Defining the pharmacokinetic/pharmacodynamic index of piperacillin/tazobactam within a hollow-fibre infection model to determine target attainment in intensive care patients.

Background: It is important to optimize dosing schemes of antibiotics to maximize the probability of therapeutic success. The recommended pharmacokinetic/pharmacodynamic (PK/PD) index for piperacillin/tazobactam therapy in clinical studies ranges widely (50%-100% fT>1-4×MIC). Dosing schemes failing to achieve PK/PD targets may lead to negative treatment outcomes. Objectives: The first aim of this study was to define the optimal PK/PD index of piperacillin/tazobactam with a hollow-fibre infection model (HFIM). The second aim was to predict whether these PK/PD targets are currently achieved in critically ill patients through PK/PD model simulation. Patients and methods: A dose-fractionation study comprising 21 HFIM experiments was performed against a range of Gram-negative bacterial pathogens, doses and infusion times. Clinical data and dose histories from a case series of nine patients with a known bacterial infection treated with piperacillin/tazobactam in the ICU were collected. The PK/PD index and predicted plasma concentrations and therefore target attainment of the patients were simulated using R version 4.2.1. Results: fT >MIC was found to be the best-fitting PK/PD index for piperacillin/tazobactam. Bactericidal activity with 2 log10 cfu reduction was associated with 77% fT>MIC. Piperacillin/tazobactam therapy was defined as clinically 'ineffective' in ∼78% (7/9) patients. Around seventy-one percent (5/7) of these patients had a probability of >10% that 2  log10 cfu reduction was not attained. Conclusions: Our dose-fractionation study indicates an optimal PK/PD target in piperacillin/tazobactam therapies should be 77% fT>MIC for 2 log10 kill. Doses to achieve this target should be considered when treating patients in ICU.

Corticosteroids in adult respiratory distress syndrome - an inconvenient truth?

OBJECTIVES: Recent studies have demonstrated mortality benefits from corticosteroid use in COVID-19 patients requiring respiratory support. However, clinical practice may warrant the use of corticosteroids outside the context of a clinical trial. Such data are rarely, if ever, reported. We explored the use of corticosteroids for adult respiratory distress syndrome (ARDS) indications in patients with non-COVID ARDS. METHODS: We retrospectively studied patients with moderate-to-severe ARDS, admitted to our intensive care unit (ICU) between January 2018 and March 2020. KEY FINDINGS: Of the 91 patients with ARDS identified, 80% were treated with a corticosteroid during their ICU admission. Of these, 73 (82%) had corticosteroids administered for reasons other than ARDS. CONCLUSIONS: Corticosteroid use for non-ARDS indications is commonplace in ARDS patients in our ICU. The use of corticosteroids outside a randomisation process in randomised clinical trials may be more common than appreciated and needs to be routinely reported.

Reducing medication errors in critical care patients: pharmacist key resources and relationship with medicines optimisation.

BACKGROUND: Medication errors are the most common type of medical errors critical care patients experience. Critical care units utilise a variety of resources to reduce medication errors; it is unknown which resources or combinations thereof are most effective in improving medication safety. OBJECTIVES: To obtain UK critical care pharmacist group consensus on the most important interventions/resources that reduce medication errors. To then classify units that participated in the PROTECTED UK study to investigate if there were significant differences in the reported pharmacist prescription intervention type, clinical impact and rates according to unit resource classification. METHODS: An e-Delphi process (three rounds) obtained pharmacist consensus on which interventions/resources were most important in the reduction of medication errors in critical care patients. The 21 units involved in the PROTECTED UK study (multicentre study of UK critical care pharmacist medicines interventions), were categorised as high-, medium- and low-resource units based on routine delivery of the final Top 5 interventions/ resources. High and low units were compared according to type, clinical impact and rate of medication interventions reported during the PROTECTED UK study. KEY FINDINGS: Consensus on the Top 5 combined medication error reduction resources was established: advanced-level clinical pharmacist embedded in critical care being ranked most important. Pharmacists working on units with high resources made significantly more clinically significant medicines optimisations compared to those on low-resourced units (OR 3.09; P = 0.035). CONCLUSIONS: Critical care pharmacist group consensus on the most important medication error reduction resources was established. Pharmacists working on high-resourced units made more clinically significant medicines optimisations.

Experience using high-dose glucose-insulin-potassium (GIK) in critically ill patients.

PURPOSE: To audit the use of GIK in terms of safety, haemodynamic effects, and impact on catecholamine dosage. MATERIALS AND METHODS: A retrospective, descriptive, evaluative audit of GIK use within the adult ICU of a London teaching hospital was conducted. Rescue therapy of GIK (up to 1.0Unitsinsulin/kg/h) was administered to improve cardiac function. Outcomes were ICU survival, change in cardiac index (CI) and blood lactate levels, events of hypoglycaemia, hyperglycaemia, hypokalaemia and hyperkalaemia, and discontinuation time of catecholamine inotropes. RESULTS: Of 85 patients treated with GIK, 13 (15.3%) survived their ICU stay and 9 (10.5%) were discharged home. In patients surviving until 72h, a trend of improved CI and lactate levels was seen, often with reductions in catecholamine dosing. Inotropes were discontinued in 35 (54%) patients. Severe hypoglycaemia (<2mmol/l), hyperglycaemia (>20mmol/l), hypokalaemia (<2.5mmol/l) and hyperkalaemia (>7mmol/l) during GIK affected 1, 6, 8 and 1 patients, respectively. These abnormalities were quickly identified. No measurable harm was noted. CONCLUSIONS: High-dose GIK can be safely used in critically ill patients, though blood glucose and potassium levels must be monitored frequently. GIK was associated with improved CI and blood lactate levels. Impact on survival requires prospective evaluation.

Reliability of clinical impact grading by healthcare professionals of common prescribing error and optimisation cases in critical care patients.

OBJECTIVE: To identify between and within profession-rater reliability of clinical impact grading for common critical care prescribing error and optimisation cases. To identify representative clinical impact grades for each individual case. DESIGN: Electronic questionnaire. SETTING: 5 UK NHS Trusts. PARTICIPANTS: 30 Critical care healthcare professionals (doctors, pharmacists and nurses). INTERVENTION: Participants graded severity of clinical impact (5-point categorical scale) of 50 error and 55 optimisation cases. MAIN OUTCOME MEASURES: Case between and within profession-rater reliability and modal clinical impact grading. METHODS: Between and within profession rater reliability analysis used linear mixed model and intraclass correlation, respectively. RESULTS: The majority of error and optimisation cases (both 76%) had a modal clinical severity grade of moderate or higher. Error cases: doctors graded clinical impact significantly lower than pharmacists (-0.25; P < 0.001) and nurses (-0.53; P < 0.001), with nurses significantly higher than pharmacists (0.28; P < 0.001). Optimisation cases: doctors graded clinical impact significantly lower than nurses and pharmacists (-0.39 and -0.5; P < 0.001, respectively). Within profession reliability grading was excellent for pharmacists (0.88 and 0.89; P < 0.001) and doctors (0.79 and 0.83; P < 0.001) but only fair to good for nurses (0.43 and 0.74; P < 0.001), for optimisation and error cases, respectively. CONCLUSIONS: Representative clinical impact grades for over 100 common prescribing error and optimisation cases are reported for potential clinical practice and research application. The between professional variability highlights the importance of multidisciplinary perspectives in assessment of medication error and optimisation cases in clinical practice and research.

PROTECTED-UK - Clinical pharmacist interventions in the UK critical care unit: exploration of relationship between intervention, service characteristics and experience level.

PURPOSE: Clinical pharmacist (CP) interventions from the PROTECTED-UK cohort, a multi-site critical care interventions study, were further analysed to assess effects of: time on critical care, number of interventions, CP expertise and days of week, on impact of intervention and ultimately contribution to patient care. METHODS: Intervention data were collected from 21 adult critical care units over 14 days. Interventions could be error, optimisation or consults, and were blind-coded to ensure consistency, prior to bivariate analysis. Pharmacy service demographics were further collated by investigator survey. KEY FINDINGS: Of the 20 758 prescriptions reviewed, 3375 interventions were made (intervention rate 16.1%). CPs spent 3.5 h per day (mean, ±SD 1.7) on direct patient care, reviewed 10.3 patients per day (±SD 4.2) and required 22.5 min (±SD 9.5) per review. Intervention rate had a moderate inverse correlation with the time the pharmacist spent on critical care (P = 0.05; r = 0.4). Optimisation rate had a strong inverse association with total number of prescriptions reviewed per day (P = 0.001; r = 0.7). A consultant CP had a moderate inverse correlation with number of errors identified (P = 0.008; r = 0.6). No correlation existed between the presence of electronic prescribing in critical care and any intervention rate. Few centres provided weekend services, although the intervention rate was significantly higher on weekends than weekdays. CONCLUSIONS: A CP is essential for safe and optimised patient medication therapy; an extended and developed pharmacy service is expected to reduce errors. CP services should be adequately staffed to enable adequate time for prescription review and maximal therapy optimisation.

Impact of the introduction of a specialist critical care pharmacist on the level of pharmaceutical care provided to the critical care unit.

OBJECTIVES: To evaluate the impact of a dedicated specialist critical care pharmacist service on patient care at a UK critical care unit (CCU). METHODS: Pharmacist intervention data was collected in two phases. Phase 1 was with the provision of a non-specialist pharmacist chart review service and Phase 2 was after the introduction of a specialist dedicated pharmacy service. Two CCUs with established critical care pharmacist services were used as controls. The impact of pharmacist interventions on optimising drug therapy or preventing harm from medication errors was rated on a 4-point scale. KEY FINDINGS: There was an increase in the mean daily rate of pharmacist interventions after the introduction of the specialist critical care pharmacist (5.45 versus 2.69 per day, P < 0.0005). The critical care pharmacist intervened on more medication errors preventing potential harm and optimised more medications. There was no significant change to intervention rates at the control sites. Across all study sites the majority of pharmacist interventions were graded to have at least moderate impact on patient care. CONCLUSION: The introduction of a specialist critical care pharmacist resulted in an increased rate of pharmacist interventions compared to a non-specialist pharmacist service thus improving the quality of patient care.

Reporting Guidelines for Clinical Pharmacokinetic Studies: The ClinPK Statement.

BACKGROUND AND OBJECTIVE: Transparent reporting of all research is essential for assessing the validity of any study. Reporting guidelines are available and endorsed for many types of research but are lacking for clinical pharmacokinetic studies. Such tools promote the consistent reporting of a minimal set of information for end users, and facilitate knowledge translation of research. The objective of this study was to create a guideline to assist in the transparent and complete reporting of clinical pharmacokinetic studies. METHODS: Preliminary content to be considered was identified from a systematic search of the literature and regulatory documents. Stakeholders were identified to participate in a modified Delphi exercise and a virtual meeting to generate consensus for items considered essential in the reporting of clinical pharmacokinetic studies. The proposed checklist was pilot tested on 100 recently published clinical pharmacokinetic studies. Overall and itemized compliance with the proposed guidance was determined for each study. RESULTS: Sixty-eight stakeholders from nine countries consented to participate. Four rounds of a modified Delphi survey and a series of small virtual meetings were required to generate consensus for a 24-item checklist considered to be essential to the reporting of clinical pharmacokinetic studies. When applied to the 100 most recently published clinical pharmacokinetic studies, 45 were determined to be compliant with at least 80 % of the checklist items. Explanatory text was prepared using examples of compliant reporting from these and other relevant studies. CONCLUSIONS: The reader's ability to judge the validity of pharmacokinetic research can be greatly compromised by the incomplete reporting of study information. Using consensus methods, we have developed a tool to guide transparent and accurate reporting of clinical pharmacokinetic studies. Endorsement and implementation of these guidelines by researchers, clinicians and journals would promote more consistent reporting of these studies and allow for better assessment of utility for clinical applications.

Management of a mixed overdose of calcium channel blockers, ß-blockers and statins.

We describe a case of extreme mixed overdose of calcium channel blockers, ß-blockers and statins. The patient was successfully treated with aggressive resuscitation including cardiac pacing and multiorgan support, glucagon and high-dose insulin for toxicity related to calcium channel blockade and ß-blockade, and ubiquinone for treating severe presumed statin-induced rhabdomyolysis and muscle weakness.

Selective decontamination of the digestive tract in critically ill patients treated in intensive care units: a mixed-methods feasibility study (the SuDDICU study).

BACKGROUND: Hospital-acquired infections (HAIs) are a major cause of morbidity and mortality. Critically ill patients in intensive care units (ICUs) are particularly susceptible to these infections. One intervention that has gained much attention in reducing HAIs is selective decontamination of the digestive tract (SDD). SDD involves the application of topical non-absorbable antibiotics to the oropharynx and stomach and a short course of intravenous (i.v.) antibiotics. SDD may reduce infections and improve mortality, but has not been widely adopted in the UK or internationally. Hence, there is a need to identify the reasons for low uptake and whether or not further clinical research is needed before wider implementation would be considered appropriate. OBJECTIVES: The project objectives were to (1) identify and describe the SDD intervention, (2) identify views about the evidence base, (3) identify acceptability of further research and (4) identify feasibility of further randomised controlled trials (RCTs). DESIGN: A four-stage approach involving (1) case studies of two ICUs in which SDD is delivered including observations, interviews and documentary analysis, (2) a three-round Delphi study for in-depth investigation of clinicians' views, including semi-structured interviews and two iterations of questionnaires with structured feedback, (3) a nationwide online survey of consultants in intensive care medicine and clinical microbiology and (4) semistructured interviews with international clinical triallists to identify the feasibility of further research. SETTING: Case studies were set in two UK ICUs. Other stages of this research were conducted by telephone and online with NHS staff working in ICUs. PARTICIPANTS: (1) Staff involved in SDD adoption or delivery in two UK ICUs, (2) ICU experts (intensive care consultants, clinical microbiologists, hospital pharmacists and ICU clinical leads), (3) all intensive care consultants and clinical microbiologists in the UK with responsibility for patients in ICUs were invited and (4) international triallists, selected from their research profiles in intensive care, clinical trials and/or implementation trials. INTERVENTIONS: SDD involves the application of topical non-absorbable antibiotics to the oropharynx and stomach and a short course of i.v. antibiotics. MAIN OUTCOME MEASURES: Levels of support for, or opposition to, SDD in UK ICUs; views about the SDD evidence base and about barriers to implementation; and feasibility of further SDD research (e.g. likely participation rates). RESULTS: (1) The two case studies identified complexity in the interplay of clinical and behavioural components of SDD, involving multiple staff. However, from the perspective of individual staff, delivery of SDD was regarded as simple and straightforward. (2) The Delphi study (n = 42) identified (a) specific barriers to SDD implementation, (b) uncertainty about the evidence base and (c) bimodal distributions for key variables, e.g. support for, or opposition to, SDD. (3) The national survey (n = 468) identified uncertainty about the effect of SDD on antimicrobial resistance, infection rates, mortality and cost-effectiveness. Most participants would participate in further SDD research. (4) The triallist interviews (n = 10) focused largely on the substantial challenges of conducting a large, multinational clinical effectiveness trial. CONCLUSIONS: There was considerable uncertainty about possible benefits and harms of SDD. Further large-scale clinical effectiveness trials of SDD in ICUs may be required to address these uncertainties, especially relating to antimicrobial resistance. There was a general willingness to participate in a future effectiveness RCT of SDD. However, support was not unanimous. Future research should address the barriers to acceptance and participation in any trial. There was some, but a low level of, interest in adoption of SDD, or studies to encourage implementation of SDD into practice. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 18, No. 25. See the NIHR Journals Library website for further project information.

An analysis of medicine costs of adult patients on a critical care unit.

PURPOSE: To evaluate the costs of medicines used to treat critically ill patients in an intensive care environment and to correlate this with severity of illness and mortality. MATERIALS AND METHODS: The study was conducted at a London Teaching Hospital Critical Care Unit. Data were collected for patients who were either discharged or died during September 2011 and stayed longer than 48 hours. The drug cost was related to 150 drugs that were then related to patient's acuity and outcome. RESULTS: The median daily drug cost of the 85 patients was £26. The highest cost patients in the 85th percentile had significantly higher daily drug costs (median, £403) and higher scores for patient acuity. Patients with hematologic malignancy had a median daily drug cost (£561) more than 20 times higher than those without. A regression analysis based on patient's diversity explained 93% of the variance in the daily drug cost. CONCLUSIONS: Although the median daily drug cost for an adult critically ill patient was low, this cost significantly escalated with patient acuity and hematologic malignancy. A reference method has been designed for an in-depth evaluation of daily drug cost that could be used to compare expenditure in other units.

Clinical components and associated behavioural aspects of a complex healthcare intervention: multi-methods study of selective decontamination of the digestive tract in critical care.

BACKGROUND: This study sought to identify and describe the clinical and behavioural components (e.g. the what, how, when, where and by whom) of 'selective decontamination of the digestive tract' (SDD) as routinely implemented in the care of critically ill patients. METHODS: Multi-methods study, consisting of semi-structured observations of SDD delivery, interviews with clinicians and documentary analysis, conducted in two ICUs in the UK that routinely deliver SDD. Data were analysed within-site to describe clinical and behavioural SDD components and synthesised across-sites to describe SDD in context. RESULTS: SDD delivery involved multiple behaviours extending beyond administration of its clinical components. Not all behaviours were specified in relevant clinical documentation. Overall, SDD implementation and delivery included: adoption (i.e. whether to implement SDD), operationalisation (i.e. implementing SDD into practice), provision (i.e. delivery of SDD) and surveillance (i.e. monitoring the ecological effects). Implementation involved organisational, team and individual-level behaviours. Delivery was perceived as easy by individual staff, but displayed features of complexity (including multiple interrelated behaviours, staff and contexts). CONCLUSIONS: This study is the first to formally outline the full spectrum of clinical and behavioural aspects of SDD. It identified points in the delivery process where complex behaviours occur and outlined how SDD can be interpreted and applied variably in practice. This comprehensive specification allows greater understanding of how this intervention could be implemented in units not currently using it, or replicated in research studies. It also identified strategies required to adopt SDD and to standardise its implementation.

Medication issues experienced by patients and carers after discharge from the intensive care unit.

PURPOSE: Medication-related problems (MRPs) frequently occur at the interfaces of care settings. We examined this further because little has been published about MRPs experienced by patients/carers after discharge from the intensive care unit (ICU). METHODS AND MATERIALS: Medication history data were collected before, during, and after ICU admission and by face-to-face semistructured interviews with 21 patients and 13 carers attending the ICU Follow-up Clinic (FC) of our 35-bed adult ICU. RESULTS: A total of 122 drugs were prescribed regularly before ICU admission, 168 on ICU discharge, 132 at hospital discharge, and 128 at the FC. Medication-related problems were identified with hypnotics/anxiolytics, antidepressants, proton pump inhibitors, and analgesics. Good follow-up was observed in all 4 cases where the antidysrhythmic agent amiodarone was initiated on ICU. Patients/carers described 20 cases of difficulty in obtaining appropriate and timely supplies and 19 of insufficient information. CONCLUSIONS: These results show that our incidence of MRPs after ICU discharge was encouragingly infrequent, in which we attribute it to targeted medicine reconciliation and the availability of our FC. However, MRPs were perceived to stem from inadequate communication at the interfaces of care and the lack of opportunity for patients/carers to obtain relevant information. We recommend that FC should focus on MRPs during their consultation and that further research in this area should be performed to examine our observations further.

Audit of audit: review of a clinical audit programme in a teaching hospital intensive care unit.

OBJECTIVE: A comprehensive review of the clinical audit programme in a teaching hospital intensive care unit. DESIGN: A retrospective analysis of the clinical audit projects undertaken within the intensive care unit over the preceding 2 years and compared with published national guidelines for clinical audit. SETTING: A 27-bedded teaching hospital intensive care unit in the UK. MEASUREMENTS: Each audit project was reviewed independently by two assessors. The following questions were assessed. 1. Were the projects true audits? 2. Were they prospective of retrospective? 3. Did the projects have input from appropriate members of the multidisciplinary team. 4. How many of the audit projects were re-audits? 5. Of the re-audits how many showed evidence of service improvement? each audit project was also scored against the Audit Project Assessment Tool produced by the UK Clinical Governance Support Team. RESULTS: Of the twenty five audit projects reviewed twenty two were considered to be true audits. All of the projects used only retrospective data. Audit projects were contributed from all sections of the multidisciplinary critical care team but there were few truly multidisciplinary projects. Four of the audit projects were re-audits, of these three showed service improvement and one showed deterioration. Of the twenty two true audit projects reviewed, eleven were classified as good quality projects using the Audit Project Assessment Tool. CONCLUSIONS: Despite the clinical audit programme being active and well supported, objective evidence of clinical governance benefit was lacking. The overall clinical audit programme has been revitalised by a series of improvements since undertaking this review and this approach is recommended to other organizations who are interested in improving their clinical audit performance.

Adsorption of insulin onto infusion sets used in adult intensive care unit and neonatal care settings.

INTRODUCTION: Insulin adsorption onto infusion equipment may affect glycaemic control. METHODS: The change in insulin concentration during delivery through tubing employed for adult ICU and neonatal patients was determined using continuous flow UV analysis. RESULTS: Insulin adsorption depended on tubing composition, dimensions and flow rate, being highest for neonatal polyvinylchloride tubing at low flow rates. CONCLUSION: In continuous insulin therapy, we should consider the nature of the infusion set and flow rate.

Improvement in glycemic control and outcome corresponding to intensive insulin therapy protocol development.

BACKGROUND: Intensive insulin therapy (IIT) has been shown to reduce mortality and morbidity in longer stay, critically ill patients. However, this has been demonstrated in a single site, whereas two multicentric studies have been terminated prematurely mainly due to hypoglycemia. Other difficulties with IIT include efficacy of glycemic control. This report describes how IIT can be improved by protocol simplification and removal of glucose supplementation. METHODS: A clinical information system established at each bedspace guided staff through the IIT algorithms. Time spent within predefined glycemic ranges was calculated assuming a linear trend between successive measurements. Three groups were investigated retrospectively: IIT1 protocol,(1) an updated IIT2 version, and intuitive nurse dosing of conventional insulin therapy (CIT). RESULTS: Fifty consecutive, critically ill patients were included in each study group. Patient characteristics were similar in each group. The frequency of CIT and IIT2 blood glucose measurements were 11.6 and 11.5 measurements per day, respectively, while the IIT1 measurements were more frequent (14.5 measurements per day). The mean proportion of time spent in the target glycemic range (4.4-6.1 mmol/liter) was highest in the IIT2 group (34.9%), as compared to the IIT1 (22.9%) and CIT groups (20.3%) (p <.001). Survival at 28 days was 74.5% for IIT2 (highest), 68% for IIT1, and 48% for CIT (p = .02). There were a similar number of those experiencing a severe hypoglycemic event in each group. CONCLUSIONS: IIT protocol optimization was associated with increased glycemic control and improved 28-day survival. The better optimized IIT2 protocol provided tighter control than either the IIT1 or CIT protocol, without increased sampling or incidence of hypoglycemia. The clinical effectiveness of the IIT algorithm appeared to be improved by simplifying the protocol to meet the needs of the critical care unit.

Tight glycaemic control: a prospective observational study of a computerised decision-supported intensive insulin therapy protocol.

INTRODUCTION: A single centre has reported that implementation of an intensive insulin protocol, aiming for tight glycaemic control (blood glucose 4.4 to 6.1 mmol/l), resulted in significant reduction in mortality in longer stay medical and surgical critically ill patients. Our aim was to determine the degree to which tight glycaemic control can be maintained using an intensive insulin therapy protocol with computerized decision support and to identify factors that may be associated with the degree of control. METHODS: At a general adult 22-bed intensive care unit, we implemented an intensive insulin therapy protocol in mechanically ventilated patients, aiming for a target glucose range of 4.4 to 6.1 mmol/l. The protocol was integrated into the computerized information management system by way of a decision support program. The time spent in each predefined blood glucose band was estimated, assuming a linear trend between measurements. RESULTS: Fifty consecutive patients were investigated, involving analysis of 7,209 blood glucose samples, over 9,214 hours. The target tight glycaemic control band (4.4 to 6.1 mmol/l) was achieved for a median of 23.1% of the time that patients were receiving intensive insulin therapy. Nearly half of the time (median 48.5%), blood glucose was within the band 6.2 to 7.99 mmol/l. Univariate analysis revealed that body mass index (BMI), Acute Physiology and Chronic Health Evaluation (APACHE) II score and previous diabetes each explained approximately 10% of the variability in tight glycaemic control. BMI and APACHE II score explained most (27%) of the variability in tight glycaemic control in the multivariate analysis, after adjusting for age and previous diabetes. CONCLUSION: Use of the computerized decision supported intensive insulin therapy protocol did result in achievement of tight glycaemic control for a substantial percentage of each patient's stay, although it did deliver 'normoglycaemia' (4.4 to about 8 mmol/l) for nearly 75% of the time. Tight glycaemic control was difficult to achieve in critically ill patients using this protocol. More sophisticated methods such as continuous blood glucose monitoring with automated insulin and glucose infusion adjustment may be a more effective way to achieve tight glycaemic control. Glycaemia in patients with high BMI and APACHE II scores may be more difficult to control using intensive insulin therapy protocols. Trial registration number 05/Q0505/1.

Medication errors: a prospective cohort study of hand-written and computerised physician order entry in the intensive care unit.

INTRODUCTION: The study aimed to compare the impact of computerised physician order entry (CPOE) without decision support with hand-written prescribing (HWP) on the frequency, type and outcome of medication errors (MEs) in the intensive care unit. METHODS: Details of MEs were collected before, and at several time points after, the change from HWP to CPOE. The study was conducted in a London teaching hospital's 22-bedded general ICU. The sampling periods were 28 weeks before and 2, 10, 25 and 37 weeks after introduction of CPOE. The unit pharmacist prospectively recorded details of MEs and the total number of drugs prescribed daily during the data collection periods, during the course of his normal chart review. RESULTS: The total proportion of MEs was significantly lower with CPOE (117 errors from 2429 prescriptions, 4.8%) than with HWP (69 errors from 1036 prescriptions, 6.7%) (p < 0.04). The proportion of errors reduced with time following the introduction of CPOE (p < 0.001). Two errors with CPOE led to patient harm requiring an increase in length of stay and, if administered, three prescriptions with CPOE could potentially have led to permanent harm or death. Differences in the types of error between systems were noted. There was a reduction in major/moderate patient outcomes with CPOE when non-intercepted and intercepted errors were combined (p = 0.01). The mean baseline APACHE II score did not differ significantly between the HWP and the CPOE periods (19.4 versus 20.0, respectively, p = 0.71). CONCLUSION: Introduction of CPOE was associated with a reduction in the proportion of MEs and an improvement in the overall patient outcome score (if intercepted errors were included). Moderate and major errors, however, remain a significant concern with CPOE.

Pharmacokinetic studies of linezolid and teicoplanin in the critically ill.

OBJECTIVES: To determine the pharmacokinetic characteristics of linezolid and teicoplanin in critically ill patients. PATIENTS AND METHODS: Serum was collected frequently during day 0 and then pre- and 1 h post-dose on days 1, 2, 3, 5, 7 and every third day thereafter during treatment. Serum linezolid concentrations were analysed using HPLC. Serum teicoplanin levels were analysed by fluorescence polarization immunoassay. RESULTS: A two-compartment model was required to characterize linezolid pharmacokinetics (n=28) and account for the accumulation seen after multiple dosing. The estimated clearance was 0.049 +/-0.016 L/h/kg (+/-s.e.m. of estimate). At steady state (dosing interval 12 h), linezolid serum concentrations exceeded the breakpoint of 4 mg/L for 10.88 h (95% CI 10.09-11.66) after a 600 mg dose with an AUC/MIC of 92.4 (95% CI 57.2-127.7). Teicoplanin was best described by a two-compartment model (n=26). The clearance was 4.97+/-1.58 L/h. Serum levels exceeded the breakpoint of 4 mg/L for the entire dosing interval in all subjects (400 mg dose every 12 h) with an AUC/MIC of 399.3 (95% CI 329.6-469.0). However, only four of 14 exceeded trough serum concentrations of 10 mg/L. For both agents, trough levels were similar in those who survived and those who died. CONCLUSIONS: Linezolid dosage at 600 mg every 12 h was adequate in the critically ill without need for adjustment for renal function. For teicoplanin, further study is needed to confirm if a trough of 10 mg/L is associated with a higher rate of cure than 5 mg/L. If so, serum drug assays would be needed to ensure a therapeutic level.