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1.
Cochrane Database Syst Rev ; 6: CD013366, 2024 Jun 28.
Article in English | MEDLINE | ID: mdl-38940297

ABSTRACT

BACKGROUND: Peripherally inserted central catheters (PICCs) facilitate diagnostic and therapeutic interventions in health care. PICCs can fail due to infective and non-infective complications, which PICC materials and design may contribute to, leading to negative sequelae for patients and healthcare systems. OBJECTIVES: To assess the effectiveness of PICC material and design in reducing catheter failure and complications. SEARCH METHODS: The University of Queensland and Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase, and CINAHL databases and the WHO ICTRP and ClinicalTrials.gov trials registers to 16 May 2023. We aimed to identify other potentially eligible trials or ancillary publications by searching the reference lists of retrieved included trials, as well as relevant systematic reviews, meta-analyses, and health technology assessment reports. We contacted experts in the field to ascertain additional relevant information. SELECTION CRITERIA: We included randomised controlled trials (RCTs) evaluating PICC design and materials. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were venous thromboembolism (VTE), PICC-associated bloodstream infection (BSI), occlusion, and all-cause mortality. Secondary outcomes were catheter failure, PICC-related BSI, catheter breakage, PICC dwell time, and safety endpoints. We assessed the certainty of evidence using GRADE. MAIN RESULTS: We included 12 RCTs involving approximately 2913 participants (one multi-arm study). All studies except one had a high risk of bias in one or more risk of bias domain. Integrated valve technology compared to no valve technology for peripherally inserted central catheter design Integrated valve technology may make little or no difference to VTE risk when compared with PICCs with no valve (risk ratio (RR) 0.71, 95% confidence interval (CI) 0.19 to 2.63; I² = 0%; 3 studies; 437 participants; low certainty evidence). We are uncertain whether integrated valve technology reduces PICC-associated BSI risk, as the certainty of the evidence is very low (RR 0.20, 95% CI 0.01 to 4.00; I² = not applicable; 2 studies (no events in 1 study); 257 participants). Integrated valve technology may make little or no difference to occlusion risk when compared with PICCs with no valve (RR 0.86, 95% CI 0.53 to 1.38; I² = 0%; 5 studies; 900 participants; low certainty evidence). We are uncertain whether use of integrated valve technology reduces all-cause mortality risk, as the certainty of evidence is very low (RR 0.85, 95% CI 0.44 to 1.64; I² = 0%; 2 studies; 473 participants). Integrated valve technology may make little or no difference to catheter failure risk when compared with PICCs with no valve (RR 0.80, 95% CI 0.62 to 1.03; I² = 0%; 4 studies; 720 participants; low certainty evidence). We are uncertain whether integrated-valve technology reduces PICC-related BSI risk (RR 0.51, 95% CI 0.19 to 1.32; I² = not applicable; 2 studies (no events in 1 study); 542 participants) or catheter breakage, as the certainty of evidence is very low (RR 1.05, 95% CI 0.22 to 5.06; I² = 20%; 4 studies; 799 participants). Anti-thrombogenic surface modification compared to no anti-thrombogenic surface modification for peripherally inserted central catheter design We are uncertain whether use of anti-thrombogenic surface modified catheters reduces risk of VTE (RR 0.67, 95% CI 0.13 to 3.54; I² = 15%; 2 studies; 257 participants) or PICC-associated BSI, as the certainty of evidence is very low (RR 0.20, 95% CI 0.01 to 4.00; I² = not applicable; 2 studies (no events in 1 study); 257 participants). We are uncertain whether use of anti-thrombogenic surface modified catheters reduces occlusion (RR 0.69, 95% CI 0.04 to 11.22; I² = 70%; 2 studies; 257 participants) or all-cause mortality risk, as the certainty of evidence is very low (RR 0.49, 95% CI 0.05 to 5.26; I² = not applicable; 1 study; 111 participants). Use of anti-thrombogenic surface modified catheters may make little or no difference to risk of catheter failure (RR 0.76, 95% CI 0.37 to 1.54; I² = 46%; 2 studies; 257 participants; low certainty evidence). No PICC-related BSIs were reported in one study (111 participants). As such, we are uncertain whether use of anti-thrombogenic surface modified catheters reduces PICC-related BSI risk (RR not estimable; I² = not applicable; very low certainty evidence). We are uncertain whether use of anti-thrombogenic surface modified catheters reduces the risk of catheter breakage, as the certainty of evidence is very low (RR 0.15, 95% CI 0.01 to 2.79; I² = not applicable; 2 studies (no events in 1 study); 257 participants). Antimicrobial impregnation compared to non-antimicrobial impregnation for peripherally inserted central catheter design We are uncertain whether use of antimicrobial-impregnated catheters reduces VTE risk (RR 0.54, 95% CI 0.05 to 5.88; I² = not applicable; 1 study; 167 participants) or PICC-associated BSI risk, as the certainty of evidence is very low (RR 2.17, 95% CI 0.20 to 23.53; I² = not applicable; 1 study; 167 participants). Antimicrobial-impregnated catheters probably make little or no difference to occlusion risk (RR 1.00, 95% CI 0.57 to 1.74; I² = 0%; 2 studies; 1025 participants; moderate certainty evidence) or all-cause mortality (RR 1.12, 95% CI 0.71 to 1.75; I² = 0%; 2 studies; 1082 participants; moderate certainty evidence). Antimicrobial-impregnated catheters may make little or no difference to risk of catheter failure (RR 1.04, 95% CI 0.82 to 1.30; I² = not applicable; 1 study; 221 participants; low certainty evidence). Antimicrobial-impregnated catheters probably make little or no difference to PICC-related BSI risk (RR 1.05, 95% CI 0.71 to 1.55; I² = not applicable; 2 studies (no events in 1 study); 1082 participants; moderate certainty evidence). Antimicrobial-impregnated catheters may make little or no difference to risk of catheter breakage (RR 0.86, 95% CI 0.19 to 3.83; I² = not applicable; 1 study; 804 participants; low certainty evidence). AUTHORS' CONCLUSIONS: There is limited high-quality RCT evidence available to inform clinician decision-making for PICC materials and design. Limitations of the current evidence include small sample sizes, infrequent events, and risk of bias. There may be little to no difference in the risk of VTE, PICC-associated BSI, occlusion, or mortality across PICC materials and designs. Further rigorous RCTs are needed to reduce uncertainty.


Subject(s)
Catheter-Related Infections , Catheterization, Peripheral , Equipment Design , Equipment Failure , Randomized Controlled Trials as Topic , Venous Thromboembolism , Humans , Catheterization, Peripheral/adverse effects , Catheterization, Peripheral/instrumentation , Catheter-Related Infections/prevention & control , Venous Thromboembolism/prevention & control , Venous Thromboembolism/etiology , Catheter Obstruction , Central Venous Catheters/adverse effects , Cause of Death , Bias , Catheterization, Central Venous/adverse effects , Catheterization, Central Venous/instrumentation , Bacteremia/prevention & control , Bacteremia/etiology
2.
Cochrane Database Syst Rev ; 5: CD013023, 2024 05 23.
Article in English | MEDLINE | ID: mdl-38780138

ABSTRACT

BACKGROUND: Peripheral arterial catheters (ACs) are used in anaesthesia and intensive care settings for blood sampling and monitoring. Despite their importance, ACs often fail, requiring reinsertion. Dressings and securement devices maintain AC function and prevent complications such as infection. OBJECTIVES: To evaluate the effectiveness of peripheral AC dressing and securement devices to prevent failure and complications in hospitalised people. SEARCH METHODS: We searched the Cochrane Wounds Specialised Register, CENTRAL, MEDLINE, Embase, and CINAHL Plus up to 16 May 2023. We also searched ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform up to 16 May 2023. SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing different dressing and securement devices for the stabilisation of ACs in hospitalised people. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials for inclusion, extracted data, and assessed risk of bias using Cochrane's RoB 1 tool. We resolved disagreements by discussion, or by consulting a third review author when necessary. We assessed the certainty of evidence using GRADE. MAIN RESULTS: We included five RCTs with 1228 participants and 1228 ACs. All included studies had high risk of bias in one or more domains. We present the following four comparisons, with the remaining comparisons reported in the main review. Standard polyurethane (SPU) plus tissue adhesive (TA) compared with SPU: we are very uncertain whether use of SPU plus TA impacts rates of AC failure (risk ratio (RR) 0.44, 95% confidence interval (CI) 0.20 to 0.98; I² = 0%; 2 studies, 165 participants; very low-certainty evidence). Neither study (165 participants) reported catheter-related bloodstream infections (CRBSI), thus we are very uncertain whether SPU plus TA impacts on the incidence of CRBSI (very low-certainty evidence). It is very uncertain whether use of SPU plus TA impacts AC dislodgement risk (RR 0.54, 95% CI 0.03 to 9.62; I² = 44%; 2 studies, 165 participants; very low-certainty evidence). We are very uncertain whether use of SPU plus TA impacts AC occlusion rates (RR 1.20, 95% CI 0.37 to 3.91; I² = 3%; 2 studies, 165 participants; very low-certainty evidence). We are very uncertain whether use of SPU plus TA impacts rates of adverse events with few reported events across groups (RR 0.89, 95% CI 0.09 to 8.33; I² = 0%; 2 studies, 165 participants; very low-certainty evidence). Bordered polyurethane (BPU) compared to SPU: we are very uncertain whether use of BPU impacts rates of AC failure (RR 0.67, 95% CI 0.21 to 2.13; 1 study, 60 participants; very low-certainty evidence). BPU may make little or no difference to CRBSI compared to SPU (RR 3.05, 95% CI 0.12 to 74.45; I² = not applicable as 1 study (60 participants) reported 0 events; 2 studies, 572 participants; low-certainty evidence). BPU may make little or no difference to the risk of AC dislodgement compared with SPU (RR 0.75, 95% CI 0.17 to 3.22; I² = 0%; 2 studies, 572 participants; low-certainty evidence). BPU may make little or no difference to occlusion risk compared with SPU (RR 0.80, 95% CI 0.60 to 1.07; I² = 0%; 2 studies, 572 participants; low-certainty evidence). It is very uncertain whether BPU impacts on the risk of adverse events compared with SPU (RR 0.33, 95% CI 0.01 to 7.87; 1 study, 60 participants; very low-certainty evidence). SPU plus sutureless securement devices (SSD) compared to SPU: we are very uncertain whether SPU plus SSD impacts risk of AC failure compared with SPU (RR 0.78, 95% CI 0.40 to 1.52; I² = 0%; 2 studies, 157 participants; very low-certainty evidence). We are very uncertain if SPU plus SSD impacts CRBSI incidence rate with no events in both groups (2 studies, 157 participants; very low-certainty evidence). It is very uncertain whether SPU plus SSD impacts risk of dislodgement (RR 0.14, 95% CI 0.01 to 2.57; I² = not applicable as 1 study (96 participants) reported 0 events; 2 studies, 157 participants; very low-certainty evidence). It is very uncertain whether SPU plus SSD impacts risk of AC occlusion (RR 1.94, 95% CI 0.50 to 7.48; I² = 38%; 2 studies, 157 participants; very low-certainty evidence). We are very uncertain whether SPU plus SSD impacts on the risk of adverse events (RR 1.94, 95% CI 0.19 to 20.24; I² = not applicable as 1 study (96 participants) reported 0 events; 2 studies, 157 participants; very low-certainty evidence). Integrated securement dressings compared to SPU: integrated securement dressings may result in little or no difference in risk of AC failure compared with SPU (RR 1.96, 95% CI 0.80 to 4.84; 1 study, 105 participants; low-certainty evidence); may result in little or no difference in CRBSI incidence with no events reported (1 study, 105 participants; low-certainty evidence); may result in little or no difference in the risk of dislodgement (RR 0.33, 95% CI 0.04 to 3.04; 1 study, 105 participants; low-certainty evidence), may result in little or no difference in occlusion rates with no events reported (1 study, 105 participants; low-certainty evidence), and may result in little or no difference in the risk of adverse events (RR 0.35, 95% CI 0.01 to 8.45; 1 study, 105 participants; low-certainty evidence). AUTHORS' CONCLUSIONS: There is currently limited rigorous RCT evidence available about the relative clinical effectiveness of AC dressing and securement products. Limitations of current evidence include small sample size, infrequent events, and heterogeneous outcome measurements. We found no clear difference in the incidence of AC failure, CRBSI, or adverse events across AC dressing or securement products including SPU, BPU, SSD, TA, and integrated securement products. The limitations of current evidence means further rigorous RCTs are needed to reduce uncertainty around the use of dressing and securement devices for ACs.


Subject(s)
Bandages , Catheter-Related Infections , Catheterization, Peripheral , Polyurethanes , Randomized Controlled Trials as Topic , Humans , Catheterization, Peripheral/adverse effects , Catheterization, Peripheral/instrumentation , Catheter-Related Infections/prevention & control , Bias , Equipment Failure
3.
Aust Crit Care ; 37(1): 34-42, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38142148

ABSTRACT

BACKGROUND: Endotracheal suction is used to maintain endotracheal tube patency. There is limited guidance to inform clinical practice for children with respiratory infections. OBJECTIVE: The objective of this study was to determine whether implementation of a paediatric endotracheal suction appropriate use guideline Paediatric AirWay Suction (PAWS) is associated with an increased use of appropriate and decreased use of inappropriate suction interventions. METHODS: A mixed-method, pre-implementation-post-implementation study was conducted between September 2021 and April 2022. Suction episodes in mechanically ventilated children with a respiratory infection were eligible. Using a structured approach, we implemented the PAWS guideline in a single paediatric intensive care unit. Evaluation included clinical (e.g., suction intervention appropriateness), implementation (e.g., acceptability), and cost outcomes (implementation costs). Associations between implementation of the PAWS guideline and appropriateness of endotracheal suction intervention use were investigated using generalised linear models. RESULTS: Data from 439 eligible suctions were included in the analysis. Following PAWS implementation, inappropriate endotracheal tube intervention use reduced from 99% to 58%, an absolute reduction (AR) of 41% (95% confidence interval [CI]: 25%, 56%). Reductions were most notable for open suction systems (AR: 48%; 95% CI: 30%, 65%), 0.9% sodium chloride use (AR: 23%; 95% CI: 8%, 38%) and presuction and postsuction manual bagging (38%; 95% CI: 16%, 60%, and 86%; 95% CI: 73%, 99%), respectively. Clinicians perceived PAWS as acceptable and suitable for use. CONCLUSIONS: Implementation of endotracheal tube suction appropriate use guidelines in a mixed paediatric intensive care unit was associated with a large reduction in inappropriate suction intervention use in paediatric patients with respiratory infections.


Subject(s)
Respiration, Artificial , Respiratory Tract Infections , Child , Humans , Suction/methods , Intubation, Intratracheal/adverse effects , Sodium Chloride
4.
BMC Health Serv Res ; 23(1): 587, 2023 Jun 07.
Article in English | MEDLINE | ID: mdl-37286977

ABSTRACT

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).


Subject(s)
Hospitals , Technology , Adult , Humans , Child , Australia , Queensland , Treatment Outcome , Randomized Controlled Trials as Topic
5.
Aust Crit Care ; 36(4): 509-514, 2023 Jul.
Article in English | MEDLINE | ID: mdl-36038459

ABSTRACT

OBJECTIVES: We aimed to (i) describe current weaning and extubation practices in children (protocols to identify weaning candidates, spontaneous breathing trials, and other aspects of care such as sedation weaning) and (ii) understand responsibilities for ventilation weaning decisions across Australia and New Zealand (ANZ). METHODS: A cross-sectional survey of ANZ intensive care units who routinely intubate and ventilate children (<18 years) was conducted. We worked with the Australian and New Zealand Intensive Care Society Paediatric Study Group to identify units and potential respondents (senior nurse representative per unit) and to administer questionnaires. Survey questions (n = 35) examined current protocols, practices, unit staffing, and decision-making responsibilities for ventilation weaning and extubation. Open-ended questions examined respondents' experiences of weaning and extubation. RESULTS: A senior nursing respondent from 18/22 intensive care units (82%) completed the survey. Across units, most used sedation assessment tools (88%), and less often, sedation weaning tools (55%). Spontaneous awakening protocols were not used; one unit (5%) reported the use of a spontaneous breathing protocol. Two respondents reported that ventilation weaning protocols (11%) were in use, with 44% of units reporting the use of extubation protocols. Weaning and extubation practices were largely perceived as medically driven, with qualitative data demonstrating a desire from most respondents for greater shared decision-making. CONCLUSION: In ANZ, ventilation weaning and extubation practices are largely medically driven with variation in the use of protocols to support mechanical ventilation weaning and extubation in children. Our findings highlight the importance of future research to determine the impact of greater collaboration of the multidisciplinary team on weaning practices.


Subject(s)
Respiration, Artificial , Ventilator Weaning , Child , Humans , Airway Extubation , Australia , Critical Illness , Cross-Sectional Studies , Intensive Care Units , New Zealand , Surveys and Questionnaires
6.
Aust Crit Care ; 36(4): 499-508, 2023 Jul.
Article in English | MEDLINE | ID: mdl-36117039

ABSTRACT

BACKGROUND/AIM: The objective of this study was to describe current surveillance platforms which support routine quality measurement in paediatric critical care. METHOD: Scoping review. The search strategy consisted of a traditional database and grey literature search as well as expert consultation. Surveillance platforms were eligible for inclusion if they collected measures of quality in critically ill children. RESULTS: The search strategy identified 21 surveillance platforms, collecting 57 unique outcome (70%), process (23%), and structural (7%) quality measures. Hospital-associated infections were the most commonly collected outcome measure across all platforms (n = 11; 52%). In general, case definitions were not harmonised across platforms, with the exception of nationally mandated hospital-associated infections (e.g., central line-associated blood stream infection). Data collection relied on manual coding. Platforms typically did not provide an evidence-based rationale for measures collected, with no identifiable reports of co-designed, consensus-derived measures or consumer involvement in measure selection or prioritisation. CONCLUSIONS: Quality measurement in critically ill children lacks uniformity in definition which limits local and international benchmarking. Current surveillance activities for critically ill children focus heavily on outcome measurement, with process, structural, and patient-reported measures largely overlooked. Long-term outcome measures were not routinely collected. Harmonisation of paediatric intensive care unit quality measures is needed and can be achieved using prioritisation and consensus/co-design methods.


Subject(s)
Critical Illness , Cross Infection , Child , Humans , Critical Care , Intensive Care Units, Pediatric
7.
BMC Health Serv Res ; 22(1): 220, 2022 Feb 17.
Article in English | MEDLINE | ID: mdl-35177041

ABSTRACT

OBJECTIVE: To develop and validate a difficult intravenous access risk assessment and escalation pathway, to increase first time intravenous insertion success in paediatrics. METHODS: Mixed methods underpinned by literature and co-production principles. Iterative development of the instrument was informed through semi-structured interviews and stakeholder workshops. The instrument includes a risk assessment, inserter skill self-assessment, and escalation pathways. Reproducibility, reliability, and acceptability were evaluated in a prospective cohort study at a quaternary paediatric hospital in Australia. RESULTS: Interview data (three parents, nine clinicians) uncovered two themes: i) Recognition of children with DIVA and subsequent escalation is ad hoc and problematic; and ii) Resources and training impact inserter confidence and ability. Three workshops were delivered at monthly intervals (February-April 2020) involving 21 stakeholders culminating in the co-production of the "DIVA Key". The DIVA Key was evaluated between May-December 2020 in 78 children; 156 clinicians. Seventy-eight paired assessments were undertaken with substantial agreement (concordance range = 81.5 to 83.0%) between the assessors. Interrater reliability of the DIVA risk assessment was moderate (kappa = 0.71, 95% CI 0.63-0.80). The DIVA Key predicted multiple insertion attempts for red (high risk) DIVA classification (relative risk ratio 5.7, 95% CI 1.2-27.1; reference low risk). Consumer and clinician satisfaction with DIVA Key was high (median (IQR) = 10 [8-10]; 8 [8-10 respectively). CONCLUSION: The DIVA Key is a straightforward, reliable instrument with inbuilt escalation pathway to support the identification of children with difficult intravenous access.


Subject(s)
Cannula , Catheterization, Peripheral , Administration, Intravenous , Child , Humans , Prospective Studies , Reproducibility of Results
8.
Aust Crit Care ; 35(4): 408-414, 2022 07.
Article in English | MEDLINE | ID: mdl-34373171

ABSTRACT

BACKGROUND: Clinically significant post-traumatic stress symptoms (PTSS) have been reported in up to a quarter of paediatric intensive care unit (PICU) survivors. Ongoing PTSS negatively impacts children's psychological development and physical recovery. However, few data regarding associations between potentially modifiable PICU treatment factors, such as analgosedatives and invasive procedures, and children's PTSS have been reported. OBJECTIVES: We sought to investigate the medical treatment factors associated with children's PTSS after PICU discharge. METHODS: A prospective longitudinal cohort study was conducted in two Australian tertiary referral PICUs. Children aged 2-16 y admitted to the PICU between June 2008 and January 2011 for >8 h and <28 d were eligible for participation. Biometric and clinical data were obtained from medical records. Parents reported their child's PTSS using the Trauma Symptom Checklist for Young Children at 1, 3, 6, and 12 months after discharge. Logistic regression was used to assess potential associations between medical treatment and PTSS. RESULTS: A total of 265 children and their parents participated in the study. In the 12-month period following PICU discharge, 24% of children exhibited clinically elevated PTSS. Median risk of death (Paediatric Index of Mortality 2 [PIM2]) score was significantly higher in the PTSS group (0.31 [IQR 0.14-1.09] v 0.67 [IQR 0.20-1.18]; p = 0.014). Intubation and PICU and hospital length of stay were also significantly associated with PTSS at 1 month, as were midazolam, propofol, and morphine. After controlling for gender, reason for admission, and PIM2 score, only midazolam was significantly and independently associated with PTSS and only at 1 month (adjusted odds ration (aOR) 3.63, 95% CI 1.18, 11.12, p = 0.024). No significant relationship was observed between the use of medications and PTSS after 1 month. CONCLUSIONS: Elevated PTSS were evident in one quarter (24%) of children during the 12 months after PICU discharge. One month after discharge, elevated PTSS were most likely to occur in children who had received midazolam therapy.


Subject(s)
Stress Disorders, Post-Traumatic , Australia , Child , Child, Preschool , Humans , Intensive Care Units, Pediatric , Longitudinal Studies , Midazolam/therapeutic use , Prospective Studies , Stress Disorders, Post-Traumatic/psychology
9.
Aust Crit Care ; 35(6): 661-667, 2022 11.
Article in English | MEDLINE | ID: mdl-34924248

ABSTRACT

OBJECTIVES: Endotracheal suction is an invasive airway clearance technique used in mechanically ventilated children. This article outlines the methods used to develop appropriate use criteria for endotracheal suction interventions in mechanically ventilated paediatric patients. METHODS: The RAND Corporation and University of California, Los Angeles Appropriateness Method was used to develop paediatric appropriate use criteria. This included the following sequential phases of defining scope and key terms, a literature review and synthesis, expert multidisciplinary panel selection, case scenario development, and appropriateness ratings by an interdisciplinary expert panel over two rounds. The panel comprised experts in the fields of paediatric and neonatal intensive care, respiratory medicine, infectious diseases, critical care nursing, implementation science, retrieval medicine, and education. Case scenarios were developed iteratively by interdisciplinary experts and derived from common applications or anticipated intervention uses, as well as from current clinical practice guidelines and results of studies examining interventions efficacy and safety. Scenarios were rated on a scale of 1 (harm outweighs benefit) to 9 (benefit outweighs harm), to define appropriate use (median: 7 to 9), uncertain use (median: 4 to 6), and inappropriate use (median: 1 to 3) of endotracheal suction interventions. Scenarios were than classified as a level of appropriateness. CONCLUSIONS: The RAND Corporation/University of California, Los Angeles Appropriateness Method provides a thorough and transparent method to inform development of the first appropriate use criteria for endotracheal suction interventions in paediatric patients.


Subject(s)
Critical Care Nursing , Respiration, Artificial , Infant, Newborn , Child , Humans , Suction/methods
10.
Paediatr Anaesth ; 31(9): 985-995, 2021 Sep.
Article in English | MEDLINE | ID: mdl-34053159

ABSTRACT

BACKGROUND: The optimal intravenous device for antibiotic administration for children with respiratory disease is uncertain. We assessed the feasibility of a randomized controlled trial comparing midline catheters with peripherally inserted central catheters. METHODS: Prospective, two-arm, feasibility randomized controlled trial in an Australian tertiary, pediatric hospital. Random assignment of 110 children (<18 years) to receive (i) midline catheter and (ii) peripherally inserted central catheters. Primary outcome was feasibility (eligibility, recruitment, retention, protocol adherence, and acceptability), and the primary clinical outcome was general anesthesia requirement for intravenous catheter insertion. SECONDARY OUTCOMES: insertion time, treatment delays, infusion efficiency, device failure, complications, and cost. RESULTS: There was 80% recruitment, 100% retention, no missing data, and high patient/staff acceptability. Mean patient experience assessed on a 0-10 numeric rating scale was 8.0 peripherally inserted central catheters and 9.0 (midline catheters), respectively. Participant eligibility was not achieved (49% of screened patients) and moderate protocol-adherence across groups (89% peripherally inserted central catheters vs. 76% midline catheter). Insertion of midline catheter for pulmonary optimization reduced the requirement for general anesthesia compared to peripherally inserted central catheters (10% vs. 69%; odds ratio = 0.01, 95% confidence interval: 0.00-0.09). Midline catheters failed more frequently (18.1 vs. 5.5 peripherally inserted central catheters per 1000 catheter-days); however, this reduced over trial duration. Midline catheter insertion compared to peripherally inserted central catheters saved AUD$1451 per pulmonary optimization episode. CONCLUSIONS: An efficacy trial is feasible with expanded eligibility criteria and intensive staff training when introducing a new device. Midline catheter for peripherally compatible infusions is acceptable to patients and staff, might negate the need for general anesthesia and results in significant cost savings.


Subject(s)
Catheterization, Central Venous , Catheterization, Peripheral , Central Venous Catheters , Anesthesia, General , Australia , Child , Feasibility Studies , Humans , Prospective Studies
11.
Aust Crit Care ; 34(1): 92-102, 2021 01.
Article in English | MEDLINE | ID: mdl-32763068

ABSTRACT

OBJECTIVE: The objective of this study was to review and critically appraise the evidence for paediatric endotracheal suction interventions. DATA SOURCES: A systematic search for studies was undertaken in the electronic databases CENTRAL, Medline, EMBASE, and EBSCO CINAHL from 2003. STUDY SELECTION: Included studies assessed suction interventions in children (≤18 ys old) receiving mechanical ventilation. The primary outcome was defined a priori as duration of mechanical ventilation. Secondary outcomes included adverse events and measures of gas exchange and lung mechanics. DATA EXTRACTION: Data extraction were performed independently by two reviewers. Study methodological quality was assessed using Cochrane's risk of bias tool for randomised trials or the Newcastle-Ottawa Scale for observational studies. Overall assessment of the certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluations criteria. RESULTS: Overall 17 studies involving 1618 children and more than 21,834 suction episodes were included in the review. The most common intervention theme was suction system (five studies; 29%). All included trials were at unclear or high risk of performance bias due to the inability to blind interventionists. Current evidence suggests that closed suction may maintain arterial saturations, normal saline leads to significant transient desaturation, and lung recruitment applied after suction offers short-term oxygenation benefit. LIMITATIONS: Lack of randomised controlled trials, inconsistencies in populations and interventions across studies, and imprecision and risk of bias in included studies precluded data pooling to provide an estimate of interventions effect. CONCLUSIONS: Based on the results of this integrative review, there is insufficient high-quality evidence to guide practice around suction interventions in mechanically ventilated children.


Subject(s)
Critical Illness , Respiration, Artificial , Child , Evidence-Based Practice , Humans , Saline Solution , Suction
12.
Aust Crit Care ; 34(6): 530-538, 2021 11.
Article in English | MEDLINE | ID: mdl-34052092

ABSTRACT

BACKGROUND/OBJECTIVE: Endotracheal suction is one of the most common and harmful procuedres performed on mechanically ventilated children. The aim of the study was to establish the feasibility of a randomised controlled trial (RCT) examining the effectiveness of normal saline instillation (NSI) and a positive end-expiratory pressure recruitment manoeuvre (RM) with endotracheal suction in the paediatric intensive care unit. METHODS: Pilot 2 × 2 factorial RCT. The study was conducted at a 36-bed tertiary paediatric intensive care unit in Australia. Fifty-eight children aged less than 16 years undergoing tracheal intubation and invasive mechanical ventilation. (i) NSI or no NSI and (ii) RM or no RM with endotracheal suction . The primary outcome was feasibility; secondary outcomes were ventilator-associated pneumonia (VAP), change in end-expiratory lung volume assessed by electrical impedance tomography, dynamic compliance, and oxygen saturation-to-fraction of inspired oxygen (SpO2/FiO2) ratio. RESULTS/FINDINGS: Recruitment, retention, and missing data feasibility criteria were achieved. Eligibility and protocol adherence criteria were not achieved, with 818 patients eligible and 58 enrolled; cardiac surgery was the primary reason for exclusion. Approximately 30% of patients had at least one episode of nonadherence. Children who received NSI had a reduced incidence of VAP; however, this did not reach statistical significance (incidence rate ratio = 0.12, 95% confidence interval = 0.01-1.10; p = 0.06). NSI was associated with a significantly reduced SpO2/FiO2 ratio up to 10 min after suction. RMs were not associated with a reduced VAP incidence (incidence rate ratio = 0.31, 95% confidence interval = 0.05-1.88), but did significantly improve end-expiratory lung volume at 2 and 5 min after suction, dynamic compliance, and SpO2/FiO2 ratio. CONCLUSION: RMs provided short-term improvements in end-expiratory lung volume and oxygenation. NSI with suction led to a reduced incidence of VAP; however, a definitive RCT is needed to test statistical differences. A RCT of study interventions is worthwhile and may be feasible with protocol modifications including the widening of participant eligibility.


Subject(s)
Respiration, Artificial , Saline Solution , Child , Humans , Lung , Positive-Pressure Respiration , Suction
13.
J Paediatr Child Health ; 56(2): 289-297, 2020 Feb.
Article in English | MEDLINE | ID: mdl-31436918

ABSTRACT

AIM: To describe practice evolution, complications and risk factors for multiple insertion attempts and device failure in paediatric central venous access devices (CVADs). METHODS: A paediatric retrospective cohort study using prospectively collected data from CVAD database 2012-2014. Data included were patient (i.e. age, condition), insertion (i.e. indication, device, technique) and removal (complications, dwell). Descriptive statistics and incidence rates were calculated per calendar year and compared. Risk factors for multiple insertion attempts and failure were explored with logistic regression and cox regression, respectively. RESULTS: A total of 1308 CVADs were observed over 273 467 catheter-days in 863 patients. Multiple insertion attempts remained static (14%) and significantly associated with non-haematological oncology (odds ratio 2.19; 95% confidence interval (CI) 1.08-4.43), respiratory (3.71; 1.10-12.5), gastroenterology (4.18; 1.66-10.5) and other (difficult intravenous access) (2.74; 1.27-5.92). CVAD failure decreased from 35% (2012) to 25% (2014), incidence rate from 1.50 (95% CI 1.25-1.80) to 1.28 (1.06-1.54) per 1000 catheter-days. Peripherally inserted CVAD failure was significantly associated with lower body weight (per kilogram decrease, hazard ratio (HR) 1.02; 95% CI 1.00-1.03), cephalic vein (1.62; 1.05-2.62), difficult access (1.92; 1.02-3.73), sub-optimal tip placement (1.69; 1.06-2.69) and gastroenterology diagnosis (2.27; 1.05-4.90). Centrally placed CVAD failure was significantly associated with younger age (per year, HR 1.04; 95% CI 1.00-1.07), tunnelled device (3.38; 2.41-4.73) and gastroenterology diagnosis (1.70; 1.06-2.73). CONCLUSIONS: While advancement in CVAD practices improved overall CVAD insertion and failure outcomes, further improvements and innovation are necessary to ensure improved vessel health and preservation for children requiring CVAD.


Subject(s)
Catheterization, Central Venous , Central Venous Catheters , Catheterization, Central Venous/adverse effects , Central Venous Catheters/adverse effects , Child , Equipment Failure , Humans , Incidence , Retrospective Studies , Risk Factors
14.
J Tissue Viability ; 29(2): 82-90, 2020 May.
Article in English | MEDLINE | ID: mdl-32249091

ABSTRACT

AIM: Evaluate the feasibility of an efficacy randomised control trial (RCT) of paediatric peripheral intravenous catheter (PIVC) securement to prevent failure without resultant skin damage. METHODS: A 3-arm, pilot RCT in an Australian paediatric hospital. Random assignment of 330 children to receive (i) bordered polyurethane dressing (BPU) + non-sterile foam (NSF), (ii) integrated securement dressing (ISD) + sterile foam (SF), or (iii) tissue adhesive (TA)+ NSF. Primary outcomes were feasibility and PIVC failure. Secondary outcomes included: skin/bloodstream infection; occlusion; infiltration; dislodgement; phlebitis; dwell; serious adverse events; acceptability and microbial colonisation of catheter tips, wound site, and foam. RESULTS: Most feasibility outcomes were confirmed; 98% of eligible patients consented, 96% received their allocated dressing and no patients were lost to follow up. Eligilbility feasibility (58%) was not met. 11 randomised patients did not require a PIVC. Of 319 patients receiving a PIVC (20,716 PIVC-hours), a significant reduction in PIVC failure was demonstrated with ISD, 31/107 (29%, p = 0.017) compared to BPU, 47/105 (45%). Although not statistically significant, compared to BPU, TA 34/107 (32%, p = 0.052) was associated with less PIVC failure. On Cox regression, no securement intervention significantly reduced PIVC failure. Older age (HR 0.92; 95% confidence interval [CI] 0.88-0.96; p = <0.01), no infection at baseline (HR 0.51; 95% CI 0.34-0.78) and insertion by vascular access specialist (HR 0.40; 95% CI 0.26-0.64) were significantly associated with reduced failure (p < 0.05). CONCLUSION: ISD and TA had reduced PIVC failure compared to BPU. A large efficacy trial to test statistical differences is feasible and needed.


Subject(s)
Catheterization, Peripheral/instrumentation , Immobilization/methods , Pediatrics/instrumentation , Adolescent , Catheterization, Peripheral/methods , Catheterization, Peripheral/standards , Chi-Square Distribution , Child , Child, Preschool , Female , Humans , Immobilization/standards , Infant , Infant, Newborn , Infusions, Intravenous/instrumentation , Infusions, Intravenous/methods , Infusions, Intravenous/standards , Male , Pediatrics/methods , Pediatrics/standards , Pilot Projects , Queensland , Statistics, Nonparametric
15.
Aust Crit Care ; 33(4): 326-332, 2020 07.
Article in English | MEDLINE | ID: mdl-31201037

ABSTRACT

INTRODUCTION: Peripheral arterial catheters (PAC) are used for haemodynamic monitoring and blood sampling in paediatric critical care. Limited data are available regarding PAC insertion and management practices, and how they relate to device function and failure. This information is necessary to inform future interventional research. OBJECTIVES: The primary objective of this study was to describe PAC insertion and management practices, and associated complications. Secondary objectives were to determine patient and clinical characteristics associated with risk of PAC successful insertion and failure. METHODS: A prospective, observational study was conducted in the anaesthetic department and paediatric intensive care unit of a tertiary paediatric facility. Data were collected on PAC insertion, PAC management and PAC removal. Standard incidence and prevalence were calculated per 1,000 device days. Risk factors for multiple insertions and PAC failure were identified using Cox regression. RESULTS: A total of 100 catheters in 89 children were examined capturing 472 device days. PACs were primarily inserted for blood sampling (78%) in the radial artery (78%) using ultrasound guidance (67%), with 31% inserted on first attempt. Heparin saline solution was used in 82% of devices. Median catheter dwell was 50.6 hours (IQR 24.0 - 158.0), with PAC failure occurring in 19 devices (20%), at a rate of 40.2 per 1000 catheter days (95% CI 25.7 - 63.1). Arm board immobilisation (HR 2.9; 95% CI 1.02-8.02; p = 0.05), higher PIM3 score (HR 1.06; 95% CI 1.03-1.09; p < 0.01) was associated with an increased the risk of PAC failure, and non-2% chlorhexidine antisepsis was associated with a decrease in PAC failure (HR 0.32; 95% CI 0.11-0.96; p = 0.04), in univariate analysis. CONCLUSIONS: PAC insertion is challenging, and failure is common. Prospective clinical trial data is needed to identify high risk patient groups and to develop interventions which optimise practices, thereby reducing failure.


Subject(s)
Catheterization, Peripheral/adverse effects , Catheterization, Peripheral/methods , Intensive Care Units, Pediatric , Child , Child, Preschool , Clinical Audit , Device Removal , Female , Humans , Infant , Infant, Newborn , Male , Prospective Studies , Queensland , Risk Factors , Treatment Failure
16.
Aust Crit Care ; 33(4): 350-357, 2020 07.
Article in English | MEDLINE | ID: mdl-31748181

ABSTRACT

OBJECTIVE: The objective of this study was to determine the incidence of endotracheal tube (ETT) suction-related adverse events (AEs) and to examine associations between AEs and patient and suction characteristics. Secondary objectives were to describe ETT suction practices in an Australian paediatric intensive care unit (PICU). METHODS: A prospective, observational study was undertaken in a mixed cardiac and general PICU. Children were eligible for inclusion if they were intubated and mechanically ventilated. Data on patient and suction variables (indication for ETT suction, number of suction episodes per mechanical ventilation episode, indication for normal saline instillation [NSI] and NSI dose) including potential predictive variables (age, Paediatric Index of Mortality 3 [PIM3], NSI, positive end-expiratory pressure, and hyperoxygenation) were collected. The main outcome variable was a composite measure of any AE. MAIN RESULTS: A total of 955 suction episodes were recorded in 100 children. AEs occurred in 211 (22%) ETT suctions. Suction-related AEs were not associated with age, diagnostic category, or index of mortality score. Desaturation was the most common AE (180 suctions; 19%), with 69% of desaturation events requiring clinician intervention. Univariate logistic regression showed the odds of desaturation decreased as the internal diameter of the ETT increased (odds ratio [OR]: 0.59; 95% confidence interval [CI]: 0.37-0.95; p = 0.028). Multivariable modelling revealed NSI was significantly associated with an increased risk of desaturation (adjusted OR [aOR]: 3.23; 95% CI: 1.99-5.40; p < 0.001) and the occurrence of an AE (aOR: 2.76; 95% CI: 1.74-4.37; p < 0.001). Presuction increases in fraction of inspired oxygen (FiO2) was significantly associated with an increased risk of experiencing an AE (aOR: 2.0; 95% CI: 1.27-3.15; p = 0.003). CONCLUSIONS: ETT suction-related AEs are common and associated with NSI and the requirement for pre-suction increases in FiO2. Clinical trial data are needed to identify high-risk patient groups and to develop interventions which optimise practice and reduce the occurrence of ETT suction-related AEs.


Subject(s)
Intensive Care Units, Pediatric/organization & administration , Intubation, Intratracheal/adverse effects , Suction/adverse effects , Adolescent , Child , Child, Preschool , Female , Humans , Infant , Infant, Newborn , Intubation, Intratracheal/standards , Male , Organizational Policy , Prospective Studies , Suction/standards
17.
Aust Crit Care ; 32(1): 13-19, 2019 01.
Article in English | MEDLINE | ID: mdl-29752213

ABSTRACT

BACKGROUND: The complex nature of the Paediatric Intensive Care Unit (PICU) patient requires the bedside nurse to make rapid, complex decisions regarding endotracheal suction (ETS) interventions. It is not understood what influences nurses' decision making in the context of ETS, however, the actions of the clinician have a direct impact on the efficacy of the ETS event and patient outcomes. OBJECTIVES: To explore and describe the use of normal saline instillation and lung recruitment with paediatric ETS in a cohort of Australian nurses, and to identify factors that influence normal saline use with ETS. METHODS: A descriptive, exploratory study. An evidence-based practice model formed the conceptual basis for the study. Semi-structured interviews were conducted with 12 nurses from an Australian tertiary referral paediatric intensive care unit. Audiotaped interviews were transcribed. Inductive thematic analysis was used to code and analyse the interview data and identify themes. FINDINGS: Data analysis revealed three themes: patient's clinical presentation, clinician judgement and unit practice norms. CONCLUSIONS: Variability in nurses ETS practice was marked. In the absence of evidence based clinical guidelines, nurses relied on knowledge derived from clinical experience and the local setting to guide NSI and LR intervention decisions. Participants reported uncertainty regarding ETS best practice and perceived the lack of research evidence as a barrier to making informed clinical decisions at the bedside. Rigorous research evaluating the safety and efficacy of NSI and LR with ETS is urgently required for patient care; however PICU nurses rely on multiple sources of evidence to inform ETS practice decision.


Subject(s)
Intensive Care Units, Pediatric , Intubation, Intratracheal/nursing , Respiratory Mechanics/physiology , Saline Solution/administration & dosage , Suction/nursing , Adult , Critical Care , Decision Making , Evidence-Based Nursing , Female , Humans , Interviews as Topic , Male , Queensland
18.
Worldviews Evid Based Nurs ; 16(1): 51-59, 2019 Feb.
Article in English | MEDLINE | ID: mdl-30604496

ABSTRACT

BACKGROUND: Internationally, there is a lack of comparative vascular access (VA) data for pediatric clinicians and organizations to benchmark outcomes, evaluate quality initiatives, and improve practice. A VA registry is needed to address these knowledge and data capture gaps. OBJECTIVES: To determine the range and heterogeneity of VA outcome measures or quality indicators reported in randomized controlled trials (RCTs) and clinical registries, to inform development of a homogeneous, reliable, minimum dataset for a pediatric VA registry. METHODS: Scoping review framework. A systematic search for RCTs reporting VA outcomes in pediatrics and neonates was undertaken in the Cochrane library, EMBASE, CINAHL, PubMed, MEDLINE, and EBSCO using a medical subject headings and key words related to VA and pediatrics. We included RCTs of children (0-18 years) reporting any VA outcome. We identified clinical registries reporting VA data in children (0-18) through web-based searches using key words related to VA and clinical or quality registries. Additional registries were identified through peer consultation. The frequency and scope of outcome measures and quality indicators were extracted from trials and registries and evaluated. RESULTS: From 93 RCTs included, 214 different VA measures were reported, reflecting 14 outcome domains. The most commonly reported outcome domains were insertion (44 RCTs; 47%), noninfectious complications (33 RCTs; 35%), and infectious complications (30 RCTs; 32%). Of the 22 registries identified, VA-associated infection was the main quality indicator routinely collected (12 registries; 55%). Outcomes such as mechanical complications and patient-reported outcomes were infrequently collected. LINKING EVIDENCE TO ACTION: Vascular access outcomes reported in pediatric and neonatal RCTs are highly heterogeneous. Internationally, clinical registries currently collect minimal VA data with the exception of infection outcomes. A core dataset of reliable, relevant measures to children and clinicians for VA device quality is needed. This will enable a VA registry that facilitates inter-institutional and international benchmarking.


Subject(s)
Pediatrics/methods , Program Development/methods , Registries , Vascular Access Devices/trends , Humans , Program Development/standards , Quality Indicators, Health Care , Vascular Access Devices/statistics & numerical data
19.
J Infus Nurs ; 47(2): 75-95, 2024.
Article in English | MEDLINE | ID: mdl-38422403

ABSTRACT

Ultrasound-guided insertion of peripheral intravenous catheters (PIVCs) is recommended for patients with difficult intravenous access, but access to ultrasound equipment is often limited to specialty departments. Compact, affordable handheld ultrasound devices are available, but the extent of their clinical adoption and impact on patient outcomes is unknown. This scoping review aimed to explore evidence regarding handheld and pocket ultrasound devices for PIVC insertion. Databases were searched for studies published in English between January 2000 and January 2023 evaluating handheld or pocket ultrasound devices weighing ≤3 kg for PIVC insertion. Data were extracted using standardized forms and summarized using descriptive statistics. Seventeen studies reporting the use of handheld or pocket ultrasound devices were identified. Most studies were conducted in adult inpatient facilities; 3 included pediatrics, and 2 reported out-of-hospital use. Participants with difficult intravenous access featured in 9 studies. Ultrasound training programs were described in 12 studies, with competency defined by number of successful PIVC insertions. Five studies reported clinician and/or patient perspectives. Ultrasound for PIVC insertion is not widely accessible in nonspecialist areas, but more compact and affordable handheld models could provide a solution, especially for patients with difficult access. More research evidence using handheld ultrasound is needed.


Subject(s)
Catheterization , Adult , Humans , Child , Administration, Intravenous , Databases, Factual
20.
J Intensive Care ; 12(1): 12, 2024 Mar 08.
Article in English | MEDLINE | ID: mdl-38459599

ABSTRACT

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.

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