OVERWHELMING POSTSPLENECTOMY INFECTION

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Create her child of spleen; that it may live.

WILLIAM SHAKESPEARE

The Tragedy of King Lear

Understanding splenic function eluded man for more than 2500 years. Hippocrates (460–377 BC) taught that the spleen “drew the watery part of food from the stomach.” Aristotle (384–322 BC) believed that it had no vital function. Pliny, in the first century AD, felt that the spleen's weight might hinder the speed of runners and could be removed “by way of incision,” resulting in the inability to laugh. The ancient Greeks also believed the spleen impaired athletic abilities, and applied hot irons to reduce its size.

Described by Galen (130–200 AD) as the “organ of mystery,” the spleen was later believed to be the source of melancholia (black bile or choler) as the theory of bodily humors arose. This theory persisted more than 1000 years, giving rise to the idea of “venting one's spleen.” In the Babylonian Talmud (second to sixth centuries) and the ancient Jewish writings of Judah Halevi (1086–1145), the notion of the spleen's role in laughter evolved. Because laughter was believed to be a cleansing process, it followed that the spleen “cleanses the blood and spirit from unclear and obscuring matter.” Maimonides (twelfth century) also stressed the spleen's function in purifying blood. The overall image of the spleen, however, was that of a nonessential organ that could be removed without adverse effects. This image persisted until the early 1900s.

In 1919, Morris and Bullock were the first to recognize the spleen's role in infection, based on animal studies, stating: “It is an observation of great antiquity that the operation of splenectomy is not followed by death. Indeed one may live for years without suffering any apparent ill effect from the absence of the organ; but this does not settle the problem as to whether or not a splenectomized person can weather a critical illness.”67 Cases of infection in splenectomized hosts were noted but roused little attention, probably because septic death was common. In 1952, King and Shumacker48 reported five cases of fulminant sepsis in splenectomized infants. Following this report, the association between splenectomy and fulminant, lethal sepsis has been firmly established, and knowledge of the spleen's role in the response to bacterial infection has expanded.* The evolution from good health to death within 1 day has been repeatedly documented in the asplenic patient. Septic death rates of up to 600 times greater than the general population have been reported for this syndrome of overwhelming postsplenectomy infection (OPSI).6, 90 Despite the large amount of published cases, insufficient data exist to determine the true incidence, exact nature of infection, risk factors, and the contribution of underlying conditions to overwhelming infection in the splenectomized host, a true medical emergency.

Section snippets

THE ROLE OF THE SPLEEN IN THE IMMUNE SYSTEM

The pathogenesis of OPSI lies in the loss of splenic immunologic function. As part of the reticuloendothelial system, splenic function can be divided into several elements: phagocytosis and clearance of unopsonized particulate matter, development of specific immune responses, and production and processing of opsonins.4

The spleen functions as a voluminous filter with strategically placed macrophages. Its extensive, sluggish microcirculation facilitates phagocytosis as splenic lymphoreticular

CONDITIONS PREDISPOSING TO HYPOSPLENISM

OPSI has been associated with asplenia for the full range of indications for splenectomy: malignancy, “benign” hematologic disorders such as hereditary spherocytosis, abdominal trauma, “incidental” splenectomy due to intraoperative injury or en bloc removal during another process.10, 31, 34, 42, 56, 64, 85, 90, 93

The concept of nonsurgical “functional” asplenia39 or hyposplenia occurs in association with disorders such as congenital asplenia, splenic atrophy, and sickle cell anemia. It is also

EPIDEMIOLOGY OF SPLENECTOMY

The importance of OPSI is its excessive morbidity and mortality despite a low incidence. With increased knowledge of the spleen's critical role in disease prevention, the indications for splenectomy have been re-evaluated, and a review of the many published series on splenectomized patients shows an increasingly conservative approach to splenic resection. Overall numbers are decreasing, as well as the percentage of cases for particular indications. This has been seen primarily in two areas:

MORBIDITY AND MORTALITY OF OPSI

Many attempts have been made to delineate the exact nature of the infection and to stratify the risks of developing OPSI. The entity may be best defined as an infection, occurring more commonly after splenectomy (or in a hyposplenic host), which evolves over a short time and produces severe symptoms, often with hypotension and a high mortality rate.85 Delineation is made difficult by the low incidence and by the heterogeneity of the patients who undergo splenectomy. An increased risk of

Bacteria

The predisposition of splenectomized patients for infection with encapsulated bacteria is well documented. Infants and young children are likely to lack exposure to these bacteria, and lacking specific antibody, rely to a greater degree on splenic sequestration and clearance. In the adult, diminished antibody response and splenic clearance contribute to the development of overwhelming infection.83 Although the frequency of causative organisms varies from series to series, published data

PRESENTING SIGNS AND SYMPTOMS

The classical manifestations of OPSI begin with a brief prodrome of fever with mild, nonspecific symptoms, rapidly evolving into overwhelming septic shock. There is usually no evidence of a local tissue infection, and the process is often accompanied by disseminated intravascular coagulation (DIC). In this markedly virulent presentation mortality ranges from 50% to 75%, with death ensuing within 24 to 48 hours.9, 52

This clinical picture has remained disturbingly unchanged. Onset is usually in

CLINICAL AND LABORATORY DIAGNOSTIC TESTING

Initial diagnosis must rely on a high index of clinical suspicion for any febrile presentation in a splenectomized patient because aggressive early management is critical. Diagnostic work-up should never delay the initiation of empiric antibiotic therapy. The most helpful initial test is the examination of the peripheral blood smear (Fig. 1) and buffy coat (Fig. 2) for the presence of bacteria. Visualization of organisms on the peripheral smear suggests a quantitative bacteremia of > 106

TREATMENT MODALITIES AND NEED FOR RAPID THERAPY

The critical point in management remains the early recognition of the patient at risk followed immediately by aggressive intervention. All asplenic patients with fevers of unknown origin should be treated as medical emergencies. Intravenous penicillin has long been the cornerstone of antibiotic therapy because it provides excellent activity against pneumococci and meningococci, frequent causes of fatal infection. But as resistance patterns change, continued reliance on penicillin may be unwise.

PREVENTIVE STRATEGIES

The area where intervention has the greatest potential to decrease the mortality of overwhelming sepsis in asplenic patients is prevention. Studies, however, have documented a poor track record to date for such preventive strategies.25, 80, 88, 102 White et al102 reported awareness of risk in only 11% of an asplenic population. Deodhar et al25 found that less than half of asplenic patients in their series had received pneumococcal vaccine, were on antibiotic prophylaxis, or had even received

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    Address reprint requests to Rajendra Kapila, M.D., Division of Infectious Diseases, U.M.D.N.J. - New Jersey Medical School, MSB Room I-509, 185 South Orange Avenue, Newark, NJ 07103

    *

    From the Division of Infectious Diseases, New Jersey Medical School, Newark, New Jersey

    *

    References 1, 8, 9, 31, 42, 64, 78, 85, 90, 92, 98.

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    Copyright © 1996 W. B. Saunders Company. Published by Elsevier Inc. All rights reserved.