Central venous access devices for the delivery of systemic anticancer therapy (CAVA): a randomised controlled trial.

BACKGROUND: Hickman-type tunnelled catheters (Hickman), peripherally inserted central catheters (PICCs), and totally implanted ports (PORTs) are used to deliver systemic anticancer treatment (SACT) via a central vein. We aimed to compare complication rates and costs of the three devices to establish acceptability, clinical effectiveness, and cost-effectiveness of the devices for patients receiving SACT. METHODS: We did an open-label, multicentre, randomised controlled trial (Cancer and Venous Access [CAVA]) of three central venous access devices: PICCs versus Hickman (non-inferiority; 10% margin); PORTs versus Hickman (superiority; 15% margin); and PORTs versus PICCs (superiority; 15% margin). Adults (aged ≥18 years) receiving SACT (≥12 weeks) for solid or haematological malignancy from 18 oncology units in the UK were included. Four randomisation options were available: Hickman versus PICCs versus PORTs (2:2:1), PICCs versus Hickman (1:1), PORTs versus Hickman (1:1), and PORTs versus PICCs (1:1). Randomisation was done using a minimisation algorithm stratifying by centre, body-mass index, type of cancer, device history, and treatment mode. The primary outcome was complication rate (composite of infection, venous thrombosis, pulmonary embolus, inability to aspirate blood, mechanical failure, and other) assessed until device removal, withdrawal from study, or 1-year follow-up. This study is registered with ISRCTN, ISRCTN44504648. FINDINGS: Between Nov 8, 2013, and Feb 28, 2018, of 2714 individuals screened for eligibility, 1061 were enrolled and randomly assigned, contributing to the relevant comparison or comparisons (PICC vs Hickman n=424, 212 [50%] on PICC and 212 [50%] on Hickman; PORT vs Hickman n=556, 253 [46%] on PORT and 303 [54%] on Hickman; and PORT vs PICC n=346, 147 [42%] on PORT and 199 [58%] on PICC). Similar complication rates were observed for PICCs (110 [52%] of 212) and Hickman (103 [49%] of 212). Although the observed difference was less than 10%, non-inferiority of PICCs was not confirmed (odds ratio [OR] 1·15 [95% CI 0·78-1·71]) potentially due to inadequate power. PORTs were superior to Hickman with a complication rate of 29% (73 of 253) versus 43% (131 of 303; OR 0·54 [95% CI 0·37-0·77]). PORTs were superior to PICCs with a complication rate of 32% (47 of 147) versus 47% (93 of 199; OR 0·52 [0·33-0·83]). INTERPRETATION: For most patients receiving SACT, PORTs are more effective and safer than both Hickman and PICCs. Our findings suggest that most patients receiving SACT for solid tumours should receive a PORT within the UK National Health Service. FUNDING: UK National Institute for Health Research Health Technology Assessment Programme.

Retained port connectors after central venous port removal.

We report three cases where the connector/sleeve, which helps fix the flexible catheter section to a port injection chamber, was inadvertently left in scar tissue during port removal. Concerned patients presented months later with a palpable subcutaneous nodule, near the port site. The nodules were variably imaged with plain X-rays, mammography or ultrasound with the diagnosis correctly made by a surgeon familiar with devices. Two connectors were removed, and one was left in place following discussions with the patient. Prevention, recognition and management of this problem are discussed.

Venous access devices for the delivery of long-term chemotherapy: the CAVA three-arm RCT.

BACKGROUND: Venous access devices are used for patients receiving long-term chemotherapy. These include centrally inserted tunnelled catheters or Hickman-type devices (Hickman), peripherally inserted central catheters (PICCs) and centrally inserted totally implantable venous access devices (PORTs). OBJECTIVES: To evaluate the clinical effectiveness, safety, cost-effectiveness and acceptability of these devices for the central delivery of chemotherapy. DESIGN: An open, multicentre, randomised controlled trial to inform three comparisons: (1) peripherally inserted central catheters versus Hickman, (2) PORTs versus Hickman and (3) PORTs versus peripherally inserted central catheters. Pre-trial and post-trial qualitative research and economic evaluation were also conducted. SETTING: This took place in 18 UK oncology centres. PARTICIPANTS: Adult patients (aged ≥ 18 years) receiving chemotherapy (≥ 12 weeks) for either a solid or a haematological malignancy were randomised via minimisation. INTERVENTIONS: Hickman, peripherally inserted central catheters and PORTs. PRIMARY OUTCOME: A composite of infection (laboratory confirmed, suspected catheter related and exit site infection), mechanical failure, venous thrombosis, pulmonary embolism, inability to aspirate blood and other complications in the intention-to-treat population. RESULTS: Overall, 1061 participants were recruited to inform three comparisons. First, for the comparison of peripherally inserted central catheters (n = 212) with Hickman (n = 212), it could not be concluded that peripherally inserted central catheters were significantly non-inferior to Hickman in terms of complication rate (odds ratio 1.15, 95% confidence interval 0.78 to 1.71). The use of peripherally inserted central catheters compared with Hickman was associated with a substantially lower cost (-£1553) and a small decrement in quality-adjusted life-years gained (-0.009). Second, for the comparison of PORTs (n = 253) with Hickman (n = 303), PORTs were found to be statistically significantly superior to Hickman in terms of complication rate (odds ratio 0.54, 95% confidence interval 0.37 to 0.77). PORTs were found to dominate Hickman with lower costs (-£45) and greater quality-adjusted life-years gained (0.004). This was alongside a lower complications rate (difference of 14%); the incremental cost per complication averted was £1.36. Third, for the comparison of PORTs (n = 147) with peripherally inserted central catheters (n = 199), PORTs were found to be statistically significantly superior to peripherally inserted central catheters in terms of complication rate (odds ratio 0.52, 95% confidence interval 0.33 to 0.83). PORTs were associated with an incremental cost of £2706 when compared with peripherally inserted central catheters and a decrement in quality-adjusted life-years gained (-0.018) PORTs are dominated by peripherally inserted central catheters: alongside a lower complications rate (difference of 15%), the incremental cost per complication averted was £104. The qualitative work showed that attitudes towards all three devices were positive, with patients viewing their central venous access device as part of their treatment and recovery. PORTs were perceived to offer unique psychological benefits, including a greater sense of freedom and less intrusion in the context of personal relationships. The main limitation was the lack of adequate power (54%) in the non-inferiority comparison between peripherally inserted central catheters and Hickman. CONCLUSIONS: In the delivery of long-term chemotherapy, peripherally inserted central catheters should be considered a cost-effective option when compared with Hickman. There were significant clinical benefits when comparing PORTs with Hickman and with peripherally inserted central catheters. The health economic benefits were less clear from the perspective of incremental cost per quality-adjusted life-years gained. However, dependent on the willingness to pay, PORTs may be considered to be cost-effective from the perspective of complications averted. FUTURE WORK: The deliverability of a PORTs service merits further study to understand the barriers to and methods of improving the service. TRIAL REGISTRATION: This trial is registered as ISRCTN44504648. FUNDING: This project was funded by the National Institute for Health Research (NHIR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 47. See the NIHR Journals Library website for further project information.

For patients who need long-term chemotherapy delivered through a vein, there are currently three options: (1) a Hickman-type device, which is a flexible tube (central line) inserted underneath the skin on the chest into a large vein; (2) a peripherally inserted central catheter, which is a long line tube inserted into a vein in the arm and passed through a large vein in the chest; and (3) a totally implantable device, which is a small chamber (accessed externally by a needle) that sits underneath the skin, usually in the chest, and goes into a large vein. The Cancer And Venous Access (CAVA) trial compared these devices in > 1000 patients and looked at complications, quality of life, acceptability and value for money. We found that totally implantable devices halved the risk of complications compared with the other two options (which had similar complication rates to each other). We found that patients' quality of life was similar for all three devices, although a quality-of-life measure specific to these devices showed some emotional and psychological benefits in favour of totally implantable devices. All three devices work, although the totally implantable devices are associated with fewer complications and are less intrusive for patients. In the CAVA trial, we found that totally implantable devices are the most costly device to use, followed by the Hickman-type device, with the peripherally inserted central device being the cheapest. This is partly because of the tendency for totally implantable devices to remain in patients for a longer period of time than the other two options. The costs could potentially be reduced by training nurse-led teams to insert totally implantable devices, as already happens with the other two devices. Totally implantable devices can be considered value for money depending on how people value avoiding complications and the quality-of-life benefits for patients.

Tracheostomy in critically ill patients.

Tracheostomy is performed in about a quarter of ICU patients requiring prolonged mechanical ventilation, weaning from assisted ventilation, airway suction and airway protection. Tracheostomy improves patient comfort compared with standard intubation. Tracheostomy performed early upon ICU admission has not shown survival benefits. Percutaneous dilatational techniques are commonly used because the procedure can be performed at the bedside. Surgical tracheostomy is often reserved for cases with abnormal anatomy or failed percutaneous tracheostomy. It is not known which of the percutaneous techniques is safer in terms of perioperative complications. Ultrasound scanning of the neck and routine endoscopy during the procedure appear to reduce early complications. Decannulation is often delayed and an intensivist-led follow-up may facilitate timely removal of tracheostomy tubes in step down areas or wards.

Hypothesis: is the skin and tissue loss associated with septic purpura fulminans temperature related? Parallels with the anatomical distribution of frostbite.

Purpura fulminans is a life threatening complication of many septic states, most notably meningococcaemia. It can also occur due to congenital deficiency of anticoagulant proteins. The pathophysiology of purpura fulminans is complex and not fully understood, but involves abnormalities of coagulation pathways, damage to vessel walls, and abnormal vasoconstriction which may lead to ischaemia and organ dysfunction. After the acute illness has resolved purpuric lesions may lead to extensive tissue loss and prolonged morbidity. Although vascular beds throughout the body are affected, and lesions can be seen in all areas of the skin, the distribution of permanent lesions is often confined to the peripheries, resulting in amputation of digits, hands and feet, or even limbs. Many pharmacological strategies have been used in attempts to reduce the tissue loss, but as yet none have proved to be consistently safe and effective. The distribution of this tissue loss is remarkably similar to that seen in frostbite, and raises the hypothesis that local temperature may have some contributing effect on the severity of these lesions. Hypothermia is known to be associated with vasoconstriction (in an attempt to preserve core temperature) and abnormalities of coagulation. This generally leads to an anticoagulated state, however the severe vasoconstriction and hypovolaemia associated with the early (pre-resuscitation) phases of acute sepsis results in peripheral skin temperatures approaching ambient. The effect on coagulation at these temperatures is not as well understood, but recent work has suggested increased platelet aggregation, adverse effects on blood rheology and increased intravascular thrombosis at temperatures of 31-34 degrees C. We hypothesise that low temperature leads to worsening of purpuric lesions and that active warming of the peripheries may reduce the tissue loss associated with resolving purpuric illnesses.

A narrative review of long-term central venous access devices for the intensivist.

Long-term central venous access devices are increasingly prevalent and consequently often encountered by intensivists. This review introduces the different types of long-term central venous access devices, outlines their potential utility, examines potential complications associated with their use and outlines an approach to the management of these complications.

Can you justify not using ultrasound guidance for central venous access?

Karakitsos and coworkers, in this journal, reported further compelling evidence on the value of ultrasound in guiding internal jugular vein catheterization. In a large, prospective, randomized study of 900 patients, comparisons were made between patients in whom the procedure was performed using landmark-based techniques and those assigned to ultrasound guidance. The key benefits from use of ultrasound included reduction in needle puncture time, increased overall success rate (100% versus 94%), reduction in carotid puncture (1% versus 11%), reduction in carotid haematoma (0.4% versus 8.4%), reduction in haemothorax (0% versus 1.7%), decreased pneumothorax (0% versus 2.4%) and reduction in catheter-related infection (10% versus 16%). The implications of these findings are discussed, and a compelling case for routine use of ultrasound to guide central venous access is made.

Outcomes following out-of-hospital cardiac arrest: What is the potential for donation after circulatory death?

We conducted a prospective observational study on 100 consecutive patients admitted to intensive care units at Leeds General Infirmary following out-of-hospital cardiac arrest. In the non-survivors, we reviewed their potential for organ donation via donation after circulatory death. Out of the 100 patients, 53 did not survive to hospital discharge. Out of these non-survivors, 13 died very suddenly within the intensive care unit and 3 other patients subsequently died in a general ward following discharge from the intensive care unit. One patient became brainstem dead, with out-of-hospital cardiac arrest secondary to a subarachnoid haemorrhage, rather than a primary cardiac cause. This patient went on to donate via the brain death mode. The remaining 36 patients had treatment withdrawn in the intensive care unit. Of these, 29 were referred to the transplant team for potential donation after circulatory death, and 14 were deemed to be medically suitable for organ donation. However, the families of only seven agreed to proceed with the donation process. Of these seven, only one went on to donate, primarily because the majority did not die within the 3-h window for acceptable warm ischaemia. In this series, the potential for donation after circulatory death following out-of-hospital cardiac arrest was limited. We would suggest an open dialogue between intensive care unit staff and transplant teams about the realistic potential for organ donation in each case. When clinicians believe it is unlikely that donation after circulatory death will proceed due to a failure to die within the pre-requisite time, then not starting with the donation after circulatory death process should be seriously considered.

Development of the UK Vessel Health and Preservation (VHP) framework: a multi-organisational collaborative.

Vascular access is an important part of many patient care management plans but has some unwanted risks. Previous work published by Moureau et al. (2012) inspired a working group led by the UK Infection Prevention Society (IPS) to produce a vessel health and preservation (VHP) framework. This was with the intention of producing a resource for frontline staff to be able to assess and select the best vascular access device to meet the individual patient's needs and to preserve veins for future use. The working group produced a framework that used available evidence, expert opinion and some small scale testing of the components of the framework. The work so far has received positive feedback but further work is required to formally evaluate the VHP framework in clinical practice to measure both staff knowledge and patient outcomes.

Arterial vessels behind the right internal jugular vein with relevance to central venous catheterisation.

During right internal jugular vein cannulation, complications can arise due to transfixion of the posterior wall and damage to other vessels. The risks to the subclavian artery and its branches are less well appreciated than the carotid artery. Example images are lacking in the literature. Using ultrasound and cadaveric studies, we aim to provide clinically relevant images of at-risk vessels posterior to the right internal jugular vein to emphasise their close proximity, and provide strategies to avoid potential complications. Using ultrasound in 24 patients, we found the presence of numerous arterial vessels (excluding the carotid) within 8.0 mm of the posterior wall of the right internal jugular vein at the levels of the mastoid, cricoid and supraclavicular region. Cadaveric dissections further highlighted the close proximity of numerous branches of the subclavian artery. Vulnerable branches of the subclavian artery include the thyrocervical trunk, inferior thyroid and vertebral arteries. More inferior approaches to right internal jugular vein cannulation are likely to put more arterial branches at risk. Higher resolution ultrasound enables visualisation of these arteries prior to cannulation. If identified, measures should be taken to avoid vein transfixion and arterial damage.

Offset of pharmacodynamic effects and safety of remifentanil in intensive care unit patients with various degrees of renal impairment.

INTRODUCTION: This open label, multicentre study was conducted to assess the times to offset of the pharmacodynamic effects and the safety of remifentanil in patients with varying degrees of renal impairment requiring intensive care. METHODS: A total of 40 patients, who were aged 18 years or older and had normal/mildly impaired renal function (estimated creatinine clearance >/= 50 ml/min; n = 10) or moderate/severe renal impairment (estimated creatinine clearance <50 ml/min; n = 30), were entered into the study. Remifentanil was infused for up to 72 hours (initial rate 6-9 microgram/kg per hour), with propofol administered if required, to achieve a target Sedation-Agitation Scale score of 2-4, with no or mild pain. RESULTS: There was no evidence of increased offset time with increased duration of exposure to remifentanil in either group. The time to offset of the effects of remifentanil (at 8, 24, 48 and 72 hours during scheduled down-titrations of the infusion) were more variable and were statistically significantly longer in the moderate/severe group than in the normal/mild group at 24 hours and 72 hours. These observed differences were not clinically significant (the difference in mean offset at 72 hours was only 16.5 min). Propofol consumption was lower with the remifentanil based technique than with hypnotic based sedative techniques. There were no statistically significant differences between the renal function groups in the incidence of adverse events, and no deaths were attributable to remifentanil use. CONCLUSION: Remifentanil was well tolerated, and the offset of pharmacodynamic effects was not prolonged either as a result of renal dysfunction or prolonged infusion up to 72 hours.

Early cuff anchorage for tunneled central venous catheters using a buried absorbable suture.

PURPOSE: Long-term tunneled cuffed central venous catheters (CVC) are widely used for the administration of chemotherapy, parenteral nutrition, and fluids. External migration and displacement of catheters have been reported to occur in 2.4% to 24% of cases, prompting the development of various anchoring strategies. We report an adaptation of previous techniques, where the cuff of a tunneled catheter is prevented from moving outwards by inserting a buried absorbable purse string suture around the catheter. Its effectiveness in catheter fixation has been assessed in a prospective audit. METHODS: The effectiveness of the anchoring suture was assessed in a cohort of 101 oncology chemotherapy patients using specific measurements of catheter movement (Dacron cuff to suture distance, Dacron cuff to exit site distance, and external catheter length), taken at catheter insertion and removal. RESULTS: Catheters were placed in situ for a median of 16 weeks. Displacement was found in 19% to 36% of lines (depending on the specific measurement taken), with a median cuff to exit site movement of 7.5 mm (range 5 to 40 mm) and a median length of external line movement of 10 mm (range 5 to 70 mm). The suture had good cosmetic results. CONCLUSIONS: This is, to our knowledge, the first study to attempt to quantify CVC movement. Our data suggest that this suture technique provides an effective and safe additional strategy for cuffed tunneled CVC fixation.

International evidence-based recommendations on ultrasound-guided vascular access.

PURPOSE: To provide clinicians with an evidence-based overview of all topics related to ultrasound vascular access. METHODS: An international evidence-based consensus provided definitions and recommendations. Medical literature on ultrasound vascular access was reviewed from January 1985 to October 2010. The GRADE and the GRADE-RAND methods were utilised to develop recommendations. RESULTS: The recommendations following the conference suggest the advantage of 2D vascular screening prior to cannulation and that real-time ultrasound needle guidance with an in-plane/long-axis technique optimises the probability of needle placement. Ultrasound guidance can be used not only for central venous cannulation but also in peripheral and arterial cannulation. Ultrasound can be used in order to check for immediate and life-threatening complications as well as the catheter's tip position. Educational courses and training are required to achieve competence and minimal skills when cannulation is performed with ultrasound guidance. A recommendation to create an ultrasound curriculum on vascular access is proposed. This technique allows the reduction of infectious and mechanical complications. CONCLUSIONS: These definitions and recommendations based on a critical evidence review and expert consensus are proposed to assist clinicians in ultrasound-guided vascular access and as a reference for future clinical research.

GALA: an international multicentre randomised trial comparing general anaesthesia versus local anaesthesia for carotid surgery.

BACKGROUND: Patients who have severe narrowing at or near the origin of the internal carotid artery as a result of atherosclerosis have a high risk of ischaemic stroke ipsilateral to the arterial lesion. Previous trials have shown that carotid endarterectomy improves long-term outcomes, particularly when performed soon after a prior transient ischaemic attack or mild ischaemic stroke. However, complications may occur during or soon after surgery, the most serious of which is stroke, which can be fatal. It has been suggested that performing the operation under local anaesthesia, rather than general anaesthesia, may be safer. Therefore, a prospective, randomised trial of local versus general anaesthesia for carotid endarterectomy was proposed to determine whether type of anaesthesia influences peri-operative morbidity and mortality, quality of life and longer term outcome in terms of stroke-free survival. METHODS/DESIGN: A two-arm, parallel group, multicentre randomised controlled trial with a recruitment target of 5000 patients. For entry into the study, in the opinion of the responsible clinician, the patient requiring an endarterectomy must be suitable for either local or general anaesthesia, and have no clear indication for either type. All patients with symptomatic or asymptomatic internal carotid stenosis for whom open surgery is advised are eligible. There is no upper age limit. Exclusion criteria are: no informed consent; definite preference for local or general anaesthetic by the clinician or patient; patient unlikely to be able to co-operate with awake testing during local anaesthesia; patient requiring simultaneous bilateral carotid endarterectomy; carotid endarterectomy combined with another operation such as coronary bypass surgery; and, the patient has been randomised into the trial previously. Patients are randomised to local or general anaesthesia by the central trial office. The primary outcome is the proportion of patients alive, stroke free (including retinal infarction) and without myocardial infarction 30 days post-surgery. Secondary outcomes include the proportion of patients alive and stroke free at one year; health related quality of life at 30 days; surgical adverse events, re-operation and re-admission rates; the relative cost of the two methods of anaesthesia; length of stay and intensive and high dependency bed occupancy. TRIAL REGISTRATION: Current Controlled Trials ISRCTN00525237.

Outcome after admission to ITU following out-of-hospital cardiac arrest: are non-survivors suitable for non-heart-beating organ donation?

We have reviewed retrospective data from two large UK teaching hospitals regarding outcome following out-of-hospital cardiac arrest and the suitability of non-survivors for non-heart-beating organ donation. Patients were selected retrospectively from consecutive admissions from two intensive care units who had presented following out-of-hospital cardiac arrest, to a total of 50 patients in each centre. They had all been resuscitated to achieve a spontaneous cardiac output at the scene, in transit or after arrival in hospital, and required further intensive care support due to cardiovascular, respiratory, or neurological impairment. Eighty-six patients (86%) died in the Intensive Care Unit and only 14 (14%) survived to discharge from the Unit. A further nine (9%) patients died in hospital before discharge home. Four patients (4%) were alive after 6 months and three (3%) were alive after 1 year. Fifty-seven (57%) of patients had active withdrawal of treatment with only four (4%) being potentially suitable for organ procurement having not been excluded because of age, medical history or the length of time to die following withdrawal of treatment. Our results show that only a small increase in donor organs could be potentially achieved from this population. Further work is required to determine whether such patients should be considered as non-heart-beating donors.