Population pharmacokinetics of fluconazole in critically ill patients receiving extracorporeal membrane oxygenation and continuous renal replacement therapy: an ASAP ECMO study.

This multicenter study describes the population pharmacokinetics (PK) of fluconazole in critically ill patients receiving concomitant extracorporeal membrane oxygenation (ECMO) and continuous renal replacement therapy (CRRT) and includes an evaluation of different fluconazole dosing regimens for achievement of target exposure associated with maximal efficacy. Serial blood samples were obtained from critically ill patients on ECMO and CRRT receiving fluconazole. Total fluconazole concentrations were measured in plasma using a validated chromatographic assay. A population PK model was developed and Monte Carlo dosing simulations were performed using Pmetrics in R. The probability of target attainment (PTA) of various dosing regimens to achieve fluconazole area under the curve to minimal inhibitory concentration ratio (AUC0-24/MIC) >100 was estimated. Eight critically ill patients receiving concomitant ECMO and CRRT were included. A two-compartment model including total body weight as a covariate on clearance adequately described the data. The mean (±standard deviation, SD) clearance and volume of distribution were 2.87 ± 0.63 L/h and 15.90 ± 13.29 L, respectively. Dosing simulations showed that current guidelines (initial loading dose of 12 mg/kg then 6 mg/kg q24h) achieved >90% of PTA for a MIC up to 1 mg/L. None of the tested dosing regimens achieved 90% of PTA for MIC above 2 mg/L. Current fluconazole dosing regimen guidelines achieved >90% PTA only for Candida species with MIC <1 mg/L and thus should be only used for Candida-documented infections in critically ill patients receiving concomitant ECMO and CRRT. Total body weight should be considered for fluconazole dose.

Antimicrobial Exposures in Critically Ill Patients Receiving Extracorporeal Membrane Oxygenation.

Rationale: Data suggest that altered antimicrobial concentrations are likely during extracorporeal membrane oxygenation (ECMO). Objectives: The primary aim of this analysis was to describe the pharmacokinetics (PKs) of antimicrobials in critically ill adult patients receiving ECMO. Our secondary aim was to determine whether current antimicrobial dosing regimens achieve effective and safe exposure. Methods: This study was a prospective, open-labeled, PK study in six ICUs in Australia, New Zealand, South Korea, and Switzerland. Serial blood samples were collected over a single dosing interval during ECMO for 11 antimicrobials. PK parameters were estimated using noncompartmental methods. Adequacy of antimicrobial dosing regimens were evaluated using predefined concentration exposures associated with maximal clinical outcomes and minimal toxicity risks. Measurements and Main Results: We included 993 blood samples from 85 patients. The mean age was 44.7 ± 14.4 years, and 61.2% were male. Thirty-eight patients (44.7%) were receiving renal replacement therapy during the first PK sampling. Large variations (coefficient of variation of ⩾30%) in antimicrobial concentrations were seen leading to more than fivefold variations in all PK parameters across all study antimicrobials. Overall, 70 (56.5%) concentration profiles achieved the predefined target concentration and exposure range. Target attainment rates were not significantly different between modes of ECMO and renal replacement therapy. Poor target attainment was observed across the most frequently used antimicrobials for ECMO recipients, including for oseltamivir (33.3%), piperacillin (44.4%), and vancomycin (27.3%). Conclusions: Antimicrobial PKs were highly variable in critically ill patients receiving ECMO, leading to poor target attainment rates. Clinical trial registered with the Australian New Zealand Clinical Trials Registry (ACTRN12612000559819).

Using a LOng peripheral intraVEnous catheter with retractable guidewire to optimize first-insertion success for patients with Difficult IntraVenous Access in the emergency department (LOVE-DIVA): a study protocol for a randomized controlled trial.

INTRODUCTION: First-insertion success rates for peripheral vascular access devices (PVADs) in patients with difficult venous access (DIVA) are low, which negatively affects staff workload, patient experience, and organizational cost. There is mixed evidence regarding the impact of a peripheral vascular access device with retractable coiled tip guidewire (GW; AccuCath™, BD) on the first-insertion success rate. The aim of this study is to investigate whether the use of long GW-PVADs, compared with standard PVADs, reduces the risk of first-time insertion failure, in patients admitted to emergency departments (EDs). METHODS AND ANALYSIS: A parallel-group, two-arm, randomized controlled trial will be carried out in two Australian EDs to compare long GW-PVADs (5.8 cm length) against standard care PVADs (short or long). Patients ≥18 years of age meeting DIVA criteria will be eligible for the trial. The sample size is 203 participants for each arm. Web-based central randomization will be used to ensure allocation concealment. Neither clinicians nor patients can be blinded to treatment allocation. Primary outcome is the first-insertion success rate. Secondary outcomes include the number of insertion attempts, time to insert PVAD, all-cause failure, dwell-time, patient-reported pain, serious adverse events, complications, subsequent vascular access devices required, patient satisfaction, staff satisfaction, and healthcare costs. Differences between the two groups will be analyzed using Cox proportional hazards regression. Cost-effectiveness analysis will also be conducted. Intention-to-treat analysis will be used. ETHICS AND DISSEMINATION: The study is approved by Metro South Ethics Committee (HREC/2022/QMS/82264) and Griffith University (2022/077). The findings will be published in a peer-reviewed journal. TRIAL REGISTRATION: ACTRN12622000299707.

Improving difficult peripheral intravenous access requires thought, training and technology (DART3): a stepped-wedge, cluster randomised controlled trial protocol.

BACKGROUND: Peripheral intravenous catheters (PIVCs) are the most used invasive medical device in healthcare. Yet around half of insertion attempts are unsuccessful leading to delayed medical treatments and patient discomfort of harm. Ultrasound-guided PIVC (USGPIVC) insertion is an evidence-based intervention shown to improve insertion success especially in patients with Difficult IntraVenous Access (BMC Health Serv Res 22:220, 2022), however the implementation in some healthcare settings remains suboptimal. This study aims to co-design interventions that optimise ultrasound guided PIVC insertion in patients with DIVA, implement and evaluate these initiatives and develop scale up activities. METHODS: A stepped-wedge cluster randomized controlled trial will be conducted in three hospitals (two adult, one paediatric) in Queensland, Australia. The intervention will be rolled out across 12 distinct clusters (four per hospital). Intervention development will be guided by Michie's Behavior Change Wheel with the aim to increase local staff capability, opportunity, and motivation for appropriate, sustainable adoption of USGPIVC insertion. Eligible clusters include all wards or departments where > 10 PIVCs/week are typically inserted. All clusters will commence in the control (baseline) phase, then, one cluster per hospital will step up every two months, as feasible, to the implementation phase, where the intervention will be rolled out. Implementation strategies are tailored for each hospital by local investigators and advisory groups, through context assessments, staff surveys, and stakeholder interviews and informed by extensive consumer interviews and consultation. Outcome measures align with the RE-AIM framework including clinical-effectiveness outcomes (e.g., first-time PIVC insertion success for DIVA patients [primary outcome], number of insertion attempts); implementation outcomes (e.g., intervention fidelity, readiness assessment) and cost effectiveness outcomes. The Consolidated Framework for Implementation Research framework will be used to report the intervention as it was implemented; how people participated in and responded to the intervention; contextual influences and how the theory underpinning the intervention was realised and delivered at each site. A sustainability assessment will be undertaken at three- and six-months post intervention. DISCUSSION: Study findings will help define systematic solutions to implement DIVA identification and escalation tools aiming to address consumer dissatisfaction with current PIVC insertion practices. Such actionable knowledge is critical for implementation of scale-up activities. TRIAL REGISTRATION: Prospectively registered (Australian and New Zealand Clinical Trials Registry; ACTRN12621001497897).

Peripheral intravenous catheter securement: An integrative review of contemporary literature around medical adhesive tapes and supplementary securement products.

AIM: To synthesise evidence related to medical adhesive tapes and supplementary securement products for peripheral intravenous catheters in adults, to prevent complications and device failure. DESIGN: Integrative review informed by Whittemore and Knafl and reported in accordance with the PRISMA 2020 statement. DATA SOURCES: The Cochrane Central Register of Controlled Trials, US National Library of Medicine National Institutes of Health, EMBASE/MEDLINE and Cumulative Index to Nursing and Allied Health were searched from 2000-21 September 2020. REVIEW METHODS: Studies enrolling hospitalised participants >16 years with peripheral intravenous catheters secured by medical adhesive tapes, or supplementary products (bandage, splint and sutureless securement device), were eligible. Quality appraisal was performed using Critical Appraisal Skills Program checklists. RESULTS: Nineteen studies met criteria, including 43,683 peripheral intravenous catheters. Quality appraisal identified high or unclear risk of bias in 58% of studies. Nonsterile tape was the most common intervention tested (14 studies), alone or in multiproduct combinations. Nonsterile tape directly over insertion sites was associated with increased PIVC failure and complications. Sutureless securement devices potentially reduce failure and complications. Multiproduct combinations were very common. Practice recommendations regarding other tapes and secondary securement products are challenging, due to conflicting, or lack of, evidence. CONCLUSION: Tapes and secondary securement product evidence are limited, and over half of the studies are of low methodological quality. This review found nonsterile tape was associated with increased failure and complications; multiproduct dressing and securement bundles were prevalent; and significant evidence gaps exist particularly regarding bandages and splints. The results provide nurses with evidence of medical adhesive tapes and supplementary product effectiveness for peripheral intravenous catheter securement, and future research directions to reduce unacceptably high failure and complication rates. Larger rigorously conducted randomised controlled trials are needed to add to current evidence.

Does longer peripheral intravenous catheter length optimise antimicrobial delivery? Protocol for the LEADER study.

BACKGROUND: Hospitalised patients receiving intravenous antimicrobial therapy require a reliable device through which this is delivered. Short peripheral intravenous catheters (PIVCs) are the default device for antimicrobial therapy but up to half fail before therapy completion, leading to suboptimal drug dosing, patient distress from repeated insertions, and increased healthcare costs. This study will investigate the use of long PIVCs to determine if they are more reliable at delivering antimicrobial therapy. METHODS: A two-arm, parallel randomised controlled trial of hospitalised adults requiring at least 3 days of peripherally compatible intravenous antimicrobials. Participants will be randomised to a short (<4 cm) or long (4.5-6.4 cm) PIVC. After interim analysis ( n=70) for feasibility and safety, 192 participants will be recruited. Primary outcome is disruption to antimicrobial administration from all-cause PIVC failure. Secondary outcomes include: number of devices to complete therapy, patient-reported pain and satisfaction, and a cost analysis. Ethical and regulatory approvals have been received.

Population Pharmacokinetics of Vancomycin in Critically Ill Adult Patients Receiving Extracorporeal Membrane Oxygenation (an ASAP ECMO Study).

Our study aimed to describe the population pharmacokinetics (PK) of vancomycin in critically ill patients receiving extracorporeal membrane oxygenation (ECMO), including those receiving concomitant renal replacement therapy (RRT). Dosing simulations were used to recommend maximally effective and safe dosing regimens. Serial vancomycin plasma concentrations were measured and analyzed using a population PK approach on Pmetrics. The final model was used to identify dosing regimens that achieved target exposures of area under the curve (AUC0-24) of 400-700 mg · h/liter at steady state. Twenty-two patients were enrolled, of which 11 patients received concomitant RRT. In the non-RRT patients, the median creatinine clearance (CrCL) was 75 ml/min and the mean daily dose of vancomycin was 25.5 mg/kg. Vancomycin was well described in a two-compartment model with CrCL, the presence of RRT, and total body weight found as significant predictors of clearance and central volume of distribution (Vc). The mean vancomycin renal clearance and Vc were 3.20 liters/h and 29.7 liters respectively, while the clearance for patients on RRT was 0.15 liters/h. ECMO variables did not improve the final covariate model. We found that recommended dosing regimens for critically ill adult patients not on ECMO can be safely and effectively used in those on ECMO. Loading doses of at least 25 mg/kg followed by maintenance doses of 12.5-20 mg/kg every 12 h are associated with a 97-98% probability of efficacy and 11-12% probability of toxicity, in patients with normal renal function. Therapeutic drug monitoring along with reductions in dosing are warranted for patients with renal impairment and those with concomitant RRT. (This study is registered with the Australian New Zealand Clinical Trials Registry [ANZCTR] under number ACTRN12612000559819.).

Effect of infusion set replacement intervals on catheter-related bloodstream infections (RSVP): a randomised, controlled, equivalence (central venous access device)-non-inferiority (peripheral arterial catheter) trial.

BACKGROUND: The optimal duration of infusion set use to prevent life-threatening catheter-related bloodstream infection (CRBSI) is unclear. We aimed to compare the effectiveness and costs of 7-day (intervention) versus 4-day (control) infusion set replacement to prevent CRBSI in patients with central venous access devices (tunnelled cuffed, non-tunnelled, peripherally inserted, and totally implanted) and peripheral arterial catheters. METHODS: We did a randomised, controlled, assessor-masked trial at ten Australian hospitals. Our hypothesis was CRBSI equivalence for central venous access devices and non-inferiority for peripheral arterial catheters (both 2% margin). Adults and children with expected greater than 24 h central venous access device-peripheral arterial catheter use were randomly assigned (1:1; stratified by hospital, catheter type, and intensive care unit or ward) by a centralised, web-based service (concealed before allocation) to infusion set replacement every 7 days, or 4 days. This included crystalloids, non-lipid parenteral nutrition, and medication infusions. Patients and clinicians were not masked, but the primary outcome (CRBSI) was adjudicated by masked infectious diseases physicians. The analysis was modified intention to treat (mITT). This study is registered with the Australian New Zealand Clinical Trials Registry ACTRN12610000505000 and is complete. FINDINGS: Between May 30, 2011, and Dec, 9, 2016, from 6007 patients assessed, we assigned 2944 patients to 7-day (n=1463) or 4-day (n=1481) infusion set replacement, with 2941 in the mITT analysis. For central venous access devices, 20 (1·78%) of 1124 patients (7-day group) and 16 (1·46%) of 1097 patients (4-day group) had CRBSI (absolute risk difference [ARD] 0·32%, 95% CI -0·73 to 1·37). For peripheral arterial catheters, one (0·28%) of 357 patients in the 7-day group and none of 363 patients in the 4-day group had CRBSI (ARD 0·28%, -0·27% to 0·83%). There were no treatment-related adverse events. INTERPRETATION: Infusion set use can be safely extended to 7 days with resultant cost and workload reductions. FUNDING: Australian National Health and Medical Research Council.

Early short course of neuromuscular blocking agents in patients with COVID-19 ARDS: a propensity score analysis.

BACKGROUND: The role of neuromuscular blocking agents (NMBAs) in coronavirus disease 2019 (COVID-19) acute respiratory distress syndrome (ARDS) is not fully elucidated. Therefore, we aimed to investigate in COVID-19 patients with moderate-to-severe ARDS the impact of early use of NMBAs on 90-day mortality, through propensity score (PS) matching analysis. METHODS: We analyzed a convenience sample of patients with COVID-19 and moderate-to-severe ARDS, admitted to 244 intensive care units within the COVID-19 Critical Care Consortium, from February 1, 2020, through October 31, 2021. Patients undergoing at least 2 days and up to 3 consecutive days of NMBAs (NMBA treatment), within 48 h from commencement of IMV were compared with subjects who did not receive NMBAs or only upon commencement of IMV (control). The primary objective in the PS-matched cohort was comparison between groups in 90-day in-hospital mortality, assessed through Cox proportional hazard modeling. Secondary objectives were comparisons in the numbers of ventilator-free days (VFD) between day 1 and day 28 and between day 1 and 90 through competing risk regression. RESULTS: Data from 1953 patients were included. After propensity score matching, 210 cases from each group were well matched. In the PS-matched cohort, mean (± SD) age was 60.3 ± 13.2 years and 296 (70.5%) were male and the most common comorbidities were hypertension (56.9%), obesity (41.1%), and diabetes (30.0%). The unadjusted hazard ratio (HR) for death at 90 days in the NMBA treatment vs control group was 1.12 (95% CI 0.79, 1.59, p = 0.534). After adjustment for smoking habit and critical therapeutic covariates, the HR was 1.07 (95% CI 0.72, 1.61, p = 0.729). At 28 days, VFD were 16 (IQR 0-25) and 25 (IQR 7-26) in the NMBA treatment and control groups, respectively (sub-hazard ratio 0.82, 95% CI 0.67, 1.00, p = 0.055). At 90 days, VFD were 77 (IQR 0-87) and 87 (IQR 0-88) (sub-hazard ratio 0.86 (95% CI 0.69, 1.07; p = 0.177). CONCLUSIONS: In patients with COVID-19 and moderate-to-severe ARDS, short course of NMBA treatment, applied early, did not significantly improve 90-day mortality and VFD. In the absence of definitive data from clinical trials, NMBAs should be indicated cautiously in this setting.

Unnecessary removal of vascular access devices due to suspected infection in Australian intensive care units.

BACKGROUND: Vascular access devices suspected of infection are often removed unnecessarily and frequently require replacement. The aim of this study was to identify the prevalence and economic impact of premature, unnecessary device removal due to suspected infection in adult patients admitted to the intensive care unit. METHODS: Secondary data analysis of a prospectively collected data set detailing central venous catheters and peripheral arterial catheters in 1458 adult patients was conducted in nine Australian intensive care units. Data extracted from the parent database included patient demographics, device, and infection-specific data including the reason for device removal. Cost estimates were based on a recently published review of device utilisation and associated costs in Queensland public hospitals. RESULTS: A total of 6144 central venous catheter days and 4696 arterial catheter days were studied. Median device dwell time was 7.2 (interquartile range: 5.6-9.0) days for central venous catheters and 6.5 (interquartile range: 4.8-8.5) days for arterial catheters. Device removal due to suspected infection occurred at a rate of 25.7 and 15.3 episodes/1000 catheter days in central venous and arterial catheters, respectively. Central venous and arterial catheter-related bloodstream infections occurred at a rate of 1.8 and 0.2 episodes/1000 catheter days, respectively. Central line-associated bloodstream infection occurred at a rate of 3.3 episodes/1000 catheter days. Local central venous and arterial catheter infection occurred at 0.16 and 0.02 episodes/1000 catheter days, respectively. The difference in incidence between devices suspected of infection and those responsible for infection resulted in AUD$67,087 unnecessarily spent on device replacement. CONCLUSIONS: Unnecessary device removal due to suspected infection presents a substantial clinical problem which is costly for the healthcare organisation and time-consuming for clinicians and places the patient at an increased risk of iatrogenic complications. There is a need for robust evidence and clinical practice guidelines to inform clinical decision-making to reduce unnecessary device removal.

Polyhexamethylene biguanide discs versus unmedicated dressings for prevention of central venous catheter-associated infection in the intensive care unit: A pilot randomised controlled trial to assess protocol safety and feasibility.

BACKGROUND: Central venous catheters are prone to infectious complications, affecting morbidity, mortality and healthcare costs. Polyhexamethylene biguanide-impregnated discs at the catheter insertion site may prevent local and bloodstream infection; however, efficacy has not been established in a critical care setting. OBJECTIVE: The objective of this study was to pilot test polyhexamethylene biguanide-impregnated discs compared to standard unmedicated dressings for central venous catheter infection prevention in critically ill patients. METHODS: This was a single-centre pilot randomised controlled trial. Adults admitted to intensive care requiring a central venous catheter for >72 h were eligible. Patients with a current bloodstream infection, concurrent central venous catheter, chlorhexidine or polyhexamethylene biguanide allergy, or sensitive skin were excluded. Patients were randomised to receive standard central venous catheter dressings with/without polyhexamethylene biguanide discs. OUTCOME MEASURES: The primary outcome was feasibility, defined by patient eligibility, recruitment, retention, protocol adherence, missing data, and staff satisfaction. Secondary outcomes included: central line-associated infection; primary bloodstream infection; local infection; skin complications; device/dressing dwell time; serious adverse events, and cost-effectiveness. RESULTS: Of 309 patients screened, 80 participants were recruited with 98% (n = 78) receiving an internal jugular catheter which dwelled for a median of 5 days (interquartile range = 4.0, 6.0). Feasibility criteria were predominantly met (recruitment 88%; retention 100%; protocol fidelity 91%); however, eligibility criteria were not met (32%; most commonly owing to short predicted catheter dwell). Staff acceptability criteria were met, with 83% of staff scoring dressing application and removal ≥7 on a numerical rating scale. There were no central line-associated bloodstream infections and no local infections. Insertion site itch occurred in 4% (control [n = 0], intervention [n = 3]) of participants, while 32% (24/76) reported pain, and 46% (35/76) tenderness. CONCLUSIONS: Polyhexamethylene biguanide discs appear safe for central venous catheter infection prevention. Feasibility of a large efficacy trial was established with some modifications to screening processes. Large, adequately powered randomised controlled trials are needed to test the infection prevention hypotheses.

Population Pharmacokinetics of Piperacillin and Tazobactam in Critically Ill Patients Receiving Extracorporeal Membrane Oxygenation: an ASAP ECMO Study.

Our study aimed to describe the population pharmacokinetics (PK) of piperacillin and tazobactam in patients on extracorporeal membrane oxygenation (ECMO), with and without renal replacement therapy (RRT). We also aimed to use dosing simulations to identify the optimal dosing strategy for these patient groups. Serial piperacillin and tazobactam plasma concentrations were measured with data analyzed using a population PK approach that included staged testing of patient and treatment covariates. Dosing simulations were conducted to identify the optimal dosing strategy that achieved piperacillin target exposures of 50% and 100% fraction of time free drug concentration is above MIC (%fT>MIC) and toxic exposures of greater than 360 mg/liter. The tazobactam target of percentage of time free concentrations of >2 mg/liter was also assessed. Twenty-seven patients were enrolled, of which 14 patients were receiving concurrent RRT. Piperacillin and tazobactam were both adequately described by two-compartment models, with body mass index, creatinine clearance, and RRT as significant predictors of PK. There were no substantial differences between observed PK parameters and published parameters from non-ECMO patients. Based on dosing simulations, a 4.5-g every 6 hours regimen administered over 4 hours achieves high probabilities of efficacy at a piperacillin MIC of 16 mg/liter while exposing patients to a <3% probability of toxic concentrations. In patients receiving ECMO and RRT, a frequency reduction to every 12 hours dosing lowers the probability of toxic concentrations, although this remains at 7 to 9%. In ECMO patients, piperacillin and tazobactam should be dosed in line with standard recommendations for the critically ill.

An appraisal of respiratory system compliance in mechanically ventilated covid-19 patients.

BACKGROUND: Heterogeneous respiratory system static compliance (CRS) values and levels of hypoxemia in patients with novel coronavirus disease (COVID-19) requiring mechanical ventilation have been reported in previous small-case series or studies conducted at a national level. METHODS: We designed a retrospective observational cohort study with rapid data gathering from the international COVID-19 Critical Care Consortium study to comprehensively describe CRS-calculated as: tidal volume/[airway plateau pressure-positive end-expiratory pressure (PEEP)]-and its association with ventilatory management and outcomes of COVID-19 patients on mechanical ventilation (MV), admitted to intensive care units (ICU) worldwide. RESULTS: We studied 745 patients from 22 countries, who required admission to the ICU and MV from January 14 to December 31, 2020, and presented at least one value of CRS within the first seven days of MV. Median (IQR) age was 62 (52-71), patients were predominantly males (68%) and from Europe/North and South America (88%). CRS, within 48 h from endotracheal intubation, was available in 649 patients and was neither associated with the duration from onset of symptoms to commencement of MV (p = 0.417) nor with PaO2/FiO2 (p = 0.100). Females presented lower CRS than males (95% CI of CRS difference between females-males: - 11.8 to - 7.4 mL/cmH2O p < 0.001), and although females presented higher body mass index (BMI), association of BMI with CRS was marginal (p = 0.139). Ventilatory management varied across CRS range, resulting in a significant association between CRS and driving pressure (estimated decrease - 0.31 cmH2O/L per mL/cmH20 of CRS, 95% CI - 0.48 to - 0.14, p < 0.001). Overall, 28-day ICU mortality, accounting for the competing risk of being discharged within the period, was 35.6% (SE 1.7). Cox proportional hazard analysis demonstrated that CRS (+ 10 mL/cm H2O) was only associated with being discharge from the ICU within 28 days (HR 1.14, 95% CI 1.02-1.28, p = 0.018). CONCLUSIONS: This multicentre report provides a comprehensive account of CRS in COVID-19 patients on MV. CRS measured within 48 h from commencement of MV has marginal predictive value for 28-day mortality, but was associated with being discharged from ICU within the same period. Trial documentation: Available at https://www.covid-critical.com/study . TRIAL REGISTRATION: ACTRN12620000421932.

A pilot randomised controlled trial of dressing and securement methods to prevent arterial catheter failure in intensive care.

BACKGROUND: Critically ill patients in an intensive care setting often require arterial catheters for blood pressure monitoring and arterial blood collection. Arterial catheter failure, which manifests in both mechanical and infective forms, remains common. Dressing and securement inadequacies may impact this failure; however, the best method for dressing and securing arterial catheters is yet to be determined. OBJECTIVES: The objective of this study was to establish the feasibility of a definitive randomised controlled trial comparing methods for dressing and securing arterial catheters and to prevent device failure in an adult intensive care setting. METHODS: A pilot, parallel-group, randomised controlled trial was conducted between April 2017 and June 2018. Patients receiving treatment in two adult intensive care units (Queensland, Australia) were eligible for inclusion and were allocated to receive either (i) an integrated securement dressing or (ii) a simple polyurethane dressing (with gauze/foam), applied to their newly inserted arterial catheters. MAIN OUTCOME MEASURES: Primary outcomes were (i) feasibility (defined by pre-established criteria: patient eligibility, consent, protocol adherence, retention, and staff acceptability) and (ii) all-cause arterial catheter failure (a composite of local and bloodstream infection, occlusion, dislodgement, infiltration/extravasation, arterial inflammation, thrombosis, and/or inaccurate trace). Secondary outcomes included: failure type, dwell time, dressing adhesion, adverse event profiles, and staff acceptability. RESULTS: In total, 109 patients were studied (n = 53 integrated securement dressing; n = 56 simple polyurethane). The feasibility criterion was met by most patients (including rates of consent [86%], protocol adherence [93%], and retention [100%]); however, the criteria for patient eligibility were not met (73%). All-cause device failure did not differ significantly between the integrated securement device group (n = 12/53, 23%) and the simple polyurethane group (n = 6/56, 11%) (hazard ratio = 2.39, 95% confidence interval = 0.89-6.37, p = 0.083). CONCLUSIONS: Findings indicate a larger study is feasible, with minor alterations to recruitment methods required. Arterial catheter failure remains unacceptably common; further research to determine optimal dressing/securement practices is urgently needed.

SECUREment bundles to prevent peripheral intravenous catheter failure-the SECURE-PIVC trial: study protocol for a pilot randomized controlled trial.

INTRODUCTION: Peripheral intravenous catheters (PIVCs) are widely used, but failure is unacceptably common with up to 69% failing before treatment is complete. PIVC securement reduces failure, but the optimal way to achieve this is unclear. Tapes and supplementary securement products are widely used, however rigorous testing of these to reduce PIVC failure remains unexplored. METHODS AND ANALYSIS: In adult medical-surgical wards at a tertiary hospital, this pilot randomized controlled trial tests standard care (bordered polyurethane dressing plus nonsterile tape over the extension tubing) against two securement interventions (intervention one: standard care plus two sterile tape strips over the PIVC hub; intervention two: intervention one plus a tubular bandage). Patients >18 years of age requiring a PIVC for >24 hours are eligible. Patients with laboratory-confirmed positive blood cultures within 24 hours of screening, known allergy to study products, current or high-risk of skin tear, or non-English speaking without interpreter are excluded. Sample size is 35 per trial arm, and central randomization is computer-generated with allocation concealed until entry. Patients and clinical staff cannot be blinded to treatment allocation. However, infection outcomes are assessed by a blinded investigator. Primary outcome is study feasibility. Secondary outcomes (PIVC failure, dwell time, skin adverse events, PIVC colonization, and cost) are compared between groups. Feasibility outcomes are reported descriptively. ETHICS AND TRIAL COMMENCEMENT: Ethical approvals were received from Royal Brisbane and Women's Hospital (HREC/18/QRBW/44571) and Griffith University (2018/1000). Trial commencement was May 2019. Trial registration: ACTRN12619000026123.

Dressings and securements for the prevention of peripheral intravenous catheter failure in adults (SAVE): a pragmatic, randomised controlled, superiority trial.

BACKGROUND: Two billion peripheral intravenous catheters (PIVCs) are used globally each year, but optimal dressing and securement methods are not well established. We aimed to compare the efficacy and costs of three alternative approaches to standard non-bordered polyurethane dressings. METHODS: We did a pragmatic, randomised controlled, parallel-group superiority trial at two hospitals in Queensland, Australia. Eligible patients were aged 18 years or older and required PIVC insertion for clinical treatment, which was expected to be required for longer than 24 h. Patients were randomly assigned (1:1:1:1) via a centralised web-based randomisation service using random block sizes, stratified by hospital, to receive tissue adhesive with polyurethane dressing, bordered polyurethane dressing, a securement device with polyurethane dressing, or polyurethane dressing (control). Randomisation was concealed before allocation. Patients, clinicians, and research staff were not masked because of the nature of the intervention, but infections were adjudicated by a physician who was masked to treatment allocation. The primary outcome was all-cause PIVC failure (as a composite of complete dislodgement, occlusion, phlebitis, and infection [primary bloodstream infection or local infection]). Analysis was by modified intention to treat. This trial is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12611000769987. FINDINGS: Between March 18, 2013, and Sept 9, 2014, we randomly assigned 1807 patients to receive tissue adhesive with polyurethane (n=446), bordered polyurethane (n=454), securement device with polyurethane (n=453), or polyurethane (n=454); 1697 patients comprised the modified intention-to-treat population. 163 (38%) of 427 patients in the tissue adhesive with polyurethane group (absolute risk difference -4·5% [95% CI -11·1 to 2·1%], p=0·19), 169 (40%) of 423 of patients in the bordered polyurethane group (-2·7% [-9·3 to 3·9%] p=0·44), 176 (41%) of 425 patients in the securement device with poplyurethane group (-1·2% [-7·9% to 5·4%], p=0·73), and 180 (43%) of 422 patients in the polyurethane group had PIVC failure. 17 patients in the tissue adhesive with polyurethane group, two patients in the bordered polyurethane group, eight patients in the securement device with polyurethane group, and seven patients in the polyurethane group had skin adverse events. Total costs of the trial interventions did not differ significantly between groups. INTERPRETATION: Current dressing and securement methods are commonly associated with PIVC failure and poor durability, with simultaneous use of multiple products commonly required. Cost is currently the main factor that determines product choice. Innovations to achieve effective, durable dressings and securements, and randomised controlled trials assessing their effectiveness are urgently needed. FUNDING: Australian National Health and Medical Research Council.

Complication and Failures of Central Vascular Access Device in Adult Critical Care Settings.

OBJECTIVES: To examine the proportion and rate of central venous access device failure and complications across central venous access device types in adult intensive care. DATA SOURCES: A systematic search was undertaken in the electronic databases Cochrane Central Register of Controlled Trials, Embase, U.S. National Library of Medicine National Institutes of Health, and Cumulative Index to Nursing and Allied Health in September 2017. STUDY SELECTION: Included studies were of observational (prospective and retrospective) or interventional design and reported central venous access device failure and complications in adult ICU settings. Studies were excluded if they were published prior to November 2006 or not reported in English. Two reviewers independently screened articles, assessed eligibility, extracted data, and assessed risk of bias. DATA EXTRACTION: Data were extracted on the primary outcome, central venous access device failure, and secondary outcomes: central venous access device complications (central line-associated bloodstream infection, catheter-related bloodstream infection, catheter-related thrombosis, occlusion, catheter removal due to suspected infection, dislodgement, breakage, and local infection). Patient and device data and study details to assess the study quality were also extracted. DATA SYNTHESIS: A total of 63 studies involving 50,000 central venous access devices (396,951 catheter days) were included. Central venous access device failure was 5% (95% CI, 3-6%), with the highest rates and proportion of failure in hemodialysis catheters. Overall central line-associated bloodstream infection rate was 4.59 per 1,000 catheter days (95% CI, 2.31-6.86), with the highest rate in nontunneled central venous access devices. Removal of central venous access device due to suspected infection was high (17%; 20.4 per 1,000 catheter days; 95% CI, 15.7-25.2). CONCLUSIONS: Central venous access device complications and device failure is a prevalent and significant problem in the adult ICU, leading to substantial patient harm and increased healthcare costs. The high proportion of central venous access devices removed due to suspicion of infection, despite low overall central line-associated bloodstream infection and catheter-related bloodstream infection rates, indicates a need for robust practice guidelines to inform decision-making surrounding removal of central venous access devices suspected of infection.

Developing a minimum dataset for nursing team leader handover in the intensive care unit: A focus group study.

BACKGROUND: Despite increasing demand for structured processes to guide clinical handover, nursing handover tools are limited in the intensive care unit. OBJECTIVES: The study aim was to identify key items to include in a minimum dataset for intensive care nursing team leader shift-to-shift handover. METHODS: This focus group study was conducted in a 21-bed medical/surgical intensive care unit in Australia. Senior registered nurses involved in team leader handovers were recruited. Focus groups were conducted using a nominal group technique to generate and prioritise minimum dataset items. Nurses were presented with content from previous team leader handovers and asked to select which content items to include in a minimum dataset. Participant responses were summarised as frequencies and percentages. RESULTS: Seventeen senior nurses participated in three focus groups. Participants agreed that ISBAR (Identify-Situation-Background-Assessment-Recommendations) was a useful tool to guide clinical handover. Items recommended to be included in the minimum dataset (≥65% agreement) included Identify (name, age, days in intensive care), Situation (diagnosis, surgical procedure), Background (significant event(s), management of significant event(s)) and Recommendations (patient plan for next shift, tasks to follow up for next shift). Overall, 30 of the 67 (45%) items in the Assessment category were considered important to include in the minimum dataset and focused on relevant observations and treatment within each body system. Other non-ISBAR items considered important to include related to the ICU (admissions to ICU, staffing/skill mix, theatre cases) and patients (infectious status, site of infection, end of life plan). Items were further categorised into those to include in all handovers and those to discuss only when relevant to the patient. CONCLUSIONS: The findings suggest a minimum dataset for intensive care nursing team leader shift-to-shift handover should contain items within ISBAR along with unit and patient specific information to maintain continuity of care and patient safety across shift changes.

Are pressure injuries related to skin failure in critically ill patients?

BACKGROUND: Pressure injuries contribute significantly to patient morbidity and healthcare costs. Critically ill patients are a high risk group for pressure injury development and may suffer from skin failure secondary to hypoperfusion. The aim of this study was to report hospital acquired pressure injury incidence in intensive care and non-intensive care patients; and assess the clinical characteristics and outcomes of ICU patients reported as having a hospital acquired pressure injury to better understand patient factors associated with their development in comparison to ward patients. METHODS: The setting for this study was a 630 bed, government funded, tertiary referral teaching hospital. A secondary data analysis was undertaken on all patients with a recorded PI on the hospital's critical incident reporting systems and admitted patient data collection between July 2006 to March 2015. RESULTS: There were a total of 5280 reports in 3860 patients; 726 reports were intensive care patients and 4554 were non-intensive care patients, with severe hospital acquired PI reported in 22 intensive care patients and 54 non-intensive care patients. Pressure injury incidence increased in intensive care patients and decreased in non-intensive care patients over the study period. There were statistically significant differences in the anatomical location of severe hospital acquired pressure injuries between these groups (p=0.008). CONCLUSION: Intensive care patients have greater than 10-fold higher hospital acquired pressure injury incidence rates compared to other hospitalised patients. The predisposition of critically ill patients leaves them susceptible to pressure injury development despite implementation of pressure injury prevention strategies. Skin failure appears to be a significant phenomenon in critically ill patients and is associated with the use of vasoactive agents and support systems such as extra corporeal membrane oxygenation and mechanical ventilation.

High-flow nasal cannulae for respiratory support in adult intensive care patients.

BACKGROUND: High-flow nasal cannulae (HFNC) deliver high flows of blended humidified air and oxygen via wide-bore nasal cannulae and may be useful in providing respiratory support for adult patients experiencing acute respiratory failure in the intensive care unit (ICU). OBJECTIVES: We evaluated studies that included participants 16 years of age and older who were admitted to the ICU and required treatment with HFNC. We assessed the safety and efficacy of HFNC compared with comparator interventions in terms of treatment failure, mortality, adverse events, duration of respiratory support, hospital and ICU length of stay, respiratory effects, patient-reported outcomes, and costs of treatment. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 3), MEDLINE, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), Embase, Web of Science, proceedings from four conferences, and clinical trials registries; and we handsearched reference lists of relevant studies. We conducted searches from January 2000 to March 2016 and reran the searches in December 2016. We added four new studies of potential interest to a list of 'Studies awaiting classification' and will incorporate them into formal review findings during the review update. SELECTION CRITERIA: We included randomized controlled studies with a parallel or cross-over design comparing HFNC use in adult ICU patients versus other forms of non-invasive respiratory support (low-flow oxygen via nasal cannulae or mask, continuous positive airway pressure (CPAP), and bilevel positive airway pressure (BiPAP)). DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for inclusion, extracted data, and assessed risk of bias. MAIN RESULTS: We included 11 studies with 1972 participants. Participants in six studies had respiratory failure, and in five studies required oxygen therapy after extubation. Ten studies compared HFNC versus low-flow oxygen devices; one of these also compared HFNC versus CPAP, and another compared HFNC versus BiPAP alone. Most studies reported randomization and allocation concealment inadequately and provided inconsistent details of outcome assessor blinding. We did not combine data for CPAP and BiPAP comparisons with data for low-flow oxygen devices; study data were insufficient for separate analysis of CPAP and BiPAP for most outcomes. For the primary outcomes of treatment failure (1066 participants; six studies) and mortality (755 participants; three studies), investigators found no differences between HFNC and low-flow oxygen therapies (risk ratio (RR), Mantel-Haenszel (MH), random-effects 0.79, 95% confidence interval (CI) 0.49 to 1.27; and RR, MH, random-effects 0.63, 95% CI 0.38 to 1.06, respectively). We used the GRADE approach to downgrade the certainty of this evidence to low because of study risks of bias and different participant indications. Reported adverse events included nosocomial pneumonia, oxygen desaturation, visits to general practitioner for respiratory complications, pneumothorax, acute pseudo-obstruction, cardiac dysrhythmia, septic shock, and cardiorespiratory arrest. However, single studies reported adverse events, and we could not combine these findings; one study reported fewer episodes of oxygen desaturation with HFNC but no differences in all other reported adverse events. We downgraded the certainty of evidence for adverse events to low because of limited data. Researchers noted no differences in ICU length of stay (mean difference (MD), inverse variance (IV), random-effects 0.15, 95% CI -0.03 to 0.34; four studies; 770 participants), and we downgraded quality to low because of study risks of bias and different participant indications. We found no differences in oxygenation variables: partial pressure of arterial oxygen (PaO2)/fraction of inspired oxygen (FiO2) (MD, IV, random-effects 7.31, 95% CI -23.69 to 41.31; four studies; 510 participants); PaO2 (MD, IV, random-effects 2.79, 95% CI -5.47 to 11.05; three studies; 355 participants); and oxygen saturation (SpO2) up to 24 hours (MD, IV, random-effects 0.72, 95% CI -0.73 to 2.17; four studies; 512 participants). Data from two studies showed that oxygen saturation measured after 24 hours was improved among those treated with HFNC (MD, IV, random-effects 1.28, 95% CI 0.02 to 2.55; 445 participants), but this difference was small and was not clinically significant. Along with concern about risks of bias and differences in participant indications, review authors noted a high level of unexplained statistical heterogeneity in oxygenation effect estimates, and we downgraded the quality of evidence to very low. Meta-analysis of three comparable studies showed no differences in carbon dioxide clearance among those treated with HFNC (MD, IV, random-effects -0.75, 95% CI -2.04 to 0.55; three studies; 590 participants). Two studies reported no differences in atelectasis; we did not combine these findings. Data from six studies (867 participants) comparing HFNC versus low-flow oxygen showed no differences in respiratory rates up to 24 hours according to type of oxygen delivery device (MD, IV, random-effects -1.51, 95% CI -3.36 to 0.35), and no difference after 24 hours (MD, IV, random-effects -2.71, 95% CI -7.12 to 1.70; two studies; 445 participants). Improvement in respiratory rates when HFNC was compared with CPAP or BiPAP was not clinically important (MD, IV, random-effects -0.89, 95% CI -1.74 to -0.05; two studies; 834 participants). Results showed no differences in patient-reported measures of comfort according to oxygen delivery devices in the short term (MD, IV, random-effects 0.14, 95% CI -0.65 to 0.93; three studies; 462 participants) and in the long term (MD, IV, random-effects -0.36, 95% CI -3.70 to 2.98; two studies; 445 participants); we downgraded the certainty of this evidence to low. Six studies measured dyspnoea on incomparable scales, yielding inconsistent study data. No study in this review provided data on positive end-expiratory pressure measured at the pharyngeal level, work of breathing, or cost comparisons of treatment. AUTHORS' CONCLUSIONS: We were unable to demonstrate whether HFNC was a more effective or safe oxygen delivery device compared with other oxygenation devices in adult ICU patients. Meta-analysis could be performed for few studies for each outcome, and data for comparisons with CPAP or BiPAP were very limited. In addition, we identified some risks of bias among included studies, differences in patient groups, and high levels of statistical heterogeneity for some outcomes, leading to uncertainty regarding the results of our analysis. Consequently, evidence is insufficient to show whether HFNC provides safe and efficacious respiratory support for adult ICU patients.