Clinical trial NCT03978845: Phrenic Nerve Block to Mitigate Self-inflicted Lung Injury
Official title: Feasibility of Phrenic Nerve Block to Mitigate Self-inflicted Lung Injury in ARF Patients Under Mechanical Ventilation on Spontaneous Breathing
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Respiratory Failure
Mechanical Ventilation
Lead sponsor: University of Sao Paulo General Hospital
Sponsor class: OTHER
First posted: 2019-06-07
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: All patients will be submitted to the same procedures. There will be no between-group comparisons.
Primary purpose: SUPPORTIVE_CARE

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Reduction of tidal volume or transpulmonary pressure
timeFrame: 20 minutes
Secondary outcomes:
measure: Reduction of the inspiratory effort
timeFrame: 20 minutes - 3 hours
measure: Consequences on mechanical ventilation
timeFrame: 20 minutes - 3 hours
measure: Time to complete weaning of the blockade
timeFrame: 30 minutes - 3 hours
measure: Reduction of the inspiratory effort
timeFrame: 20 minutes - 3 hours
Other outcomes:
Locations:
city: São Paulo
country: Brazil
facility: Hospital das Clínicas - Faculdade de Medicina da Universidade de Sao Paulo
Study officials:
affiliation: University of Sao Paulo School of Medicine
name: Joaquim E Vieira, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Sao Paulo School of Medicine
name: Marcelo BP Amato, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: