Diaphragmatic Ultrasound in Acute Hypoxic - Hypercapnic Respiratory Failure (ARF) (DiaDea)

Ultrasound Diaphragmatic Evaluation in Acute Hypoxic - Hypercapnic Respiratory Failure (ARF) Patients Undergoing Non Invasive Ventilation: A Pilot Feasibility Study

Mortality of acute hypoxic - hypercapnic respiratory failure (ARF) patients underwent invasive mechanical ventilation is demonstrated to be higher than in patients who underwent only non invasive mechanical ventilation (NIV).

There is an increased need to detect more predictive factors for NIV failure, in order to better identify patients most at risk of facing negative outcomes.

The aim of this experimental pilot study is to evaluate the feasibility of the ultrasound of diaphragm in ARF patients underwent non invasive mechanical ventilation ( primary endpoint ).

Furthermore the secondary aim is to observe any relationship between diaphragmatic function (excursion), diaphragmatic thickening and the timing of arterial blood gases (ABGs) compensation in patients with ARF undergoing NIV treatment; additional outcomes are: correlation with dyspnea level, time of mechanical ventilation, NIV failure, rate of tracheostomy, length of stay in ICU and in-hospital and 90-day mortality.

Study Overview

• Status: Completed
• Conditions: Acute Hypoxic - Hypercapnic Respiratory Failure (ARF)
• Intervention / Treatment: Diagnostic test: D-US ARF

Detailed Description

Inclusion criteria: respiratory failure resulting in respiratory acidosis to be treated with NIV, age> = 18 years

Exclusion criteria: acute pulmonary edema, coexisting interstitial pathologies, neuromuscular pathologies, thoracic cage's deformity, previous diaphragmatic paralysis, hemodynamic instability, intracranial hypertension, pregnancy, absolute contraindications to NIV, need for immediate intubation, recent thoracotomy, presence of pneumothorax or pneumomediastinum.

After patient's triage, transfer to Shock Room and primary assessment by emergency department staff ,diaphragmatic ultrasound is performed when NIV indication is given.

NIV is delivered with a facial mask; ventilation is set in NIV application, pressure support mode. Positive end expiratory pressure (PEEP) and Inspired oxygen fraction (FiO2) are adjusted to obtain a peripheral oxygen saturation (Spo2) between 88-92%. The pressure support is set to achieve a target volume of between 6-8 (ml / kg) and a respiratory rate < 30 respiratory acts per minute.

Respectively one and two hours after starting NIV, diaphragmatic ultrasonography and ABGs analysis are again performed.

NIV failure criteria are defined by the need for endotracheal intubation or by death.

Criteria for NIV failure: unchanging or worsening blood gases despite NIV; need to protect airways due to neurological deterioration or massive secretions; haemodynamic instability or major electrocardiographic abnormalities; uncontrolled dyspnea and NIV intolerance/ refusal.

General measures On admission clinical severity is recorded by Glasgow Coma Scale (GCS), Acute Physiology and Chronic Health Evaluation II Score (APACHE II).

ABGs values ( PH, arterial oxygen tension (paO2), arterial carbon dioxide tension (paCo2), paO2/FiO2, bicarbonates (HCO3), lactate) will be recorded before NIV, at 1 hour and 2 hours later.

Chest X-ray and peripheral blood sample (hemochrome with band cell count, C-reactive protein (CRP) and electrolytes) will be performed within 24 hours of admission.

The presence of pneumonia, sepsis and previous treatment with systemic or inhaled steroids will be recorded.

Diaphragm Ultrasound

Ultrasound evaluation of diaphragm function is performed on admission before starting NIV, 1 hour and 2 hours later.

Diaphragmatic function is assessed by a B-Mode ultrasound device connected to a linear probe ( 7-12 MHz) at the patient's bedside.

Measurements are performed on a patient in supine position with a recessed back angle between 20 and 40 degrees.

Probe position is set between 8th and 10th intercostal space on the mid axillary line to find the apposition zone of the diaphragm, where lung, diaphragm and abdominal parenchyma are identifiable.

Diaphragmatic thickness is measured at end-inspiration ( Ti) and end- expiration (Te).

The percentage change in diaphragmatic thickness (ΔTdi) is calculated as follows:

ΔTdi % = (Ti- Te) / Te * 100 Measurements are performed three times and the average value of the three measurements is considered.

Diaphragmatic excursion is also evaluated.

Statistical analysis As it is an experimental pilot feasibility study, 20 patients will be initially enrolled.

Descriptive statistics for continuous variables will be presented as median and interquartile. Non-parametric continuous variables will be evaluated by non-parametric Wilcoxon test (Mann-Whitney).

Categorical variables will be evaluated by chi-square or Fisher's test.

The influence of diaphragmatic thickening and muscle thickness on NIV failure, mortality and hospitalization's days wil be assessed through correlation analysis A P-value <0.05 will be considered significant.

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Italy
  • Novara, Italy, 28100
    • A.O.U Maggiore della Carità

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• respiratory failure resulting in respiratory acidosis to be treated with NIV
• Age> = 18 years

Exclusion Criteria:

• acute pulmonary edema
• coexisting interstitial pathologies
• neuromuscular pathologies
• thoracic cage's deformity
• previous diaphragmatic paralysis
• hemodynamic instability
• intracranial hypertension
• pregnancy
• absolute contraindications to NIV
• need for immediate intubation,
• recent thoracotomy
• presence of pneumothorax or pneumomediastinum

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: D-US ARF; Diaphragmatic evaluation, i.e thickening fraction (%) and excursion (millimeters), will be performed 3 times in the first two hours after acute hypoxic - hypercapnic respiratory failure (ARF) patients admission	Diagnostic test: D-US ARF; Diaphragm ultrasound evaluation in acute hypoxic - hypercapnic respiratory failure (ARF) patients undergoing non invasive ventilation, with regard to thickening (%) and excursion (millimeters)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility of diaphragm ultrasound function evaluation (excursion and thickening) in acute hypoxic - hypercapnic respiratory failure (ARF) during the first two hours after emergency department admission.	Ultrasound will be performed before starting NIV, after 1 and 2 two hours of NIV application	2 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Arterial blood carbon dioxide (PaCO2) compensation evaluation	PaCO2 at time of starting NIV, after one hour from NIV application and after two hours of NIV application	0 hour
Arterial blood carbon dioxide (PaCO2) compensation evaluation	PaCO2 at time of starting NIV, after one hour from NIV application	1 hour
Arterial blood carbon dioxide (PaCO2) compensation evaluation	PaCO2 after two hours from NIV application	2 hours
Monitoring diaphragmatic function in terms of thickening at 0 hour	Diaphragmatic thickening (%) [(inspiratory thickness - expiratory thickness)]/expiratory thickness * 100	0 hour
Monitoring diaphragmatic function in terms of thickening at 1 hour	Diaphragmatic thickening (%) [(inspiratory thickness - expiratory thickness)]/expiratory thickness * 100	1 hour
Monitoring diaphragmatic function in terms of thickening at 2 hours	Diaphragmatic thickening (%) [(inspiratory thickness - expiratory thickness)]/expiratory thickness * 100	2 hours
Monitoring diaphragmatic function in terms of excursion at 0 hour	Diaphragmatic excursion (millimeters) computed as diaphragmatic displacement during breath	0 hour
Monitoring diaphragmatic function in terms of excursion at 1 hour	Diaphragmatic excursion (millimeters) computed as diaphragmatic displacement during breath	1 hour
Monitoring diaphragmatic function in terms of excursion at 2 hours	Diaphragmatic excursion (millimeters) computed as diaphragmatic displacement during breath	2 hours
Days spent in intensive care unit	Amount of days spent in ICU	28 days
Days spent in in hospital	Amount of days spent in hospital	90 days
dyspnea level at 0 hour	dyspnea level evaluated via visual analogical scale	0 hour
dyspnea level at 1 hour	dyspnea level evaluated via visual analogical scale	1 hour
dyspnea level at 2 hours	dyspnea level evaluated via visual analogical scale	2 hours

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Relationship with mechanical ventilation length	mechanical ventilation length expressed in days for both invasive and non invasive ventilation	28 days
Mortality in intensive care unit	Number of death in intensive care unit	28 days
Tracheostomy	Rate of tracheostomy (ratio between number of tracheostomy in study group)	28 days
Relation with gravity index	value of APACHE score in study population	24 hours
Mortality in hospital	Number of death in hospital	90 days

Collaborators and Investigators

• Sponsor: Azienda Ospedaliero Universitaria Maggiore della Carita

Publications and helpful links

General Publications

• Cammarota G, Sguazzotti I, Zanoni M, Messina A, Colombo D, Vignazia GL, Vetrugno L, Garofalo E, Bruni A, Navalesi P, Avanzi GC, Della Corte F, Volpicelli G, Vaschetto R. Diaphragmatic Ultrasound Assessment in Subjects With Acute Hypercapnic Respiratory Failure Admitted to the Emergency Department. Respir Care. 2019 Dec;64(12):1469-1477. doi: 10.4187/respcare.06803. Epub 2019 Aug 27.

Study record dates

Study Major Dates

• Study Start (Actual): October 9, 2017
• Primary Completion (Actual): May 4, 2018
• Study Completion (Actual): May 4, 2018

Study Registration Dates

• First Submitted: September 22, 2017
• First Submitted That Met QC Criteria: October 15, 2017
• First Posted (Actual): October 19, 2017

Study Record Updates

• Last Update Posted (Actual): May 7, 2018
• Last Update Submitted That Met QC Criteria: May 3, 2018
• Last Verified: May 1, 2018

More Information

Terms related to this study

• Keywords: Ultrasound; Diaphragm; Non Invasive Ventilation
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Respiration Disorders; Signs and Symptoms, Respiratory; Respiratory Insufficiency; Hypoxia; Hypercapnia
• Other Study ID Numbers: CE 112/17

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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