Prevention of sepsis in asplenia or functional hyposplenia (Guidelines)

TAM (Treatments and Medicines) NHS Highland
NHS Highland

The role of the spleen in protecting against overwhelming sepsis due to encapsulated bacteria has long been established.1 The absence of the spleen results in an increased risk of serious sepsis and associated mortality. The risk of death as a result of overwhelming post splenectomy infection (OPSI) has been calculated to be up to 600 times greater than that in the general population, and the estimated lifetime risk of OPSI is 5%.2 Although the greatest risk is in the first two years a degree of risk will be lifelong.3 There is some perception that the risk only applies to people in whom there is underlying haematological disease, but a review has concluded that OPSI after splenectomy for trauma in adults is indeed a potential risk.4 Analysis of Scottish data 5 indicates that: 

  • the risk of severe infection or death is highest in the first three years after splenectomy and then declines significantly;
  • the risk of a second or third infection is particularly high among those who have a first severe infection, particularly within six months of the first occurrence;
  • the greatest risk is amongst those who have had a splenectomy for haematological malignancy.

A review in 20076 suggests that factors associated with high risk of invasive pneumococcal disease include:

  • aged less than 16 years or greater than 50 years
  • inadequate serological response to pneumococcal vaccine
  • a history of previous invasive disease
  • splenectomy for underlying haematological malignancy, particularly in the context of on-going immunosuppression

It has been known for several decades that immunisation, antibiotic prophylaxis and good advice can reduce the risk of sepsis. Despite this, there is ample evidence that management of asplenic patients is sub-optimal.7 In addition to patients who have undergone splenectomy, other categories of patients may be functionally hyposplenic; those suffering from sickle cell anaemia, thalassaemia major, essential thrombocythaemia, lymphoproliferative diseases and coeliac syndrome. Chronic graft versus host disease will also result in hyposplenia.

Guidelines were published in 19968 and updated in 20019 , 200210 and most recently in 20116. Research indicates that even since their publication best practice preventive measures are not being followed.11

After splenectomy, patients are most at long-term risk of infection from Streptococcus pneumoniae, but other encapsulated organisms such as Haemophilus influenzae and Neisseria meningitidis have also been reported as significant pathogens. There is also a greater risk of infections with Escherichia coli and Pseudomonas aeruginosa; Capnocytophaga canimorsus (formerly DF-2) can cause fulminant sepsis following dog bites; blood-borne protozoal infections such as malaria and babesiosis. Salmonella is also a common pathogen in sickle cell disease.

Recommended immunisations

  1. Pneumococcal. Streptococcus pneumoniae is a bacterial pathogen that affects children and adults world-wide. The organism colonises the upper respiratory tract, but severe infection can result from dissemination of the bacteria into the bloodstream and the central nervous system. Asplenic individuals are at the highest risk from pneumococcal infection due to reduced clearance of encapsulated bacteria from the bloodstream. Children in this group are at particular risk of fulminant pnemococcal sepsis and subsequent high mortality. Where possible, the vaccine should be given, together with advice about the increased risk of pneumococcal infection, four to six weeks (but at least two weeks) before splenectomy or the initiation of chemotherapy or other immunosuppressive treatment. In the case of splenectomy following trauma there is evidence that better functional antibody responses seems to occur if vaccination is delayed for 14 days after surgery. 12

    Revaccination: Antibody levels are likely to decline rapidly in individuals who have asplenia or splenic dysfunction and therefore revaccination with 23-valent PPV is recommended every five years. Testing of antibodies prior to vaccination is not required.13

  1. Hib and meningococcal. Asplenic/hyposplenic children and adults may be at increased risk of invasive disease caused by Haemophilus influenzae type b, and meningococci, and require appropriate immunisation, as per summary table below.
  1. Influenza. In asplenic/hyposplenic patients, influenza vaccination is associated with a 54% reduced risk of death compared to unimmunised asplenic persons14. Annual vaccination against influenza is recommended, preferably in September. Asplenic/hyposplenic individuals are not thought to be at more risk of catching influenza but vaccination may reduce the risk of secondary bacterial infection.

In practice it is difficult to know whether some individuals (e.g. those with coeliac syndrome) are hyposplenic, as there is no readily available diagnostic test, and to some extent it therefore depends on clinical judgement.

In the absence of evidence of hyposplenia, only influenza and pneumococcal vaccines are recommended for those with coeliac syndrome.

Summary Table

First diagnosed under one year

Children should be fully immunised according to the national schedule, and should also receive

  • Two doses of MenACWY vaccine at least one month apart during infancy
  • One additional dose of PCV 13* and one dose of MenACWY conjugate vaccine two
    months after the routine 12-month vaccinations: and
  • After the second birthday, an additional dose of Hib/MenC should be given, along with
    the pneumococcal polysaccharide vaccine (PPV23).

First diagnosed at 12-23 months of age

If not yet administered, give the routine 12 month vaccines i.e. Hib/MenC, PCV13, MMR and Men B, plus

  • One additional dose of PCV13* and one dose of MenACWY conjugate vaccine two
    months after 12-month vaccinations: and
  • One additional dose of Hib/MenC and one dose of PPV23** after the second birthday

If not already received, two primary doses of Men B vaccine should be given two months apart at the same time as the other vaccinations.

First diagnosed at from two years to under 10 years of age

Ensure children are fully immunised according to the national schedule, and they should also receive:

  • One additional dose of Hib/MenC and one dose of PPV23*: and then
  • A single dose of MenACWY conjugate vaccine two months later

If not already received, two primary doses of MenB vaccine should be given two months apart at the same visit as the other vaccinations

First diagnosed at age ten years onwards

Older children and adults, regardless of previous vaccination, should receive:

  • A single dose of Hib/MenC and a single dose of PPV23*:and then
  • A single dose of MenACWY conjugate vaccine one month later

If not already received 2 primary doses of Men B vaccine should be given one month apart at the same time as the other vaccinations

*Patients on Eculizumab (Soliris) therapy are not at increased risk of pneumococcal disease and do not require PPV23 or additional doses of PCV13
** Patients with splenic dysfunction should receive boosters of PPV at five yearly intervals

Guidance on the use of zanamivir, oseltamivir and amantadine for the treatment of influenza produced by the National Institute for Clinical Excellence (NICE) and endorsed by Health Improvement Scotland should be followed15. This advises that when there is evidence that influenza is circulating in the community at levels above the baseline, antiviral medication for the treatment of influenza in the community may be prescribed for those at risk, provided that treatment can be started within 48 hours of the onset of symptoms. The Scottish Government Health Department issues advice when prescribing of antivirals in general practice becomes appropriate.

Antibiotic prophylaxis

The 1996 Guidelines8 recommended that prophylactic antibiotics should be offered in all cases. There are no data to support or refute the previously published recommendations for antibiotic prophylaxis and treatment of infection in asplenic individuals10. However, it is recognised that compliance may be a problem, (and there has also been more recent discussion concerning the increase in penicillin resistance of pneumococci). Overall pneumococcal resistance to penicillins remains low in the UK10. Though not common in the UK, rates of up to 43% of isolates with some degree of resistance have been reported in Spain16 and travel will bring about increased exposure to resistant strains. The reluctance of some people to take antibiotics on a lifelong basis must also be taken into consideration. Given these factors, people in the following groups should be strongly recommended to receive prophylaxis:

  • All people in the first three years after splenectomy5
  • All children up to the age of 16 and those over 50 years6
  • Individuals in whom there is underlying impaired immune function, (malignancy or haematological condition)
  • Individuals who have suffered one severe infection

 Regardless of whether prophylaxis is used, patient education is of paramount importance regarding:

  • The fact that immunisation and antibiotic prophylaxis does not guarantee protection against invasive disease.
  • The need for rapid medical assessment of suspected infections
  • The requirement to keep a course of antibiotics at home in order to commence treatment prior to medical assessment when this is delayed.

Recommended doses for antibiotic prophylaxis:20,21

PENICILLIN (1st choice in adults) (phenoxymethylpenicillin):

Adult and child over 5 years

250mg twice daily

Child aged 1 to 5 years

125mg twice daily

Child under 1

62.5mg twice daily

ERYTHROMYCIN: (2nd choice – for use in those with penicillin allergy)

Adult and child over 8 years

500mg twice daily

Child aged 2 to 8

250mg twice daily

Child 1 month to 2 years

125mg twice daily

AMOXICILLIN: (Preferred choice in children17)

Adult and child over 12 year

500mg twice daily

Child aged 5 to 12

250mg twice daily

Child 1 month to 5

125mg twice daily

Antibiotic Treatment

Asplenic individuals should receive a supply of stand by antibiotic whether or not they receive prophylactic antibiotics17,18,19, with clear instructions on when to take. Recommended courses for adults include amoxicillin or levofloxacin for those with penicillin allergy.

Travel

Patients should be made aware of the need to seek travel advice early, even for travel in Europe and the potential risks of overseas travel particularly with regard to malaria and unusual infection such as those from animal bites10. Those not taking regular antibiotic prophylaxis should be advised to do so on holiday. Asplenics can have live vaccines unless there is an underlying immunosuppressive disorder. 

  1. Malaria. All asplenic patients should be made aware of the increased risk of severe falciparum malaria, and the requirement for antimalarial prophylaxis cannot be overemphasised. Travel to areas where malaria is endemic should be discouraged. Depending on sensitivities in the area of intended travel, doxycycline may offer a combination of antibiotic and antimalarial prophylaxis17. 
  2. Tick bites. Babesiosis is a rare potentially severe tick-borne disease caused by infection with a protozoan parasite. Most infections are asymptomatic, though the clinical syndrome can include fever, chills, myalgia, fatigue and jaundice secondary to haemolytic anaemia that may last from a few days to several months. Geographic distribution of the species of ticks that carry the disease is worldwide. Asplenic patients should be educated about the need for protective clothing when walking in areas of forestry or long grass. 
  3. Meningococcal disease. There is an increased risk of serogroup A, W135 or Y disease in some countries. Ensure that individuals have been immunised with MenACWY conjugate vaccine as per summary table page 4.

Animal Bites

Capnocytophaga canimorsus can cause febrile illness in patients with impaired immune systems who have been licked, bitten or scratched by dogs or cats. Co-amoxiclav, the antibiotic of choice for these infections, should be given prophylactically to high risk individuals who are bitten by a dog or cat.

Treatment of acute infection

General Practitioners attending a known asplenic patient with clinically significant infection should (provided there is no history of anaphylaxis to penicillin) give an immediate dose of intramuscular or intravenous ceftriaxone before transfer to hospital:

Age

Dosage

IM Dilution & administration

IV Dilution & administration

Children under 50kg

80mg/kg

Dissolve each 1g vial in 3.5mLof 1% lidocaine hydrochloride, resulting in a total of 4mL.

Administer intra-muscularly.

IM injections of more than 1g should be divided between different sites

Dissolve each 1g vial in 10ml of water for injection and infuse over 30 minutes, OR

Adults and children over 50kg

2g

Dissolve each 2g vial in 40ml of glucose 5% or sodium chloride 0.9% and administer as an infusion over at least 30 minutes

If ceftriaxone is not available, give benzylpenicillin as below:

Age

Dosage

Dilute with water or

sodium chloride 0.9%

IM

IV

Infant under 1 year

300mg

1mL

2mL

Child 1 to 9 years

600mg

2mL

4mL

Child 10 years and over and adult

1200mg

4mL

8mL

Intravenous administration should be at a rate of 300mg per minute maximum. So for example, 1200mg, reconstitute with 8mL and give over 4 minutes. 

If there is a history of anaphylaxis to penicillin chloramphenicol may be used.

General - Roles & Responsibilities

This guidance is provided to assist general practices in providing appropriate treatment and prophylaxis to their patients who have asplenia or functional hyposplenia. As historically management of patients in these categories has been found to be sub-optimal7 the Health Protection Team have agreed to assist General Practitioners by notifying them of patients potentially in this category, obtaining data by the following means:

  • Patients undergoing elective splenectomy - Clinicians are requested to ensure that the In-patient Report (Appendix 1) is completed and forwarded to the Health Protection Team.
  • The Health Protection Team also actively seeks to identify relevant patients using data supplied by the Pathology Department and SMR data from the Health Intelligence & Knowledge team in Public Health. This is undertaken quarterly.

All patients identified as described above will be sent a leaflet, A guide for people without a working spleen which includes an alert card (Appendix 2) to be carried in a purse/wallet.

Some patients may additionally wish to purchase a MedicAlert bracelet and details are available at www.medicalert.org.uk , or by telephoning 01908 951045. Patients may also be encouraged to obtain further information on splenectomy: http://www.patient.co.uk/health/Splenectomy-Ongoing-Prevention-of-Infection.htm

Splenectomy In-patient Report - Adults (Appendix 1)

All patients who undergo splenectomy should receive the following vaccines and be advised regarding antibiotic prophylaxis.

Please complete this form prior to discharge and forward to the Health Protection Team, Larch House, Stoneyfield Business Park Inverness. The Health Protection Team will write to the patient’s GP to ensure that they are aware of the relevant guidance.

For detailed guidance regarding protection against sepsis following splenectomy please refer to NHS Highland Guidelines for the Prevention of Sepsis in Patients with Asplenia or Functional Hyposplenia which are available on the Intranet, under Policies and Procedures.

Vaccine

Where possible, the vaccination course should be started four to six weeks (at least 2 weeks) before surgery.

Date

Hib/MenC (Menitorix)

MenACWY conjugate vaccine

(2 month after Hib/MenC)

Pneumovax

MenB (Bexsero) (First dose with Hib/MenC; second dose with MenACWY 2 months after Hib/MenC)

Influenza (if appropriate time of year)

Please note antibiotic prescribed, or reason if not prescribed:

Antibiotic prophylaxis

Date

Phenyoxymethylpenicillin 1st choice

Dose: 250mg twice daily

Erythromycin: (2nd choice – for use in penicillin allergy)

Dose: 500mg twice daily

Other – please specify and state reason for use

Please sign below to indicate that the ‘information about splenectomy for patients’ leaflet has been given to the patient, and the card on the back of the leaflet has been completed:

Leaflet

Date

Signature

A guide for people without a working spleen (NHS Health Scotland 2015)

 Affix patient identification label here

Alert Card (Appendix 2)

Editorial Information

Last reviewed: 08/01/2018

Next review date: 30/10/2020

Author(s): Health Protection Team.

Version: 7

Approved By: TAM Subgroup of ADTC

Document Id: TAM351