Overwhelming Post-Splenectomy Infection (OPSI)

Splenectomy is a treatment for haematological disorders, palliation of hypersplenism, symptom relief in patients with symptomatic splenomegaly, splenic trauma and as a diagnostic procedure when tha pathology can not be ascertained by any other intervention. Sickle cell anaemia results in “autosplenectomy” and loss of splenic function. One of the risk of loss of splenic function is overwhelming post-splenectomy sepsis, a condition that proceeds from a mild flu-like illness to fulminating sepsis in a short time and when fully established has a mortality of 50-80%.

Pathogenesis

Microbiology

Pneumococcus is the commonest organism responsible for about 50-90% of the infections.  H. influenza, Meningococcus, Streptococcus, Staphylococcus and E. Coli are the other organisms responsible for OPSI.

Role of spleen in Immunity

The spleen is involved in production of IgM producing memory cells to polysaccharide antigens. These responses are T cell independent. The spleen also produces the following molecules

  1.  Properdin which is an activator of C3 by the alternate pathway
  2. Tuftsin a tetrapeptide that stimulates phagocytosis
  3. C3a is a chemotactic factor
  4. Factor B is a component of the alternate complement pathway

Splenectomized individuals have a defect in cell mediated immunity because of depletion of CD45RA+

Clinical Presentation
The risk of OPSI appears to vary with the underlying pathology. Conditions that impair immunity are associated with a higher risk of OPSI. The risk is about 1-2% in splenectomies because of trauma or idiopathic thrombocytopaenic purport, 6% in Hodgkin Lymphoma and increases to as high 11% in patients with thalassaemia.

The risk diminishes with age at splenectomy. Infants have a risk of 15%, children 10.4% older children 4.4% and adults about 0.9%. Splenectomized patients are at a higher risk of death from infection. Though the adults with splenectomy as predisposed to infection as those without splenectomy the risk of mortality in those with splenectomy is 58 times higher than those without.

About half the infections occur within 2 years and about three-fourth within 5 years of splenectomy. However OPSI may be seen decades after splenectomy.

OPSI presents as a mild illness upper respiratory infection that rapidly progresses to a fulminant illness. The patients develop septic shock, multi system organ failure and disseminated intravascular coagulation within hours. Early suspicion and initiation of antibiotics is the key to success.

Investigations

The focus of management of patients with OPSI is early initiation of antibiotics. When recognised early the mortality of OPSI can be reduced to 10%. There is no test that can predict the risk of OPSI. Haematological and biochemical test as appropriate for patients with sepsis should be performed. Blood culture should be performed to identify the organism. Antibiotics therapy should be initiated immediately and not await the results of blood culture.

Management

Patient Education: The key to successful treatment of  OPSI is the timely initiation of antibiotics. The importance of seeking medical consultation as soon as symptoms occur should be emphasised to the patient. The patient must carry a card or a bracelet identifying him/her as a person who has undergone splenectomy.

Initial Antibiotics: The antibiotics chosen for initial treatment of OPSI are directed against pneumococcus, H. Influenzae and meningococcus. Penicillin for many years was the drug of choice but with the emergence of penicillin resistant pneumococcus it is no longer an appropriate first line antibiotic in OPSI. The patient should be instructed to take oral antibiotics at the first sign of infection making it very clear that this is not a substitute for seeking immediate medical consultation. This strategy ensures that some effective antibiotic is administered at the earliest but these antibiotics are insufficient to treat OPSI. The oral antibiotics recommended include a combination of amoxicillin and clavlunate, cefuroxime aexetil or a fluoroquinolone with a gram positive cover like moxifloxacin. If a patient of suspected OPSI is seen in the clinic an intramuscular dose ceftriaxone 100mg/kg (maximum 2g) should be administered before immediately transporting the patient to the nearest intensive care facility for further treatment.

The initial choice of antibiotics for OPSI is as follows

  1. Patient not Hypersensitive to β-lactams: Vancomycin 10–15mg/kg  i.v. every 12 hours (maximum 1g, dose to be adjusted according to creatinine clearance) with Ceftriaxone 2g i.v. daily (50mg/kg i.v. every 12 hours for children)
  2. Patients Hypersensitive to β-lactams: Vancomycin 10–15mg/kg  i.v. every 12 hours (maximum 1g, dose to be adjusted according to creatinine clearance) with Levofloxacin 750mg i.v. q 24h

The local treatment recommendations need to be followed in case of a significant prevalence of penicillin resistant pneumococci. The therapy should be modified according to microbiological results and antibiotic sensitivity.

Prevention of OPSI

Prevention of OPSI rests on patient education, vaccination and use of prophylactic antibiotics.

Patient Education

The patients must be made aware of the symptoms of OPSI. The importance of seeking prompt professional opinion in case of fever. They should carry a card/bracelet identifying them as patients having undergone splenectomy. They should keep a supply of antibiotics listed above to be taken immediately in case of fever.

Vaccination

(See British Committee for Standards in Haematology guidelines for prevention and treatment of infection  in patients with an absent or dysfunctional spleen)

Patients should be vaccinated against pneumococcus, meningococcus and H. influenzae. The three vaccines may be administered together but at different locations.

  1. Pneumococcal Vaccination: Two pneumococcal vaccines are available. The 23 valent polysaccharide vaccine  (PPV) and the 13 valent protein conjugated vaccine (PCV).  PPV is ineffective in children younger than two years. The vaccination should be administered at least two weeks, ideally six weeks before the splenectomy. In case it is not possible, vaccinations should be delayed to two weeks after splenectomy. The vaccination schedule in the link mentioned above may be followed.
  2. H. Influenzae: H. Influenzae vaccine is a conjugate between capsular polysaccharide of H. influenzae type b and either non-toxic variant of diphtheria toxin or tetanus toxoid. Hib is a part of primary vaccination. If splenectomy is performed before primary immunisation is completed the primary vaccination should be continued as per schedule. If splenectomy is performed after completion of primary immunisation an additional dose of Hib vaccination should be given
  3. Meningococcus: Meningococcal vaccines may be polysaccharide or conjugated. Conjugated vaccines may be monovalent only against serogroup C or quadravalent against serogroups A, C, W and Y. Patients should be vaccinated at least 2 weeks (6 weeks) before splenectomy.

Prophylactic Antibiotics

Despite there being no evidence to prove their efficacy, most agree with the use of prophylactic antibiotics in patients with splenectomy. The main concern is infection by resistant stains. While the British Committee for standards in Haematology has taken the position that antibiotic prophylaxis should be administered lifelong (Br J Haematol 2011;155:308-17), the American and the French advocate use of prophylactic antibiotics in adults for 1-2 years after splenectomy when the risk of infection is the highest (Mayo Clin Proc. 2011; 86: 686–701). Children with splenectomy should be administered antibiotics directed against Pneumococcus till the age of 5 years. If the child remains free of infection one may consider discontinuation of antibiotics.  Penicillin V (125mg twice a day till the age of 3 and 250mg twice a day thereafter) is the drug of choice in areas where penicillin resistant pneumococcus are not prevalent. Other antibiotics including macrolides, co-trimoxazole and a fluoroquinolone with a gram positive cover like moxifloxacin may be used where penicillin resistant pneumococcus is prevalent.

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