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Blood Transfusion

Intravenous Immunoglobulin Guideline

  • This document guides how to safely prescribe, administer and manage patients receiving intravenous immunoglobulin (IVIg) at the RCH.

    Description

    • IVIg is manufactured from human plasma. It contains IgG antibodies and is used in the treatment of a growing number of immune, haematology, neurology and rheumatology conditions.  
    • All IVIg products undergo several steps to minimise the possibility of pathogen transmission.  

    Authorisation to administer IVIg

    • The use of IVIg in Australia is governed by the National Blood Authority (NBA) and is issued by the Australian Red Cross Lifeblood. 
    • The Criteria for the clinical use of immunoglobulin in Australia (the Criteria) outlines conditions where IVIg has been established to be approved and access to IVIg is based on the patient meeting specific requirements as listed in the Criteria.
    • IVIg authorisations are processed via an online system called BloodSTAR.  All treating medical staff at RCH must register with BloodSTAR to request IVIg. Medical staff need to register at each hospital they prescribe IVIg. To be eligible to register at RCH an APHRA number and RCH email address are required. For assistance registering call 13 000 BLOOD (13 000 25663).
    • For any request the clinician will require:
      • Patient demographics
      • Diagnosis
      • Patient weight
      • The dose (g) of IVIg prescribed will vary according to the indication
    • Consent - BloodSTAR requires a specific ‘Record of privacy consent’. This indicates that the patient understands their personal information will be recorded in BloodSTAR.
    • For any medical conditions that do not meet the criteria for funded IVIG under the National Blood Arrangements, an application to the Drug Usage Committee (DUC) for hospital funded IVIg (Issued via Pharmacy) may be made. There should be careful consideration for approval balancing potential side effects with any possible alternate treatments.
    • Nursing staff can register in the same process as above and can view patient information related to IVIg authorisations, previous and planned treatments, planning sheets and the record of privacy consent.   

    IVIg products available in Australia

    Consent and patient information

    • Document the consent for the administration of IVIg on the Patient Consent to Blood Products MR634/A. This is separate from the BloodSTAR consent and is specific to RCH.
    • Inform the patient of:
      • The reason why IVIg is needed, any risks of not receiving it and any potential alternate treatments.
      • The risks and benefits of IVIg and potential side effects (e.g. acute reactions and delayed adverse events including aseptic meningitis).
    • Consent is valid for the duration of the admission. However, consent for patients receiving regular IVIg is valid for 12 months. This should be indicated on the MR634/A. 
    • Ask patients and families:
      • To alert nursing staff/treating team of any adverse event during or following their IVIg infusion.  

    Contraindications

    • True anaphylactic reactions to human immunoglobulins
    • IgA deficient patients with anti-IgA antibodies
      • Flebogamma 5% and 10% is contraindicated in patients with hereditary problem of fructose intolerance. Babies and young children (< 2years) may not yet be diagnosed with this condition (which may be fatal) and should not receive this product. 

      Precautions

      •  Reactions and adverse events to IVIg may relate to:
        • Higher infusion rates (e.g., >3mL/kg/hr)
        • Patients receiving higher doses of IVIg (e.g., 2g/kg)
        • Patients naive to IVIg
        • When changing from one IVIg product to another
        • When there has been a long interval between infusions.
      • Ensure patients are well hydrated prior to IVIg.
      • Patients with a previous severe adverse event to IVIg (e.g., aseptic menangitis)
      • Patients with history of or current cerebral oedema.
      • IgA deficient patients
      • Renal impairment
        • Assess renal function prior to product commencement.

      Special considerations

      IVIg infusion may impair the efficacy of live attenuated virus vaccines such as measles, rubella, mumps and varicella and there are specific deferral periods. 

      Indication   Dose g/kg Deferral interval
      IVIg for treatment of immune thrombocytopenic purpura (ITP) IV 0.4g/kg 8 months
      IVIg for treatment of ITP IV 1g/kg 10 months
      IVIg for treatment of ITP or Kawasaki disease IV 1.6 – 2g/kg 11 months

      https://immunisationhandbook.health.gov.au/contents/vaccination-for-special-risk-groups/vaccination-for-people-who-have-recently-received-normal-human-immunoglobulin-and-other-blood-products


      Medical order

      • Order IVIg in EMR.
        • Type of IVIg product and concentration (e.g., Privigen AU, Privigen 10%, Flebogamma 5%, Flebogamma 10%, Kiovig 10%, Gammunex 10% and Octagam 10%)
        • The IVIg product approved in BloodSTAR will need to be the IVIg product prescribed in EPIC.
        • Dose (g)
        • Rate of infusion – this will include the starting rate, the incremental changes and maximum rates.
      • Pre-hydration
        • Ensure patients are well hydrated prior to IVIg infusion, consider hydration with 0.9% saline (10ml/kg bolus).
      • Pre-medications
        • Consider anti-pyretics (e.g., Paracetamol), anti-histamines (e.g. Cetirizine) or anti-emetics (e.g. Ondansetron) if prior rate-related reactions to IVIg.

      Dose

      • The dose (g) of IVIg prescribed will vary according to the indication.
      • Please prescribe the dose authorised by BloodSTAR. BloodSTAR will approve a dose that is rounded to the nearest vial size to reduce wastage.
      • In neonates, the dose in g/kg may be smaller than the minimum vial size of 5g, and an aliquot should be prescribed.

      IVIg product descriptions and comparisons

      Description

      Privigen AU* 10%
      (Australian)

      		 Privigen 10%
      (Imported)             		Kiovig 10%
      (Imported)

      Gammunex 10%
      (Imported)

      Octagam 10%
      (Imported)

      Flebogamma 10% DIF
      (Imported)

      Flebogamma 5% DIF
      (Imported)
      Concentration 10% 10% 10% 10% 10% 10% 5%
      Presentation

      5g in 50 mL

      10 g in 100 mL

      20g in 200 mL

      2.5g in 50 mL

      5g in 100 mL

      10g in 200 mL

      20g in 400 mL
      Stabilising agent Proline Proline Glycine Glycine Maltose Sorbitol Sorbitol
      IgA level < 0.025 mg/mL < 0.025 mg/mL <0.14 mg/mL ≤0.084 mg/mL ≤0.4 mg/mL <0.1 mg/mL < 0.05 mg/mL

      Storage*

      (All products stored in blood bank)

      		 Below 25°C 2 – 8°C* Below 30°C
      Compatible fluids 0.9% Normal Saline – may be used to flush IV-line post infusion
      Consumer product information Privigen AU Privigen Kiovig® Gammunex Octagam Flebogamma 10%            Flebogamma 5%


      IVIg administration rates

      • Administration rates vary between 5% and 10% products.
      • Patients receiving IVIg for the first time or switching IVIg brands, should commence at the slowest rate and grade up according to the table provided below.
      • Infusion rates should be individualised to the patient’s risk factors, comorbidities and tolerability with previous infusions.
      • Patients at risk for Aseptic Meningitis Syndrome (AMS), renal failure or thromboembolic adverse events should have IVIg administered at the minimum rate of infusion practicable.

      First infusion

      • Use this rate for:
        • First infusion
        • Switching between IVIg products
        • Significant gap between infusions.
      • The first infusion will run slowly. 
      Description

      Privigen AU* 10%
      (Domestic)

      		 Privigen 10%
      (Imported)             		Kiovig 10%
      (Imported)

      Gammunex 10%
      (Imported)

      Octagam 10%
      (Imported)

      Flebogamma 10% DIF
      (Imported)

      Flebogamma 5% DIF
      (Imported)
      Commencement rate (initial infusion) 0.25 mL/kg/hr 0.5 mL/kg/hr 1 mL/kg/hr

      Incremental rates:

      increase every 30 minutes only if tolerated

      0.5 mL/kg/hr

      1.0 mL/kg/hr

      1.5 mL/kg/hr

      2.0 mL/kg/hr

      2.5 mL/kg/hr

      1 mL/kg/hr

      2 mL/kg/hr

      3 mL/kg/hr

       

      2 mL/kg/hr

      4 mL/kg/hr

      6 mL/kg/hr
      Maximum rate for first infusion  Do not exceed 150 mL/hr Do not exceed 300 mL/hr






      Subsequent infusions

      Only follow this process if no adverse event to the first infusion (e.g., absence of headache, fever, tachycardia, nausea, vomiting, pain, or significant BP or heart rate change during and within 72 hours of first infusion).

      Description

      Privigen AU* 10%
      (Domestic)

      		 Privigen 10%
      (Imported)             		Kiovig 10%
      (Imported)

      Gammunex 10%
      (Imported)

      Octagam 10%
      (Imported)

      Flebogamma 10% DIF
      (Imported)

      Flebogamma 5% DIF
      (Imported)
      Commencement rate (subsequent infusion) 0.5 mL/kg/hr   1 mL/kg/hr

      Incremental rates:

      increase every 30 minutes only if tolerated

      1.0 mL/kg/hr

      1.5 mL/kg/hr

      2.0 mL/kg/hr

      2.5 mL/kg/hr

      1 mL/kg/hr

      2 mL/kg/hr

      3 mL/kg/hr

      2 mL/kg/hr

      4 mL/kg/hr

      6 mL/kg/hr

      Maximum rate Do not exceed 240 mL/hr Do not exceed 300 mL/hr Do not exceed 600 mL/hr*

      Foot Notes: * Please consider infusion rate and patient comorbidities. Consider slower rates in patients receiving doses of 2 g/kg. 

      Bottle sizes:

      • Blood bank will issue some smaller bottle sizes related to the dose the patient is ordered. This will decrease the chance of a bottle expiring at 6 hours, before all the dose has been administered.  
      • For example:
        • 20g IVIg ordered. Blood bank will issue 2 x 10g bottles.
        • 60g IVIg ordered. Blood bank will issue 2 x 10g bottles and 2 x 20g bottles.
        • Please administer the smallest bottle first. 

      *Storage

      • Please note different storage temperatures for the different IVIg products (Table 1).
      • Once removed from blood bank store IVIg at room temperature. Do not place in fridges in clinical areas.
      • If IVIg treatment is delayed for any reason return the product to blood bank.. 

      Administering and completing IVIg

      • Allow IVIg to reach room temperature.
      • IVIg does not contain any antimicrobial preservative, therefore each bottle of IVIg must be administered within 6 hours of spiking the bottle. 
        • Use a vented system. Do not use a burette.
        • Standard IV infusion giving set. IVIg does not need to be filtered; however, filtering will not harm the product.
        • Dedicate an IV line – do not mix with other medications or IV solutions (other than 0.9% saline).
        • Prime the IV infusion line with the IVIg product.
        • Ensure the correct infusion rate is prescribed and programmed into infusion pumps. 
        • Commence with the smallest bottles first.
          • Document rate changes in EMR.
          • It is not necessary to flush between bottles/batches. 
          • Flush with 0.9% Saline at conclusion of the infusion to ensure the entire dose is received.
          • Document the completion time and total amount infused in the EMR.
          • During EMR downtime IVIg will be issued with a compatibility report. Complete all details and send to HIS for scanning.

          Requesting replacement/additional bottles for an incomplete IVIg dose:

          Replacement or additional bottles may be requested if the current bottle has been spiked for 6 hours, or needs to be discarded, due to an adverse event or issues with IV access.

          • Calculate the ‘missing’ IVIg dose. 
            • 1g = 10 mL for all 10% IVIg products
          • For example:
            • 20g IVIg ordered = 200mL, patient received total of 150mL = 15g and ‘Missing’ dose is 5g
          • Call blood bank on ext. 55829 and explain the issue.
            • e.g., IVIg adverse event and infusion unable to be completed at fast administration rate and bottled expired.
            • Patient was ordered 20g and is ‘missing’ 5g of this dose.
            • Request replacement/additional bottle to make up ‘missing’ 5g dose.
          • Reprint the EMR IVIg order and take to blood bank.
            • NOTE: this will state the original EMR order (e.g., 20g). Do not take receipt of the full order, only the ‘missing’ dose. (e.g., 5g).
          • Only administer the ‘missing’ dose.

          Observing the patient receiving IVIg

          Time point Observations

          Baseline 

          (within 60 minutes before commencing transfusion)

          		 Temperature, pulse, respiratory rate, blood pressure, SaO2
          15 minutes after commencing document observations & close visual observation for at least 30 minutes Temperature, pulse, respiratory rate, blood pressure, SaO2
           At each rate changeTemperature, pulse, respiratory rate, blood pressure, SaO2, rate and IV pump volume 
          Hourly until transfusion is completed Temperature, pulse, respiratory rate, blood pressure, SaO2, rate and IV pump volume
          Conclusion

          Temperature, pulse, respiratory rate, blood pressure, SaO2, rate and IV pump volume.

          Observe the patient post the infusion.

          • Ask the patient and parents to report any pain at the IV site, or symptoms during the infusion (e.g., headache, nausea, chills).
                              

          Adverse events

            ADVERSE EVENTS 
          Acute (during or within 6 hours of infusion)
          Mild to moderate Severe
          Symptoms
          • Chills/rigor
          • Headache
          • Nausea/vomiting
          • Pain – abdominal, extremity, chest and back pain
          • Rash/urticaria/flushing
          • Dizziness
          • Dyspnoea
          • Anaphylaxis
          • Transfusion related circulatory overload (TACO)
           
          Signs
          • Fever
          • Changes in BP or HR
          • Changes in RR or SaO2.
          Management
          • Pause IVIg
          • Request medical review
          • Treat as appropriate (e.g., paracetamol, anti-histamines or IV fluids)
          • If the symptoms resolve and observations stabilise then cautiously restart at previously tolerated rate
          • Monitor patient closely
          • If symptoms return or escalate cease IVIg.
          • Cease infusion, follow MET/Rapid review process, treat as guided by symptoms (e.g., oxygen, adrenaline)
          • Anaphylaxis is a rare but documented adverse effect of IVIg.  Please refer to the Anaphylaxis guideline for management
          Future IVIg infusions

          Consider pre-hydration (0.9% saline bolus) and/or pre-medication (e.g., paracetamol, antihistamine) for future IVIg infusions related to symptoms.

          Consider capping future IVIg infusions at tolerated rate.

          REPORT ALL POTENTIAL ACUTE OR DELAYED ADVERSE EVENTS (including mild events)

          1. Call Blood bank on ext: 55829.
          2. Order a “Transfusion Reaction evaluation” in EMR.
          3. Document any adverse effects in EMR (e.g., headache, fever, nausea).
          4. Blood bank staff will contact the on-call haematologist who can provide support/advice for management of the current IVIg infusion (e.g., medication to treat, hydration, slower infusion rates or changing IVIg product) and future infusions.
          5. Report any other adverse event (e.g., administration issue) or near miss via VHIMS.
          Adverse events and near misses are discussed at the Blood Management Committee and are reported to CSL as needed.

          Poster - Recognition and management of ACUTE IVIg adverse events


            ADVERSE EVENTS 
          Delayed (6 hours to 72 hours post IVIg infusion)
          Mild to moderate Severe
          Symptoms
          • Headache
          • Fever
          • Nausea/vomiting
          • Flu-like illness
          • Pain, muscle aches or arthralgias
          • Fatigue
          • Rash
           
          • Aseptic meningitis (*see below for further information)
            • Typically within 72 hours of IVIg
            • Characterized by fever, headache, altered mental status, nausea/vomiting, neck stiffness and photophobia.
            • CSF evaluation not required for diagnosis. 
            • Increased frequency in those with history of migraines
            • Increased frequency with high dose IVIg
          • Thromboembolic events
            • Infusion of IVIg may lead to increased blood viscosity
          • Renal impairment
          • Haemolytic anaemia
          (IVIg contains Anti-A and Anti-B, these can cause haemolysis and a positive DAT, particularly in blood group A patients)
          Management
          • Treatment of symptoms with simple measures (e.g., Paracetamol, anti-emetics).
           
          • May need admission to hospital
          • See investigation below for severe headache.
          • IV fluids, supportive care with analgesia (e.g., Paracetamol and Nurofen [if not contraindicated]) and anti-emetics
          • Seek haematology guidance.
          Future IVIg infusions

          Consider pre-hydration (0.9% saline bolus) and/or pre-medication (e.g., paracetamol, antihistamine for future IVIg infusions related to symptoms.

          Consider capping future IVIg infusions at tolerated rate.

          REPORT ALL POTENTIAL ACUTE OR DELAYED ADVERSE EVENTS (including mild events)

          1. Call Blood bank on ext: 55829.
          2. Order a “Transfusion Reaction evaluation” in EMR.
          3. Document any adverse effects in EMR (e.g., headache, fever, nausea).
          4. Blood bank staff will contact the on-call haematologist who can provide support/advice for management of the current IVIg infusion (e.g., medication to treat, hydration, slower infusion rates or changing IVIg product) and future infusions.
          5. Report any other adverse event (e.g., administration issue) or near miss via VHIMS.
          Adverse events and near misses are discussed at the Blood Management Committee and are reported to CSL as needed.

          Poster - Recognition and management of DELAYED IVIg adverse events


          * Management of the patient with a severe headache (e.g., possible aseptic meningitis) post IVIg
          Symptoms
          • Headache
          • Nausea/vomiting
          • Fever
          • Altered mental status
          • Neck stiffness
          • Photophobia
          Investigations for consideration
          • Venous gas
          • Electrolytes including calcium, magnesium and phosphate
          • Ammonia
          • Consider neuroimaging (e.g., CT or MRI) in discussion with the reviewing doctor, considering the underlying diagnosis (e.g., ITP), presence of neurological symptoms, and severity of symptoms.
          • Lumbar puncture is not required to make the diagnosis of aseptic meningitis.
          Management
          • May need admission to hospital
          • IV fluids, supportive care with analgesia (e.g., Paracetamol and Nurofen [if not contraindicated]) and anti-emetics
          Seek haematology advice if you suspect aseptic meningitis and report.


          Management of patients with history of aseptic meningitis, requiring ongoing treatment with IVIg


          Asceptic meningitis flowchart IVIg Guideline