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Intensive care unit (ICU)-acquired weakness is a frequent complication of critical illness. It is unclear whether it is a marker or mediator of poor outcomes. To determine acute outcomes, 1-year mortality, and costs of ICU-acquired weakness among long-stay (≥8 d) ICU patients and to assess the impact of recovery of weakness at ICU discharge. Data were prospectively collected during a randomized controlled trial. Impact of weakness on outcomes and costs was analyzed with a one-to-one propensity-score-matching for baseline characteristics, illness severity, and risk factor exposure before assessment. Among weak patients, impact of persistent weakness at ICU discharge on risk of death after 1 year was examined with multivariable Cox proportional hazards analysis. A total of 78.6% were admitted to the surgical ICU; 227 of 415 (55%) long-stay assessable ICU patients were weak; 122 weak patients were matched to 122 not-weak patients. As compared with matched not-weak patients, weak patients had a lower likelihood for live weaning from mechanical ventilation (hazard ratio [HR], 0.709 [0.549-0.888]; P = 0.009), live ICU (HR, 0.698 [0.553-0.861]; P = 0.008) and hospital discharge (HR, 0.680 [0.514-0.871]; P = 0.007). In-hospital costs per patient (+30.5%, +5,443 Euro per patient; P = 0.04) and 1-year mortality (30.6% vs. 17.2%; P = 0.015) were also higher. The 105 of 227 (46%) weak patients not matchable to not-weak patients had even worse prognosis and higher costs. The 1-year risk of death was further increased if weakness persisted and was more severe as compared with recovery of weakness at ICU discharge (P < 0.001). After careful matching the data suggest that ICU-acquired weakness worsens acute morbidity and increases healthcare-related costs and 1-year mortality. Persistence and severity of weakness at ICU discharge further increased 1-year mortality. Clinical trial registered with www.clinicaltrials.gov (NCT 00512122).

Severe acute respiratory failure in adults causes high mortality despite improvements in ventilation techniques and other treatments (eg, steroids, prone positioning, bronchoscopy, and inhaled nitric oxide). We aimed to delineate the safety, clinical efficacy, and cost-effectiveness of extracorporeal membrane oxygenation (ECMO) compared with conventional ventilation support. In this UK-based multicentre trial, we used an independent central randomisation service to randomly assign 180 adults in a 1:1 ratio to receive continued conventional management or referral to consideration for treatment by ECMO. Eligible patients were aged 18–65 years and had severe (Murray score >3·0 or pH <7·20) but potentially reversible respiratory failure. Exclusion criteria were: high pressure (>30 cm H 2O of peak inspiratory pressure) or high FiO 2 (>0·8) ventilation for more than 7 days; intracranial bleeding; any other contraindication to limited heparinisation; or any contraindication to continuation of active treatment. The primary outcome was death or severe disability at 6 months after randomisation or before discharge from hospital. Primary analysis was by intention to treat. Only researchers who did the 6-month follow-up were masked to treatment assignment. Data about resource use and economic outcomes (quality-adjusted life-years) were collected. Studies of the key cost generating events were undertaken, and we did analyses of cost-utility at 6 months after randomisation and modelled lifetime cost-utility. This study is registered, number ISRCTN47279827. 766 patients were screened; 180 were enrolled and randomly allocated to consideration for treatment by ECMO (n=90 patients) or to receive conventional management (n=90). 68 (75%) patients actually received ECMO; 63% (57/90) of patients allocated to consideration for treatment by ECMO survived to 6 months without disability compared with 47% (41/87) of those allocated to conventional management (relative risk 0·69; 95% CI 0·05–0·97, p=0·03). Referral to consideration for treatment by ECMO treatment led to a gain of 0·03 quality-adjusted life-years (QALYs) at 6-month follow-up. A lifetime model predicted the cost per QALY of ECMO to be £19 252 (95% CI 7622–59 200) at a discount rate of 3·5%. We recommend transferring of adult patients with severe but potentially reversible respiratory failure, whose Murray score exceeds 3·0 or who have a pH of less than 7·20 on optimum conventional management, to a centre with an ECMO-based management protocol to significantly improve survival without severe disability. This strategy is also likely to be cost effective in settings with similar services to those in the UK. UK NHS Health Technology Assessment, English National Specialist Commissioning Advisory Group, Scottish Department of Health, and Welsh Department of Health.

Purpose To evaluate the efficacy of a quality improvement (QI) program for protocol-directed weaning from mechanical ventilation. Methods This was a prospective, cluster randomized controlled trial. The study consisted of a baseline phase and a QI phase. Fourteen intensive care units (ICUs) in Beijing, China, were randomized into the QI group and non-QI group. The QI group received a QI program to improve the compliance with protocol-directed weaning during the QI phase. Results A total of 444 patients were enrolled in the non-QI group (193 for the baseline, 251 for the QI phase) and 440 in the QI group (199 for the baseline, 241 for the QI phase). During the QI phase in the QI group, compared with the non-QI group, total duration of mechanical ventilation decreased from 7.0 to 3.0 days ( p  = 0.003), the time before the first weaning attempt decreased from 3.63 to 1.96 days ( p  = 0.003), length of ICU stay decreased from 10.0 to 6.0 days ( p  = 0.004), length of hospital stay decreased from 23.0 to 19.0 days ( p  < 0.001). These differences were also significant in the QI group when the QI phase was compared with the baseline phase. In addition, there was a significant reduction in the percentage of mechanical ventilation exceeding 21 days ( p  = 0.001) when the baseline phase was compared with the QI phase in the QI group. Conclusions The QI program involving protocol-directed weaning is associated with beneficial clinical outcomes in mechanically ventilated patients.

For over two decades, physicians have attempted to define the best methods of discontinuing mechanical ventilation in patients recovering from respiratory failure. An early study of weaning 1 noted that the clinical decision to discontinue mechanical ventilation is often arbitrary, based on “judgment and experience.” With increasing recognition of the risks and economic consequences of prolonged ventilation, identifying strategies that reduce the duration of mechanical ventilation remains a high priority, 2 , 3 but no single approach has been established as the best one. Many measures have been proposed to identify patients ready for extubation, 1 , 4 – 15 ranging from simple maneuvers, such as . . .

Background Preventive nebulization of mucolytic agents and bronchodilating drugs is a strategy aimed at the prevention of sputum plugging, and therefore atelectasis and pneumonia, in intubated and ventilated intensive care unit (ICU) patients. The present trial aims to compare a strategy using the preventive nebulization of acetylcysteine and salbutamol with nebulization on indication in intubated and ventilated ICU patients. Methods/Design The preventive nebulization of mucolytic agents and bronchodilating drugs in invasively ventilated intensive care unit patients (NEBULAE) trial is a national multicenter open-label, two-armed, randomized controlled non-inferiority trial in the Netherlands. Nine hundred and fifty intubated and ventilated ICU patients with an anticipated duration of invasive ventilation of more than 24 hours will be randomly assigned to receive either a strategy consisting of preventive nebulization of acetylcysteine and salbutamol or a strategy consisting of nebulization of acetylcysteine and/or salbutamol on indication. The primary endpoint is the number of ventilator-free days and surviving on day 28. Secondary endpoints include ICU and hospital length of stay, ICU and hospital mortality, the occurrence of predefined pulmonary complications (acute respiratory distress syndrome, pneumonia, large atelectasis and pneumothorax), and the occurrence of predefined side effects of the intervention. Related healthcare costs will be estimated in a cost-benefit and budget-impact analysis. Discussion The NEBULAE trial is the first randomized controlled trial powered to investigate whether preventive nebulization of acetylcysteine and salbutamol shortens the duration of ventilation in critically ill patients. Trial registration NCT02159196 , registered on 6 June 2014.

Abstract Objective: To evaluate the cost effectiveness of standard treatment with and without the addition of ward based non-invasive ventilation in patients admitted to hospital with an acute exacerbation of chronic obstructive pulmonary disease. Design: Incremental cost effectiveness analysis of a randomised controlled trial. Setting: Medical wards in 14 hospitals in the United Kingdom. Participants: The trial comprised 236 patients admitted to hospital with an acute exacerbation of chronic obstructive pulmonary disease and mild to moderate acidosis (pH 7.25-7.35) secondary to respiratory failure. The economic analysis compared the costs of treatment that these patients received after randomisation. Main outcome measure: Incremental cost per in-hospital death. Results: 24/118 died in the group receiving standard treatment and 12/118 in the group receiving non-invasive ventilation (P=0.05). Allocation to the group receiving non-invasive ventilation was associated with a reduction in costs of £49 362 ($78 741; €73 109), mainly through reduced use of intensive care units. The incremental cost effectiveness ratio was −£645 per death avoided (95% confidence interval −£2310 to £386), indicating a dominant (more effective and less costly) strategy. Modelling of these data indicates that a typical UK hospital providing a non-invasive ventilation service will avoid six deaths and three to nine admissions to intensive care units per year, with an associated cost reduction of £12 000–53 000 per year. Conclusions: Non-invasive ventilation is a highly cost effective treatment that both reduced total costs and improved mortality in hospital. What is already known on this topic Non-invasive ventilation reduces the need for intubation and mortality in hospital in patients with acute exacerbations of chronic obstructive pulmonary disease and acute respiratory failure The procedure is feasible in the ward or intensive care environment What this study adds Non-invasive ventilation given on wards reduces the need for intubation by 44% and halves mortality in hospital in patients with chronic obstructive pulmonary disease and mild to moderate acidosis The early use of non-invasive ventilation on the ward reduces costs and improves outcomes compared with traditional medical treatment The main cost saving is in preventing the use of intensive care facilities

Closed endotracheal suctioning (CES) may impact ventilator-associated pneumonia (VAP) risk by reducing environmental contamination. In developing countries where resource limitations constrain the provision of optimal bed space for critically ill patients, CES assumes greater importance. In this prospective, open-labeled, randomized controlled trial spanning 10 months, we compared CES with open endotracheal suctioning (OES) in mechanically ventilated patients admitted to the medical intensive care unit (ICU) of a university-affiliated teaching hospital. Patients were followed up from ICU admission to death or discharge from hospital. Primary outcome was incidence of VAP. Secondary outcomes included mortality, cost, and length of stay. Two hundred patients were recruited, 100 in each arm. The incidence of VAP was 23.5%. Closed endotracheal suctioning was associated with a trend to a reduced incidence of VAP (odds ratio, 1.86; 95% confidence interval, 0.91-3.83; P = .067). A significant benefit was, however, observed with CES for late-onset VAP (P = .03). Mortality and duration of ICU and hospital stay were similar in the 2 groups. The cost of suction catheters and gloves was significantly higher with CES (Rs 272 [US $5.81] vs Rs 138 [US $2.94], P < .0001). Nine patients need to be treated with CES to prevent 1 VAP (95% confidence interval, −0.7 to 22). In the ICU setting in a developing country, CES may be advantageous in reducing the incidence of VAP, particularly late-onset VAP. These results mandate further studies in this setting before specific guidelines regarding the routine use of CES are proposed.

Ventilator-associated pneumonia (VAP) is associated with significant morbidity and mortality in pediatric intensive care unit (PICU). Our purpose was to evaluate the effects of ventilator circuit change on the rate of VAP in the PICU. A prospective randomized controlled trial was conducted at a university hospital PICU. Children (younger than 18 years) who received mechanical ventilation from December 2006 to November 2007 were randomly assigned to receive ventilator circuit changes every 3 or 7 days. Of 176 patients, 88 were assigned to receive ventilator circuit every 3 days and 88 patients had a change weekly. The rate of VAP was 13.9/1000 ventilator days for the 3-day circuit change (n = 12) vs 11.5/1000 ventilator days (n = 10) for the 7-day circuit change (odds ratio, 0.8; confidence interval, 0.3-1.9; P = .6). There was a trend toward decreased PICU stay and mortality rate in 7-day change group compared to 3-day change group but did not reach statistical significance. Furthermore, switching from a 3-day to a 7-day change policy could save costs up to US $22,000/y. The 7-day ventilator circuit change did not contribute to increased rates of VAP in our PICU. Thus, it may be used as a guide to save workload and supply costs.

Background The best criteria for surfactant treatment in the perinatal period are unknown and this makes it of interest to consider the possible economic implications of lessening the use of more restrictive criteria. Objective The objective of this study is the evaluation of the costs of respiratory care for preterm infants with Respiratory Distress Syndrome (RDS) treated with \"early rescue\" surfactant compared to a \"late rescue\" strategy. Methods The study was carried out applying the costs of materials used, of staff and pharmacological therapy calculated in the Neonatal Intensive Care Unit (NICU) of an Italian hospital to the Verder et al . study (Pediatrics 1999) clinical data. Results The cost for patients treated with early strategy was slightly lower than for patients treated with late strategy (Euro 4,901.70 vs. Euro 4,960.07). The cost of treatment with surfactant was greater in the early group (Euro 458.49 vs. Euro 311.74), but this was compensated by the greater cost of treatment with Mechanical Ventilation (MV) in the late group (respectively Euro 108.85 vs. Euro 259.25). Conclusions The cost-effectiveness analysis performed in this study shows how early treatment with surfactant in preterm infants with RDS, as well as being clinically more effective, is associated with a slightly lower cost.

Background:Trials of inhaled nitric oxide (iNO) used short term in preterm infants with severe respiratory failure have to date shown no evidence of benefit, and there have been no trials reporting follow-up to 4 years of age. The INNOVO trial recruited 108 infants (55 iNO arm and 53 controls) from 15 neonatal units. By 1 year of age 59% had died, and 84% of the survivors had signs of impairment or disability.Objective:This paper reports the long-term clinical effectiveness and costs of adding NO to the ventilator gases of preterm infants with severe respiratory failure.Patients and methods:Children were assessed at age 4–5 years by interview, examination, cognitive and behavioural assessments. The outcome data were divided into seven domains and were described as normal, impaired or disabled (mild, moderate or severe) by the degree of functional loss.Results:38 of the 43 survivors had follow-up assessments. In the iNO group 62% (34/55) had died or were severely disabled, compared to 70% (37/53) in the no iNO group (RR 0.89, 95% CI 0.67 to 1.16). There was no evidence of difference in the levels of impairment or disability between the two groups in any of the domains studied, or of cost differences, amongst the survivors.Conclusion:For this group of babies with severe respiratory failure there was no evidence of difference in the longer-term outcome between those babies allocated to iNO and those who were allocated to no iNO. The challenge is to identify those premature babies who are able to respond to NO with clinically important health improvements.Trial registration number:17821339.