Driving Pressure and Mortality: in the Pediatric Intensive Care Unit (PICU)

Respiratory Failure Clinical Trial

Official title:

Driving Pressure and Mortality: in the Pediatric Intensive Care Unit (PICU)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04419376
• Other study ID #: 2019-344
• Status: Completed
• Start date: March 30, 2018
• Est. completion date: April 15, 2020

Study information

• Verified date: June 2020
• Source: Dr. Behcet Uz Children's Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial Summary

Respiratory failure is one of the most common causes of both hospitalization and mortality in patients in the pediatric intensive care unit (PICU). Recently, it is recommended to target driving pressure (ΔP) in patients with ARDS to achieve better results with the administration of optimal mechanical ventilation. In many studies, higher ΔP was associated with mortality in adult ARDS patients; non-ARDS patients' studies showing the relationship between driving pressure and mortality are few, but contradictory results have come out.

This study aimed to determine whether ΔP was associated with mortality in pediatric patients diagnosed as pARDS and non-pARDS who received mechanical ventilation support due to respiratory failure. Patients who received invasive mechanical ventilation support due to respiratory failure in the pediatric intensive care unit over 1 month and under 18 years were included in our study Driving pressure was significantly associated with an increased risk of mortality among mechanically ventilated both pARDS and non-pARDS patients. Future prospective randomized clinical trials are needed to determine a protocol targeting DP can be developed and defining optimum cutoff values.

Description:

Respiratory failure is one of the most common causes of both hospitalization and mortality in patients in the pediatric intensive care unit (PICU). Recently, it is recommended to target driving pressure (ΔP) in patients with ARDS to achieve better results with the administration of optimal mechanical ventilation. ΔP is calculated as the difference between Plateau pressure (Pplat) and positive end-expiratory pressure (PEEP) and is determined by the ratio of the tidal volume to the compliance of the respiratory system (ΔP = Pplat − PEEP = VT/CRS). ΔP estimates how much mechanical strain (dynamic strain) the tidal volume causes in the lung. It is a non-invasive and simple method and can be easily calculated at the bedside. In many studies, higher ΔP was associated with mortality in adult ARDS patients; non-ARDS patients' studies showing the relationship between driving pressure and mortality are few, but contradictory results have come out.

This study aimed to determine whether ΔP was associated with mortality in pediatric patients diagnosed as pARDS and non-pARDS who received mechanical ventilation support due to respiratory failure.

Single-center, prospective, observational study of patients admitted to pediatric intensive care units (PICU) in Turkey. In our study, the ethics committee was approved by The Health Sciences University Izmir Behcet Uz Child Health and Diseases education and research hospital ethics committee (protocol no: 2019-344).In our study, patients who received invasive mechanical ventilation support due to respiratory failure in the pediatric intensive care unit over 1 month and under 18 years were included in the study between March 2018 and April 2020. Mechanically ventilated patients (via ETT or trachestomy) were recorded for patients whose ventilation duration lasted at least 24 hours. We divided the patients into two groups by calculating the oxygenation index (OI): [mean airway pressure(MAP) × fraction of inspired oxygen (FiO2) ]/ partial pressure of oxygen in arterial blood (PaO2) × 100) used in the classification of PALICC, including ARDS and non-ARDS. PARDS definition was also identified based on the PALICC criteria. Data were prospectively recorded on day 1 including patient demographics, ventilator settings (VT, VT / ideal body weight (IBW), respiratory rate (RR), peak inspiratory pressure (PIP), plateau pressure (Pplat), mean airway pressure (Pmean), minute volume (VE), end-expiratory pressure (PEEP), static compliance (Cstat), fraction of inspired oxygen FIO2, inspiratory time ( IT), expiratory time (ET) and we calculated oxygenation index (OI), cstat (VT/∆P), partial pressure of oxygen in arterial blood (PaO2) /FiO2, driving pressure (ΔP), the pediatric index of mortality (PRISM) III scores and pediatric sequential organ failure assessment (pSOFA) scores.

All patients were ventilated with volume control (VCV) or pressure control (PCV) mode during the hospitalization. İn order to measure the driving pressure of patients, Pplat was measured in the mechanical ventilator every 12 hours using an inspiratory hold maneuver. The average Pplat was calculated using the mean of 2 measurements within 24 hours. Then, the total PEEP was measured by expiratory hold maneuver and ΔP was calculated with the Pplat-PEEP formula. Patients were followed for 30 days until hospital discharge. We used ΔP compared to other mechanic ventilator parameters between survivors and non-survivors at day 30. Besides, ΔP and other parameters of patients in the ARDS and non-ARDS groups were compared with their 30-day mortality.

Statistical Analyses Primarily, we evaluated the relationship between ΔP and mortality in patients with ARDS and non-ARDS. Our second target was to evaluate the relationship between mortality and ΔP and other mechanical ventilator parameters.

Driving pressure and other lung dynamics; according to the type and distribution of the data was compared with chi-square, Wilcoxon, Independent-T-test or Mann-Whitney-U test and p <0.05 was considered statistically significant. The strength of the association between the two variables was measured using the correlation coefficient. We used Pearson correlation to parametric variable and Spearman correlation to the nonparametric variable to detect covariances before logistic regression analysis. We evaluated with spearman's correlation analysis to detect covariances before logistic regression analysis. Parameters found significant with mortality in univariate analyzes were evaluated by Logistic Regression analysis. (odds ratio [OR] and 95 % confidence intervals [CI]) Model fit was assessed using Hosmer-Lemeshow statistics.

For the multivariable analysis, we identified covariates that may be associated with mortality. VT /IBW, PaO2, OI, FiO2, PRISM III score, Days of ventilation and pSOFA score were not collinear with ΔP. We did not include Pplat, PIP, Pmean in logistic regression models containing ΔP given concerns for collinearity Individual covariates included age, gender, PRISM III score, PaO2, OI, FiO2, Days of ventilation and pSOFA score. We created 3 other modeling analyzes for Pplat, PIP, Pmean, because of collinearity with driving pressure. We evaluated this model to determine the best parameter related to mortality in whole patients under mechanical ventilation support due to respiratory failure. ΔP cut off (13 cmH2O) values in adult studies in the literature were categorized and mortality was estimated by a receiver operating characteristic (ROC). We performed all statistical analyses using IBM SPSS Statistics for Windows version 22 (Armonk, NY) for analysis.

Mechanical ventilation is one of the most common indications for admission to a pediatric intensive care unit (PICU), with up to 64% of admitted children requiring mechanical ventilation. Driving pressure (ΔP), which is calculated as end-inspiratory plateau pressure (Pplat) minus applied positive end-expiratory pressure (PEEP) and is equivalent to the ratio between the VT and compliance of the respiratory system, can reduce mortality with children who received mechanical ventilator support due to respiratory failure. ΔP is a non-invasive and simple method and can be easily calculated at the bedside.

Recent data in the adult ARDS population have shown that the ΔP is most related to mortality. Our study, we have shown that the ΔP on day 1 was associated with hospital mortality in with pARDS patients.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 116
• Est. completion date: April 15, 2020
• Est. primary completion date: April 1, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Month to 18 Years

Eligibility

Inclusion Criteria:

• In our study, patients who received invasive mechanical ventilation support for at least 24 hours due to respiratory failure in the pediatric intensive care unit over 1 month and under 18 years were included in the study between March 2018 and April 2020.

Exclusion Criteria:

• patients who died within the first 24 hours and patients whose desired respiratory mechanics were not measured and data deficiencies were detected

Related Conditions & MeSH terms

• ARDS, Human
• Respiratory Distress Syndrome, Adult
• Respiratory Failure
• Respiratory Insufficiency

Intervention

Device:
• driving pressure
Mechanically ventilated patients (via ETT or trachestomy) were recorded for patients whose ventilation duration lasted at least 24 hours.We divided the patients into two groups by calculating the oxygenation index (OI): [mean airway pressure(MAP) × fraction of inspired oxygen (FiO2) ]/ partial pressure of oxygen in arterial blood (PaO2) × 100) used in the classification of PALICC, including pARDS and non-pARDS.

Locations

Country	Name	City	State
Turkey	The Health Sciences University Izmir Behçet Uz Child Health and Diseases education and research hospital	Izmir	Turkey/izmir

Sponsors (1)

Lead Sponsor	Collaborator
Dr. Behcet Uz Children's Hospital

Country where clinical trial is conducted

Turkey, 

References & Publications (28)

Acute Respiratory Distress Syndrome Network, Brower RG, Matthay MA, Morris A, Schoenfeld D, Thompson BT, Wheeler A. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress sy — View Citation

Amato MB, Meade MO, Slutsky AS, Brochard L, Costa EL, Schoenfeld DA, Stewart TE, Briel M, Talmor D, Mercat A, Richard JC, Carvalho CR, Brower RG. Driving pressure and survival in the acute respiratory distress syndrome. N Engl J Med. 2015 Feb 19;372(8):74 — View Citation

Aoyama H, Pettenuzzo T, Aoyama K, Pinto R, Englesakis M, Fan E. Association of Driving Pressure With Mortality Among Ventilated Patients With Acute Respiratory Distress Syndrome: A Systematic Review and Meta-Analysis. Crit Care Med. 2018 Feb;46(2):300-306 — View Citation

Bellani G, Laffey JG, Pham T, Fan E, Brochard L, Esteban A, Gattinoni L, van Haren F, Larsson A, McAuley DF, Ranieri M, Rubenfeld G, Thompson BT, Wrigge H, Slutsky AS, Pesenti A; LUNG SAFE Investigators; ESICM Trials Group. Epidemiology, Patterns of Care, — View Citation

Briel M, Meade M, Mercat A, Brower RG, Talmor D, Walter SD, Slutsky AS, Pullenayegum E, Zhou Q, Cook D, Brochard L, Richard JC, Lamontagne F, Bhatnagar N, Stewart TE, Guyatt G. Higher vs lower positive end-expiratory pressure in patients with acute lung i — View Citation

Chen Z, Wei X, Liu G, Tai Q, Zheng D, Xie W, Chen L, Wang G, Sun JQ, Wang S, Liu N, Lv H, Zuo L. Higher vs. Lower DP for Ventilated Patients with Acute Respiratory Distress Syndrome: A Systematic Review and Meta-Analysis. Emerg Med Int. 2019 Jul 18;2019:4 — View Citation

Chiumello D, Carlesso E, Brioni M, Cressoni M. Airway driving pressure and lung stress in ARDS patients. Crit Care. 2016 Aug 22;20:276. doi: 10.1186/s13054-016-1446-7. — View Citation

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Laffey JG, Bellani G, Pham T, Fan E, Madotto F, Bajwa EK, Brochard L, Clarkson K, Esteban A, Gattinoni L, van Haren F, Heunks LM, Kurahashi K, Laake JH, Larsson A, McAuley DF, McNamee L, Nin N, Qiu H, Ranieri M, Rubenfeld GD, Thompson BT, Wrigge H, Slutsk — View Citation

Lanspa MJ, Peltan ID, Jacobs JR, Sorensen JS, Carpenter L, Ferraro JP, Brown SM, Berry JG, Srivastava R, Grissom CK. Driving pressure is not associated with mortality in mechanically ventilated patients without ARDS. Crit Care. 2019 Dec 27;23(1):424. doi: — View Citation

Neto AS, Simonis FD, Barbas CS, Biehl M, Determann RM, Elmer J, Friedman G, Gajic O, Goldstein JN, Linko R, Pinheiro de Oliveira R, Sundar S, Talmor D, Wolthuis EK, Gama de Abreu M, Pelosi P, Schultz MJ; PROtective Ventilation Network Investigators. Lung- — View Citation

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 Jun;16(5):428-39. doi: 10.1097/PCC.0000 — View Citation

Randolph AG, Meert KL, O'Neil ME, Hanson JH, Luckett PM, Arnold JH, Gedeit RG, Cox PN, Roberts JS, Venkataraman ST, Forbes PW, Cheifetz IM; Pediatric Acute Lung Injury and Sepsis Investigators Network. The feasibility of conducting clinical trials in infa — View Citation

Raymondos K, Dirks T, Quintel M, Molitoris U, Ahrens J, Dieck T, Johanning K, Henzler D, Rossaint R, Putensen C, Wrigge H, Wittich R, Ragaller M, Bein T, Beiderlinden M, Sanmann M, Rabe C, Schlechtweg J, Holler M, Frutos-Vivar F, Esteban A, Hecker H, Ross — View Citation

Santschi M, Jouvet P, Leclerc F, Gauvin F, Newth CJ, Carroll CL, Flori H, Tasker RC, Rimensberger PC, Randolph AG; PALIVE Investigators; Pediatric Acute Lung Injury and Sepsis Investigators Network (PALISI); European Society of Pediatric and Neonatal Inte — View Citation

Schmidt MFS, Amaral ACKB, Fan E, Rubenfeld GD. Driving Pressure and Hospital Mortality in Patients Without ARDS: A Cohort Study. Chest. 2018 Jan;153(1):46-54. doi: 10.1016/j.chest.2017.10.004. Epub 2017 Oct 14. — View Citation

Serpa Neto A, Cardoso SO, Manetta JA, Pereira VG, Espósito DC, Pasqualucci Mde O, Damasceno MC, Schultz MJ. Association between use of lung-protective ventilation with lower tidal volumes and clinical outcomes among patients without acute respiratory dist — View Citation

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* Note: There are 28 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Driving pressure and mortality with all patients	Driving pressure and other lung dynamics; according to the type and distribution of the data was compared with chi-square, Wilcoxon, Independent-T-test or Mann-Whitney-U test and p <0.05 was considered statistically significant.	march 2018-april 2020
Secondary	Driving pressure with mortality in patients with pARDS and non-pARDS patients	we conducted separately to determine the relationship between ?P and mortality in patients non-ARDS and ARDS	march 2018-april 2020