Long-term adherence to a 5 day antibiotic course guideline for treatment of intensive care unit (ICU)-associated Gram-negative infections.

OBJECTIVES: To determine long-term adherence to a 5 day antibiotic course guideline for treating intensive care unit (ICU)-acquired Gram-negative bacteria (GNB) infections. METHODS: Descriptive analysis of patient-level data on all GNB-active antibiotics prescribed from day 3 and all GNB identified in clinical samples in 5350 patients admitted to a 30 bed general ICU between 2002 and 2009. RESULTS: Four thousand five hundred and eleven of 5350 (84%) patients were treated with one or more antibiotics active against GNB commenced from day 3. Gentamicin was the most frequently prescribed antibiotic (92.2 days of therapy/1000 patient-days). Only 6% of courses spanned >6 days of therapy and 89% of antibiotic therapy days were with a single antibiotic active against GNB. There was no significant difference between gentamicin and meropenem in the number of first courses in which a resistant GNB was identified in blood cultures [11/1177 (0.9%) versus 5/351 (1.4%); P = 0.43] or respiratory tract specimens [59/951 (6.2%) versus 17/246 (6.9%); P = 0.68] at the time of starting therapy. CONCLUSIONS: This study demonstrates long-term adherence to a 5 day course antibiotic guideline for treatment of ICU-associated GNB infections. This guideline is a potential antibiotic-sparing alternative to currently recommended dual empirical courses extending to ≥7 days.

Quetiapine in refractory hyperactive and mixed intensive care delirium: a case series.

INTRODUCTION: Delirium affects up to 80% of patients admitted to intensive care units (ICUs) and contributes to increased morbidity and mortality. Haloperidol is the gold standard for treatment, although quetiapine has been successfully used in the management of delirium. METHODS: We conducted a retrospective study of patients admitted to the ICU between February 2008 and May 2010 who were prescribed quetiapine by the attending clinician. Data collected included demographics, history of drug and/or alcohol dependence, ICU and hospital length of stay, length of mechanical ventilation and the duration of treatment with sedatives and medications for delirium. The daily dose of quetiapine was recorded. Hyperactive or mixed delirium was identified by a validated chart review and a Richmond Agitation Sedation Scale (RASS) score persistently greater than 1 for 48 hours despite therapy. RESULTS: Seventeen patients were included. Delirium onset occurred after a median of five days. Patients were being given at least four agents for delirium prior to the introduction of quetiapine, and they had a median RASS score of 3. Quetiapine was initiated at a 25 mg daily dose and titrated to a median daily dose of 50 mg. The median duration of delirium prior to quetiapine therapy was 15 days. Quetiapine commencement was associated with a reduction in the need for other medications (within 0 to 6 days) and resolution of delirium within a median of four days. Adverse events included somnolence and transient hypotension. CONCLUSIONS: This case series provides an initial effort to explore a possible role for quetiapine in the management of refractory hyperactive and mixed ICU delirium.

Differentiating midazolam over-sedation from neurological damage in the intensive care unit.

INTRODUCTION: Midazolam is used routinely to sedate patients in the intensive care unit (ICU). We suspected that midazolam over-sedation was occurring in the ICU of the Guy's and St. Thomas' Trust and that it could be difficult to differentiate this from underlying neurological damage. A sensitive assay for detecting midazolam and 1-hydroxymidazolam glucuronide (1-OHMG) in serum was developed and applied in the clinical setting. METHODS: In the present study we evaluated a series of cases managed in a mixed medical, surgical and trauma ICU. Serum was collected from 26 patients who received midazolam, were 'slow to wake' and in whom there was suspicion of neurological damage. Patient outcome was followed in terms of mortality, neurological recovery and neurological damage on discharge. RESULTS: Out of 26 patients, 13 had detectable serum levels of midazolam and/or 1-OHMG after a median of 67 hours (range 36-146 hours) from midazolam cessation. Of these 13 patients in whom midazolam/1-OHMG was detectable, 10 made a full neurological recovery. Of the remaining 13 patients with no detectable midazolam/1-OHMG, three made a full neurological recovery; 10 patients were subsequently found to have suffered neurological damage (P < 0.002), eight of whom died and two were discharged from the ICU with profound neurological damage. CONCLUSION: These findings confirm that prolonged sedation after midazolam therapy should be considered in the differential diagnosis of neurological damage in the ICU. This can be reliably detected by the assay method described. The effects of midazolam/1-OHMG persist days after administration of midazolam has ceased. After prolonged sedation has been excluded in this patient group, it is highly likely that neurological damage has occurred.

A web-based survey of United Kingdom sedation practice in the intensive care unit.

PURPOSE: The purpose of this work was to obtain a detailed perspective of sedation practice. Sedation included sedative and opioid choice, presence of local guidelines, and use of scoring systems. METHODS: A Web-based survey was designed. The aim was to gain sufficient detail of UK sedation while also being succinct enough to complete in 15 minutes. It was composed of relevant demographics, policy, sedative choice, and analgesia. The survey was piloted before launch. The investigators selected the intensive care unit (ICU) pharmacist as the respondent. RESULTS: One hundred fifty-seven ICUs responded. Eighty-nine (59%) reported use of sedation guidelines, 78% undertook sedation holds, and 87% use sedation scores. Only 42% used a daily sedation target. Seventy (43%) assess for delirium; 27 of those use a validated tool. Propofol (89%) use was common, followed by midazolam (49%). Morphine (49%), fentanyl (34%), and alfentanil (34%) were the most frequently used opioids. CONCLUSION: This survey confirmed expected variation in UK sedation practice. Recognized strategies such as target sedation score and sedation policy are underused. A 43% uptake in delirium screening suggests that larger engagement is required to meet national standards.

Levosimendan: a retrospective single-center case series.

PURPOSE: The purpose of this study is to describe the effect of levosimendan (without loading dose) on hemodynamics, inotropes/vasopressors, and mortality in acute heart failure (AHF). MATERIALS AND METHODS: Patients who received levosimendan for AHF were analyzed. Levosimendan dose, hemodynamic data, inotrope/vasopressor requirements, and fluid balance before commencement, at conclusion of, and 24 hours after levosimendan were collected. Mortality is also reported. RESULTS: Eighty-seven patients were analyzed. The mean levosimendan dose (without loading) was 0.096 µg/kg per minute (±0.014), and mean duration, 26 (±7.2) hours. There was no change in heart rate (start, post, and 24 hours post) (92 [±19], 92 [±26], and 92 [±15]) or mean arterial pressure (69 [±10], 72 [±8], and 72 [±10] mm Hg, respectively). There was a significant reduction in median dobutamine from 7.27 to 0 µg/kg per minute and noradrenaline from 0.20 to 0.1 µg/kg per minute before and 24 hours after. There was a significant increase in both mean cardiac index from 2.38 ± 0.0.72 to 2.98 ± 0.0.77 L/min per square meter and in markers of perfusion: base excess from -2.77 to 0.39 mmol/L, and lactate from 2.1 to 1.4 mmol/L before and 24 hours after infusion. Survival was 53%. CONCLUSIONS: Levosimendan, without a loading dose, improved cardiac index and perfusion while allowing a reduction in inotropic/vasopressor requirements in patients with AHF.