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Objective Computerised order sets have the potential to reduce clinical variation and improve patient safety but the effect is variable. We sought to evaluate the impact of changes to the design of an order set on the delivery of chlorhexidine mouthwash and hydroxyethyl starch (HES) to patients in the intensive care unit. Methods The study was conducted at University Hospitals Bristol NHS Foundation Trust, UK. Our intensive care unit uses a clinical information system (CIS). All drugs and fluids are prescribed with the CIS and drug and fluid charts are stored within a database. Chlorhexidine mouthwash was added as a default prescription to the prescribing template in January 2010. HES was removed from the prescribing template in April 2009. Both interventions were available to prescribe manually throughout the study period. We conducted a database review of all patients eligible for each intervention before and after changes to the configuration of choices within the prescribing system. Results 2231 ventilated patients were identified as appropriate for treatment with chlorhexidine, 591 before the intervention and 1640 after. 55.3% were prescribed chlorhexidine before the change and 90.4% after (p<0.001). 6199 patients were considered in the HES intervention, 2177 before the intervention and 4022 after. The mean volume of HES infused per patient fell from 630 mL to 20 mL after the change (p<0.001) and the percentage of patients receiving HES fell from 54.1% to 3.1% (p<0.001). These results were well sustained with time. Conclusions The presentation of choices within an electronic prescribing system influenced the delivery of evidence-based interventions in a predictable way and the effect was well sustained. This approach has the potential to enhance the effectiveness of computerised order sets.

Background Extubation failure, defined as reintubation within 48 h, is associated with increased intensive care unit (ICU) length of stay and higher mortality risk. One cause of extubation failure is secretion retention, resulting from an inability to cough effectively. Mechanical insufflation-exsufflation (MI-E) simulates a cough aiding secretion clearance. However, MI-E is not routinely used in the ICU for invasively ventilated patients. This study aims to determine feasibility and acceptability of a randomised controlled trial (RCT) examining MI-E use to promote extubation success in intubated, ventilated adults. Methods It is a single-centre, feasibility RCT with semi-structured interviews, economic scoping, and exploratory physiology study. The feasibility RCT ( n  = 50) will compare standard care to a MI-E protocol including a minimum of two MI-E sessions via the endotracheal tube prior to extubation. Post-extubation, MI-E will be delivered via facemask or mouthpiece up to two times/day for 48 h. MI-E settings will be individualised. All patients will receive standard care (no MI-E) in relation to mechanical ventilation, weaning, rehabilitation, physiotherapy techniques such as positioning, manual airway clearance techniques, manual/ventilator hyperinflation, endotracheal suctioning, and nebulisation. Clinical data collection will occur before, on completion, and 5-min post-physiotherapy sessions (intervention/control arms). Resource use will be calculated for each 24-h period. Analyses will be descriptive and address feasibility outcomes including participant recruitment and attrition, proportion of MI-E treatment sessions completed, dataset completeness, and frequency of adverse events and acceptability. Semi-structured online interviews informed by the Theoretical Framework of Acceptability (TFA) with patients, clinicians, and family members will explore the acceptability of the MI-E intervention and study processes. Interview data will be analysed using reflexive thematic analysis based on TFA domains through first-level coding. The embedded physiology study will use electrical impedance tomography and lung ultrasound to explore lung recruitment and de-recruitment during MI-E in a subset of 5–10 patients. Discussion This study will examine feasibility and acceptability of a RCT protocol of MI-E to promote extubation success. Study findings will inform design modification and conduct of a future adequately powered trial. Furthermore, the study will contribute and advance the understanding of MI-E use in critically ill intubated adults. Trial registration ISRCTN 24603037; IRAS 303674

EDITOR-In her review of acute renal failure Hilton acknowledges that the immediate care of most such patients in the United Kingdom is provided in intensive care units by intensivists but does not sufficiently emphasise the effective clinical approach to resuscitation in intensive care. 1 In particular, adequate renal perfusion pressure must be maintained in patients who have a raised intra-abdominal pressure, and this can often prevent the need for renal replacement therapy.

In a trial involving patients with coma after out-of-hospital cardiac arrest, a strategy targeting mild hypercapnia for 24 hours did not improve neurologic outcomes at 6 months as compared with targeted normocapnia.

Background This study aimed to evaluate the safety and efficacy of inhaled pegylated adrenomedullin (PEG-ADM) for the management of acute respiratory distress syndrome in critically ill patients on mechanical ventilation. Methods A Phase 2a/b randomised, double-blind, placebo-controlled multicentre trial was conducted. Patients with acute respiratory distress syndrome were assigned to receive PEG-ADM 960 μg or 1920 μg, or placebo. The primary endpoints were safety, efficacy, and ventilator-free survival at Day 28. Efficacy was assessed using ventilator-free survival and the clinical utility index, a composite endpoint that includes extravascular lung water index, oxygenation index, non-pulmonary Sequential Organ Failure Assessment score. Results Ninety patients were randomised (PEG-ADM 960 μg: n = 29; PEG-ADM 1920 μg: n = 30; placebo: n = 31). Both dosages of PEG-ADM were well tolerated, with adverse event profiles similar to placebo. However, no significant efficacy was observed on the clinical utility index. Ventilator-free survival at Day 28 was lower in the PEG-ADM 960 μg group (52%) compared with the PEG-ADM 1920 μg (67%) and placebo (65%) groups. No significant differences were noted in overall mortality or the need for continued ventilation at Days 28 and 60. Conclusion Inhaled PEG-ADM was well tolerated in patients with acute respiratory distress syndrome, but it did not improve clinical outcomes, which led to the early discontinuation after the first part of the trial for futility. Trial registration ClinicalTrials.gov: NCT04417036 (date of registration: 4 June 2020). Key message What is already known on this topic  -  summarise the state of scientific knowledge on this subject before you did your study and why this study needed to be done Acute respiratory distress syndrome (ARDS) is known to have a high 28-day mortality rate with no effective specific pharmacologic interventions currently available. PEGylated adrenomedullin (PEG-ADM) was hypothesised to reduce vascular permeability of lung endothelial cells and, therefore, improve pulmonary function and patient outcomes. An inhaled formulation was further developed to increase lung selectivity and reduce hypotensive systemic effects. What this study adds  - summarise what we now know as a result of this study that we did not know before This Phase 2 randomised controlled trial investigated the safety and efficacy of inhaled PEG-ADM in ARDS patients on mechanical ventilation. Main efficacy outcomes included 28-day ventilator-free survival and the clinical utility index, which comprised the extravascular lung water index, change in oxygenation index, and change in non-pulmonary Sequential Organ Failure Assessment score. While PEG-ADM was well tolerated with a safety profile comparable to placebo, no meaningful clinical benefits were observed in both efficacy outcomes at either of the two investigated doses. How this study might affect research, practice or policy  - summarise the implications of this study Further Phase IIB/IIA studies with inhaled ADM-PEG in ARDS are not warranted.

A case of death from severe paracetamol poisoning which presented early and received appropriate treatment according to evidence-based guidelines is presented here. It is very rare for patients to die from paracetamol poisoning when they receive N-acetylcysteine (NAC) within 8 h of ingestion. The patient had a marked lactic acidosis on presentation to hospital. This case demonstrates that a patient can die from paracetamol poisoning despite early and appropriate treatment, and raises the question whether lactic acidosis in a patient following paracetamol overdose should prompt the initiation of NAC treatment while awaiting paracetamol levels.

Time spent lying by lactating Holstein-Friesian cows of varying body condition scores (BCS) and milk yield was measured using an animal activity monitor. A 3-week average BCS was calculated for each cow; and in total, 84 cows were selected with 28 cows each among three BCS categories (Thin: BCS<2·75; Moderate: 2·75 >or= BCS<3·25; Heavy: BCS >or= 3·25) and two stage of lactation categories (<150 days in milk or >150 days in milk). Cows were kept in two management systems: parlour/freestall (n=60) or automated milking system/freestall (n=24). Behaviour was recorded for 5·3±0·1 d for each cow. Production levels were considered using a 28-d rolling average of daily milk production. Cows that exhibited clinical lameness before or during the observation period were excluded from analyses. For cows exhibiting oestrus, the day prior to, day of, and day following breeding were removed. The final analysis included 77 cows (408 d of observation). A mixed model was fitted to describe average daily hours spent lying. Results demonstrated that lying time increased as days in milk (DIM) increased (P=0·05). Variables that were tested but not significant (P>0·05) were BCS category, parity category (1 or >or= 2) and 28-d rolling average daily milk production. Although a numerical trend for increasing hours spent lying with increasing BCS was observed, after accounting for other factors in the mixed model, BCS did not significantly impact lying time. Continued investigation of these management factors that impact lying time and bouts, using new technologies, more cows, and more herds will help dairy owners better manage facilities and cow movements to optimize this essential behaviour.