Biomarker-guided antibiotic stewardship in suspected ventilator-associated pneumonia (VAPrapid2): a randomised controlled trial and process evaluation.

BACKGROUND: Ventilator-associated pneumonia is the most common intensive care unit (ICU)-acquired infection, yet accurate diagnosis remains difficult, leading to overuse of antibiotics. Low concentrations of IL-1ß and IL-8 in bronchoalveolar lavage fluid have been validated as effective markers for exclusion of ventilator-associated pneumonia. The VAPrapid2 trial aimed to determine whether measurement of bronchoalveolar lavage fluid IL-1ß and IL-8 could effectively and safely improve antibiotic stewardship in patients with clinically suspected ventilator-associated pneumonia. METHODS: VAPrapid2 was a multicentre, randomised controlled trial in patients admitted to 24 ICUs from 17 National Health Service hospital trusts across England, Scotland, and Northern Ireland. Patients were screened for eligibility and included if they were 18 years or older, intubated and mechanically ventilated for at least 48 h, and had suspected ventilator-associated pneumonia. Patients were randomly assigned (1:1) to biomarker-guided recommendation on antibiotics (intervention group) or routine use of antibiotics (control group) using a web-based randomisation service hosted by Newcastle Clinical Trials Unit. Patients were randomised using randomly permuted blocks of size four and six and stratified by site, with allocation concealment. Clinicians were masked to patient assignment for an initial period until biomarker results were reported. Bronchoalveolar lavage was done in all patients, with concentrations of IL-1ß and IL-8 rapidly determined in bronchoalveolar lavage fluid from patients randomised to the biomarker-based antibiotic recommendation group. If concentrations were below a previously validated cutoff, clinicians were advised that ventilator-associated pneumonia was unlikely and to consider discontinuing antibiotics. Patients in the routine use of antibiotics group received antibiotics according to usual practice at sites. Microbiology was done on bronchoalveolar lavage fluid from all patients and ventilator-associated pneumonia was confirmed by at least 104 colony forming units per mL of bronchoalveolar lavage fluid. The primary outcome was the distribution of antibiotic-free days in the 7 days following bronchoalveolar lavage. Data were analysed on an intention-to-treat basis, with an additional per-protocol analysis that excluded patients randomly assigned to the intervention group who defaulted to routine use of antibiotics because of failure to return an adequate biomarker result. An embedded process evaluation assessed factors influencing trial adoption, recruitment, and decision making. This study is registered with ISRCTN, ISRCTN65937227, and ClinicalTrials.gov, NCT01972425. FINDINGS: Between Nov 6, 2013, and Sept 13, 2016, 360 patients were screened for inclusion in the study. 146 patients were ineligible, leaving 214 who were recruited to the study. Four patients were excluded before randomisation, meaning that 210 patients were randomly assigned to biomarker-guided recommendation on antibiotics (n=104) or routine use of antibiotics (n=106). One patient in the biomarker-guided recommendation group was withdrawn by the clinical team before bronchoscopy and so was excluded from the intention-to-treat analysis. We found no significant difference in the primary outcome of the distribution of antibiotic-free days in the 7 days following bronchoalveolar lavage in the intention-to-treat analysis (p=0·58). Bronchoalveolar lavage was associated with a small and transient increase in oxygen requirements. Established prescribing practices, reluctance for bronchoalveolar lavage, and dependence on a chain of trial-related procedures emerged as factors that impaired trial processes. INTERPRETATION: Antibiotic use remains high in patients with suspected ventilator-associated pneumonia. Antibiotic stewardship was not improved by a rapid, highly sensitive rule-out test. Prescribing culture, rather than poor test performance, might explain this absence of effect. FUNDING: UK Department of Health and the Wellcome Trust.

SoundEar noise warning devices cause a sustained reduction in ambient noise in adult critical care.

INTRODUCTION: Elevated sound levels in critical care are associated with sleep deprivation and an increased incidence of delirium. We aimed to determine whether a sound-activated visual noise display meter could cause a sustained reduction in sound levels overnight in an adult critical care unit. METHOD: Sound levels were recorded overnight for eight days before and after the introduction of a visual noise display meter, with a further eight days recorded four months later after continued use of the visual noise display meter. RESULTS: Median ambient sound levels were significantly reduced from 57.4 dB by 3.9 dB, with a sustained reduction of 3.6 dB from baseline after four months of the device operating. Peak ambient sound levels had a small but significant reduction from 66.0 dB by 0.7 dB, with a sustained reduction of 0.8 dB after four months. DISCUSSION: Sound-activated visual noise display meters can be effective in providing a sustained reduction in ambient sound overnight in adult critical care units, which would appear to be driven by behavioural change.

Intensive care decision-making: Identifying the challenges and generating solutions to improve inter-specialty referrals to critical care.

INTRODUCTION: Decision-making regarding admission to UK intensive care units is challenging. Demand for beds exceeds capacity, yet the need to provide emergency cover creates pressure to build redundancy into the system. Guidelines to aid clinical decision-making are outdated, resulting in an over-reliance on professional judgement. Although clinicians are highly skilled, there is variability in intensive care unit decision-making, especially at the inter-specialty level wherein cognitive biases contribute to disagreement. METHOD: This research is the first to explore intensive care unit referral and admission decision-making using the Critical Decision Method interviewing technique. We interviewed intensive care unit (n = 9) and non-intensive care unit (n = 6) consultants about a challenging referral they had dealt with in the past where there was disagreement about the patient's suitability for intensive care unit. RESULTS: We present: (i) a description of the referral pathway; (ii) challenges that appear to derail referrals (i.e. process issues, decision biases, inherent stressors, post-decision consequences) and (iii) potential solutions to improve this process. DISCUSSION: This research provides a foundation upon which interventions to improve inter-specialty decision-making can be based.

Decision-making in intensive care medicine - A review.

Decision-making by intensivists around accepting patients to intensive care units is a complex area, with often high-stakes, difficult, emotive decisions being made with limited patient information, high uncertainty about outcomes and extreme pressure to make these decisions quickly. This is exacerbated by a lack of clear guidelines to help guide this difficult decision-making process, with the onus largely relying on clinical experience and judgement. In addition to uncertainty compounding decision-making at the individual clinical level, it is further complicated at the multi-speciality level for the senior doctors and surgeons referring to intensive care units. This is a systematic review of the existing literature about this decision-making process and the factors that help guide these decisions on both sides of the intensive care unit admission dilemma. We found many studies exist assessing the patient factors correlated with intensive care unit admission decisions. Analysing these together suggests that factors consistently found to be correlated with a decision to admit or refuse a patient from intensive care unit are bed availability, severity of illness, initial ward or team referred from, patient choice, do not resuscitate status, age and functional baseline. Less research has been done on the decision-making process itself and the factors that are important to the accepting intensivists; however, similar themes are seen. Even less research exists on referral decision and demonstrates that in addition to the factors correlated with intensive care unit admission decisions, other wider variables are considered by the referring non-intensivists. No studies are available that investigate the decision-making process in referring non-intensivists or the mismatch of processes and pressure between the two sides of the intensive care unit referral dilemma.

Diagnostic accuracy of pulmonary host inflammatory mediators in the exclusion of ventilator-acquired pneumonia.

BACKGROUND: Excessive use of empirical antibiotics is common in critically ill patients. Rapid biomarker-based exclusion of infection may improve antibiotic stewardship in ventilator-acquired pneumonia (VAP). However, successful validation of the usefulness of potential markers in this setting is exceptionally rare. OBJECTIVES: We sought to validate the capacity for specific host inflammatory mediators to exclude pneumonia in patients with suspected VAP. METHODS: A prospective, multicentre, validation study of patients with suspected VAP was conducted in 12 intensive care units. VAP was confirmed following bronchoscopy by culture of a potential pathogen in bronchoalveolar lavage fluid (BALF) at >10(4) colony forming units per millilitre (cfu/mL). Interleukin-1 beta (IL-1ß), IL-8, matrix metalloproteinase-8 (MMP-8), MMP-9 and human neutrophil elastase (HNE) were quantified in BALF. Diagnostic utility was determined for biomarkers individually and in combination. RESULTS: Paired BALF culture and biomarker results were available for 150 patients. 53 patients (35%) had VAP and 97 (65%) patients formed the non-VAP group. All biomarkers were significantly higher in the VAP group (p<0.001). The area under the receiver operator characteristic curve for IL-1ß was 0.81; IL-8, 0.74; MMP-8, 0.76; MMP-9, 0.79 and HNE, 0.78. A combination of IL-1ß and IL-8, at the optimal cut-point, excluded VAP with a sensitivity of 100%, a specificity of 44.3% and a post-test probability of 0% (95% CI 0% to 9.2%). CONCLUSIONS: Low BALF IL-1ß in combination with IL-8 confidently excludes VAP and could form a rapid biomarker-based rule-out test, with the potential to improve antibiotic stewardship.

Glucose control in critical illness using a web-based insulin dose calculator.

OBJECTIVE: We describe a modified version of a web-based insulin calculator for the control of blood glucose in critical care. DESIGN: We modified a previously described calculator by incorporating bolus doses of insulin to be given. The calculator is now also able to store blood glucose concentrations, insulin rates, bed number and the date and time of calculation. We modified our feeding protocol to restrict the target enteral feed from 1800 to 1500 kcal per day and removed the night time rest period. SETTING: A 16-bedded intensive care unit. PATIENTS AND PARTICIPANTS: All patients admitted to the ICU between June 2005 and May 2006. MEASUREMENTS AND RESULTS: Six hundred and sixty-one patients admitted (mean APACHE II score 16 [S.D. 7]), mean age 51 years [S.D. 17]. One hundred and forty-six patients died prior to ICU discharge. Total of 5573 patient days with 13,029 recorded calculation data points. Mean blood glucose concentration was 6.7 mmol (95CI 3.7-12.1). There were 34 episodes of treated hypoglycaemia of which 11 were on an insulin infusion. There were two troughs in the time of data entry that corresponded with staff handover. There was no evidence of diurnal variation in blood glucose concentration. The mean value of the insulin infusion rate was 4.3 units/h (S.D. 3.7). CONCLUSIONS: The web-based insulin calculator facilitates the dosing of insulin in critical care. The lack of diurnal blood glucose concentrations suggests that once daily estimation of blood glucose may be an acceptable method of monitoring blood glucose concentrations in critical care.