Catherine McKenzie

Antibiotic dosing in critical illness

Early and effective antibiotic therapy is essential in the management of infection in critical illness. The loading dose is probably the most important dose and is a function of the volume of distribution of the drug and the desired plasma concentration but independent of renal function. Antibiotics are classified in a number of ways that have implications for dosing. Doses of hydrophilic agents such as β-lactams should be increased in the early stages of sepsis as the extravascular space increases. For lipophilic agents such as macrolides, the inflammatory process is less important, although factors such as obesity will affect dosing. Classification can also be based on pharmacodynamic properties. Concentration-dependent antibiotics such as aminoglycosides should be administered by extended interval regimens, which maximize bactericidal effect, minimize nephrotoxicity and allow time between doses for the post-antibiotic effect. The critical factor for time-dependent agents, such as β-lactams, is time above the MIC. Ideally administration of these agents should be continuous, although vascular access availability can restrict infusion time to between 4 and 6 h, which is probably adequate. As well as antibiotic factors, patient factors such as hepatic and renal failure will affect dosing. Hepatic failure will affect antibiotic metabolism, although it is most important in end-stage failure. Renal failure and support will affect drug elimination. Knowledge of these factors is essential. Patient safety and prevention of unnecessary harm is a weighty consideration in critical illness. To ensure effective treatment and minimize adverse effects, therapy should be reviewed daily and adjusted in the light of changes in patient organ function and underlying pathology.

A cost‐effectiveness analysis of caspofungin vs. liposomal amphotericin B for treatment of suspected fungal infections in the UK

Objective:  To evaluate the cost‐effectiveness of caspofungin vs. liposomal amphotericin B in the treatment of suspected fungal infections in the UK.

Pharmacist's review and outcomes: Treatment-enhancing contributions tallied, evaluated, and documented (PROTECTED-UK)

PURPOSE The purpose was to describe clinical pharmacist interventions across a range of critical care units (CCUs) throughout the United Kingdom, to identify CCU medication error rate and prescription optimization, and to identify the type and impact of each intervention in the prevention of harm and improvement of patient therapy. MATERIALS AND METHODS A prospective observational study was undertaken in 21 UK CCUs from November 5 to 18, 2012. A data collection web portal was designed where the specialist critical care pharmacist reported all interventions at their site. Each intervention was classified as medication error, optimization, or consult. In addition, a clinical impact scale was used to code the interventions. Interventions were scored as low impact, moderate impact, high impact, and life saving. The final coding was moderated by blinded independent multidisciplinary trialists. RESULTS A total of 20517 prescriptions were reviewed with 3294 interventions recorded during the weekdays. This resulted in an overall intervention rate of 16.1%: 6.8% were classified as medication errors, 8.3% optimizations, and 1.0% consults. The interventions were classified as low impact (34.0%), moderate impact (46.7%), and high impact (19.3%); and 1 case was life saving. Almost three quarters of interventions were to optimize the effectiveness of and improve safety of pharmacotherapy. CONCLUSIONS This observational study demonstrated that both medication error resolution and pharmacist-led optimization rates were substantial. Almost 1 in 6 prescriptions required an intervention from the clinical pharmacist. The error rate was slightly lower than an earlier UK prescribing error study (EQUIP). Two thirds of the interventions were of moderate to high impact.

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.

Maintaining Normal Levels of Ionized Calcium during Citrate-Based Renal Replacement Therapy Is Associated with Stable Parathyroid Hormone Levels

Background/Aims: Citrate is an effective anticoagulant during continuous renal replacement therapy (CRRT). Previous studies showed raised parathyroid hormone (PTH) levels when aiming for serum ionized calcium [Cai] between 0.8 and 1.1 mmol/l. Our objective was to assess whether citrate-based CRRT with physiologic target systemic [Cai] between 1.12 and 1.20 mmol/l could maintain stable PTH levels. Methods: Measurement of intact PTH (PTHi) in 30 consecutive critically ill patients treated with citrate-based CRRT. Results: Thirty patients [mean age: 70.4 (SD 11.3) years; 56.7% males] were enrolled. Mean serum [Cai] was 1.16 mmol/l (SD 0.09), 1.13 mmol/l (SD 0.09), 1.17 mmol/l (SD 0.05) and 1.16 mmol/l (SD 0.04) at baseline, 12, 24 and 48 h, respectively (p = 0.29). Median PTHi levels (interquartile range) at baseline, 12, 24 and 48 h were 66.5 (43-111), 109 (59.5-151.5), 88.5 (47-133) and 85 pg/ml (53-140), respectively. The differences between baseline and 12 h and across all time points were statistically not significant (p = 0.16 and p = 0.49, respectively). In a mixed-effects model, each 0.1 mmol/l increase in serum [Cai] was associated with a 31.2% decrease in PTHi (p < 0.001). Results were unchanged after adjustment for age, gender, magnesium, phosphate, arterial pH and time spent on CRRT. Conclusions: Maintaining systemic [Cai] within the physiologic range was associated with stable PTHi levels.

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

IntroductionDelirium 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.MethodsWe 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.ResultsSeventeen 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.ConclusionsThis case series provides an initial effort to explore a possible role for quetiapine in the management of refractory hyperactive and mixed ICU delirium.

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.

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.

Beyond the randomized clinical trial: citrate for continuous renal replacement therapy in clinical practice.

Background: Premature circuit clotting is a major problem during continuous renal replacement therapy (CRRT). Six randomized controlled trials confirmed that regional anticoagulation with citrate is superior to heparin. Our objective was to compare circuit patency with citrate, heparin and epoprostenol in routine clinical practice. Methods: We retrospectively analysed data on circuit patency of all circuits used in a single centre between September 2008 and August 2009. We differentiated between premature filter clotting, elective discontinuation and waste. Results: 309 patients were treated with CRRT (n = 2,059 circuits). The mean age was 65.7; 63.8% were male. The methods to maintain circuit patency were unfractionated heparin (42.3%), epoprostenol (23.0%), citrate (14.7%), combinations of different anticoagulants (14.6%) and no anticoagulation (4.7%). Premature clotting was the most common reason for circuit discontinuation among circuits anticoagulated with heparin, epoprostenol or combinations of different anticoagulants (59-62%). Among circuits anticoagulated with citrate the main reason for discontinuation was elective (61%). Hazard regression analysis confirmed significantly better circuit survival with citrate. Changing from heparin to citrate decreased the risk of premature circuit clotting by 75.8%. Conclusion: In routine clinical practice, regional anticoagulation with citrate is associated with significantly better circuit patency than heparin or epoprostenol.

Critical care pharmacy workforce: UK deployment and characteristics in 2015

Clinical pharmacists reduce medication errors and optimize the use of medication in critically ill patients, although actual staffing level and deployment of UK pharmacists is unknown. The primary aim was to investigate the UK deployment of the clinical pharmacy workforce in critical care and compare this with published standards.