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Closed-Loop-Systeme bei maschinell beatmeten pädiatrischen Patienten: die jüngsten wissenschaftlichen Erkenntnisse

Artikel

Autor: Caroline Brown

Datum: 07.12.2022

Zwei neue Studien untersuchten die Verwendung eines Closed-Loop-Beatmungsmodus und einer Closed-Loop-Steuerung der Fraktion des inspirierten Sauerstoffs (FiO2) bei pädiatrischen Patienten.
Closed-Loop-Systeme bei maschinell beatmeten pädiatrischen Patienten: die jüngsten wissenschaftlichen Erkenntnisse

Während für die Verwendung von Closed-Loop-Systemen bei Erwachsenen umfangreiche Erkenntnisse zur Verfügung stehen, gibt es nur beschränkte Daten zu ihrem Einsatz in der Pädiatrie. Auch über die Auswirkung des Driving Pressure (∆P) auf den Behandlungserfolg bei Kindern ist wenig bekannt. Immerhin ist dies die Variable, die bei erwachsenen ARDS-Patienten am engsten mit der Mortalität im Zusammenhang steht (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​). Eine neue retrospektive Kohortenstudie bei Kindern mit akutem hypoxämischem Atemversagen, die mit hohem ∆P (≥ 15 mbar) oder niedrigem ∆P (< 15 mbar) beatmet wurden, stellte keinen Unterschied hinsichtlich der Mortalität, aber eine signifikante Abnahme beim Sterblichkeitsrisiko in der Gruppe mit niedrigem ∆P fest. Die Probanden der Gruppe mit niedrigem ∆P verzeichneten auch mehr Tage ohne Unterstützung durch das Beatmungsgerät sowie kürzere Aufenthalte auf der Intensivstation und im Krankenhaus (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​). Ein Team von Studienärzten am chirurgischen Lehr- und Forschungskrankenhaus für Kinderkrankheiten Dr. Behcet Uz in Izmir, Türkei, stellte einen Vergleich an zwischen dem durch Adaptive Support Ventilation (ASV 1.1) erzeugten Driving Pressure bei pädiatrischen Patienten mit Atemversagen und einem der am häufigsten bei Kindern verwendeten Modi, nämlich der kontrollierten mandatorischen Beatmung mit adaptiver Druckbeatmung (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 im Vergleich mit APV-CMV

Diese randomisierte kontrollierte Studie untersuchte 26 Patienten mit einem Alter von 16 Monaten im Median und verschiedenen Lungenzuständen (restriktiv, obstruktiv und normal). Sie wurden für zwei Zeiträume von je 60 Minuten beatmet, einmal mit dem Modus ASV 1.1 und dem Modus APV-CMV. Für beide Modi wurde dasselbe Minutenvolumen aufrechterhalten. APV-CMV passt den angewendeten Druck an, um niedrige bzw. hohe Tidalvolumina bei Änderungen in der Compliance zu vermeiden, erhält aber das vom klinischen Personal eingestellte Ziel-Tidalvolumen (VT) aufrecht, solange der Druck unter dem eingestellten Grenzwert bleibt. ASV hingegen bestimmt die optimale Kombination aus Atemfrequenz (AF) und VT für das vom klinischen Personal eingestellte Minutenvolumen. Dazu wird die Atemmechanik des Patienten bei jedem Atemhub analysiert. Dieses Vorgehen entspricht der Empfehlung der Pediatric Acute Lung Injury Consensus Conference, VT gemäß der Schwere der Erkrankung des einzelnen Patienten auszuwählen (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​). Die Studienärzte stellten folglich die Hypothese auf, dass die von ASV 1.1 automatisch ausgewählten Einstellungen zu einem niedrigeren Driving Pressure führen als beim vom Arzt angepassten APV-CMV-Modus.

Niedrigere Werte für Druck und Tidalvolumen

Driving Pressure wurde berechnet als die Differenz zwischen dem Plateaudruck und dem positiven endexspiratorischen Gesamtdruck (Gesamt-PEEP). Diese Parameter wurden mit einem endinspiratorischen bzw. endexspiratorischen Hold-Manöver gemessen. Der Medianwert des ∆P während der ASV 1.1-Phase war signifikant niedriger als während der APV-CMV-Phase (10,4 [8,5−12,1 {IQR}] bzw. 12,4 [10,5−15,3 {IQR}] mbar [p < 0,001]).  Zudem war der Medianwert für das Tidalvolumen in der Gruppe mit ASV 1.1 ebenso deutlich niedriger (6,4 ml/kg gegenüber 7,9 ml/kg; p < 0,001), wie auch der maximale Inspirationsdruck (19,1 mbar gegenüber 22,5 mbar; p = 0,001) und der Plateaudruck (16,9 mbar gegenüber 18,4 mbar; p < 0,001). Der endtidale CO2-Wert lag deutlich höher (41 mmHg gegenüber 38 mmHg; p = 0,001). In keiner der beiden Gruppen überstiegen die Beatmungsparameter oder die arteriellen Blutgaswerte die aktuellen Empfehlungen für maschinelle Beatmung bei Kindern; alle Patienten befanden sich stets im sicheren Bereich (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​). 

Es ist zwar möglich, ähnliche Resultate in druckregulierten, volumenkontrollierten Modi zu erzielen, indem das Ziel-VT reduziert wird, allerdings wird für die Anpassungen ausreichend medizinisches Personal benötigt. Besonders wenn Ressourcen knapp sind, ist es von großem Vorteil, dass ASV 1.1 die Einstellungen für VT und AF automatisch anpasst, sobald sich die Atemmechanik des Patienten verändert. Selbst bei ausreichenden Ressourcen liegt es auf der Hand, dass die automatische Titrierung der Beatmung rund um die Uhr das Personal auf der Intensivstation entlasten kann.

FiO2-Titrierung: Manuell im Vergleich mit Closed-Loop

In der zweiten Studie verglichen dieselben Studienärzte die manuelle FiO2-Titrierung mit der Verwendung eines Closed-Loop-FiO2-Titrierungssystems bei pädiatrischen Patienten (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​). Eine Meta-Analyse bei Frühgeborenen, die Beatmungsunterstützung mit positivem Druck erhielten, deutete auf eine Verbindung zwischen automatischer FiO2-Titrierung und längeren Verweilzeiten im Zielbereich der Sauerstoffsättigung (SpO2) hin (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​). Die Auswirkungen auf pädiatrische Patienten sind jedoch nicht klar. Eine frühere Pilotstudie an einer kleinen Kohorte von maschinell beatmeten Kindern belegte, dass die Zeit der normalen Beatmung in Prozent (Anzahl der normalen Atemhübe dividiert durch Gesamtanzahl der erfassten Atemhübe) bei ASV zusammen mit der Closed-Loop-Steuerung der Beatmung und Oxygenierung ähnlich der Zeit bei der druckunterstützten Beatmung war (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​). 

Die aktuelle Studie untersuchte eine Kohorte von 30 Patienten mit einem Durchschnittsalter von 21 Monaten und verschiedenen Lungenzuständen, 12 davon mit pädiatrischem 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​). Alle Patienten wurden mit ASV 1.1 für je zwei Phasen à 2,5 Stunden beatmet. Während einer Phase war der automatische FiO2-Kontroller aktiviert; bei der anderen wurde FiO2 manuell titriert. Die ersten 30 Minuten jeder Phase wurden als Anlaufzeit betrachtet. Daten wurden nur für zwei Stunden pro Phase erfasst. Das Minutenvolumen und PEEP wurden für beide Phasen auf demselben Niveau gehalten. Der primäre Endpunkt war der Prozentsatz der Zeit, die sich der Patient innerhalb eines vordefinierten optimalen SpO2-Bereichs befand. Zu den sekundären Endpunkten gehörte die Zeit in akzeptablen, suboptimalen und inakzeptablen Bereichen sowie die Anzahl der FiO2-Veränderungen pro Patient.

Mehr Zeit im optimalen SpO2-Bereich

Die Ergebnisse belegten, dass Patienten mit aktiviertem FiO2-Kontroller signifikant mehr Zeit im optimalen Bereich verbrachten als bei der manuellen FiO2-Titrierung (96,1 % [93,7–98,6 {IQR}] gegenüber 78,4 % [51,3–94,8 {IQR}]; [p < 0,001]). Zudem waren lagen die FiO2-Werte bei der automatischen Steuerung auch signifikant weniger Zeit in den inakzeptabel niedrigen, suboptimal niedrigen, akzeptabel niedrigen und suboptimal hohen Bereichen (p-Werte 0,032, 0,008, 0,004 und 0,001 respektive). Ein weiteres Ergebnis war ein geringerer FiO2-Prozentsatz im Median bei der automatischen FiO2-Steuerung. Zieht man eine Studie an Kindern mit VV-ECMO-Behandlung in Betracht, die einen Zusammenhang zwischen hohem FiO2-Wert und Mortalität nahe legte (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​), kann ein niedrigerer FiO2-Wert mit Closed-Loop-FiO2-Steuerung eine positive Auswirkung auf den Behandlungserfolg haben.

Wirksamkeit von Closed-Loop-Systemen

Was die Wirksamkeit angeht, haben die Autoren mehrere verschiedene Aspekte hervorgehoben. Erstens war die Anzahl der Anpassungen pro Patient beim FiO2-Kontroller deutlich höher als bei der manuellen Titrierung (52 [11,8–67 {IQR}] gegenüber 1 [0–2 {IQR}], p < 0,001). Selbst wenn nur eine Änderung alle zwei Stunden bei 30 Patienten durchgeführt werden muss, kann dies ein Krankenhaus an die Grenzen seiner Ressourcen bringen; mehrere Änderungen innerhalb einer zweistündigen Phase manuell vorzunehmen, ist kaum realistisch. Zweitens waren sowohl der Oxygenierungsindex im Median als auch die O2-Verwendung im Median in der automatischen Phase niedriger als in der manuellen Phase, was auf einen effizienteren Gebrauch des Sauerstoffs für die Behandlung hinweist. 

Diese zwei Studien erweitern den eingeschränkten Datenpool zur Verwendung automatischer Beatmungsmodi bei pädiatrischen Patienten. Zudem belegen diese Studien die potenziellen Vorzüge der Automatisierung hinsichtlich der Wirksamkeit. Automatische Beatmungsmodi ermöglichen nicht nur eine größere Anzahl an Anpassungen als Reaktion of Veränderungen im Patientenzustand; sie können auch die Belastung für das klinische Personal verringern. Gerade in der kürzlichen Pandemie hat dieser Aspekt sehr an Bedeutung gewonnen.

Fußnoten

Referenzen

  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.