Splenic trauma

SPLENIC TRAUMA DAVID D. OAKES, M.D., F.A.C.S.

0011-3840/81/060341-0401-$06.50 9 1981, Year Book Medical Publishers, Inc.

TABLE OF CONTENTS SELF-ASSESSMENT QUESTIONS . FOREWORD

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INTRODUCTION: "CONVENTIONAL WISDOM"

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SPLENIC SURGERY: AN HISTORICAL PERSPECTIVE

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POSTSPLENECTOMY SEPSIS ANATOMY .

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SPLENIC FUNCTION

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PATHOPtIYSIOLOGY OF OVERWHELMING POSTSPLENECTOMY INFECTION .

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SPLENIC SALVAGE

EXPERIENCE WITtI SPLENIC SALVAGE: SANTA CLARA VALLEY MEDICAL CENTER, APRIL, 1979, TO SEPTEMBER, 1 9 8 0 . . . . . RECALL OF PREVIOUSLY SPLENECTOMIZED PATIENTS SUMMARY .

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ACKNOWLEDGMENT

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SELF-ASsESSMENT ANSWERS

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393 393 396

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SELF-ASSESSMENT QUESTIONS 1. Not until the 1970s did surgeons attempt to treat splenic injuries by suture repair or partial splenectomy. True or false? 2. The first suggestion that serious sepsis might be related to prior splenectomy was a report by King and Schumacker in which of the following years? a. 1941 b. 1952 c. 1963 d. 1968 3. Approximately 80% of fatal overwhelming postsplenectomy infections occur within two years of splenectomy. True or false? 4. Episodes of overwhelming sepsis that occur more than two years after splenectomy are less fulminant and carry a better prognosis. True of false? 5. Patients suffering from overwhelming postsplenectomy infection frequently progress from good health to death within several: a. Minutes. b. Hours. c. Days. d. Weeks. 6. The number of pneumococci per milliliter of peripheral blood is how many times greater in patients with overwhelming postsplenectomy infection than in routine cases of pneumococcal septicemia,associated with lobar pneumonia? a. 10 b. 100 c. 1000 d. 10,000 7. Overwhelming postsplenectomy infection is characterized by: a. Abrupt onset. b. Fulminant course. c. Obscure source. d. High mortality. e. All of the above. 8. The risk of fatal sepsis in the general population is estimated to be: a. 0.001%. b. 0.01%. c. 0.1%. d. 1.0%. 343

9. The risk of fatal sepsis after splenectomy for t r a u m a is approximately: a. 0.006%. b. 0.06%. c. 0.6%. d. 6%. 10. The risk of fatal sepsis after splenectomy for thalassemia is approximately: a. 0.01%. b. 0.11%. c. 1.1%. d. 11.0%. 11. Pneumococci have been identified as the causative organism in about what percent of patients with postsplenectomy sepsis? a. 0.5% b. 5% c. 50% d. 75% 12. Overwhelming postsplenectomy sepsis has never been reported to occur more than ten years after splenectomy. True or false? 13. In the adult, t h e spleen comprises approximately what percent of the total body lymphoid mass? a. 5% b. 10% c. 25% d. 5O% 14. Asplenic patients cannot be immunized against pneumococcal surface antigens. True or false? 15. Tuftsin is a tetrapeptide that stimulates phagocytosis by attaching to the surface of: a. Encapsulated bacteria. b. Nonencapsulated bacteria. c. Polymorphonuclear leukocytes. 16. Nonoperative m a n a g e m e n t of splenic ruptures is contraindicated when: a. The patient is less than two years old. b. The patient is hemodynamically stable. c. Damage to other intraabdominal organs cannot be ruled out. d. Splenic injury can be demonstrated by a liver-spleen scan. 17. Once the initial bleeding has ceased, the injured spleen is capable of satisfactory healing. True or false? 18. Indications for splenectomy include all of the following except: a. Total avulsion from the hilum. b. Life-threatening-associated injuries. 344

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c. The presence of a large subcapsular hematoma. d. Inadequate hemostasis after attempted splenorrhaphy. When splenectomy is unavoidable the surgeon should: a. Document the need for this course of action. b. Inform the patient of his potentially vulnerable state. c. Administer antipneumococcal vaccine. d. Urge early aggressive treatment of all febrile illnesses in asplenic patients. e. All of the above. Death from postsplenectomy sepsis has never been reported in any patient with splenosis or accessory spleens. True or false? There are both practical and theoretical limitations to the use of continuous prophylactic antibiotics in patients who have undergone splenectomy. True or false? Patients who have undergone splenectomy in the past should b e recalled and informed of the potential for serious septic complications. True or false?

Answers to these questions appear at the end of the article.

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is Assistant Professor of Surgery at the Stanford University School of Medicine. He received his M.D. degree from Harvard Medical School in 1968, obtained his surgical training at the Peter Bent Brigham Hospital, and spent two years as a staff surgeon on the organ transplant service at Walter Reed Army Medical Center. Since joining the Stanford faculty in 1977, Dr. Oakes has become Chief of General and Thoracic Surgery at Santa Clara Valley Medical Center, San Jose, California. His major areas of clinical interest include care of the multiply injured patient and management of noncardiac surgical diseases of the chest.

FOREWORD One of the significant advances in surgery in the last decade is the emphasis on preservation of the injured spleen, first championed by pediatric surgeons. In this monograph, David Oakes provides a lucid view of postsplenectomy sepsis, demonstrates that it affects adults as well as infants, a n d m o n the basis of data from the literature as well as his own experience--proves that the injured spleen can usually be salvaged at little risk to the patient. MARK M. RAVITCH, M.D.

INTRODUCTION: "CONVENTIONAL WISDOM" U N T I L THE 1970s, LITTLE CONTROVERSY existed with regard to management of the patient with splenic injury. There was essentially universal agreement that once the diagnosis was secure, prompt splenectomy was indicated. Interest centered on ways of establishing the diagnosis in the most reliable and expeditious fashion, with particular concern for those patients who presented with "delayed rupture." The "conventional wisdom" with regard to m a n a g e m e n t of splenic injury is summarized in the following paragraph from the 1979 edition of a leading surgical textbook on the surgery of trauma: 1 "Splenectomy remains the only acceptable t r e a t m e n t for splenic injury. Even a slight non-bleeding tear of the splenic capsule may lead to recurrent fatal bleeding. Also, it is likely 346

that a splenic hematoma will increase in size secondary to increasing osmotic pressure of the hematoma and imbibition of fluid, even though no further hemorrhage occurs. The splenic hematoma eventually reaches such size that the spleen ruptures either spontaneously or following slight trauma, causing massive bleeding which may be rapidly fatal." The authors refer briefly to the suggestion that fatal sepsis may occasionally occur in patients who have undergone splenectomy for trauma, but conclude: "There is no large series of carefully evaluated patients having had splenectomy for trauma in which overwhelming infection has developed. Without more proof that splenectomy in a patient with a normal reticulo-endothelial system predisposes to infection, it is difficult to justify conservative management or partial splenectomy for splenic trauma, even in infants." The belief that all splenic t r a u m a - - n o matter how m i n o r - demands splenectomy is based on two fundamental assumptions: (1) that the spleen is an essentially useless organ that can be extirpated with impunity, and (2) that a damaged spleen will never heal spontaneously, cannot be repaired, and hence must be removed to achieve hemostasis. During the past decade an ever-increasing number of reports have called both assumptions into serious question. The purpose of this monograph is to review and evaluate these recent data concerning both the desirability and the feasibility of splenic preservation following traumarie rupture. Optimal management of the patient in whom splenectomy is unavoidable is also discussed. Finally, the management of 24 consecutive patients with splenic injuries treated at the Santa Clara Valley Medical Center, San Jose, California, between April, 1979, and September, 1980, is presented and analyzed. SPLENIC SURGERY: AN HISTORICAL PERSPECTIVE

In his presidential address to the American Association for the Surgery of Trauma in 1979, Sherman2 provided a detailed review of the history of splenic surgery. The first reported successful splenectomy for disease was performed by Adrian Zacarelli in Naples in 1549. 3 The patient, a 24-year-old woman, was said to suffer from massive splenomegaly; later reviewers have questioned the diagnosis and suggested that the organ removed may in fact have been a large ovarian cyst. In 1590 Rousset4 described what may have been the first splenectomy for trauma; a Dr. Viard removed a spleen that allegedly "protruded through a wound" in the patient's left side. It is interesting to note t h a t the six other reports of splenic resection for trauma in the 17th and 18th centuries all involved evisceration of the spleen through wounds in the left flank. Given the rarity with which splenic evisceration is noted today, one wonders whether in347

flamed omentum might have been mistaken for the spleen in at least some of these patients. The first well-documented case of survival after splenectomy for blunt trauma was reported by Reigner~ in 1893. The operation was undertaken only as a last and desperate resort in a 14year-old patient whose condition was deteriorating several hours after injury. The spleen was found to be totally transected and was removed. The patient survived in spite of an almost total lack of physiologic support. He subsequently did well, although four weeks later he required above-knee amputation for gangrene of the left foot--probably secondary to compression bandages with which he had been treated following operation, conceivably aggravated by postsplenectomy thrombocytosis. In the early 1900s, in the absence of techniques to combat hemorrhagic shock, the mortality of nonoperative management of patients with ruptured spleens was 90% to 100%. 8 Thus splenectomy continued to be performed, in spite of the formidable operative risk. As late as 1940 splenectomy for traumatic rupture was reported to carry a 30% mortality. 7 Although splenectomy came to be the most commonly performed operation on the spleen, lesser procedures such as splenotomy (incision of the spleen), splenorrhaphy (suture of the spleen), splenopexy (fixation of the spleen), and partial resection have been practiced and described intermittently for the past 400 years. In 1972 Morgenstern8 addressed the 23rd Annual Congress of the History of Medicine on the topic, "The Surgical Inviolability of the Spleen: Historical Evolution of a Concept." He cited several surgeons who reported successful amputation of portions of spleens that had eviscerated following penetrating injuries (Matthias, 1678; Ferguson, 1732; Hyatt, 1867; Markham, 1874; Faris, 1874; Deeble, 1889). Although histologic proof is lacking that it was indeed spleen that was amputated, it seems likely that at least some of these cases in fact represent successful partial splenectomies. There seems little doubt that the later reports of James 9 (1892) and Zikoffi~ (1895) are, as represented, examples of successful suture of splenic lacerations. Operative procedures' short of total splenectomy were described in surgical textbooks until the late 1930s: "Under some circumstances--for instance in cysts or partial crushing--only a portion of the spleen should be removed; the hemorrhage from the surface of the incision arrested by tamponade, by indirect ligature or with thermocautery; also by elastic constriction with a rubber tube, portions of the spleen can be ligated" (Von Esmarch, 11 1901); "If the spleen is damaged, we may do splenectomy, total or partial, may use the suture, the cautery, or the tampon" (Da Costa, 12 1919); " . . . suture of the spleen is indicated where the rent is small and the condition appears remediable" (Thorek, ~3 1938). Thereafter, for reasons that remain obscure, conservative procedures were almost totally abandoned in 348

the management of splenic trauma: "Splenectomy is usually the operation of choice when surgery of the spleen is indicated" (Orr, 14 1949); "It is imperative to remove the spleen when it is injured, whether hemorrhage occurs immediately or after an interval" (Hunt, '5 1968); "Splenectomy remains the only acceptable treatment for splenic injury" (Shires, '6 1969, and Thal et al., ' 1979). Morgenstern8 observes that "somewhere between the late 19th and the mid-20th centuries, lesser procedures on the spleen seem to fall into disrepute and total splenectomy became the procedure of choice in any surgical condition involving the spleen . . . . Presumably there were an increasing number of complications of conservative procedures accumulating at the same time as the operation of splenectomy became increasingly safe. However, there are scarcely any detailed reports of such adverse results." Also impressed by the lack of reported complications following these lesser procedures, Sherman 2 concluded: "The concept of removal of the spleen as the procedure of choice was clearly based on lack of evidence that removal of the spleen might be harmful to the host, rather than upon failure of more conservative measures." What then is the evidence that splenectomy for trauma or other indications is harmful to the host? POSTSPLENECTOMY SEPSIS RECOGNITION AND DEFINITION OF THE SYNDROME: 1952--1962

Operative mortality of splenectomy--even for benign condit i o n s - a v e r a g e d 50% in the late 19th century. By the 1920s the mortality for removing an injured spleen was still 34%. 8 Those patients who survived operation, however, appeared to live essentially normal lives--hence the belief that the spleen could be removed without significant adverse sequelae. This belief persisted in spite of the fact (or because of the fact) that the spleen's physiologic function had yet to be defined. The first suggestion that the spleen could not be removed with total impunity was made by King and Schumacker'7 in their classic report of 1952. They reviewed approximately 100 splenectomies performed in their institution and were struck by the fact that all five patients who had been operated on within the first six months of life developed meningitis or overwhelming septicemia. All suffered from congenital hemolytic anemia. Sep: sis occurred as early as six weeks and as late as three years after operation. Two of the five patients died. One child had undergone splenectomy at 15 days of age and returned eight months later with overwhelming meningococcemia and meningococcal meningitis. He died within 24 hours of the onset of his illness. Autopsy revealed bilateral adrenal hemorrhage. The second fatality occurred in a patient whose splenectomy was per349

formed at the age of two and one half months. About three and one half weeks later she died of a rapidly progressive febrile illness. Autopsy was refused and cultures were negative, but the clinical picture was clearly one of overwhelming sepsis. King and Schumacker~7 could find only one additional case report of sepsis following splenectomy in infancy: a premature infant (35 weeks' gestation) underwent splenectomy 14 hours after birth because of acute thrombocytopenic purpura. The baby did well for three weeks, then succumbed to a sudden overwhelming bacteremia. Although the experience was small--three deaths amongst six infants--the authors were stimulated to seek a causal relationship between splenectomy in infancy and an increased susceptibility to infection. They cited the following observations as evidence that the spleen probably plays a role in resistance to infection: (1) Splenomegaly occurs in certain infections; (2) latent infections may become active after splenectomy;~9 (3) splenectomy decreases the natural resistance of certain species (rats and mice, for example) to acute and chronic infections2~ and (4) splenectomy decreases the ability to mount an antibody response to intravenously administered antigens in both rats and human beings. 22 The authors concluded cautiously: "Our experience would suggest . . . that when splenectomy is performed during the first few months of life there may follow, at least for a time, an increased susceptibility to infection." This report was greeted with initial skepticism. An addendum to the original article noted that Ferguson found no instances of serious infection among nine infants with congenital hemolytic anemia treated by splenectomy at six months of age or earlier at Children's Hospital Medical Center in Boston and followed for one to six years thereafter. (A tenth child, however, who was treated at seven and o~e half months, died of tracheobronchitis one year later!) Further evidence that the absence of normal splenic function might in some way predispose to overwhelming infection was provided the following year in a case report by Parr and associates. 2~ One evening a 17-year-old girl who suffered from juvenile rheumatoid arthritis developed anorexia, chills, and fever. The following morning she was admitted to the hospital "desperately ill" and died within six hours. Routine slides of the peripheral blood revealed encapsulated gram-positive cocci, and postmortem cultures grew pneumococci. Autopsy findings included bilateral adrenal hemorrhages and pulmonary congestion with petechial hemorrhages. The spleen was "small and fibrous" and weighed only 35 gm; the capsule and trabeculae were thickened, and the internal architecture was distorted by hemorrhage into the pulp. The authors discussed the possibility that the overwhelming infection was due to "lack of resistance by the host" and that the presence of an atrophic spleen may have been a 35o

contributing factor. Review of the existing literature did not allow them to confirm either of these postulates. In 1958 Huntley 24 reported the experience with splenectomy in patients 13 years of age and younger at Duke Hospital during the years 1933 through 1954. Seven serious infections occurred in 46 children who could be followed for at least six months. Five of the seven were under one year of age at the time of operation; a sixth child was 14 months old. All but two of the seven patients suffered from underlying diseases associated with increased susceptibility to infection: Letterer-Siwe disease, sickle cell anemia, and the syndrome of eczema, purpura, and draining ears (later designated Wiskott-Aldrich syndrome). Huntley speculated that splenectomy somehow leads to diminution of host resistance and that, when it is added to the basic susceptibility of these patients, it results in a marked increase in septic complications. "In other splenectomized patients, [ who are] less basically affected, this change in incidence may become significant only in a larger series than is presented here." (Note that her review contained only two patients who had undergone splenectomy for trauma.) During the ensuing years, numerous authors addressed the relationship between splenectomy and sepsis--primarily in infants. These reports were critically analyzed by Horan and Colebatch25 in a comprehensive review published in 1962. They noted that conflicting views had been expressed and that the published data provided no convincing proof of any clear-cut relationship between splenectomy and subsequent serious infection. They then analyzed the experience with splenectomy in children in Melbourne, Australia, from 1938 to 1958. Among 142 patients evaluated there were 17 who developed serious infections, five of which were fatal. The incidence of severe infection was particularly remarkable in patients less than one year of age at the time of splenect~my: five septic episodes leading to three deaths among ten patients; all five episodes occurred within 22 months of operation. By contrast, only two fatal infections were noted among 132 older patients. Of the 64 patients who underwent splenectomy for trauma, the incidence of serious infection was 6.3% (four patients), and there were no deaths. This compares with 13 serious infections (16.7%) and five deaths (6.4%) among 78 patients whose spleens were removed because of underlying disease, such as hereditary spherocytosis, acquired hemolytic anemia, thrombocytopenic purpura, portal hypertension, and thalassemia. The authors combined their experience with 540 "adequately documeiited cases" from the literature. They calculated that fatal or life-threatening infections occurred in between 5.6% and 8.7% of children who had undergone splenectomy. In a large epidemiologic study, the expected incidence of such infections among the general population of children was estimated to be 351

0.7%. 26 The clinical features of these infections were remarkably similar. They were fulminant and frequently fatal, and tended to recur if the patient survived. Of 41 patients with documented septicemia, 30 (73%) died. In more than half of the fatal cases, death occurred within 18 hours; one third of the patients died within ten hours of the onset of their symptoms. There was an apparent tendency toward repeated attacks of infection. Of asplenic children surviving one episode of major sepsis, 20% had subsequent attacks of septicemia or meningitis. Encapsulated organisms predominated. Positive cultures were obtained from 65 major infections in 57 children. The causative organisms were pneumococci in 36 (55%) cases, Escherichia coli in eight, Hemophilus influenzae in six, meningococci in four, Streptococcus hemolytica in three, Staphylococcus pyogenes in three, Salmonella typhimurium in two, and miscellaneous organisms in three. The interval between splenectomy and late infection (more t h a n two weeks after operation) could be analyzed in 82 patients who suffered a total of 93 serious infections. Of 47 fatal infections, 20 (43%) occurred within the first six months following splenectomy, 31 (66%) within one year, and 41 (87%) within two years. Of the 46 nonfatal infections, 11 (24%) occurred within six months, 21 (46%) within one year, and 30 (65%) within two years. Although the majority of infectious complications thus appeared within 24 months of splenectomy, eighteen later infections were recorded. Of these, seven were characterized by septicemia and in three patients the illness proved fatal within ten hours. Five patients developed recurrent attacks of serious infection. The causative organism was isolated in 16 cases; nine of these proved to be pneumococcal infections. Thus, "fatal and lifethreatening infections that occur more than two years after splenectomy show the same characteristics as do those that occur e a r l i e r - - f u l m i n a t i n g course, with pneumococci . . . . high mortality, and a tendency to recur if not fatal . . . . " When infectious complications were examined as a function of underlying disease, an increased risk could be documented for thalassemia and portal ~hypertension compared with hereditary spherocytosis, thrombocytopenic purpura, and trauma. The data were felt to be inadequate to state "categorically" that spherocytosis and thrombocytopenic purpura did not carry a greater risk following splenectomy than did traumatic rupture. There was felt to be a "negligible" incidence of postsplenectomy infection in patients over one year of age whose spleens were removed for trauma. Fortunately, the authors observed, traumatic rupture rarely occurs within the first year of l i f e - - t h e period of greatest risk for postsplenectomy sepsis. Reference was also made to patients in whom congenital asplenia existed as an isolated anomaly. Since these patients are apparently normal in all other respects, they are analogous to 352

normal individuals who have undergone splenectomy for trauma. In seven reported autopsy cases in children, five died of meningitis or Waterhouse-Friderichsen syndrome, and infection was noted in the other two. Of six adults with isolated congenital asplenia coming to autopsy since 1918, three died of infection. One of these followed a course strikingly similar to postsplenectomy sepsis: he survived two attacks of pneumonia and one episode of meningitis, but eventually succumbed to a septicemic illness that produced pneumonia, meningitis, purulent cystitis, and bilateral adrenocortical hemorrhage. "Such reports," the authors observed, "lend considerable weight to the hypothesis that the absence of the spleen p e r s e does lead to increased susceptibility to serious infection." Based on their local experience and on their review of the existing literature, the authors concluded that septicemia and meningitis were much more common in infants who had undergone splenectomy than in the normal population. Although infants were most commonly affected, children over one year of age were still at "appreciable" risk. Whenever possible, elective splenectomy should therefore be deferred "well beyond the dangerous period of infancy," that is, until the child has reached school age. FURTHER DEFINITION OF THE POPULATION AT RISK: 1967-1980

By the mid-1960s, it was generally accepted that severe infections occurred more frequently in some infants and children who had undergone splenectorriy than in the normal population. Considerable debate continued over the exact degree of increased risk and the precise subpopulation subjected to it. In 1967 Eraklis et al. 2~ observed that in spite of more than one dozen papers on the topic reviewing mor~ than 800 patients, "considerable confusion" and "contradictory conclusions" abounded. They felt that the previous studies were deficient in the number of patients described, the reliability of the diagnoses, the sparseness of follow-up information, and the failure to distinguish a m o n g the diverse types of disease for which splenectomy had been performed. To correct this, they reviewed the records of 467 children who had undergone splenectomy at Children's Hospital Medical Center in Boston from 1930 to 1960. The review considered only "serious infection," defined as proved bacteremia and bacterial meningitis. Unfortunately, follow-up data were available in only 366 patients (78%), which weakened the force of the conclusions. Nevertheless, certain findings deserve mention. Eighty-six of the 467 patients died during a follow-up period of three to 25 years (mean, 6.1 years). Sixty-one of these died from progression of the chronic disease from which they originally suffered. Oyerwhelming infection accounted for all of the other 25 deaths, an incidence of 5.4%--remarkably consistent with 353

the findings of Horan and Colebatch cited above. Mortality from sepsis was greater in patients who were four years of age or younger at the time of splenectomy (8.1% vs 3.3% for the older age group). Twenty-one (84%) of the 25 deaths from sepsis occurred within four years of splenectomy. Patients who died of sepsis followed a characteristic clinical course: sudden overwhelming meningitis and septicemia, or fulminating pneumonias with septicemia, with death frequently ensuing within 12 to 24 hours, and autopsy evidence of bilateral adrenal hemorrhages. Pneumococci were isolated in 50% of the fatal cases, with meningococcus and Hemophilus influenzae as the next most common organisms. Patients were characterized according to indications for splenectomy, and the relative risk determined for each condition. No septic deaths were observed among 176 children whose spleens were removed for trauma, idiopathic thrombocytopenic purpura, portal vein thrombosis with congestive splenomegaly, or local tumors. Likewise, only three deaths from overwhelming infection were found among 171 patients with hereditary spherocytosis or hypoplastic or aplastic anemia (1.8%). Therefore, they said, in these categories of disease, splenectomy '~may be carried out without fear of increased susceptibility to fatal infection." By contrast, infection led to 20 deaths among 97 patients (21%) with histiocytoses and inborn errors of metabolism, hepatitis with portal hypertension, thalassemia major, and Wiskott-Aldrich syndrome. Splenectomy was clearly implicated in these deaths because 87 patients with similar diagnoses who were treated without operation developed-only two fatal infections. The authors conclude that for this high risk group--the patients with "serious primary disease"--splenectomy should be undertaken only with "due caution" and that its benefits weighed against a well-documented increased risk of subsequent fatal infection. Continuous prophylactic penicillin therapy "for a number of years" was recommended when patients in this high-risk group undergo splenectomy. Further, "it is advisable to evaluate carefully any unexplained 'cold' or fever in the child who has had a splenectomy." The above recommendations were sharpened further by Diamond, 2s one of Eraklis' co-authors, in a subsequent communication. Based once again on the Boston Children's Hospital experience, he discounted the risk of infection after splenectomy for trauma: " . . . with other organs and systems functioning normally, the risk of [overwhelming infection] may well be negligible." (Note, however, that the Boston series included only 55 patients with splenectomy for traumatic rupture.) His recommendations with regard to idiopathic thrombocytopenic purpura ("no risk disease") and hereditary spherocytosis ("minimal risk disease") are conservative. Although there is an extremely low risk of infection in these settings, splenectomy is rarely neces354

sary during the early years of life--hence, he implies, it might better be postponed. But if crises (uncontrolled bleeding, severe hemolysis leading to chronic or recurrent acute anemia) develop, splenectomy should not be "unduly delayed" for fear of subsequent sepsis. On the other hand, he urges caution in dealing with patients with thalassemia, Wiskott-Aldrich syndrome, and other "high risk diseases." In such patients, splenectomy "might offer less benefit" and the risk of severe sepsis might be "far greater." He offers a commonsense approach to the prevention of sepsis in the child for whom a splenectomy has been performed. Until a child is old enough to complain of the symptoms of a cold or sore throat, use daily prophylactic antibiotics (for example, penicillin or sulfisoxazole). Once a child is three or four years old, stop daily prophylaxis but impress upon the parents and local physician the importance of instituting antibiotic therapy at the earliest sign of any infectious process, even a "simple cold." In this same communication, Diamond coins the term overwhelming postsplenectomy infection (OPSI) to describe the syndrome now recognized as characteristic of severe sepsis in these patients. His concise formulation is worth quoting directly: ~The syndrome of overwhelming post-splenectomy infection (OPSI) is unlike most fulminating bacteremias and septicemias in ordinary (spleen-containing) individuals. Very few patients with bacteremia progress from good health to death in less than 24 hours, whereas the OPSI syndrome constitutes a distinct entity which often lasts only 12 to 18 hours. It may begin abruptly with slight sore throat, fever, and 'feeling or looking sick,' proceed to headache, vomiting, and hyperpyrexia; and be followed within a few hours by convulsions or coma and death. In the uncomplaining infant, the prodromata of spreading infection may be absent or missed . . . . The pneumococcus is usually the invading organism. The meningococcus or influenza bacillus have also been blamed, but these infections last several days and are less fulminant. In a typical OPSI, earliest blood cultures will yield pneumococci in large numbers and the first lumbar puncture may show relatively clear or only slightly cloudy fluid and relatively few leukocytes. However, microscopic examination usuaUy shows innumerable organisms. The patient has usually collapsed before the typical spinal fluid leukocytosis can develop." Subsequent writers have added little to this description of overwhelming postsplenectomy infection except to stress that the mortality is high and the source of the infection usually obscure. 29 (Other characteristics of OPSI are abrupt onset, florid bacteremia, and a fulminant course.) Fatal cases often show manifestations of disseminated intravascular coagulopathy, Waterhouse-Friderichsen syndrome, or b o t h - - f e a t u r e s not usually associated with pneumococcal sepsis in patients with normal splenic function. The magnitude of the bacterial burden in OPSI is indicated by the fact that bacteria are frequently seen in routine smears of 355

the peripheral blood (Fig 1). Laboratory studies suggest that this requires at least 1,000,000 organisms per milliliter, a figure 10,000 times greater than that observed in the usual case of pneumococcal septicemia associated with lobar pneumonia.3~ In summary, OPSI is characterized by abrupt onset of florid sepsis, massive bacteremia--usually pneumococcal--arising from an obscure source, and a fatal outcome in a majority of patients. This pattern and its frequent association with disseminated intravascular coagulopathy and bilateral adrenal hemorrhage make this syndrome clearly distinguishable from pneumococcal sepsis in patients who are not asplenic. 31 In an attempt to determine more exactly the morbidity, mortality, and long-term complications of infection following splenectomy, the surgical section of the American Academy of Pediatrics surveyed 37 major institutions and 14 individual members with regard to their experience with splenectomy in childhood. The results were reported by Eraklis and Filler 3~ in 1972. There were 1,413 patients who had undergone splenectomy prior to their 16th birthday and who had been followed for a minimum of four years. All operations occurred between 1956 and 1965. The patients were classified and results were analyzed according to the indication for splenectomy: congenital hemolytic Fig 1.mEncapsulated diploccocci are clearly visible in this blood smear from a patient who died of overwhelming postsplenectomy infection (OPSI). Studies suggest that at least 1,000,000 bacteria/ml must be present for the organisms to be demonstrable in smears of unspun peripheral blood. By contrast, the bacterial burden associated with pneumococcemia secondary to lobar pneumonia is approximately 200 organisms/ml, 10,000 times less than that observed in the OPSI syndrome.

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356

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anemia, 395 patients; idiopathic thrombocytopenic purpura, 265 patients; trauma, 348 patients; thalassemia, 45 patients; and "other," 360 patients. The latter group included portal hypertension, splenectomy incidental to other surgery, histiocytoses and inborn errors of metabolism, hypersplenism, hypoplastic anemia or pancytopenia, lymphoma, leukemia, Hodgkin's disease, acquired hemolytic anemia, aplastic anemia, primary splenic disease (cysts), unspecified anemia, and torsion of the spleen. The overall hospital mortality was 3.3%, including ten intraoperative deaths, eight of them from multiple traumatic injuries. Late mortality from overwhelming infection was high for thalassemia and "other" diagnoses (2 of 45 and 20 of 323, respectively), and low for congenital hemolytic anemia (2 of 394), idiopathic thrombocytopenic purpura (7 of 262), and trauma (3 of 342). The conclusion is drawn that " . . . overwhelming infection as a cause of late mortality was unusual in the older children without a serious underlying systemic disease." In addition to the usual imprecision inherent in multi-institutional studies, the value of this review is limited by the fact that only patients with fatal sepsis are reported. Nonetheless, for the first time, death from overwhelming sepsis is noted in patients without underlying disease who had undergone splenectomy for t r a u m a t a 3 of 342 patients (0.88%). In 1973 Singer3a reviewed the problem of postsplenectomy sepsis in adults as well as children. His report remains the most definitive and widely quoted analysis of the problem. Beginning with a review of patients treated at Texas Children's Hospital, he examined 23 additional series from the literature that dealt with the topic of sepsis in splenectomized patients. He defined postsplenectomy sepsis as " . . . septicemia, meningitis or pneumonia, usually fulminant, but not always fatal, occurring days to years after removal of the ~pleen. The disease is characteristically sudden in onset and rapidly reaches a crescendo in hours or in one or two days. In the fatal cases, adrenal hemorrhage (Waterhouse-Friderichsen syndrome) may occur regardless of the causative organism. Repeated episodes of severe infection may occur in some patients, regardless of the reason for removal of the spleen. No limits are set on the interval between splenectomy and onset of sepsis, because some of the cases occurred as early as 13 days and as late as 14 years following splenectomy." A total of 2,795 patients were studied. They were grouped into nine categories of disease and the incidence of postsplenectomy sepsis was calculated for each category. The results are summarized in Table 1. The overall risk of sepsis ranged from a low of 1.45% in patients who had undergone splenectomy for trauma to a high of 24.8% in those suffering from thalassemia. Likewise, the risk of death from overwhelming infection varied from 0.58% to 11.0% in these two categories respectively. These results were contrasted with an estimated 0.01% incidence of mor357

TABLE 1.--INCIDENCE OF POSTSPLENECTOMYSEPSIS*

FINDING

NO. OF PATIENTS

Trauma Incidental to other surgical operations Idiopathic thrombocytopenia Congenital spherocytosis Acquired hemolytic anemia Portal hypertension Primary anemia Reticuloendothelial disease Thalassemia TOTAL

688 233 489 850 67 221 70 69 109 2,795

PATIENTSWITH MAJORSEPSIS (~)

10 (1.45) 5 (2.10) 10 (2.05) 30 (3.52) 5 (7.50) 18 (8.20) 6 (8.50) 8 (11.50) 27 {24.80) 119 (4.25%) Normal population

DEATHFROM SEPSIS (~) 4 2 7 19 2 13 5 7 12 71

(0.58) (0.86) (1.43) (2.23) (2.90) (5.90) (7.01) (10.10) (11.00) (2.52%) 0.01%

*Adapted from Singer D. B.: Post-splenectomy sepsis, in Rosenberg H.S., et al. (eds): Perspectives in Pediatric Pathology. Chicago: Year Book Medical Publishers, Inc., 1973, vol 1, pp 285-311.

tality from sepsis in the general population, including all agesJ 4 The category of "traumatic splenic rupture" contained 688 patients, 388 of whom were children. Four patients died, an incidence of fatal sepsis of 0.58%; this figure, although low, is 58 times that in the general population. The occurrence of severe nonfatal infection (6 of 688) was about the same as predicted by the Newcastle upon Tyne study. 2~ These figures do not include 15 isolated case reports of major sepsis after splenectomy for trauma, seven of which led to the death of the patient. In these 15 patients, sepsis appeared between two and ten years after splenectomy and involved pneumococcal infection in nine patients, meningococcal in one, and streptococcal in another. The patients who died were found to have adrenal hemorrhage. Since the total number of s'plenectomies from which these 15 were drawn is not known, they cannot be included in calculating incidence of the complication. Yet, these reports add credence to the observation that overwhelming sepsis can occur in otherwise healthy individuals foil.owing splenectomy for trauma. A closely related category, "splenectomy incidental to other surgical operations," contained 43 children and 190 adults. The indications for operation were not specified in all cases, but gastrectomy for ulcer disease and hiatal herniorrhaphy were said to account "for many of these cases." Severe sepsis occurred in five (2.1%) of the 233 patients; two (0.86%) died. Once again, although the incidence of fatal sepsis is low, it represents an 86fold increase over that of the normal control population. Two case reports of fatal fulminant sepsis after incidental splenectomy were also cited, one in which operation had been undertaken for benign and one for malignant disease. In summary, if one combines the data on postsplenectomy sepsis in patients without underlying disease Ctrauma" plus "inci358

dental"), one finds an incidence of 15 septic episodes among 921 patients (1.63%) with a mortality of 6 (0.65%) of 921. This represents a clear excess mortality in surgically asplenic patients when compared with the population at large (0.01%). Moreover, 16 isolated case reports also attest to the occurrence of overwhelming postsplenectomy sepsis in otherwise healthy patients without serious underlying disease. The organisms responsible for postsplenectomy sepsis were identified in 72 of the 119 Patients and are listed in Table 2. In order of decreasing incidence they were pneumococcus, 50%; meningococcus, 12%; E. coli, 11%; Hemophilus influenzae, 8%; staphylococcus, 8%; and streptococcus, 7%. This was compared with the organisms cultured from all children with septicemia and/or meningitis at Texas Children's Hospital .in 1970: Hemophilus influenzae, 27%; staphylococcus, 16.5%; streptococcus, 15%; pneumococcus, 8.5%; meningococcus, 7%; E. coli, 7%; and Pseudomonas organisms, 6.5%. Singer draws several important conclusions: '~Post-splenectomy sepsis is an infrequent but genuine hazard that may be anticipated in all patients, regardless of age or the reason for removal of the spleen . . . . Younger patients, especially infants, are particularly susceptible . . . but older children and adults are by no means excepted. . . . There seems to be no time limit beyond which an asplenic person may be considered safe from infection." In 1977 Gopal and Bisno 29reported a collected experience with fulminant pneumococcal infections in "normal" asplenic hosts. They cited 26 episodes of severe sepsis in 25 patients, none of whom suffered from a serious underlying disease. Two patients had congenital asplenia as an isolated anomaly. Two patients had ~'splenic atrophy" of undetermined etiology. One patient had autopsy evidence of remote splenic infarction. Of the 20 patients who were '~surgically asplenic," 17 had undergone splenectomy for trauma, and three had had their spleens removed incidenTABLE 2.--ORGANIS~ISPRODUCINGPOSTSPLENECTOMY SEPSIS* ORGANISM Pneumococcus Meningococcus

Escherichia coli Hemophilus influenzae Staphylococcus Streptococcus

PATIENTS FREQUENCY(%) 36 9 8

50 12 11

6

8

6 5

8 7

*Adapted from Singer D. B.: Post-splenectomy sepsis, in Rosenberg H.S. et al. (eds): Perspectives in Pediatric Pathology. Chicago: Year Book Medical Publishers, Inc., 1973, vol 1, pp 285-311. 359

tally during operations for benign disease. Only cases of documented pneumococcal bacteremia in patients over four years of age were included. At the time of overwhelming infection these 20 otherwise healthy patients ranged in age from seven to 71 years (average age, 32.8). Sepsis occurred between seven months and 25 years after splenectomy (mean, 5.8 years). Age at splenectomy was five to 71 (mean, 18.6). Thirteen of the 20 patients were ten years of age or older at the time of operation, and one half of the patients were over 16 years of age. Nine episodes of sepsis occurred five or more years after splenectomy, and six occurred after ten or more years. Fourteen of the 20 patients died, a mortality rate of 70%. Accessory spleens were noted in six patients and apparently failed to protect against the overwhelming pneumococcemia. Although only limited data are available regarding pneumococcal serotypes, the results are intriguing. Three serotypes (XII, XXII, XXIII) accounted for all eight isolates reported. Half of the isolates belong to Type XII, in spite of the fact that Type XII generally accounts for less than 10% of blood isolates of pneumococci. This cluster of serotypes suggests that a polyvalent vaccine might be "highly efficacious." The authors stress that there is a ~ . . . growing body of evidence that fulminant pneumococcal infections are prone to occur in otherwise healthy persons with congenital or acquired asplenia." Contrary to the prevailing belief, most of the examples cited occurred in adults, and 60% happened more than two years after splenectomy. Given the indefinite period at risk, the authors questioned the efficacy of prophylactic antibiotics, but observed that ~'when nondescript febrile episodes develop in such patients, prompt blood culture followed by vigorous empiric antibiotic therapy seems entirely justified." They recommended penicillin on older children and adults, and ampicillin ifi younger children in whom Hemophilus influenzae and E. coli might be implicated. The 20 surgically asplenic patients who suffered subsequent fulminant pneumococcemia described by Gopal and Bisno are listed in Table 3 according to the year of report. Certain clinical data are also included. Note that peripheral blood smears demonstrated bacteria in five patients, and that 12 patients developed disseminated intravascular coagulopathy, bilateral adrenal hemorrhage, or both. A subsequent review of the English-language medical literature reveals at least 14 additional cases of well-documented overwhelming postsplenectomy pneumococcal septicemia in individuals without underlying disease. Clinical data are summarized in Table 4. One spleen was removed incidentally during operation for peptic ulcer disease; the other 13 splenectomies were performed for traumatic rupture. Age at splenectomy ranged from 4 to 46 (average, 16.4). Nine of the 14 patients were 360

over 15 years of age at the time of splenic injury. Sepsis occurred between six months and 31 years after splenectomy (average, 8.1 years); nine episodes developed after five or more years. Mortality was 93% (13 of 14 patients). Fulminant sepsis was manifested in all patients; eight patients died within 14 hours of admission. Eight patients had clinical evidence of disseminated intravascular coagulation, and five had adrenal hemorrhage noted at autopsy. Accessory spleens were found at autopsy in five patients, including one patient with 92 gm of splenic tissue present in nodules up to 4.5 cm in diameter. The 34 patients listed in Tables 3 and 4 are all well-documented examples of pneumococcal sepsis occurring in surgically asplenic patients without serious underlying disease. For the sake of clarity, patients were not included if the causative organism was not isolated or was other than pneumococcus--no matter how compellingly the clinical presentation suggested overwhelming postsplenectomy infection. For example, one case described by Davis et al. ~s in 1963 is almost certainly an example of this syndrome, but the only bacteriologic result reported was a sputum culture that showed a ~'heavy growth of streptococcus organism." Likewise, case #4 (1968) of Erickson et al. 59 was deficient only in lacking laboratory isolation of the infecting agent. Patients were also excluded if they suffered from any systemic disease, whether or not that disease has been known to predispose to infection. Undoubtedly, present calculations underestimate the true risk of overwhelming sepsis following splenectomy for trauma. Surgeons do not, as a rule, maintain long-term follow-up on otherwise healthy patients once they have recovered from their traumatic injuries. 2 One can only speculate how often the syndrome has occurred but gone unrecognized, or if recognized, gone unreported. Moreover, not all reported cases may have come to the reviewers' attention. Finally, since the risk of postsplenectomy sepsis seems to continue indefinitely, many susceptible individuals who are currently healthy may yet fall victim to this devastating complication. Thus, although the exact risk of overwhelming sepsis in patients who have undergone splenectomy for trauma cannot presently be calculated, there can be no doubt that this highly characteristic, highly lethal, and otherwise unusual syndrome can occur in a small percentage of asplenic individuals without serious underlying disease. An outline of selected historical milestones in the elucidation of postsplenectomy sepsis is presented in Table 5. Although the precise pathophysiologic mechanism of this phenomenon is not understood, certain hypotheses can be formed based upon a consideration of our present knowledge of splenic structure and function. 361

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TABLE 5.--HISTORICALI~IILESTONESIN THE ELUCIDATIONOFPOSTSPLENECTOMY SEPSIS YR 1952

AUTHOR(S)

1953 1958

King and Schumacker Parr Huntley

1962

Horan and Colebatch

1967

Eraklis

1969 1972

Diamond Eraklis

1973

Singer

366

MILESTONE Five infants with congenital hemolytic a n e m i a Meningitis or septicemia 6 weeks to 3 yr after splenectomy Fatal pneumococcal sepsis in patient with atrophic spleen 7 Serious infections among 46 children (<: 13 yr of age) All h a d underlying disease Serious infection in 17/142 children 5/10 children < 1 yr of age Five deaths from sepsis 3/10 children < 1 yr of age 2/132 children > 1 yr of age Trauma 46 Patients 4 Serious infections 0 Deaths Interval after splenectomy (93 infections/82 patients) Fatal 20/47 (43%) within 6 mo 31/47 (66%) within 1 yr 41/47 (87%) within 2 yr Nonfatal 11/46 (24%) within 6 mo 21/46 (46%) within 1 yr 30/46 (65%) within 2 yr Predisposing conditions Thalassemia Portal hypertension 467 P a t i e n t s 25 Deaths from sepsis 21/25 within 4 yr (84%) Incidence vs age at splenectomy 0 - 4 yr: 8.1% 4+ yr: 3.3% High risk "Thalassemia Portal hypertension Histiocytoses/errors of metabolism Wiskott-Aldrich syndrome Definition of overwhelmingpostsplenectomy infection (OPSI) Combined series 1,413 Patients 47 Hospital deaths 34/1,366 late deaths from sepsis Thalassemia 2/45 (4.34%) "Other" (see text) 20/323 (6.19%) ITP* 7/262 (2.67%) CHAt 2/394 (0.51%) Trauma 3/342 (0.88%) 2,795 Patients 119 With sepsis (4.25%) 71 Fatal (2.52%) Trauma: 688 Patients 10 With sepsis (1.45%) 4 Fatal (0.58%)

TABLE 5 . - - C O N T I N U E D YR

AUTHOR[S)

1977

Gopal and Bisno

1980

Oakes a n d C h a r t e r s

I~IILESTONE Incidental: 233 P a t i e n t s 5 With sepsis (2.10%) 2 Fatal (0.86%) Pneumococcal sepsis/20 "normal" asplenics Average age: 32.8 yr (7 to 71 yr) Interval from splenectomy: 7 mo to 25 yr Mortality: 70% Pneumococcal sepsis/14 "normal" asplenics Average age: 16.4 yr (4 to 46 yr) Interval from splenectomy: 6 mo to 31 yr Mortality: 93%

*ITP = idiopathic thrombocytopenic purpura. tCHA = congenital hemolytic anemia.

ANATOMY

Embryologically the spleen first appears at the 8.5-mm stage (the beginning of the sixth week) as a collection of mesodermal cells on the left side of the mesogastrium.6~By the 29-mm stage (the beginning of the third month) the cells have become organized into a recognizable structure, which by the fourth month has assumed its final position in the left upper quadrant. At birth the spleen is larger in relation to body weight than at any other time during life, but it is histologically immature, containing few lymphoid follicles and no germinal centers. During the first year of life it undergoes a threefold to fourfold increase in weight and becomes morphologically mature. At puberty it attains its maximal weight (100 to 150 gm), thereafter decreasing by 25% to 30% in the normal adult. The spleen eventually comes to contain approximately 25% of the total body lymphoid mass. ~1 Blood enters via the splenic artery, which divides in the hilum into a series of trabecular branches. The trabecular arteries are segmental in distribution, a fact of some importance when one considers the feasibility of partial splenectomy (see below). After leaving the trabeculae, the vessels enter the white pulp and are termed central arteries. They are surrounded at this point by masses of lymphocytes, plasma cells, and fixed macrophages. Leaving the white pulp, the blood passes through an ill-defined vascular space termed the marginal zone before it enters the venous sinuses of the red pulp. The details of the microcirculation of this region are not fully elucidated, but there is a richly interlacing network of vascular sinuses and channels that contain many fenestrations in their basement membranes and that are undoubtedly important in the filtration of blood and bloodborne particles. Sinusoidal blood flow is thought to be relatively slow and thus to allow time for effective interaction between 367

blood and splenic macrophages. Total circulation through the spleen is large; it is estimated to be between 150 to 250 ml/min, which represents approximately 5% of the cardiac output. 62'63In the words of Ellis: "The spleen is unique in that it is the only organ having a high blood flow, an active macrophage system, an abundance of immunoglobulin-producing lymphocytes, and a structure designed for filtering the blood." SPLENIC FUNCTION

The spleen serves two distinct roles in host defense mechanisms: the clearance of particulate matter by phagocytosis and the elaboration of antibody. These two functions are in fact interrelated. The clearance of certain antigens, particularly encapsulated bacteria, depends heavily upon the prior elaboration of specific antibodies to facilitate phagocytosis. On the other hand, the production of antibody against certain blood-borne antigens requires that the material first be ingested and processed by splenic macrophages before it can effectively interact with immunocompetent, antibody-producing cells. PHAGOCYTOSIS IN THE C L E A R A N C E OF PARTICULATE M A T T E R

Blood-borne particulate antigens are cleared from the circulation by phagocytic cells of the reticuloendothelial system. These cells reside primarily in the liver and spleen. In 1967 Schulkind and associates64 sought to evaluate the relative importance of these two organs in the phagocytosis of pneurnococci in both immune and nonimmune rabbits. Because of its greater size the liver was found to bear the greater total organ burden under all circumstances, but was dependent upon type-specific antibody for m a x i m u m clearance. The spleen, on the other hand, had a consistently higher capacity for uptake of the organisms per unit of weight, and the difference was especiallymarked in the nonimmune animal. They speculated that "the capacity of the spleen for clearance of a single episode of bacteremia m a y have considerable significance in the absence of specific antibody." Thus, when opsonizing antibody is not present, the spleen is the preferential organ of clearance of pneumococci borne hematogenously. Recently, Chaudry and colleagues6s have studied reticuloendothelial function in both normal and splenectomized rats by measuring the clearance of 1311-trioleingelatinized lipid emulsion. This experimental system provides another means of evaluating nonimmune clearance. They found that asplenic rats had a 2 5 % mortality after the lipid injection;there were no deaths in the control animals. Hepatic retention of the emulsion was depressed for two days following splenectomy, but lung uptake was markedly and persistently increased. They concluded that 368

"splenectomy may not only cause a transient depression in systemic RE phagocytosis, with importance in terms of host effects against bacteremia, but . . . may also cause prolonged susceptibility of the host to pulmonary microvascular embolism and]or localization of blood-borne particulate matter." ANTIBODY PRODUCTION

Although the spleen is thus important in the nonimmune clearance of blood-borne particulate matter, its primary role in host defense against infection probably arises from the generation of specific antibodies that facilitate phagocytosis. PRIMARY IMMUNIZATION:INTRAVENOUS ANTIGEN

One of the earliest and most significant observations with regard to the spleen's role in antibody production was provided by Rowley2~ in 1950. Using small intravenous (IV) doses of sheep erythrocytes (1 ml of a 2% suspension), he showed that, following splenectomy, neither rats nor humans could produce a normal antibody response.. If splenectomized rats were given the same dose of antigen by another route (intraperitoneally, intraportally, or intradermally), they responded as well as the control animals. Thus the spleen appears necessary for a normal primary response to some intravenously administered antigens. The possible relationship of this defect to postsplenectomy sepsis is discussed below. Sullivan et al. 66 studied the immune response to intravenously injected bacteriophage and to subcutaneously administered tridecavalent pneumococcal polysaccharide vaccine in 31 patients with anatomical or functional asplenia. None of the patients responded normally to primary" challenge with IV bacteriophage. After a second IV immunization, 18 of 30 patients had antibody responses within one standard deviation of the normal mean. The class of antibody produced, however, was IgM rather than the IgG antibody usually seen after secondary immunization. They referred to this as a "failure of maturation of the secondary response," but did not speculate on the underlying mechanism. On the other hand, except for four patients with Hodgkin's disease who were being treated by a combination of radiation and chemotherapy, all patients responded well to subcutaneous im9munization with pneumococcal vaccine. Sullivan et al. concluded: '~These studies further support the concept that the spleen is necessary for a normal immune response to blood-borne antigens but that other parenteral (subcutaneous) routes of immunization circumvent the need for the splenic immune response." They suggested that patients with Hodgkin's disease who have undergone splenectomy be immunized with pneumococcal vaccine before radiation or chemotherapy. 369

SERUM IMMUNOGLOBULINS

Seeking an explanation for postsplenectomy sepsis, Claret et al. 67 measured IgG, IgM, IgA, and globulin [3-1 metal binding in 52 children who had undergone splenectomy for a variety of reasons. The results were compared with two control groups (30 children postappendectomy and 76 children after other surgical procedures). They found that splenectomy resulted in a significant decrease in IgM (P = 0.001), a significant increase in IgA (P = 0.001), a small increase in IgG (P -- 0.025), and no change in globulin [3-1 metal binding. Several other investigators have also observed reduction in IgM following splenectomy (Schumacher, 6s 1970; Winkelstein and Lambert, 69 1975; Chaimoff et al., v~1978). Since IgM is the first species of immunoglobulin produced after primary exposure to an antigen, its reduction following splenectomy may be related to the immunologic defect (failure of primary response to intravenous antigen) described by Rowley and Sullivan. Regardless of the etiology of this decrease, it is interesting to note that Hobbs et al. 71described an increased susceptibility to pneumococcal septicemia (one of the leading causes of postsplenectomy infection) in individuals with congenital ~/-M deficiency. SERUM OPSONIZINGACTIVITY

Pneumococci and other encapsulated organisms are not cleared from the blood in a normal fashion unless they are coated with specific antibodies (opsonins) that facilitate phagocytosis.~2 It can be shown that the spleen of the rabbit is responsible for the elaboration of early opsonizing antibody in response to IV pneumococcal challenge. Ellis and Smith 6~ demonstrated the extreme rapidity of this response. If young rabbits are immunized intravenously with 5,000 killed pneumococci and challenged only eight hours later with a lethal dose of live organisms, protection is seen in normal but not in splenectomized animals. Heat labile opsonin activity was first described by Wright and Douglas v3 in 1903 and has subsequently been found to be caused by (1) specific antibody induced by immunization with relatively large amounts of antigen; (2) "natural antibody" probably resulting from stimulation by smaller amounts of antigen in the environment; (3) several or all components of complement; and (4) certain serum proteins termed phagocytosis promoting factors detectable under defined experimental conditions. Normally, serum opsonizing activity for pneumococcus is absent or very low at three to four weeks after birth, but gradually reaches adult levels by about two years of age. This suggests that "natural" antigenic stimulation by casual contact with 370

pneumococci in the environment is necessary for the developm e n t of this activity. TM In 1968 Winkelstein and Drachman TM reported a deficiency of pneumococcal serum opsonizing activity in 14 children with sickle cell disease (mean phagocytic index, 6.5%, compared with 35.1% in control children). Based upon the current concepts of splenic physiology, they proposed the following model to explain the evolution of pneumococca ! infection in children with sickle cell disease: "A few pneumococci from the respiratory tract enter the circulation. Little or no antibody or opsonin is present in the serum. As a result, the spleen becomes the primary site of clearance for pneumococci from the circulation. Owing to plugging, thrombosis, and infarction in the spleen, as well as to the lack of opsonin, ingestion by macrophages of the reticuloendothelial system is inefficient or ineffective. The same conditions prevent or impair the development of early antibody or opsonin, which normally facilitates clearance after several hours. In the absence of adequate clearance, pneumococci lodge in other tissues and multiply. Mobile macrophages, such as polymorphonuclear leukocytes, migrate into the infected tissues, but the lack of serum opsonin prevents adequate phagocytosis and killing of the pneumococcus. Bacterial multiplication therefore continues unabated, eventually causing overwhelming infection. '~4 Such a model is realistic, given the fact that the pneumococcus has a doubling time of only 20 to 30 minutes. 33 The formulation was given additional support as an explanation for overwhelming postsplenectomy infection when, in 1975, Likhite ~5 reported decreased opsonin and leukophilic ~-globulin activity (see "Tuftsin" below) in chronically splenectomized rats. A subsequent study by Winkelstein and Lambert, 6~ however, demonstrated normal serum opsonizing activity in 24 children who had undergone splenectomy for a variety of indications. Since his assay apparently used only one capsular type of pneumococcus to measure opsonizing activity (Type XXV), deficiencies with regard to other types of the organism might have been overlooked. TUFTSIN In 1970 Najjar and co-workers TM described a circulating peptide that stimulates phagocytosis by acting directly on blood ]eukocytes rather than on the target particle. The activity resides within a specific fraction of immunoglobulins termed leukophilic ~-globulin. About 2% of normal ~-globulin shows this specific binding affinity to the leukocyte membrane. The active moiety is a tetrapeptide that acts in hormone-like concentrations to stimulate phagocytic activity of polymorphonuclear leukocytes. The material has been termed Tuftsin after Tufts University, where it was discovered. It is covalently bound to leu371

kophilic ~-globulin (leukokinin) and cleaved from the parent molecule by a membrane enzyme (leukokinase). The evidence suggests that Tuftsin is attached to the carrier molecule in the spleen and that the tetrapeptide is probably manufactured there. Following splenectomy in dogs, Tuftsin activity is lost within six to eight weeksY In rats, leukophilic ~-globulin activity is depleted between nine and 12 weeks after splenectomy, a depletion that parallels the half-life of ~-globulin. 7~Patients who had undergone "uncomplicated" splenectomy showed complete absence of Tuftsin effect, but adequate Tuftsin activity has been found in one patient with an accessory spleen and in two cases following splenectomy for traumatic rupture. Patients with congenital Tuffsin deficiency may suffer from recurrent infections. However, these infections characteristically present as bronchitis, pneumonitis, skin lesions, or suppurative lymphadenitis and are thus clearly distinguishable from the syndrome of overwhelming postsplenectomy infection. OTHER MECHANISMSOF HOST DEFENSE: COMPLEMENT, PROPERDIN, SPLENIC INFLUENCE ON THYMUS-DERIVED LYMPHOCYTES, AND SUPPRESSOR CELL ACTIVITY

The complement system is a group of serum proteins that bind together sequentially to hemolyze erythrocytes or to destroy other suitably sensitized target cells. Complement has also been shown to be an essential part of the "heat labile opsonin system," a system in which phagocytosis of pneumococci is enhanced by factors present in the normal serum of nonimmune animals. TM When acting in this latter capacity, C3 and to a lesser extent C5, the third and fifth components of complement, become bound to the surface of pneumococci in the absence of C1, C4, and C2, their us~ual activators. They are therefore said to operate via the "alternate" or "properdin" pathway of complem e n t fixation. In the nonimmune animal this activation is mediated by a serum enzyme termed Factor B. In 1959 Carlisle and Saslaw 79 studied 105 ,splenectomized individuals and demonstrated a highly significant decrease in properdin levels compared with 113 normal controls. This suggested that such patients might be less able to resist pneumococcal infection during the early preantibody stages. Recently, however, Winkelstein and Lambert 69 reported normal levels of C3, C5, and Factor B in 24 asplenic children. Thus, although the alternate pathway of complement activation produces the majority of serum opsonizing activity in nonimmune individuals, its import a n c e - i f a n y m i n postsplenectomy sepsis remains to be defined. Although splenic lymphocytes are B cells Cbursa-derived" lymphocytes) and hence are concerned primarily with antibody production, there is evidence to suggest that the spleen somehow 372

interacts with the thymus in the regulation of cell-mediated imm u n i t y via the thymus-derived T cells. In 1970 Ernstrom and Sandberg 8~found that splenectomy in guinea pigs resulted in an increased release of lymphocytes from the thymus. By 28 days a generalized lymphocytosis was established, associated with hypertrophy of cervical lymph nodes. They therefore postulated that the spleen acts hormonally to inhibit both the release of lymphocytes from the thymus and the production of lymphocytes by nonthymic tissue. More recent studies have demonstrated that appropriately timed splenectomy can influence the growth of tumors in mice and rats. 81'82 This is associated with changes in suppressor cell activity, a function generally attributed to thymus-derived lymphocytes (T cells). This suggests that the spleen m a y act as a transient reservoir of suppressor cells during the early stages of tumor gr0owth. In spite of this and other fragmentary evidence, little is k/iown of the nature, extent, and clinical relevance of the spleen's influence on the release and function of thymus-derived lymphocytes. PATHOPHYSIOLOGY OF OVERWHELMING POSTSPLENECTOMY INFECTION The above data are consistent with the explanation of fulminating postsplenectomy sepsis proposed by Ellis and Smith 6~ in 1966: "It may be postulated that the spleen is capable of rapidly and effectively mobilizing a specific immune response through encounter with the relatively few organisms that might reach the circulation early in the course of pneumococcal pneumonia or otitis media. Thus, the spleen could initiate rapid specific antibody synthesis and then release this antibody in high local concentration into a slow moving capillary bed where phagocytosis may occur ~fficiently. The way would therefore be prepared to deal effectively with subsequent phases of the bacteremia which determine the outcome of infection. 'The splenectomized infant deprived of an organ capable both of recognizing small doses of particulate antigen and of phagocytosis in the absence of antibody would not react to the small antigenic challenge presented by the few organisms which enter the circulation during an early bacteremic episode. Since the liver is relatively ineffective in phagocytosis of encapsulated organisms, such as pneumococci, in the absence of antibody, increasing numbers of microorganisms would circulate freely. Thus rapid and fulminating pneumococcal sepsis of the type observed clinically might be established." Since "natural antibody" appears only gradually during the first y e a r or two of life, one would predict an increased incidence of overwhelming sepsis in asplenic infants and young children. A previously unencountered type of encapsulated bacteria could enter the circulation at any time, however, and thus account for the occurrence of fulminating postsplenectomy sepsis at any age. 373

Sepsis would be most likely to occur in individuals whose defense mechanisms were further compromised by systemic diseases affecting the lymphoid or reticuloendothelial systems. Given an organism encountered for the first time, however, the asplenic state per se could predispose to overwhelming infection even in otherwise healthy individuals who had undergone splenectomy for trauma. SPLENIC SALVAGE

If there were no means of salvaging splenic tissue, every patient who sustained injury to the spleen would face the unfortunate but inevitable risk of overwhelming postsplenectomy infection. During the past decade an impressive body of evidence has accumulated indicating that splenic injuries are not necessarily progressive and that the damaged spleen is capable of satisfactory healing either spontaneously or following surgical intervention. NONOPERATIVE OBSERVATION

The first experience with nonoperative management of splenic injuries using present techniques of monitoring and physiologic support was reported from the Hospital for Sick Children in Toronto in 1971. s3 Interestingly enough, this therapeutic approach was adopted, not because of fear of postsplenectomy septic complications, but because of the chance observation that a child suspected of having sustained a splenic injury in the remote past was found at autopsy to have a well-healed complete transection of the spleen. The authors reported on 16 children in whom the diagnosis of splenic rupture was considered "highly probable" on clinical grounds. The patients were not felt to have associated intra-abdominal injuries. They were treated with IV fluids and frequent monitoring of their vital signs. Complete bed rest was prescribed (in hospital or at home) for two weeks and activities were restricted for an ' additional four weeks. Hospital stay ranged from four to 42 days and averaged 16 days. Nine children received blood transfusions and two of these also received plasma. The volume of blood and colloid infused ranged from 18% to 90% of their estimated blood volume. None of the patients developed delayed rupture, splenic pseudocyst, enlarging hematomas, clinically apparent splenosis, or other late complications. The authors thus felt that disrupted splenic tissue was capable of healing by the usual sequence of hemostasis, clot absorption, and spontaneous repair. They stressed that the nonoperative approach should be restricted to "children whose injury involved minor trauma, whose clinical presentation is not considered grave, and in whom the spleen is felt to be the only organ damaged." Close observation is essential, and facilities must 374

be available to permit prompt laparotomy if the patient's condition deteriorates. In a follow-up report from the same institution (1978), the authors reviewed their experience from 1972 to 1977 with 56 children whose splenic injuries were documented by radioisotope scanning. 84 Twenty-one children were considered unstable and underwent laparotomy; at operation, only 12 were actively bleeding from the damaged spleen. Thirty-five patients were successfully managed nonoperatively. Fourteen of these required blood transfusion. Healing was documented by follow-up radioisotope scans. The scans frequently did not become completely normal, often demonstrating residual defects. Such defects, however, were stable and showed no tendency to increase in size. None of these children developed delayed or secondary ruptures or injuries to the spleen. (The authors cited two cases of delayed rupture of subcapsular hematomas in children treated nonoperatively at other hospitals. Both ruptures occurred within one week of injury and presented with the usual signs and symptoms.) They stressed that very few children bleed suddenly and massively from splenic injuries. If operation is undertaken and the spleen is found to have a small capsular tear that is not bleeding, they suggest that the organ ' ~ . . . may best be left in place." A similar experience has been reported from Children's Hospital Medical Center in Boston. 85 Twenty children treated nonoperatively over a three-year period were followed by splenic scintigraphy using 99~TC sulfur colloid. All patients did well clinically. Only three of 13 patients followed for two or more months showed scintigraphic evidence of complete healing. The others had residual defects two to 12 months after injury. In no patient, however, did the initial splenic defect enlarge on subsequent scans to suggest a traumatic cyst or enlarging hematoma. Delayed rupture was not seen in any of the 20 patients. The authors suggest that a two-month to three-month scintigraphic follow-up is sufficient in the asymptomatic patient. If pain subsequently develops or if a left upper quadrant mass appears, a repeat scan should b~ obtained promptly. Nonoperative observation thus appears to be a safe and satisfactory approach to the patient with an isolated splenic injury who is hemodynamically stable and who is in a facility where he can be closely monitored. Once the initial bleeding has ceased, these patients do not seem prone to delayed or secondary rupture, splenic cyst formation, or other adverse long-term sequelae. SURGICAL REPAIR OF THE INJURED SPLEEN

Given that nonoperative observation is applicable only to a highly selected group of patients--those who are hemodynami375

cally stable and in whom associated intra-abdominal injuries are deemed unlikely--what options are available to the surgeon who is confronted with an injured spleen at the time of celiotomy? Must splenectomy be performed, or can hemostasis and healing be reliably achieved without total extirpation of the organ? During the first half of this century, splenectomy became established as the standard operation for all cases of splenic injury, no matter how trivial. The first indication in recent times that lesser procedures might suffice in some patients was a report by Campos Christo 86 in 1962 of segmental resection of the spleen in eight patients following traumatic injury. There were six penetrating injuries (four bullet wounds and two knife wounds) and two cases of blunt trauma suffered in motor vehicle accidents. The operative approach was based on the belief that the spleen is made up of several segmental units, united in a common capsule, but each possessing-its own unique blood supply. The "'parenchymatous units" were felt to be separated by nonvascular or "almost nonvascular" planes, making segmental resection feasible. The splenic pedicle was reached by dividing the gastrosplenic ligament. The hilar vessels supplying the injured portion of the spleen were identified and ligated. The devascularized segment was observed to demarcate from the rest of the organ and was resected so as to leave about 0.5 cm of devitalized tissue. Bleeding from the cut surface was minimal and was easily controlled by ligation of individual vessels and the application of Gelfoam or omentum. Campos Christo thought that the spleen should not be mobilized for fear of "dangerous post-operative dislocation" of the organ. (Subsequent experience of other surgeons shows that this is not a valid concern.) The operation was felt to be successful in all patients, although one patient who also had a gastric perforation with original wounding died 30 days later following drainage of a left subphrenic abscess. At autopsy the spleen showed " . . . adhesions with stomach and omentum in the hilar region but failed to reveal other abnormalities." No late complications were observed, but the period of follow-up ranged from 28 days to five months, averaging only two and a half months. This report has been much quoted by subsequent authors, but because it appeared in a Brazilian medical journal it probably was not widely read at the time. It does, however, serve to dispel the myth that only splenectomy can assure prompt and lasting hemostasis following injury to the splenic parenchyma. In 1964 Morgenstern et al. 87 reported a subtotal splenectomy in a patient with massive splenomegaly from myelofibrosis. He based the preserved segment upon the short gastric vessels. Intrasplenic vessels were secured by figure-of-eight suture ligatures of 5 - 0 silk. Surface hemostasis was achieved using methyl-2-cyanoacrylate, the first reported clinical use of this 376

material for splenic bleeding. (Methyl-2-cyanoacrylate is no longer available for this application in this country.) The operation was performed without the need for blood transfusion and the patient was reported well one year later. The author notes that "the firm consistency of the splenic parenchyma in this diso r d e r make suture placement and ligation easier than in the normal organ." Although Bodon and Verzosa8s acknowledged the conventional teaching that "injury to the spleen means splenectomy, no matter what the type, size, or location of injury," they reported three patients with small capsular tears suffered accidentally during hiatal herniorrhaphy who were successfully managed by the application of Gelfoam (in 1967). They stressed that hemostasis with Gelfoam should be attempted only with superficial injuries in easily accessible areas of the spleen. The patients apparently had no significant problems during their hospitalization. One of the first reports of successful suture repair of a major splenic injury was that of Mishalany89 in 1974. An eight-yearold boy underwent laparotomy for abdominal pain and hemorrhagic shock following a fall. At operation the spleen was actively bleeding from a full-thickness tear that involved the hilum. The tissue on each side of the fracture site was reapproximated using through-and-through sutures of 3 - 0 chromic catgut on an atraumatic needle. Additional sutures were placed through the capsule, some incorporating the omentum. Excellent hemostasis was achieved. The integrity of the repair was documented at nine days and at two months by both arteriography and isotope scanning. Mishalany reported similar success in eight of ten consecutive cases of traumatic rupture of the spleen. It was his contention that "no matter what plane the injuries assume it is worthwhile saving all or portions of the spleen. Even the most brisk bleeding can be controlled by suture approximation." That year Morgenstern9~ described the use of a new topical hemostatic agent, microcrysta!line collagen hemostat (Avitene), in a patient who suffered a small area of capsular avulsion from the lower pole of the spleen dUring vagotomy and hemigastrectomy. Complete hemostasis was achieved and the patient was well one month later. Avitene was felt to be particularly wellsuited for control of this type of bleeding because of its ability to adhere to wet surfaces, to maintain its pliability in the face of motion and manipulation, and to be resistant to breakthrough bleeding. Bleeding is apparently arrested by a combination of platelet entrapment and prompt fibrin deposition. As with earlier topical hemostatics, use of this agent was recommended only for superficial capsular avulsions. Within three years Morgenstern 91 reported a total of 21 patients whose iatrogenic capsular avulsion injuries were successfully managed by topical hemostatics. In the first six patients the agents employed were 3??

charged gold leaf, methyl-2-cyanoacrylate, or collagen sponge. The subsequent 15 patients received Avitene as the only topical hemostatic agent. Once it became clear that splenic injuries could heal in a satisfactory fashion either spontaneously or after surgical repair, it remained only for surgeons to develop a larger experience with splenic salvage procedures and to describe additional operative techniques. One of the earliest efforts to apply splenic salvage to all splenic injuries was reported by Ratner et al. 92 in 1977. Seventeen children who suffered splenic disruption secondary to blunt trauma were considered for splenic salvage. Repair was successful in 15 patients. Only two spleens were removed: one because of "extensive hilar injury" and the other because of severe associated injuries. One patient who underwent splenic repair died eight days later from brain injuries. At autopsy the splenic repair was intact and there was no significant hemoperitoneum. No complications were observed secondary to splenic repair, but Ratner et al. cautioned that the possibility of increased susceptibility to future trauma must be considered and that the ability of splenorrhaphy to prevent or decrease postsplenectomy sepsis had yet to be verified. The techniques used in this series included (1) full mobilization of the spleen into the wound, (2) use of large chromic suture material (0-0, 2-0, 3-0) as simple or figure-of-eight sutures without pledgets, (3) individual ligation of large bleeding vessels, (4) use of omentum or topical hemostatic agents for oozing surfaces, and (5) use of no drains. Repair was not to be attempted in the face of extensive vascular laceration, extensive splenic fragmentation, or patient instability due to major associated injuries. To be acceptable, the degree of hemostasis should be comparable to that achieved following repair of hepatic or renal injuries. About this same tifile, Burrington 9a reported successful repair in eight of ten consecutive patients treated for splenic injury. To the above list of techniques he added partial splenectomy, thus confirming Campos Christo's contention that segmental splenic resections were feasible in man. Mattress sutures of 0 - 0 or 2 - 0 chromic catgut were inserted to compress raw surfaces, and the ends tied over a piece of omentum to reinforce the suture line. Reports of successful splenic repair accumulated rapidly. By late 1978 Strauch 94 could cite 227 patients with partial splenectomy or surgical repair of the spleen. The basic techniques employed were (1) ligation of segmental vessels in the hilum, (2) suture ligation of individual intrasplenic vessels, (3) direct suture of the splenic parenchyma, (4) partial splenectomy, and (5) the application of topical hemostatic agents. Buntain and Lynn 95 have recently published a detailed review of the techniques reported useful in splenic repair. To these they added two previously unreported maneuvers: the use of an absorbable suture "ladder" tied around the spleen like a tire chain or hairnet to 378

exert gentle but firm hemostatic pressure, and the use of large through-and-through mattress sutures passed through the entire organ perpendicular to the plane of injury by means of a #20 spinal needle. Keramidas 96 has reported the successful application of splenic artery ligation in combination with splenorrhaphy in the treatment of two children with injury to major segmental vessels. It is significant that among the 227 splenic repairs cited above, in only one was there a need to remove a repaired or partially resected spleen. In that patient a large perisplenic hematoma developed five weeks after repair of a relatively minor injury. The spleen, which was covered with thick fibrous adhesions, was damaged during reexploration and had to be removed.9~ How effective is splenic function following partial resection, and how much spleen can be removed without compromising the host's ability to resist pneumococcal septicemia? No patient has been reported to have experienced overwhelming infection following partial resection or any other type of splenorrhaphy, but the number of patients at risk is much too small and the period of follow-up much too short to draw any meaningful conclusions. In 1976 Grossfeld and Ranochak98 reported that hemisplenectomy resulted in essentially normal protection against pneumococcal sepsis in 19 rats operated on at one week of age and challenged intraperitoneally one week later. Mortality rates were 85.5% for splenectomized animals, 10% for sham operated controls, and 15% for those undergoing hemisplenectomy. Goldthorn et al. 99 found that rats with preservation of approximately 25% of the spleen demonstrated a greater resistance to IV pneumococci when challenged six months later than did asplenic animals, but resistance still was less than in normal controls. In 1980, Van Wyck and colleagues1~176 performed graded partial splenectomies in rats and found that "a critical mass of spleen (more than one-third) is needed to restore host resistance to fatal blood-borne infection" from Streptococcus pneumoniae type III. Using mice exposed to an aerosol of pneumococci, Coil et al. 1~ showed that animals undergoing 50% splenectomy retained normal rates of protection against pneumococcal pneumonia. Thus, laboratory studies suggest that if 30% to 50% of the spleen is preserved, a normal level of host resistance to infection can be anticipated. In summary, splenorrhaphy has been shown to be a safe and effective alternative to splenectomy in the management of almost all patients with splenic trauma. A variety of effective surgical techniques have been described to be used alone or in combination. To date, spleens that have undergone surgical repair do not seem to be at increased risk for future injury, nor (with a single exception) has splenorrhaphy resulted in any adverse long-term problems such as delayed rupture, expanding hema379

toma, or traumatic cyst formation. The ability of a salvaged spleen to protect the individual against overwhelming sepsis has yet to be definitely established; however, it seems highly likely t h a t completely normal splenic function will be preserved by most of these techniques. Based upon their review and personal experience with splenorrhaphy, Buntain and Lynn 95 observe: "Splenectomy should become more infrequent, and the documentation for necessity of the procedure will become important to every surgeon." PREVENTION OFIATROGENIC SPLENIC INJURY

Intraoperative injury to the spleen has accounted for approximately 25% of all splenectomies performed in this country in recent years. 91 Avulsion injuries are most common. These may arise from excessive traction on the major suspensory ligaments of the spleen, primarily the gastrosplenic or the splenocolic ligaments. In many patients, however, avulsion injury occurs secondary to traction on minor peritoneal folds that arise from the greater omentum, gastrosplenic omentum, or diaphragm and attach directly to the splenic capsule on its anterior or medial surfaces. Such folds are probably related to the fact that embryologically the spleen develops from the dorsal part of the mesogastrium. Lord and Gourevitch 1~ have published a detailed description of the peritoneal anatomy of the spleen based on a study of 100 cadavers. Awareness of these peritoneal attachm e n t s will help the surgeon avoid this type of avulsion injury. No more than the most gentle palpation should be performed in the left upper quadrant prior to visualizing and dividing any and all minor adhesions between the splenic capsule and adjacent intraperitoneal ~tructures. Extensive manipulation of the gastric fundus should be preceded by ligation and division of the short gastric vessels. The splenocolic ligament should be divided early in the mobilization of the splenic flexure of the colon. By the same token, in mobilizing the splenic flexure of the colon, the splenocolic ligament should be divided by the scissors, and traction upon it should be avoided. If these simple rules are followed, the incidence of intraoperative splenic injury should be markedly reduced. If injury does occur, especially if it is a minor capsular avulsion, splenectomy is not mandatory. Successful repair will usually be possible by means of topical hemostatic agents with or without the other techniques of splenorrhaphy described above. PROTECTION OF THE ASPLENIC PATIENT

There remain three primary indications for splenectomy after traumatic rupture: (1) total avulsion or extensive fragmentation of the spleen, (2) life-threatening associated injuries that de380

mand prompt attention and make splenectomy an advisable expedient, and (3) failure of splenorrhaphy to produce an acceptable degree of hemostasis. Possible treatment of patients in whom splenectomy has proved inevitable includes some form of splenic autotransplantation, the use of prophylactic antibiotics, and vaccination to provide immunity against the surface antigens of the encapsulated bacteria associated with postsplenectomy sepsis. The advantages and limitations of each of these approaches are discussed below. AUTOTRANSPLANTATION Numerous investigators have reported attempts to protect various laboratory animals against severe postsplenectomy sepsis by the autotransplantation of splenic tissue intraperitoneally, subcutaneously, or into the retroperitoneal space. I~ With the exception of one study of subcutaneous autotransplantation of one third of the spleen in mice, I~ all investigators have found that such autotransplanted tissue will not provide a normal degree of protection against subsequent IV challenge with pneumococci. Recent experiments in our laboratory indicate that intraportal splenic autotransplantation in rats, although technically feasible, is likewise ineffective in preventing postsplenectomy sepsis. H6 Pearson et al. 117 have suggested that incidental splenosis frequently occurs following traumatic rupture. Such implants are capable of removing from the circulation erythrocytes with abnormal surface characteristics and may occasionally be demonstrable on liver-spleen scintograms. The suggestion that these "born-again spleens" may account for the low incidence of overwhelming postsplenectomy infection after splenectomy for trauma has led some cliniciahs to attempt the deliberate production of splenosis at the time of splenectomyJ TM The fact that such splenic implants may appear on scintigrams and that small amounts of splenic tissue may result in the recurrence of hematologic disease should not lead one to conclude that they will be capable of protecting the host against postsplenectomy sepsis. The evidence, in fact, is to the contrary: overwhelming postsplenectomy infection has occurred in at least 11 otherwise healthy patients in spite of the presence of accessory spleens or evidence of splenosis (Table 6). This failure is probably related to the decreased mass of splenic tissue that regenerates, and to its less satisfactory access to the circulation. 1~2a~9 Schwartz and associates ~1~ demonstrated that subcutaneous splenic autotransplants render asplenic rats more capable of developing antibody against intravenously administered sheep erythrocytes. Such autotransplants, however, afford no significant protection against IV challenge with Streptococcus pneumoniae type XXV. m Splenic regeneration, measured by both 381

TABLE 6.--FATAL POSTSPLENECTOMYSEPSIS IN PATIENTSWITH RESIDUALSPLENIC TISSUE: AUTOPSY FINDINGS1N 11 PATIENTS AUTHOR

YR

PATIENT

FINDING

Coler

1963

8-year-old girl

Coler Scully

1963 1975

13-year-old boy 23-year-old man

Balfanz Gopal

1976 1977

8-year-old girl ll-year-old girl

Gopal Reay

1977 1979

Reay

1979

17-year-old girl 19-year-old woman 21-year-old man

Sher

1979

29-year-old man

Rice

1980

12-year-old girl

Rice

1980

19-year-old man

"An accessory spleen, 3 cm in diameter, was adherent to the tail of the pancreas." "A small accessory spleen was present." "In the region of the tail of the pancreas there were multiple nodules of splenic tissue, the longest 3.5 cm in diameter. The total weight of the splenic tissue was estimated to be 15 gm. The nodules had obviously developed from splenic implants that occurred at the time of the trauma. Microscopically, the nodules proved to be surrounded by dense fibrous tissue in which numerous dilated blood vessels were evident. The parenchyma contained very little white pulp but otherwise resembled normal splenic tissue." "A small 1.5-cm accessory spleen was found." "There were several small ectopic spleens in the omentum and tail of the pancreas. The largest weighed 12 gm." "A 4-gm accessory spleen was present in the mesocolon." "Multiple splenic deposits were present in the omentum and in the pelvic serosa." "Splenic implants throughout the serosa of the peritoneal cavity were noted." '~l~vo small hemorrhagic subcapsular nodules 1 cm and 0.7 cm in diameter were prominent on the surface of the liver. (Histologically they) were found to resemble splenunculi." "Scattered over the peritoneal surfaces of the abdominal wall, diaphragm, stomach, intestine, and ovaries and in the greater omentum were over 100 smooth, firm, encapsulated deposits of solid, fleshy, purple tissue, of varying size. Most were 2 - 4 mm in diameter. The largest, 2.6 cm in maximum diameter and 0.8 cm in thickness, weighed 3 grn. The largest aggregate was 4 cm in maximum extent and 0.5 em in depth. Histologically the largest deposit showed normal splenic parenchyma but fibrous trabeculae and associated vessels were absent." "A loculated splenunculus 4.5 cm in maximum diameter (weight 42 gm) was found in the splenic bed. Scattered , deposits of splenic tissue up to 3 cm in diameter were present throughout the upper abdomen. The total splenic weight was 92 gm."

weight gain and structure, is superior following partial splenectomy to that after heterotopic implantation (Alvarez and Greco, '2~ 1980). This is true even if the splenic remnant is vascularized only via the short gastric vessels. Cooney et al. '~ demonstrated that in rats partial (approximately 50%) splenectomy is preferable to retroperitoneal splenic autotransplantation " . . . because it is associated with higher antibody titers after immunization, better pneumococcal splenic uptake, and improved survival." Goldthorn and Schwartz 1'9 have also observed 382

that subcutaneous splenic implants regenerate but fail to restore normal host resistance to the asplenic rat. They speculate that "there is something unique about the normal blood supply to the spleen that is necessary for the spleen to play its protective role in the host's defense against bacterial infection." To date, all laboratory studies agree that partial splenectomy is preferable to attempts at autotransplantation as a means of retaining essential splenic functions. Based on existing experimental and clinical data, the deliberate induction of splenosis or other attempts at autotransplantation at the time of splenectomy cannot be recommended. Partial splenectomy seems justified if at least one third of the splenic mass can be preserved.9s1~ 12~ PROPHYLACTIC ANTIBIOTICS

The limitations of prophylactic antibiotics in the prevention of overwhelming postsplenectomy infection are both theoretical and practical. Sepsis may arise from organisms that are not sensitive to the antibiotic employed; moreover, resistant strains of bacteria may evolve during therapy. Patient compliance has been shown to be poor in long-term programs using prophylactic antibiotics in the management of patients with rheumatic fever. 122 Since the risk of overwhelming postsplenectomy infection continues indefinitely, antibiotics would have to be continued for the life of the individual. If antibiotics are to be employed, the recommendations of Diamond2s cited above seem reasonable: use continuous prophylactic antibiotics only until the child is old enough to complain of the symptoms of impending infection (sore throat, headache, malaise). Thereafter use antibiotics only therapeutically, but use them early and for even trivial complaints in the asplenic individual. The most important thing is to make the patient and those caring for him aware of the potential risk and the insidious way in which serious septic episodes may present. 2s VACCINES

The use of the polyvalent antipneumococcal vaccine, now commercially available, may diminish but cannot completely abolish the risk of overwhelming postsplenectomy infection. The vaccine is not 100% effective,123"124and even if it were, the pneumococcus accounts for only about 50% of serious postsplenectomy infection. 125Fatal sepsis has bee.n reported from pneumococcal strains not included in the vaccine12G'~2~ as well as from failure of the patient to respond adequately to all of the components of the vaccine.1~81~~Vaccination with pneumococcal antigen should be performed in all patients who undergo splenectomy and will undoubtedly decrease the incidence of overwhelming postsplenec383

tomy infection in these individuals. ~31'132 It cannot, however, provide absolute protection, and therefore is not equivalent in protection to splenorrhaphy in patients in whom splenic repair is feasible. In view of the extreme safety of pneumococcal vaccine, 13~"132 its use should be considered in all patients who have sustained major splenic injury, even if splenorrhaphy has been successfully performed. As discussed above, the long-term ability of such spleens to protect against overwhelming sepsis has yet to be completely established. In summary, at the present time the only sure way of preventing overwhelming postsplenectomy infection is by avoiding splenectomy. When splenectomy is inevitable, the patient must be informed of his vulnerable state and protected as much as possible by application of present and future vaccines against pneumococci, meningococci, and other organisms associated with overwhelming postsplenectomy infection. Young children who cannot adequately communicate the symptoms of impending sepsis should be considered for continuous antibiotic prophylaxis. Deliberate induction of splenosis at the time of splenectomy is of doubtful value and is not recommended. To quote Winkelstein 1~3 (1977): "The most important element in the care of these patients is the awareness that any patient without a spleen is an abnormal host and at risk for developing sepsis." EXPERIENCE WITH SPLENIC SALVAGE: SANTA CLARA VALLEY MEDICAL CENTER, APRIL, 1979, TO SEPTEMBER, 1980

Beginning in April, 1979, every patient with an injured spleen who presented to the. Santa Clara Valley Medical Center, San Jose, California, was considered a candidate for splenic salvage. By September, 1980, we had accumulated 24 patients, 19 males and 5 females, whose ages ranged from six to 71 (average age, 39.6). Blunt trauma, usually secondary to motor vehicle accidents, produced splenic disruption in 15 patients. Two patients sustained penetrating injuries of the spleen, both secondary to knife wounds. In seven patients the spleen was damaged during celiotomy for other indications. A protocol form was developed and used to describe and diagram the location, extent, and nature of the splenic injury (Fig 2). Injuries were defined as minor in seven patients, with damage limited to a small area of capsular disruption. The other 17 patients had major injuries with deep fractures extending into the splenic parenchyma (12 patients), large subcapsular hematomas (three patients), or total avulsion and fragmentation of the spleen (two patients). Repair was attempted in 20 of the 24 patients. The technique employed in each was selected on an empirical basis depending 384

DESCRIPTION OF SPLENIC INJURY

CLASSIFICATION (one or more) 1.

Simple capsular fracture

2.

Small capsular tear

3.

Major capsular avulsion

4.

Major parenchymal fracture

5.

Complete transection or avulsion

6.

Hilar arterial injury

7.

Hilar venous injury

Diaphragmatic Surface

Hilar Surface

Fig 2 . - - T o assess the efficacy of splenic salvage procedures it is necessary to document the exact location and extent of injury. This illustration shows a portion of the reporting protocol used in our series.

upon the nature, location, and extent of the injury. In all but the most minor injuries, the spleen was fully mobilized to provide optimal exposure and facilitate repair. Topical hemostatic agents were used on 17 occasions; in four patients this was all that was needed to produce satisfactory hemostasis. Figure 3 shows the use of this technique in the management of a patient with a large subcapsular hematoma. This 42-year-old man fell from a s and fractured his l l t h rib on the left, presenting with abdominal pain. Paracentesis was positive. Exploration disclosed a subcapsular hematoma measuring approximately 10 cm in diameter on the diaphragmatic surface of the spleen (Fig 3, A). The capsule had ruptured transversely, allowing slow but steady hemorrhage into the peritoneal cavity. After debriding the capsule and gently removing the clots (Fig 3, B and C), there was little bleeding from the exposed splenic parenchyma except at the periphery of the lesion. It seemed that the expanding clot was gradually stripping the capsule from the underlying spleen, producing a zone of fresh injury around the circumference. By removing the nonadherent portion of the capsule, progression of the injury was prevented. Bleeding from the raw surface was controlled by applying a layer of Avitene held in place by strips of Gelfoam (Fig 3, D). After about 45 minutes essentially total hemostasis was achieved (Fig 3, E). The patient did well and a radionuclide scan on postoperative day seven was entirely within normal limits (Fig 3, F). 385

/

~

:. ;.,. ERONTAL

POSTERtOR

Fig 3.--This figure illustrates steps used to treat a large subcapsular hematoma that involved superolateral aspect of spleen. After spleen had been mobilized into wound, the lesion was found to measure approximately 10 cm in diameter (A). The nonadherent capsule was removed, revealing a large, well-formed clot (B). The clot could be easily peeled away from the underlying parenchyma. Active bleeding was confined almost exclusively to periphery of lesion, where capsule had been most recently pulled away by the expanding clot (C). Avitene was placed on a large piece of Gelfoam and then applied directly to the raw surface (D). Several applications were required, but after a few minutes essentially complete hemostasis was achieved (E). A splenic scintogram obtained on the seventh postoperative day was entirely within normal limits, with no evidence of intraparenchymal, subcapsular, or extrasplenic hematoma (F).

In 13 patients topical hemostatic agents were used in combination with other techniques, such as direct suture of the splenic parenchyma by means of 3 - 0 chromic catgut suture on atraumatic needles, ligation of segmental vessels in the hilum, and partial splenectomy. The frequency with which these various maneuvers were used to achieve intraoperative hemostasis fol386

Fig 4.--This figure illustrates intraoperative finclings in a patient who sustained a stab wound to the left hemithorax, about the ninth intercostal space in the mid-axillary line. Knife passed through diaphragm into diaphragmatic surface of spleen (A) and out hilar aspect (B). Hilar structures were not injured, and there was no active bleeding. Spleen was not mobilized. After repair of hole in diaphragm, spleen was simply left in situ--without repair and without drainage. The patient did well, and a follow-up splenic scintogram was completely normal.

lowing splenic injury in 20 patients is as follows: topical hemostatics, 17; suture of parenchyma, 14; full mobilization, 13; ligation of segmental vessels, 6; partial splenectomy, 2; observation only, 2. It is apparent, that in most patients multiple techniques were employed, tailored to the individual situation. In two cases (one minor capsular disruption and one through-andthrough stab wound) there was no active bleeding and the spleens were left undisturbed (Fig 4). We did not in any patient 387

ligate the main splenic artery, nor did we use omentum or pledgets to buttress the repairs. Wrapping of the spleen with omentum or catgut sutures was not found to be necessary. For all extensive injuries, the spleen was fully mobilized to permit accurate assessment of damage and to facilitate repair. Satisfactory intraoperative hemostasis was achieved in all 20 patients. Drains were left or omitted at the discretion of the attending surgeons (D.D. Oakes and A. Crane Charters, III). Figure 5 illustrates the use of segmental devascularization and partial splenectomy in the t r e a t m e n t of a major parenchymal injury. This 64-year-old m a n fell from a ladder and sustained fractures of ribs 2, 3, and 4 on the left side and a left tibial plateau fracture. In the emergency room he was hypotensive and abdominal paracentesis yielded free blood. At celiotomy the actively bleeding spleen was fully mobilized. The superior pole contained several deep parenchymal fractures that extended into the hilum. A superficial longitudinal laceration was present on the anterolateral aspect of the lower pole. Bleeding was initially controlled by ligating the segmental vessels to the Fig 5.--This figure shows method of repair of an extensive injury to upper pole. After ligation of segmental vessels leading to area of injury, a clear line of vascular demarcation developed, which helped to define amount of tissue to be resected (A). Hemostasis was achieved by suture ligation of individual vessels, followed by fullthickness mattress sutures of 3 - 0 chromic catgut. A smaller disruption of lower pole was repaired with chromic sutures and topical hemostatic agents (B). A follow-up radionuclide scan showed loss of activity where upper pole had been resected, but demonstrated preservation of 60% to 70% of splenic parenchyma (C).

s L

POSTERIOR 388

FRONTAL

upper pole. This produced a clear line of vascular demarcation. The capsule was cauterized and the parenchyma was sharply resected so as to leave about 1 cm of devitalized tissue (Fig 5, A). Bleeding was controlled with 3 - 0 silk sutures, 3 - 0 chromic catgut suture ligatures, and topical Avitene and Gelfoam (Fig 5, B). The lower pole injury was managed with deep sutures of 3 0 chromic catgut and topical hemostatics. A closed suction catheter drained 700 ml of serosanguineous fluid the first 24 hours and insignificant amounts thereafter. A radionuclide scan obtained on the seventh postoperative day showed a defect consistent with resection of the upper quarter of the spleen (Fig 5, C). Postoperatively all patients were closely monitored in the hospital for at least seven days. In most patients the length of hospitalization was determined by the presence of associated injuries or of medical conditions unrelated to splenic repair. Baseline radionuclide scans were obtained at six to seven days afterward and repeated at one, three, and six months afterward. A representative series of scans demonstrating progressive healing is shown in Figure 6. As of October, 1980, follow-up averaged 9.4 months (2 weeks to 17 months). The decision to repair rather than to remove an injured spleen undoubtedly added to the operative time and intraoperative blood loss, but the extent of these differences is difficult or impossible to document. Treatment of associated injuries or, in the case of iatrogenic damage, the primary disease was the major determinant of the length of operation. Moreover, splenic repair was not always done at one isolated time: attention was often directed intermittently to the spleen, while we attended to other aspects of the procedure. Transfusion requirements were affected primarily by the extent of the preexisting hemoperitoneum or blood loss from othe~ injuries. Although we could not measure the exact excess blood loss associated with splenic repair, it was obvious that a moderate amount of bleeding occurred while assessing the injury and evaluating the degree of hemostasis achieved at various stages of the repair. Twenty-one early complicatio'ns were observed in 13 of 20 patients who underwent splenic repair. Twelve patients had 20 minor complications (atelectasis, 6 times; postoperative transfusion, 6; effusion, 5; pneumonia, 2; hyperamylasemia~ 1), most of which were related to associated chest wall trauma. All 20 minor complications were those commonly seen after left upper quadrant t r a u m a with or without splenectomy and were not unique to the splenic salvage procedures. One repair failed, a major complication that led to recurrent hemorrhage on the sixth postoperative day. In addition to his splenic injury, the patient, a 30-year-old man who had been involved in a motor vehicle accident, sustained rib and pelvic fractures, an extraperitoneal rupture of the bladder, and a minor liver laceration. His 389

R

4-19-79

6-20-79

10.23-79 FRONTAL

POSTERIOR

Fig 6.--This series of liver-spleen scans demonstrates progressive healing of a major laceration that occurred at about the junction of lower and middte thirds of spleen. Initial scan (4-19-79) was made one week after splenorrhaphy and shows an obvious transverse defect in frontal proiection and marked loss of function in lower pole on posterior projection. Two months later (6-20-79), defect has almost totally disappeared on frontal projection, and lower pole appears to be functioning normally on posterior projection. Six months after injury (10-23-79) scan has assumed a normal configuration in all projections.

splenic injury (shown in Fig 7, A) was thought to be only moderately severe. According to the operative note, '~the spleen had a rupture extending across its midportion approximately 0.5 cm deep and another tear on its anterior midsurface of approximately the same depth. There was no evidence of splenic hilar injury." Several short gastric vessels were ligated and the fractures were repaired with horizontal mattress sutures of 3 - 0 390

A

Fig 7.--One splenic repair was unsuccessful. The initial injury (A) extended only about 0.5 cm into splenic parenchyma~. It was repaired with 3 - 0 chromic sutures plus topical Avitene. Excellent intraoperative hemostasis was achieved. Postoperatively, however, the patient had a continuing transfusion requirement, attributed at first to associated injuries (pelvic fracture and extraperitoneal rupture of the bladder). A splenic scintogram obtained six days later, however, revealed multiple intraparenchymal defects (B) and presaged free rupture, which became manifest the following day. The spleen was irreparable (C); there were extensive intraparenchymal and subcapsular disruption and hematoma formation. Splenectomy was performed. The patient was given pneumococcal vaccine and warned of his need to seek prompt medical attention should he develop any febrile illness in the future.

chromic catgut. Avitene and Gelfoam were applied to the areas of injury. "No further bleeding was noted" following repair. Postoperatively the patient required repeated blood transfusions, but this was attributed to the large retroperitoneal hematoma associated with his pelvic fractures. A suction drain in the left upper quadrant produced only scant amounts of serosanguineous fluid. Because of the patient's continuing transfusion requirement, a radionuclide scan was obtained on the fifth post391

operative day (Fig 7, B). The spleen was enlarged and contained multiple intraparenchymal defects. The following day the patient developed diffuse abdominal pain and was returned to the operating room where splenectomy was performed. The specimen, shown in Figure 7, C, showed extensive areas of subcapsular and intraparenchymal hemorrhage. The patient's subsequent course was uncomplicated except for asymptomatic hyperamylasemia. He was treated with pneumococcal vaccine and warned of the possibility of future septic complications. Two of nineteen patients had late complications. These complications were felt to be unrelated to the splenic salvage procedures. One patient developed a small bowel obstruction three months after undergoing a Nissen fundoplication during which the lower pole of the spleen had been slightly injured and repaired with chromic sutures and Avitene. At reoperation an obstructing band was found in the midabdomen;this seemed totally unrelated to the area of splenic injury. The second patient, a C-5 quadriplegic, died seven months after repair of a small capsular avulsion of the spleen. The injury occurred during the closure of a perforated posterior gastric ulcer. The spleen was not mobilized, and the bleeding was easily controlled with topical Avitene. The patient subsequently suffered several episodes of respiratory arrest, which were attributed to his central nervous system injuries. Following one such episode five months after splenic repair, he was fully anticoagulated for several days for a presumptive diagnosis of pulmonary emboli. There was no evidence of intraperitoneal bleeding during this period of heparinization. Two months later he died at home following another respiratory arrest. A postmortem examination was not permitted, but there was no clinical evidence to suggest that his death was in any way related to the splenic repair. To date there have'been no other late complications. Except for the case described above, there have been no episodes of delayed bleeding. No patient has developed symptoms suggestive of a traumatic splenic cyst or of an expanding splenic hematoma. It is not yet known whether or not these spleens will be at a greater than normal risk for traumatic rupture in the future. One patient sustained blunt trauma to the abdomen two weeks after discharge without evidence of reinjury to the splenic repair. In four patients splenectomy was performed without any attempt at salvaging the damaged organ. In every case the decision was based on evaluation of the patient's overall status rather than on the extent of the splenic injury per se. Two of the patieflts sustained massive head, chest, abdominal, and extremity injuries in motor vehicle accidents. They were hypotensive and could not be resuscitated in spite of aortic crossclamping and rapid infusion of blood and crystalloid. Their 392

spleens, which had been almost totally avulsed, were removed as the most rapid means of achieving hemostasis at that site, allowing attention to be turned promptly to the management of associated injuries. Both patients died in the operating room before any definitive procedures could be performed. One patient sustained an iatrogenic injury during operation for gastrointestinal bleeding. Several years earlier he had undergone a hemigastrectomy and Billroth II reconstruction for peptic ulcer disease; he also had a history of portal hypertension. Endoscopy demonstrated an actively bleeding anastomotic ulcer. During lysis of adhesions in the left upper quadrant, the spleen was badly damaged. Since the patient had already received ten units of blood, since his ulcer was still bleeding, and since splenic repair would have been complicated by the dense adhesions and by the portal hypertension, splenectomy was elected as the fastest and safest means of achieving hemostasis. The fourth patient, a 19-year-old woman, suffered head and lower extremity injuries in a motor vehicle accident. An emergency craniotomy was required to drain an acute subdural hematoma. Three days later she was anesthetized to permit repair of ligaments in her left knee. The following day she developed abdominal pain, hypotension, and a falling hematocrit. She was found to have a major parenchymal injury involving the upper pole of the spleen. Repair was technically feasible, but splenectomy was chosen as the most expedient procedure in this multiply injured patient who was undergoing her third general anesthetic in five days. (Based on our subsequent experience with splenic repair, we would probably attempt splenorrhaphy if faced with this situation now.) Both surviving patients were subsequently given pneumococcal vaccine and warned that they should seek medical attention whenever they developed fever or "flu-like" symptoms. RECALL OF PREVIOUSLY SPLENECTOMIZED PATIENTS We are presently instituting a program to recall patients who underwent splenectomy at our institution prior to April, 1979. The patients are informed that they may be at slightly increased risk of major infection and that they should seek medical attention promptly at the earliest sign of a cold or fever. They are advised to see us or their local physician to obtain immunization with pneumococcal vaccine. SUMMARY 1. Overwhelming postsplenectomy infection is a highly distinctive syndrome characterized by abrupt onset, massive bacteremia, and a fulminant, frequently fatal course. In the major393

ity of patients it is caused by pneumococcal infection, but other organisms, including meningococcus, Escherichia coli, Hemophilus influenzae, staphylococci, and streptococci have been isolated in some patients. Unlike the situation in most septicemias, the source of the infection is usually obscure. There is a high incidence of disseminated intravascular coagulation and bilateral adrenal hemorrhage. Death frequently occurs within 24 to 48 hours of the onset of vague, flu-like symptoms (headache, fever, malaise, nausea, vomiting, and diarrhea). 2. Overwhelming postsplenectomy infection occurs most frequently in splenectomized patients with serious systemic disease affecting the lymphoid system or the reticuloendothelial system. It can, however, occur in otherwise healthy individuals who have undergone splenectomy for trauma or incidental to operation for benign disease. The incidence of overwhelming postsplenectomy infection in such patients is quite low (0.58% to 0.86%), but is still considerably higher than that in the normal population (0.01%). 3. Overwhelming postsplenectomy infection most commonly affects patients who undergo splenectomy within the first four years of life, but it can afflict individuals splenectomized at any age. Approximately 80% of septic episodes occur within two years of operation, but the syndrome has appeared as late as 25 and 31 years later. The clinical manifestations of overwhelming infection are the same whether splenectomy is recent or remote. 4. The spleen appears to be important in the nonimmune clearance of particulate matter from the bloodstream, the elaboration of a primary immune response to blood-borne antigens, and the production of antibodies that facilitate phagocytosis and of proteins that activate the alternate pathway of complement. Overwhelming postsl~lenectomy infection appears to occur when the asplenic individual encounters, via the bloodstream, an encapsulated organism to which he has not had prior exposure. In the absence of efficient nonimmune clearance and in the absence of specific phagocytosis-enhancing antibodies, rapid bacterial proliferation occurs and the host is quickly overwhelmed. Infants and children will be at greatest risk, since they have had less time to acquire '~natural antibody" to common organisms in the environment. Although this defect in host resistance will be most apparent in those persons with systemic diseases that predispose to infection, it arises from the absence of the spleen per se, and hence will to some degree affect all asplenic individuals. 5. Contrary to traditional surgical teaching, the injured spleen is capable of satisfactory healing--either spontaneously or after operative repair; that is, splenic injury does not inevitably lead to delayed rupture, enlarging splenic hematomas, or traumatic cyst formation. 394

6. Nonoperative management can be successfully applied to patients with isolated splenic injuries who are hemodynamically stable and who can be observed in an intensive care setting. One must be absolutely certain that there are no other significant intra-abdominal injuries t h a t require repair. 7. It is now well established that repair is feasible, safe, and effective in controlling hemorrhage in a large percentage of patients who present with splenic injury. Attempts at splenic repair will inevitably increase operating time and intraoperative blood loss. Although splenorrhaphy is probably indicated in most patients with isolated splenic injuries who are hemodynamically stable, it should not be attempted in the critically ill patient whose survival would be jeopardized by continuing or delayed hemorrhage. Although only two failures have been reported after splenic repair, this complication seems inevitable in a certain percentage of patients, and the patient should be warned of the possible need for a second operation. (On the other hand, reexploration is occasionally necessary following splenectomy, either for inadequate hemostasis or for later abscess formation.) The possibility that these spleens may be more susceptible to future trauma must be considered, but there is no evidence of that to date. After the first six weeks we have therefore not placed our patients on restricted activity. Only further experience will allow us to define the exact risks--early and l a t e m o f splenic salvage procedures. At the moment, splenorrhaphy seems to be both safe and effective in most patients. 8. When the performance of a splenectomy is felt to be unavoidable, the surgeon should document his reasons for electing that course of action. The patient should be informed of his potentially vulnerable state and protected insofar as possible by current and future vaccines and by early aggressive treatment of all infections. Infants and ~children who cannot adequately communicate the symptoms of early infection should be protected by continuing prophylactic antibiotics. The deliberate induction of splenosis at the time of splenectomy is probably ineffective in preventing future sepsis and is not recommended. 9. Patients who have undergone splenectomy in the past should be recalled and informed of the potential for serious septic complications. They should receive pneumococcal vaccine and be told to seek medical attention at the first sign of "cold" or "flu" symptoms. 10. Patients who have sustained major splenic injuries should probably be treated with pneumococcal vaccine, even if the spleen has been preserved. The risk of the vaccine is minimal, and the long-term effectiveness of the salvaged spleen in preventing overwhelming infection is still a matter of speculation. This is particularly true if less than one third of the splenic mass remains. 395

ACKNOWLEDGMENT

The author wishes to acknowledge the excellent secretarial assistance provided by Mrs. Janis Donaker Finch and Mrs. Pat Jones Ford in the preparation of the manuscript for this review. BIBLIOGRAPHY 1. Thal E.R., McClellandR.N., Shires G.T.:Abdominaltrauma, in Shires G.T. (ed): Care of the Trauma Patient, ed 2. New York: McGraw-HillBook Co., 1979, p 337. 2. Sherman R.: Perspectives in management of trauma to the spleen: 1979 presidential address, American Associationfor the Surgery of Trauma. J. Trauma 20:I, 1980. 3. Fioravanti L.: Il Tesoro della Vita Humana: Diviso in Libri Quattro. Venice: Appresso Gli Heredi di MelchiorSessa, 1570, L. If, chap 8. 4. Rousset F.: Hysterotomotokia.s, id est, caesarei partus assertio historilogia. Paris, D. Dural, 1590, p 323. 5. Reigner O.: Ueber einen fall yon exstirpation der traumatisch zerrissenen milz. Berl. Klin. Wochenschr. 30:177, 1893. 6. Berger E.: Die verletzunger der mi]z und ihre chirurgische behandlung. Arch. Kiln. Chir. 68:56, 1902. 7. Foster J.M. Jr., Prey D.: Rupture of the spleen:An analysis of twenty cases. Am. J. Surg. 47:487, 1940. 8. Morgenstern L.: The surgical inviolability of the spleen: Historical evolution of a concept, Proceedings of the XXIII International Congress of the History of Medicine, London, September 2-9, 1972. WellcomeInstitute of the History of Medicine, 1974, p 62. 9. James R.L.: A ease of gunshot wound of the spleen: Suturing of the diaphragrn: Recovery. North Am. Praet. 4:232, 1892. 10. ZikoffV.: Suturing of the spleen. Vraeh 16:995, 1895 (in the Russian). 11. Von Esmarch F., Kowa]zig E.: in Seva N. (ed): Surgical Technic. A Textbook for Operative Surgery. New York: MacMillan,1901, p 739. 12. Da Costa J.C.: Modern Surgery, ed 8. Philadelphia: W. B. Saunders Co., 1919, p 1203. 13. Thorek M.: Modern Surgical Techniques. Philadelphia: J. B. Lippincott, 1938, vo] 3, p 648. 14. Orr T.G.: Operations~fGeneral Surgery. Philadelphia:W.B. Saunders Co., 1949, p 682. 15. Hunt A.H.: Splenectomy,in Rob C., et al. (eds): Operative Surgery, ed 2. Philadelphia:J.B. Lippincott, 1968, vol 4, p 254. 16. Shires G.T.: Trauma, in Schwartz S.I. (ed): Principles of Surgery. New York: McGrawHill Book Co., 1969, p 195. 17. King H., SchumackerH.B. Jr.: Splenicstudies: I. Susceptibilityto infection after splenectomyperformed in infancy. Ann. Surg. 136:239, 1952. 18. Gruber S., Redner B., Kogut B.: Congenital idiopathic thrombocytopenia purpura in a premature infant with splenectomy. N.Y. State J. Med. 51:649, 1951. 19. Perla D., MarmorstonJ.: The Spleen and Resistance. Baltimore: Williams & Wilkins Co., 1935. 20. Marmorston J.: The effect of splenectomy on acute bacterium enteritidis infectionsin white mice. Proc. Soc. Exp. Biol. ivied. 32:981, 1935. 21. Morris D.H., Bullock F.D.: The importance of the spleen in resistance to infection. Ann. Surg. 70:513, 1919. 22. RowleyD.A.: The effect of splenectomyon the formationof circulating antibody in the adult male albino rat. J. Immunol. 64:289, 1950. 23. Parr L.J.A., Shipton E.A., Holland E.H.: A fatal case of Still's disease associated with Waterhouse-Friderichsensyndromedue to pneumococcalsepticemia. Med. J. Aust. 1:300, 1953. 396

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SELF-ASSESSMENT ANSWERS 1. F a l s e 2. b

3. T r u e 4. F a l s e 5. 6. 7. 8.

b d e b

9. c 10. 11. 12. 13. 14. 15. 16.

d c

False c

False

17. 18. 19. 20. 21. 22.

True c e

False True True

c c

401