Utilizing respiratory rate in APRV-TCAV protocol on Puritan Bennett ventilator. A case report

Abstract

Background Airway Pressure Release Ventilation (APRV), particularly with the Time-Controlled Adaptive Ventilation (TCAV) protocol, is known to improve oxygenation and respiratory mechanics. However, its role in managing refractory hypercapnia remains underexplored. This case report highlights APRV with TCAV as a potential strategy to tackle refractory hypercapnia. Case Report A 43-year-old woman with acute hypoxic and hypercapnic respiratory failure was admitted to our intensive care unit. Over the first 24 hours of management via conventional ventilation modes, she progressed to refractory hypercapnia, leading us to initiate modified APRV settings with TCAV protocol on the Puritan Bennett 980 ventilator (PB 980). This intervention led to rapid improvement in PaCO2, successful transition to PSV, and eventual liberation. Discussion Our literature review revealed limited research on the use of higher controlled respiratory rates in APRV with TCAV. This case demonstrates the potential of this approach, emphasizing the importance of adhering to TCAV principles while optimizing respiratory rate settings. Additionally, we provide insights into APRV titration on the PB 980. Conclusion This report supports the use of APRV with higher controlled respiratory rates, adhering to TCAV protocols, as an effective strategy for managing refractory hypercapnia. Further research is warranted to establish evidence-based guidelines. Keywords: CPAP, Time-Controlled Adaptive Ventilation (TCAV), Refractory Hypercapnia, Ventilation Strategies, Airway Pressure Release Ventilation (APRV)

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Journal of Mechanical Ventilation
Journal of Mechanical Ventilation 2025 Volume 6, Issue 1
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Utilizing respiratory rate in APRV-TCAV protocol on Puritan Bennett ventilator. A case report
Jiaxiao Li, 1 Mohammed S O Al-Amoudi 2
DOI: https://doi.org/10.53097/JMV10121
Cite: Li J, Al-Amoudi MSO. Utilizing Respiratory Rate in APRV-TCAV protocol on Puritan Bennett Ventilator. A Case
Report. J Mech Vent 2025; 6(1):44-51.
Abstract
Background
Airway Pressure Release Ventilation (APRV), particularly with the Time-Controlled Adaptive Ventilation (TCAV) protocol, is
known to improve oxygenation and respiratory mechanics. However, its role in managing refractory hypercapnia remains
underexplored. This case report highlights APRV with TCAV as a potential strategy to tackle refractory hypercapnia.
Case Report
A 43-year-old woman with acute hypoxic and hypercapnic respiratory failure was admitted to our intensive care unit. Over
the first 24 hours of management via conventional ventilation modes, she progressed to refractory hypercapnia, leading us to
initiate modified APRV settings with TCAV protocol on the Puritan Bennett 980 ventilator (PB 980). This intervention led to
rapid improvement in PaCO2, successful transition to PSV, and eventual liberation.
Discussion
Our literature review revealed limited research on the use of higher controlled respiratory rates in APRV with TCAV. This
case demonstrates the potential of this approach, emphasizing the importance of adhering to TCAV principles while
optimizing respiratory rate settings. Additionally, we provide insights into APRV titration on the PB 980.
Conclusion
This report supports the use of APRV with higher controlled respiratory rates, adhering to TCAV protocols, as an effective
strategy for managing refractory hypercapnia. Further research is warranted to establish evidence-based guidelines.
Keywords: CPAP, Time-Controlled Adaptive Ventilation (TCAV), Refractory Hypercapnia, Ventilation Strategies, Airway
Pressure Release Ventilation (APRV)
Authors
1. RRT, Brockville General Hospital, Brockville, and department of surgery, Queen's University, Ontario, Canada
2. MD, FRCSC, FACS, Critical Care Brockville, and department of surgery, Queen's University, Ontario, Canada
Corresponding author: jiaxiaoli17@gmail.com
Conflict of interest/Disclosures: None

Li J Utilizing Respiratory Rate in APRV-TCAV protocol on Puritan Bennett Ventilator: A case report
Journal of Mechanical Ventilation 2025 Volume 6, Issue 1 45
Introduction
Airway Pressure Release Ventilation (APRV) has been
demonstrated to improve oxygenation and respiratory
mechanics. 1 When utilized with the Time-Controlled
Adaptive Ventilation (TCAV) protocol, it offers favorable
hemodynamic profiles. 2 However, evidence on APRV with
TCAV using a higher set respiratory rate to manage
refractory hypercapnia remains limited. Here, we describe a
43-year-old woman with acute hypoxic and hypercapnic
respiratory failure managed successfully with this approach.
Case Description
This is a 43-year-old woman with a history of bronchial
asthma, morbid obesity, chronic kidney disease, and other
comorbidities, presented to the emergency department with
a four-day history of shortness of breath, increased
respiratory distress, tachypnea, and oxygen saturation of
67% on room air. Examination revealed diffuse wheezing
despite continuous nebulization with salbutamol and
ipratropium bromide while on Non-Invasive Ventilation.
Non-Invasive Ventilation therapy failed for refractory
hypercapnia, and she was intubated and admitted to the ICU.
Investigations: Her initial blood work is reflected in Table 1.
Chest CT showed bilateral consolidation, multifocal
opacities, and trace pleural effusion. Venous blood gas
(VBG) analysis showed pH of 7.05, PaCO2 of 58 mmHg post
Non-Invasive Ventilation therapy, and bicarbonate of 17.6
mmol/L.
Interventions: Bronchoscopy was performed which showed
no significant airway secretions. Continuous salbutamol
nebulization, magnesium sulfate, methylprednisolone, and
sodium bicarbonate infusion were initiated. Propofol and
fentanyl achieved sedation targeting a Richmond Agitation-
Sedation Scale (RASS) of -1 to -2.
Initially, the patient was placed on a PB 980 ventilator in
assisted control/volume control plus (AC/VC+) mode, which
is an adaptive ventilation mode rather than traditional
volume controlled mode, targeting low tidal volumes (4-6
mL/kg ideal body weight) and plateau pressure (Pplat) <30
cmH2O, peak pressures < 40 cm H2O. The respiratory rate
(RR) was adjusted to optimize minute ventilation while
limiting auto-PEEP to < 2 cmH2O. FiO2 was titrated to
maintain SpO2 > 92%. To ensure measurement accuracy,
Pplat was measured post intubation during paralytic state,
which showed 30 cmH2O, and static compliance (Cstat) was
11 mL/cmH2O. Airway resistance was reflected by the
difference between Ppeak and Pplat. Pplat was measured at
30 cmH2O, and static compliance (Cstat) was 11 mL/cmH2O.
Lung volume recruitment maneuvers showed no
improvement. Table 2A shows blood gas trends before
APRV, day 1 of admission.
Overnight, ketamine was added for its bronchodilator effect,
but transitioning from propofol to ketamine alone caused
agitation and ventilator asynchrony. Propofol was
reintroduced but asynchrony could not be resolved. Attempts
at pressure support ventilation (PSV) were unsuccessful. The
Minute Ventilation after optimizing the settings before APRV
initiation was 5.7L, with Ppeak of 32 cm H2O. APRV was
subsequently initiated with TCAV protocols with the
following settings:
● P-high: 30 cmH2O
● P-low: 0 cmH2O
● T-high: 2.18 seconds
● T-low: 0.55 seconds
● Respiratory Rate (RR): 22 breaths/min
These settings achieved a minute ventilation (MV) of 7.2 L
and a tidal volume of ~330 mL per breath release. The
patient, sedated only with ketamine at the time, had no
spontaneous breathing. Fentanyl and propofol had been
discontinued 4 and 6 hours earlier, respectively. Settings
were titrated per TCAV protocol every two hours, reaching a
maximum controlled RR of 24. She exhibited intermittent
spontaneous respiration of up to 3 breaths/minute. Blood gas
analysis is listed in Table 3A.
Overnight adjustments per TCAV protocol included titrating
T-low to maintain an end-exhalation flow rate ≥75% of the
peak expiratory flow rate. By morning, APRV settings were
adjusted to a P-high of 26 cmH2O, RR of 20, T-high of 2.7
seconds, and T-low of 0.3 seconds.
As the patient’s condition improved, sedation was adjusted
with the reintroduction of propofol for better comfort.
Salbutamol nebulization was switched to
salbutamol/ipratropium every 2 hours, and sodium
bicarbonate infusion was stopped. P-high was weaned to
target 6–8 ml/kg IBW before reducing RR. By the end of the
day, APRV settings were P-high 16 cmH2O, P-low 0 cmH2O,
RR 10, T-high 5.6 seconds, T-low 0.4 seconds, PS 26 cmH2O
(actual PS was 10 cmH2O, discussed later). These settings
yielded an MV of ~8.5L, total RR of 24, and Vt ~250ml per
controlled breath drop. After assessing sufficient
spontaneous breathing, the patient was transitioned to
Pressure Support mode (PSV) with PEEP 11 cmH2O, PS 12
cmH2O, and FiO2 0.45. Blood gas analysis are listed in Table
3B.
She was transitioned to PSV, then extubated to Non Invasive
Ventilation (NIV), and finally to nasal cannula. The patient

Li J Utilizing Respiratory Rate in APRV-TCAV protocol on Puritan Bennett Ventilator: A case report
Journal of Mechanical Ventilation 2025 Volume 6, Issue 1 46
expressed gratitude, emphasizing her preference to avoid
future intubation.
Table 1: Initial laboratory values.
Venous Blood
Gas pH
7.22
Platelet
128 x
10^9/L
Sodium
136
mmol/L
Creatinine
436 μmol/L
PvCO2
49 mmHg
Neutrophil
8.83 x
10^9/L
Potassium
3.2
mmol/L
eGFR
<15
mL/min/1.73m2
HCO3
20.1 mmHg
Lymphocyte
0.74
x10^9/L
Chloride
104
mmol/L
Total
Bilirubin
5 µmol/L
Lactate
1.1 mmol/L
Eosinophil
0 x 10^9/L
Anion Gap
15
Albumin
36 g/L
WBC
10.67 x
10^9/L
Protein
97 g/L
Magnesium
0.72
mmol/L
ALP
12 U/L
Hbg
108 g/L
Glucose
6.4
mmol/L
Calcium
1.77
mmol/L
ALT
9 U/L
Hct
0.332 L/L
Troponin
38 µg/L
Phosphate
1.36
mmol/L
Table 2A: Blood Gas Trends Before APRV, Day 1 of Admission.
Time
pH
PaCO2
(mmHg)
HCO3
(mmHg)
PaO2
(mmHg)
FiO2
Note
0757
7.15
53
18.5
66
0.65
After one hour in the ICU
1017
7.16
57
20.3
85
1.0
Pre-bronchoscopy. FiO2 was increased to 1.0 for
preoxygenation for bronchoscopy
1512
7.14
66
22.5
78
0.8
Post-bronchoscopy. Ppeak = 34 cmH2O, Pplat =
30 cmH2O. FiO2 titrated to 0.8 to maintain SpO2 >
92%
1759
7.20
65
25.4
72
0.8
2054
7.17
68
24.8
85
0.75
Table 2B: Blood Gas Trends Before APRV, Day 2 of Admission
Time
pH
PaCO2
(mmHg)
HCO3
(mmHg)
PaO2
(mmHg)
Notes
0046
7.21
67
26.8
AC/VC+, RR controlled at 28
0241
7.22
67
27.4
PSV (initiated at 0150), PS 18 cmH2O, PEEP 8 cmH2O, total RR
of 12
0538
7.21
71
28.4
PSV, PS 18 cmH2O, PEEP 8 cmH2O, total RR of 13. Placed back
on AC/VC+ due to worsening blood gas result
1011
7.20
76
29.7
Propofol was stopped two hours prior. Patient switched back to
PSV two hours prior to this blood gas. PS 18 cmH2O, PEEP 8
cmH2O, total RR of 12. PEEP increased, fentanyl stopped.
1455
7.23
74
31
67
PSV, PS 18 cmH2O, PEEP of 12 cmH2O, total RR of 15, FiO2 0.5.
APRV initiated

Li J Utilizing Respiratory Rate in APRV-TCAV protocol on Puritan Bennett Ventilator: A case report
Journal of Mechanical Ventilation 2025 Volume 6, Issue 1 47
Table 3A: Blood Gas Trends on APRV, Day 2 of Admission
Time
pH
PaCO2
(mmHg)
HCO3
(mmHg)
Notes
1707
7.28
65
30.5
This is after 90 minutes of being on APRV. Titrated settings to TCAV
protocol, RR increased to 24
2256
7.29
66
31.7
After 90 min of being on titrated settings.
Table 3B: Blood Gas Trends on APRV, Day 3 of Admission
Time
pH
PaCO2 (mmHg)
HCO3
(mmHg)
Notes
0205
7.32
65
33.5
0539
7.30
69
34
0941
7.30
67
33
1424
7.33
64
33.7
1730
7.33
63
33.2
P-high 16 cmH2O, P-low 0 cmH2O, RR 10, I:E 14:1
2159
7.34
63
34
PS 12 cmH2O PEEP 15 cmH2O
0208
7.39
58
35.1
PS 12 cmH2O PEEP 13 cmH2O
Literature Review and Discussion
Application of TCAV in Hypercapnia
The TCAV protocol, pioneered by Dr. Habashi, 3 emphasizes
personalizing T-low during the expiratory phase to match
individual lung mechanics, allowing the majority of the
respiratory cycles to stay at the mandatory inspiratory
pressure phases. The most up-to-date published review on
TCAV explicitly involves adjusting expiratory time to
maintain end-exhalation flow at ≥ 75% of the peak expiratory
flow rate. This allows prevention of complete exhalation,
promotes lung recruitment through auto-PEEP, mitigates
volutrauma, and ensures effective CO2 elimination during
the "release" phases. 4 TCAV also facilitates spontaneous
breathing, reducing patient-ventilator asynchrony, and
employs a prolonged I:E ratio for personalized tidal volumes.
4,5 Consistent with Jain et al.'s emphasis on personalized T-
low settings, 1 we strictly adhered to our patient’s lung
mechanics, ensuring appropriate flow rates to prevent
ventilator induced lung injury while optimizing recruitment.
Despite its potential, the efficacy of true TCAV approach
with strict protocol adherence remains a research gap. We
conducted a PubMed and Cochrane library search with text
word “TCAV” or “Time Controlled Adaptive Ventilation”
provided several reviews outlining potential physiological
benefits when TCAV is applied alongside APRV, only one
meta-analysis in humans was identified, which provided
inconclusive evidence regarding its advantages, alongside
one ongoing pilot study in France. 6
This systematic review and preplanned meta-analysis by
Katzenschlager et al., failed to identify clinical trials that
demonstrated the superiority of APRV with strict adherence
to TCAV over other ventilation modes. Notably,
Katzenschlager et al. highlighted a tendency to extend the
release phase in randomized controlled trials on hypercapnia,
rather than strictly titrating the respiratory rate per TCAV
principles. 7,8
Our application of TCAV in this case study demonstrates
practical insights into addressing this research gap. To
address refractory hypercapnia and acidosis after the failure
of other ventilation strategies, we implemented APRV with
strict TCAV principles, meanwhile increased respiratory rate
to 24 breaths per minute to augment PaCO2 clearance by
creating more frequent release phases, with T-low settings
adjusted every two hours based on real-time monitoring of
end-expiratory flow to match evolving lung mechanics.
While the calculated mean PaCO2 levels before and after
APRV initiation were similar (Mean PaCO2 before APRV
initiation was 66.4, mean PaCO2 post APRV initiation was
64.4), the overall clinical trend was not reflected as the
PaCO2 level was trending upwards with worsening acidemia.
Although permissive hypercapnia is an accepted strategy to
minimize ventilator-induced lung injury (VILI), its tolerance
depends on the clinical context. In this case, a pH of 7.23
with a PaCO2 of 74 mmHg, if worsening, could pose risks
beyond ventilator mechanics. The fact that PaCO2 was
stabilized after APRV suggests that the intervention helped
prevent further deterioration and demonstrated its potential
role in ventilatory management.

Li J Utilizing Respiratory Rate in APRV-TCAV protocol on Puritan Bennett Ventilator: A case report
Journal of Mechanical Ventilation 2025 Volume 6, Issue 1 48
Though it is not recommended adding pressure support (PS)
during APRV with TCAV protocol, as it may counteract the
intended recruitment effects of spontaneous breathing, its use
in this case was for assisting the patient in increasing minute
ventilation during emergence from sedation and evolving
respiratory efforts.
While APRV has demonstrated improved gas exchange
compared to other ventilation modes under similar minute
ventilation, 9,10 studies have yet to explore the potential of
increasing respiratory rates (release phases) to enhance
PaCO2 clearance. Despite limited studies on increasing
respiratory rates in TCAV for PaCO2 clearance, our search
(‘APRV’ and ‘Hypercapnia’) revealed only 13 results on
PubMed and two Cochrane trials, none offering
definitive guidance. Jain et al.’s review (1987–2016) noted
just three human studies incorporating higher respiratory
rates, 1 and subsequent research since 2017 has included only
a few cases with higher controlled rates. Furthermore, these
studies often lacked methodological clarity or deviated from
TCAV principles.
Our findings align with emerging evidence suggesting that
higher respiratory rates in TCAV could be a valuable strategy
for managing refractory hypercapnia. Table 4 summarizes
the variability and limitations of existing studies, showing
the need for further investigation in this area.
Table 4: Overview of Studies on APRV and Higher Controlled Respiratory Rate Organized by Publication Year
Study
Population
RR (bpm)
Key Findings
Limitations
Räsänen et al.
(1991) 11
Adults
20
Higher RR used.
TCAV adherence unclear.
Sydow et al.
(1994) 12
Adults
24
Higher RR applied; unclear TCAV
adherence.
Combined spontaneous and set RR
not distinguished.
Yoshida et al.
(2009) 13
Adults
Not
controlled
Spontaneous respiration improved
cardiac index and venous return
compared to PSV.
Respiratory rate is not controlled.
Kamath et al.
(2010) 14
Pediatrics
20
Pediatric-specific RR; spontaneous
contributions unclear.
Applicability to adults limited.
Arshad et al.
(2016) 15
Case report
Not recorded
APRV corrected hypercapnia but
deviated from TCAV (I:E = 1:4).
Controlled RR, inconsistent with
TCAV protocol.
Miller et al.
(2017) 16
Survey
20-30 (8%)
Majority of clinicians opted for a lower
set RR; 8% used 20-30 bpm.
Survey-based data, not clinical
outcomes.
Kreyer et al.
(2021) 17
Adults
35
Applied T-high : T-low of 1:2 to manage
hypercapnia.
Controlled RR
Inconsistent with TCAV protocol.
Rola et al.
(2022) 18
Theoretical
concept
~25
Hypothesized approach to approximate
TCAV for patient transfer under sedation
with pressure control mode.
Theoretical; not validated in
clinical practice.
Simón et al.
(2023) 19
Adults
29.35
Observational study comparing APRV
and PSV; promoted spontaneous
ventilation.
Controlled RR not recorded.
While the increase in RR helped clear PaCO2 in this case, it is
important to recognize that a higher RR also increases
mechanical power, linking to VILI. Raising RR without
considering alveolar ventilation, dead space, and the risk of
auto-PEEP may be harmful. Clinicians should be
mindful of these factors when adjusting ventilator settings.
In addition, while TCAV is designed to improve
lung recruitment and protection, some aspects of its
implementation remain unclear. The recommended end-
exhalation flow rate adjusted to 75% of peak exhalation
flow rate criteria for setting T-low does not have a fully
established physiological basis. Other methods such as setting
the T-low according to the expiratory time constant may also
be feasible. 20 More research is needed to establish the best
method.
With increased RR, clinicians should also pay close attention
to hemodynamic changes during titration as raising RR poses
patients to increased risk of obstructive shock due to increased

Li J Utilizing Respiratory Rate in APRV-TCAV protocol on Puritan Bennett Ventilator: A case report
Journal of Mechanical Ventilation 2025 Volume 6, Issue 1 49
total PEEP. An expiratory hold maneuver is commonly
performed for measuring total PEEP, which may not be
feasible for some ventilators.
Ventilators such as Getinge Servo and Hamilton ventilators
allow for an expiratory hold maneuver, whereas others, like
PB ventilators, do not. Drager ventilators offer an expiratory
hold function, but the maneuver is often prolonged, increasing
the risk of derecruitment. These differences in ventilator
functionality should be considered when applying APRV.
Tracking the trend of static compliance through measurement
of driving pressure is also valuable. However, keep in mind
that the accuracy in spontaneously breathing patients is
questionable as spontaneous respiration alters accuracy of
measurement.
In such cases, estimating driving pressure by incorporating
total PEEP measurements may provide a more practical
approach.
Transitioning from Deep Sedation with APRV
APRV supports PaCO2 clearance by integrating
spontaneous breathing with a controlled respiratory rate,
making it effective for patients emerging from deep sedation.
Initially, our patient’s spontaneous breathing was
insufficient. Putensen et al. showed that spontaneous
breathing improves V/Q distribution in ARDS, but
APRV without spontaneous breathing is similar to PCV. 21
By employing a higher controlled respiratory rate, we
achieved effective gas exchange while supporting the gradual
recovery of spontaneous breathing and
enhancing V/Q distribution. Effective sedation is crucial
during APRV to prevent agitation, which can impair gas
exchange and exacerbate bronchoconstriction.
Zhou et al. emphasized balancing sedation with
spontaneous breathing, 22 highlighting the importance of
individualized sedation strategies, especially in patients
with complex comorbidities. 23
Technical Considerations on PB 980 Ventilators
When titrating T-low on the PB 980 ventilator, the peak point
on the exhalation flow waveform should not be used as the
peak exhalation flow rate. Instead, the second-highest flow
rate, which descends smoothly during exhalation, represents
the true peak exhalation flow rate. This distinction arises
because the ventilator’s exhalation valve, defined as
controlling PEEP, 24 causes the initial peak in the waveform
when transitioning from P-high to P-low, reflecting valve
mechanics rather than lung exhalation. In addition, the PS
setting should be set as Ppeak, meaning the actual PS equals
the gradient between Ppeak and P-high, allowing PS breaths
to be delivered (Figure 1A and Figure 1B).
What’s more, spontaneous breaths taken at the end of P-high
may prolong T-low due to synchronization settings potentially
altering the intended lung protection strategy. These
variations emphasize the need for careful adjustments when
applying TCAV.
Figure 1A Figure 1B
Figure 1A showed the distinction between valve mechanism and actual exhalation phases. Figure 1B showed the relationship between PS
setting and Ppeak.

Li J Utilizing Respiratory Rate in APRV-TCAV protocol on Puritan Bennett Ventilator: A case report
Journal of Mechanical Ventilation 2025 Volume 6, Issue 1 50
Conclusion
APRV with TCAV protocol, incorporating a higher
controlled respiratory rate, successfully managed refractory
hypercapnia in this case. Clinicians should consider tailoring
APRV settings to individual lung mechanics and leveraging
higher respiratory rate when conventional strategies fail.
Further research is warranted to establish evidence-based
guidelines for this approach.
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brary/us/en/product/acute-care-
ventilation/PuritanBennett980Ventilator_OperatorsManual_
en_OUS_PT00094084A00.pdf.