Central venous catheter infection for infants ( excluding neonates on the NICU ) and children - Guidelines for the management of suspected

Publication: 31/12/2010  --
Last review: 09/01/2020  
Next review: 09/01/2023  
Clinical Guideline
CURRENT 
ID: 2165 
Approved By: Improving Antimicrobial Prescribing Group 
Copyright© Leeds Teaching Hospitals NHS Trust 2020  

 

This Clinical Guideline is intended for use by healthcare professionals within Leeds unless otherwise stated.
For healthcare professionals in other trusts, please ensure that you consult relevant local and national guidance.

Guidelines for the management of suspected central venous catheter infection for infants (excluding neonates on the Neonatal Intensive Care Unit (NICU)) and children

Summary
Central venous catheter infection for infants ( excluding neonates on the NICU ) and children

Intravascular catheter-related infections affecting long-term vascular access devices include exit site, “tunnel” infections and bloodstream infection; these are collectively known as Catheter Related Blood Stream Infections (CRBSI).

History & Examination

  • Clinical diagnoses of line infections are unreliable
  • CRBSI usually presents with a fever or other signs of a systemic inflammatory response.
    • Rigors, chills or fever after line use is highly suggestive
    • Other symptoms of CRBSI are those of bloodstream infection from any source and include general malaise, anorexia, vomiting
  • Sepsis or septic shock may be present.
  • There may be no signs of exit site or tunnel infection.
  • Exit site infections present with either erythema at the exit site [>1cm] and/or a purulent exudate. There may be pain at the site.
  • Tunnel infections present with inflammation and/or tenderness along the subcutaneous portion of tunnelled catheters.

Investigations required

  • Paired peripheral and central Blood Cultures should be sent from all potentially infected lumens when CRBSI is suspected - take same volume, generally up to 3mL
  • FBC, CRP
  • U&E’s, LFT, calcium, magnesium & phosphate
  • Urine for culture and sensitivity
  • Exit site infection: pus sample (preferred) or exit site swab for microbiology.

Non-Antimicrobial Management

  • CVC removal
  • Administer plasma expanders if required (10ml/kg of 0.9% Sodium Chloride over 30 minutes).
  • Administer antipyretic (i.e. Paracetamol) when temperature 38°C or above.

Empirical antimicrobial treatment

  • First line antibiotics are Vancomycin Description: electronic Medicines Compendium information on Vancomycin (if allergic use Teicoplanin Description: electronic Medicines Compendium information on Teicoplanin) and Ceftazidime Description: electronic Medicines Compendium information on Ceftazidime (if allergic use Aztreonam Description: electronic Medicines Compendium information on Aztreonam) via the CVC. See table 1 detailing administration and monitoring of antibiotic therapy.
  • For oncology patients follow Neutropenic Sepsis/Febrile Neutropenia guidelines
  • If CVC salvage is planned give the appropriate IV antibiotics for 10-14 days.
  • If the infected CVC is removed 5-14 days treatment is recommended depending on the pathogen and clinical response.

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Background

The central venous catheter (CVC) is essential for the management of children requiring long term treatment with intravenous therapies. Catheter types in use are peripherally inserted central catheters (PICC), tunnelled surgical lines (e.g. Broviac/Hickman) and implanted venous access devices (e.g. Port-a-Cath).

There are often a limited number of sites for CVC placement; therefore treatment of the infection without removal of the CVC is often necessary. When the infection is life threatening or there is a confirmed fungal infection or when conservative management of a bacterial catheter related blood stream infections (CRBSI) has failed (i.e. if the same organism is grown again, post-treatment) the CVC should be removed. The Microbiologist and Paediatric Consultant /Surgeon and medical staff must discuss the nature of the organism, the clinical condition and venous access limitations of the patient to ensure that line removal is warranted.

Infection is the major complication associated with long-term CVCs and can have serious consequences such as bloodstream infection, metastatic infection (osteomyelitis, endocarditis) and death.
CRBSI can be divided clinically into local (exit site) and bloodstream infections, but these entities may coexist.

CRBSI begins with colonisation of the:

  • internal lumen of the CVC - micro-organisms can gain access to the lumen of a catheter via a contaminated hub or infusate. This is more common in long-term CVC.
  • external surface of a CVC - may become colonized as a result of contamination during insertion, via exit site colonisation or secondary to a bacteraemia from a distant source5.

A CVC must be colonized before invasion of tissues or bloodstream can occur. The longer a catheter remains in place, the more likely it is to become colonised (Sandoe et al., 2003).
The most common causative organisms of significance are:

  • Gram negative bacilli
  • Staphylococcus aureus
  • Enterococcus species
  • Coagulase negative Staphylococcus
  • Candida species

Definition

  1. Exit site infection - purulent exudate or erythema surrounding the exit site
  2. CVC related bloodstream infection (CRBSI), meaning
    • A positive blood culture taken through the CVC
    • A positive peripheral blood culture taken before CVC removal
    • Differential time to positivity [DTP]
    • The same microorganism isolated from both sites.

However, in many cases the only information will be a positive blood culture in a sick patient with a CVC and no other focus for infection

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Clinical Diagnosis

Assess the child's general clinical condition

  1. An infant or child developing CRBSI may present with
    • Temperature above 38°C
    • Tachycardia
    • Tachypnoea and / or grunting respiration
    • A fall in blood pressure
    • Peripheral shut down, may feel cold and clammy
    • Irritability and lethargy
    • Enteral feed intolerance e.g. increased diarrhoea/stoma output and/or vomiting
    • Apnoeic episodes
    • Unstable blood sugars (particularly in neonates)
    • Take note of parent’s concerns – they know their child best; be worried if they are worried.
    • Wobbliness after line access
  2. Exit site infection is diagnosed on clinical grounds (exudate and erythema) and may or may not be associated with CRBSI.

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Severity Assessment

Catheters should ideally be removed in the following situations: [Evidence level C]

  • Bacteraemia, sepsis or local complications that become life threatening. Micro-organisms known to be difficult to eradicate [e.g. S. aureus, Bacillus spp., mycobacteria, and fungi].
  • Relapse of infection after antibiotics have been discontinued.

Salvaging the CVC is recommended in preference to removing the CVC in consultation with the children’s medical team and microbiology in patients that lack of venous access can become life limiting.

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Investigation
  • Paired peripheral and central Blood Cultures should be sent from all potentially infected lumens when CRBSI is suspected - take same volume, generally up to 3mL.
  • Differential time to positivity [DTP] is a blood culture-based method for diagnosing luminal colonisation or CRBSI. The DTP is the difference in time taken to show a positive result for the same organism in both the central and peripheral venous samples (i.e. a paired set). A DTP >2 hours in favour of central blood cultures has a sensitivity of 72-94%, and specificity of 91-95% for CRBSI (Blot et al, 1999; Catton et al, 2005). DTP >2 hours will fail to detect some CRBSI, but a positive result has a high probability of being CRBSI. A negative central blood culture at >100 hours incubation had a negative predictive value of 100%.
  • FBC, CRP
  • U&E’s, LFT, calcium, magnesium & phosphate
  • Urine for culture and sensitivity
  • Exit site infection: pus sample (preferred) or exit site swab for microbiology.

[Evidence level D]

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Treatment
Non-Antimicrobial Treatment
  • CVC removal - The definitive treatment for CVC infection is removal of the CVC and thus the source of infection, usually in combination with antimicrobial therapy. [Evidence level B].
  • Administer plasma expanders if required (10ml/kg of 0.9% Sodium Chloride over 30 minutes).
  • Administer antipyretic (i.e. Paracetamol when temperature 38°C or above).

[Evidence level D]

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Empirical Antimicrobial Treatment

Recommendation: First line empirical intravenous (IV) antibiotics are Vancomycin Description: electronic Medicines Compendium information on Vancomycin (if allergic use Teicoplanin Description: electronic Medicines Compendium information on Teicoplanin) and Ceftazidime Description: electronic Medicines Compendium information on Ceftazidime (if allergic use Aztreonam Description: electronic Medicines Compendium information on Aztreonam) via the CVC . See table 1 detailing administration and monitoring of antibiotic therapy.
[Evidence level D]

For oncology patients follow Neutropenic Sepsis/Febrile Neutropenia guidelines

Recommendation: If attempting to salvage a CVC administer systemic antimicrobials via the infected line.
[Evidence level B]

Recommendation: For multi-lumen CVCs, alternate lumens for administration of antimicrobials every 24 hours.

Recommendation: Review the antibiotic treatment when culture sensitivities are obtained

Recommendation: If CVC salvage is being attempted, antimicrobial line locks should be used together with systemic antimicrobials, where possible. If the patient was receiving line locks for prophylaxis then a different line lock agent should be chosen. Discuss with Microbiology.
[Evidence level B/D]

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Directed Antimicrobial Treatment (when microbiology results are known)

Recommendation: If only Gram positive bacteria are cultured, Ceftazidime Description: electronic Medicines Compendium information on Ceftazidime/Aztreonam Description: electronic Medicines Compendium information on Aztreonam can be stopped and gram positive therapy modified according to susceptibilities.

Recommendation: If only Gram negative bacteria are cultured, Vancomycin Description: electronic Medicines Compendium information on Vancomycin/Teicoplanin Description: electronic Medicines Compendium information on Teicoplanin can be stopped and gram negative therapy modified according to susceptibilities.

For oncology patients follow Neutropenic Sepsis/Febrile Neutropenia guidelines

Recommendation: If cultures are negative consider alternative diagnoses because negative cultures have a high negative predictive value.
[Evidence level C]

Prophylactic use of Antimicrobial line locks

Antimicrobial lock therapy should be considered for confirmed luminal catheter infections caused by the Gram positive organisms coagulase negative staphylococci, enterococci, streptococci, and coryneforms.

The agent that should normally be used is taurolidine (Taurolock TM).

If Taurolock TM contra-indicated, an alternative is Vancomycin Description: electronic Medicines Compendium information on Vancomycin (concentration 5mg/ml).

Antimicrobial lock therapy should also be considered for confirmed luminal catheter infections (i.e differential time to positivity of 2 hours or more in paired peripheral and through-line blood cultures) caused by “coliforms” [Enterobacteriaceae].

Suitable agents would include taurolidine or Gentamicin. [Evidence Level D]

Normally taurolidine (Taurolock TM ) should be considered as first line lock therapy for “coliforms” (Enterobacteriaceae) and other Gram-negative bacilli.

If Taurolock TM contra-indicated, an alternative is Gentamicin (concentration 2mg/ml)

Salvage of long-term catheters confirmed to be infected with organisms other than those listed above should also only be attempted after discussion with Microbiology. [Evidence level D].

Although the duration of antimicrobial lock therapy has varied among different studies; it most often is two weeks. [Evidence level C].
If an antimicrobial lock is being used, then depending on the clinical scenario and microbiological results, it may be in addition to, or instead of, systemic therapy. [Evidence level C].

If the patient has been receiving prophylactic line locks, then an alternative agent should be used for salvage therapy

Recommendation: Prophylaxis with antimicrobial line locks should be used in children with recurrent CRBSI (2 episodes in a 6 month period), as a lack of venous access becomes life limiting.
[Evidence level D]

Recommendation: If a patient has 2 bacterial CRBSIs in a 6 month period, initial prophylaxis should be Taurolock™,
[Evidence level D]

Guidelines for use of Taurolock in infants and children

  • Recommendation: Taurolock™ should be commenced when a course of antimicrobial treatment is completed and the clinical decision for prophylactic line lock has been made. Patients should remain on Taurolock™ until treatment is no longer required and the CVC is removed or they require a change of prophylactic agent. [Evidence level D]
  • 1-2mL* of Taurolock™ should be instilled into the line slowly (max 1mL per 5 seconds) to lock the line whilst not in use.
  • Taurolock™ may cause mild hypocalcaemic symptoms if instillation is not done slowly as directed.
  • Taurolock™ should be aspirated prior to accessing the CVC.

* see Appendix 1 for ‘Prime, flush and line lock volume table

See appendix 2 - TaurolockTM use in PN dependent patients

See table of antimicrobials below for details of the presentation and administration of line locks and refer to the Department of Microbiology Protected (restricted) antimicrobial Prescribing Guidelines: - Taurolidine - based catheter lock solutions (TauroLock™) for further information.

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Duration of Treatment

Recommendation: If CVC salvage is planned give the appropriate IV antibiotic/s for 10-14 days.
[Evidence level B]

Recommendation: If the infected CVC is removed 5-14 days treatment is recommended depending on the pathogen and clinical response.
[Evidence level B]

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Switch to oral agent(s)

Exit site infections without systemic signs of infection of positive blood cultures can be treated with oral antimicrobials.

When treating suspected or microbiologically confirmed CRBSI with the intravascular catheter in situ, antimicrobials must be infused via all potentially infected lumens. Oral antimicrobials only have a place in this setting if clinically and microbiologically appropriate in conjunction with antimicrobial lock[s], or if the infection has been confirmed to be solely extra-luminal.

Once an infected catheter has been removed, if a patient has made a good clinical recovery IV antimicrobials can be switched to an oral alternative if clinically appropriate. [Caution should be exercised in this respect for Staphylococcus aureus bloodstream infection which has a high propensity to seed distant sites and relapse - longer courses of intravenous therapy are usually recommended]

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Treatment Failure
See CVC removal and discuss with microbiology

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Provenance

Record: 2165
Objective:
  • To improve the diagnosis and management of suspected CVC infections in infants and children
  • To provide evidence-based recommendations for appropriate diagnosis and investigation of suspected CVC infection
  • To ensure rapid assessment and treatment of suspected CVC infection and prevent metabolic acidosis and septic shock.
  • To provide evidence-based recommendations for appropriate non-antimicrobial management of suspected CVC infection
  • To provide evidence-based recommendations for appropriate empirical and directed antimicrobial therapy of suspected CVC infection
  • To recommend appropriate dose, route of administration and duration of antimicrobial agents.
  • To advise in the event of antimicrobial allergy.
  • To set-out criteria for referral to specialists.
Clinical condition:
  • Infants and children receiving parenteral nutrition (PN) in hospital or at home with a suspected central venous catheter (CVC) infection
  • Infants and children post PN with CVC in situ with a suspected central venous catheter infection, in hospital or at home
Target patient group: Infants (excluding neonates on the NICU) and children with intestinal failure requiring parenteral nutrition with a CVC in situ
Target professional group(s): Secondary Care Doctors
Pharmacists
Allied Health Professionals
Secondary Care Nurses
Adapted from:

Evidence base

References

  1. Bishop et al (2007) Guidelines on the insertion and management of central venous access devices in adults. International Journal of Lab Hem. 29; 261-278.
  2. Blot et al (1999). Diagnosis of catheter-related bacteraemia: a prospective comparison of the time to positivity of hub-blood versus peripheral-blood cultures. Lancet 354, 1071-1077.
  3. BNF for children (2018) www.bnfc.org
  4. Catton et al (2005). In situ diagnosis of intravascular catheter-related bloodstream infection: a comparison of quantitative culture, differential time to positivity, and endoluminal brushing. Critical Care Medicine 33, 787-791.
  5. Elliott et al (1997). Can antimicrobial central venous catheters prevent associated infection? Br J Haematol 107:235-241
  6. Guidelines for preventing infections associated with insertion and maintenance of CVC. Journal of Hospital Infection (2001) 47 (supplement) S47-S67.
  7. Handrup et al (2013) Central venous catheters and catheter locks in children with cancer: a prospective randomized trial of taurolidine versus heparin. Pediatr Blood Cancer 60(8):1292-8
  8. Ince et al (2014). Complications of total implantable access ports and efficacy of Taurolidine-citrate lock solution against catheter-related infections. Afr J Paediatr Surg. 11(2):138-42
  9. Lambe et al (2018). Strategies to reduce catheter-related bloodstream infecions in paediatric patients receiving home parenteral nutrition: The efficacy of Taruolidine-citrate prophylactic-locking. JPEN 42:1017-25
  10. LTHT Department of Microbiology Restricted Antimicrobial Prescribing Guidelines: - Taurolidine - based catheter lock solutions (TauroLock™)
  11. Malassezia Furfur (1991) Catheter infection cured with antibiotic lock therapy. The American Journal of Medicine 90:128 – 129.
  12. Medicines for Children (2003) RCPCH.
  13. Mermel, L et al. Clinical practise guidelines for the diagnosis and management of intravascular catheter-related infection:2009 update by the infectious diseases society of America. Clin Infect Dis . 2009;49:1-45.
  14. NICE (2007) CG47 Feverish illness in children. www.nice.org.uk/CG047quickrefguide
  15. NICE (2009) CG84 Diarrhoea and vomiting in children under 5. www.nice.org.uk/CG084quickrefguide
  16. Sandoe JAT, Ian R. Witherden IR , Cove JH, Heritage J, Wilcox MH. Correlation between enterococcal biofilm formation in vitro and medical-device-related infection potential in vivo. J Med Microbiol 2003;52:547-550

Evidence levels:
A. Meta-analyses, randomised controlled trials/systematic reviews of RCTs
B. Robust experimental or observational studies
C. Expert consensus.
D. Leeds consensus. (where no national guidance exists or there is wide disagreement with a level C recommendation or where national guidance documents contradict each other)

Approved By

Improving Antimicrobial Prescribing Group

Document history

LHP version 2.0

Related information

Table 1. First Line Antibiotics

Antibiotics

Dose

Presentation

Administration

Monitoring

Vancomycin Description: electronic Medicines Compendium information on Vancomycin
Vancomycin should be prescribed at the same time as Ceftazidime to prevent excessive accessing of the line.

15mg/kg FOUR times daily
(Max 2 gram daily) for paediatric patients only.
Please refer to local vancomycin prescribing guidelines for infants on the neonatal unit.

5mg/mL in Sodium Chloride 0.9% (for peripheral administration) or 10mg/mL for central administration (also compatible with 5% glucose)

IV infusion over at least 60 minutes (it can run alongside PN If necessary)

Pre Vancomycin Description: electronic Medicines Compendium information on Vancomycin levels taken before the fifth dose. Pre dose (trough) level 10 - 20mg/L - adjust dose as necessary.
Rate must not exceed 10mg/minute

Ceftazidime Description: electronic Medicines Compendium information on Ceftazidime
Ceftazidime should be prescribed at the same time as Vancomycin to prevent excessive accessing of the line

25mg/kg THREE times daily
(TWICE daily in mild renal impairment)
(Max 6 gram daily)

100mg/mL
in water for injection (WFI)

Slow IV bolus given over 3-5 minutes. (Doses over 2g should be given as an infusion over 30 minutes in 50mL/100ml Sodium Chloride 0.9% or glucose 5%)

Ceftazidime Description: electronic Medicines Compendium information on Ceftazidime and aminoglycosides should not be mixed in the same giving sets or syringe. Precipitation has been reported with Vancomycin Description: electronic Medicines Compendium information on Vancomycin, therefore giving sets and lines should be flushed between administration of these two agents.

Teicoplanin Description: electronic Medicines Compendium information on Teicoplanin (IN VANCOMYCIN ALLERGY ONLY)

2m -17 y 10mg/kg (max 400mg) every 12 hours for 3 doses, then 6mg/kg (max 200mg) DAILY.

200mg or 400mg vial in 3mL WFI. Might be further diluted with sodium chloride 0.9% or glucose 5%

Slow IV bolus over 3-5 minutes
In neonates IV infusion over 30 minutes preferred

Plasma Teicoplanin Description: electronic Medicines Compendium information on Teicoplanin concentration is not measured routinely

Aztreonam Description: electronic Medicines Compendium information on Aztreonam (IN CEFTAZIDIME ALLERGY ONLY)

Child 1 month-11 years
30mg/kg every 6-8 hours
Child 12-17 years
1g every 8 hours or 2g every 12 hours

100mg/mL in water for injection. It can be further diluted with glucose 5% or sodium chloride 0.9% to a concentration of less than 20mg/mL

Slow IV bolus over 3-5 minutes

Can be given as an intermittent IV infusion over 20-60 minutes (if further diluted)

None

 

Table 2. Alternative antibiotics based on sensitivities

Antibiotics

Dose

Presentation

Administration

Monitoring

Flucloxacillin Description: electronic Medicines Compendium information on Flucloxacillin

12.5–25mg/kg FOUR times daily.
(Max 1 gram every 6 hours)

Made in aseptics*
50mg/mL in WFI

Slow IV bolus given over 3-5 minutes

None

Gentamicin

7 mg/kg OD for children aged 1 month - 18 years

Ready diluted 10mg/mL

IV infusion
Add to 50mL sodium chloride 0.9% bag and give over 30 minutes (see gentamicin chart)

Gentamicin levels taken 18-23 hours from the end of the first dose. Trough level target less than 1mg/mL

 

Table 3. First Line Antifungals

ANTIFUNGAL

Dose

Presentation

Administration

Monitoring

Fluconazole Description: electronic Medicines Compendium information on Fluconazole

12mg/kg DAILY (max 400mg)

Ready diluted (2mg/mL)

Infuse over 10-30 minutes (max infusion rate of 5-10mL/minute)

None

 

Table 4. Line Locks

LINE LOCK

Dose

Presentation

Administration

Monitoring

TauroLock™
(Taurolidine)

1-2mL *

Ready diluted

Instil 1-2mL into each lumen of line and leave for as long as possible. Aspirate before using the line e.g. to give next dose of antibiotics

None

Gentamicin

4mg/2mL

Made in aseptics 2mg/mL pre-filled syringe

Instil 1-2mL into each lumen of line and leave for as long as possible. Aspirate before using the line e.g. to give next dose of antibiotics

None

Vancomycin Description: electronic Medicines Compendium information on Vancomycin

10mg/2mL

Made in aseptics 5mg/mL pre-filled syringe

Instil 1-2mL into each lumen of line and leave for as long as possible. Aspirate before using the line e.g. to give next dose of antibiotics

None

Appendix 1 - Prime, flush and line lock volumes for Central Venous Catheters (CVC)

Type of Centeral Venous Ccatheter (CVC)

Size Fr

Maximum prime volume

Prime volume with Smartsite

Minimum 0.9% Sodium Chloride flush volume

Line lock volume

PICC (Cook)

3 Fr

0.5mL

0.6mL

1.0mL

0.6mL

PICC (Cook)

4 Fr

0.6mL

0.7mL

1.0mL

0.7mL

Broviac - Single
(Vygon Lifecath)

2.7 Fr

0.3mL

0.4mL

1.0mL

0.4mL

Broviac
(Vygon Lifecath)

4.2 Fr

0.4mL

0.5mL

1.0mL

0.5mL

Broviac
(Vygon Lifecath)

5.0 Fr

0.75mL

0.85mL

2.0mL

1.0mL

Broviac
(Vygon Lifecath)

6.6 Fr

1.2mL

1.3mL

2.0mL

1.5mL

Hickman
(Vygon Lifecath)

9.6 Fr

1.7mL

1.8mL

5.0mL

2.0mL

Broviac - Double
(Vygon Lifecath)

7 Fr

White 0.75mL
Red 1.1mL

0.85mL
1.2mL

2.0mL
3.0mL

1.0mL
1.5mL

Broviac - Double
(Vygon Lifecath)

9 Fr

White 0.75mL
Red 1.6mL

0.85mL
1.7mL

2.0mL
3.0mL

1.0mL
2.0mL

Broviac - Triple
(Vygon Lifecath)

12.5 Fr

White 0.9mL
Blue 0.9mL
Red 1.9mL

1.0mL
1.0mL
2.0mL

2.0mL
2.0mL
5.0mL

1.0mL
1.0mL
2.0mL

If Fr size of CVC not known use age as a guide

Type of CVC

Age of patient

Minimum 0.9% Sodium Chloride flush volume

Line lock volume

PICC

under 2 years old

1.0mL

1.0mL

Broviac or Hickman line

2 years old & over

2.0mL

2.0mL

Appendix 2 - TaurolockTM use in PN dependent patients

  • Prophylaxis with Taurolock™ should be used in ‘high risk’ PN dependent patients, as lack of venous access becomes life limiting.
  • PN dependency, in this instance, includes all infants and children who have undergone surgery resulting in a short bowel, intestinal failure and an inability to survive without PN. This also includes children who are born with a congenital abnormality, resulting in dysmotility and enteral feed intolerance which prevents their survival without PN.
  • This ‘high risk‘ group includes infants and children with short bowel, predominantly following surgery for gastroschisis or necrotising enterocolitis (NEC), those with intestinal failure associated liver disease (IFALD) and those in whom long term PN dependence is predicted.
  • Taurolock™ should only be used when infants are having their PN ‘cycled’ i.e. PN infusing over less than 24 hours

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