The present authors hypothesised that in severe acute respiratory distress syndrome (ARDS), pronation may reduce ventilator-induced overall stress (i.e. transpulmonary pressure (PL)) and strain of lung parenchyma (i.e. tidal volume (VT)/end-expiratory lung volume (EELV) ratio), which constitute major ventilator-induced lung injury determinants. The authors sought to determine whether potential pronation benefits are maintained in post-prone semirecumbent (SRPP) posture under pressure-volume curve-dependent optimisation of positive end-expiratory pressure (PEEP).A total of 10 anesthetised/paralysed, mechanically ventilated (VT59.0¡0.9 mL?kg -1 predicted body weight; flow50.91¡0.04 L?s -1 ; PEEP59.4¡1.3 cmH 2 O) patients with early/severe ARDS were studied in pre-prone semirecumbent (SRBAS), prone, and SRPP positions. Partitioned respiratory mechanics were determined during iso-flow (0.91 L?s -1 ) experiments (VT varied within 0.2-1.0 L), along with haemodynamics, gas exchange, and EELV. Compared with SRBAS, pronation/SRPP resulted in reduced peak/plateau PL at VTso0.6 L; static lung elastance and additional lung resistance decreased and chest wall elastance (in prone position) increased; EELV increased (23-33%); VT/EELV decreased (27-33%); arterial oxygen tension/inspiratory oxygen fraction and arterial carbon dioxide tension improved (21-43/10-14%, respectively), and shunt fraction/physiological dead space decreased (21-50/20-47%, respectively).In early/severe acute respiratory distress syndrome, pronation under positive end-expiratory pressure optimisation may reduce ventilator-induced lung injury risk. Pronation benefits may be maintained in post-prone semirecumbent position.

In acute respiratory distress syndrome (ARDS), recruitment sessions of highfrequency oscillation (HFO) and tracheal gas insufflation (TGI) with short-lasting recruitment manoeuvres (RMs) may improve oxygenation and enable reduction of subsequent conventional mechanical ventilation (CMV) pressures. We determined the effect of adding HFO-TGI sessions to lung-protective CMV on early/severe ARDS outcome.We conducted a prospective clinical trial, subdivided into a first single-centre period and a second two-centre period. We enrolled 125 (first period, n554) patients with arterial oxygen tension (Pa,O 2 )/inspiratory oxygen fraction (FI,O 2 ) of ,150 mmHg for .12 consecutive hours at an end-expiratory pressure of o8 cmH 2 O. Patients were randomly assigned to an HFO-TGI group (receiving HFO-TGI sessions with RMs, interspersed with lung-protective CMV; n561) or CMV group (receiving lung-protective CMV and RMs; n564). The primary outcome was survival to hospital discharge.Pre-enrolment ventilation duration was variable. During days 1-10 post-randomisation, Pa,O 2 / FI,O 2 , oxygenation index, plateau pressure and respiratory compliance were improved in the HFO-TGI group versus the CMV group (p,0.001 for group6time). Within days 1-60, the HFO-TGI group had more ventilator-free days versus the CMV group (median (interquartile range) 31.0 (0.0-42.0) versus 0.0 (0.0-23.0) days; p,0.001), and more days without respiratory, circulatory, renal, coagulation and liver failure (pf0.003). Survival to hospital discharge was higher in the HFO-TGI group versus the CMV group (38 (62.3%) out of 61 versus 23 (35.9%) out of 64 subjects; p50.004).Intermittent recruitment with HFO-TGI and RMs may improve survival in early/severe ARDS.

Nasal continuous positive airway pressure (CPAP) can cause undesirable nasal symptoms, such as congestion to obstructive sleep apnoea (OSA) patients, whose symptoms can be attenuated by the addition of heated humidification. However, neither the nature of nasal symptoms nor the effect of heated humidification on nasal pathophysiology and pathology are convincingly known.20 patients with OSA on nasal CPAP who exhibited symptomatic nasal obstruction were randomised to receive either 3 weeks of CPAP treatment with heated humidification or 3 weeks of CPAP treatment with sham-heated humidification, followed by 3 weeks of the opposite treatment, respectively. Nasal symptom score, nasal resistance, nasal lavage interleukin-6, interleukin-12 and tumour necrosis factor-a and nasal mucosa histopathology were assessed at baseline and after each treatment arm.Heated humidification in comparison with sham-heated humidification was associated with decrease in nasal symptomatology, resistance and lavage cytokines, and attenuation of inflammatory cell infiltration and fibrosis of the nasal mucosa.In conclusion, nasal obstruction of OSA patients on CPAP treatment is inflammatory in origin and the addition of heated humidification decreases nasal resistance and mucosal inflammation.

Some patients with obstructive sleep apnoea syndrome (OSAS; respiratory distress index (RDI) of .5 events?h -1 ) experience residual excessive daytime subjective sleepiness (Epworth Sleepiness Scale (ESS) score of .10), despite adequate use of continuous positive airway pressure (CPAP) therapy. The aim of the present study was to identify clinical and polysomnographic predictors of this sleepiness.Clinical and polysomnographic variables and ESS score were evaluated in 208 OSAS patients with an ESS score of .10 before (initial assessment) and after o6 months of adequate (o4 h?day -1 ) CPAP use. Following CPAP treatment, 114 (55%) patients showed an abnormal ESS score (.10; CPAP nonresponders), whereas 94 (45%) showed a normal ESS score (,11; CPAP responders). Of the CPAP responders, none had a history of depression, whereas the converse was true for 38.8% of CPAP nonresponders. In addition, multivariate logistic regression analysis revealed that the independent predictors of residual excessive daytime sleepiness following CPAP therapy were a history of diabetes and heart disease, and a higher ESS score and lower RDI on initial assessment.In conclusion, predictors of residual excessive sleepiness in adequately CPAP-treated OSAS were a history of depression, diabetes and heart disease, and a higher ESS score and lower RDI on initial assessment.

Background: Not all patients with severe chronic obstructive pulmonary disease (COPD) progressively hyperinflate during symptom limited exercise. The pattern of change in chest wall volumes (Vcw) was investigated in patients with severe COPD who progressively hyperinflate during exercise and those who do not. Methods: Twenty patients with forced expiratory volume in 1 second (FEV 1 ) 35 (2)% predicted were studied during a ramp incremental cycling test to the limit of tolerance (Wpeak). Changes in Vcw at the end of expiration (EEVcw), end of inspiration (EIVcw), and at total lung capacity (TLCVcw) were computed by optoelectronic plethysmography (OEP) during exercise and recovery. Results: Two significantly different patterns of change in EEVcw were observed during exercise. Twelve patients had a progressive significant increase in EEVcw during exercise (early hyperinflators, EH) amounting to 750 (90) ml at Wpeak. In contrast, in all eight remaining patients EEVcw remained unchanged up to 66% Wpeak but increased significantly by 210 (80) ml at Wpeak (late hyperinflators, LH). Although at the limit of tolerance the increase in EEVcw was significantly greater in EH, both groups reached similar Wpeak and breathed with a tidal EIVcw that closely approached TLCVcw (EIVcw/TLCVcw 93 (1)% and 93 (3)%, respectively). EEVcw was increased by 254 (130) ml above baseline 3 minutes after exercise only in EH. Conclusions: Patients with severe COPD exhibit two patterns during exercise: early and late hyperinflation. In those who hyperinflate early, it may take several minutes before the hyperinflation is fully reversed after termination of exercise.

Although restrictive lung disease is the predominant abnormality of pulmonary function in patients with thalassaemia major (TM), its aetiology and its association with pulmonary hypertension (PH) detected in some patients with TM remains unknown. We report a patient with TM, iron overload, frequent pulmonary infections, and progressive severe precapillary PH over the previous 5 years. A severe restrictive pattern and interstitial lung fibrosis were revealed by pulmonary function tests and high resolution computed tomography, respectively. This presentation suggests that interstitial fibrosis may complicate lung involvement in TM and can significantly contribute to the development of PH. (Thorax 2001;56:737-739) Keywords: thalassaemia major; pulmonary hypertension; interstitial lung fibrosis Impairment of cardiac function is a well documented complication of thalassaemia major (TM) attributed to haemochromatosis, and congestive heart failure resulting from decreased left ventricular systolic function is the main cause of early mortality.1 2 Pulmonary hypertension (PH) is relatively rare, 3 4 especially in the absence of left ventricular dysfunction. Its aetiology remains uncertain.The predominant abnormality of pulmonary function in TM is restrictive disease.5 6 Although transfusional iron burden and increasing age seem to play a role, 5 the nature of this restrictive pattern is still unknown as no systematic pathological studies or studies using computed tomographic (CT) scanning have been performed.We report a patient with TM who presented with severe PH, markedly increased pulmonary vascular resistance (PVR), right ventricular failure, preserved left ventricular function, a severe restrictive pattern in pulmonary function tests, and interstitial fibrosis revealed by high resolution CT (HRCT) scanning of the lung. Case reportA 29 year old man with TM who had never smoked was admitted to the intensive care unit (ICU) with pneumonia requiring the use of a non-rebreathing mask (FiO 2 ≅ 100%) to maintain an SaO 2 of >90%. The patient had bronze coloured skin and had started blood transfusions at the age of 4, having received a total of 640 blood units to maintain haematocrit values of 26-30%. Inadequate iron chelation therapy with subcutaneous injection of desferrioxamine had been started 5 years previously (25 mg/kg/day, 2 days per week). At this time splenectomy was performed and mild systolic PH (36 mm Hg) was diagnosed by continuous wave (C-W) Doppler echocardiography through minimal tricuspid regurgitation. 7More severe systolic PH was detected 2 years later (48 mm Hg) when dyspnoea on exertion was present. PH progressed to 57 mm Hg at the age of 27; a magnetic resonance imaging (MRI) scan of the heart was within normal limits. Frequent pulmonary infections were reported during the previous 4 years.On admission right heart failure was present (audible S 3 , prominent jugular veins to the angle of the jaw, pitting ankle oedema, palpable liver 15 cm below the right costal margin, and bilateral transud...

Critical Care 2017, 21(Suppl 1):P349 Introduction Imbalance in cellular energetics has been suggested to be an important mechanism for organ failure in sepsis and septic shock. We hypothesized that such energy imbalance would either be caused by metabolic changes leading to decreased energy production or by increased energy consumption. Thus, we set out to investigate if mitochondrial dysfunction or decreased energy consumption alters cellular metabolism in muscle tissue in experimental sepsis. Methods We submitted anesthetized piglets to sepsis (n = 12) or placebo (n = 4) and monitored them for 3 hours. Plasma lactate and markers of organ failure were measured hourly, as was muscle metabolism by microdialysis. Energy consumption was intervened locally by infusing ouabain through one microdialysis catheter to block major energy expenditure of the cells, by inhibiting the major energy consuming enzyme, N+/K + -ATPase. Similarly, energy production was blocked infusing sodium cyanide (NaCN), in a different region, to block the cytochrome oxidase in muscle tissue mitochondria. Results All animals submitted to sepsis fulfilled sepsis criteria as defined in Sepsis-3, whereas no animals in the placebo group did. Muscle glucose decreased during sepsis independently of N+/K + -ATPase or cytochrome oxidase blockade. Muscle lactate did not increase during sepsis in naïve metabolism. However, during cytochrome oxidase blockade, there was an increase in muscle lactate that was further accentuated during sepsis. Muscle pyruvate did not decrease during sepsis in naïve metabolism. During cytochrome oxidase blockade, there was a decrease in muscle pyruvate, independently of sepsis. Lactate to pyruvate ratio increased during sepsis and was further accentuated during cytochrome oxidase blockade. Muscle glycerol increased during sepsis and decreased slightly without sepsis regardless of N+/K + -ATPase or cytochrome oxidase blocking. There were no significant changes in muscle glutamate or urea during sepsis in absence/presence of N+/K + -ATPase or cytochrome oxidase blockade. ConclusionsThese results indicate increased metabolism of energy substrates in muscle tissue in experimental sepsis. Our results do not indicate presence of energy depletion or mitochondrial dysfunction in muscle and should similar physiologic situation be present in other tissues, other mechanisms of organ failure must be considered. , and long-term follow up has shown increased fracture risk [2]. It is unclear if these changes are a consequence of acute critical illness, or reduced activity afterwards. Bone health assessment during critical illness is challenging, and direct bone strength measurement is not possible. We used a rodent sepsis model to test the hypothesis that critical illness causes early reduction in bone strength and changes in bone architecture. Methods 20 Sprague-Dawley rats (350 ± 15.8g) were anesthetised and randomised to receive cecal ligation and puncture (CLP) (50% cecum length, 18G needle single pass through anterior and posterior wa...

In healthy subjects expiratory flow limitation (EFL) during exercise can lower O 2 delivery to the working muscles. We hypothesized that if this affects exercise performance it should influence O 2 kinetics at the end of exercise when the O 2 debt is repaid. We performed an incremental exercise test on six healthy males with a Starling resistor in the expiratory line limiting expiratory flow to~1 l s -1 to determine maximal EFL exercise workload (W max ). In two more square-wave exercise runs subjects exercised with and without EFL at W max for 6 min, while measuring arterial O 2 saturation (% SaO 2 ), end-tidal pressure of CO 2 (P ET CO 2 ) and breath-by-breath O 2 consumption ð _ VO 2 Þ taking into account changes in O 2 stored in the lungs. Over the last minute of EFL exercise, mean P ET CO 2 (54.7 ± 9.9 mmHg) was significantly higher (P < 0.05) compared to control (41.4 ± 3.9 mmHg). At the end of EFL exercise %SaO 2 fell significantly by 4 ± 3%. When exercise stopped, EFL was removed, and we continued to measure _ VO 2 : During recovery, there was an immediate step increase in _ VO 2 ; so that repayment of EFL O 2 debt started at a higher _ VO 2 than control. Recovery _ VO 2 kinetics after EFL exercise was best characterized by a double-exponential function with fundamental and slow time constants of 27 ± 11 and 1,020 ± 305 s, compared to control values of 41 ± 10 and 1,358 ± 320 s, respectively. EFL O 2 debt was 52 ± 22% greater than control (2.19 ± 0.58 vs. 1.49 ± 0.38 l). We conclude that EFL exercise increases the O 2 debt and leads to hypoxemia in part due to hypercapnia.