To measure serum thrombopoietin levels and to investigate their relationship with platelet counts and other potential determinants in septic patients. Prospective study comparing septic patients and healthy volunteers. General intensive care units in two tertiary university hospitals. A total of 152 consecutive septic patients (69 with sepsis, 24 with severe sepsis, and 59 with septic shock). Twenty-two healthy volunteers served as control subjects. Sepsis severity was determined by grading septic patients in those having sepsis, severe sepsis, and septic shock. None. After blood sampling, platelet counts, and serum thrombopoietin, interleukin-6 and C-reactive protein levels were measured. Platelets did not decrease in patients with sepsis, but they significantly decreased in patients with severe sepsis and septic shock (p < .01 vs. controls and sepsis). In contrast, thrombopoietin levels (median [range]) increased in patients with sepsis (159 [34–1272] pg/mL) compared with controls (57 [33–333] pg/mL, p < .001), exhibiting further significant increase in patients with severe sepsis and septic shock (461 [73–1550] and 522 [45–2313] pg/mL, respectively, p < .001 vs. sepsis). In multiple regression analysis, thrombopoietin levels were independently related only to sepsis severity (higher in patients with increased sepsis severity, p < .001) and platelet counts (higher in patients with lower platelet counts, p = .004). Sepsis severity accounted for most of the variance explained by the model. Thrombopoietin was significantly related to interleukin-6 (r 2 = .26) and C-reactive protein (r 2 = .37, p < .001 for both). In serial measurements, interleukin-6 peak values constantly preceded those of thrombopoietin, whereas peaks in thrombopoietin levels coincided with clinical episodes of septic shock. Sepsis severity is the major determinant of elevated thrombopoietin levels in septic patients, whereas platelet count is a secondary determinant. Thrombopoietin represents a potential marker of sepsis severity.

Among the multiple causes of weaning failure from mechanical ventilation, cardiovascular dysfunction is increasingly recognized as a quite frequent cause that can be treated successfully. In this review, we summarize the contemporary evidence of the most important clinical and diagnostic aspects of weaning failure of cardiovascular origin with special focus on treatment. Pathophysiological mechanisms are complex and mainly include increase in right and left ventricular preload and afterload and potentially induce myocardial ischemia. Patients at risk include those with preexisting cardiopulmonary disease either known or suspected. Clinically, cardiovascular etiology as a predominant cause or a contributor to weaning failure, though critical for early diagnosis and intervention, may be difficult to be recognized and distinguished from noncardiac causes suggesting the need of high suspicion. A cardiovascular diagnostic workup including bedside echocardiography, lung ultrasound, electrocardiogram and biomarkers of cardiovascular dysfunction or other adjunct techniques and, in selected cases, right heart catheterization and/or coronary angiography, should be obtained to confirm the diagnosis. Official clinical practice guidelines that address treatment of a confirmed weaning-induced cardiovascular dysfunction do not exist. As the etiologies of weaning-induced cardiovascular dysfunction are diverse, principles of management depend on the individual pathophysiological mechanisms, including preload optimization by fluid removal, guided by B-type natriuretic peptide measurement, nitrates administration in excessive afterload and/or myocardial ischemia, contractility improvement in severe systolic dysfunction as well as other rational treatment in specific indications in order to lead to successful weaning from mechanical ventilation.

Summary: Although daytime sleepiness is commonly associated with obstructive sleep apnoea (OSA), the relationship between OSA severity and subjective sleepiness has been documented elusive. This study aimed to identify clinical and polysomnographic determinants of subjective sleepiness among patients suspected of having OSA. A sleep clinic‐based sample of 915 patients was interviewed with a structured questionnaire and underwent diagnostic overnight polysomnography. Subjective sleepiness was quantified by Epworth Sleepiness Scale (ESS). Excessive daytime sleepiness (defined as ESS score > 10) was present in 38.8% of patients. In multiple linear regression analysis, respiratory disturbance index [RDI; used to define (whenever RDI was >5) and quantify OSA], depression and diabetes were the most important determinants of ESS score accounting for 17%, 11% and 6% of its variability respectively. Chronic obstructive pulmonary disease (COPD), stroke, heart disease, alcohol use and body mass index were less important determinants of ESS score explaining 1–3% of its variability. In conclusion, OSA should not be considered the sole potential cause of increased subjective sleepiness in patients suspected of having OSA. Primarily depression and diabetes, but also COPD, stroke, heart disease, alcohol use and increased body mass index may contribute to increased subjective sleepiness.

Introduction: Both experimental and clinical data give convincing evidence to acute cardiac dysfunction as the origin or a cofactor of weaning failure in patients with chronic obstructive pulmonary disease. Therefore, treatment targeting the cardiovascular system might help the heart to tolerate more effectively the critical period of weaning. This study aims to assess the hemodynamic, respiratory and clinical effects of nitroglycerin infusion in difficult-to-wean patients with severe chronic obstructive pulmonary disease. Methods: Twelve difficult-to-wean (failed ≥ 3 consecutive trials) chronic obstructive pulmonary disease patients, who presented systemic arterial hypertension (systolic blood pressure ≥ 140mmHg) during weaning failure and had systemic and pulmonary artery catheters in place, participated in this prospective, interventional, non-randomized clinical trial. Patients were studied in two consecutive days, i.e., the first day without (Control day) and the second day with (Study day) nitroglycerin continuous intravenous infusion starting at the beginning of the spontaneous breathing trial, and titrated to maintain normal systolic blood pressure. Hemodynamic, oxygenation and respiratory measurements were performed on mechanical ventilation, and during a 2-hour T-piece spontaneous breathing trial. Primary endpoint was hemodynamic and respiratory effects of nitroglycerin infusion. Secondary endpoint was spontaneous breathing trial and extubation outcome. Results: Compared to mechanical ventilation, mean systemic arterial pressure, rate-pressure product, mean pulmonary arterial pressure, and pulmonary artery occlusion pressure increased [from (mean ± SD) 94 ± 14, 13708 ± 3166, 29.9 ± 4.8, and 14.8 ± 3.8 to 109 ± 20mmHg, 19856 ± 4877mmHg b/min, 41.6 ± 5.8mmHg, and 23.4 ± 7.4 mmHg, respectively], and mixed venous oxygen saturation decreased (from 75.7 ± 3.5 to 69.3 ± 7.5%) during failing trials on Control day, whereas they did not change on Study day. Venous admixture increased throughout the trial on both Control day and Study day, but this increase was lower on Study day. Whereas weaning failed in all patients on Control day, nitroglycerin administration on Study day enabled a successful spontaneous breathing trial and extubation in 92% and 88% of patients, respectively. Conclusions: In this clinical setting, nitroglycerin infusion can expedite the weaning by restoring weaning-induced cardiovascular compromise.