Incidence and risk factors for central venous access device failure in hospitalized adults: A multivariable analysis of 1892 catheters.

BACKGROUND: Central venous access devices (CVADs) allow intravenous therapy, haemodynamic monitoring and blood sampling but many fail before therapy completion. OBJECTIVE: To quantify CVAD failure and complications; and identify risk factors. DESIGNS, SETTINGS AND PARTICIPANTS: Secondary analysis of multicentre randomised controlled trial including patients aged ≥16 years with a non-tunnelled CVAD (NTCVAD), peripherally-inserted central catheter (PICC) or tunnelled CVAD (TCVAD). Primary outcome was incidence of all-cause CVAD failure (central line-associated bloodstream infection [CLABSI], occlusion, accidental dislodgement, catheter fracture, thrombosis, pain). Secondary outcomes were CLABSI, occlusion and dislodgement. Cox regression was used to report time-to-event associations. RESULTS: In 1892 CVADs, all-cause failure occurred in 10.2% of devices: 49 NTCVADs (6.1%); 100 PICCs (13.2%); 44 TCVADs (13.4%). Failure rates for CLABSI, occlusion and dislodgement were 5.3%, 1.8%, and 1.7%, respectively. Independent CLABSI predictors were blood product administration through PICCs (hazard ratio (HR) 2.62, 95% confidence interval (CI) 1.24-5.55); and in TCVADs, one or two lumens, compared with three to four (HR 3.36, 95%CI 1.68-6.71), intravenous chemotherapy (HR 2.96, 95%CI 1.31-6.68), and diabetes (HR 3.25, 95%CI 1.40-7.57). Independent factors protective for CLABSI include antimicrobial NTCVADs (HR 0.23, 95%CI 0.08-0.63) and lipids in TCVADs (HR 0.32, 95%CI 0.14-0.72). NTCVADs inserted at another hospital (HR 7.06, 95%CI 1.48-33.7) and baseline infection in patients with PICCs (HR 2.72, 95%CI 1.08-6.83) were predictors for dislodgement. No independent occlusion predictors were found. Modifiable risk factors were identified for CVAD failure, which occurred for 1-in-10 catheters. Strict infection prevention measures and improved CVAD securement could reduce CLABSI and dislodgement risk.

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.

Exploring clinicians' insertion experience with a new peripheral intravenous catheter in the emergency department.

BACKGROUND: Hospitals frequently introduce new medical devices. However, the process of clinicians adapting to these new vascular access devices has not been well explored. The study aims to explore clinicians' experience with the insertion of a new guidewire peripheral intravenous catheter (PIVC) introduced in the emergency department (ED) setting. METHODS: The study was conducted at two EDs in Queensland, Australia, utilising a qualitative explorative approach. Interviews were conducted with guidewire PIVC inserters, including ED doctors and nurses, and field notes were recorded by research nurses during insertions. Data analysis was performed using inductive content analysis, from which themes emerged. RESULTS: The study compiled interviews from 10 participants and field notes from 191 observation episodes. Five key themes emerged, including diverse experience, barriers related to the learning process, factors influencing insertion success, and recommendations to enhance clinicians' acceptance. These themes suggest that the key to successful adoption by clinicians lies in designing user-friendly devices that align with familiar insertion techniques, facilitating a smooth transfer of learning. CONCLUSION: Clinician adaptation to new devices is vital for optimal patient care. Emergency nurses and doctors prefer simplicity, safety, and familiarity when it comes to new devices. Providing comprehensive device training with diverse training resources, hands-on sessions, and continuous expert support, is likely to enhance clinician acceptance and the successful adoption of new devices in ED settings.

Risk factors for arterial catheter failure and complications during critical care hospitalisation: a secondary analysis of a multisite, randomised trial.

OBJECTIVES: Arterial catheters (ACs) are critical for haemodynamic monitoring and blood sampling but are prone to complications. We investigated the incidence and risk factors of AC failure. METHODS: Secondary analysis of a multi-centre randomised controlled trial (ACTRN 12610000505000). Analysis included a subset of adult intensive care unit patients with an AC. The primary outcome was all-cause device failure. Secondary outcomes were catheter associated bloodstream infection (CABSI), suspected CABSI, occlusion, thrombosis, accidental removal, pain, and line fracture. Risk factors associated with AC failure were investigated using Cox proportional hazards and competing-risk models. RESULTS: Of 664 patients, 173 (26%) experienced AC failure (incidence rate [IR] 37/1000 catheter days). Suspected CABSI was the most common failure type (11%; IR 15.3/1000 catheter days), followed by occlusion (8%; IR 11.9/1,000 catheter days), and accidental removal (4%; IR 5.5/1000 catheter days). CABSI occurred in 16 (2%) patients. All-cause failure and occlusion were reduced with ultrasound-assisted insertion (failure: adjusted hazard ratio [HR] 0.43, 95% CI 0.25, 0.76; occlusion: sub-HR 0.11, 95% CI 0.03, 0.43). Increased age was associated with less AC failure (60-74 years HR 0.63, 95% CI 0.44 to 0.89; 75 + years HR 0.36, 95% CI 0.20, 0.64; referent 15-59 years). Females experienced more occlusion (adjusted sub-HR 2.53, 95% CI 1.49, 4.29), while patients with diabetes had less (SHR 0.15, 95% CI 0.04, 0.63). Suspected CABSI was associated with an abnormal insertion site appearance (SHR 2.71, 95% CI 1.48, 4.99). CONCLUSIONS: AC failure is common with ultrasound-guided insertion associated with lower failure rates. Trial registration Australian New Zealand Clinical Trial Registry (ACTRN 12610000505000); date registered: 18 June 2010.

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.

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).

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.

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).

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.

A pilot randomized controlled trial of securement bundles to reduce peripheral intravenous catheter failure.

BACKGROUND: Peripheral intravenous catheters (PIVCs) are ubiquitous in acute care settings however failure rates are unacceptably high, with around half failing before prescribed treatment is complete. The most effective dressing and securement option to prolong PIVC longevity is unclear. OBJECTIVES: To determine feasibility of conducting a definitive randomized controlled trial (RCT) investigating evidence-based securement bundles (medical adhesive tapes and supplementary securement products) to reduce PIVC failure. METHODS: In this pilot non-masked 3-group RCT, adults requiring a PIVC for >24 hrs were randomized to Standard care (bordered polyurethane dressing plus non-sterile tape over extension tubing), Securement Bundle 1 (two sterile tape strips over PIVC hub plus Standard care) or Securement Bundle 2 (Bundle 1 plus tubular bandage) with allocation concealed until study entry. EXCLUSIONS: laboratory-confirmed positive blood culture, current/high-risk of skin tear, or study product allergy. PRIMARY OUTCOME: feasibility (eligibility, recruitment, retention, protocol fidelity, participant/staff satisfaction). SECONDARY OUTCOMES: PIVC failure, PIVC dwell time, adverse skin events, PIVC colonization and cost. RESULTS: Of 109 randomized participants, 104 were included in final analyses. Feasibility outcomes were met, except eligibility criterion (79%). Absolute PIVC failure was 38.2% (13/34) for Bundle 2, 25% (9/36) for Bundle 1 and 23.5% (8/34) for Standard care. Incidence rate ratio for PIVC failure/1000 catheter days, compared to Standard care, was 1.1 (95% confidence interval [CI] 0.4-2.7) and 2.1 (95% CI 0.9-5.1) for Bundles 1 and 2, respectively. CONCLUSIONS: A large RCT testing securement bundles is feasible, with adjustment to screening processes. Innovative dressing and securement solutions are needed to reduce unacceptable PIVC failure rates. Trial registration ACTRN12619000026123.

Securing jugular central venous access devices with dressings fixed to a liquid adhesive in an intensive care unit population: a randomised controlled trial.

BACKGROUND: Central venous access devices (CVADs) can have high rates of failure due to dressing-related complications. CVADs placed in the internal jugular vein are at particular risk of dressing failure-related complications, including catheter-associated bloodstream infection and medical adhesive-related skin injury. Application of Mastisol liquid adhesive (MLA) may reduce CVAD dressing failure and associated complications, by reducing the frequency of dressing changes. The aim of this study is to investigate whether, in an intensive care unit (ICU) population, standard dressing care with or without the addition of MLA, improves internal jugular CVAD dressing adherence. METHODS: This two-arm, parallel group randomised controlled trial will be conducted in three Australian ICUs. A total of 160 patients (80 per group) will be enrolled in accordance with study inclusion and exclusion criteria. Patients will be randomised to receive either (1) 'standard' (in accordance with local hospital policy) CVAD dressings (control) or (2) 'standard' dressings in addition to MLA (intervention). Patients will be followed from the time of CVAD insertion to 48 h after CVAD removal. The primary outcome is 'dressing failure' defined as requirement for initial CVAD dressing to be replaced prior to seven days (routine replacement). DISCUSSION: This study will be the first randomised controlled trial to evaluate the clinical effectiveness of MLA in the adult intensive care unit population and will also provide crucial data for patient-important outcomes such as infection and skin injury. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12621001012864 . Registered on 2 August 2021.

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.

Population pharmacokinetics of ciprofloxacin in critically ill patients receiving extracorporeal membrane oxygenation (an ASAP ECMO study).

INTRODUCTION: This study aimed to describe the pharmacokinetics (PK) of ciprofloxacin in critically ill patients receiving ECMO and recommend a dosing regimen that provides adequate drug exposure. METHODS: Serial blood samples were taken from ECMO patients receiving ciprofloxacin. Total ciprofloxacin concentrations were measured by chromatographic assay and analysed using a population PK approach with Pmetrics®. Dosing simulations were performed to ascertain the probability of target attainment (PTA) represented by the area under the curve to minimum inhibitory concentration ratio (AUC0-24/MIC) ≥ 125. RESULTS: Eight patients were enrolled, of which three received concurrent continuous venovenous haemodiafiltration (CVVHDF). Ciprofloxacin was best described in a two-compartment model with total body weight and creatinine clearance (CrCL) included as significant predictors of PK. Patients not requiring renal replacement therapy generated a mean clearance of 11.08 L/h while patients receiving CVVHDF had a mean clearance of 1.51 L/h. Central and peripheral volume of distribution was 77.31 L and 90.71 L, respectively. ECMO variables were not found to be significant predictors of ciprofloxacin PK. Dosing simulations reported that a 400 mg 8 -hly regimen achieved > 72% PTA in all simulated patients with CrCL of 30 mL/min, 50 mL/min and 100 mL/min and total body weights of 60 kg and 100 kg at a MIC of 0.5 mg/L. CONCLUSION: Our study reports that established dosing recommendations for critically ill patients not on ECMO provides sufficient drug exposure for maximal ciprofloxacin activity for ECMO patients. In line with non-ECMO critically ill adult PK studies, higher doses and therapeutic drug monitoring may be required for critically ill adult patients on ECMO.

Population Pharmacokinetics and Dosing Simulations of Ceftriaxone in Critically Ill Patients Receiving Extracorporeal Membrane Oxygenation (An ASAP ECMO Study).

BACKGROUND: Despite the surge in use of extracorporeal membrane oxygenation (ECMO) in the adult intensive care unit, little guidance is available on the appropriate dosing of antimicrobials in this setting. Ceftriaxone is an antimicrobial with a high affinity to plasma protein, a property identified in the literature as susceptible to sequestration into extracorporeal circuits and hypothesised to require dosage adjustments in this setting. OBJECTIVE: The aim of this study was to describe the pharmacokinetics of ceftriaxone and identify the best dosing regimen for critically ill adult patients receiving ECMO. METHODS: Serial blood samples were taken from patients receiving both ECMO and ceftriaxone. Total and unbound drug concentrations were measured in plasma by chromatographic assay and analysed using a population pharmacokinetic approach with Pmetrics®. Dosing simulations were performed to identify the optimal dosing strategy: 60 and 100% of time with free (unbound) drug concentration exceeding the minimum inhibitory concentration (fT>MIC). RESULTS: In total, 14 patients were enrolled, of which three were receiving renal replacement therapy (RRT). Total and unbound ceftriaxone was best described in a two-compartment model with total body weight, serum albumin concentrations, creatinine clearance (CrCL), and the presence of RRT included as significant predictors of pharmacokinetics. Patients not on RRT generated a mean renal clearance of 0.90 L/h, non-renal clearance of 0.33 L/h, and central volume of distribution of 7.94 L. Patients on RRT exhibited a mean total clearance of 1.18 L/h. ECMO variables were not significant predictors of ceftriaxone pharmacokinetics. Steady-state dosing simulations found that dosages of 1 g every 12 h and 2 g every 24 h achieved >90% probabilities of target attainment in patients with CrCL of 0 mL/min with RRT and 30 and 100 mL/min and various serum albumin concentrations (17 and 26 g/L). CONCLUSIONS: Dosing recommendations for critically ill adult patients not on ECMO appear to be sufficient for patients on ECMO. Patients exhibiting augmented renal clearance (> 130 mL/min) or treatment of less susceptible pathogens may require higher doses, which requires further investigation.

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.

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.).

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.

Assessment of 28-Day In-Hospital Mortality in Mechanically Ventilated Patients With Coronavirus Disease 2019: An International Cohort Study.

Factors associated with mortality in coronavirus disease 2019 patients on invasive mechanical ventilation are still not fully elucidated. OBJECTIVES: To identify patient-level parameters, readily available at the bedside, associated with the risk of in-hospital mortality within 28 days from commencement of invasive mechanical ventilation or coronavirus disease 2019. DESIGN SETTING AND PARTICIPANTS: Prospective observational cohort study by the global Coronavirus Disease 2019 Critical Care Consortium. Patients with laboratory-confirmed coronavirus disease 2019 requiring invasive mechanical ventilation from February 2, 2020, to May 15, 2021. MAIN OUTCOMES AND MEASURES: Patient characteristics and clinical data were assessed upon ICU admission, the commencement of invasive mechanical ventilation and for 28 days thereafter. We primarily aimed to identify time-independent and time-dependent risk factors for 28-day invasive mechanical ventilation mortality. RESULTS: One-thousand five-hundred eighty-seven patients were included in the survival analysis; 588 patients died in hospital within 28 days of commencing invasive mechanical ventilation (37%). Cox-regression analysis identified associations between the hazard of 28-day invasive mechanical ventilation mortality with age (hazard ratio, 1.26 per 10-yr increase in age; 95% CI, 1.16-1.37; p < 0.001), positive end-expiratory pressure upon commencement of invasive mechanical ventilation (hazard ratio, 0.81 per 5 cm H2O increase; 95% CI, 0.67-0.97; p = 0.02). Time-dependent parameters associated with 28-day invasive mechanical ventilation mortality were serum creatinine (hazard ratio, 1.28 per doubling; 95% CI, 1.15-1.41; p < 0.001), lactate (hazard ratio, 1.22 per doubling; 95% CI, 1.11-1.34; p < 0.001), Paco2 (hazard ratio, 1.63 per doubling; 95% CI, 1.19-2.25; p < 0.001), pH (hazard ratio, 0.89 per 0.1 increase; 95% CI, 0.8-14; p = 0.041), Pao2/Fio2 (hazard ratio, 0.58 per doubling; 95% CI, 0.52-0.66; p < 0.001), and mean arterial pressure (hazard ratio, 0.92 per 10 mm Hg increase; 95% CI, 0.88-0.97; p = 0.003). CONCLUSIONS AND RELEVANCE: This international study suggests that in patients with coronavirus disease 2019 on invasive mechanical ventilation, older age and clinically relevant variables monitored at baseline or sequentially during the course of invasive mechanical ventilation are associated with 28-day invasive mechanical ventilation mortality hazard. Further investigation is warranted to validate any causative roles these parameters might play in influencing clinical outcomes.