Acetaminophen Use Concomitant with Long-Lasting Flucloxacillin Therapy: A Dangerous Combination.

Acetaminophen and flucloxacillin both interfere with the γ-glutamyl cycle. Long-lasting concomitant use of flucloxacillin and acetaminophen can lead to 5-oxoproline accumulation and severe high anion gap metabolic acidosis. Females and patients with sepsis, impaired kidney and/or liver function, malnutrition, advanced age, congenital 5-oxoprolinase deficiency and supratherapeutic acetaminophen and flucloxacillin dosage are associated with increased risk. Therefore, a critical attitude towards the prescription of acetaminophen concomitant with flucloxacillin in these patients is needed. We present the case of a 79-year-old woman with severe 5-oxoprolinaemia after long-lasting treatment with flucloxacillin and acetaminophen, explaining the toxicological mechanism and risk factors, and we make recommendations for acetaminophen use in patients with long-lasting flucloxacillin treatment. LEARNING POINTS: Although rare, long-lasting treatment with flucloxacillin concomitant with acetaminophen can lead to severe high anion gap metabolic acidosis.When prescribing long-lasting flucloxacillin therapy in combination with acetaminophen, regular blood gas analysis is needed to evaluate pH and the anion gap.In cases of 5-oxoproline-induced high anion gap metabolic acidosis in patients with long-lasting acetaminophen and flucloxacillin therapy, acetaminophen prescription should be stopped immediately. Replacing flucloxacillin with another antibiotic agent should be considered.

Vasopressors Do Not Influence Cerebral Critical Closing Pressure During Systemic Inflammation Evoked by Experimental Endotoxemia and Sepsis in Humans.

AIM: The aim of this study was to investigate the effects of different vasopressors on the cerebral vasculature during experimental human endotoxemia and sepsis. We used the critical closing pressure (CrCP) as a measure of cerebral vascular tone. METHODS: We performed a prospective pilot study, at the intensive care department (ICU) of a tertiary care university hospital in the Netherlands, in 40 healthy male subjects during experimental human endotoxemia (administration of bacterial lipopolysaccharide [LPS]) and in 10 patients with severe sepsis or septic shock.Subjects in the endotoxemia study were randomized to receive a 5 h infusion of either 0.05 µg/kg/min noradrenaline (n = 10, "LPS-nor"), 0.5 µg/kg/min phenylephrine (n = 10, "LPS-phenyl"), 0.04 IU/min vasopressin (n = 10, "LPS-AVP"), or saline (n = 10, "LPS-placebo") starting 1 h before intravenous administration of 2 ng/kg LPS. In patients with sepsis, fluid resuscitation and vasopressor use was at the discretion of the medical team, aiming at normovolemia and a mean arterial pressure (MAP) > 65 mm Hg, using noradrenaline.The mean flow velocity in the middle cerebral artery (MFVMCA) was measured by transcranial Doppler (TCD) with simultaneously recording of heart rate, arterial blood pressure, respiratory rate, and oxygen saturation. CrCP was estimated using the cerebrovascular impedance model. RESULTS: The CrCP decreased in the LPS-placebo group from 52.6 [46.6-55.5] mm Hg at baseline to 44.1 [41.2-51.3] mm Hg at 270 min post-LPS (P = 0.03). Infusion of phenylephrine increased the CrCP in the period before LPS administration from 46.9 [38.8-53.4] to 53.8 [52.9-60.2] mm Hg (P = 0.02), but after LPS administration, a similar decrease was observed compared with the LPS-placebo group. Noradrenaline or vasopressin prior to LPS did not affect the CrCP. The decrease in CrCP after LPS bolus was similar in all treatment groups. The CrCP in the sepsis patients equaled 35.7 [34.4-42.0] mm Hg, and was lower compared with that in the LPS-placebo subjects from baseline until 90 min after LPS (P < 0.01). CONCLUSIONS: Experimental human endotoxemia results in a decreased CrCP due to a loss of vascular resistance of the arterial bed. Vasopressors did not prevent this decrease in CrCP. Findings in patients with sepsis are comparable to those found in subjects after LPS administration.Patients with sepsis, despite treatment with vasopressors, have a risk for low cerebral blood flow and ischemia.

Barriers and facilitators to improve safety and efficiency of the ICU discharge process: a mixed methods study.

BACKGROUND: Evidence indicates that suboptimal clinical handover from the intensive care unit (ICU) to general wards leads to unnecessary ICU readmissions and increased mortality. We aimed to gain insight into barriers and facilitators to implement and use ICU discharge practices. METHODS: A mixed methods approach was conducted, using 1) 23 individual and four focus group interviews, with post-ICU patients, ICU managers, and nurses and physicians working in the ICU or general ward of ten Dutch hospitals, and 2) a questionnaire survey, which contained 27 statements derived from the interviews, and was completed by 166 ICU physicians (21.8%) from 64 Dutch hospitals (71.1% of the total of 90 Dutch hospitals). RESULTS: The interviews resulted in 66 barriers and facilitators related to: the intervention (e.g., feasibility); the professional (e.g., attitude towards checklists); social factors (e.g., presence or absence of a culture of feedback); and the organisation (e.g., financial resources). A facilitator considered important by ICU physicians was a checklist to structure discharge communication (92.2%). Barriers deemed important were lack of a culture of feedback (55.4%), an absence of discharge criteria (23.5%), and an overestimation of the capabilities of general wards to care for complex patients by ICU physicians (74.7%). CONCLUSIONS: Based on the barriers and facilitators found in this study, improving handover communication, formulating specific discharge criteria, stimulating a culture of feedback, and preventing overestimation of the general ward are important to effectively improve the ICU discharge process.

Improving clinical handover between intensive care unit and general ward professionals at intensive care unit discharge.

PURPOSE: To systematically review and evaluate the effectiveness of interventions in order to improve the safety and efficiency of patient handover between intensive care unit (ICU) and general ward healthcare professionals at ICU discharge. METHODS: PubMed, CINAHL, PsycINFO, EMBASE, Web of Science, and the Cochrane Library were searched for intervention studies with the aim to improve clinical handover between ICU and general ward healthcare professionals that had been published up to and including June 2013. The methods for article inclusion and data analysis were pre-specified and aligned with recommendations outlined in the PRISMA guideline. Two reviewers independently extracted data (study purpose, setting, population, method of sampling, sample size, intervention characteristics, outcome, and implementation activities) and assessed the quality of the included studies. RESULTS: From the 6,591 citations initially extracted from the six databases, we included 11 studies in this review. Of these, six (55 %) reported statistically significant effects. Effective interventions included liaison nurses to improve communication and coordination of care and forms to facilitate timely, complete and accurate handover information. Effective interventions resulted in improved continuity of care (e.g., reduced discharge delay) and in reduced adverse events. Inconsistent effects were observed for use of care, namely, reduction of length of stay versus increase of readmissions to higher care. No statistically significant effects were found in the reduction of mortality. The overall methodological quality of the 11 studies reviewed was relatively low, with an average score of 4.5 out of 11 points. CONCLUSIONS: This review shows that liaison nurses and handover forms are promising interventions to improve the quality of patient handover between the ICU and general ward. More robust evidence is needed on the effectiveness of interventions aiming to improve ICU handover and supportive implementation strategies.

A strategy to enhance the safety and efficiency of handovers of ICU patients: study protocol of the pICUp study.

BACKGROUND: To use intensive care unit (ICU) facilities efficiently and ensure high quality of care, an optimal patient flow is necessary. Discharging patients relieves the pressure on ICU beds but the risk of premature discharge must be managed carefully. Suboptimal patient discharge may result in ICU readmissions and in patients' death.The aim of this study is to obtain insight into the safety and efficiency of current ICU discharge practices and into barriers and facilitators to the implementation of effective ICU discharge interventions, and to develop an implementation strategy tailored to the barriers and facilitators identified. METHODS/DESIGN: This study exists of five phases. Phase A: analysis of routinely registered data on variation in ICU readmissions and hospital mortality after ICU discharge of all ICUs participating in the Dutch National Intensive Care Evaluation registry (n=83). Phase B: systematic review of effective interventions aiming to improve the efficiency and safety of the ICU discharge process. Phase C: assessing the intervention adherence with a questionnaire survey among all Dutch ICUs (n=90). Phase D: assessing barriers and facilitators to the implementation of effective ICU discharge interventions with a questionnaire survey among all Dutch intensivists (n=700). The questionnaire will be based on barriers and facilitators identified by focus groups (n=4) and individual interviews with professionals of ICUs and general wards and adult discharged ICU patients (n=25 to 30). Phase E: systematic development of an implementation strategy based on the sampled data in phase A to D, and effective implementation strategies from the literature using the intervention mapping method. DISCUSSION: Using theory and empirical data, an implementation strategy will be developed to improve the safety and efficiency of the ICU discharge process. The developed strategy will be evaluated in a subsequent study. The knowledge obtained in this study should be used for further implementation of ICU discharge interventions, and can be used for implementation of handover interventions in other healthcare transition settings.