Long term iv access: A narrative review of long-term central venous access devices for the intensivist

02.08.197024.07.2021 by alexxlab

Содержание

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

J Intensive Care Soc. 2018 Aug; 19(3): 236–246.

Anaesthesia and Intensive Care Medicine, Leeds
Teaching Hospital, Leeds, UK

David Moir, Anaesthesia and Intensive Care
Medicine, Leeds Teaching Hospital, Great George Street, Leeds LS1 3EX, UK.
Email: [email protected] article has been cited by other articles in PMC.

Abstract

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.

Keywords: Catheter, catheter complication, catheter infection, central venous catheter, long-term central venous access, thrombosis, vascular access

Introduction

Intensivists are familiar with standard short-term central venous access catheters;
however, they increasingly encounter long-term central venous access devices
(LCVADs). LCVADs are most commonly seen in patients receiving chemotherapy, home
TPN, antimicrobial therapy or haemodialysis. Often dedicated multidisciplinary teams
look after these devices, however in out-of-hours or emergency situations the
intensivist may be required to use or manage problems with LCVADs. Different types
of LCVADs exist and an awareness of how to use them appropriately and how to manage
associated complications is therefore important.

Types of long-term central venous access catheter

LCVADs are usually defined as venous access devices intended to be in place greater
than six weeks.¹ LCVADs include external exiting catheters, which may or may not be tunnelled,
have an anchoring cuff or be totally implanted devices (Ports).

Devices come in multiple variants but functionally can be broadly categorised as:

Single, double or multi-lumen
Small or large bore
Designed for antegrade or retrograde tunnelling
Preformed catheter tips, or tip cut to length
Implanted port or catheter which exits to Luer connector(s) via a skin
incision
Rated as computed tomography (CT)/magnetic resonance imaging (MRI)
pressure infusion compatible (e. g. 325 psi)
Rated for high volume flows suitable for dialysis
Presence of an anchoring cuff

Tunnelled cuffed externally exiting catheters

These catheters exit externally and are most commonly sited on the chest wall.
They have single, double or triple lumens in variable sizes. The anchoring cuff
provides internal fixation once tissue ingrowth occurs. It was previously
believed that the cuffs reduced infection rates, but this has been challenged
over recent years.^2,3 The cuff generally prevents line removal by simple traction
and should be surgically removed by an experienced operator.

Broviac and Hickman type catheters

The Broviac catheter was the prototype from which the Hickman catheter was
developed. The Broviac catheter has a 1 mm internal diameter and allows flow
rates of 25–65 ml/min.⁴ Although originally designed for children, it is frequently used in
adults. Smaller neonatal versions are available. The Hickman catheter has an
internal diameter of 1.6 mm allowing faster flow rates.⁵ Larger devices are also available with double or triple lumens.

Valved catheters

The Groshong catheter is similar in function to Broviac and Hickman
catheters; however, it differs as it has a slit like orifice adjacent to the
distal end which functions as a valve. The valve resists negative
intrathoracic pressure and therefore potential air embolism. Equally the
valve requires a positive pressure for opening. Closure of the valve as the
positive pressure diminishes prevents back flow of venous blood into the
catheter. The valve therefore requires that a pressurised system be used for
the delivery of infusions and may alter the speed of continuous drug
delivery. It also prevents the catheter being used for CVP monitoring. A
Groshong catheter is recognisable by the labelling, blue colour and absence
of an external clamp (an external clamp is found on both Broviac and Hickman
catheters). This technology is being seen in other types of catheter as it
obviates the requirement for external clamps and heparin locks.⁶ Some devices now also have a valve in their Luer hub working on the
same principle. Despite theoretical attractions, valved catheters are more
expensive and overall less widely used.

Long-term central venous vascular access for dialysis and apheresis (e.g.
Tesio lines and Permcaths)

LCVADs may be used in haemodialysis patients without a functioning AV fistula
or graft. They are also less commonly used in haematology patients having
regular red cell exchange or apheresis. These may be two separate catheters,
inserted side-by-side (e.g. Tesio) or a single dual lumen line (e.g.
Permcath). Due to the diameter of the lumens, the catheters are often locked
with high concentration anticoagulants (e.g. heparin 5000 units/ml). The
volume used is variable (depending on catheter length and is stated on the
hub end of the catheter typically around 1. 6 ml). If this heparin is
inadvertently flushed into the circulation, it can cause systemic
anti-coagulation. Protocols for use therefore must involve aspiration of the
locking volume before use. Some centres use thrombolytic agents or
alternative anti-coagulant/anti-microbial solutions (e.g. Taurolock) to lock
lines. A recent Cochrane review of anti-coagulants for preventing central
venous catheter malfunction in haemodialysis patients reported that
recombinant tissue plasminogen was the only locking solution shown to reduce
catheter malfunction when compared to unfractionated heparin; however, this
conclusion was based on the data from a single study.^7,8 There is
some evidence that alternative locking such as citarate solutions or
antibiotic locks may reduce the risk of catheter-related blood stream
infections although further high quality randomized trials are needed.⁷

Non-tunnelled externally exiting catheters

PICCs’ (peripherally inserted central catheters)

PICCs are usually inserted in the upper arm assisted by an external measuring
technique and the aid of an ECG electrode or under fluoroscopy. They are
used in increasing numbers for medium term access after insertion by
non-medical staff in ward environments. Despite being relatively low cost
and straightforward to insert, there is a higher thrombosis and occlusion
rate due to their narrow lumens and reduced flow rates.⁹ With movement of the arm migration rates of up to 9 cm have been documented.¹⁰ This can cause endothelial damage and consequent vessel thrombosis or
cardiac perforation,¹¹ and arrhythmic episodes.^12,13 PICCs do not possess a
cuff and can be removed in a similar manner to standard central lines. They
are traditionally anchored with a suture wing or adhesive device (e.g.
Statlock), but a newer device (SecurAcath) () uses a blunt double Anchor
(also referred to as legs and feet) inserted below the dermis into the
subcutaneous tissue to secure devices. Removal of the legs and feet requires
the base of the SecurAcath to be closed together by compressing the outside
wings and the device can then be lifted out using one of two removal
techniques (see website Interradmedical. com).

The sequence of steps required when removing the SecurAcath
device.

Port catheters

Ports are typically seen or felt on the chest wall or upper arm as a circular
subcutaneous protuberance. They utilise the skin as a natural barrier to
infection and patients can swim and bathe without issue. They have the lowest
infection rates of all long-term central venous catheters, require little in the
way of ongoing care, prolonged flush intervals (three to four weeks) and tend
towards longevity.¹⁴ Each port membrane has a quoted survival of 1000–2000 punctures until it
risks failure but this depends on needle size, operator skill and other factors.
The system requires a non-coring Huber needle () for delivery through the skin,
subcutaneous tissue and membrane into the chamber. The needle can be easily
dislodged interrupting infusions and risking extravasation. Different sizes and
lengths of needles (for different skin fat thicknesses over the port) are
available. In an emergency situation, a standard (orange, blue or green) needle
may be used. The needle is usually left in situ for a period after the port has
been sited due to pain on repeated insertion (most centres cite up to seven
days). The skin will denervate after a period of time, otherwise EMLA cream can
be utilised. Correct needle placement is confirmed by the needle passing through
a high resistance silicone membrane, with a loss or resistance, and then hitting
the metal back wall of the port chamber. Blood should then be able to be
aspirated and easy flushing occurs. Many adults and children have such devices
in permanently or semipermanently, e.g. cancer chemotherapy, those with cystic
fibrosis, life threatening asthma or allergies (for emergency use).

Large double lumen port with 12 Fr catheter (Angiodynamics UK). There
are two separate injection membranes, which are accessed with a
non-coring Huber tip needle. The two lumens can be used at the same
time or the injection site rotated to allow skin recovery.

Utilisation of LCVADs

LCVADs offer a lifeline for treatment or nutrition. Further venous access may be
difficult and all central and peripheral venous sites may have been exhausted.¹⁵ Therefore, the parent team should be consulted regarding catheter use
except in true emergency situations.

LCVADs’ can be used in critical care for the induction of anaesthesia for
intubation and ventilation and the delivery of drugs, fluids and blood products.
Attention to sterility and line care is of paramount importance. The line should
be tested to ensure it is working adequately with ease of aspiration of blood. A
10-ml syringe should be the smallest syringe used for drug delivery (other than
line locks) to reduce the risk of catheter rupture. All lines should be
adequately flushed after use, clamping the line as the last 0.5 ml of fluid is
flushed, to prevent negative pressure from drawing blood into the tip of the catheter.⁶ Not using an existing line may reduce the likelihood of complications;
however, the patients’ wishes as well as the likelihood of successfully
obtaining alternative access have to be considered. LCVADs’ also allow central
venous pressure measurement, with the exception of those with a Groshong valve
or in lines which have developed a fibrin sleeve. The Groshong valve may also
result in the pulsed delivery of infusing fluids, particularly undesirable when
considering vasopressor use. Long-term dialysis lines can be used for
haemofiltration on intensive care to avoid further line insertions.

As ports rely on the blunt needle staying in situ, it is usual practice to
establish further access after emergency use. A dislodged needle runs the risk
of extravasation and unsuccessful delivery of drugs.

A LCVAD may be the only existing venous access in patients requiring contrast
enhanced CT imaging. Radiology traditionally has used peripheral access, as
there are risks associated with contrast medium delivery through central
catheters. Viscous contrast is delivered via an automated powered injector to
ensure adequate high flow rates for imaging; consequently, there is a risk of
catheter fracture leading to extravasation and possibly embolisation. ¹⁶ Increasingly manufacturers are producing LCVADs, which tolerate this delivery.¹⁷ These are identifiable by external labelling which stipulates maximum
acceptable pressure and flow rates, non-standard colour coding and manufacturers
handbooks. In implantable devices, the patient’s case notes will have to be
referred to or alternatively there may be labelling evident on radiographs (an
etched CT label may be seen with X-ray of a port). Most contrast delivery
systems deliver pressures up to 325 Psi and flows up to 10 ml/s.¹⁷ In most instances, discussion with radiology explaining the catheter you
have in situ will allow a risk assessment to be made and reduced pressures may
provide satisfactory imaging.¹⁶ High flow devices like dialysis catheters, even if not CT rated, are
unlikely to rupture due to their wide bores and stiff catheter walls.

Complications and their management

Understanding and recognising potential complications of LCVADs will allow a safe
approach to their management. There are often risks and benefits that must be
weighed up when considering removal of a LCVAD. Whilst line removal may be the only
solution in certain instances, line insertions are not without risk and it is often
prudent to consider whether it is possible, and in the patient’s interest, to try
and salvage an existing line. The immediate complication profile of an LCVAD is
similar to that of short-term central venous lines and should be managed accordingly.¹⁸ Long-term complications can be divided into two broad categories: occlusion
and infection.

Catheter occlusion

This may be due to mechanical causes, precipitation of drugs or parenteral
nutrition, and thrombosis. Catheter occlusion is described as complete when
unable to aspirate or flush, and partial when flushing is still possible
(so-called persistent withdrawal occlusion).

Mechanical causes

Mechanical causes include simply resolved problems such as kinks in the
external portion of a line, clamps left on, tightly placed sutures and
dislodged Huber needles. Other mechanical causes include a suboptimal
catheter tip position, kinking of the intra-luminal portion and pinching.
Catheter tips can abut the vessel wall and this may be seen on a chest
radiograph. Repositioning the patient may relieve the obstruction. If a
tunnelled cuffed line is malpositioned, withdrawal may be difficult and
require a trained expert. If an internal kink has occurred, this may be
managed by re-insertion of a guide wire or repositioning of the line under
fluoroscopic guidance.¹⁹ However, a new line is often required due to the risk of vessel or
catheter damage when repositioning.

Precipitation of medicines and parenteral nutrition

Medicines that are alkaline or acidic in final solution may precipitate in
the catheter and, therefore, it is important that protocols for preparation
and delivery of medicines via a central venous catheter are referred to Lois et al.¹⁹ Parenteral nutrition may leave a lipid residue resulting in blockage
of the lumen. Acidic preparations which precipitate in an alkaline
environment have been treated with 0.1% hypochloric acid and alkaline
preparations, which have precipitated in an acidic environment have been
treated with sodium bicarbonate and sodium hydroxide.^20–22
Ethanol 70% has also been used to clear obstructing lipid emulsion deposits
from parenteral nutrition use; however, these patients may report side
effects in keeping with excess alcohol intake.²²

Pinch off syndrome

Sub-clavicular LCVADs are potentially exposed to shear forces between the
first rib and clavicle. The risk is thought to be higher with more medial
vein punctures (as per landmark techniques) as the catheter passes
anteriorly between the clavicle and first rib before entering the subclavian
vein.^23,24 If repeatedly trapped it then fractures. More
lateral punctures with ultrasound guidance into the axillary vein are
thought to reduce this risk.²⁵ The risk is greater in active patients where repeated intermittent
compression of the catheter risks the complications of line fracture,
extravasation, translocation and embolisation. ²¹ The patient or nursing staff may report a postural effect on the ease
of line use. Notably the catheter more easily aspirates and flushes in the
supine position, with the ipsilateral arm raised than when the patient is
upright. The patient may report infra-clavicular pain as a consequence of
extravasation from a fractured line and inspection, may reveal skin changes
and swelling in this area. A chest X-ray film may demonstrate scalloping of
the catheter²¹ (
and ). If pinch off
syndrome is suspected, then infusions will need to be stopped and the parent
team involved with a view to replacing the line.

Pinch off. Plain X-ray show scalloping in subclavian access.
Hickman line within four days of insertion. Catheter started to
leak and, on removal, a leak was evident with pressurized
injection and catheter occlusion.

Contrast leak from catheter damaged by shear forces between
clavicle and first rib (pinch off).

Extravasation

Extravasation occurs when a drug enters the patients’ soft tissue. The severity
and presentation vary depending on the drug, concentration and volume
extravasated. The typical presentation is pain at the site of extravasation and
overlying skin changes. If untreated, tissue necrosis requiring amputation can
result. Other consequences include infection, complex regional pain syndrome and
loss of limb function. The management will vary depending on the responsible
drug, volume involved and amount of resulting damage, however in all cases the
infusion or injection should be stopped immediately and the site aspirated to
remove as much drug as possible. If a port catheter is being used, the Huber
needle should be removed immediately. Subsequently, the drug should be
identified and guidance sought on specific management.²⁶

External fracture

This is usually due to repeated clamping of a line. If an external line is
fractured, it risks entraining air and therefore should immediately be clamped
proximal to the fracture using artery forceps or similar apparatus. It is
sometimes possible to repair an external fracture by replacing the damaged
portion of the line with a manufacturer’s repair kit. Ports or cuffs can also
erode through the skin and usually require removal and replacement.

Thrombosis

Prevention and identification of this complication is important as it may lead to
catheter-related infection, pulmonary embolus and post thrombotic syndrome.
Catheter-related thrombosis (CRT) is broadly divided into extra-luminal and
intra-luminal.

Extra luminal thrombosis

Fibrin sheath

This is a commonly occurring phenomenon. The sheath may begin to form as
early as 24 h after insertion.²⁷ Sheaths usually initiate at the vessel entry site where there is
endothelial damage and progress towards the tip. They may also initiate more
distally as a result of the catheter rubbing on the endothelial lining of
the vessel. A partial obstruction usually results and staff find difficulty
aspirating as negative pressure sucks the sheath over the catheter tip.
Drugs may collect and mix within the sheath and there is potential for drugs
to backtrack to the skin entry point and consequently extravasate. Fibrin
sheaths can be managed using thrombolytic locks or internal snare techniques
and rarely necessitate catheter removal.²⁸ These can sometimes be seen as a so-called “Ghost” in the vein after
catheter removal ().

Flouroscopy image shows long-term catheter whose tip was
misplaced in the left innominate vein and could not be resited
due to a fibrin sleeve attached to vein wall. The catheter has
been withdrawn so that its tip is in upper SVC (arrow) and
injection of contrast shows a fibrin sleeve full of contrast
(wider than catheter) with leak into the SVC shown by blush of
contrast. The tip of the fibrin sleeve remains in the innominate
vein and will remain in situ post catheter removal to hopefully
be resorbed over time.

Venous thrombosis (CRT)

This may be mural (adhering to the vessel wall and potentially obstructing
the catheter) or a deep venous thrombosis (completely obstructing flow
within the vessel and therefore the catheter). Both typically present
adjacent to the catheter and are collectively termed CRT.

CRT may be asymptomatic, however there are often reports of pain, swelling,
erythema and occlusion of the catheter.²⁹ Patients with malignancy are at particular risk.³⁰ Diagnosis may be confirmed by ultrasonography or contrast imaging.
The thrombotic process may progress to affect central veins such as the SVC
and IVC. The occurrence of progressive central thrombosis, or stenosis,
should be considered when prominent superficial collaterals are visible.
Some local thrombosis around the catheter entry site is very common and does
not warrant anticoagulation unless symptomatic. More extensive or
symptomatic thrombosis usually requires anticoagulation.^31,32
Catheter-directed thrombolysis (CDT) may be considered as heparin and
coumarins have no thrombolytic properties.³³ The catheter should usually remain in situ for the parent team to
assess. Acute SVC obstruction can result from CRT or a catheter inserted
into a stenosed vessel. This may rarely cause airway compromise and, in this
instance, the patient may require intubation and catheter removal.³⁴

Clinically significant pulmonary embolus and post-thrombotic syndrome are
complications of deep vein thrombosis.³⁵ In those with deep vein thrombosis, long-term anticoagulation may be required.³¹ Post-thrombotic syndrome is characterised by chronic oedema, pain and
functional limitation of the affected limb. It is caused by persistent
thrombosis and valvular dysfunction.³⁶ The affected side should be avoided if future venous access is
required.

Various strategies have been utilised to prevent CRT including heparin
impregnated catheters, low dose warfarin³⁷ and heparin administration.³⁸ There is no evidence to support the routine use of these prophylactic
measures in all patients with LCVADs³⁹; however, treatment dose anticoagulation can be considered in
high-risk cases.

Intra-luminal thrombosis

This refers to thrombus formation within the catheter itself. It can present
as a partial or complete obstruction and accounts for 25% of all catheter obstructions.⁴⁰ In order to prevent this, LCVADs are often locked with anticoagulants.⁴¹ The thrombus can be confirmed by ultrasound or venogram if this is
felt necessary. A line blocked by thrombus may be salvaged and most centres
have protocols for the use of thrombolytic agents for this purpose.⁴² If this fails, a guide wire or snare may be used to remove a clot at
the tip of a catheter.

Thrombotic material provides an excellent medium for bacterial growth and
many bacterial species produce thrombogenic proteins, consequently
thrombosis and infection are risk factors for one another.^43,44

Central venous stenoses

Central venous stenosis can become a significant problem for those requiring
LCVADs. The risk of stenosis increases with the length of time a catheter is
used and is consequently higher in those who have had previous LCVADs.
Subclavian catheters pose a higher risk (42%) than internal jugular catheters
(10%) and left-sided catheters carry an increased risk.⁴⁵ Larger calibre lines (such as those used for haemodialysis) are also
thought to increase the risk. Stenoses may be asymptomatic or symptomatic.
Collaterals may be seen on physical examination of the face, arm and torso.
Subclavian stenosis may also cause ipsilateral breast and upper limb swelling
and innominate stenosis can also cause facial swelling. In addition to physical
signs on examination of the patient, blockage or distention and a loss of
variation in venous diameter with respiration on duplex ultrasound scanning
should alert the operator to a potential central stenosis. Central venography is
the diagnostic gold standard,⁴⁶ however CTA and MRA studies may also be helpful in diagnosing central
stenoses. Endovascular intervention including balloon angioplasty and stenting
are the mainstay of treatment, however patients commonly require repeated interventions. ⁴⁶ Venous bypass procedures are rarely performed.

Catheter-related infection

(See EPIC⁴⁷ or USA CDC guidelines for detail beyond the scope of this review.)

Catheter-related infections include exit site, tunnel and catheter-related blood
stream infections (CRBSIs). Exit-site infections usually respond well to wound
management and antibiotics, whereas tunnel infections usually require line
removal and treatment with intravenous antibiotics. CRBSIs’ occur from the skin
puncture site, hub contamination or spread to the catheter from another sight of
infection. A diagnosis of CRBSI can be made from blood cultures taken
peripherally and from the catheter at the same time. Diagnosing a CRBSI does not
require line removal,⁴⁸ and it may be possible to salvage the catheter with antibiotic treatment.
However, catheter salvage does carry the risk of serious complications from
metastatic spread including septic arthritis, osteomyelitis, spinal epidural
abscess and septic emboli. Catheter removal should always be considered in those
with persistent CRBSIs not responding to treatment.⁴⁹

Antibiotic delivery via alternate ports increases the likelihood of clearing a
catheter infection.⁵⁰ If an indwelling port reservoir becomes infected, antibiotics should be
administered via alternative access (unless the Huber needle remains in situ) as
needle introduction may introduce infection into the blood stream.

Prophylactic antibiotics

Locking LVCADs in paediatric and adult oncology patients with a combination
of heparin and vancomycin and the use of prophylactic antibiotics prior to
line insertion appear to reduce the rate of Gram positive infection of these lines.⁵¹ Antibiotic locks may also be considered in patients with repeated
line infections.⁴⁹ There is some evidence that antibiotic line locks and anti-microbial
locking solutions may reduce the risk of CRBSIs; however, there is concern
that their use may increase the risk of antibiotic resistance and that
trials have not adequately assessed their potential harm.⁵² National guidelines for patients, such as those being treated with
haemodialysis, have therefore not recommended their routine use in all patients.⁵³

Removal of LCVAD

LCVADs may require urgent removal due to an unremitting infection and
deteriorating clinical condition. Non-tunnelled LCVADs can be removed
following the same general principles utilised in the removal of standard
short-term central venous lines. Tunnelled catheters with a cuff sited less
than three weeks ago can be removed using the same technique unless
resistance is met when applying gentle traction. Some centres suggest
traction alone can be used to remove the majority of cuffed catheters, but
in our experience, this leads to patient discomfort, snapped catheters and
retained cuffs. If the device had been in beyond three to four weeks or had
additional internal anchoring sutures around the cuff, then removal requires
infiltration of local anaesthetic and a cutdown to free the cuff. A
superficial incision is made just above the cuff followed by blunt
dissection to free the catheter from the surrounding soft tissue (). Ideally the
venous section of catheter is removed prior to any sharp dissection to avoid
cutting the catheter and losing it internally as a catheter embolus (). The cuff
can then be sharp dissected free and removed. The external portion can then
be pulled out from the exit site and the incision closed with appropriate
sutures. Port catheter removal follows similar principles but requires a
larger incision.⁵⁴

Cuffed catheter removal. (a) An incision has been made over the
venous end of the anchoring cuff. Blunt dissection with artery
forceps has allowed the catheter and its covering fibrous sheath
to be brought to the skin surface. A very superficial
longitudinal incision in this sheath reveals the white silicone
catheter. (b) The catheter can be pulled from the sheath and out
from the vein. Pressure is applied to allow clot to block the
tract leading to the vein. (c) The cuff can then be freed with
sharp dissection using small scissors. The concept is to
minimise sharp dissection until the catheter is out of the vein
to avoid catheter damage and loss centrally as a catheter
embolus (see ).

An operator has inadvertently cut though a Hickman line whilst
attempting to dissect out the cuff and has tried to retrieve the
venous section but failed. (a) An image intensifier shows the
proximal cut catheter lying in the subclavian vein. (b) This
image shows the catheter has migrated centrally (embolised)
crossing the tricuspid with its tip in the right ventricle. The
catheter was snared from a femoral vein sheath and removed
intact by interventional radiology. The patient developed
arrhythmias when lying on her left side relieved by turning to
the right.

Summary

LCVADs are increasingly used in a wide range of patients of all age groups
and are therefore more likely to be encountered by intensivists. LCVADs
provide critical access for patients and can enhance their quality of life.
Those working in critical care should therefore be familiar with the
different types of LCVADs and have a good working knowledge of potential
complications and their management. This knowledge will encourage
appropriate use, identification of complications and prevent unnecessary
line removal.

Declaration of conflicting interests

The author(s) declared the following potential conflicts of interest with respect to
the research, authorship, and/or publication of this article: DM declared no
potential conflicts of interest with respect to the research, authorship, and/or
publication of this article. AB has been on the Editorial Board of JICS and has
received consultancy payments from catheter manufacturers in relation to new
devices.

Funding

The author(s) received no financial support for the research, authorship, and/or
publication of this article.

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

J Intensive Care Soc. 2018 Aug; 19(3): 236–246.

Anaesthesia and Intensive Care Medicine, Leeds
Teaching Hospital, Leeds, UK

David Moir, Anaesthesia and Intensive Care
Medicine, Leeds Teaching Hospital, Great George Street, Leeds LS1 3EX, UK.
Email: [email protected] article has been cited by other articles in PMC.