₂ elimination per breath, and when combined with a brief T_Low, can cause hypercapnia.

Thus, maintaining P_Low at 0 cmH₂O is crucial for maintaining dynamic, patient-specific control of EELV and reducing the risk of ventilator-induced lung injury in APRV.

In a translational porcine ARDS model comparing ARDSnet LV_T with APRV, it was observed that 48 h after injury (peritoneal sepsis plus gut ischemia/reperfusion), using P_Low = 0 cmH₂O resulted in a TC-PEEP of 17.8 ± 2.0 cmH₂O. The lung remained well-inflated, and ARDS was prevented (Figure 4) (50).

The P_Low should always be set to 0 cmH₂O, but PEEP will be maintained because of the brief expiratory period (TC-PEEP) (Figure 2, red dashed line) (50). Setting P_Low to 0 cmH₂O also improves CO₂ clearance and mucus removal. A P_Low of 0 cmH₂O enables expiratory flow to identify lung C_RS, similar to spirometry, on a breath-by-breath basis for precise setting and adjustment of T_Low.

Direct observation of subpleural alveoli shows that a P_Low of 0 cmH₂O does not cause RACE when T_Low is determined using a fraction of F_EE at 75% of F_PE (Figure 5, II). Although P_Low is set to 0 cmH₂O, the lung does not have enough time to depressurize, maintaining a TC-PEEP (Figure 2, red dashed line) (50). Research indicates that alveoli are better stabilized with a brief expiratory time that generates TC-PEEP compared to using a non-zero PEEP level with a longer expiratory duration that results in the same end-expiratory lung volume (Supplementary File 3, Figure S9) (5). In the acutely injured lung, gas distribution within the alveoli and ducts closely resembles normal conditions, with a P_Low of 0 cmH₂O and a T_Low set using Equation 1 (Figure 5, I). This results in dynamic alveolar homogeneity similar to that of a normal lung (11), thereby facilitating CO₂ and mucus removal (5).

Investigate alternative methods to determine T_Low beyond using expiratory flow magnitude alone. These methods might allow P_Low to exceed 0 cmH₂O without compromising the primary benefits of APRV, provided that CO₂ retention and mucus clearance are not adversely affected.

Alveolar RD is a dynamic process influenced by both time and pressure. When increased pressure is applied to a derecruited lung, alveolar units gradually open even if the pressure remains constant (53). In specific lung injuries characterized by slow recruitment kinetics, this process may persist throughout the entire T_High and across multiple consecutive breaths. Although the volume of lung recruited during a single T_High block may be small, the overall effect across multiple breaths can be significant, provided derecruitment is avoided during each T_Low. Therefore, using a prolonged T_High while still achieving sufficient expired minute volume (MVe), combined with a brief T_Low set according to Equation 1, can effectively gradually ‘ratchet’ open atelectatic lung regions that do not respond to conventional PEEP strategies (49). However, increasing T_High lowers the respiratory rate (RR) and, consequently, reduces MVe. Although an intuitive misconception to increase MVe is to increase the T_Low thereby increasing V_T. However, this increases the risk of RACE-induced atelectrauma and should be avoided. This is explained below in the recommendations for the T_Low setting. The more appropriate method is to decrease T_High transiently to increase RR and MVe. Although this might slow lung recruitment, it will prevent RACE-induced VILI. As the lung is progressively ‘ratcheted’ open, gas exchange improves, and the T_High can be gradually increased.

The appropriate T_High should be customized according to the severity of lung dysfunction and adjusted based on the patient’s ventilatory efficiency to achieve normocapnia as lung function improves. Initially, T_Hgh is set to ensure adequate bulk (convective) ventilation and MVe, particularly in patients with severe lung injury who require a higher RR. The T_High is the rate controller in APRV and is similar to increasing the RR in conventional ventilation.

For example, in patients with established ARDS and hypercapnia transitioning to APRV, an initial T_High of 1–2 s is typically used, yielding an RR of approximately 24–35 breaths per minute. In this setup, a brief T_High is combined with a brief T_Low to keep the fraction of F_EE at 75% of F_PE (Equation 1), thereby maintaining functional EELV and normalizing lung E_RS. This creates a respiratory cycle characterized primarily by inspiration (Figure 2, CPAP Phase).

The T_High controls convective and diffusive ventilation and also regulates end-inspiratory lung volume by recruiting additional alveoli with each breath, due to the time-dependent nature of recruitment (Figure 6) (35). Reopening the lung increases the surface area for gas exchange, thereby improving CO₂ clearance through diffusive ventilation. Reopening also reduces local stress concentrators in the tissue (Supplementary File 3, Figure S2), thereby eliminating a significant mechanism of VILI (11–13).

In contrast, for stable patients recovering from ARDS or receiving APRV as a preventive or lung-protective strategy, a longer initial T_High (e.g., 4–6 s) may be used. This approach reduces RR and MVe; however, because most of the lung remains open, there is sufficient diffusion surface area to maintain normal PaCO₂.

Although permissive hypercapnia may be acceptable in selected cases at the clinician’s discretion, inducing hypercapnia is not a goal of APRV. Reports of hypercapnia in the literature are most commonly attributable to an excessively prolonged T_High, particularly when ventilator settings are not appropriately adjusted to the degree of lung dysfunction during the early transition phase. Accordingly, initial APRV parameters should not be selected to target hypercapnia or to employ a prolonged T_High that reduces MVe relative to prior ventilator settings. Instead, the primary objective is to maintain normocapnia with adequate MVe, even when the initial T_High is brief—though still approximately twice the duration of conventional inspiratory times. Lung reopening is initiated within this time frame.

As a patient’s ventilatory efficiency improves, T_High can be gradually increased. This adjustment is usually guided by trends toward normocapnic or even hypocapnic, which indicate effective CO₂ removal. Increasing T_High shifts ventilation from mainly convective, RR-driven mechanisms to a combination of convective and diffusive processes. This transition allows for significant reductions in both RR and MVe without compromising overall ventilation.

The recruitment of alveolar lung tissue at three different airway pressures over time was measured using a rat ARDS model (Figure 6) (35). Gross lung recruitment was assessed by imaging the lung surface and calculating the recruitment rate (the proportion of red tissue that turned pink). Alveolar recruitment was evaluated using in vivo microscopy, and the proportion of the microscopic field occupied by alveoli was quantified by computer image analysis. Rapid recruitment occurred within the first 2 s, followed by gradual recruitment over the next 40 s. The results were accurately predicted by a mathematical model that incorporated both time and pressure. Extending the T_High will continuously recruit lung tissue without additional mechanical power or ΔP costs (35).

A T_High of 4–6 s is typical for patients with routine post-operative atelectasis or normal lungs, but it may be too long when used as a rescue strategy for patients in respiratory failure. In these cases, a brief T_High of 2–3 s may be necessary to increase MVe until the lung has recruited enough to exchange an adequate volume of CO₂. This may not occur for 12–24 h, or even 24–48 h in lungs with severe ARDS (Figure 7) (54).

Note that if V_T falls below 3 mL/kg of ideal body weight after switching from conventional ventilation to APRV, it may be necessary to lower T_High and raise P_High to maintain or exceed the pre-transition MVe. When switching from another ventilation mode, set T_High to match the previous RR using the formula: 60/RR – T_Low = T_High.

For example, with an RR of 26 during conventional ventilation and a T_Low of 0.5 s, the T_High is 60/26 = 2.3 s minus 0.5 s (T_Low), yielding 1.8 s. When using APRV as the primary mode, set T_High to 2–4 s for Mild ARDS, 2–3 s for Moderate ARDS, and 1–3 s for Severe ARDS. After obtaining blood gas results, T_High can be adjusted up or down to maintain a normal PaCO₂.

When switching from conventional ventilation to APRV for a patient with severe ARDS, the T_High should be brief to match the required conventional ventilation RR and MVe, ensuring that ventilation remains sufficient to maintain normocarbia. As the lung gradually recruits, the gas-exchange surface area increases, allowing T_High to be extended to promote lung recruitment while maintaining normocarbia.

Currently, the optimal combination of T_High and P_High for optimizing V_T and MVe is determined empirically. Future work should focus on developing a computational approach to identify the optimal combination for each patient’s lung condition, using techniques such as fuzzy logic.

Personalizing T_Low based on lung pathophysiology is essential for achieving lung-protective effects with APRV. T_Low is adjusted using C_RS (Equation 1), which effectively prevents RACE. RACE causes tissue injury by over-distending open alveoli near collapsed lung regions and avoids harmful stresses on opposing epithelial walls during inflation (Supplementary File 3, Figure S3) (55). Recently, we demonstrated in a pig model of surfactant deficiency that the energy dissipated in parenchymal tissues due to RACE correlates with outcomes (Supplementary File 3, Figure S5) (56), and that alveolar collapse is more effectively prevented using a brief expiratory time combined with TC-PEEP than with the same set-PEEP and a longer expiratory duration (Supplementary File 3, Figure S9) (5). When T_Low is set using Equation 1, it prevents progressive EELV loss and steers the lung away from the VILI Vortex (37).

The T_Low influences V_T, which is affected by changes in C_RS. A low C_RS, common in Severe ARDS, results in a brief T_Low when using the TCAV method. This reduces the amount of gas that escapes during exhalation, often resulting in a V_T below 6 mL/kg. As the lung heals and C_RS increases, both T_Low and V_T also increase (Figure 3). Therefore, when correctly set, APRV will not deliver dangerously large V_T into a severely injured lung because it adjusts with changes in C_RS, keeping ΔP (V_T/C_RS) within safe limits (Figure 3).

The T_Low controls V_T and EELV, and therefore the level of TC-PEEP (Figure 3). After expiration begins, expiratory flow quickly reaches its peak value, F_PE, then decreases progressively. The rate of decrease depends on the mechanical properties of the lungs, which change with acute lung injury, and remains approximately constant during the brief period defined by T_Low. This means that T_Low can be calculated from the expiratory flow curve, assuming it is a straight line, by identifying the point at which flow reaches 75% of F_PE (Equation 1).

During the Release Phase (P_Low/T_Low) (Figure 2), gas flow decreases at an approximately steady rate, reflecting the mechanical properties of the respiratory system. Since the duration of the Release Phase is calculated as F_PE × 75% = F_EE (Equation 1), the T_Low is customized to the patient’s respiratory mechanics’ timeline (Figure 3). This strategy has been validated clinically (Figure 7) and experimentally (Figure 5) to optimize alveolar stability, meaning it prevents alveolar collapse during exhalation and reinflation during inhalation (atelectrauma) (11–13, 40, 41, 57).

The T_Low is the key parameter that personalizes APRV settings based on lung pathophysiology and regulates V_T, TC-PEEP, and EELV (Figure 8). The Slope_EF is a breath-by-breath measure of C_RS. A decrease in C_RS increases expiratory flow rate, resulting in a steeper slope and a more rapid attainment of the calculated F_EE (Equation 1), thereby shortening T_Low (Figure 3). Figure 8 illustrates the relationship between C_RS, T_Low, and Slope_EF.

Substantial experimental evidence supports the idea that effectively using expiratory time stabilizes alveoli (Figure 5) (11–13), preventing RACE-induced energy dissipation (Supplementary File 3, Figure S5, S6) and tissue damage (Figure 4) (5). In a clinically relevant 48-h porcine model of peritoneal sepsis and gut ischemia/reperfusion, personalized T_Low, along with the other recommended parameters, offered significant lung protection (Figure 4) (28, 50, 58). We showed that personalized T_Low prevents EELV loss, maintains normal C_RS and ΔP even with a V_T of 12 mL/kg (28). When T_Low is set using Equation 1, together with the three other recommended settings, it progressively increases C_RS while maintaining ΔP within the safe range (ΔP = V_T/C_RS) (Figure 7).

Histologic analysis of alveoli and alveolar ducts during inspiration and expiration (Figure 5, I) (13), along with direct observation of subpleural alveoli using in vivo microscopy (11, 12), highlights the critical role of personalized T_Low in lung stability (alveoli and ducts) (Figure 5, II). Using computational models, we confirmed the influence of time on alveolar recruitment and stabilization, as shown in animal studies (29–33), along with computational validation of the biological data (Supplementary File 6) (35, 36).

The relationship between T_Low, C_RS, and Slope_EF was examined in a recent study (Figure 8) (14). The study used normal pigs and a Tween-induced surfactant deactivation ARDS model. The C_CW was decreased by peritoneal CO₂ insufflation to elevate abdominal pressures (0, 6, 8, 10, 12, 14, 15 mmHg). The T_Low, Slope_EF (liters/s²), EELV, and the time to reach complete expiration to functional residual capacity (T_Exp) were measured at each level of C_CW.

As C_RS decreased with increasing intra-abdominal pressure, T_Low, T_Exp, and Slope_EF all progressively declined in both normal and Tween-injured (ARDS model) lungs (Figure 8). This study demonstrates the interconnected relationship between T_Low, T_Exp, and Slope_EF, and how T_Low is coupled with C_RS, which Slope_EF measures on a breath-by-breath basis. Changes in the Slope_EF can also be used to detect worsening lung injury and estimate EELV (14).

The clinician adjusts T_Low until the calculated F_EE is achieved (Equation 1). For example, if F_PE is 60 L/min, then F_EE would be 60 × 75% = 45 L/min, so the clinician adjusts T_Low so that the next expiration begins when F_EE reaches 45 L/min (Figure 3). A patient with mild lung injury shows a slight decrease in C_RS along with a small increase in lung recoil and normal EELV (Figure 3A). Because gas exits the lung slowly, the Slope_EF is gradual, and terminating expiration at F_EE = 45 L/min, as calculated by Equation 1, results in a T_Low of 0.48 s. Severe ARDS significantly reduces C_RS, increases lung recoil, and decreases EELV (Figure 3B). High lung recoil quickly expels gas, creating a steep Slope_EF so that the same F_EE (−45 L/min) results in a T_Low of only 0.38 s. As mentioned earlier, T_Low is guided by changes in C_RS.

Setting T_Low using Equation 1 typically yields a V_T < 6 mL/kg in a severely injured lung (Figure 3B). This occurs because V_T and C_RS are coupled, and this relationship varies with Slope_EF angle (Low C_RS = low V_T and vice versa). In cases of mild lung injury with relatively normal C_RS and EELV, a shallower Slope_EF results in an increase in T_Low. This leads to greater Release Gas Volume (V_R) and lung pressure, resulting in a relatively high V_T (>6 mL/kg) and a lower TC-PEEP (Figure 3A).

In contrast, severe ARDS, characterized by low C_RS and EELV, increases lung recoil, leading to a steeper Slope_EF and a significant reduction in T_Low. This decreased V_R requires a similar small V_T during inflation (<6 mL/kg) while increasing TC-PEEP (Figure 3B). At the end of a 48-h porcine model of peritoneal sepsis and gut ischemia/reperfusion (PS + I/R)-induced ARDS, the APRV group, with settings similar to those recommended in this consensus conference, had a V_T of 12 mL/kg and C_RS of 42 mL/cmH₂O, compared to the LV_T group with a V_T of 5.8 mL/kg and C_RS of 9 mL/cmH₂O. Even with a V_T of 12 mL/kg—believed to cause VILI—the APRV group maintained a safe ΔP because of the high C_RS (ΔP = V_T/C_RS) (Figure 4). Therefore, it is not just the size of the delivered V_T that causes injury, but also the volume and lung pathophysiology into which it is introduced that determine whether a mechanical breath is harmful or protective.

When switching from another ventilation mode, initially set T_Low to 0.3–0.6 s. When starting with ARPV for Mild ARDS, use 0.4–0.6 s; for Moderate ARDS, use 0.3–0.5 s; and for Severe ARDS, use 0.2–0.3 s.

Once the patient stabilizes, T_Low is customized based on the Slope_EF of the expiratory flow waveform (Equation 1). Figure 9 shows the clinician’s observation when T_Low is calculated and set according to Equation 1. In this example, F_PE is approximately 75 L/min. Therefore, using Equation 1 (F_PE 75 L/min x 75% = F_EE 56 L/min), the clinician should adjust T_Low until the calculated F_EE (56 L/min) is reached (Figure 9). Thus, the clinician does not set T_Low to a specific time but instead to reach the calculated F_EE. The time taken for the lung to empty from F_PE to F_EE represents the desired T_Low (Figure 9, red bracket). Ideally, T_Low is fine-tuned in 0.01-s steps for precise control. If V_T is decreased, thereby decreasing MVe, the T_Low should not be increased beyond 75% to achieve MVe to increase V_T or improve CO₂ removal as this has been shown to increase the risk of RACE-induced atelectrauma (41).

Histological analysis of a rat ARDS model, with lungs fixed at inspiration and expiration, showed that the T_Low set, using Equation 1, effectively distributes gas throughout the alveoli and ducts, closely resembling normal lung function (Figure 5, I). In contrast, T_Low determined using the equation F_PE x 10% = F_EE (APRV 10%) extends T_Low, leading to overdistension of the alveolar ducts (Figure 5, I). Direct in vivo visualization of subpleural alveoli revealed that the T_Low set using Equation 1 was the most effective in recruiting and stabilizing alveoli. The APRV 10% group successfully recruited alveoli during inspiration with the extended T_High but failed to prevent collapse during exhalation, resulting in RACE (Figure 5, II). Using the same methodology, it was shown that T_Low set with Equation 1 was most effective in achieving uniform alveolar behavior compared to T_Low set with the following cofactors: F_PE x 10, 25, 50% = F_EE (11).

Three studies using a clinically relevant 48-h porcine PS + I/R ARDS model showed that setting T_Low based on Equation 1, along with three other consensus conference-recommended settings, provided significant lung protection (Figure 4) (28, 50, 58). Additionally, case studies (Figure 7) (59, 60) and a statistical comparison involving ICU patients (Figure 10) (57) suggest that the T_Low set, as defined by Equation 1, in combination with the three other recommended settings, provides significant lung protection.

Extensive scientific and clinical evidence support using the recommended Equation 1 to set T_Low when employing the APRV mode (Supplementary Files 3–7). Of the four APRV parameters, the recommendations for setting T_Low and P_Low have the most published scientific backing (Supplementary File 2). Future work to refine T_High and P_High settings, potentially through computational modeling and fuzzy logic, could help maximize APRV’s lung-protective capabilities.