Differences in cerebral oxygenation during exercise in patients with idiopathic pulmonary fibrosis with and without exertional hypoxemia: does exercise intensity matter?

INTRODUCTION AND OBJECTIVES: Patients with idiopathic pulmonary fibrosis (IPF) present respiratory derangements at rest and during exercise, accompanied by exercise intolerance. Some patients may develop profound exertional desaturation even without resting hypoxemia. Evidence suggests the involvement of reduced cerebral-oxygenation in exercise intolerance. We aimed to examine (i) differences in cerebral-oxygenation during exercise between IPF patients with and without isolated exertional desaturation, (ii) whether the impairments in cerebral-oxygenation are detected at similar exercise intensity, and (iii) correlations between cerebral-oxygenation indices, disease severity, and 6-min walk test (6MWT). MATERIALS AND METHODS: Patients with IPF (n = 24; 62.1 ± 9.3 years) without resting hypoxemia underwent cardiopulmonary exercise testing (CPET) with cerebral-oxygenation monitoring via near-infrared-spectroscopy (NIRS). Βased on their pulse-oxymetry saturation (SpO2) during CPET, patients were divided into the "exertional-desaturators" group (SpO2nadir≤89% and ≥6% drop in SpO2) and the "non-exertional-desaturators" group (SpO2nadir≥90% and ≤5% drop). RESULTS: During CPET, the "exertional-desaturators" group exhibited lower oxygenated-hemoglobin (-0.67 ± 1.48 vs. 0.69 ± 1.75 µmol/l; p < 0.05) and higher deoxygenated-hemoglobin (1.67 ± 1.13 vs. 0.17 ± 0.62 µmol/l; p < 0.001) than the "non-exertional-desaturators" group. A different pattern (p < 0.01) in cerebral-oxygenation responses was observed in the two groups. In exertional-desaturators oxygenated-hemoglobin declined below baseline even at low/moderate-intensity exercise (p < 0.05), whereas, in non-exertional-desaturators cerebral-oxygenation declined (p < 0.05) at high-intensity exercise. Cerebral-NIRS indices correlated (p < 0.05) with CPET-duration, dyspnea, diffusion capacity, and 6MWT. CONCLUSIONS: During incremental exercise, patients with IPF and exertional desaturation present a significant decline in cerebral-oxygenation even during low-intensity exercise. Our findings support the implementation of longer-duration rehabilitation programs in IPF so that lower intensity exercise can be applied at the initial stages. (NCT03683082).

Phenotyping exercise limitation of patients with Interstitial Fibrosing Lung Disease: the importance of exercise hemodynamics.

INTRODUCTION AND OBJECTIVE: Left-heart dysfunction and pulmonary vasculopathy are increasingly recognized as contributing factors of exercise capacity limitation in interstitial fibrosing lung disease (IFLD). Moreover, the clinical significance of exercise pulmonary hypertension (ePH) in pulmonary and cardiac diseases has been documented, representing a risk factor for decreased exercise capacity and survival, progression to resting pulmonary hypertension (PH) and overall clinical worsening. We conducted a prospective study aiming at: (a) assessing the prevalence of PH and ePH in a cohort of 40 functionally limited patients with IFLD, (b) determining the post-capillary (postC) or pre-capillary (preC) etiology of either PH or ePH in this cohort, and (c) examining the correlations between invasively and non-invasively measured exercise variables among hemodynamic groups. PATIENTS AND METHODS: 40 IFLD patients underwent cardiopulmonary evaluation, including: clinical examination, lung function tests, 6-minute walking test, heart ultrasonography, cardiopulmonary exercise test and, finally, right heart catheterization (RHC). Resting hemodynamic evaluation was followed by the exercise protocol proposed by Herve et al, using a bedside cycle ergometer in the supine position. Abnormal elevation of mean pulmonary artery pressure (mPAP) above 30mmHg during exercise, with respect to abnormal elevation of cardiac output (CO) below 10 L/min (mPAP-CO ratio ⩾3 mmHg·min·L-1) was used to define ePH (Herve et al, 2015). Secondary hemodynamic evaluation involved detection of abnormal pulmonary arterial wedge pressure (PAWP) increase at peak exercise in relation to CO. Specifically, ΔPAWP/ΔCO >2 mmHg/L per minute determined an abnormal PAWP elevation (Bentley et al, 2020). RESULTS: Among the 40-patient cohort, 25% presented postC PH, 37.5% preC PH, 27.5% ePH, with the remaining 10% recording normal hemodynamics. PAWP evaluation during exercise revealed a postC etiology in 4 out of the 11 patients presenting ePH, and a postC etiology in 6 out of the 15 patients presenting resting preC PH. Mean values of non-invasive variables did not display statistically significant differences among hemodynamic groups, except for: diffusing capacity for carbon monoxide (DLCO), carbon monoxide transfer coefficient (KCO) and the ratio of functional vital capacity to DLCO (FVC%/DLCO%), which were lower in both ePH and PH groups (p < 0.05). Resting values of CO, cardiac index (CI), stroke volume (SV) and pulmonary vascular compliance (PVC) were significantly impaired in ePH, preC-PH and postC-PH groups when compared to the normal group. CONCLUSIONS: Both PH and ePH were highly prevalent within the IFLD patient group, suggesting that RHC should be offered more frequently in functionally limited patients. Diffusion capacity markers must thus guide decision making, in parallel to clinical evaluation. ePH was associated to lower resting CO and PVC, in a similar way to resting PH, indicating the relevance of cardiopulmonary function to exercise limitation. Finally, the use of the ΔPAWP/ΔCO>2 criterion further uncovered PH of postcapillary etiology, highlighting the complexity of hemodynamics in IFLD. CLINICALTRIALS: gov ID: NCT03706820.

Nursing errors in intensive care unit and their association with burnout, anxiety, insomnia and working environment: a cross-sectional study.

BACKGROUND: In intensive care units (ICU), commonly identified nursing errors may have a negative impact on short- and long-term patient outcomes. Current data is scarce regarding nurses' burnout, insomnia, and anxiety impact on medication and several other types of nursing errors. This study aimed to record the commonness of various nursing errors, including checking patient data, medication preparation and administration, and infection control measures. It also aimed to investigate if "nurse-related" or "ICU-related" features may be associated with nursing error occurrence. MATERIAL-METHODS: A sample of nurses employed in four Greek ICUs was evaluated using the self-completed Athens Insomnia Scale, the State-Trait Anxiety Inventory Form Y, and the Maslach Burnout Inventory. Moreover, we also recorded the sociodemographic characteristics of the ICU nurses, data regarding nursing errors and common practices, and variables regarding the working environment. We conducted a multinominal regression analysis to identify the variables independently associated with each error/mistake. RESULTS: Ninety ICU nurses from the 99 addressed returned the completed questionnaires. The most frequent mistakes referred to drug preparation and administration, with 43.3 % of nurses reporting being "always/very often" distracted when preparing a drug and 90 % that "half of the times" they administer medication at unscheduled hours, followed in frequency by errors regarding the proper use of antiseptic solutions. Medication errors were independently predicted by state anxiety, satisfaction regarding training, emotional exhaustion score, number of ICU beds, and weekdays off work per month. In contrast, errors regarding infection control were independently associated with weekdays off work per month. CONCLUSION: Medication errors are the commonest type of nursing error. Although several risk factors have been identified, no universal "nurse-related" or "ICU-related" factor can predict all types of errors. HIPPOKRATIA 2022, 26 (3):110-117.

Burnout syndrome among emergency medicine physicians: an update on its prevalence and risk factors.

OBJECTIVE: Training in and practising emergency medicine are very stressful conditions that pose a significant emotional burden on physicians, placing them at high risk of developing burnout. The purpose of the current manuscript is to review the published literature on burnout prevalence among emergency medicine physicians and to identify the risk factors associated with its occurrence. MATERIALS AND METHODS: A search of MEDLINE (January 1980-March 2019) was conducted using the terms "burnout", "emergency", "physicians", "emotional exhaustion", "depersonalization" in various combinations. All studies, which assessed burnout prevalence (as primary or secondary outcome) among emergency medicine physicians and were published as full-text articles in English, were included in the review. RESULTS: Twenty-seven studies met eligibility criteria. Although the prevalence of burnout among emergency medicine physicians is high, the exact incidence widely varies ranging between 25% and 77.8%, because of the unique characteristics of each population under study, and also due to the different definitions, tools, and cut-offs used for burnout diagnosis. Several work-related parameters (heavy work-load, low job satisfaction, a problematic co-workers relationship, and difficulty in balancing personal with professional life), personality traits and stress-copying methods, life-style parameters, and other mental disorders (such as stress and sleep disorders) are associated with the establishment of burnout. CONCLUSIONS: Emergency medicine physicians are of a high risk of burnout, although further agreement is needed regarding the use of the Maslach Burnout Inventory as a diagnostic tool. Furthermore, the identification of the potential risk factors for this disorder is crucial so that high-risk groups could be early identified and properly addressed.

Levels of inflammatory mediators in chronic obstructive pulmonary disease patients with anemia of chronic disease: a case-control study.

BACKGROUND: Although a subset of patients with chronic obstructive pulmonary disease (COPD) display anemia, the role of elevated pro-inflammatory cytokines in COPD-related anemia of chronic disease (ACD) has not been fully investigated. AIM: To examine the levels of interleukin (IL)-1ß, IL-6, IL-10, tumor necrosis factor-alpha (TNFα), interferon-gamma (IFNγ), C-reactive protein (CRP) and erythropoietin in stable COPD outpatients with and without ACD. DESIGN: A case-control design was followed. METHODS: Fifty-four patients with stable COPD were studied. Among them, 27 had ACD according to strict clinical and laboratory criteria (group of cases), while another 27 nonanemic COPD patients, carefully matched to cases for age, gender, height, lung function and smoking status represented the controls. Serum levels of IL-1ß, IL-6, IL-10, TNFα, IFNγ, CRP and erythropoietin were measured in both groups. RESULTS: Patients with ACD had significantly higher levels of IL-10 [25.6 (1.9-95.2) vs. 4.1 (1.9-31.9) pg/ml, P = 0.049] and IFNγ [15.2 (2.2-106.9) vs. 2 (1.2-18.3) pg/ml, P = 0.026] and had more frequently elevated CRP than controls. Levels of IL-1ß [26.2 (9.8-96.4) vs. 7.9 (2.1-28.4) pg/ml, P = 0.073], IL-6 [20.3 (2.1-125.4) vs. 6.2 (1.2-33.8) pg/ml, P = 0.688] and TNFα [30.1 (3.2-107.5) vs. 10.1 (3.2-50.4) pg/ml, P = 0.131] were also higher in cases, but the differences did not reach statistical significance. Patients with ACD also displayed significantly higher erythropoietin levels than controls [(21.9 (8.4-101.7) vs. 9.7 (6.3-21.7) mIU/ml, P = 0.010], indicating erythropoietin resistance. CONCLUSION: This study shows that in stable COPD outpatients with strictly defined ACD, levels of inflammatory mediators and erythropoietin are elevated compared to nonanemic controls.

Prevalence of pulmonary hypertension in patients with idiopathic pulmonary fibrosis: correlation with physiological parameters.

The aim of this study was to prospectively evaluate the prevalence of pulmonary hypertension (PH) in patients with idiopathic pulmonary fibrosis (IPF). One hundred thirty-nine patients (101 male, mean age = 68.6 ± 9 years), with confirmed IPF and who were admitted to eight Pulmonary Departments in Greece between November 2005 and December 2006 were included in the study. Pulmonary artery systolic pressure (PASP) was estimated by echocardiography, and PH was defined as PASP > 36 mmHg. We compared demographics, pulmonary function tests, NYHA functional status, 6-min walk distance (6MWD), B-type natriuretic peptide (BNP), PaO(2), and P(A-a)O(2) at rest data between patients with PH and without PH (PASP ≤ 36 mmHg). Increased estimated right ventricular systolic pressure was present in 55% of patients (mean PASP = 47.1 ± 11.2 mmHg vs. 30.3 ± 3.8 mmHg, respectively). Patients with PH had a lower but not statistically significant DL(CO) (47.1 ± 18.8 vs. 52.5 ± 20.1), lower PaO(2) at rest (64.6 ± 12.2 vs. 71.1 ± 11.3, P = 0.004), and lower mean 6MWD (282 ± 118 vs. 338 ± 91, P = 0.007). Significant differences were also observed in the NYHA functional status between the two groups (P = 0.02). Statistically significant correlations were observed between PASP and PaO(2) at rest (r = -0.331, P = 0.00), P(A-a)O(2) at rest (r = 0.494, P = 0.00)(,) 6MWD (r = -0.264, P = 0.01), SpO(2) at rest (r = -0.293, P = 0.00), SpO(2) at the end of exercise (r = -0.364, P = 0.00), and also BNP values (r = 0.319, P = 0.01). Moreover, PaO(2) (P = 0.02), P(A-a)O(2) (P = 0.005), and SpO(2) at the end of exercise (P = 0.023) were independent predictors of the presence of estimated PH. Using Doppler echocardiography as a screening tool for the estimation of PH, we found that PH is common in patients with IPF. Gas exchange parameters at rest and exercise desaturation might indicate underlying PH in IPF.

Left ventricular diastolic dysfunction in idiopathic pulmonary fibrosis: a tissue Doppler echocardiographic [corrected] study.

It was hypothesised that, apart from right ventricular (RV) dysfunction, patients with idiopathic pulmonary fibrosis (IPF) also exhibit left ventricular (LV) impairment, which may affect disease progression and prognosis. The aim of the present study was to evaluate LV performance in a cohort of IPF patients using conventional and tissue Doppler ECG. IPF patients exhibiting mild-to-moderate pulmonary arterial hypertension (mean age 65+/-9 yrs; n = 22) and healthy individuals (mean age 61+/-6 yrs; n = 22) were studied. Conventional and tissue Doppler ECG were used for the evaluation of RV and LV systolic and diastolic function. In addition to the expected impairment in RV function, all patients showed a characteristic reversal of LV diastolic filling to late diastole compared with controls (early diastolic peak filling velocity (E)/late diastolic peak filling velocity 0.7+/-0.2 versus 1.5+/-0.1, respectively). Patients with IPF also exhibited lower peak myocardial velocities in early diastole (E(m); 5.7+/-1.1 versus 10.3+/-1.6 cm x s(-1), respectively), higher in late diastole (A(m); 8.9+/-1.3 versus 5.5+/-0.8 cm x s(-1), respectively), lower E(m)/A(m) ratio (0.6+/-0.1 versus 1.9+/-0.5, respectively) and higher E/E(m) ratio (10.8+/-3 versus 6+/-0.6, respectively), all indicative of LV diastolic dysfunction. Moreover, LV propagation velocity was significantly lower in IPF patients (46+/-13 versus 83+/-21 cm x s(-1), respectively). Physicians should be aware that patients with idiopathic pulmonary fibrosis exhibit early impairment of left ventricular diastolic function.

Sildenafil may facilitate weaning in mechanically ventilated COPD patients: a report of three cases.

We report three cases of mechanically ventilated chronic obstructive pulmonary disease patients who were intubated due to an exacerbation of their disease and who presented with repeated spontaneous breathing trial failures. Patients were given 50 mg of sildenafil through the nasogastric tube, under close monitoring of haemodynamic and ventilatory parameters. After sildenafil, pulmonary artery pressure, pulmonary artery occlusion pressure, the respiratory frequency to tidal volume ratio and the P(a)CO2-P(ET)CO2 (arterial minus end-tidal carbon dioxide pressure) decreased. Cardiac output increased in two of the patients, while all of them were successfully extubated. This is the first report of successful extubation after sildenafil use.

Tumor necrosis factor-alpha serum levels, weight loss and tissue oxygenation in chronic obstructive pulmonary disease.

Weight loss has been recognized as a feature of advanced emphysema and a factor of poor prognosis, but its mechanisms remain obscure. Studies have demonstrated high serum concentrations of TNF-a (cachexin) in chronic obstructive pulmonary disease (COPD) patients with emphysema. Pink puffers (PP) COPD patients have worse tissue oxygenation when compared with blue bloaters (BB) COPD patients. Consequently, PP patients would become cachectic, whereas BB patients with better tissue oxygenation would not. The aim of this study is to test the hypothesis that malnutrition in emphysema is a cytokine-mediated marker of chronic progressive tissue hypoxia. Thirty male COPD patients, without clinical or laboratory evidence of infection and severe air way obstruction (FEV1 < 1.5 l) were allocated: 16 as pink puffers (PP) and 14 as blue bloaters (BB). Lung function measurements included FEV1, FVC, RV, TLC, DLCO and arterial blood gases on room air. TNF-a serum levels were measured by immunoenzymic method (ELISA). Tissue oxygenation was assessed from oxygen delivery (DO2), PvO2 and oxygen extraction ratio (O2ER) obtained after right heart catheterization with Swan Ganz catheter. PP patients demonstrated lower DLCO and higher TLC, FRC and PaO2 from BB. We found that oxygen delivery was better in our BB than in PP patients (CI 2.9 +/- 0.2 vs 2.5 +/- 0.4 l/min/m2--P < 0.01, DO2 16.1 +/- 2.1 vs 13.1 +/- 0.2 ml/min/kg--P < 0.001) and the same was found for tissue oxygenation (PvO2 34.6 +/- 2.9 vs 31.2 +/- 3.8 mmHg--P < 0.01, O2ER 0.27 +/- 0.02 vs 0.34 +/- 0.06%--P < 0.001). The TNF-a values were higher in PP (31.3 +/- 26 pg/ml vs 15.2 +/- 9.9 pg/ml--P < 0.05) and their percent fat-free mass (%FFM) was 49.6 +/- 11.5 vs 42 +/- 8%--P < 0.001. We found that COPD patients with lower DO2 had increased TNF-a levels; but the correlations between TNF-a serum levels and PvO2 or O2ER were not statistically significant. TNF-a levels were elevated in PP patients with tissue hypoxia and may be a factor contributing to the weight loss of these patients.

Reversible platypnoea and orthodeoxia after surgical removal of an hydatid cyst from the liver.

A patient with a large hydatid cyst of the liver developed a positionally symptomatic right to left shunting across a patent foramen ovale with both platypnoea and orthodeoxia, despite normal pulmonary arterial pressures and normal pulmonary function tests. When the patient was in the supine position the calculated right to left shunt was 15.1% and 29.5% when seated. The shunt was attributed to the compression of the right atrium and ventricle by the cyst. Surgical evacuation of the cyst relieved the symptoms and the positionally induced shunting.