Clinical trial NCT02598713: Validation of Aspiration Markers in Intubated Patients
Official title: Validation of Markers for Aspiration for Endotracheal Tube Cuff Leak
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Pneumonia
Aspiration
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
First posted: 2015-11-06
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief summary: The goal of this interventional study is to test Quinine as marker of aspiration (endotracheal tube \[ETT\] cuff leakage) in mechanically ventilated, critically ill patients.

Detailed description: At present there is no standard method for the evaluation of in vivo cuff leak and aspiration. Most of the tested techniques have major pitfalls that render their routine application infeasible. Lacking a practical and reliable marker, any possible intervention aimed at improving cuff seal and ETT performance in order to reduce VAP occurrence is going to be hindered by the inability to truly evaluate its efficacy. Radio-labeled markers are expensive, expose the patient to considerable radiological risk, and require transport to a radiological department, which would expose critically ill patients to additional risk. Dyes have the potential to give useful information about the presence of a cuff leak, but due to persistent staining of secretions, they do not allow continuous monitoring of aspiration. Amylase detection could be a good marker of aspiration, but its ability to detect aspiration is poor even when compared to pepsin. Pepsin and bile acids have the potential to detect some of the aspirations and cuff leaks that happen daily in mechanically ventilated patients, but due to their gastrointestinal nature, they do not offer any kind of information about aspiration of contaminated oropharyngeal secretions. With this research protocol, the investigators would like to validate the use of Quinine suspended in sterile water as marker for determining cuff leakage and aspiration events in an ICU population. Quinine is compound commonly used in food manufacturing. His pharmacokinetic and -dynamic has extensively been studied. The chemical structure of this molecule allows the detection up to pico-molar concentration by spectrophotometry.

The investigators will challenge the oropharyngeal cavity with a known concentration of Quinine suspended in sterile water. The investigators hypothesized that the detection by spectrophotometry of the same substance in the tracheal secretions will prove aspiration.

The investigators specific aims are:

1. To quantify the measurements of Quinine in the tracheal sample and compare with the measurements of Quinine in the oral sample.
2. To assess association between the amount of oropharyngeal aspiration and the development of upper and lower respiratory complications (i.e. ventilator associated pneumonia \[VAP\], tracheobronchitis, ventilator-associated events, acute respiratory distress syndrome \[ARDS\], etc.).
3. To determine patient's risk factors associated with oropharyngeal aspiration. The introduction of this new, safe and inexpensive markers for evaluating ETT cuff performance and for detecting aspiration will improve the design of future studies aimed at VAP prevention.

Eligibility criteria: Inclusion Criteria:

* Age ≥ 18 years
* Admission to Surgical ICUs (MGH Ellison 4 or Blake 12)
* Patients expected to be intubated for at least 48 hours or longer from the time of enrollment.

Exclusion Criteria:

* High PEEP requirement at enrollment (PEEP higher than 8 cmH2O)
* Diagnosis of ARDS (any severity)
* Status asthmatics
* Current or past participation in another interventional trial conflicting with the present study
* Pregnant women
* Prisoner status
* Patients who had partial or total gastrectomy.

Primary outcomes:
measure: Oropharyngeal aspiration: change in concentration of quinine in tracheal samples.
timeFrame: After the beginning of the study, samples will be collected at hours: 0,1 and 24, 25
Secondary outcomes:
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachussets General Hospital
state: Massachusetts
Study officials:
affiliation: Massachusetts General Hospital
name: Lorenzo Berra, MD
role: PRINCIPAL_INVESTIGATOR
References:
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citation: Berra L, Panigada M, De Marchi L, Greco G, Z -Xi Y, Baccarelli A, Pohlmann J, Costello KF, Appleton J, Mahar R, Lewandowski R, Ravitz L, Kolobow T. New approaches for the prevention of airway infection in ventilated patients. Lessons learned from laboratory animal studies at the National Institutes of Health. Minerva Anestesiol. 2003 May;69(5):342-7.
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citation: Li Bassi G, Luque N, Marti JD, Aguilera Xiol E, Di Pasquale M, Giunta V, Comaru T, Rigol M, Terraneo S, De Rosa F, Rinaudo M, Crisafulli E, Peralta Lepe RC, Agusti C, Lucena C, Ferrer M, Fernandez L, Torres A. Endotracheal tubes for critically ill patients: an in vivo analysis of associated tracheal injury, mucociliary clearance, and sealing efficacy. Chest. 2015 May;147(5):1327-1335. doi: 10.1378/chest.14-1438.
citation: Metheny NA, Clouse RE, Chang YH, Stewart BJ, Oliver DA, Kollef MH. Tracheobronchial aspiration of gastric contents in critically ill tube-fed patients: frequency, outcomes, and risk factors. Crit Care Med. 2006 Apr;34(4):1007-15. doi: 10.1097/01.CCM.0000206106.65220.59.
citation: Mietto C, Pinciroli R, Patel N, Berra L. Ventilator associated pneumonia: evolving definitions and preventive strategies. Respir Care. 2013 Jun;58(6):990-1007. doi: 10.4187/respcare.02380.