Immunoglobulin infusions: intravenous and subcutaneous

The purpose of this guideline is to provide guidance about intravenous and subcutaneous immunoglobulin infusions at Great Ormond Street Hospital.

Introduction

Immunoglobulin is a blood product used in the treatment of children with primary antibody deficiency and other complex immune deficiency disorders, to prevent life threatening infections (Wood et al, 2007) (Rationale 1).

In addition, it can be used as supportive therapy for secondary immunodeficiency where extrinisic factors such as chemotherapy cause damage to the immune system, eg following stem cell transplantation where immunoglobulin levels remain low (Department of Health, 2008).

Immunoglobulin has also been shown to be effective in a wide range of diseases where 'modulation' of the immune system is required, although the mechanism of action is not well understood.

Licensed indications other than in Primary Immune Deficiency include Kawasaki disease, idiopathic thrombocytopaeniac purpura, Guillain-Barre syndrome and chronic inflammatory demyelinating polyneuropathy. It may also be used selectively in intensive care (Department of Health, 2008).

There is some anecdotal evidence for the use of immunoglobulin in autoimmune disease, and some other conditions, although these are unlicensed at present.  

Immunoglobulin can be given either by the intravenous or subcutaneous route. Specific preparations are used for the two routes. Both routes provide good protection against infection (Chapel et al, 2000).

The choice of route will depend on the reason for which immunoglobulin is given, venous access and patient choice. Children requiring regular infusion have the option of home treatment, and parents or older children can be taught how to give their own infusions, either by the intravenous or subcutaneous route.

SCIg has advantages over IVIg in relation to the ease of administration, reduction in the incidence of side effects and reduced administration time, although the frequency of administration is greater.

Background

Immunoglobulin is a blood product, made from pooled collections of human plasma. As for all blood products, there is a small risk of transmitting infections such as hepatitis.

British plasma has not been used in the manufacture of immunoglobulin since 1998, due to the possible risk of transmitting variant Creutzfeldt Jacob disease (vCJD), for which there is no screening process at present.

The supply of immunoglobulin is limited and demand in recent years has risen. National guidelines for use of immunoglobulin have been produced by the Department of Health in order to ensure that an appropriate supply and demand balance can be maintained (Department of Health, 2008).

When prescribing immunoglobulin for the first time, an immunoglobulin request form must be completed. 

For children requiring regular immunoglobulin replacement, it is considered good practice not to change products once commenced on a particular brand. Different commercial products are not identical and chldren who tolerate one product may not necessarily tolerate another (Department of Health, 2008).

In addition, switching products exposes the recipient to another large donor plasma pool and increases the risk of exposure to acquired infection such as hepatitis C virus (Chapel et al, 2000).

Preparation

Carry out a risk assessment to ensure the family understand the need for treatment and how it is administered (Power, 1997) (Rationale 2). The benefits of treatment should always outweigh the potential risk of infections from IgG (Wood et al, 2007).

It can be given by one of two routes: 

• Intravenous - for use in immunomodulation and for giving higher doses of IgG and for some children on long-term replacement. 

• Subcutaneous - suitable for IgG replacement doses and ideal in younger children with poor venous access. Use with caution if patient has low platelets, but it is not contraindicated (Rationale 3). The risk of adverse reactions is also reduced (Abrahamsen et al, 1996).

Select the most appropriate route in consultation with the family. Explain the procedure to the child and family and gain consent (Department of Health, 2001). Explanation of the procedure must include (Rationale 2):   

• the reason for treatment   

• the risks and benefits   

• the plan and options for ongoing treatment (Rationale 4)

Supply the child and their parents with the appropriate information (Rationale 5). Prepare the child for cannulation or subcutaneous needle insertions, using appropriate topical anaesthetics and distraction therapy (Broome, 1990).

Asses that the child is fit for treatment and perform baseline observation of (Cochrane, 1997) (Rationales 6 and 7):   

• temperature      

• respiration rate       

• heart rate   

• weight (Rationale 8)

Complete pre-treatment blood tests and investigations (Wood et al, 2007):

• immunoglobulin trough levels (IgGAM) (Rationale 9)   

• serum and plasma for long term storage (Store Ig) (Rationale 10)     

• liver function tests (Rationale 10)    

• hepatitis B and C screen (Rationale 10) 

• other investigations as indicated

Prescription

Immunoglobulin is a human blood product and must not be administered unless it is prescribed on the child's prescription chart (Power, 1997) (Rationale 11).

Calculate the dose (Rationale 12):

• replacement therapy: 300-500mg/kg/3 weeks

• modulation: 1-2g/kg in as a single or divided dose

Please note: Doses should be rounded to the nearest whole bottle size (Department of Health, 2008) (Rationale 13).

Prescribe the named product to be used (Rationale 14). Read the product insert to calculate the infusion rate in mls/hr (Rationale 15).

Prescribe premedication if required. Premedication is usually only given if there has been a recent adverse reaction (Rationale 16).

Check the product, dose, batch number and expiry date (Rationale 17).

Record the product, dose, batch numbers and expiry date in the patient's medical notes and blood product register (Rationale 18).

Ensure the immunoglobulin is at room temperature (Rationale 19).

Check the child's identity band and prescription according to the hospital policy before starting the infusion (NMC, 2008) (Rationales 17 and 20).

Equipment

Clean the preparation area (Rationale 21). Gather the appropriate equipment:

Intravenous

• local anaesthetic cream (usually Ametop) may be applied to the venous access site (Rationales 22 and 23)

• immunoglobulin product for intravenous use (Appendix 1)

• IV infusion pump (Rationale 24)

• IV infusion set with an integral air inlet

• saline flush

• cannula (22g/24g), short connector/T-piece, alcohol wipes (peripheral infusion)

• IV Tegaderm™/Opsite™ tape (to secure the cannula)

Subcutaneous

Local anaesthetic cream (usually EMLA) may be applied to the infusion sites for 1-2 hours prior to infusion (Rationales 23 and 25). Immunoglobulin product for subcutaneous/intramuscular use (Appendix 1).

• two portable infusion pumps, eg Graseby™ MS16A, Micrel™ MP101, Cane Crono PID (Groves, 2003; McNeilly et al, 2004)

• two luer lock syringes (10ml/20ml or 30ml) (Rationale 24)

• 21g needles (for drawing up the infusions)

• two infusion needles with priming volumes of <0.5mls, e.g. 25g/27g butterfly needles (60cm extensions), 27g thalasets© (Ross et al, 2002; Torre, 2002) (Rationales 23 and 24).

• Micropore tape™ (to secure the infusions)

Procedure

Intravenous infusion

Prime the intravenous administration set with immunoglobulin using universal precautions and aseptic non-touch technique (Rationales 21 and 26).

Check the child's identity and the prescription according to the medication policy (NMC, 2008) (Rationale 20).

Infuse the immunoglobulin at the prescribed rate, starting slowly, and increasing to the maximum prescribed rate over 30-60 minutes (Rationale 27).

Do not leave the child unattended during the infusion. This may be negotiated with any family members in attendance and they should be advised to call the nurse if they have any concerns about their child during the infusion (Rationale 28).

It is not necessary to record observations on a child having regular infusions, providing a family member is present (Rationale 27).

Check the peripheral infusion site half hourly for inflammation (tenderness, swelling, redness) and leakage (Rationale 29). STOP the infusion if there are any signs of inflammation. 

Check the infusion line is intact and record the infusion rate, pressures, volume infused hourly (Rationale 30).

On completion of the infusion, flush the administration set with 0.9% sodium chloride solution if the total amount of immunoglobulin infused was less than 100mls (Rationale 31).

Subcutaneous infusions

Select suitable infusion sites: abdomen, thighs or buttocks (Workman, 1999) (Rationales 23 and 32).

• Thighs are preferred in chldren under two. The thighs become more muscular as the child gets older (Rationale 33, Rationale 34).  

• The abdomen is preferred in older children as the skin is more pliable and allows larger volumes to be infused (Rationale 33, Rationale 34). 

Remove the local anaesthetic cream (if used) five minutes before the needles are inserted (Rationale 35).

Draw up the immunoglobulin into the syringe and prime the administration line using a non-touch technique (Rationale 21).

Lift a skin fold and insert the needle into the subcutaneous tissue (Fleming, 1999) (Rationale 36). The angle of insertion will depend on the needle type, length and amount of subcutaneous tissue.

The whole needle must lie within the numbed area of skin where local anaesthetic is used (Rationale 23).

Secure the needle with tape or occlusive dressing as appropriate (Rationale 37).  

Assess the chld's subcutaneous tissue to decide on the infusion rate. The rate can be increased as the child grows up (Rationale 23, Rationale 34), for example:

• 5-10 mls can be infused in babies 1-6 months over one hour

• 10mls can be infused in 40-60 minutes in chldren over six months

• 10-25mls can be infused in 40-90 minutes in older chldren

• >30mls may need to be divided into more than one site

Set the appropriate rate for the syringe size (Rationale 23).

Observe the child and monitor the infusion rate (Rationale 30).

Record details of the infusion, site, rate and syringe size.

Please note: Swelling and redness at the site of the infusion is normal and will disappear around 24 hours after the infusion has finished.

Do not leave the child unattended during the infusion as there is always a risk of adverse reactions (Rationale 28). 

Adverse reaction management

Adverse reactions to immunoglobulin are uncommon if infusions are given according to guidelines.

There may be acute reactions, occurring during an infusion, shortly after a subcutaneous infusion, or delayed (occurring 24-48 hours after the infusion) (Wood et al, 2007).

Most reactions are minor and respond to slowing down the infusion, but severe reactions may occur requiring prompt intervention.

Serious adverse reactions are extremely unlikely if instructions are followed. It is vital however, that those responsible or giving the infusions know how to recognise a serious reaction and what action to take should one occur.

The most common cause of reactions is administration of immunoglobulin when there is active untreated bacterial infection.

The risk of adverse reactions can be minimised by adhering to the following guidelines:

• do not give an infusion if the child is unwell or has a fever 

• give the infusion at the prescribed rate 

• first infusions should be given more slowly 

Completing the infusions

Remove the needles or cannula using universal pracautions and dispose of in a sharps bin in accordance with Trust Waste policy (Rationale 11, Rationale 21).

Document in the child's medical and medical health care records the following (Rationale 11, Rationale 18):

• immunoglobulin dose and batch numbers (Rationale 10)

• date and time for starting and completing the infusion (Rationale 18)

• sign that you are responsible for the administration of the infusion (Rationale 11)

Home treatment

For many children with primary immune deficiencies, immunoglobulin treatment is life long.

Treatment needs to be acceptable and convenient so that the family can incorporate it into their family routine (Cochrane, 1997). Training for home infusions can be organised through the immunology nurses.

Training should include:

• risk assement of the home environment

• practical apsects of treatment including non-touch technique

• management of potential adverse events

• recording of the infusion details

Organisation of home treatment must include regular provision of the treatment, equipment and all disposable supplies, as well as an appropriate means for the safe disposal of sharps and contaminated equipment.

The home therapy training centre is responsible for all aspects of homecare: 

• obtaining funding for homecare

• prescribing treatment

• monitoring treatment

• look-back in the event of any transmissible infections

The child must be reviewed at least every 12 months by the prescribing team. During this review, an Annual Follow-up form must be completed as per the Department of Health's Demand Management Programme (Department of Health, 2008):

• for non-primary immunodeficiency patients this should be returned to Pharmacy

• for primary immunodeficiency patients at GOSH, these should be completed by the Immunology team and returned to the data manager within the Immunology department

In addition to routine monitoring, an annual store of Ig (save serum and plasma) and Hepatitis C screen should be obtained (Rationale 10).

Appendix 1: Immunoglobulin products available in the UK

*Products usually available in GOSH Pharmacy.

However, should patients need a different product for a particular reason, pharmacy needs to be notified as early as possible so that the specific products can be ordered in for the patient.

Rationale

Rationale 1: Immunoglobulin provides passive immunity by replacing a wide variety of antibodies, which have been purified from a large pool of human plasma donors.

Rationale 2: To prepare the family for treatment and obtain consent.

Rationale 3: To reduce the risk of severe bleeding and bruising.

Rationale 4: To plan ahead and liaise with local services.

Rationale 5: To address any information needs and answer any questions or concerns.

Rationale 6: To establish what is normal and rule out pre-existing disease processes if an infusion reaction is suspected.

Rationale 7: Alterations in vital signs could indicate an infusion reaction.

Rationale 8: To calculate the appropriate dose.

Rationale 9: To monitor the effectiveness of treatment.

Rationale 10: To enable look-back in the event of an outbreak of infection.

Rationale 11: To maintain hospital policy.

Rationale 12: To give appropriate treatment.

Rationale 13: To prevent wastage.

Rationale 14: To avoid product switching.

Rationale 15: The rate is product specific and must be calculated in mls/hr. It will be dependant on the child's weight.

Rationale 16: Premedication is usually only given if there has been a recent adverse reaction.

Rationale 17: To avoid medication errors.

Rationale 18: To enable accurate recording of the infusion details.

Rationale 19: To avoid chilling the patient and increase their comfort.

Rationale 20: To ensure the treatment is given to the right child.

Rationale 21: To minimise the risk of infection.

Rationale 22: Ametop gel promotes vasodilation and may aid cannulation.

Rationale 23: To minimise the discomfort of the procedure.

Rationale 24: To enable the infusion to be given safely.

Rationale 25: EMLA cream may be left in situ for up to five hours - longer contact times may increase the effectiveness.

Rationale 26: To prevent air embolism.

Rationale 27: To reduce the risk of adverse reactions.

Rationale 28: To enable prompt detection and treatment of any adverse events.

Rationale 29: To detect for signs of extravasation.

Rationale 30: To ensure the correct amount is being given and the infusion pump is working correctly.

Rationale 31: To ensure the whole amount is given (the infusion set may retain up to 20mls of the infusion).

Rationale 32: To promote steady absorption.

Rationale 33: To reduce swelling.

Rationale 34: To maximise mobility.

Rationale 35: To allow the skin to dry and to maxmxise its effect.

Rationale 36: To prevent the needle penetrating the underlying muscle, which would increase the discomfort and increase the risk of adverse reactions.

Rationale 37: To prevent the infusions being dislodged.

References

Reference 1:
Abrahamsen TG, Sandersen H, Bustnes A (1996) Home therapy with subcutaneous immunoglobulin infusions in children with congenital immunodeficiencies. Pediatrics 98 (6 Pt 1): 1127-31.

Reference 2:
Broome ME (1990) Preparation of children for painful procedures. Pediatric Nursing 16 (6): 537-41.

Reference 3:
Chapel HM, Spickett GP, Ericson D, Engl W, Eibl MM, Bjorkander J (2000) The comparison of the efficacy and safety of intravenous versus subcutaneous immunoglobulin replacement therapy. Journal of Clinical Immunology 20 (2): 94-100.

Reference 4:
Cochrane S (1997) Care of patients undergoing immunoglobulin therapy. Nursing Standard 11 (41): 44-6.

Reference 5:
Department of Health (2008) Clinical Guidelines for Immunoglobulin Use (Second edition). www.dh.gov.uk/en/Publicationsandstatistics/Publications/PublicationsPolicyAndGuidance/DH_085235. Viewed on: 16/02/2009

Reference 6:
Department of Health (2001b) Consent - what you have a right to expect: a guide for children and young people. www.dh.gov.uk/en/Publicationsandstatistics/Publications/PublicationsPolicyAndGuidance/DH_4008977. Viewed on: 16/02/2009

Reference 7:
Department of Health (2001a) Consent - what you have a right to expect: a guide for parents. www.dh.gov.uk/en/Publicationsandstatistics/Publications/PublicationsPolicyAndGuidance/DH_4005202. Viewed on: 16/02/2009

Reference 8:
Fleming DR (1999) Challenging traditional insulin injection practices. American Journal of Nursing 99 (2): 72-4.

Reference 9:
Groves KE (2003) An introduction to the Micrel Micropump MP Daily portable syringe driver. International Journal of Palliative Nursing 9 (11): 468-73.

Reference 10:
McNeilly P, Price J, McCloskey S (2004) The use of syringe drivers: a paediatric perspective. International Journal of Palliative Nursing 10 (8): 399-404.

Reference 11:
Nursing and Midwifery Council (NMC) (2008) Standards for medicine management. www.nmc-uk.org/ Viewed on: 16/02/2009

Reference 12:
Power KJ (1997) The legal and ethical implications of consent to nursing procedures. British Journal of Nursing 6 (15): 885-8.

Reference 13:
Ross JR, Saunders Y, Cochrane M, Zeppetella G (2002) A prospective, within-patient comparison between metal butterfly needles and Teflon cannulae in subcutaneous infusion of drugs to terminally ill hospice patients. Palliative Medicine 16 (1): 13-6.

Reference 14:
Torre MC (2002) Subcutaneous infusion: non-metal cannulae vs metal butterfly needles. British Journal of Community Nursing 7 (7): 365-9.

Reference 15:
Wood P, Stanworth S, Burton J, Jones A, Peckham DG, Green T, Hyde C, Chapel H, UK Primary Immunodeficiency Network (2007) Recognition, clinical diagnosis and management of patients with primary antibody deficiencies: a systematic review. Clinical and Experimental Immunology 149 (3): 410-23.

Reference 16:
Workman B (1999) Safe injection techniques. Nursing Standard 13 (39): 47-53; quiz 54.

Document control information

Lead author(s)
Wendy Mills, Clinical Nurse Specialist, Immunology

Document owner
Claire Gilmour, Clinical Nurse Specialist, Immunology

Approved by
Clinical Practice Committee 

First introduced: 4 February 2009 
Date approved: 19 October 2011
Review schedule: Two years
Next review: 21 October 2013
Document version: 2.0
Replaces version: 1.0