Madhu Sasidhar

Exhaled breath analysis with a colorimetric sensor array for the identification and characterization of lung cancer.

Introduction: The pattern of exhaled breath volatile organic compounds represents a metabolic biosignature with the potential to identify and characterize lung cancer. Breath biosignature-based classification of homogeneous subgroups of lung cancer may be more accurate than a global breath signature. Combining breath biosignatures with clinical risk factors may improve the accuracy of the signature. Objectives: To develop an exhaled breath biosignature of lung cancer using a colorimetric sensor array and to determine the accuracy of breath biosignatures of lung cancer characteristics with and without the inclusion of clinical risk factors. Methods: The exhaled breath of 229 study subjects, 92 with lung cancer and 137 controls, was drawn across a colorimetric sensor array. Logistic prediction models were developed and statistically validated based on the color changes of the sensor. Age, sex, smoking history, and chronic obstructive pulmonary disease were incorporated in the prediction models. Results: The validated prediction model of the combined breath and clinical biosignature was moderately accurate at distinguishing lung cancer from control subjects (C-statistic 0.811). The accuracy improved when the model focused on only one histology (C-statistic 0.825–0.890). Individuals with different histologies could be accurately distinguished from one another (C-statistic 0.864 for adenocarcinoma versus squamous cell carcinoma). Moderate accuracies were noted for validated breath biosignatures of stage and survival (C-statistic 0.785 and 0.693, respectively). Conclusions: A colorimetric sensor array is capable of identifying exhaled breath biosignatures of lung cancer. The accuracy of breath biosignatures can be optimized by evaluating specific histologies and incorporating clinical risk factors.

The effect of metformin and thiazolidinedione use on lung cancer in diabetics

BackgroundMetformin and the thiazolidinediones (TZDs) may have a protective effect against the development of lung cancer.MethodsPatients with diabetes mellitus (DM) were identified from the electronic medical records of the Cleveland Clinic. Diabetics with lung cancer were identified then verified by direct review of their records. Control subjects were matched with cancer subjects 1:1 by date of birth, sex, and smoking history. The frequency and duration of diabetic medication use was compared between the groups. The cancer characteristics were compared between those with lung cancer who had and had not been using metformin and/or a TZD.Results93,939 patients were identified as having DM. 522 lung cancers in 507 patients were confirmed. The matched control group was more likely to have used metformin and/or a TZD (61.0% vs. 41.2%, p < 0.001 for any use; 55.5% vs. 24.6%, p < 0.001 for >24 months vs. 0–12 months). In the group with lung cancer, those who had used metformin alone had a different histology distribution than those who received neither metformin nor a TZD, were more likely to present with metastatic disease (40.8% vs. 28.2%, p = 0.013), and had a shorter survival from the time of diagnosis (HR 1.47, p < 0.005).ConclusionsThe use of metformin and/or the TZDs is associated with a lower likelihood of developing lung cancer in diabetic patients. Diabetics who develop lung cancer while receiving metformin may have a more aggressive cancer phenotype.

Caring for VIPs: Nine principles

Caring for very important persons (VIPs), including celebrities and royalty, presents medical, organizational, and administrative challenges, often referred to collectively as the “VIP syndrome.” The situation often pressures the health care team to bend the rules by which they usually practice medicine. Caring for VIP patients requires innovative solutions so that their VIP status does not adversely affect the care they receive. We offer nine guiding principles in caring for VIP patients. When the patient is a “very important person,” the health care team should resist pressure to bend the rules.

Tidal Volume Variability During Airway Pressure Release Ventilation: Case Summary and Theoretical Analysis

Airway pressure-release ventilation (APRV) is used in the management of patients with severe or refractory respiratory failure. In addition to reversal of inspiratory-expiratory ratios, this pressure control mode also allows unrestricted spontaneous breathing. The spontaneous tidal volume (VT), as well as the VT resulting from transition between the high and low airway pressures, is uncontrolled. There are limited data on the within-patient variation of actual VT and the safety of these modes. The authors present a patient with severe ARDS who was managed with biphasic modes (APRV and bi-level positive airway pressure). Serial VT measurements showed that VT ranged from 4 to 12 mL/kg predicted body weight. Computed tomography scan images and chest radiographs obtained before and following APRV showed lung parenchyma changes that may be related to ventilator-induced lung injury. We also present a mathematical model that is useful for simulating APRV and demonstrating the issues related to volume delivery for mandatory breaths during the transition between the 2 pressure levels. A key finding of this analysis is the interdependence of release volume, autoPEEP, and the Tlow time setting. Furthermore, it is virtually impossible to target a specific PaCO2 with a desired level VT and autoPEEP in a passive model, emphasizing the importance of spontaneous breathing with this mode. This case report suggests caution when using these modes, and that end-inspiratory lung volumes and VT should be limited to avoid lung injury. The important point of this case study and model analysis is that the application of APRV is more complex than it appears to be. It requires a lot more knowledge and skill than may be apparent from descriptions in the literature.

Noninferiority of Inhaled Epoprostenol to Inhaled Nitric Oxide for the Treatment of ARDS

Background: Inhaled nitric oxide and inhaled epoprostenol have been evaluated for the management of hypoxemia in acute respiratory distress syndrome, with clinical trials demonstrating comparable improvements in oxygenation. However, these trials have several limitations, making it difficult to draw definitive conclusions regarding clinical outcomes. Objective: The aim of this study was to evaluate the noninferiority and safety of inhaled epoprostenol compared with inhaled nitric oxide in mechanically ventilated acute respiratory distress syndrome (ARDS) patients with a primary outcome of ventilator-free days from day 1 to day 28. Methods: This was a retrospective, noninterventional, propensity-matched, noninferiority cohort study. Propensity score for receipt of inhaled nitric oxide was developed and patients were matched accordingly using a prespecified algorithm. Secondary objectives included evaluating day 28 intensive care unit–free days, changes in PaO2/FiO2 ratio after inhalation therapy initiation, and hospital mortality. Safety endpoints assessed included hypotension, methemoglobinemia, renal dysfunction, rebound hypoxemia, significant bleeding, and thrombocytopenia. Results: Ninety-four patients were included, with 47 patients in each group. Patients were well-matched with similar baseline characteristics, except patients in inhaled nitric oxide group had lower PaO2/FiO2 ratio. Management of ARDS was similar between groups. Mean difference in ventilator-free days between inhaled epoprostenol and inhaled nitric oxide was 2.16 days (95% confidence interval = −0.61 to 4.9), with lower limit of 95% confidence interval greater than the prespecified margin, hence satisfying noninferiority. There were no differences in any secondary or safety outcomes. Conclusions: Inhaled epoprostenol was noninferior to inhaled nitric oxide with regard to ventilator-free days from day 1 to day 28 in ARDS patients.

Characteristics and Outcomes of Patients With Lung Transplantation Requiring Admission to the Medical ICU

BACKGROUND There are few data on characteristics and outcomes among patients with lung transplantation (LT) requiring admission to the medical ICU (MICU) beyond the perioperative period. METHODS We interrogated the registry database of all admissions to the MICU at Cleveland Clinic (a 53-bed closed unit) to identify patients with history of LT done > 30 days ago (n = 101; mean age, 55.4 ± 12.6 years; 53 men, 48 women). We collected data regarding demographics, history of bronchiolitis obliterans syndrome, preadmission FEV1, clinical and laboratory variables at admission, MICU course, length of stay, hospital survival, and 6-month survival. RESULTS The most common indication for MICU admission was acute respiratory failure (n = 51, 50.5%). Infections were most frequently responsible for respiratory failure, whereas acute rejection (cellular or humoral) was less likely (16%). Nearly one-fourth of the patients required hemodialysis (24.1%), and more than one-half required invasive mechanical ventilation (53.5%). Despite excellent hospital survival (88 of 101), 6-month survival was modest (56.4%). APACHE (Acute Physiology and Chronic Health Evaluation) III score at admission and single LT were independent predictors of hospital survival but did not predict outcome at 6 months. Functional status at discharge was the only independent predictor of 6-month survival (adjusted OR, 5.1; 95% CI, 1.1-22.7; P = .035). CONCLUSIONS Acute rejection is an infrequent cause of decompensation among patients with LT requiring MICU admission. For patients admitted to the MICU, 6-month survival is modest. Functional status at the time of discharge is an independent predictor of survival at 6 months.

Tidal volume measurement error in pressure control modes of mechanical ventilation

UNLABELLED Tidal volume (VT) measurement during pressure control (PC) ventilation with preset inspiratory time may produce errors due to patient inspiratory effort. We evaluated VT error in 3 common ICU ventilators. METHODS Simulated patient: 60kg adult with ARDS using IngMar Medical ASL 5000 having moderate inspiratory effort. Ventilators evaluated: Covidien PB 840, Maquet Servo-i, and Dräger Evita XL, PC breaths at preset inspiratory time (TI) 0.6-1.4s. VT error was defined as ventilator displayed VT minus the simulator displayed VT (mL/kg or % of true). RESULTS Relaxation of inspiratory effort caused flow reversal (exhalation) during TI, which led to VT error. For the PB 840, VT error was proportional to TI (maximum -2.0mL/kg, -19%). For the Servo-i, VT error was not related to TI (maximum error -0.2mL/kg or -1.2%). Volume error for Evita XL was not related to TI (maximum error was -0.7mL/kg or -6%). CONCLUSIONS Calculation of VT as the integral of flow over the preset inspiratory time rather than the period between zero crossings of flow may result in underestimation of both inhaled and exhaled volumes. The size of VT error can be large enough to potentially affect patient outcomes on some ventilators.

Accuracy of the Electronic Health Record: Patient Height

BACKGROUND: Protective lung ventilation requires calculating predicted body weight (BW) from height. Thus, inaccuracy of height data in the electronic health record (EHR) is a risk factor for ventilator-induced lung injury. Charted height data often have uncertain accuracy. Study purposes were (1) to evaluate the difference between patient height charted in the EHR and predicted height (PH) from ulnar length and (2) to determine how the height data source affects predicted BW and the resulting values for protective tidal volume (VT). METHODS: Subject height data from the EHR were collected from several ICUs. Simultaneous ulnar data were collected by measuring ulnar length (cm): male PH (cm) = 79.2 ± 3.60 × ulnar length; female PH = 95.6 ± 2.77 × ulnar length. For each subject, BW (kg) was calculated from height charted in EHR and from predicted height: male BW = 50 ± 0.91 × (height − 152.4); female BW = 45.5 ± 0.91 × (height − 152.4). Then VT was calculated as 8 mL/kg BW. Bland-Altman analysis of height and VT differences (charted − predicted) determined the limits of agreement. RESULTS: For white males (n = 27) the mean (SD) height from EHR was 177 (7.5); predicted height was 178 (6.9). The limits of agreement for height in males were −18.5 and 17.8 cm. The limits of agreement for females were −23.1 and 21.3 cm. The limits of agreement for VT in males were −1.8 and 1.8 mL/kg. The limits of agreement for VT in females were −3.0 and 2.9 mL/kg. CONCLUSIONS: For overall populations, mean height calculated from values charted in the EHR is similar to that estimated from ulnar length. However, for individuals, differences in height between the 2 sources can be large, leading to large differences in predicted BW and resultant VT set in terms of mL/kg.

Airway Pressure Release Ventilation May Result in Occult Atelectrauma in Severe ARDS

To the Editor: In a recent issue of Respiratory Care, Mireles-Cabodevila and Kacmarek[1][1] did an excellent job reviewing the pros and cons of airway pressure release ventilation (APRV). The paper and the discussion session raised serious concerns about ARPV, particularly regarding imposed work

Non-invasive positive pressure ventilation in lung transplant recipients with acute respiratory failure: Beyond the perioperative period

Purpose: The purpose of this study is to evaluate outcomes in MICU lung transplant recipients with acute respiratory failure treated with non‐invasive positive pressure ventilation (NPPV) and identify factors associated with NPPV failure (need for intubation). Methods: Retrospective chart review of all lung transplant recipients who were admitted with acute respiratory failure to the MICU from January 2009–August 2016 was completed. Logistic regression analysis was performed to determine which factors were independently associated with NPPV failure. Results: Of 156 patients included in the study, 125 (80.1%) were tried on NPPV. Sixty‐eight (54.4%) were managed successfully with NPPV with a hospital survival rate of 94.1%. Subjects who failed NPPV had higher hospital mortality, similar to those intubated from the outset (15 [48.3%]; 22 [38.6%], p = .37). In multivariate analyses, APACHE III scores >78 (9.717 [3.346, 28.22]) and PaO2/FiO2 ≤ 151 (4.54 [1.72, 11.99]) were associated with greater likelihood of NPPV failure. There was no difference in NPPV failure based on the presence of BOS. In patients with high severity of illness, there was no difference in mortality between initial IMV and NPPV failure when stratified on the basis of hypoxemia (PaO2/FiO2 > 151, p‐value 0.34; PaO2/FiO2 ≤ 151, p‐value 0.99). Conclusions: NPPV is a viable option for lung transplant recipients with acute respiratory failure. Extreme caution should be exercised when used in patients with high severity of illness (APACHE III >78) and/or severe hypoxemia (PaO2/FiO2 ≤ 151). HighlightsLung transplant recipients with acute respiratory failure are at high risk of death.NPPV is a viable option for lung transplant recipients with acute respiratory failure.NPPV should be used sparingly in lung transplant recipients on vasopressors, with high severity of illness (APACHE III score > 78) and/or severe hypoxemia (PaO2/FiO2 ≤ 151).