Correlation Between PaCO2 and Respiratory Effort in Patients With COVID-19 With Extracorporeal Membrane Oxygenation

Correlation Between Level of Partial Pressure of Carbon Dioxide and Respiratory Effort in Patients With COVID-19 Undergoing Pressure Support Ventilation With Extracorporeal Membrane Oxygenation

Excessive respiratory effort may cause self-inflicted lung injury (SILI) and inspiratory muscle injuries , stimulate desynchronization between the patient and ventilator , and worsen the perfusion of extrapulmonary organs . Appropriate respiratory drive and effort should be maintained during the treatment of patients with respiratory failure . In contrast, respiratory drive and effort are commonly increased in patients with COVID-19 pneumonia , and this phenomenon may persist in critically ill patients with COVID-19, even after receiving venovenous ECMO (vv-ECMO) support, owing to low pulmonary compliance and a high systemic inflammatory state .

To reduce respiratory effort and drive, ICU physicians often administer high doses of sedative drugs, analgesics, and muscle relaxants. The prolonged use of high doses of these drugs can cause loss of the spontaneous cough reflex, which in turn impairs sputum drainage and eventually worsens pulmonary consolidation and lung infections.

As the partial pressure of carbon dioxide in arterial blood (PaCO2) could affect the respiratory drive from the respiratory center (1), it has been shown that altering different levels of extracorporeal carbon dioxide removal in patients undergoing ECMO recovering from acute respiratory distress syndrome (ARDS) could alter respiratory drive. We hope to find a more appropriate target for maintaining PaCO2 to control respiratory effort in patients with COVID-19 undergoing ECMO.

Study Overview

• Status: Completed
• Conditions: Extracorporeal Membrane Oxygenation Complication; COVID-19 Acute Respiratory Distress Syndrome; Respiratory Effort-Related Arousal
• Intervention / Treatment: Device: PaCO2

Detailed Description

A stable environment was maintained during the study to avoid stress and abrupt stimulation.

Before the start of the study, sedative drugs were titrated to Richmond agitation sedation scale values of -3 to -2, an assisted breathing mode trial was conducted, and support pressure level were adjusted to achieve tidal volume < 6 mL/kg. The ECMO GF was adjusted to achieve stable baseline conditions, defined as PaCO2 < 40 mmHg, respiratory rate < 25 bpm, and peak airway pressure < 25 cm H2O. PEEP, fraction of inspired oxygen, pressure support ventilation (PSV), ECMO blood flow, and dose of vasoconstrictors, sedatives, and analgesics remained unchanged throughout the study.

The study protocol was initiated when the baseline parameters s were stable. The baseline parameters, including ventilation settings, arterial and arterial blood gas analysis, hemodynamics, and indicators of respiratory effort were measured in the baseline group. Then, the ECMO GF was modified to 50% of the baseline, and etCO2 values were monitored. ECMO GF was adjusted at 5-min intervals (increasing or decreasing by 0.5 L/min each time) until etCO2 stabilized at a level 5-10 mmHg higher than the baseline. After 20 min, the parameters were measured for the second time in the high-CO2 group (Figure 1).

The study was stopped if the heart rate (HR) was > 140 beats/min and/or respiratory rate was > 40 bpm and/or systolic blood pressure > 180 mmHg and/or patients experienced anxiety or diaphoresis.

• Study Type: Observational
• Enrollment (Actual): 10

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100730
      • Peking Union Medical College Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

The study was conducted in the ICU of Peking Union Medical College Hospital in China. Patients with COVID-19 who had undergone ECMO and pressure support ventilation (PSV) via tracheal intubation between December 2022 and March 2023 were considered eligible for inclusion.

Description

Inclusion Criteria:

Patients with COVID-19 who had undergone ECMO and pressure support ventilation (PSV) via tracheal intubation.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
baseline group; PaCO2 35~40mmHg
High-CO2 group; PACO2 increases by 5-10mmHg compared to baseline value and >40mmHg	Device: PaCO2; Level of partial pressure of carbon dioxide

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pressure muscle index	During the pressure support mode, the inspiratory hold button was pressed and a physician performed an end-inspiratory occlusion maneuver. After a certain period, the patient completely stopped inspiratory effort. The difference between the end-inspiratory obstructive plateau pressure and pre-obstructive airway pressure (Paw) was used to estimate the patient's inspiratory effort and referred to as Pressure muscle index	Not exceeding 1 hour
airway pressure swing during occlusion	is defined as the swing in the Paw generated by the force of the respiratory muscle under assisted ventilation when the airway is temporarily blocked (3). The expiratory airway occlusion of the ventilator was performed at random intervals during each recording. Each occlusion persisted for a single breath, as verified by the normal recovery of Paw. The maximum deviation of Paw from positive end-expiratory pressure (PEEP) during each occlusion was documented as airway pressure swing during occlusion	Not exceeding 1 hour

Collaborators and Investigators

• Sponsor: Peking Union Medical College Hospital

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2022
• Primary Completion (Actual): March 30, 2023
• Study Completion (Actual): March 30, 2023

Study Registration Dates

• First Submitted: May 27, 2023
• First Submitted That Met QC Criteria: May 27, 2023
• First Posted (Actual): May 31, 2023

Study Record Updates

• Last Update Posted (Actual): May 31, 2023
• Last Update Submitted That Met QC Criteria: May 27, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Respiration Disorders; Pneumonia, Viral; Pneumonia; Lung Diseases; Infant, Newborn, Diseases; Lung Injury; Infant, Premature, Diseases; COVID-19; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Acute Lung Injury
• Other Study ID Numbers: 2023-PUMCH-A-216-2

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Basic characteristics, vital signs, monitoring indicators, and other information of enrolled patients

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No