Juliana Carvalho Ferreira

Bilevel vs ICU Ventilators Providing Noninvasive Ventilation: Effect of System Leaks: A COPD Lung Model Comparison

BACKGROUND Noninvasive positive-pressure ventilation (NPPV) modes are currently available on bilevel and ICU ventilators. However, little data comparing the performance of the NPPV modes on these ventilators are available. METHODS In an experimental bench study, the ability of nine ICU ventilators to function in the presence of leaks was compared with a bilevel ventilator using the IngMar ASL5000 lung simulator (IngMar Medical; Pittsburgh, PA) set at a compliance of 60 mL/cm H(2)O, an inspiratory resistance of 10 cm H(2)O/L/s, an expiratory resistance of 20 cm H(2)O/ L/s, and a respiratory rate of 15 breaths/min. All of the ventilators were set at 12 cm H(2)O pressure support and 5 cm H(2)O positive end-expiratory pressure. The data were collected at baseline and at three customized leaks. MAIN RESULTS At baseline, all of the ventilators were able to deliver adequate tidal volumes, to maintain airway pressure, and to synchronize with the simulator, without missed efforts or auto-triggering. As the leak was increased, all of the ventilators (except the Vision [Respironics; Murrysville, PA] and Servo I [Maquet; Solna, Sweden]) needed adjustment of sensitivity or cycling criteria to maintain adequate ventilation, and some transitioned to backup ventilation. Significant differences in triggering and cycling were observed between the Servo I and the Vision ventilators. CONCLUSIONS The Vision and Servo I were the only ventilators that required no adjustments as they adapted to increasing leaks. There were differences in performance between these two ventilators, although the clinical significance of these differences is unclear. Clinicians should be aware that in the presence of leaks, most ICU ventilators require adjustments to maintain an adequate tidal volume.

Effects of Dietary Phosphate on Adynamic Bone Disease in Rats with Chronic Kidney Disease – Role of Sclerostin?

High phosphate intake is known to aggravate renal osteodystrophy along various pathogenetic pathways. Recent studies have raised the possibility that dysregulation of the osteocyte Wnt/β-catenin signaling pathway is also involved in chronic kidney disease (CKD)-related bone disease. We investigated the role of dietary phosphate and its possible interaction with this pathway in an experimental model of adynamic bone disease (ABD) in association with CKD and hypoparathyroidism. Partial nephrectomy (Nx) and total parathyroidectomy (PTx) were performed in male Wistar rats. Control rats with normal kidney and parathyroid function underwent sham operations. Rats were divided into three groups and underwent pair-feeding for 8 weeks with diets containing either 0.6% or 1.2% phosphate: sham 0.6%, Nx+PTx 0.6%, and Nx+PTx 1.2%. In the two Nx+PTx groups, serum creatinine increased and blood ionized calcium decreased compared with sham control group. They also presented hyperphosphatemia and reduced serum parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23) levels. Fractional urinary excretion of phosphate increased in Nx+PTx 1.2% rats despite lower PTH and FGF23 levels than in sham group. These biochemical changes were accompanied by a decrease in bone formation rates. The Nx+PTx 1.2% group had lower bone volume (BV/TV), higher osteoblast and osteocyte apoptosis, and higher SOST and Dickkopf-1 gene expression than the Nx+PTx 0.6% group. Nx+PTx 0.6% rat had very low serum sclerostin levels, and Nx+PTx 1.2% had intermediate sclerostin levels compared with sham group. Finally, there was a negative correlation between BV/TV and serum sclerostin. These results suggest that high dietary phosphate intake decreases bone volume in an experimental model of CKD-ABD, possibly via changes in SOST expression through a PTH-independent mechanism. These findings could have relevance for the clinical setting of CKD-ABD in patients who low turnover bone disease might be attenuated by optimal control of phosphate intake and/or absorption.

Risk factors for noninvasive ventilation failure in cancer patients in the intensive care unit: A retrospective cohort study

PURPOSE The purpose of the study is to identify risk factors for noninvasive ventilation (NIV) failure in cancer patients with acute respiratory failure (ARF). MATERIALS AND METHODS A retrospective cohort study of adult patients admitted to intensive care unit (ICU), who received NIV for treatment of ARF, was conducted. We conducted a chart review to estimate the NIV failure rate and used logistic regression to identify risk factors. RESULTS Of 2258 patients admitted to the ICU during the study period, 114 (5%) received NIV for ARF. Noninvasive ventilation was successful in 67 patients (59%) and failed for 47 (41%), of whom 36 were intubated and 11 were sedated for palliation. Factors associated with NIV failure were infection as the primary cause of ARF (odds ratio [OR], 4.90; 95% confidence interval [CI], 1.78-13.45; P = .002), male sex (OR, 2.58; 95% CI, 1.20-5.56; P = .015), and Simplified Acute Physiology Score 3 (OR, 1.04; 95% CI, 1.01-1.07; P = .006). Overall ICU mortality was 40%, and hospital mortality was 56%. Noninvasive ventilation failure was the only independent predictor of ICU mortality (OR, 16.6; 95% CI, 6.5-41.5; P < .001). CONCLUSIONS Noninvasive ventilation can avert ARF for most ICU cancer patients with ARF. For patients with pulmonary infections and high severity scores, NIV should be used with caution. Identifying risk factors for NIV failure using a comprehensive diagnostic approach and monitoring of NIV are paramount to improve outcomes.

A sigmoidal fit for pressure-volume curves of idiopathic pulmonary fibrosis patients on mechanical ventilation: clinical implications

OBJECTIVE: Respiratory pressure-volume curves fitted to exponential equations have been used to assess disease severity and prognosis in spontaneously breathing patients with idiopathic pulmonary fibrosis. Sigmoidal equations have been used to fit pressure-volume curves for mechanically ventilated patients but not for idiopathic pulmonary fibrosis patients. We compared a sigmoidal model and an exponential model to fit pressure-volume curves from mechanically ventilated patients with idiopathic pulmonary fibrosis. METHODS: Six idiopathic pulmonary fibrosis patients and five controls underwent inflation pressure-volume curves using the constant-flow technique during general anesthesia prior to open lung biopsy or thymectomy. We identified the lower and upper inflection points and fit the curves with an exponential equation, V = A-B.e-k.P, and a sigmoid equation, V = a+b/(1+e-(P-c)/d). RESULTS: The mean lower inflection point for idiopathic pulmonary fibrosis patients was significantly higher (10.5±5.7 cm H2O) than that of controls (3.6±2.4 cm H2O). The sigmoidal equation fit the pressure-volume curves of the fibrotic and control patients well, but the exponential equation fit the data well only when points below 50% of the inspiratory capacity were excluded. CONCLUSION: The elevated lower inflection point and the sigmoidal shape of the pressure-volume curves suggest that respiratory system compliance is decreased close to end-expiratory lung volume in idiopathic pulmonary fibrosis patients under general anesthesia and mechanical ventilation. The sigmoidal fit was superior to the exponential fit for inflation pressure-volume curves of anesthetized patients with idiopathic pulmonary fibrosis and could be useful for guiding mechanical ventilation during general anesthesia in this condition.

Outcomes of 847 childhood-onset systemic lupus erythematosus patients in three age groups.

Objective The objective of this study was to assess outcomes of childhood systemic lupus erythematosus (cSLE) in three different age groups evaluated at last visit: group A early-onset disease (<6 years), group B school age (≥6 and <12 years) and group C adolescent (≥12 and <18 years). Methods An observational cohort study was performed in ten pediatric rheumatology centers, including 847 cSLE patients. Results Group A had 39 (4%), B 395 (47%) and C 413 (49%). Median disease duration was significantly higher in group A compared to groups B and C (8.3 (0.1–23.4) vs 6.2 (0–17) vs 3.3 (0–14.6) years, p < 0.0001). The median Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SLICC/ACR-DI) (0 (0–9) vs 0 (0–6) vs 0 (0–7), p = 0.065) was comparable in the three groups. Further analysis of organ/system damage revealed that frequencies of neuropsychiatric (21% vs 10% vs 7%, p = 0.007), skin (10% vs 1% vs 3%, p = 0.002) and peripheral vascular involvements (5% vs 3% vs 0.3%, p = 0.008) were more often observed in group A compared to groups B and C. Frequencies of severe cumulative lupus manifestations such as nephritis, thrombocytopenia, and autoimmune hemolytic anemia were similar in all groups (p > 0.05). Mortality rate was significantly higher in group A compared to groups B and C (15% vs 10% vs 6%, p = 0.028). Out of 69 deaths, 33/69 (48%) occurred within the first two years after diagnosis. Infections accounted for 54/69 (78%) of the deaths and 38/54 (70%) had concomitant disease activity. Conclusions This large multicenter study provided evidence that early-onset cSLE group had distinct outcomes. This group was characterized by higher mortality rate and neuropsychiatric/vascular/skin organ damage in spite of comparable frequencies of severe cumulative lupus manifestations. We also identified that overall death in cSLE patients was an early event mainly attributed to infection associated with disease activity.

Influences of Duration of Inspiratory Effort, Respiratory Mechanics, and Ventilator Type on Asynchrony With Pressure Support and Proportional Assist Ventilation

BACKGROUND: Pressure support ventilation (PSV) is often associated with patient-ventilator asynchrony. Proportional assist ventilation (PAV) offers inspiratory assistance proportional to patient effort, minimizing patient-ventilator asynchrony. The objective of this study was to evaluate the influence of respiratory mechanics and patient effort on patient-ventilator asynchrony during PSV and PAV plus (PAV+). METHODS: We used a mechanical lung simulator and studied 3 respiratory mechanics profiles (normal, obstructive, and restrictive), with variations in the duration of inspiratory effort: 0.5, 1.0, 1.5, and 2.0 s. The Auto-Trak system was studied in ventilators when available. Outcome measures included inspiratory trigger delay, expiratory trigger asynchrony, and tidal volume (VT). RESULTS: Inspiratory trigger delay was greater in the obstructive respiratory mechanics profile and greatest with a effort of 2.0 s (160 ms); cycling asynchrony, particularly delayed cycling, was common in the obstructive profile, whereas the restrictive profile was associated with premature cycling. In comparison with PSV, PAV+ improved patient-ventilator synchrony, with a shorter triggering delay (28 ms vs 116 ms) and no cycling asynchrony in the restrictive profile. VT was lower with PAV+ than with PSV (630 mL vs 837 mL), as it was with the single-limb circuit ventilator (570 mL vs 837 mL). PAV+ mode was associated with longer cycling delays than were the other ventilation modes, especially for the obstructive profile and higher effort values. Auto-Trak eliminated automatic triggering. CONCLUSIONS: Mechanical ventilation asynchrony was influenced by effort, respiratory mechanics, ventilator type, and ventilation mode. In PSV mode, delayed cycling was associated with shorter effort in obstructive respiratory mechanics profiles, whereas premature cycling was more common with longer effort and a restrictive profile. PAV+ prevented premature cycling but not delayed cycling, especially in obstructive respiratory mechanics profiles, and it was associated with a lower VT.

Comparison of 3 modes of automated weaning from mechanical ventilation: A bench study

PURPOSE Automated weaning modes are available in some mechanical ventilators, but no studies compared them hitherto. We compared the performance of 3 automated modes under standard and challenging situations. METHODS We used a lung simulator to compare 3 automated modes, adaptive support ventilation (ASV), mandatory rate ventilation (MRV), and Smartcare, in 6 situations, weaning success, weaning failure, weaning success with extreme anxiety, weaning success with Cheyne-Stokes, weaning success with irregular breathing, and weaning failure with ineffective efforts. RESULTS The 3 modes correctly recognized the situations of weaning success and failure, even when anxiety or irregular breathing were present but incorrectly recognized weaning success with Cheyne-Stokes. MRV incorrectly recognized weaning failure with ineffective efforts. Time to pressure support (PS) stabilization was shorter for ASV (1-2 minutes for all situations) and MRV (1-7 minutes) than for Smartcare (8-78 minutes). ASV had higher rates of PS oscillations per 5 minutes (4-15), compared with Smartcare (0-1) and MRV (0-12), except when extreme anxiety was present. CONCLUSIONS Smartcare, ASV, and MRV were equally able to recognize weaning success and failure, despite the presence of anxiety or irregular breathing but performed incorrectly in the presence of Cheyne-Stokes. PS behavior over the time differs among modes, with ASV showing larger and more frequent PS oscillations over the time. Clinical studies are needed to confirm our results.

Anti-ribosomal P antibody: a multicenter study in childhood-onset systemic lupus erythematosus patients:

Objectives Anti-ribosomal P protein (anti-P) autoantibodies are highly specific for systemic lupus erythematosus (SLE). However, the evaluation of this autoantibody in childhood-onset SLE (cSLE) populations has been limited to a few small series, hampering the interpretation of the clinical and laboratorial associations. Therefore, the objective of this multicenter cohort study was to evaluate demographic, clinical/laboratorial features, and disease damage score in cSLE patients with and without the presence of anti-P antibody. Methods This was a retrospective multicenter study performed in 10 pediatric rheumatology services of São Paulo state, Brazil. Anti-P antibodies were measured by ELISA in 228 cSLE patients. Results Anti-P antibodies were observed in 61/228 (27%) cSLE patients. Frequencies of cumulative lymphadenopathy (29% vs. 15%, p = 0.014), acute confusional state (13% vs. 5%, p = 0.041), mood disorder (18% vs. 8%, p = 0.041), autoimmune hemolytic anemia (34% vs. 15%, p = 0.001), as well as presence of anti-Sm (67% vs. 40%, p = 0.001), anti-RNP (39% vs. 21%, p = 0.012) and anti-Ro/SSA antibodies (43% vs. 25%, p = 0.016) were significantly higher in cSLE patients with anti-P antibodies compared to those without these autoantibodies. A multiple regression model revealed that anti-P antibodies were associated with autoimmune hemolytic anemia (odds ratio (OR) = 2.758, 95% confidence interval (CI): 1.304–5.833, p = 0.008) and anti-Sm antibody (OR = 2.719, 95% CI: 1.365–5.418, p = 0.004). The SLICC/ACR damage index was comparable in patients with and without anti-P antibodies (p = 0.780). Conclusions The novel association of anti-P antibodies and autoimmune hemolytic anemia was evidenced in cSLE patients and further studies are necessary to determine if anti-P titers may vary with this hematological manifestation.

Herpes zoster infection in childhood-onset systemic lupus erythematosus patients: a large multicenter study

Objective The aim of this multicenter study in a large childhood-onset systemic lupus erythematosus (cSLE) population was to assess the herpes zoster infection (HZI) prevalence, demographic data, clinical manifestations, laboratory findings, treatment, and outcome. Methods A retrospective multicenter cohort study (Brazilian cSLE group) was performed in ten Pediatric Rheumatology services in São Paulo State, Brazil, and included 852 cSLE patients. HZI was defined according to the presence of acute vesicular-bullous lesions on erythematous/edematous base, in a dermatomal distribution. Post-herpetic neuralgia was defined as persistent pain after one month of resolution of lesions in the same dermatome. Patients were divided in two groups for the assessment of current lupus manifestations, laboratory findings, and treatment: patients with HZI (evaluated at the first HZI) and patients without HZI (evaluated at the last visit). Results The frequency of HZI in cSLE patients was 120/852 (14%). Hospitalization occurred in 73 (61%) and overlap bacterial infection in 16 (13%). Intravenous or oral aciclovir was administered in 113/120 (94%) cSLE patients at HZI diagnosis. None of them had ophthalmic complication or death. Post-herpetic neuralgia occurred in 6/120 (5%). After Holm–Bonferroni correction for multiple comparisons, disease duration (1.58 vs 4.41 years, p < 0.0001) was significantly lower in HZI cSLE patients compared to those without HZI. Nephritis (37% vs 18%, p < 0.0001), lymphopenia (32% vs 17%, p < 0.0001) prednisone (97% vs 77%, p < 0.0001), cyclophosphamide (20% vs 5%, p < 0.0001) and SLE Disease Activity Index 2000 (6.0 (0–35) vs 2 (0–45), p < 0.0001) were significantly higher in the former group. The logistic regression model showed that four independent variables were associated with HZI: disease duration < 1 year (OR 2.893 (CI 1.821–4.597), p < 0.0001), lymphopenia <1500/mm3 (OR 1.931 (CI 1.183–3.153), p = 0.009), prednisone (OR 6.723 (CI 2.072–21.815), p = 0.002), and cyclophosphamide use (OR 4.060 (CI 2.174–7.583), p < 0.0001). Conclusion HZI is an early viral infection in cSLE with a typical dermatomal distribution. Lymphopenia and immunosuppressive treatment seem to be major factors underlying this complication in spite of a benign course.

What does the p value really mean

Consider an experiment in which 10 subjects receive a placebo, and another 10 receive an experimental diuretic. After 8 h, the average urine output in the placebo group is 769 mL, versus 814 mL in the diuretic group—a difference of 45 mL (Figure 1). How do we know if that difference means the drug works and is not just a result of chance? of 45 mL in the average urine output between groups under the null hypothesis. Because this is a very small probability, we reject the null hypothesis. It does not mean that the drug is a diuretic, nor that there is 97% chance of the drug being a diuretic.