小児人工呼吸患者でのクローズドループシステム：最新のエビデンス

Article

Author: Caroline Brown

Date of first publication: 07.12.2022

最近、小児患者におけるクローズドループ換気モードの使用と吸入酸素分画（FiO2）のクローズドループコントロールの使用について調べた研究が2件発表されました。

今日、成人でのクローズドループシステムの使用については多数のエビデンスが存在しますが、小児でのクローズドループシステムの使用に関するデータは限られています。同様に、ドライビングプレッシャー（∆P）が転帰に及ぼす影響についても、小児ではエビデンスがほとんどありません。成人では、∆PはARDS患者の死亡率に密接に関連する変数であることが報告されています（Amato MB, Meade MO, Slutsky AS, et al. Driving pressure and survival in the acute respiratory distress syndrome. The New England Journal of Medicine 2015;372(8):747-755. doi:10.1056/NEJMsa14106391）。最近発表された、高∆P（≥ 15 cmH2O）または低∆P（< 15 cmH2O）で人工呼吸を受けている小児急性低酸素呼吸不全患者を対象とした後ろ向きコホート研究によると、死亡率の点では両群に差はありませんでしたが、罹患率については低∆P群の方が有意に低いという結果になりました。また、低∆P群の患者は高∆P群よりも人工呼吸器離脱日数が多く、ICU入室期間および入院期間が短いということも示されました（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）。Dr Behcet Uz Children's Disease and Surgery Training and Research Hospital（トルコ、イズミル）の研究者チームは、小児の呼吸不全患者において、アダプティブサポートベンチレーション（ASV 1.1）と小児患者でよく使用されるAPV-CMV（アダプティブプレッシャー換気による制御式強制換気）モードの間でドライビングプレッシャーを比較しました（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とAPV-CMVの比較

この無作為化対照試験では、異種の肺疾患（拘束性、閉塞性、正常）を持つ26例の患者（年齢中央値は16か月）が登録され、ASV 1.1とAPV-CMVでそれぞれ60分ずつ人工呼吸を受けました。どちらのモードでも同じ分時換気量が維持されました。APV-CMVは、コンプライアンスが変化したときに一回換気量が低下または増加しないように適用圧を調整しますが、圧力が設定限度内にある限り、臨床医が設定した目標一回換気量（VT）を維持します。それに対してASVは、1呼吸ごとの患者の呼吸メカニクスの分析に基づいて、臨床医が設定した分時換気量を達成する最適な呼吸回数（RR）とVTの組み合わせを決定します。この動作は、Pediatric Acute Lung Injury Consensus Conferenceが推奨している「個々の患者の疾患重症度に応じてVTを選択する」という指針に一致します（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）。したがって研究者らは、ASV 1.1によって自動的に選択された設定の方が、医師が設定したAPV-CMVモードよりもドライビングプレッシャーは低くなると仮定しました。

圧力と一回換気量が低くなる

ドライビングプレッシャーは、プラトー圧と総PEEP（呼気終末陽圧）の差として計算されました。プラトー圧の測定には吸気終末ホールド、総PEEPの測定には呼気終末ホールドが使用されました。∆Pの中央値は、ASV 1.1期間の方がAPV-CMV期間よりも有意に低くなりました（それぞれ10.4［8.5～12.1｛IQR｝］cmH2O、12.4［10.5～15.3｛IQR｝］cmH2O、p < 0.001）。さらに、一回換気量の中央値（6.4 mL/kg対7.9 mL/kg、p < .001）とピーク吸気圧（19.1 cmH2O対22.5 cmH2O、p = 0.001）およびプラトー圧（16.9 cmH2O対18.4 cmH2O、p < 0.001）も、ASV 1.1群の方が有意に低くなりました。呼気終末CO2は有意に高くなりました（41 mmHg対38 mmHg、p = 0.001）。どちらの群でも、小児の人工呼吸に関する最新の推奨事項を超える換気パラメータまたは動脈血ガス値は認められず、すべての患者が常に安全ゾーン内に留まっていました（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）。

圧制御従量式換気でも、目標VTを下げることで同様の結果を達成できますが、そのためには、十分な人数のスタッフがいて、VTをこまめに調整する必要があります。特に人的資源が限られている場合、ASV 1.1には、呼吸メカニクスの変化に応じて直ちにVTとRRを自動調整するというメリットがあります。人的資源が十分に確保されている場合でも、24時間絶えず換気が自動調整されればICUスタッフの負担が軽減されるのは明らかです。

FiO2の手動タイトレーションとクローズドループタイトレーションの比較

2つ目の研究では、同じ研究者らが、小児患者で手動のFiO2タイトレーションとクローズドループのFiO2タイトレーションシステムの使用を比較しました（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. 2022年8月25日発行。doi:10.3389/fmed.2022.9692185）。陽圧呼吸補助を受けている早産児のメタ分析により、自動的なFiO2タイトレーションと、目標酸素飽和度（SpO2）の範囲内にある時間がより長いこととの間に関連性があることが示唆されていますが（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）、小児患者での影響は明らかになっていません。少人数の人工呼吸小児患者を対象とした初期のパイロット研究では、患者を正常な換気状態に維持した時間の割合（正常呼吸の回数を全呼吸回数で除算して算出）は、ASVと換気および酸素化のクローズドループコントロールを組み合わせた場合とプレッシャーサポート換気との間でほぼ同じでした（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. 2012年5月16日発行。doi:10.1186/cc113437）。

最近の研究では、異種の肺疾患を持つ30例の小児患者のコホート（12例が小児ARDS、平均年齢は21か月）が使用されました（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. 2022年8月25日発行。doi:10.3389/fmed.2022.9692185）。ASV 1.1で換気を受けている患者に対し、2通りの条件でそれぞれ2.5時間ずつ換気が行われました。1つ目の条件はFiO2自動コントローラを有効にすることで、2つ目の条件はFiO2を手動でタイトレーションすることでした。どちらの条件においても、最初の30分間は導入期間とし、残り2時間についてデータを収集しました。分時換気量とPEEPは、どちらの条件の間も同じレベルに維持されました。主要評価項目は、SpO2が事前定義された最適なゾーンにあった時間の割合で、副次的評価項目は、許容可能ゾーン、準最適ゾーン、および許容不可ゾーンにあった時間と、患者あたりのFiO2の変更回数でした。

SpO2が最適範囲内にある時間が長い

この試験では、患者のSpO2が最適範囲内にあった時間は、FiO2コントローラを有効にした場合の方がFiO2を手動でタイトレーションした場合よりも有意に長いという結果になりました（96.1%［93.7～98.6｛IQR｝］対78.4%［51.3～94.8｛IQR｝］、p < 0.001）。さらに、許容不可の低ゾーン、準最適な低ゾーン、許容可能な低ゾーン、および準最適な高ゾーンにあった時間についても、FiO2自動コントロールの方が有意に短くなりました（p値はそれぞれ0.032、0.008、0.004、0.001）。その他に、FiO2の中央値はFiO2自動コントロールの方が低いことも示されました。VV-ECMOを受けている小児患者の研究において、FiO2高値と死亡率との関連性が示唆されていることから（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）、FiO2を低下させるクローズドループFiO2コントロールは、転帰に好影響を与える可能性があります。

クローズドループシステムの効率

効率の観点から、著者らはいくつかの異なる側面を指摘しています。まず、患者あたりの調整回数は、FiO2コントローラの方が手動タイトレーションよりもはるかに多くなりました（52［11.8～67｛IQR｝］回対1［0～2｛IQR｝］回、p < 0.001）。2時間にたった1回調整することでさえ、30人も患者がいるとスタッフの手が回らないのに、ましてや2時間に複数回手動で調整するとなると、ほとんど実施不可能です。次に、酸素化指数の中央値と酸素使用量の中央値はどちらも、自動タイトレーションの方が手動タイトレーションより低くなりました。これは、治療用酸素の使用効率が高いことを表します。

これら2件の研究は、小児での自動換気モードの使用に関する限られたエビデンスを増やすとともに、自動化は効率面でメリットをもたらす可能性があることを実証しています。自動換気モードは、患者の状態変化に応じた調整の回数を大幅に増やすだけでなく、医療スタッフの負担も軽減します。特に最近のパンデミック状況下では、この点ははるかに大きな重要性を持ちます。

Footnotes

References

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. 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. 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. 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. 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. 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. 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. 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

Link to article

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

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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

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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.