Ronny Schnabel

Analysis of volatile organic compounds in exhaled breath to diagnose ventilator-associated pneumonia

Ventilator-associated pneumonia (VAP) is a nosocomial infection occurring in the intensive care unit (ICU). The diagnostic standard is based on clinical criteria and bronchoalveolar lavage (BAL). Exhaled breath analysis is a promising non-invasive method for rapid diagnosis of diseases and contains volatile organic compounds (VOCs) that can differentiate diseased from healthy individuals. The aim of this study was to determine whether analysis of VOCs in exhaled breath can be used as a non-invasive monitoring tool for VAP. One hundred critically ill patients with clinical suspicion of VAP underwent BAL. Before BAL, exhaled air samples were collected and analysed by gas chromatography time-of-flight mass spectrometry (GC-tof-MS). The clinical suspicion of VAP was confirmed by BAL diagnostic criteria in 32 patients [VAP(+)] and rejected in 68 patients [VAP(−)]. Multivariate statistical comparison of VOC profiles between VAP(+) and VAP(−) revealed a subset of 12 VOCs that correctly discriminated between those two patient groups with a sensitivity and specificity of 75.8% ± 13.5% and 73.0% ± 11.8%, respectively. These results suggest that detection of VAP in ICU patients is possible by examining exhaled breath, enabling a simple, safe and non-invasive approach that could diminish diagnostic burden of VAP.

Electronic nose analysis of exhaled breath to diagnose ventilator-associated pneumonia.

BACKGROUND Exhaled breath analysis is an emerging technology in respiratory disease and infection. Electronic nose devices (e-nose) are small and portable with a potential for point of care application. Ventilator-associated pneumonia (VAP) is a common nosocomial infection occurring in the intensive care unit (ICU). The current best diagnostic approach is based on clinical criteria combined with bronchoalveolar lavage (BAL) and subsequent bacterial culture analysis. BAL is invasive, laborious and time consuming. Exhaled breath analysis by e-nose is non-invasive, easy to perform and could reduce diagnostic time. Aim of this study was to explore whether an e-nose can be used as a non-invasive in vivo diagnostic tool for VAP. METHODS Seventy-two patients met the clinical diagnostic criteria of VAP and underwent BAL. In thirty-three patients BAL analysis confirmed the diagnosis of VAP [BAL+(VAP+)], in thirty-nine patients the diagnosis was rejected [BAL-]. Before BAL was performed, exhaled breath was sampled from the expiratory limb of the ventilator into sterile Tedlar bags and subsequently analysed by an e-nose with metal oxide sensors (DiagNose, C-it, Zutphen, The Netherlands). From further fifty-three patients without clinical suspicion of VAP or signs of respiratory disease exhaled breath was collected to serve as a control group [control(VAP-]). The e-nose data from exhaled breath were analysed using logistic regression. RESULTS The ROC curve comparing [BAL+(VAP+)] and [control(VAP-)] patients had an area under the curve (AUC) of 0.82 (95% CI 0.73-0.9). The sensitivity was 88% with a specificity of 66%. The comparison of [BAL+(VAP+)] and [BAL-] patients revealed an AUC of 0.69; 95% CI 0.57-0.81) with a sensitivity of 76% with a specificity of 56%. CONCLUSION E-nose lacked sensitivity and specificity in the diagnosis of VAP in the present study for current clinical application. Further investigation into this field is warranted to explore the diagnostic possibilities of this promising new technique.

Mimivirus is not a frequent cause of ventilator-associated pneumonia in critically ill patients.

Acanthamoeba polyphaga mimivirus (APMV) belongs to the amoebae‐associated microorganisms. Antibodies to APMV have been found in patients with pneumonia suggesting a potential role as a respiratory pathogen. In addition, positive serology for APMV was associated with an increased duration of mechanical ventilation and intensive care unit stay in patients with ventilator‐associated pneumonia. The aim of the present study was to assess the presence of APMV in bronchoalveolar lavage fluid samples of critically ill patients suspected of ventilator‐associated pneumonia. The study was conducted in the intensive care unit of the Maastricht University Medical Centre. All consecutive bronchoalveolar lavage fluid samples obtained between January 2005 and October 2009 from patients suspected of ventilator‐associated pneumonia were eligible for inclusion. All samples were analyzed by real‐time PCR targeting the APMV. A total of 260 bronchoalveolar lavage fluid samples from 214 patients (139 male, 75 female) were included. Bacterial ventilator‐associated pneumonia was confirmed microbiologically in 105 out of 260 (40%) suspected episodes of ventilator‐associated pneumonia (86 patients). The presence of APMV DNA could not be demonstrated in the bacterial ventilator‐associated pneumonia positive or in the bacterial ventilator‐associated pneumonia negative bronchoalveolar lavage fluid samples. Although suspected, APMV appeared not to be present in critically ill patients suspected of ventilator‐associated pneumonia, and APMV does not seem to be a frequent cause of ventilator‐associated pneumonia. J Med. Virol. 85:1836–1841, 2013.

Candida Pneumonia in Intensive Care Unit

It has been questioned if Candida pneumonia exists as a clinical entity. Only histopathology can establish the definite diagnosis. Less invasive diagnostic strategies lack specificity and have been insufficiently validated. Scarcity of this pathomechanism and nonspecific clinical presentation make validation and the development of a clinical algorithm difficult. In the present study, we analyze whether Candida pneumonia exists in our critical care population. We used a bronchoalveolar lavage (BAL) specimen database that we have built in a structural diagnostic approach to ventilator-associated pneumonia for more than a decade consisting of 832 samples. Microbiological data were linked to clinical information and available autopsy data. We searched for critically ill patients with respiratory failure with no other microbiological or clinical explanation than exclusive presence of Candida species in BAL fluid. Five cases could be identified with Candida as the likely cause of pneumonia.

Ventilator-associated pneumonia rates after introducing selective digestive tract decontamination

Abstract The incidence of ventilator-associated pneumonia (VAP) before and after the introduction of selective oral decontamination (SOD) only and selective digestive tract decontamination (SDD) in a general intensive care population was examined. SOD as standard of care was introduced in December 2010 and SDD, including SOD, in January 2012 for all patients with an expected length of intensive care unit (ICU) stay of at least 48 h. The diagnosis of VAP was based on clinical criteria and quantitative cultures of bronchoalveolar lavage fluid. A total of 4945 mechanically ventilated patients accounting for 37 554 ventilator days in the period from 2005 to 2013 were analyzed. The incidence of VAP per 1000 ventilator days declined significantly from 4.38 ± 1.64 before to 1.64 ± 0.43 after introduction of SOD/SDD (p = 0.007). Implementation of SOD/SDD as standard of care in ICUs may thus be effective in preventing VAP.

The influence of a change in septic shock definitions on intensive care epidemiology and outcome: comparison of sepsis-2 and sepsis-3 definitions

Abstract Background: Clear definitions for septic shock assist clinicians regarding recognition, treatment and standardized reporting of characteristics and outcome of this entity. Sepsis-3 definition of septic shock incorporates a new criterion, a lactate level >2 mmol/L. Differences in epidemiology and outcome of septic shock based upon both definitions were studied in an intensive care (ICU) population of septic patients. Methods: We analyzed a prospectively collected cohort of data in the ICU of the Maastricht University Medical Centre. 632 septic patients were included. ICU mortality was compared between the patient group fulfilling Sepsis-3 definition for septic shock and those that met Sepsis-2 definition. Furthermore, association between lactate levels and ICU mortality was studied. Results: Of 632 septic patients, 482 (76.3%) had septic shock according to Sepsis-2 and 300 patients (48.4%) according to Sepsis-3 definition, respectively. Patients meeting Sepsis-3 definition had a higher mortality than patients meeting Sepsis-2 definition (38.9 vs. 34.0%). Serum lactate levels between 2 and 4 mmol/L (25.0 vs. 26.2%, OR 0.94 (0.5–1.5)) and between 4 and 6 mmol/L (23.8 vs. 26.2%, OR 0.88 (0.4–1.7)) compared to levels ≤2 mmol/L were not associated with significantly higher ICU mortality. Serum lactate values ≥6 mmol/L, were significantly associated with increased ICU mortality. Conclusion: Patients classified according to Sepsis-3 criteria had a higher ICU mortality compared with Sepsis-2 criteria. Lactate levels <6 mmol/L were not able to identify patients with increased ICU mortality. Lactate threshold of 2 mmol/L may be too low to point out patients with actual increased ICU mortality.

Alternative diagnosis in the putative ventilator-associated pneumonia patient not meeting lavage-based diagnostic criteria

Abstract Background: The clinical picture of ventilator-associated pneumonia (VAP) can be mimicked by other infectious and non-infectious diseases. The aim of this study was to determine the alternative diagnoses and to develop a diagnostic flow chart for patients suspected of having VAP not meeting the diagnostic broncho-alveolar lavage (BAL) criteria. Methods: Adult intensive care patients with a clinical suspicion of VAP and negative BAL results were included. The clinical suspicion of VAP was based on the combination of clinical, radiological, and microbiological criteria. BAL was considered positive if cell differentiation revealed ≥ 2% cells with intracellular organisms and/or quantitative culture results of ≥ 104 cfu/ml. The most likely alternative diagnosis of fever and pulmonary densities was retrospectively determined by two authors independently. Results: In all, 110 of 207 patients with suspected VAP did not meet the diagnostic BAL criteria and required further diagnostic evaluation. In 67 patients an alternative diagnosis for fever could be found. In 51 patients an alternative diagnosis of both fever and pulmonary densities could be established. In almost 40% of patients no alternative diagnosis could be provided. Non-bacterial pneumonia was diagnosed in 10 patients with Herpes simplex virus 1 (HSV-1) as the most common pathogen. In eight patients non-infectious pneumonitis was diagnosed. Conclusion: Due to the wide range of alternative diagnoses and applied tests the diagnostic work-up proved to be necessarily individualized and guided by repeated clinical assessment. The most frequently found alternative diagnoses were viral pneumonia and non-infectious pneumonitis.