Phrenic Nerve Block to Mitigate Self-inflicted Lung Injury

Study Overview
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Brief Summary
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The purpose of this single-centered, proof of concept study is to determine whether it is feasible to perform a phrenic nerve block to reduce diaphragm electrical activity and, therefore, inspiratory effort and if such block reduces self-inflicted lung injury on patients under mechanical ventilation on spontaneous breathing. Ten patients will be monitored with electrical impedance tomography, NAVA catheter, and esophageal balloon. Using a nerve stimulator and an ultrasound, we will identify the phrenic nerve on its cervical portion bilaterally and administer perineural low-dose lidocaine. Diaphragm electrical activity, transpulmonary pressure and data on ventilation distribution will be continuously collected. The study will be over once the patient presents the same diaphragm electrical activity and transpulmonary pressure as before the phrenic nerve block.

Detailed Description
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The use of protective mechanical ventilation has improved prognosis on patients with Acute Respiratory Failure. The association of neuromuscular blockade in the first 48-72h has additionally contributed to a higher survival rate. Such improvement may be due to the reduction of transpulmonary pressures caused by the patient's inspiratory effort. To achieve appropriate neuromuscular blockade, highes doses of both neuromuscular blocking agents and sedatives are required. Therefore, such a strategy usually causes muscular atrophy, including the diaphragm. Because of the augmented neural drive of such patients, exacerbated by inflammation and pulmonary edema, the consequent high tidal volume and transpulmonary pressure cannot be reduced by the newest sedatives. In fact, some of these sedatives may even deteriorate ventilatory dyssynchrony. Our intention is to verify a novel approach: whether is possible to reduce the inspiratory effort of patients without the use of systemic neuromuscular blocking agents. Our objective in this proof of concept study is to determine the feasibility the use of phrenic nerve blockade to decrease transpulmonary pressure and tidal volume, as well as quantify its effects on esophageal pressure, diaphragmatic electrical activity, transpulmonary pressure and ventilation distribution in patients on spontaneous breathing. It is expected that such intervention will reduce diaphragm electrical activity, leading to lower transpulmonary pressure, tidal volume and driving pressures. All patients will be submitted to the same intervention. Respiratory mechanics, ventilation distribution, diaphragm electrical activity, heart rate, mean arterial pressure and peripheral saturation will be collected throughout the study. Once the patient presents the same diaphragmatic electrical activity and transpulmonary pressure as before the phrenic nerve block, the study will be over.

Official Title
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Feasibility of Phrenic Nerve Block to Mitigate Self-inflicted Lung Injury in ARF Patients Under Mechanical Ventilation on Spontaneous Breathing

Conditions
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Respiratory Failure, Mechanical Ventilation

Intervention / Treatment
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* Drug: Lidocaine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age > 17 years-old; Under mechanical ventilation on spontaneous breathing, capable of triggering the ventilator with P/F < 300; Tidal volume > 10ml/kg with inspiratory pressure of 12 cmH2O OR driving pressure > 15 cm H2O with inspiratory pressure of 12 cmH2O Exclusion Criteria: Use of neuromuscular blocking agents less than 3h; Richmond Agitation-Sedation Scale (RASS) > 0; Arterial pH < 7.25; Hemodynamically unstable or with increasing doses of vasopressors in the last 2h; Intracranial hypertension; Thoracic or abdominal tubes; Any neuromuscular disease; Spinal injury; Ascitis; Thoracic burn injury; Tetanus; Pregnancy.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Intervention Model: Single Group Assignment
Interventional Model Description: All patients will be submitted to the same procedures. There will be no between-group comparisons.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Phrenic Nerve Blockade<br>All patients will be submitted to bilateral phrenic nerve block on its cervical portion. | Drug: Lidocaine<br>* Using an ultrasound and a nerve stimulator, the phrenic nerve will be identified and low-dose lidocaine will be administered perineurally.<br>* Other names: Local anesthetic;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reduction of tidal volume or transpulmonary pressure | Tidal volume or transpulmonary pressure measured using EIT, Servo-I and an esophageal balloon | 20 minutes | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reduction of the inspiratory effort | Diaphragm electrical activity using NAVA | 20 minutes - 3 hours | 
| Consequences on mechanical ventilation | Tidal volume, pendellfut and asynchronies measured by EIT | 20 minutes - 3 hours | 
| Time to complete weaning of the blockade | Patients will be monitored until full recover of inspiratory effort or diaphragm electrical activity | 30 minutes - 3 hours | 
| Reduction of the inspiratory effort | Esophageal pressure using an esophageal catheter | 20 minutes - 3 hours |