Daytime measurements underestimate nocturnal oxygen desaturations in pulmonary arterial and chronic thromboembolic pulmonary hypertension

Background: Nocturnal hypoxemia is important in precapillary pulmonary hypertension (pPH) as it worsens pulmonary hemodynamics. Whether daytime oxygen saturation (SpO(2)) predicts nocturnal hypoxemia in pPH patients has not been conclusively studied. Objectives: To investigate the prevalence of nocturnal hypoxemia in comparison to daytime SpO(2) and disease severity in ambulatory patients with pulmonary hypertension. Methods: Consecutive patients diagnosed with pPH classified as either pulmonary arterial (PAH) or chronic thromboembolic pPH (CTEPH) had daytime resting and exercise SpO(2) (at the end of a 6-min walk test); thereafter, they underwent overnight pulse oximetry at home. Functional class, pro-brain natriuretic peptide (pro-BNP) and the tricuspid pressure gradient were assessed. Results: Sixty-three patients [median (quartiles) age 62 (53; 71), 43 females] with PAH (n = 44) and CTEPH (n = 19) were included. The resting SpO(2), exercise SpO(2), and mean nocturnal SpO(2) were 95% (92; 96), 88% (81; 95), and 89% (85; 92), respectively. Forty-nine patients (77%) spent >10% of the night with SpO(2) 50% of the night with SpO(2) 90% for being a nocturnal nondesaturator or sustained nondesaturator were 25 and 53%, respectively. Nocturnal SpO(2) was negatively correlated with the tricuspid pressure gradient, but not with functional class, 6-min walk test, or pro-BNP. Conclusions: Nocturnal hypoxemia is very common in PAH and CTEPH despite often normal daytime SpO(2) and reflects disease severity. Nocturnal pulse oximetry should be considered in the routine evaluation of pPH patients and research should be directed toward the treatment of nocturnal desaturation in pPH

Effect of nocturnal oxygen and acetazolamide on exercise performance in patients with pre-capillary pulmonary hypertension and sleep-disturbed breathing: randomized, double-blind, cross-over trial

Aim Sleep-disturbed breathing (SDB) is common in pre-capillary pulmonary hypertension (PH) and impairs daytime performance. In lack of proven effective treatments, we tested whether nocturnal oxygen therapy (NOT) or acetazolamide improve exercise performance and quality of life in patients with pre-capillary PH and SDB. Methods This was a randomized, placebo-controlled, double-blind, three period cross-over trial. Participants received NOT (3 L/min), acetazolamide tablets (2 × 250 mg), and sham-NOT/placebo tablets each during 1 week with 1-week washout between treatment periods. Twenty-three patients, 16 with pulmonary arterial PH, 7 with chronic thromboembolic PH, and with SDB defined as mean nocturnal oxygen saturation 10 h−1 with daytime PaO2 ≥7.3 kPa participated. Assessments at the end of the treatment periods included a 6 min walk distance (MWD), SF-36 quality of life, polysomnography, and echocardiography. Results Medians (quartiles) of the 6 MWD after NOT, acetazolamide, and placebo were 480 m (390;528), 440 m (368;468), and 454 m (367;510), respectively, mean differences: NOT vs. placebo +25 m (95% CI 3-46, P= 0.027), acetazolamide vs. placebo −9 m (−34-17, P = 0.223), and NOT vs. acetazolamide +33 (12-45, P < 0.001). SF-36 quality of life was similar with all treatments. Nocturnal oxygen saturation significantly improved with both NOT and acetazolamide. Right ventricular fractional area change was greater on NOT compared with placebo (P = 0.042) and acetazolamide (P = 0.027). Conclusions In patients with pre-capillary PH and SDB on optimized pharmacological therapy, NOT improved the 6 MWD compared with placebo already after 1 week along with improvements in SDB and haemodynamics. ClinicalTrials.gov NTC0142719

Predisposing and precipitating risk factors for delirium in gastroenterology and hepatology: Subgroup analysis of 718 patients from a hospital-wide prospective cohort study

BACKGROUND AND AIMS Delirium is the most common acute neuropsychiatric syndrome in hospitalized patients. Higher age and cognitive impairment are known predisposing risk factors in general hospital populations. However, the interrelation with precipitating gastrointestinal (GI) and hepato-pancreato-biliary (HPB) diseases remains to be determined. PATIENTS AND METHODS Prospective 1-year hospital-wide cohort study in 29'278 adults, subgroup analysis in 718 patients hospitalized with GI/HPB disease. Delirium based on routine admission screening and a DSM-5 based construct. Regression analyses used to evaluate clinical characteristics of delirious patients. RESULTS Delirium was detected in 24.8% (178/718). Age in delirious patients (median 62 years [IQR 21]) was not different to non-delirious (median 60 years [IQR 22]), p = 0.45). Dementia was the strongest predisposing factor for delirium (OR 66.16 [6.31-693.83], p < 0.001). Functional impairment, and at most, immobility increased odds for delirium (OR 7.78 [3.84-15.77], p < 0.001). Patients with delirium had higher in-hospital mortality rates (18%; OR 39.23 [11.85-129.93], p < 0.001). From GI and HPB conditions, cirrhosis predisposed to delirium (OR 2.11 [1.11-4.03], p = 0.023), while acute renal failure (OR 4.45 [1.61-12.26], p = 0.004) and liver disease (OR 2.22 [1.12-4.42], p = 0.023) were precipitators. Total costs were higher in patients with delirium (USD 30003 vs. 10977; p < 0.001). CONCLUSION Delirium in GI- and HPB-disease was not associated with higher age per se, but with cognitive and functional impairment. Delirium needs to be considered in younger adults with acute renal failure and/or liver disease. Clinicians should be aware about individual risk profiles, apply preventive and supportive strategies early, which may improve outcomes and lower costs

Improving animal welfare using continuous nalbuphine infusion in a long-term rat model of sepsis

Abstract Background Sepsis research relies on animal models to investigate the mechanisms of the dysregulated host response to infection. Animal welfare concerns request the use of potent analgesics for the Refinement of existing sepsis models, according to the 3Rs principle. Nevertheless, adequate analgesia is often missing, partly because the effects of analgesics in this particular condition are unknown. We evaluated the use of nalbuphine, an opioid with kappa agonistic and mu antagonistic effects, in rats with and without experimental sepsis. Methods Male Wistar rats were anesthetized with isoflurane and instrumented with a venous line for drug administration. Arterial cannulation allowed for blood pressure measurements and blood sampling in short-term experiments of non-septic animals. Nalbuphine (or placebo) was administered intravenously at a dose of 1 mg/kg/h. Long-term (48 h) experiments in awake septic animals included repetitive clinical scoring with the Rat Grimace Scale and continuous heart rate monitoring by telemetry. Sepsis was induced by intraperitoneal injection of faecal slurry. Nalbuphine plasma levels were measured by liquid chromatography—high resolution mass spectrometry. Results In anesthetized healthy animals, nalbuphine led to a significant reduction of respiratory rate, heart rate, and mean arterial pressure during short-term experiments. In awake septic animals, a continuous nalbuphine infusion did not affect heart rate but significantly improved the values of the Rat Grimace Scale. Nalbuphine plasma concentrations remained stable between 4 and 24 h of continuous infusion in septic rats. Conclusions In anaesthetised rats, nalbuphine depresses respiratory rate, heart rate, and blood pressure. In awake animals, nalbuphine analgesia improves animal welfare during sepsis

Effects of exercise and vasodilators on cerebral tissue oxygenation in pulmonary hypertension

BACKGROUND: Arterial and thromboembolic pulmonary hypertension (PH) lead to arterial hypoxaemia. OBJECTIVE: To investigate whether cerebral tissue oxygenation (CTO) in patients with PH is reduced and whether this is associated with reduced exercise tolerance. METHODS: 16 patients with PH (mean pulmonary arterial pressure ≥25 mmHg, 14 arterial, 2 chronic thromboembolic) and 15 controls underwent right heart catheterisation with monitoring of CTO at rest, during maximal bicycle exercise and during inhalation of oxygen and NO. The 6 min walk distance (6MWD) was measured. RESULTS: Median CTO in PH-patients at rest was 62 % (quartiles 53; 71), during exercise 60 % (53; 65); corresponding values in controls were 65 % (73; 73) (P = NS) and 68 % (66; 70) (p = .013 vs. PH). Inhalation of NO and oxygen improved CTO in PH. In multivariate regression analysis CTO at maximal exercise predicted the work load achieved when controlled for age, pulmonary vascular resistance and mixed venous oxygen saturation (R (2) = .419, p < .000); in addition, the 6MWD was predicted by CTO (adjusted R (2) = .511, p < .000). CONCLUSION: In PH-patients but not in controls CTO decreased during exercise. Since CTO was an independent predictor of the work load achieved and the 6MWD cerebral hypoxia may contribute to exercise limitation in PH. Clinicaltrials.gov: NCT01463514

Evaluation of soluble suppression of tumorigenicity 2 (sST2) as serum marker for liver fibrosis

Background & aims With the increase in patients at risk of advanced liver disease due to the obesity epidemic, there will be a need for simple screening tools for advanced liver fibrosis. Soluble suppression of tumorigenicity 2 (sST2) is a serum biomarker for fibrotic processes. The aim of this study was to evaluate sST2 as marker for liver fibrosis in patients successfully treated for chronic hepatitis C. Methods 424 patients from the Swiss Hepatitis C Cohort Study were screened for inclusion in this post-hoc cohort study. Inclusion criteria were sustained virological response (SVR), available elastography (VCTE) and serum samples for biomarker analysis before and after treatment. For the validation of sST2, values were compared to VCTE, FIB-4 and APRI using Spearman’s correlation and AUROC analyses. Results Data of 164 subjects were finally analyzed. Median sST2 values slightly increased with VCTE-derived fibrosis stages and remained stable after reaching SVR within the respective fibrosis stage, suggesting that sST2 is not influenced by liver inflammation. However, correlation of sST2 pre- and post-treatment with VCTE was fair (Spearman’s rho = 0.39 and rho = 0.36). The area under the curve (AUROC) for sST2 in detecting VCTE-defined F4 fibrosis (vs. F0-F3) before therapy was 0.74 (95%CI 0.65–0.83), and 0.67(95%CI 0.56–0.78) for the discrimination of F3/F4 fibrosis vs. F0-F2. Adding sST2 to either APRI or FIB-4, respectively, increased diagnostic performance of both tests. Conclusions sST2 can potentially identify patients with advanced fibrosis as a single serum marker and in combination with APRI and FIB-4

Improving animal welfare using continuous nalbuphine infusion in a long-term rat model of sepsis

Abstract Background Sepsis research relies on animal models to investigate the mechanisms of the dysregulated host response to infection. Animal welfare concerns request the use of potent analgesics for the Refinement of existing sepsis models, according to the 3Rs principle. Nevertheless, adequate analgesia is often missing, partly because the effects of analgesics in this particular condition are unknown. We evaluated the use of nalbuphine, an opioid with kappa agonistic and mu antagonistic effects, in rats with and without experimental sepsis. Methods Male Wistar rats were anesthetized with isoflurane and instrumented with a venous line for drug administration. Arterial cannulation allowed for blood pressure measurements and blood sampling in short-term experiments of non-septic animals. Nalbuphine (or placebo) was administered intravenously at a dose of 1 mg/kg/h. Long-term (48 h) experiments in awake septic animals included repetitive clinical scoring with the Rat Grimace Scale and continuous heart rate monitoring by telemetry. Sepsis was induced by intraperitoneal injection of faecal slurry. Nalbuphine plasma levels were measured by liquid chromatography—high resolution mass spectrometry. Results In anesthetized healthy animals, nalbuphine led to a significant reduction of respiratory rate, heart rate, and mean arterial pressure during short-term experiments. In awake septic animals, a continuous nalbuphine infusion did not affect heart rate but significantly improved the values of the Rat Grimace Scale. Nalbuphine plasma concentrations remained stable between 4 and 24 h of continuous infusion in septic rats. Conclusions In anaesthetised rats, nalbuphine depresses respiratory rate, heart rate, and blood pressure. In awake animals, nalbuphine analgesia improves animal welfare during sepsis

A low resting heart rate at diagnosis predicts favourable long-term outcome in pulmonary arterial and chronic thromboembolic pulmonary hypertension. A prospective observational study

<p>Abstract</p> <p>Background</p> <p>A low resting heart rate (HR) is prognostically favourable in healthy individuals and in patients with left heart disease. In this study we investigated the impact of HR at diagnosis on long-term outcome in patients with differently classified precapillary pulmonary hypertension (pPH).</p> <p>Methods</p> <p>pPH patients diagnosed as pulmonary arterial (PAH) or inoperable chronic thromboembolic pulmonary hypertension (CTEPH) were registered and regularly followed at our centre Baseline characteristics and events defined as either death or lung transplantation were noted. The prognostic value of HR was analysed using Kaplan Meier estimates, live tables and Cox regression.</p> <p>Results</p> <p>206 patients with PAH (148) and inoperable CTEPH (58) were included. The median HR was 82 bpm. pPH with a HR below 82 bpm had a significantly longer overall event-free survival (2409 vs.1332 days, p = .000). This advantage was similarly found if PAH and CTEPH were analysed separately. Although a lower HR was associated with a better hemodynamic and functional class, HR was a strong and independent prognostic marker for transplant free survival even if corrected for age, sex, hemodynamics and functional status.</p> <p>Conclusion</p> <p>We show that resting HR at diagnosis is a strong and independent long-term prognostic marker in PAH and CTEPH. Whether reducing HR by pharmacological agents would improve outcome in pPH has to be assessed by future trials with high attention to safety.</p

Reference values for the 6-minute walk test in healthy children and adolescents in Switzerland

BACKGROUND: The six-minute walk test (6MWT) is a simple, low tech, safe and well established, self-paced assessment tool to quantify functional exercise capacity in adults. The definition of normal 6MWT in children is especially demanding since not only parameters like height, weight and ethnical background influence the measurement, but may be as crucial as age and the developmental stage. The aim of this study is establishing reference values for the 6MWT in healthy children and adolescents in Switzerland and to investigate the influence of age, anthropometrics, heart rate, blood pressure and physical activity on the distance walked. METHODS: Children and adolescents between 5-17 years performed a 6MWT. Short questionnaire assessments about their health state and physical activities. anthropometrics and vitals were measured before and after a 6-minute walk test and were previously defined as secondary outcomes. RESULTS: Age, height, weight and the heart rate after the 6MWT all predicted the distance walked according to different regression models: age was the best single predictor and mostly influenced walk distance in younger age, anthropometrics were more important in adolescents and females. Heart rate after the 6MWT was an important distance predictor in addition to age and outreached anthropometrics in the majority of subgroups assessed. CONCLUSIONS: The 6MWT in children and adolescents is feasible and practical. The 6MWT distance depends mainly on age; however, heart rate after the 6MWT, height and weight significantly add information and should be taken into account mainly in adolescents. Reference equations allow predicting 6-minute walk test distance and may help to better assess and compare outcomes in young patients with cardiovascular and respiratory diseases and are highly warranted for different populations

Discharge Destinations of Delirious Patients: Findings From a Prospective Cohort Study of 27,026 Patients From a Large Health Care System

Objectives Delirium is known to contribute to increased rates of institutionalization and mortality. The full extent of adverse outcomes, however, remains understudied. We aimed to systematically assess the discharge destinations and mortality risk in delirious patients in a large sample across all hospital services. Design Pragmatic prospective cohort study of consecutive admissions to a large health care system. Setting and Participants A total of 27,026 consecutive adults (>18 years old) with length of stay of at least 24 hours in a tertiary care center from January 1 to December 31, 2014. Methods Presence of delirium determined by routine delirium screening. Clinical characteristics, discharge destination, and mortality were collected. Calculation of odds ratios (ORs) with logistic regression with adjustment for age, sex, and Charlson comorbidity index (CCI). Results Delirium was detected in 19.7% of patients (5313 of 27,026), median age of delirious patients was 56 years (25–75 interquartile range = 37–70). The electronic health record (DSM-5-based) delirium algorithm correctly identified 93.3% of delirium diagnoses made by consultation-liaison psychiatrists. Across services, the odds of delirious patients returning home was significantly reduced [OR 0.12; confidence interval (CI) 0.10–0.13; P < .001]. Rather, these patients were transferred to acute rehabilitation (OR 4.15; CI 3.78–4.55; P < .001) or nursing homes (OR 4.12; CI 3.45–4.93; P < .001). Delirious patients had a significantly increased adjusted mortality risk (OR 30.0; CI 23.2–39.4; P < .001). Conclusions and Implications This study advances our understanding of the discharge destination across all services in adults admitted to a large hospital system. Delirium was associated with reduced odds of returning home, increased odds of discharge to a setting of higher dependency, and excess mortality independent of comorbidity, age, and sex. These findings emphasize the potentially devastating outcomes associated with delirium and highlight the need for timely diagnosis and hospital-wide management