Overwhelming post-splenectomy infection

Very Ill
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Diagnosis and reasoning

This patient has presented with signs and symptoms suggestive of acute infection, in association with altered mentation, tachypnea, tachycardia, and hypotension. Furthermore, his complete blood count is significant for a marked neutrophilia. The above findings immediately raise the specter of sepsis and septic shock. Urgent resuscitation and stabilization, including intravenous (IV) fluid therapy, is a must, along with close observation in a critical care setting. Evaluation of baseline function is also important. In this regard, arterial blood gases reveal metabolic acidosis, an ominous finding. However, the coagulation profile is normal, as are renal and liver profiles, suggesting that disseminated intravascular coagulation (DIC) and multi-organ failure are yet to set in. Following stabilization, an urgent search should be made for the source of sepsis. Unfortunately, examination fails to throw up any localizing signs of infection, while the negative chest x-rays and urinalysis make pneumonia and urinary tract infection further unlikely. That said, the history does provide a very important clue: namely, the splenectomy three years ago. Asplenic patients are highly susceptible to infection by encapsulated bacteria such as S. pneumoniae, N. meningiditis, and H. influenzae. These infections may progress into fulminant sepsis within a matter of hours, with this being termed overwhelming post-splenectomy infection (OPSI). The uncertainty about his vaccination status adds more fuel to this fear. Where OPSI is likely, aggressive empirical antibiotic therapy is essential, with the combination of intravenous (IV) vancomycin and ceftriaxone being preferred. Blood, urine, and CSF cultures should be obtained beforehand, and the drug regimen adjusted appropriately once culture results are available. Note that noradrenaline therapy is not indicated immediately, but may be required if fluid replacement fails to stabilize the patient.


Discussion

Overwhelming post-splenectomy infection (OPSI) is a progressive and fulminant bacteremia affecting hyposplenic or asplenic patients. It is a medical emergency, with a mortality rate of 38% to 70%, even with optimal treatment. The incidence of OPSI is estimated to be 2-5 per 1,000 asplenic patients per year. Overall, each asplenic patient will have a 5% lifetime risk of developing the condition. To understand the underlying pathophysiology, one must recall that the spleen is the key site of production of antigen-specific IgM antibodies, which opsonize encapsulated bacteria. Those opsonized bacteria are then removed by macrophages present in the splenic circulation. Thus, in hyposplenic or asplenic patients, humoral immunity is greatly affected, rendering them highly susceptible to infection by encapsulated bacteria. Such infections can then proliferate rapidly and cause a fulminant sepsis. S. pneumoniae accounts for over half of all cases of OPSI; N. meningitidis and H. influenzae are also commonly encountered. C. canimorsus is encountered occasionally, following dog bites. Patients are at the highest risk of developing OPSI within the first two years following splenectomy, although cases have been reported as long as 20 years afterward. Other known risk factors include age below 16 or above 50 years, co-existing hematological disorders or malignancies, ongoing immunosuppression, previous invasive pneumococcal disease, and poor or no response to vaccination against the common pathogens. Initially, these patients experience mild and nonspecific symptoms such as fatigue, malaise, abdominal pain, or nausea. Subsequently, fever, headache, arthralgias, myalgias, vomiting, or rashes may occur. If not detected and treated promptly, septic shock and disseminated intravascular coagulation (DIC) will occur, followed by multi-organ failure. Very importantly, the time from the onset of symptoms to death may be as short as 24 to 48 hours. Where OPSI is suspected, several urgent steps need to be taken. Close supportive care is essential, including fluid resuscitation to maintain tissue perfusion; vasopressors or inotropes may also be required. Adequate oxygenation is also important, with intubation needed if respiratory distress occurs. Aggressive intravenous empirical antibiotic therapy is also a must, with the combination of vancomycin and ceftriaxone being preferred. The former has excellent gram-positive coverage, including against penicillin-resistant S. pneumoniae, while the latter adds double coverage of gram-positive organisms, while further including gram-negative coverage against N. meningitidis and H. influenzae. Extensive and comprehensive diagnostic testing should proceed in parallel. Complete blood counts often reveal a leukocytosis, although leukopenia is also possible. Coagulation profiles may reveal features suggestive of DIC. Where there is multi-organ failure, liver and renal profiles may be abnormal. A complete septic screen is also important, including blood and urine, and cerebrospinal fluid (CSF) cultures, as well as chest x-rays. Note, however, that lumbar punctures are contraindicated in patients with DIC. Given the high mortality and morbidity of OPSI, prevention is far preferable. Following splenectomy, patients should be educated about the condition and instructed to seek medical help promptly should they notice any symptoms of infection. Furthermore, vaccination against pneumococcus, meningococcus, and H. influenzae is essential. These individuals should also receive annual vaccinations against influenza, to avoid secondary bacterial infection. The use of prophylactic antibiotics is controversial, given the known negatives of development of bacterial resistance, non-compliance and a false sense of security. However, this may yet be considered in patients at continued high risk of pneumococcal infection. Patients may also be provided with a supply of appropriate antibiotics for emergency use, to be self-administered in case of infection.


Take home messages

  1. Overwhelming post-splenectomy infection (OPSI) is a rapidly progressive, fulminant bacteremia which occurs in hyposplenic or asplenic patients.
  2. Affected individuals initially present with mild and nonspecific symptoms, but then rapidly progress to septic shock and multi-organ failure if not treated promptly.
  3. Early empirical antibiotic therapy is key to the management, with the combination of intravenous (IV) vancomycin and ceftriaxone preferred currently.
  4. Vaccination against pneumococcus, meningococcus and H. influenzae is key to the prevention of OPSI.

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