Identification of implementation barriers for adherence to guidelines pertaining to delirium is feasible with a survey. Results of this study may help to design-targeted implementation strategies for ICU delirium management.

Objectives: Implementation of delirium guidelines at ICUs is suboptimal. The aim was to evaluate the impact of a tailored multifaceted implementation program of ICU delirium guidelines on processes of care and clinical outcomes and draw lessons regarding guideline implementation. Design: A prospective multicenter, pre-post, intervention study. Setting: ICUs in one university hospital and five community hospitals. Patients: Consecutive medical and surgical critically ill patients were enrolled between April 1, 2012, and February 1, 2015. Interventions: Multifaceted, three-phase (baseline, delirium screening, and guideline) implementation program of delirium guidelines in adult ICUs. Measurements and Main Results: The primary outcome was adherence changes to delirium guidelines recommendations, based on the Pain, Agitation and Delirium guidelines. Secondary outcomes were brain dysfunction (delirium or coma), length of ICU stay, and hospital mortality. A total of 3,930 patients were included. Improvements after the implementation pertained to delirium screening (from 35% to 96%; p < 0.001), use of benzodiazepines for continuous sedation (from 36% to 17%; p < 0.001), light sedation of ventilated patients (from 55% to 61%; p < 0.001), physiotherapy (from 21% to 48%; p < 0.001), and early mobilization (from 10% to 19%; p < 0.001). Brain dysfunction improved: the mean delirium duration decreased from 5.6 to 3.3 days (–2.2 d; 95% CI, –3.2 to –1.3; p < 0.001), and coma days decreased from 14% to 9% (risk ratio, 0.5; 95% CI, 0.4–0.6; p < 0.001). Other clinical outcome measures, such as length of mechanical ventilation, length of ICU stay, and hospital mortality, did not change. Conclusions: This large pre-post implementation study of delirium-oriented measures based on the 2013 Pain, Agitation, and Delirium guidelines showed improved health professionals’ adherence to delirium guidelines and reduced brain dysfunction. Our findings provide empirical support for the differential efficacy of the guideline bundle elements in a real-life setting and provide lessons for optimization of guideline implementation programs.

Purpose We studied the pharmacokinetics of paracetamol and determine the incidence of hypotension after intravenous administration in medium-(MCU) and intensive care (ICU) patients. Methods All patients on the ICU/MCU starting with paracetamol i.v. were included, yielding 38 patients. Blood samples were collected at predetermined time points to determine paracetamol serum concentration. The number of patients with a clinically relevant reduction in systolic blood pressure (SBP) and the number of patients that needed intervention to regain an acceptable blood pressure level were assessed. Results Overall, pharmacokinetic data were roughly comparable with earlier publications, but differences were noted in the subgroup ICU patients. Also, there was a trend to a larger peak serum concentration (p=0.052) and a significantly smaller volume of distribution (p=0.033) in MCU patients compared with ICU patients. Twenty-two percent (22%) and 33% of patients had a clinically relevant reduction in systolic blood pressure (SBP) 15 and 30 min after start of paracetamol infusion, respectively. In six patients (16%), an intervention was needed to correct blood pressure. Overall, SBP was significantly reduced at T=15 min and 30 min postinfusion (p<0.003 at both time points) when compared with SBP at the start of paracetamol infusion. Conclusions Further research on differences in paracetamol pharmacokinetics between ICU and MCU patients is warranted, as these differences might result in differences in efficacy. Furthermore, administration of paracetamol i.v. as potential cause of hypotension in the critically ill patient must not be overlooked.

There is still debate as to the preferred extracorporeal treatment modality for severe lithium intoxication. Because lithium is readily diffusable, intermittent hemodialysis is usually performed. However, this bares the risk of a post-dialysis rebound concentration and, in the case of severe lithium poisoning collapse, aggravation of hemodynamic instability. Because of the relatively slow but continuous solute removal, continuous renal replacement therapy (CRRT) may be advantageous. We report the first case in the literature of severe lithium intoxication treated effectively with high-volume continuous venovenous hemofiltration (HV-CVVH). Results compared favorably to other forms of CRRT in terms of lithium clearance. Ease of implementation, the excellent tolerability and the superior lithium clearance without rebound phenomenon may make HV-CVVH the preferred treatment modality for severe lithium poisoning.

IntroductionDelirium in critically ill adults is associated with prolonged hospital stay, increased mortality and greater cognitive and functional decline. Current practice guideline recommendations advocate the use of non-pharmacological strategies to reduce delirium. The routine use of scheduled haloperidol to treat delirium is not recommended given a lack of evidence regarding its ability to resolve delirium nor improve relevant short-term and longer-term outcomes. This study aims to evaluate the efficacy and safety of haloperidol for the treatment of delirium in adult critically ill patients to reduce days spent with coma or delirium.Methods and analysisEuRIDICE is a prospective, multi-centre, randomised, double-blind, placebo-controlled trial. Study population consists of adult intensive care unit (ICU) patients without acute neurological injury who have delirium based on a positive Intensive Care Delirium Screening Checklist (ICDSC) or Confusion Assessment Method for the ICU (CAM-ICU) assessment. Intervention is intravenous haloperidol 2.5 mg (or matching placebo) every 8 hours, titrated daily based on ICDSC or CAM-ICU positivity to a maximum of 5 mg every 8 hours, until delirium resolution or ICU discharge. Main study endpoint is delirium and coma-free days (DCFD) up to 14 days after randomisation. Secondary endpoints include (1) 28-day and 1-year mortality, (2) cognitive and functional performance at 3 and 12 months, (3) patient and family delirium and ICU experience, (4) psychological sequelae during and after ICU stay, (4) safety concerns associated with haloperidol use and (5) cost-effectiveness. Differences in DCFDs between haloperidol and placebo group will be analysed using Poisson regression analysis. Study recruitment started in February 2018 and continues.Ethics and disseminationThe study has been approved by the Medical Ethics Committee of the Erasmus University Medical Centre Rotterdam (MEC2017-511) and by the Institutional Review Boards of the participating sites. Its results will be disseminated via peer-reviewed publication and conference presentations.Trial registrationNCT03628391

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