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Closed-loop oxygen control vs. manual oxygen titration: Is there a benefit?

Article

Author: Justin Tse, RRT

Date of first publication: 11.09.2025

The authors' point? Pediatric patients with acute hypoxemic respiratory failure spend more time in optimal SpO2 ranges with closed-loop oxygen control.

Clinical question

In pediatric patients receiving invasive mechanical ventilation (IMV) for acute hypoxemic respiratory failure (AHRF), does using a closed-loop oxygen control system have benefits over manual oxygen titration in terms of time spent within optimal oxygen saturation (SpO2) ranges, enhanced safety, and reduced overall oxygen consumption, regardless of the ventilation mode applied?

Clinical background

Oxygen therapy is crucial for managing respiratory failure in pediatric patients, ensuring adequate oxygenation when the lungs are compromised. 

Recommendations made by the Pediatric Mechanical Ventilation Conference (PEMVECC):

  • All ventilated children should have continuous SpO2 monitoring using pulse oximetry 
  • Arterial oxygen pressure (PaO2) should be measured in those with moderate-to-severe respiratory conditions
     

Clinical challenges:

  • Prevention of hypoxemia and hyperoxemia, both linked to poor outcomes
  • Manual titration of FiO2 can be an annoyance for staff, especially during high-demand periods
  • Increased oxygen utilization (overuse of oxygen resources)

Closed-loop oxygen control systems that automatically adjust FiO2 based on real-time SpO2 monitoring may address these issues. To date however, the use of these systems in pediatric  patients undergoing invasive mechanical ventilation for AHRF has been insufficiently studied.

Design and settings

  • The study employed a multicenter, single-blinded, randomized, crossover design and was conducted across four medical facilities in Turkey
  • Enrolment period: June 2022 to October 2022
  • Participants were randomly assigned to begin with either closed-loop oxygen control or manual oxygen titration for 2 hours, followed by a switch to the other method after a 30-minute washout period
  • Randomization was done in a 1:1 ratio with sealed opaque envelopes, using blocks of 4

Patients

Thirty-three pediatric patients were randomized for the study.
Inclusion criteria Aged 1 month to 18 years
Receiving IMV with FiO2 > 25% to maintain SpO2 within clinician-defined parameters
Exclusion criteria Diseases or conditions affecting SpO2 measurement (e.g., dyshemoglobinemia, CO poisoning, sickle cell disease)
Requirement for continuous infusion of epinephrine or norepinephrine at rates > 1 mg/h
Immediate need for noninvasive ventilation (NIV) or high flow oxygen therapy
Poor quality SpO2 measurements using finger or ear sensors
Severe acidosis
High risk of requiring NIV or transportation to another unit or hospital
Formalized ethical decision to withhold or withdraw life support
Participation in another research study
Previous enrolment in the study during a prior episode of acute respiratory failure

Intervention

Intervention Details
Intubation and positioning Appropriately sized endotracheal tube (ETT)
Semi-recumbent position
Ventilation and oxygen control IMV using HAMILTON–C1 or HAMILTON-C6 ventilators with closed-loop oxygen control
Sedation Sedatives as needed
Sedation levels constant throughout the study
Patient care Routine tasks (e.g., suctioning and nutrition) were performed without interruption during both intervention periods
Oxygen saturation targets The attending pediatric intensivist determined each patient's optimal SpO2 range based on their clinical condition and factors such as lung compliance, driving pressure (∆P), plateau pressure (Pplat), and PEEP to ensure adequate oxygenation, while minimizing the risks from excessively high or low oxygen levels

Measurements

Analysis Details
Primary Comparison of the percentage of time spent within optimal SpO2 ranges using closed-loop vs. manual titration
Secondary Percentage of time spent in suboptimal and unacceptable SpO2 ranges
FiO2 and SpO2/FiO2 ratio
Frequency of manual oxygen changes
Number of alarms
Percentage of time with an available SpO2 signal
Total oxygen consumption
Sensitivity Wilcoxon signed-rank test used to compare the time spent in optimal SpO2 ranges between closed-loop and manual oxygen titration
Statistical power: 95% for detecting an effect size of Cohen's d = 0.68 with 35 patients

Primary outcome

Outcome

Closed-loop oxygen control

Manual oxygen titration

Difference / P-value

Time within optimal SpO2 range (%)

95.7% (IQR: 92.1% - 100%)  

65.6% (IQR: 41.6% - 82.5%)

Mean difference: 33.4% (95% CI: 24.5% - 42%)
P < 0.001

Secondary outcomes

Outcome

Closed-loop oxygen control

Manual oxygen titration

P-value

Time in unacceptable and suboptimal SpO2 ranges (%)

Significantly lower

Higher

--

Time in unacceptably high SpO2 range (%)

Significantly reduced

Higher

--

Mean FiO2

32.1 (23.9–54.1)

40.6 (31.1–62.8)

P < 0.001

Total oxygen utilization (l/h)

19.8 (4.6–64.8)

39.4 (16.8–79.9)

P < 0.001

SpO2/FiO2 ratio

329.4 (180–411.1)

246.7 (151.1–320.5)

P < 0.001

Manual adjustments (n/hr)

0 (0–0)

1 (0–2.2)

P < 0.001

Conclusions

This evaluation of closed-loop oxygen control versus manual oxygen titration in pediatric patients with AHRF shows significant benefits of the closed-loop system. It improves the duration of time spent within optimal SpO2 ranges and reduces the time spent in oxygenation zones that may pose risks (Atakul G, Ceylan G, Sandal O, et al. Closed-loop oxygen usage during invasive mechanical ventilation of pediatric patients (CLOUDIMPP): a randomized controlled cross-over study. Front Med (Lausanne). 2024;11:1426969. Published 2024 Sep 10. doi:10.3389/fmed.2024.14269691​).

Additionally, it enhances overall oxygenation, conserves oxygen resources, and reduces the need for manual adjustments. These findings highlight the potential clinical advantages of implementing closed-loop systems in managing pediatric AHRF.

Limitations

  • The 2-hour study duration may not capture long-term effects or variability in patient responses, especially in critical care.
  • The study did not examine key long-term outcomes such as the duration of invasive ventilation or the transition to NIV.
  • Excluding patients with darker skin types (Fitzpatrick scale > 4) limits the applicability of results to a diverse population and does not address potential pulse oximetry biases.
  • The lack of clear definitions for "optimal" and "ideal oxygenation" makes it difficult to apply results in practice. More research is needed to establish guidelines for the best oxygen levels for patients.

Food for thought

  • The closed-loop oxygen controller significantly improved the stability of optimal SpO2 levels and reduced the time spent in potentially harmful oxygenation zones (hypoxemia and hyperoxia). This suggests enhanced patient safety and more reliable oxygenation management in critically  ill pediatric patients with AHRF.
  • By delivering oxygen more precisely and only when necessary, the closed-loop system reduced overall oxygen consumption. This has notable implications for both cost-effectiveness and sustainability in healthcare, particularly in resource-limited settings.
  • The study demonstrated that closed-loop oxygen control worked effectively across various ventilation modes, both assisted and passive. This broad applicability is a key strength, suggesting that the system could be beneficial across a wide range of patient populations.
  • Closed-loop oxygenation control can improve the efficiency of care delivery, reduce human error, and alleviate the clinician’s workload. This feature is especially beneficial in busy or understaffed ICUs, enhancing both patient care and operational efficiency.
     

How can I incorporate these findings into my daily work with Hamilton Medical technology?

  • Selected Hamilton Medical ventilators offer the integrated O2 assist feature to support precise oxygen management. Once the clinician has set the desired SpO2 target range according to clinical protocols, O2 assist continually adjusts FiO2 to help keep patients within range, reducing time spent in hypo- or hyperoxemia  (Atakul G, Ceylan G, Sandal O, et al. Closed-loop oxygen usage during invasive mechanical ventilation of pediatric patients (CLOUDIMPP): a randomized controlled cross-over study. Front Med (Lausanne). 2024;11:1426969. Published 2024 Sep 10. doi:10.3389/fmed.2024.14269691,​ Sandal O, Ceylan G, Topal S, et al. Closed-loop oxygen control improves oxygenation in pediatric patients under high-flow nasal oxygen-A randomized crossover study. Front Med (Lausanne). 2022;9:1046902. Published 2022 Nov 16. doi:10.3389/fmed.2022.10469022​, Trottier M, Bouchard PA, L'Her E, Lellouche F. Automated Oxygen Titration During CPAP and Noninvasive Ventilation in Healthy Subjects With Induced Hypoxemia. Respir Care. 2023;68(11):1553-1560. doi:10.4187/respcare.098663​).

  • The continuous adjustment function responds to changing measured SpO2 values, which is particularly beneficial for patients with fluctuating needs (Atakul G, Ceylan G, Sandal O, et al. Closed-loop oxygen usage during invasive mechanical ventilation of pediatric patients (CLOUDIMPP): a randomized controlled cross-over study. Front Med (Lausanne). 2024;11:1426969. Published 2024 Sep 10. doi:10.3389/fmed.2024.14269691​, Sandal O, Ceylan G, Topal S, et al. Closed-loop oxygen control improves oxygenation in pediatric patients under high-flow nasal oxygen-A randomized crossover study. Front Med (Lausanne). 2022;9:1046902. Published 2022 Nov 16. doi:10.3389/fmed.2022.10469022​, Roca O, Caritg O, Santafé M, et al. Closed-loop oxygen control improves oxygen therapy in acute hypoxemic respiratory failure patients under high flow nasal oxygen: a randomized cross-over study (the HILOOP study). Crit Care. 2022;26(1):108. Published 2022 Apr 14. doi:10.1186/s13054-022-03970-w4​), such as those with acute hypoxemic respiratory failure. This minimizes the need for frequent manual interventions (Atakul G, Ceylan G, Sandal O, et al. Closed-loop oxygen usage during invasive mechanical ventilation of pediatric patients (CLOUDIMPP): a randomized controlled cross-over study. Front Med (Lausanne). 2024;11:1426969. Published 2024 Sep 10. doi:10.3389/fmed.2024.14269691​, Roca O, Caritg O, Santafé M, et al. Closed-loop oxygen control improves oxygen therapy in acute hypoxemic respiratory failure patients under high flow nasal oxygen: a randomized cross-over study (the HILOOP study). Crit Care. 2022;26(1):108. Published 2022 Apr 14. doi:10.1186/s13054-022-03970-w4​), allowing clinicians to focus on other aspects of patient care.

  • Trend monitoring capabilities provide valuable data on SpO2 and FiO2 over time, enabling clinicians to evaluate oxygenation patterns, assess the impact of interventions, and optimize treatment strategies.

  • By combining automated regulation with actionable trend data, O2 assist helps ensure more stable oxygenation, supports adherence to guidelines, and may promote better patient outcomes  (Atakul G, Ceylan G, Sandal O, et al. Closed-loop oxygen usage during invasive mechanical ventilation of pediatric patients (CLOUDIMPP): a randomized controlled cross-over study. Front Med (Lausanne). 2024;11:1426969. Published 2024 Sep 10. doi:10.3389/fmed.2024.14269691​, Sandal O, Ceylan G, Topal S, et al. Closed-loop oxygen control improves oxygenation in pediatric patients under high-flow nasal oxygen-A randomized crossover study. Front Med (Lausanne). 2022;9:1046902. Published 2022 Nov 16. doi:10.3389/fmed.2022.10469022​, Trottier M, Bouchard PA, L'Her E, Lellouche F. Automated Oxygen Titration During CPAP and Noninvasive Ventilation in Healthy Subjects With Induced Hypoxemia. Respir Care. 2023;68(11):1553-1560. doi:10.4187/respcare.098663​, Roca O, Caritg O, Santafé M, et al. Closed-loop oxygen control improves oxygen therapy in acute hypoxemic respiratory failure patients under high flow nasal oxygen: a randomized cross-over study (the HILOOP study). Crit Care. 2022;26(1):108. Published 2022 Apr 14. doi:10.1186/s13054-022-03970-w4​).

Footnotes

References

  1. 1. Atakul G, Ceylan G, Sandal O, et al. Closed-loop oxygen usage during invasive mechanical ventilation of pediatric patients (CLOUDIMPP): a randomized controlled cross-over study. Front Med (Lausanne). 2024;11:1426969. Published 2024 Sep 10. doi:10.3389/fmed.2024.1426969
  2. 2. Sandal O, Ceylan G, Topal S, et al. Closed-loop oxygen control improves oxygenation in pediatric patients under high-flow nasal oxygen-A randomized crossover study. Front Med (Lausanne). 2022;9:1046902. Published 2022 Nov 16. doi:10.3389/fmed.2022.1046902
  3. 3. Trottier M, Bouchard PA, L'Her E, Lellouche F. Automated Oxygen Titration During CPAP and Noninvasive Ventilation in Healthy Subjects With Induced Hypoxemia. Respir Care. 2023;68(11):1553-1560. doi:10.4187/respcare.09866
  4. 4. Roca O, Caritg O, Santafé M, et al. Closed-loop oxygen control improves oxygen therapy in acute hypoxemic respiratory failure patients under high flow nasal oxygen: a randomized cross-over study (the HILOOP study). Crit Care. 2022;26(1):108. Published 2022 Apr 14. doi:10.1186/s13054-022-03970-w

Closed-loop oxygen usage during invasive mechanical ventilation of pediatric patients (CLOUDIMPP): a randomized controlled cross-over study.

Atakul G, Ceylan G, Sandal O, et al. Closed-loop oxygen usage during invasive mechanical ventilation of pediatric patients (CLOUDIMPP): a randomized controlled cross-over study. Front Med (Lausanne). 2024;11:1426969. Published 2024 Sep 10. doi:10.3389/fmed.2024.1426969

BACKGROUND The aim of this study is the evaluation of a closed-loop oxygen control system in pediatric patients undergoing invasive mechanical ventilation (IMV). METHODS Cross-over, multicenter, randomized, single-blind clinical trial. Patients between the ages of 1 month and 18 years who were undergoing IMV therapy for acute hypoxemic respiratory failure (AHRF) were assigned at random to either begin with a 2-hour period of closed-loop oxygen control or manual oxygen titrations. By using closed-loop oxygen control, the patients' SpO2 levels were maintained within a predetermined target range by the automated adjustment of the FiO2. During the manual oxygen titration phase of the trial, healthcare professionals at the bedside made manual changes to the FiO2, while maintaining the same target range for SpO2. Following either period, the patient transitioned to the alternative therapy. The outcomes were the percentage of time spent in predefined SpO2 ranges ±2% (primary), FiO2, total oxygen use, and the number of manual adjustments. FINDINGS The median age of included 33 patients was 17 (13-55.5) months. In contrast to manual oxygen titrations, patients spent a greater proportion of time within a predefined optimal SpO2 range when the closed-loop oxygen controller was enabled (95.7% [IQR 92.1-100%] vs. 65.6% [IQR 41.6-82.5%]), mean difference 33.4% [95%-CI 24.5-42%]; P < 0.001). Median FiO2 was lower (32.1% [IQR 23.9-54.1%] vs. 40.6% [IQR 31.1-62.8%]; P < 0.001) similar to total oxygen use (19.8 L/h [IQR 4.6-64.8] vs. 39.4 L/h [IQR 16.8-79]; P < 0.001); however, median SpO2/FiO2 was higher (329.4 [IQR 180-411.1] vs. 246.7 [IQR 151.1-320.5]; P < 0.001) with closed-loop oxygen control. With closed-loop oxygen control, the median number of manual adjustments reduced (0.0 [IQR 0.0-0.0] vs. 1 [IQR 0.0-2.2]; P < 0.001). CONCLUSION Closed-loop oxygen control enhances oxygen therapy in pediatric patients undergoing IMV for AHRF, potentially leading to more efficient utilization of oxygen. This technology also decreases the necessity for manual adjustments, which could reduce the workloads of healthcare providers. CLINICAL TRIAL REGISTRATION This research has been submitted to ClinicalTrials.gov (NCT05714527).

Closed-loop oxygen control improves oxygenation in pediatric patients under high-flow nasal oxygen-A randomized crossover study.

Sandal O, Ceylan G, Topal S, et al. Closed-loop oxygen control improves oxygenation in pediatric patients under high-flow nasal oxygen-A randomized crossover study. Front Med (Lausanne). 2022;9:1046902. Published 2022 Nov 16. doi:10.3389/fmed.2022.1046902

BACKGROUND We assessed the effect of a closed-loop oxygen control system in pediatric patients receiving high-flow nasal oxygen therapy (HFNO). METHODS A multicentre, single-blinded, randomized, and cross-over study. Patients aged between 1 month and 18 years of age receiving HFNO for acute hypoxemic respiratory failure (AHRF) were randomly assigned to start with a 2-h period of closed-loop oxygen control or a 2-h period of manual oxygen titrations, after which the patient switched to the alternative therapy. The endpoints were the percentage of time spent in predefined SpO2 ranges (primary), FiO2, SpO2/FiO2, and the number of manual adjustments. FINDINGS We included 23 patients, aged a median of 18 (3-26) months. Patients spent more time in a predefined optimal SpO2 range when the closed-loop oxygen controller was activated compared to manual oxygen titrations [91⋅3% (IQR 78⋅4-95⋅1%) vs. 63⋅0% (IQR 44⋅4-70⋅7%)], mean difference [28⋅2% (95%-CI 20⋅6-37⋅8%); P < 0.001]. Median FiO2 was lower [33⋅3% (IQR 26⋅6-44⋅6%) vs. 42⋅6% (IQR 33⋅6-49⋅9%); P = 0.07], but median SpO2/FiO2 was higher [289 (IQR 207-348) vs. 194 (IQR 98-317); P = 0.023] with closed-loop oxygen control. The median number of manual adjustments was lower with closed-loop oxygen control [0⋅0 (IQR 0⋅0-0⋅0) vs. 0⋅5 (IQR 0⋅0-1⋅0); P < 0.001]. CONCLUSION Closed-loop oxygen control improves oxygenation therapy in pediatric patients receiving HFNO for AHRF and potentially leads to more efficient oxygen use. It reduces the number of manual adjustments, which may translate into decreased workloads of healthcare providers. CLINICAL TRIAL REGISTRATION [www.ClinicalTrials.gov], identifier [NCT05032365].

Automated Oxygen Titration During CPAP and Noninvasive Ventilation in Healthy Subjects With Induced Hypoxemia.

Trottier M, Bouchard PA, L'Her E, Lellouche F. Automated Oxygen Titration During CPAP and Noninvasive Ventilation in Healthy Subjects With Induced Hypoxemia. Respir Care. 2023;68(11):1553-1560. doi:10.4187/respcare.09866

BACKGROUND Automated oxygen titration to maintain a stable SpO2 has been developed for spontaneously breathing patients but has not been evaluated during CPAP and noninvasive ventilation (NIV). METHODS We performed a randomized controlled crossover, double-blind study on 10 healthy subjects with induced hypoxemia during 3 situations: spontaneous breathing with oxygen support, CPAP (5 cm H2O), and NIV (7/3 cm H2O). We conducted in random order 3 dynamic hypoxic challenges of 5 min (FIO2 0.08 ± 0.02, 0.11± 0.02, and 0.14 ± 0.02). For each condition, we compared automated oxygen titration and manual oxygen titration by experienced respiratory therapists (RTs), with the aim to maintain the SpO2 at 94 ± 2%. In addition, we included 2 subjects hospitalized for exacerbation of COPD under NIV and a subject managed after bariatric surgery with CPAP and automated oxygen titration. RESULTS The percentage of time in the SpO2 target was higher with automated compared with manual oxygen titration for all conditions, on average 59.6 ± 22.8% compared to 44.3 ± 23.9% (P = .004). Hyperoxemia (SpO2 > 96%) was less frequent with automated titration for each mode of oxygen administration (24.0 ± 24.4% vs 39.1 ± 25.3%, P < .001). During the manual titration periods, the RT made several changes to oxygen flow (5.1 ± 3.3 interventions that lasted 122 ± 70 s/period) compared to none during the automated titration to maintain oxygenation in the targeted SpO2 . Time in the SpO2 target was higher with stable hospitalized subjects in comparison with healthy subjects under dynamic-induced hypoxemia. CONCLUSIONS In this proof-of-concept study, automated oxygen titration was used during CPAP and NIV. The performances to maintain the SpO2 target were significantly better compared to manual oxygen titration in the setting of this study protocol. This technology may allow decreasing the number of manual interventions for oxygen titration during CPAP and NIV.

Closed-loop oxygen control improves oxygen therapy in acute hypoxemic respiratory failure patients under high flow nasal oxygen: a randomized cross-over study (the HILOOP study).

Roca O, Caritg O, Santafé M, et al. Closed-loop oxygen control improves oxygen therapy in acute hypoxemic respiratory failure patients under high flow nasal oxygen: a randomized cross-over study (the HILOOP study). Crit Care. 2022;26(1):108. Published 2022 Apr 14. doi:10.1186/s13054-022-03970-w

BACKGROUND We aimed to assess the efficacy of a closed-loop oxygen control in critically ill patients with moderate to severe acute hypoxemic respiratory failure (AHRF) treated with high flow nasal oxygen (HFNO). METHODS In this single-centre, single-blinded, randomized crossover study, adult patients with moderate to severe AHRF who were treated with HFNO (flow rate ≥ 40 L/min with FiO2 ≥ 0.30) were randomly assigned to start with a 4-h period of closed-loop oxygen control or 4-h period of manual oxygen titration, after which each patient was switched to the alternate therapy. The primary outcome was the percentage of time spent in the individualized optimal SpO2 range. RESULTS Forty-five patients were included. Patients spent more time in the optimal SpO2 range with closed-loop oxygen control compared with manual titrations of oxygen (96.5 [93.5 to 98.9] % vs. 89 [77.4 to 95.9] %; p < 0.0001) (difference estimate, 10.4 (95% confidence interval 5.2 to 17.2). Patients spent less time in the suboptimal range during closed-loop oxygen control, both above and below the cut-offs of the optimal SpO2 range, and less time above the suboptimal range. Fewer number of manual adjustments per hour were needed with closed-loop oxygen control. The number of events of SpO2 < 88% and < 85% were not significantly different between groups. CONCLUSIONS Closed-loop oxygen control improves oxygen administration in patients with moderate-to-severe AHRF treated with HFNO, increasing the percentage of time in the optimal oxygenation range and decreasing the workload of healthcare personnel. These results are especially relevant in a context of limited oxygen supply and high medical demand, such as the COVID-19 pandemic. Trial registration The HILOOP study was registered at www. CLINICALTRIALS gov under the identifier NCT04965844 .