Bilateral Bronchoalveolar Lavage in Ventilator-associated Pneumonia

Bilateral Bronchoalveolar Lavage Cultures for Diagnosing Ventilator-associated Pneumonia. Microbiologic Concordance and Impact on the Efficacy of Treatment Decisions.

The purpose of this study is to assess microbiologic concordance rates between right- and left-lung bronchoalveolar lavage cultures from patients with suspected ventilator-associated pneumonia, identify predictors of concordance, and evaluate the impact of discordant microbiology on clinicians' ability to prescribe appropriate antibiotic treatments, the investigators conducted a prospective observational study in the general intensive care unit of a large university hospital.

Study Overview

• Status: Completed
• Conditions: Pneumonia, Ventilator-Associated
• Intervention / Treatment: Procedure: Bilateral BAL

Detailed Description

Bronchoscopic sampling of lower respiratory tract secretions is widely used in intensive care units (ICUs) for the microbiological diagnosis of ventilator-associated pneumonia (VAP). However, the importance of selecting a specific lung segment for sampling is still a matter of debate.

Non-bronchoscopic blind mini-bronchoalveolar lavage (BAL) is currently used for the diagnosis of VAP with satisfactory sensitivity and specificity. In the presence of pneumonia, microbiologic concordance between the left and right lungs becomes crucial. If concordance is low, the reliability of blind sampling becomes questionable.

When the bacterial distribution in the right and left lungs of VAP patients has been investigated using bronchoscopic sampling techniques, rates of microbiological concordance between the two specimens have varied widely (from 53% to 92%). The factors potentially associated with concordant culture yields have never been explored, and it is unclear whether the use of guided, bilateral lung sampling would actually improve the appropriateness of the antibiotic regimens prescribed for patients with suspected VAP.

The primary objective of this study is to assess the frequency of microbiologic concordance between the right- and left-lung samples in ICU patients undergoing bronchoscopic BAL performed with two different fiberoptic bronchoscopes for the suspicion of VAP. Secondary objectives are to identify factors associated with such concordance and to evaluate the suitability of treatments prescribed based on unilateral vs. bilateral BAL cultures.

• Study Type: Interventional
• Enrollment (Actual): 79
• Phase: Not Applicable

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:

• invasive mechanical ventilation of ≥ 48 hours
• clinically suspected pneumonia (simplified Clinical Pulmonary Infectious Score exceeded 6 or chest radiographs with a new or progressive pulmonary infiltrate in a patient with at least two of the following: purulent respiratory secretions, temperature >38°C or <36°C, white blood cell count >12,000/mm3 or <4,000/mm3)

Exclusion Criteria:

• age <18 years
• pregnancy
• absence of informed consent
• an arterial oxygen partial pressure to inspired oxygen fraction ratio (PaO2:FiO2) of ≤150
• use of positive end-expiratory pressure (PEEP) >10 cmH2O
• active uncontrolled bronchospasm
• unstable angina or recent (<6 weeks) myocardial infarction
• unstable arrhythmia
• intracranial hypertension
• platelet count ≤20,000/mm3
• international normalized ratio (INR) or activated partial thromboplastin time (aPTT) ratio >1.5
• documented treatment-limitation orders in the patient's chart

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: Bilateral BAL; Bronchoscopies are performed in strict accordance with consensus guidelines. The left or right lung is examined with a flexible fiberoptic bronchoscope. If localized infiltrates are present on the chest radiograph, the tip of the scope is wedged into a subsegment of the area displaying the most marked opacity. In the presence of diffuse opacity or when no clear roentgenographic abnormalities are observed, the tip is positioned in the lingula or right middle lobe. Five 20-ml aliquots of sterile normal saline are then injected and reaspirated with a syringe. Bronchoscopy is then repeated in the same manner in the contralateral lung with a second, sterile bronchoscope of the same brand and model.

Procedure: Bilateral BAL

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of microbiologic concordance between the right- and left-lung samples	Pneumonia is microbiologically confirmed when the quantitative culture of one or both BAL specimens is positive at significant growth for at least one potential bacterial pathogen. Right and left BAL cultures are classified as concordant when both are positive for the same organism(s) or when neither show any growth. Cultures are classified as discordant when at least one of the microorganisms isolated from one specimen is not recovered from the contralateral specimen.	After at least 48 hours of invasive mechanical ventilation

Secondary Outcome Measures

Outcome Measure	Time Frame
Possible association between purulent secretions and microbiologic concordance between right- and left-lung BAL cultures	At an expected average of 48 hours after bronchoscopy
Possible association between duration of mechanical ventilation and microbiologic concordance between right- and left-lung BAL cultures	At an expected average of 48 hours after bronchoscopy
Possible association between duration of ICU stay and microbiologic concordance between right- and left-lung BAL cultures	At an expected average of 48 hours after bronchoscopy
Possible association between duration of hospital stay and microbiologic concordance between right- and left-lung BAL cultures	At an expected average of 48 hours after bronchoscopy
Possible association between immunosuppression and microbiologic concordance between right- and left-lung BAL cultures	At an expected average of 48 hours after bronchoscopy
Possible association between antibiotic treatment and microbiologic concordance between right- and left-lung BAL cultures	At an expected average of 48 hours after bronchoscopy
Possible association between radiological infiltrate and microbiologic concordance between right- and left-lung BAL cultures	At an expected average of 48 hours after bronchoscopy
Possible association between body temperature and microbiologic concordance between right- and left-lung BAL cultures	At an expected average of 48 hours after bronchoscopy
Possible association between WBC count and microbiologic concordance between right- and left-lung BAL cultures	At an expected average of 48 hours after bronchoscopy
Possible association between PaO2:FiO2 and microbiologic concordance between right- and left-lung BAL cultures	At an expected average of 48 hours after bronchoscopy
Possible association between PEEP and microbiologic concordance between right- and left-lung BAL cultures	At an expected average of 48 hours after bronchoscopy
Possible association between CPIS and microbiologic concordance between right- and left-lung BAL cultures	At an expected average of 48 hours after bronchoscopy
Possible association between type of humidification and microbiologic concordance between right- and left-lung BAL cultures	At an expected average of 48 hours after bronchoscopy
Possible association between procalcitonin and microbiologic concordance between right- and left-lung BAL cultures	At an expected average of 48 hours after bronchoscopy
Possible association between C-reactive protein and microbiologic concordance between right- and left-lung BAL cultures	At an expected average of 48 hours after bronchoscopy

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Comparison of antibiotic regimens chosen on the basis of right or left-lung culture results alone with regimens chosen on the basis of bilateral culture results, by performing a simulated prescribing experiment.	For each enrolled patient, actual treatment decisions are made by the ICU attending physicians in charge of the case on the basis of the results of bilateral BAL culture and sensitivity analyses. Later, at the end of the study, data for patients with discordant BAL cultures are reviewed in a simulated prescribing session by a second team composed of an ICU physician and an infectious disease specialist. The team is asked to propose an appropriate antimicrobial regimen based on the culture and in vitro antimicrobial susceptibility data for the right-lung BAL sample alone, the left-lung BAL sample alone, and the right and left BAL samples. Each microbiological report is presented separately to the team with a summary of the patient's relevant clinical data. The prescribed regimen is defined as appropriate if it provides active coverage for all of the organisms identified in both BAL specimens.	At 18 months after study initiation

Collaborators and Investigators

• Sponsor: Catholic University of the Sacred Heart
• Investigators: Principal Investigator: Giuseppe Bello, MD, Università Cattolica del Sacro Cuore, Rome, Italy

Publications and helpful links

General Publications

• Meduri GU, Chastre J. The standardization of bronchoscopic techniques for ventilator-associated pneumonia. Chest. 1992 Nov;102(5 Suppl 1):557S-564S. doi: 10.1378/chest.102.5_supplement_1.557s. No abstract available.
• Marquette CH, Herengt F, Saulnier F, Nevierre R, Mathieu D, Courcol R, Ramon P. Protected specimen brush in the assessment of ventilator-associated pneumonia. Selection of a certain lung segment for bronchoscopic sampling is unnecessary. Chest. 1993 Jan;103(1):243-7. doi: 10.1378/chest.103.1.243.
• Meduri GU, Reddy RC, Stanley T, El-Zeky F. Pneumonia in acute respiratory distress syndrome. A prospective evaluation of bilateral bronchoscopic sampling. Am J Respir Crit Care Med. 1998 Sep;158(3):870-5. doi: 10.1164/ajrccm.158.3.9706112.
• Butler KL, Best IM, Oster RA, Katon-Benitez I, Lynn Weaver W, Bumpers HL. Is bilateral protected specimen brush sampling necessary for the accurate diagnosis of ventilator-associated pneumonia? J Trauma. 2004 Aug;57(2):316-22. doi: 10.1097/01.ta.0000088858.22080.cb.
• Jackson SR, Ernst NE, Mueller EW, Butler KL. Utility of bilateral bronchoalveolar lavage for the diagnosis of ventilator-associated pneumonia in critically ill surgical patients. Am J Surg. 2008 Feb;195(2):159-63. doi: 10.1016/j.amjsurg.2007.09.030.
• Zaccard CR, Schell RF, Spiegel CA. Efficacy of bilateral bronchoalveolar lavage for diagnosis of ventilator-associated pneumonia. J Clin Microbiol. 2009 Sep;47(9):2918-24. doi: 10.1128/JCM.00747-09. Epub 2009 Jul 15.
• Esperatti M, Ferrer M, Theessen A, Liapikou A, Valencia M, Saucedo LM, Zavala E, Welte T, Torres A. Nosocomial pneumonia in the intensive care unit acquired by mechanically ventilated versus nonventilated patients. Am J Respir Crit Care Med. 2010 Dec 15;182(12):1533-9. doi: 10.1164/rccm.201001-0094OC. Epub 2010 Aug 6.
• Bello G, Pennisi MA, Di Muzio F, De Pascale G, Montini L, Maviglia R, Mercurio G, Spanu T, Antonelli M. Clinical impact of pulmonary sampling site in the diagnosis of ventilator-associated pneumonia: A prospective study using bronchoscopic bronchoalveolar lavage. J Crit Care. 2016 Jun;33:151-7. doi: 10.1016/j.jcrc.2016.02.016. Epub 2016 Mar 3.

Study record dates

Study Major Dates

• Study Start: February 1, 2013
• Primary Completion (Actual): July 1, 2014
• Study Completion (Actual): July 1, 2014

Study Registration Dates

• First Submitted: August 25, 2015
• First Submitted That Met QC Criteria: September 3, 2015
• First Posted (Estimate): September 7, 2015

Study Record Updates

• Last Update Posted (Estimate): September 7, 2015
• Last Update Submitted That Met QC Criteria: September 3, 2015
• Last Verified: August 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases; Disease Attributes; Cross Infection; Iatrogenic Disease; Healthcare-Associated Pneumonia; Pneumonia; Pneumonia, Ventilator-Associated
• Other Study ID Numbers: Bilateral BAL in VAP