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Closed-loop systems in mechanically ventilated pediatric patients: The latest evidence

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Autore: Caroline Brown

Data: 07.12.2022

Two recent studies investigated the use of a closed-loop ventilation mode and closed-loop control of the fraction of inspired oxygen (FiO2) in pediatric patients.
Closed-loop systems in mechanically ventilated pediatric patients: The latest evidence

While considerable evidence now exists on the use of closed-loop systems in adults, there is only limited data available on their use in pediatrics. Similarly, there is little evidence on the effect of driving pressure (∆P) on outcomes in children, which has been found in adults to be the variable most closely associated with mortality in adult ARDS patients (Amato MB, Meade MO, Slutsky AS, et al. Driving pressure and survival in the acute respiratory distress syndrome. N Engl J Med. 2015;372(8):747-755. doi:10.1056/NEJMsa14106391​). A recent retrospective cohort study in children with acute hypoxemic respiratory failure ventilated with high ∆P (≥ 15 cmH2O) or low ∆P (< 15 cmH2O) found no difference in terms of mortality, but a significant decrease in morbidity in the low ∆P group. Those in the low ∆P group also had more ventilator-free days, and shorter ICU and hospital stays (Rauf A, Sachdev A, Venkataraman ST, Dinand V. Dynamic Airway Driving Pressure and Outcomes in Children With Acute Hypoxemic Respiratory Failure. Respir Care. 2021;66(3):403-409. doi:10.4187/respcare.080242​). A team of investigators at the Dr Behcet Uz Children's Disease and Surgery Training and Research Hospital in Izmir, Turkey, set out to compare the driving pressure generated by Adaptive Support Ventilation (ASV 1.1) in pediatric patients with respiratory failure with one of the most commonly used modes in pediatrics, controlled mandatory ventilation with adaptive pressure ventilation (APV-CMV) (Ceylan G, Topal S, Atakul G, et al. Randomized crossover trial to compare driving pressures in a closed-loop and a conventional mechanical ventilation mode in pediatric patients. Pediatr Pulmonol. 2021;56(9):3035-3043. doi:10.1002/ppul.255613​).

ASV 1.1 versus APV-CMV

This randomized controlled trial included 26 patients with a median age of 16 months and heterogenous lung conditions (restrictive, obstructive, and normal). They were ventilated for two 60-minute periods, one in ASV 1.1 and one in APV-CMV. The same minute ventilation was maintained in both modes. APV-CMV adjusts the applied pressure to avoid low or high tidal volumes when compliance changes, but maintains the target tidal volume (VT) set by the clinician as long as pressure remains under the set limit. In contrast, ASV determines the optimal combination of respiratory rate (RR) and VT for the clinician-set minute volume based on a breath-by-breath analysis of the patient’s respiratory mechanics. This behavior corresponds with the Pediatric Acute Lung Injury Consensus Conference recommendation to select VT according to the disease severity of the individual patient (Pediatric Acute Lung Injury Consensus Conference Group. Pediatric acute respiratory distress syndrome: consensus recommendations from the Pediatric Acute Lung Injury Consensus Conference. Pediatr Crit Care Med. 2015;16(5):428-439. doi:10.1097/PCC.00000000000003504​). The investigators therefore hypothesized that the settings automatically selected by ASV 1.1 would result in lower driving pressure than in the physician-tailored APV-CMV mode.

Lower pressures and tidal volume

Driving pressure was calculated as the difference between plateau pressure and the total positive end-expiratory pressure (total PEEP). These parameters were measured by means of an end-inspiratory and end-expiratory hold, respectively. The median ∆P during the ASV 1.1 phase was found to be significantly lower than during the APV-CMV period (10.4 [8.5−12.1 {IQR}]) and 12.4 [10.5−15.3 {IQR}] cmH2O, respectively [p < 0.001]).  In addition, the median tidal volume was also significantly lower in the ASV 1.1 group (6.4 ml/kg vs 7.9 ml/kg; p < .001), as were peak inspiratory pressure (19.1 cmH2O vs 22.5 cmH2O; p = 0.001) and plateau pressure (16.9 cmH2O vs 18.4 cmH2O; p < 0.001). End-tidal CO2 was significantly higher (41 mmHg vs 38 mmHg; p = 0.001). In neither group did any of the ventilation parameters or arterial blood gas values exceed the current recommendations for mechanical ventilation in pediatrics, so all patients remained within safe zones at all times (Ceylan G, Topal S, Atakul G, et al. Randomized crossover trial to compare driving pressures in a closed-loop and a conventional mechanical ventilation mode in pediatric patients. Pediatr Pulmonol. 2021;56(9):3035-3043. doi:10.1002/ppul.255613​). 

While it is possible to achieve similar results in pressure-regulated volume control by lowering the targeted VT, this requires sufficient staff on hand to make the adjustments. Particularly where resources are limited, ASV 1.1 has the benefit of automatically adjusting VT and RR according to a change in respiratory mechanics as soon as it occurs. Even in the case of adequate resources, it is clear that automatic titration of ventilation around the clock can lower the burden on ICU staff.

Manual versus closed-loop FiO2 titration

In the second study, the same investigators compared manual FiO2 titration with use of a closed-loop FiO2 titration system in pediatric patients (Soydan E, Ceylan G, Topal S, et al. Automated closed-loop FiO2 titration increases the percentage of time spent in optimal zones of oxygen saturation in pediatric patients-A randomized crossover clinical trial. Front Med (Lausanne). 2022;9:969218. Published 2022 Aug 25. doi:10.3389/fmed.2022.9692185​). While a meta-analysis in preterm infants undergoing positive pressure respiratory support suggested an association between automated FiO2 titration and more time spent in target oxygen saturation (SpO2) ranges (Mitra S, Singh B, El-Naggar W, McMillan DD. Automated versus manual control of inspired oxygen to target oxygen saturation in preterm infants: a systematic review and meta-analysis. J Perinatol. 2018;38(4):351-360. doi:10.1038/s41372-017-0037-z6​), the effect in pediatric patients is not clear. In an earlier pilot study in a small cohort of mechanically ventilated children, ASV together with closed-loop control of ventilation and oxygenation had been found to keep them in normal ventilation (number of normal breaths divided by total number of breaths collected) for a similar percentage of time as pressure-support ventilation (Jouvet P, Eddington A, Payen V, et al. A pilot prospective study on closed loop controlled ventilation and oxygenation in ventilated children during the weaning phase. Crit Care. 2012;16(3):R85. Published 2012 May 16. doi:10.1186/cc113437​). 

The current study included a cohort of 30 patients with an average age of 21 months and heterogenous lung conditions, 12 of them with pediatric ARDS (Soydan E, Ceylan G, Topal S, et al. Automated closed-loop FiO2 titration increases the percentage of time spent in optimal zones of oxygen saturation in pediatric patients-A randomized crossover clinical trial. Front Med (Lausanne). 2022;9:969218. Published 2022 Aug 25. doi:10.3389/fmed.2022.9692185​). All patients were ventilated in ASV 1.1 for two phases of 2.5 hours each. During one phase the automated FiO2 controller was activated and during the second, FiO2 was titrated manually. The first 30 minutes of each phase were considered a run-in period; data was collected for two hours of each phase. Minute ventilation and PEEP were maintained at the same level during the two phases. The primary endpoint was the percentage of time spent in predefined optimal SpO2 zones, while secondary outcomes included the time spent in acceptable, suboptimal and unacceptable zones, as well as the number of FiO2 changes per patient.

More time spent in the optimal SpO2 range

Results showed patients spent significantly more time in the optimal range with the FiO2 controller activated than with manual FiO2 titration (96.1% [93.7–98.6 {IQR}] vs 78.4% [51.3–94.8 {IQR}; [p < 0.001]). In addition, they also spent significantly less time in the unacceptably low, suboptimally low, acceptably low, and suboptimally high zones with automated FiO2 control (p-values 0.032, 0.008, 0.004, and 0.001, respectively). An additional finding was the lower median FiO2 percentage with automated FiO2 control. Based on a study in children receiving VV-ECMO that suggested an association between higher FiO2 and mortality (Friedman ML, Barbaro RP, Bembea MM, et al. Mechanical Ventilation in Children on Venovenous ECMO. Respir Care. 2020;65(3):271-280. doi:10.4187/respcare.072148​), lower FiO2 with closed-loop FiO2 control may have a positive effect on outcomes.

Efficiency of closed-loop systems

In terms of efficiency, the authors noted several different aspects. Firstly, the far higher number of adjustments per patient that were made by the FiO2 controller than were made manually (52 [11.8–67 {IQR}] vs 1 [0–2 {IQR}], p < 0.001). Even making just one change every two hours in 30 patients may stretch hospital resources; making multiple changes manually within a two-hour period is hardly feasible. Secondly, both the median oxygenation index and the median O2 usage were lower during the automated phase than the manual phase, representing a more efficient use of therapeutic oxygen. 

As well as adding to the limited evidence on the use of automated ventilation modes in pediatrics, these two studies demonstrate the potential benefits of automation in terms of efficiency. Not only do automated ventilation modes enable a greater number of adjustments in response to changes in the patient’s condition, they may also lower the workload of healthcare staff. Particularly during the recent pandemic situation, this aspect has taken on much greater significance.

Note

Bibliografia

  1. 1. Amato MB, Meade MO, Slutsky AS, et al. Driving pressure and survival in the acute respiratory distress syndrome. N Engl J Med. 2015;372(8):747-755. doi:10.1056/NEJMsa1410639
  2. 2. Rauf A, Sachdev A, Venkataraman ST, Dinand V. Dynamic Airway Driving Pressure and Outcomes in Children With Acute Hypoxemic Respiratory Failure. Respir Care. 2021;66(3):403-409. doi:10.4187/respcare.08024
  3. 3. Ceylan G, Topal S, Atakul G, et al. Randomized crossover trial to compare driving pressures in a closed-loop and a conventional mechanical ventilation mode in pediatric patients. Pediatr Pulmonol. 2021;56(9):3035-3043. doi:10.1002/ppul.25561
  4. 4. Pediatric Acute Lung Injury Consensus Conference Group. Pediatric acute respiratory distress syndrome: consensus recommendations from the Pediatric Acute Lung Injury Consensus Conference. Pediatr Crit Care Med. 2015;16(5):428-439. doi:10.1097/PCC.0000000000000350
  5. 5. Soydan E, Ceylan G, Topal S, et al. Automated closed-loop FiO2 titration increases the percentage of time spent in optimal zones of oxygen saturation in pediatric patients-A randomized crossover clinical trial. Front Med (Lausanne). 2022;9:969218. Published 2022 Aug 25. doi:10.3389/fmed.2022.969218
  6. 6. Mitra S, Singh B, El-Naggar W, McMillan DD. Automated versus manual control of inspired oxygen to target oxygen saturation in preterm infants: a systematic review and meta-analysis. J Perinatol. 2018;38(4):351-360. doi:10.1038/s41372-017-0037-z
  7. 7. Jouvet P, Eddington A, Payen V, et al. A pilot prospective study on closed loop controlled ventilation and oxygenation in ventilated children during the weaning phase. Crit Care. 2012;16(3):R85. Published 2012 May 16. doi:10.1186/cc11343
  8. 8. Friedman ML, Barbaro RP, Bembea MM, et al. Mechanical Ventilation in Children on Venovenous ECMO. Respir Care. 2020;65(3):271-280. doi:10.4187/respcare.07214

Driving pressure and survival in the acute respiratory distress syndrome.

Amato MB, Meade MO, Slutsky AS, et al. Driving pressure and survival in the acute respiratory distress syndrome. N Engl J Med. 2015;372(8):747-755. doi:10.1056/NEJMsa1410639

BACKGROUND Mechanical-ventilation strategies that use lower end-inspiratory (plateau) airway pressures, lower tidal volumes (VT), and higher positive end-expiratory pressures (PEEPs) can improve survival in patients with the acute respiratory distress syndrome (ARDS), but the relative importance of each of these components is uncertain. Because respiratory-system compliance (CRS) is strongly related to the volume of aerated remaining functional lung during disease (termed functional lung size), we hypothesized that driving pressure (ΔP=VT/CRS), in which VT is intrinsically normalized to functional lung size (instead of predicted lung size in healthy persons), would be an index more strongly associated with survival than VT or PEEP in patients who are not actively breathing. METHODS Using a statistical tool known as multilevel mediation analysis to analyze individual data from 3562 patients with ARDS enrolled in nine previously reported randomized trials, we examined ΔP as an independent variable associated with survival. In the mediation analysis, we estimated the isolated effects of changes in ΔP resulting from randomized ventilator settings while minimizing confounding due to the baseline severity of lung disease. RESULTS Among ventilation variables, ΔP was most strongly associated with survival. A 1-SD increment in ΔP (approximately 7 cm of water) was associated with increased mortality (relative risk, 1.41; 95% confidence interval [CI], 1.31 to 1.51; P<0.001), even in patients receiving "protective" plateau pressures and VT (relative risk, 1.36; 95% CI, 1.17 to 1.58; P<0.001). Individual changes in VT or PEEP after randomization were not independently associated with survival; they were associated only if they were among the changes that led to reductions in ΔP (mediation effects of ΔP, P=0.004 and P=0.001, respectively). CONCLUSIONS We found that ΔP was the ventilation variable that best stratified risk. Decreases in ΔP owing to changes in ventilator settings were strongly associated with increased survival. (Funded by Fundação de Amparo e Pesquisa do Estado de São Paulo and others.).

Dynamic Airway Driving Pressure and Outcomes in Children With Acute Hypoxemic Respiratory Failure.

Rauf A, Sachdev A, Venkataraman ST, Dinand V. Dynamic Airway Driving Pressure and Outcomes in Children With Acute Hypoxemic Respiratory Failure. Respir Care. 2021;66(3):403-409. doi:10.4187/respcare.08024

BACKGROUND Limited adult data suggest that airway driving pressure might better reflect the potential risk for lung injury than tidal volume based on ideal body weight, and the parameter correlates with mortality in ARDS. There is a lack of data about the effect of driving pressure on mortality in pediatric ARDS. This study aimed to evaluate the effect of driving pressure on morbidity and mortality of children with acute hypoxemic respiratory failure. METHODS This retrospective cohort study was performed in a tertiary level pediatric ICU. Children who received invasive mechanical ventilation for acute hypoxemic respiratory failure (defined as [Formula: see text] < 300 within 24 h after intubation), in a 2-y period were included. The cohort was divided into 2 groups based on the highest dynamic driving pressure (ΔP, calculated as the difference between peak inspiratory pressure and PEEP) in the first 24 h, with a cutoff value of 15 cm H2O. RESULTS Of the 380 children who were mechanically ventilated during the study period, 101 children who met eligibility criteria were enrolled. Common diagnoses were pneumonia (n = 51), severe sepsis (n = 24), severe dengue (n = 10), and aspiration pneumonia (n = 7). In comparison to the group with high ΔP (ie, ≥ 15 cm H2O), children in the group with low ΔP (ie, < 15 cm H2O) had significantly lower median (interquartile range) duration of ventilation (5 [4-6] d vs 8 [6-11] d, P < .001], ICU length of stay (6 [5-8] d vs 12 [8-15] d, P < .001], and more ventilator-free days at day 28 (23 [20-24] vs 17 [0-22] d, P < .001). Logistic regression analysis also suggested driving pressure as an independent predictor of morbidity after adjusting for confounding variables. However, there was no statistically significant difference in mortality between the 2 groups (17% in low ΔP vs 24% in high ΔP, P = .38). Subgroup analysis of 65 subjects who fulfilled ARDS criteria yielded similar results with respect to mortality and morbidity. CONCLUSIONS Below a threshold of 15 cm H2O, ΔP was associated with significantly decreased morbidity in children with acute hypoxemic respiratory failure.

Randomized crossover trial to compare driving pressures in a closed-loop and a conventional mechanical ventilation mode in pediatric patients.

Ceylan G, Topal S, Atakul G, et al. Randomized crossover trial to compare driving pressures in a closed-loop and a conventional mechanical ventilation mode in pediatric patients. Pediatr Pulmonol. 2021;56(9):3035-3043. doi:10.1002/ppul.25561

INTRODUCTION In mechanically ventilated patients, driving pressure (ΔP) represents the dynamic stress applied to the respiratory system and is related to ICU mortality. An evolution of the Adaptive Support Ventilation algorithm (ASV® 1.1) minimizes inspiratory pressure in addition to minimizing the work of breathing. We hypothesized that ASV 1.1 would result in lower ΔP than the ΔP measured in APV-CMV (controlled mandatory ventilation with adaptive pressure ventilation) mode with physician-tailored settings. The aim of this randomized crossover trial was therefore to compare ΔP in ASV 1.1 with ΔP in physician-tailored APV-CMV mode. METHODS Pediatric patients admitted to the PICU with heterogeneous-lung disease were enrolled if they were ventilated invasively with no detectable respiratory effort, hemodynamic instability, or significant airway leak around the endotracheal tube. We compared two 60-min periods of ventilation in APV-CMV and ASV 1.1, which were determined by randomization and separated by 30-min washout periods. Settings were adjusted to reach the same minute ventilation in both modes. ΔP was calculated as the difference between plateau pressure and total PEEP measured using end-inspiratory and end-expiratory occlusions, respectively. RESULTS There were 26 patients enrolled with a median age of 16 (9-25 [IQR]) months. The median ΔP for these patients was 10.4 (8.5-12.1 [IQR]) and 12.4 (10.5-15.3 [IQR]) cmH2O in the ASV 1.1 and APV-CMV periods, respectively (p < .001). The median tidal volume (VT) selected by the ASV 1.1 algorithm was 6.4 (5.1-7.3 [IQR]) ml/kg and RR was 41 (33 50 [IQR]) b/min, whereas the median of the same values for the APV-CMV period was 7.9 (6.8-8.3 [IQR]) ml/kg and 31 (26-41[IQR]) b/min, respectively. In both ASV 1.1 and APV-CMV modes, the highest ΔP was used to ventilate those patients with restrictive lung conditions at baseline. CONCLUSION In this randomized crossover trial, ΔP in ASV 1.1 was lower compared to ΔP in physician-tailored APV-CMV mode in pediatric patients with different lung conditions. The use of ASV 1.1 may therefore result in continued, safe ventilation in a heterogeneous pediatric patient group.

Pediatric acute respiratory distress syndrome: consensus recommendations from the Pediatric Acute Lung Injury Consensus Conference.

Pediatric Acute Lung Injury Consensus Conference Group. Pediatric acute respiratory distress syndrome: consensus recommendations from the Pediatric Acute Lung Injury Consensus Conference. Pediatr Crit Care Med. 2015;16(5):428-439. doi:10.1097/PCC.0000000000000350

OBJECTIVE To describe the final recommendations of the Pediatric Acute Lung Injury Consensus Conference. DESIGN Consensus conference of experts in pediatric acute lung injury. SETTING Not applicable. SUBJECTS PICU patients with evidence of acute lung injury or acute respiratory distress syndrome. INTERVENTIONS None. METHODS A panel of 27 experts met over the course of 2 years to develop a taxonomy to define pediatric acute respiratory distress syndrome and to make recommendations regarding treatment and research priorities. When published, data were lacking a modified Delphi approach emphasizing strong professional agreement was used. MEASUREMENTS AND MAIN RESULTS A panel of 27 experts met over the course of 2 years to develop a taxonomy to define pediatric acute respiratory distress syndrome and to make recommendations regarding treatment and research priorities. When published data were lacking a modified Delphi approach emphasizing strong professional agreement was used. The Pediatric Acute Lung Injury Consensus Conference experts developed and voted on a total of 151 recommendations addressing the following topics related to pediatric acute respiratory distress syndrome: 1) Definition, prevalence, and epidemiology; 2) Pathophysiology, comorbidities, and severity; 3) Ventilatory support; 4) Pulmonary-specific ancillary treatment; 5) Nonpulmonary treatment; 6) Monitoring; 7) Noninvasive support and ventilation; 8) Extracorporeal support; and 9) Morbidity and long-term outcomes. There were 132 recommendations with strong agreement and 19 recommendations with weak agreement. Once restated, the final iteration of the recommendations had none with equipoise or disagreement. CONCLUSIONS The Consensus Conference developed pediatric-specific definitions for acute respiratory distress syndrome and recommendations regarding treatment and future research priorities. These are intended to promote optimization and consistency of care for children with pediatric acute respiratory distress syndrome and identify areas of uncertainty requiring further investigation.

Automated closed-loop FiO2 titration increases the percentage of time spent in optimal zones of oxygen saturation in pediatric patients-A randomized crossover clinical trial.

Soydan E, Ceylan G, Topal S, et al. Automated closed-loop FiO2 titration increases the percentage of time spent in optimal zones of oxygen saturation in pediatric patients-A randomized crossover clinical trial. Front Med (Lausanne). 2022;9:969218. Published 2022 Aug 25. doi:10.3389/fmed.2022.969218

Introduction We aimed to compare automated ventilation with closed-loop control of the fraction of inspired oxygen (FiO2) to automated ventilation with manual titrations of the FiO2 with respect to time spent in predefined pulse oximetry (SpO2) zones in pediatric critically ill patients. Methods This was a randomized crossover clinical trial comparing Adaptive Support Ventilation (ASV) 1.1 with use of a closed-loop FiO2 system vs. ASV 1.1 with manual FiO2 titrations. The primary endpoint was the percentage of time spent in optimal SpO2 zones. Secondary endpoints included the percentage of time spent in acceptable, suboptimal and unacceptable SpO2 zones, and the total number of FiO2 changes per patient. Results We included 30 children with a median age of 21 (11-48) months; 12 (40%) children had pediatric ARDS. The percentage of time spent in optimal SpO2 zones increased with use of the closed-loop FiO2 controller vs. manual oxygen control [96.1 (93.7-98.6) vs. 78.4 (51.3-94.8); P < 0.001]. The percentage of time spent in acceptable, suboptimal and unacceptable zones decreased. Findings were similar with the use of closed-loop FiO2 controller compared to manual titration in patients with ARDS [95.9 (81.6-98.8) vs. 78 (49.5-94.8) %; P = 0.027]. The total number of closed-loop FiO2 changes per patient was 52 (11.8-67), vs. the number of manual changes 1 (0-2), (P < 0.001). Conclusion In this randomized crossover trial in pediatric critically ill patients under invasive ventilation with ASV, use of a closed-loop control of FiO2 titration increased the percentage of time spent within in optimal SpO2 zones, and increased the total number of FiO2 changes per patient. Clinical trial registration ClinicalTrials.gov, identifier: NCT04568642.

Automated versus manual control of inspired oxygen to target oxygen saturation in preterm infants: a systematic review and meta-analysis.

Mitra S, Singh B, El-Naggar W, McMillan DD. Automated versus manual control of inspired oxygen to target oxygen saturation in preterm infants: a systematic review and meta-analysis. J Perinatol. 2018;38(4):351-360. doi:10.1038/s41372-017-0037-z

OBJECTIVES To conduct a systematic review of clinical trials comparing automated versus manual fraction of inspired oxygen (FiO2) control to target oxygen saturation (SpO2) in preterm infants. DESIGN The authors searched MEDLINE, Embase, CENTRAL, and CINAHL from inception upto December 2016, reviewed conference proceedings and sought results of unpublished trials. Studies were included if automated FiO2 control was compared to manual control in preterm infants on positive pressure respiratory support. The primary outcome was percentage of time spent within the target SpO2 range. Summary mean differences (MD) were computed using random effects model. RESULTS Out of 276 identified studies 10 met the inclusion criteria. Automated FiO2 control significantly improved time being spent within the target SpO2 range [MD: 12.8%; 95% CI: 6.5-19.2%; I2 = 90%]. Periods of hyperoxia (MD:-8.8%; 95% CI: -15 to -2.7%), severe hypoxia(SpO2  < 80%)(MD: -0.9%;95%CI: -1.5 to -0.4%) and hypoxic events (MD: -5.6%; 95% CI: -9.1 to -2.1%) were significantly reduced with automated control. CONCLUSION Automated FiO2 adjustment provides significant improvement of time in target saturations, reduces periods of hyperoxia, and severe hypoxia in preterm infants on positive pressure respiratory support.

A pilot prospective study on closed loop controlled ventilation and oxygenation in ventilated children during the weaning phase.

Jouvet P, Eddington A, Payen V, et al. A pilot prospective study on closed loop controlled ventilation and oxygenation in ventilated children during the weaning phase. Crit Care. 2012;16(3):R85. Published 2012 May 16. doi:10.1186/cc11343

INTRODUCTION The present study is a pilot prospective safety evaluation of a new closed loop computerised protocol on ventilation and oxygenation in stable, spontaneously breathing children weighing more than 7 kg, during the weaning phase of mechanical ventilation. METHODS Mechanically ventilated children ready to start the weaning process were ventilated for five periods of 60 minutes in the following order: pressure support ventilation, adaptive support ventilation (ASV), ASV plus a ventilation controller (ASV-CO2), ASV-CO2 plus an oxygenation controller (ASV-CO2-O2) and pressure support ventilation again. Based on breath-by-breath analysis, the percentage of time with normal ventilation as defined by a respiratory rate between 10 and 40 breaths/minute, tidal volume > 5 ml/kg predicted body weight and end-tidal CO2 between 25 and 55 mmHg was determined. The number of manipulations and changes on the ventilator were also recorded. RESULTS Fifteen children, median aged 45 months, were investigated. No adverse event and no premature protocol termination were reported. ASV-CO2 and ASV-CO2-O2 kept the patients within normal ventilation for, respectively, 94% (91 to 96%) and 94% (87 to 96%) of the time. The tidal volume, respiratory rate, peak inspiratory airway pressure and minute ventilation were equivalent for all modalities, although there were more automatic setting changes in ASV-CO2 and ASV-CO2-O2. Positive end-expiratory pressure modifications by ASV-CO2-O2 require further investigation. CONCLUSION Over the short study period and in this specific population, ASV-CO2 and ASV-CO2-O2 were safe and kept the patient under normal ventilation most of the time. Further research is needed, especially for positive end-expiratory pressure modifications by ASV-CO2-O2. TRIAL REGISTRATION ClinicalTrials.gov: NCT01095406.

Mechanical Ventilation in Children on Venovenous ECMO.

Friedman ML, Barbaro RP, Bembea MM, et al. Mechanical Ventilation in Children on Venovenous ECMO. Respir Care. 2020;65(3):271-280. doi:10.4187/respcare.07214

BACKGROUND Venovenous extracorporeal membrane oxygenation (VV-ECMO) is used when mechanical ventilation can no longer support oxygenation or ventilation, or if the risk of ventilator-induced lung injury is considered excessive. The optimum mechanical ventilation strategy once on ECMO is unknown. We sought to describe the practice of mechanical ventilation in children on VV-ECMO and to determine whether mechanical ventilation practices are associated with clinical outcomes. METHODS We conducted a multicenter retrospective cohort study in 10 pediatric academic centers in the United States. Children age 14 d through 18 y on VV-ECMO from 2011 to 2016 were included. Exclusion criteria were preexisting chronic respiratory failure, primary diagnosis of asthma, cyanotic heart disease, or ECMO as a bridge to lung transplant. RESULTS Conventional mechanical ventilation was used in about 75% of children on VV-ECMO; the remaining subjects were managed with a variety of approaches. With the exception of PEEP, there was large variation in ventilator settings. Ventilator mode and pressure settings were not associated with survival. Mean ventilator FIO2 on days 1-3 was higher in nonsurvivors than in survivors (0.5 vs 0.4, P = .009). In univariate analysis, other risk factors for mortality were female gender, higher Pediatric Risk Estimate Score for Children Using Extracorporeal Respiratory Support (Ped-RESCUERS), diagnosis of cancer or stem cell transplant, and number of days intubated prior to initiation of ECMO (all P < .05). In multivariate analysis, ventilator FIO2 was significantly associated with mortality (odds ratio 1.38 for each 0.1 increase in FIO2 , 95% CI 1.09-1.75). Mortality was higher in subjects on high ventilator FIO2 (≥ 0.5) compared to low ventilator FIO2 (> 0.5) (46% vs 22%, P = .001). CONCLUSIONS Ventilator mode and some settings vary in practice. The only ventilator setting associated with mortality was FIO2 , even after adjustment for disease severity. Ventilator FIO2 is a modifiable setting that may contribute to mortality in children on VV-ECMO.