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Overwhelming Post-splenectomy Infection (OPSI)
A Case Report and Review of the Literature
Trent L. Morgan, MD, CPT, MC, USAF, Eric B. Tomich, DO, CPT, MC, USA
J Emerg Med. 2012;43(4):758-763.
Abstract and Introduction
Abstract
Background Overwhelming post-splenectomy infection (OPSI) is a serious disease t
hat can progress from a mild flu-like illness to fulminant sepsis in a short tim
e period. Although relatively rare, it has a high mortality rate with delayed or
inadequate treatment, and therefore, it is important for Emergency Physicians t
o be familiar with it. Patients who are asplenic or hyposplenic are at an increa
sed risk for infection and death from encapsulated organisms and other dangerous
pathogens.
Objectives There is an abundance of literature discussing OPSI from the perspect
ive of hematologists and infectious disease specialists, but an Emergency Medici
ne perspective is necessary to truly understand the acute nature of the disease.
The objective of this article is to present a careful examination of the litera
ture with a focus on early diagnosis and management to provide Emergency Physici
ans with the ability to positively affect outcomes of this deadly disease.
Case Report We present the case of a well-appearing 5-month-old girl with congen
ital asplenia who presented to the Emergency Department with fever, and rapidly
progressed to septic shock as a result of OPSI. Aggressive resuscitation was ini
tiated, including empiric antibiotics, and after a prolonged hospital course in
the pediatric intensive care unit, the child recovered.
Conclusion Rapid identification of patients at risk for OPSI, followed by admini
stration of intravenous antibiotics, usually vancomycin and ceftriaxone, combine
d with early goal-directed therapy, are the keys to successful treatment. If ini
tiated early in the patient's course, the 70% mortality rate can be reduced to t
he 1040% range.
Introduction
Overwhelming post-splenectomy infection (OPSI) is a serious disease that can pro
gress from a mild flu-like illness to fulminant sepsis in a short time period. A
lthough relatively rare, it has a high mortality rate with delayed or inadequate
treatment, and therefore it is important for Emergency Physicians to be familia
r with it. Patients who are asplenic or hyposplenic are at an increased risk for
infection and death from encapsulated organisms and other dangerous pathogens.
The objectives of this article are to review the literature discussing OPSI from
the perspective of the Emergency Physician and to understand the acute nature o
f the disease. Careful examination of the literature with a focus on early diagn
osis and management provides Emergency Physicians with the ability to positively
affect outcomes of this deadly disease.
Case Report
A 5-month-old girl was brought to the Emergency Department (ED) by her mother wi
th a chief complaint of fever (38.1C oral), fussiness, and cough for several hour
s. The patient had a history of duodenal atresia, midgut malrotation, congenital
asplenia, and an undiagnosed liver disorder. She was born at 36 weeks gestation
and spent some time in the neonatal intensive care unit. She was hospitalized 1
month before presentation for a fever of unknown origin that was treated with e
mpiric intravenous (i.v.) antibiotics, from which she recovered without incident
. Her immunizations were up to date. The patient's mother denied sick contacts,
diarrhea, bloody stools, difficulty breathing, rhinorrhea, or lethargy. The pati
ent was taking oral feeds with adequate urine output and had a single episode of
vomiting. She was given a dose of acetaminophen before arrival. On examination,
the patient was afebrile (37.6C [99.8F] rectal), non-toxic, smiling, and interact
ive. She was diffusely jaundiced and had scleral icterus that had been present f
or weeks. The remainder of her physical examination was unremarkable. Laboratory
tests were significant for a white blood cell count (WBC) of 36,000 cells/mm 3
with 23% bands, and venous hemoglobin of 6 gm/dL. Liver function studies were gr
ossly abnormal, with coagulation times mildly prolonged. Venous lactate was 2.1.
Urinalysis and serum chemistry were unremarkable. Two sets of blood cultures we
re also obtained. A chest radiograph was normal. After discussion with a pediatr
ic infectious disease specialist, ceftriaxone 50mg/kg i.v. was ordered. The pati
ent was admitted to the pediatric service, where several hours later she develop
ed respiratory depression, lethargy, and signs of septicemia and disseminated in
travascular coagulopathy (DIC). She was intubated and central venous access was
obtained. Ceftriaxone dose was increased to 100mg/kg and vancomycin was added. C
rystalloid and blood product resuscitation was initiated along with vasopressor
agents. A lumbar puncture was unremarkable. In<24h from the time they were ob
tained, the blood cultures were positive for Gram-positive, lancet-shaped diploc
occi, presumed to be Streptococcus pneumoniae. She was transferred to a pediatri
c intensive care unit at another institution where, after a prolonged hospital c
ourse, she recovered.
Discussion
This case is an illustrative example of how OPSI can present. A patient may not
be ill-appearing initially, but can quickly decompensate into fulminant sepsis.
The spleen is the largest accumulation of lymphoid tissue in the body, filtering
1015% of the body's blood volume per minute. [1] When its function is absent or
reduced, the ability to fight off infection is impaired, particularly from encap
sulated bacterial organisms. Mortality rates from OPSI range from 50% to 70%; ho
wever, with aggressive and early medical care, the mortality rate may be as low
as 10%. [2] There are few infectious conditions that progress as rapidly as OPSI
, making it especially important for Emergency Physicians to identify it and sta
rt appropriate antibiotics and other critical interventions.
Pathophysiology
When examining the pathophysiology of OPSI, two factors must be considered: the
conditions that predispose to asplenism or hypopslenism, and the organisms that
thrive in these patients. The spleen has an abundance of lymphoid tissue, includ
ing splenic macrophages that attack encapsulated organisms. In their absence, th
e ability to fight off these pathogens is severely diminished. The spleen is als
o a major site of early immunoglobulin M production, which is important in the a
cute clearance of pathogens from the bloodstream. [3] The most common etiologies
of asplenia or hyposplenism are congenital and splenectomy after trauma or hema
tologic disease. Children aged 2 years or less and those splenectomized secondar
y to hematologic disease have poorer outcomes than those patients with splenecto
my after trauma. This may be due to trauma patients retaining an accessory splee
n or splenic implants, giving them some ability to mount an immune response. You
nger patients are thought to lack the circulating antibodies present to encourag
e opsonization by macrophages during phagocytosis. In immunocompetent patients,
antibodies will opsonize, or coat a pathogen, marking it for destruction by the
macrophage. Patients with hematologic disease do not have as many mechanisms of
protection due to an anatomic or functional deficit. Several conditions are asso
ciated with functional hyposplenism, indicating the situation where the patient
has a spleen but it is not functioning in a normal capacity. The most common con
ditions associated with functional hyposplenia are severe liver disease, ulcerat
ive colitis, celiac sprue, and lupus. [2] Hemoglobinopathies such as sickle cell
disease and the thalassemias must also be remembered as an important cause of f
unctional hyposplenia. As the spleen filters out abnormal red blood cells from t
he circulation, splenomegaly will develop in these patients due to increased spl
enic sequestration. [4] Eventually, the spleen is no longer able to filter and t
he patients have essentially succumbed to autosplenectomy.
Encapsulated organisms are the most virulent pathogens to patients with decrease
d or absent splenic function. The most important pathogen is Streptococcus pneum
oniae, but Haemophilus influenza and Neisseria meningitidis are also significant
. These are all encapsulated organisms that thrive in the absence of the opsoniz
ation and phagocytosis provided by splenic macrophages. In one study of 349 epis
odes of sepsis in patients with asplenia, 57% of infections and 59% of deaths we
re caused by S. pneumoniae. Furthermore, 6% of infections were caused by H. infl
uenza, with a mortality rate of 32%. N. meningitidis was the organism in 3.7% of
cases in the same study. [5] Diseases such as malaria and babesiosis are also k
nown to affect asplenic patients more severely. Plasmodium falciparum replicates
within erythrocytes, and in the competent spleen, these erythrocytes are seques
tered, allowing for a more brisk immune response and treatment effect. Interesti
ngly, asplenic patients account for around one-third of all cases of babesiosis.
[6] This is likely due to the fact that Babesia microti is an intraerythrocytic
parasite. [7] The spleen serves as a filter to defective erythrocytes, and the
asplenic patient is therefore more susceptible to these types of infections. Mor
e recently, Capnocytophaga canimorsus has been recognized as causing OPSI after
dog bites. [2,3] The entire clinical presentation and patient history must be ta
ken into account when trying to determine the exact etiology of the OPSI, howeve
r, the initial treatment in the ED will usually be unaffected.
Epidemiology
The most impressive statistic regarding OPSI is the mortality rate of 3870% despi
te adequate treatment; however, one source cites the mortality rate to be as low
as 10%. [2,8] The true incidence of OPSI varies depending on the source, but th
e most consistent data show an incidence of "serious bacterial infections after
splenectomy" to be around 0.23% per year. [9] The same study showed a lifetime r
isk to be 5%. Asplenic patients have different rates of OPSI, depending on sever
al factors, most importantly age, indication for splenectomy, and ongoing immuno
suppression. Early literature showed the incidence of OPSI to be 33% within the
first 10 years after splenectomy, but it is commonly accepted that the greatest
risk for OPSI is within the first 2 years after splenectomy. [2,10,11] Compared
to the general population, a splenectomized patient within the first 91365 days p
ost-operation has a 4.6-fold increased risk of OPSI. The risk is decreased to 2.
5-fold increased risk after 1 year. [12]
Splenectomy performed after trauma seems to carry a lower risk of OPSI than thos
e secondary to hematologic disease. Patients with splenectomy from hematologic d
isease are also more likely to be on immunosuppressive therapy, which increases
the risk of severe infection. Patients without a spleen are 12 to 25 times more
likely to have invasive pneumococcal disease than the general population as well
. This is consistent with previous data that S. pneumoniae is the most common or
ganism in OPSI.
Although extremely rare, congenital asplenia is also a major predisposing risk f
actor for OPSI. Only 50 cases were reported between 1956 and 2004, but 33 of the
se cases were inherited in an autosomal dominant pattern, indicating a familial
trait for a large majority of these patients. [13] Males are more likely to be a
ffected than females, and race does not seem to be a factor. The incidence of as
plenia and hyposplenia, however, is unknown, as there are numerous etiologies, a
nd many patients go undiagnosed.
Presentation
Most patients will know if they have had a splenectomy, but as these patients ma
y present to the ED extremely ill and unable to give detailed history, the Emerg
ency Physician may have to rely on medical records and family members for inform
ation. Young children with congenital asplenia may present to the ED well appear
ing or in septic shock. Patients with hematologic disease may not know that they
are functionally asplenic. Therefore, in the emergency setting, patients with r
eported history of sickle cell disease or other hemoglobinopathies must be treat
ed as if they are asplenic. Also, patients with bone marrow transplants may have
impaired splenic function and be unaware of this aspect of their disease. [14]
A key element of the history in a patient with known asplenia is their vaccinati
on status. The Centers for Disease Control and Prevention recommends that patien
ts with asplenia receive the 23-valent pneumococcal vaccine to prevent OPSI, as
this covers around 7390% of strains causing OPSI. [9,15] Asplenic children are re
vaccinated every 36 years, as levels of circulating antibodies to the pneumococca
l antigens are lower 5 years after vaccination in asplenic children compared to
children with intact splenic function. [15] Other vaccines available to asplenic
patients are the Haemophilus influenzae type B vaccine and the meningococcal va
ccine. Unfortunately, these vaccines do not completely protect a patient from de
veloping OPSI, and the treatment should still be aggressive and aimed at the enc
apsulated organisms mentioned above.
Asplenic patients should not only be vaccinated, but also educated concerning th
eir disease process and steps to take when fever occurs. Many patients decide ei
ther to wait and see if the fever will break, or to take oral antibiotics from a
previous infection. These patients will present with a history of fever not res
ponding to home remedies or antibiotics. The previously prescribed antibiotics m
ay cloud the picture, but the treatment will always include admission and i.v. a
ntibiotics, even if the history is not absolutely clear, as the risk of the dise
ase outweighs that of the treatment.
The initial prodrome of OPSI is usually mild, consistent with a flu-like illness
that can be representative of many other disease processes. The earliest sympto
ms may be fatigue, abdominal pain, or nausea, and may progress to fever, headach
e, rigors, myalgias, and vomiting. [16] Rash will likely become present as the d
isease progresses. The rash may be mild and non-specific, but may also progress
rapidly and appear similar to meningococcemia. [2] A rapid clinical deterioratio
n is the hallmark of this disease.
On examination, the patient may be febrile, tachycardic, hypotensive, and in ext
remis, or, if in early stages of the disease process, well appearing. It is impo
rtant to localize the source of infection. For example, meningitis or pneumonia
may be the inciting disease process, but can quickly become systemic as bacterem
ia develops. A petechial or purpuric rash may be seen, evident of DIC. [2] OPSI'
s clinical course may be similar to that of meningococcemia, which also may pres
ent with a petechial or purpuric rash. Post-mortem examination of patients with
OPSI may reveal bilateral adrenal hemorrhages, which are also found in Waterhous
e-Friderichsen syndrome from severe meningococcemia. [14] Respiratory distress a
nd multi-system organ failure may ensue and rapidly progress to coma and death w
ithin 2448h. [14] The exact timeline of symptoms and physical examination finding
s is variable. Patients with suspected OPSI therefore require frequent reassessm
ent while in the ED, even when appearing non-toxic.
Differential Diagnosis
As patients with OPSI progress in their illness, their symptoms will typically r
esemble that of any patient in septic shock. The differential diagnosis is broad
to include urinary tract infection, pneumonia, meningitis, spontaneous bacteria
l peritonitis, or bacteremia of unknown source. As mentioned earlier, meningococ
cemia also must be included in the differential diagnosis, as the two diseases m
ay present with a similar rash and rapid clinical deterioration. In the early st
ages of illness, such as in the child in this case report, the differential diag
nosis is much broader. It would include any viral illness that causes fatigue an
d low-grade fever.
ED Work-up
The ED work-up of a patient with suspected OPSI is quite extensive. A complete b
lood count may show an elevated or depressed WBC count with bandemia. Peripheral
blood smear may show Howell-Jolly bodies present in erythrocytes of patients wi
thout a spleen, although therapy usually must be started before the return of su
ch studies. Coagulation studies may reveal signs of DIC. If multi-system organ f
ailure is present, elevations of serum creatinine, liver function studies, and l
actate will be present. Blood and urine cultures should be obtained to help focu
s antimicrobial therapy at a later time. Urinalysis may help localize the infect
ion, as will a chest X-ray study. Lumbar puncture should be done only if there i
s heightened suspicion for meningitis, keeping in mind that DIC is a contraindic
ation, and performing it should not delay treatment in a critically ill patient.
Treatment and Disposition in the ED
As with any case of sepsis, supportive care is very important. Optimizing tissue
perfusion through aggressive fluid resuscitation and possibly vasopressor agent
s is key. Perhaps the most critical action in the treatment of OPSI is the immed
iate use of broad-spectrum i.v. antibiotics, ideally after blood cultures have b
een collected. Diagnostic work-up should never delay the initiation of empiric a
ntibiotics. [1] The initial empiric antibiotic choice for adults with normal ren
al function presenting with OPSI is vancomycin 1g i.v. every 12h and ceftriaxone
2g i.v. daily. However, it must be noted that vancomycin dosing is weight based
, depending on creatinine clearance (CrCl). Patients with CrCl over 60mL/min are
dosed at 1015mg/kg i.v. every 12h, which approximates to 1g i.v. for a 70-kg pat
ient. Vancomycin has excellent Gram-positive coverage, including against penicil
lin-resistant S. pneumoniae. [1] Ceftriaxone is added for double coverage of Gra
m-positive organisms, but includes Gram-negative coverage for N. meningitidis an
d H. influenzae. If meningitis is suspected, the regimens are more aggressive. I
f a patient is allergic to these antibiotics, it is important for the Emergency
Physician to determine if this is a true allergy, as these drugs are considered
first line; however, if they cannot be used, another combination of antibiotics
to cover S. pneumoniae, N. meningitidis, and H. influenza is indicated (). The u
se of i.v. immunoglobulin (IVIG) is controversial in OPSI. Several experts on th
e subject claim that IVIG has a theoretical benefit at doses of 0.4g/kg daily fo
r 3 days, although there have been no studies that have shown a difference. If I
VIG is desired, consultation with an infectious disease specialist is recommende
d. As an inpatient, the patient should continue to receive antibiotics and suppo
rtive care. The return of culture results will help narrow antibiotic coverage.
In a study of 318 patients, those who had "good knowledge" of their risk of infe
ction had a 1.4% incidence of OPSI, whereas those with "poor knowledge" had an i
ncidence of 16.5%. [17] These patients, when encountered in the ED for other rea
sons, should be reminded of their risk for OPSI. Patient education is one of the
strongest methods of prevention. If patients understand their elevated risk of
OPSI, they may present to the ED in the earlier stages of disease progression.
Table 1. Emergent Antibiotic Options for OPSI
Antibiotic Regimen
First-line regimen Vancomycin 1015mg/kg i.v. q 12h if CrCl>60mL/min (appr
oximates 1g i.v. q 12h for 70kg adult)
PLUS
Ceftriaxone 2g i.v. daily (children=50mg/kg i.v. q 12h)OR
Cefotaxime 2g i.v. q 8h (children=2550mg/kg i.v. q 6h)
Regimen if anaphylaxis to -lactam Vancomycin 1015mg/kg i.v. q 12h if CrCl&g
t;60mL/min (approximates 1g i.v. q 12h for 70kg adult)
PLUS
Levofloxacin 750mg i.v. q 24h
Add if concern for Capnocytophaga canimorsus Clindamycin 300600mg i.v. q 6h (c
hildren>1 month old=2540mg/kg/day i.v./i.m. divided q 68h with max 4.8g/day)
OR
Imipinem/cilastatin 500 mg1g i.v. q 6h (children=60100mg/kg/day i.v. div q 6h with
max 24g/day)
OR
Piperacillin/tazobactam 3.3754.5g i.v. q 6h if CrCl>40mL/min (children=300mg/k
g/day i.v. div q 8h)
OPSI=overwhelming post-splenectomy infection; i.v.=intravenous; i.m.=intramuscul
ar; q=every; CrCl=creatinine clearance.
Conclusion
OPSI is an extremely serious infection that often quickly progresses to fulminan
t sepsis, resulting in high mortality rates. Emergency Physicians are well train
ed to diagnose and treat sepsis, but not specifically in asplenic patients. This
subclass of patients progress from healthy to clinically septic so quickly that
it is imperative that Emergency Physicians not only recognize OPSI, but effecti
vely treat it early. Current literature suggests a combination of i.v. vancomyci
n and ceftriaxone in combination with early goal-directed therapy. The use of IV
IG is unproven, and may not be immediately available in the ED. If used, it like
ly will be given as an inpatient treatment with consultation from infectious dis
ease specialists. Implementation of these strategies may reduce mortality from 7
0% to around 1040%. [2]
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J Emerg Med. 2012;43(4):758-763. 2012 Elsevier Science, Inc.