Surgical Management of Infective Endocarditis in Children Michael Citak, MD, Allan Rees, MD, and Constantine Mavroudis, MD Departments of Surgery and Pediatrics, University of Louisville, Louisville, Kentucky
Infective endocarditis occurs infrequently in the general pediatric population, occurring mostly in patients with congenital heart disease. This study reviews our surgical experience with infective endocarditis based on a policy of aggressive intervention, conservative operative debridement, and creative reconstruction options using pericardium and prosthetic heart valves. From 1982 to 1989,16 patients, 3 weeks to 16 years of age, underwent 19 intracardiac operations for infective endocarditis therapy at Kosair Children’s Hospital. Eight (42%) were for resection of vegetations alone; an additional 11 operations (58%) involved more extensive debridements requiring either valve replacement or valvuloplasty using pericardium for exclusion of an abscess cavity, closure of
a fistula, or for valve repair. Operative mortality was 25% (4 patients) and related to preoperative disease severity. There was one late death. Offending organisms included Stuphylococcus species (31%), Huemophilus influenzue (13%), pneumococcus (5% ), gram-negative organisms (13%), and Cundidu (13%); no organism grew on culture in 25%. We conclude that aggressive surgical exploration in patients with infective endocarditis is indicated and often requires resection of vegetations alone. More extensive procedures should preserve as much valvular tissue as possible. Pericardium is useful for reconstruction after debridement.
I
function. The purpose of this retrospective analysis is to report our surgical experience with infective endocarditis in children and emphasize guidelines for conservative and restorative therapy.
nfective endocarditis occurs relatively infrequently in children under 17 years of age [l-31. At highest risk are those patients with congenital heart disease [l-81. To a lesser degree, endocarditis complicates patients with rheumatic heart disease, and rarely those with no major heart disease [l, 4-7, 91. Reports by Johnson and Rhodes [l]and Karl and associates [4] have shown that the most frequent congenital malformations that predispose to the development of endocarditis are tetralogy of Fallot, ventricular septa1 defect, and patent ductus arteriosus [5, 7, 101. Endocarditis complicating open heart operations is associated with a higher mortality rate than those cases occurring in patients who have not had a recent cardiac operation [4]. The organisms most commonly isolated are Stuphylococcus uureus, Streptococcus viriduns, and Streptococcus hemolyticus [l, 4, 5, 71. Less frequently infecting organisms are Huemophilus influenzue, various gram-negative organisms, and Cundidu ulbicuns [l,3-5, 7, 101. Bloodstream entry of the infecting organism is infrequently identified. Bone, pulmonary, and cutaneous infections, as well as dental manipulations, have all been described as possible sources for bacteremia [l, 4-7, 10, 111. However, in more than 50% of patients with documented bacteremias, no source of contamination has been identified. Patient survival is dependent on several factors, which include early diagnosis, initiation of appropriate antimicrobial therapy, and preservation or restoration of cardiac Accepted for publication Feb 24, 1992. Address reprint requests to Dr Mavroudis, Division of CardiovascularThoracic Surgery, The Children’s Memorial Hospital, M/C #22, 2300 Children‘s Plaza, Chicago, IL 60614.
0 1992 by The Society of Thoracic Surgeons
( A n n Thoruc Surg 1992;54:755-60)
Material a n d Methods From 1982 to 1989, 21 patients were treated for infective endocarditis at Kosair Children’s Hospital, Louisville, Kentucky. In 5 patients (4 of whom had preexisting congenital heart disease) medical management, consisting of specific long-term antibiotic therapy, resulted in resolution without further complications. Table 1 summarizes the clinical characteristics and outcome of these patients. The remaining 16 patients (76%)underwent one or more cardiac operations as part of their treatment for infective endocarditis and are the subjects of this report. The age at operation ranged from 3 weeks to 16 years, with 7 patients being less than 2 years old. Patients received a multidisciplinary approach to their care, involving thoracic surgery, pediatric medicine, cardiology, and infectious disease consultation. Endocarditis was diagnosed on the basis of clinical and laboratory criteria that included cardiac murmur development or change in a septic patient, fever with no other identifiable source, signs of systemic septic embolization, and positive blood cultures. All patients had abnormal echocardiograms revealing hemodynamically significant valvular abnormalities, the presence of vegetations, or both (Fig 1). Indications for operation included unresolving sepsis in patients with vegetations on echocardiography or persistent heart failure stemming from damaged valves. All but 1 patient had exploration in the acute phase of infection. Operations were performed 0003-4975/92/$5.00
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Table 1. Clinical Characteristics of Medical Theraw Patients Age
Patient
Sex
A
F
2
B
F
1.3
C
M
7
D
M
10
E
M
(y)
0.3
Clinical Presentation Fever, anorexia, anemia; tricuspid vegetation (septal leaflet) on ECHO Fever, anorexia, anemia; leukocytosis, iESR; vegetation on right side of atrial septum by ECHO Fever, anorexia, anemia; leukocytosis, iESR; no vegetations by ECHO Fever, anorexia, leukocytosis, iESR; mitral and pulmonary valvular vegetations by ECHO Fever, leukocytosis, iESR; no vegetations by ECHO
Preexisting Defect
Blood Culture Isolates
Treatment and Outcome
Small VSD
Haemophilus influenzae type €3
6 wk IV ceftriaxone; vegetation resolved by ECHO; VSD closed 1 year later
No congenital heart defect
Coagulase-positive Staphylococcus aureus
6 wk IV oxacillin; vegetation resolved by ECHO; patient recovered
Remote postop for IAA (tube graft) and VSD (closure) Double-inlet single left ventricle with d-transposition; PS
Haemophilus influenzae type €3
6 wk IV ceftriaxone; ECHO remained normal; patient recovered 6 wk IV penicillin; vegetations resolved on ECHO; successful modified Fontan 1 y later
Tricuspid atresia with PS; postop systemic-to-PA shunt
Coagulase-negative Staphylococcus aureus
a-Hemolytic Streptococcus
6 wk IV vancomycin; ECHO remained normal; awaiting Fontan procedure
ECHO = echocardiography; IAA = interrupted aortic arch; iESR = increased erythrocyte sedimentation rate; VSD = ventricular septal defect. pulmonary atresia; PS = pulmonary stenosis;
in conjunction with complete courses of antibiotic therapy targeted at specific organisms when known. Fifteen patients have known follow-up from the time of their operation to the present. In general, patients with a central venous line in place, in whom bacteremia developed, underwent catheter removal. Furthermore, venous access was maintained
Fig 1. (A)Apical preoperative echocardiogram showing echogenic mass (arrow) attached to septal leaflet of the tricuspid valve. ( B ) Postoperative echocardiogram showing absence of previously visualized mass related to septal leaflet of tricuspid valve. (LA = left atrium; LV = left ventricle; RA = right atrium; RV = right ventricle.)
IV = intravenous;
PA
=
through a peripheral site when possible. When required, new central lines were placed through a different site and antibiotics were continued. Adherence to this protocol cleared nearly all cases of central line sepsis. However, endocarditis did develop in 5 patients, presumably related to central venous lines. Their special circumstances are addressed elsewhere in this report.
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Results Nineteen operations in 16 patients were performed for the treatment of endocarditis, as shown in Table 2. Three patients required a second operation. One had initial aortic valve replacement and pericardial exclusion of a subannular abscess. Persistent sepsis and a newly formed right ventricular vegetation resulted in the second operation for debridement. The patient died of arrhythmias and cardiac failure. The second patient with an unoperated ventricular septal defect had development of right ventricular and tricuspid vegetations and underwent debridement. Continued sepsis resulted in a second operation to debride recurrent vegetations on the tricuspid valve and pericardial ventricular septal defect closure. This was followed by complete recovery. Congestive failure developed in the third patient after aortic valve replacement for sepsis and was complicated by a left ventricular-to-right atrial fistula. The aortic valve was re-replaced and the fistula closed with pericardium and Dacron, which was followed by complete recovery [12]. Nine patients (56%) had previously identifiable cardiac disease. Six of these had previously undergone some type of corrective procedure. The other 3 of these had small unoperated ventricular septal defects (2) and preexisting rheumatic heart disease (1).Endocarditis developed in 5 patients (31%) as a result of indwelling central venous Table 2. Operations for Endocarditis No. of Operationsa
Procedure Resection of vegetation (a) Vegetation resection, VSD closure with pericardium (second operation for 1 of the patients in a) Aortic valve replacement (No. 17 Bjork-Shiley valve) (b) Aortic valve replacement (No. 19 Bjork-Shiley valve) and closure of left ventricular-to-right atrial fistula (second operation after b) Aortic valve replacement (No. 19 St. Jude valve) and pericardial exclusion of subannular abscess (c) Resection of right ventricular vegetation and debridement of outflow tract (second operation after c) Mitral valve replacement (No. 27 CarpentierEdwards porcine valve) Tricuspid valve replacement (No. 1 StarrEdwards, No. 27 Carpentier-Edwards porcine valve) Closure of VSD Excision of vegetation and septal leaflet of tricuspid valve, reconstruction with pericardium Excision of vegetation from tricuspid valve and portion of papillary muscle Removal of torn Eustachian valve and debridement of vegetations ~~
a
~
~
Nineteen operahons were performed in 16 pahents
VSD
=
ventricular septal defect.
7 1
1
1 1
2 1 1
757
Table 3. Organisms Isolated From 16 Patients Who Underwent Operation for Endocarditis Number
% Total
Gram-negative organisms (Escherichia coli,
3 2 2 1 2
19 12.5 12.5 6 12.5
None recovered
2 4
12.5 25
0rg an ism -
Staphylococcus aureus Staphylococcus epidermidis Haemophilus influenzae Streptococcus pneumoniae Klebsiella) Candida species
catheterization. Four of these were treated by removal of infected thrombus from the superior vena cava or right atrium only, and the other required a tricuspid valvuloplasty using pericardium for reconstruction. The remaining 2 patients had normal cardiac anatomy, but endocarditis developed from a remote extracardiac source. One of these was from a pneumococcal pneumonia, and the other from dental caries. The organisms obtained by blood cultures or specimen cultures are listed in Table 3. No single organism was predominant. Four patients failed to grow an organism on culture but did have endocarditis based on clinical and operative findings. There were four operative deaths in this series resulting in a 25% mortality (70% confidence limits, 13%to 40%). The only late death occurred 9 months after tricuspid valve replacement in a 16-year-old patient who died of congestive failure due to underlying cardiac disease (31% overall mortality; 70% confidence limits, 18% to 47%). Autopsy showed the prosthetic porcine valve to be intact, and there was no evidence of endocarditis. Three of the four perioperative deaths occurred in patients less than 2 years of age. Operative mortality rate in this age group was 43% compared with 11% in patients 2 years of age or older. Although the difference is striking, statistical significance was not achieved due to the small number of patients in the study. No single infecting organism or type of operation affected operative mortality.
Comment The association of infective endocarditis and congenital heart disease has been well described [l,2, 4-71. Surgical treatment for endocarditis in children was initiated in 1940 by Touroff and Vesell[13], who reported successful recovery of a patient with endocarditis and patent ductus arteriosus after ligation. In 1961 Kay and associates [14] reported the cure of an adult patient with Candida endocarditis by ventricular septal defect closure and partial tricuspid valve excision. Four years later, Zakrzewski and Keith [2) described successful treatment of staphylococcal endocarditis after removal of the infected pledgets that were used to anchor the sutures after ventricular septal defect closure. Other authors have outlined guidelines and indications for surgical therapy in pediatric patients with endocarditis [5, 61. The patients in our series under-
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Table 4. Five Patients Requiring Resection of Vegetation Resulting From Central Venous Catheters Operation
Type of Catheter
Duration of Catheter Placement
1
3 wk
ECMO cannulas
6 d, 4 d
2
6 wk
1.9F Silastic
15 d
Candida albicans
3
8 wk
1.9F Silastic
20 d
S epidermidis
4
4 mo
2.8F Silastic
13 d
E coli, Klebsiella
5
15 wk
2.7F Broviac
Patient No.
Age at
x2
6 wk
Organism
Circumstances
S epidermidis & group B Streptococcus
Candida tropicalis
ECMO x 10 days; catheter change on day 6 for clots in circuit 28-wk gestation, NEC, laparotomy ~ 2 gram; negative sepsis 27-wk gestation, hyaline membrane disease, hydrocephalus, parenteral nutrition 28-wk gestation, NEC, laparotomy; gramnegative sepsis Acute lymphocytic leukemia,
Outcome Recovery Died of MSOF
Recovery
Died of MSOF Recovery
chemotherapy, leukopenia ECMO
=
extracorporeal membrane oxygenation;
MSOF = multisystem organ failure;
went operations for indications that include: (1)persistent endocarditis and sepsis uncontrolled by antibiotic therapy, (2) threatened, embolized, or recurrent systemic embolization of vegetative material, and (3) cardiac decompensation, severe congestive heart failure, and cardiac arrhythmias due to myocardial structural damage. The overall mortality in our series was 31%. One death occurred 9 months after tricuspid valve replacement in a 16-year-old boy. At autopsy the valve was without evidence of defect or infection and did not contribute to the patient’s death. Of the four operative deaths, three occurred in patients less than 2 years of age. Johnson and Rhodes [l] have reported on the grave prognosis of children less than 2 years of age with endocarditis. Two of our patients were premature neonates with severe infections, and the third was a child with complex congenital heart lesions who had already undergone two previous corrective procedures. Half of the patients operated on for endocarditis in Schollin and associates’ series died [6]. Schollin and associates note that surgical treatment may be necessary in a ”few cases,” and that it would be wise to consider operative intervention earlier as opposed to a last desperate effort, which is associated with a high operative mortality. Of the 9 patients greater than 2 years of age operated on for endocarditis in our series, there was only one death for an operative mortality rate of 11%. This trend toward a better outcome reflects a philosophy of early operative intervention for infection or heart failure when it becomes apparent that medical management alone will not be successful. The spectrum of infective organisms included staphylococcal species as well as pneumococcal, gram-negative rods, and fungal species. This is similar to that found by other authors [l,3, 5 , 7, 101 who report staphylococcal or streptococcal species as those most frequently encountered. One-fourth of our operated patients had negative blood cultures. This is higher than that reported in other
NEC
=
necrotizing enterocolitis.
series, which range from 3% to 13% [l, 3, 7, lo]. These cases of endocarditis were diagnosed based on clinical, echocardiographic, and operative findings, and all patients had received lengthy courses of antibiotics before operative intervention. Five patients (34%)with otherwise normal hearts had development of endocarditis as a complication of central line sepsis. These cases are outlined in Table 4. One patient, a 15-week-oldgirl with leukemia, had a long-term implantable catheter in place for chemotherapy administration. While she was immunocompromised as a result of chemotherapy, fungal endocarditis developed, which did not resolve after catheter removal and amphotericin-B therapy. She made a complete recovery after vegetation excision. Another patient was a neonate with group B Streptococcus sepsis, who required extracorporeal membrane oxygenation for 10 days. The extracorporeal membrane oxygenator venous cannula had to be changed on day 6 due to clots in the circuit. This cannula manipulation is not common, but probably played a role in the development of this patient’s endocarditis. This patient also did well after operative removal of his vegetation. The remaining three catheter-related infections were in premature neonates, who had soft Silastic (Ethicon, Somerville, NJ) catheters placed through basilic arm veins. All had other complications of prematurity including necrotizing enterocolitis, hyaline membrane disease, or hydrocephalus. Despite catheter removal and antibiotic therapy, endocarditis with vegetations developed. Two of these patients died postoperatively of sepsis and multisystem organ failure due to gram-negative and fungal organisms. The presence of a central venous catheter may have contributed to, but was not primarily responsible for, their septic condition. In the third patient, endocarditis was due to Staphylococcus epidermidis, probably related to the central line itself. Operative excision of the vegetation was required and this patient recovered. The two
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Ann Thorac Surg 1992;54:75560
fatalities in this group were in patients whose sepsis was primarily either abdominal or pulmonary, and removal of their vegetations did not resolve the focus of infection. Endocarditis due to central line sepsis has not been noted frequently in other series [3, 51, but accounted for one-third of the cases in ours. With the advent of neonatal and pediatric intensive care units, central venous catheterization for the delivery of fluids, medications, and nutrition has become more commonplace. This problem is certain to be encountered more frequently as the use of central lines in very young infants continues to grow [15-171. Intracardiac vegetations associated with active infection represent a serious management problem due to persistent sepsis, myocardial structural damage, and threat of embolization. Appropriate antibiotic therapy may control the septic episode and even result in vegetation resolution, as was the case in 3 of our medically treated patients (see Table 1). Under these circumstances, the threat of embolization after sepsis resolution must be weighed against the morbidity and mortality of an open heart procedure to remove the vegetation. The decision to operate is much easier when intracardiac vegetations are associated with persistent sepsis despite antibiotic therapy. A conservative operation, such as the excision of vegetations alone, may be all that is required to effect sterilization of the bloodstream. We performed seven such procedures for ongoing sepsis with demonstrable vegetations by echocardiogram (see Fig l) that were unresponsive to antibiotic therapy alone. Karl and associates [4] reported 3 patients requiring vegetation excision who failed medical therapy. Vegetations form through the deposition of platelets and fibrin on injured vascular endothelium. Endocarditis ensues when circulating bacteria colonize a thrombotic vegetation. Growth of the vegetation continues through further deposition of platelets and fibrin, isolating the bacteria from neutrophils and antibiotics in the bloodstream. This phenomenon of protecting bacteria from phagocytosis has been termed a “zone of agranulocytosis” [3] and is one reason why a long duration of intravenous antibiotics is indicated for the eradication of organisms on infected vegetations. Operative debridement of vegetations results in nearcomplete eradication of the infected focus in the bloodstream, allowing antibiotics and phagocytosis to complete the sterilization process. Patients with persistent sepsis, candidemia, systemic emboli, and vegetations demonstrated by echocardiography should be considered candidates for vegetation excision. Larger operations are frequently needed to properly clear the focus of infection and correct any associated hemodynamic problems. These may range from valve replacement to more complex reconstructive procedures. Several reports in the adult literature have showed that, although not desirable, it is possible to replace infected cardiac valves in the presence of bacteremia as long as adequate debridement of the valvular annulus is performed [18-201. In general, we prefer to implant pros-
759
thetic heart valves for infective endocarditis unless other pressing indications call for a porcine or homograft valve. In our series, 5 patients had six valve replacements, of which four were prosthetic and two were porcine. Five of the native valves grew various microorganisms. There was one death, in a 10-year-oldboy who, after aortic valve replacement with debridement of a subannular abscess, required a second operation for debridement of a right ventricular vegetation. Valve cultures were positive for S auyeus, although he died of persistent congestive failure and cardiac arrhythmias rather than sepsis. The remaining patients all cleared their bacteremias after valve replacement. These data support the published conclusions that valve replacement or other reconstructive procedures are safe and efficacious in patients with ongoing bacteremia from a cardiac source [19, 201. A selected number of cases involving valvular lesions may be treated with a more conservative resection and reconstruction rather than total valve replacement. Yee and Ullyot [21] reported good results in treating rightsided lesions in adults by partial valve resection and or defect repair using a pericardial patch. Initial insufficiency after valvuloplasty on right-sided valves is well tolerated and usually improves over time. We obtained good results in 1 patient who underwent excision of vegetation and the septal leaflet of the tricuspid valve, using pericardium for reconstruction. Two other patients had excisions of chorda or portions of papillary muscle of the tricuspid valve with good results. We used pericardium as an autologous tissue patch for valvular reconstruction and additionally for closure of ventricular septal defects, closure of an intracardiac fistula, and for the exclusion of a subannular abscess cavity from the left ventricle. In summary, we report our experience with operative procedures used to treat endocarditis in children. Early operation before the onset of major hemodynamic problems should be practiced. Conservative resection of vegetations or valvuloplasty may provide adequate treatment. Pericardium provides an autologous tissue patch that is useful for repair of intracardiac and valvular defects.
References 1. Johnson CM, Rhodes KH. Pediatric endocarditis. Mayo Clin Proc 1982;5786-94. 2. Zakrzewski T, Keith JD. Bacterial endocarditis in infants and children. J Pediatr 1965;67:1179-93. 3. King K, Harkness JL. Infective endocarditis in the 1980s. Part 1. Aetiology and diagnosis. Med J Aust 1986;144:53&40. 4. Karl T, Wensley D, Stark J, de Leva1 M, Rees P, Taylor JFN. Infective endocarditis in children with congenital heart disease: comparison of selected features in patients with surgical correction or palliation and those without. Br Heart J 1987;58:57-65. 5. Schollin J, Bjarke B, Wesstrom G. Infective endocarditis in Swedish children. I. Incidence, etiology, underlying factors and port of entry of infection. Acta Paediatr Scand 1986;75: 993-8. 6. Schollin J, Bjarke B, Wesstrom G. Infective endocarditis in Swedish children. 11. Location, major complications, laboratory findings, delay of treatment, treatment and outcome. Acta Paediatr Scand 1986;75:999-1004.
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CITAK ET AL ENDOCARDITIS IN CHILDREN
7. Johnson DH, Rosenthal A, Nadas AS. A forty-year review of bacterial endocarditis in infancy and childhood. Circulation 1975;51:581-8. 8. Cutler JG, Ongley PA, Shwachman H, Massell BF, Nadas AS. Bacterial endocarditis in children with heart disease. Pediatrics 1958;22:706-13. 9. Johnson DH, Rosenthal A, Nadas AS. Bacterial endocarditis in children under 2 years of age. Am J Dis Child 1975;129:
183-6.
10. Sholler GF, Hawker RE, Celermajer JM. Infective endocarditis in childhood. Pediatr Cardiol 1986;6:183-6. 11. Macaulay D. Acute endocarditis in infancy and early childhood. Am J Dis Child 1954;88:715-31. 12. Mavroudis C, Wampler J, Hodsden JE, Rees AH, Solinger RE, Elbl F. Modified aortoseptoplasty for anular abscess and erosion of the membranous septum. Chest 1984;85:442-4. 13. Touroff ASW, Vesell H. Subacute Streptococcus viriduns endarteritis complicating patent ductus arteriosus. JAMA 1940;115: 1270-2. 14. Kay JH, Bernstein S, Feinstein D, Biddle M. Surgical cure of
15. 16. 17. 18. 19. 20. 21.
Candida albicuns endocarditis with open-heart surgery. N Engl J Med 1961;264:907-10. McGuinness GA, Schieken RM, Maguire GF. Endocarditis in the newborn. Am J Dis Child 1980;134:577-80. Oelberg DG, Fisher DJ, Gross DM, Denson SE, Adcock EW 111. Endocarditis in high risk neonates. Pediatrics 1983;71: 392-7. Blieden LC, Morehead RR, Burke B, Kaplan EL. Bacterial endocarditis in the neonate. Am J Dis Child 1972;124:747-9. Crosby IK, Carrel1 R, Reed WA. Operative management of valvular complications of bacterial endocarditis. J Thorac Cardiovasc Surg 1972;6423546. Wilson WR, Danielson GK, Giuliani ER, Washington JA 11, Jaumin PM, Geraci JE. Valve replacement in patients with active infective endocarditis. Circulation 1978;58:585-8. Stinson EB, Griepp RB, Vosti K, Copeland JG, Shumway NE. Operative treatment of active endocarditis. J Thorac Cardiovasc Surg 1976;71:659-65. Yee ES, Ullyot DJ. Reparative approach for right-sided endocarditis. Operative considerations and results of valvuloplasty. J Thorac Cardiovasc Surg 1988;96:133-40.
Infective endocarditis occurs infrequently in the general pediatric population, occurring mostly in patients with congenital heart disease. This study reviews our surgical experience with infective endocarditis based on a policy of aggressive intervention, conservative operative debridement, and creative reconstruction options using pericardium and prosthetic heart valves. From 1982 to 1989,16 patients, 3 weeks to 16 years of age, underwent 19 intracardiac operations for infective endocarditis therapy at Kosair Children’s Hospital. Eight (42%) were for resection of vegetations alone; an additional 11 operations (58%) involved more extensive debridements requiring either valve replacement or valvuloplasty using pericardium for exclusion of an abscess cavity, closure of
a fistula, or for valve repair. Operative mortality was 25% (4 patients) and related to preoperative disease severity. There was one late death. Offending organisms included Stuphylococcus species (31%), Huemophilus influenzue (13%), pneumococcus (5% ), gram-negative organisms (13%), and Cundidu (13%); no organism grew on culture in 25%. We conclude that aggressive surgical exploration in patients with infective endocarditis is indicated and often requires resection of vegetations alone. More extensive procedures should preserve as much valvular tissue as possible. Pericardium is useful for reconstruction after debridement.
I
function. The purpose of this retrospective analysis is to report our surgical experience with infective endocarditis in children and emphasize guidelines for conservative and restorative therapy.
nfective endocarditis occurs relatively infrequently in children under 17 years of age [l-31. At highest risk are those patients with congenital heart disease [l-81. To a lesser degree, endocarditis complicates patients with rheumatic heart disease, and rarely those with no major heart disease [l, 4-7, 91. Reports by Johnson and Rhodes [l]and Karl and associates [4] have shown that the most frequent congenital malformations that predispose to the development of endocarditis are tetralogy of Fallot, ventricular septa1 defect, and patent ductus arteriosus [5, 7, 101. Endocarditis complicating open heart operations is associated with a higher mortality rate than those cases occurring in patients who have not had a recent cardiac operation [4]. The organisms most commonly isolated are Stuphylococcus uureus, Streptococcus viriduns, and Streptococcus hemolyticus [l, 4, 5, 71. Less frequently infecting organisms are Huemophilus influenzue, various gram-negative organisms, and Cundidu ulbicuns [l,3-5, 7, 101. Bloodstream entry of the infecting organism is infrequently identified. Bone, pulmonary, and cutaneous infections, as well as dental manipulations, have all been described as possible sources for bacteremia [l, 4-7, 10, 111. However, in more than 50% of patients with documented bacteremias, no source of contamination has been identified. Patient survival is dependent on several factors, which include early diagnosis, initiation of appropriate antimicrobial therapy, and preservation or restoration of cardiac Accepted for publication Feb 24, 1992. Address reprint requests to Dr Mavroudis, Division of CardiovascularThoracic Surgery, The Children’s Memorial Hospital, M/C #22, 2300 Children‘s Plaza, Chicago, IL 60614.
0 1992 by The Society of Thoracic Surgeons
( A n n Thoruc Surg 1992;54:755-60)
Material a n d Methods From 1982 to 1989, 21 patients were treated for infective endocarditis at Kosair Children’s Hospital, Louisville, Kentucky. In 5 patients (4 of whom had preexisting congenital heart disease) medical management, consisting of specific long-term antibiotic therapy, resulted in resolution without further complications. Table 1 summarizes the clinical characteristics and outcome of these patients. The remaining 16 patients (76%)underwent one or more cardiac operations as part of their treatment for infective endocarditis and are the subjects of this report. The age at operation ranged from 3 weeks to 16 years, with 7 patients being less than 2 years old. Patients received a multidisciplinary approach to their care, involving thoracic surgery, pediatric medicine, cardiology, and infectious disease consultation. Endocarditis was diagnosed on the basis of clinical and laboratory criteria that included cardiac murmur development or change in a septic patient, fever with no other identifiable source, signs of systemic septic embolization, and positive blood cultures. All patients had abnormal echocardiograms revealing hemodynamically significant valvular abnormalities, the presence of vegetations, or both (Fig 1). Indications for operation included unresolving sepsis in patients with vegetations on echocardiography or persistent heart failure stemming from damaged valves. All but 1 patient had exploration in the acute phase of infection. Operations were performed 0003-4975/92/$5.00
756
CITAK ET AL
Ann Thorac Surg
ENDOCARDITIS IN CHILDREN
1992;54: 75560
Table 1. Clinical Characteristics of Medical Theraw Patients Age
Patient
Sex
A
F
2
B
F
1.3
C
M
7
D
M
10
E
M
(y)
0.3
Clinical Presentation Fever, anorexia, anemia; tricuspid vegetation (septal leaflet) on ECHO Fever, anorexia, anemia; leukocytosis, iESR; vegetation on right side of atrial septum by ECHO Fever, anorexia, anemia; leukocytosis, iESR; no vegetations by ECHO Fever, anorexia, leukocytosis, iESR; mitral and pulmonary valvular vegetations by ECHO Fever, leukocytosis, iESR; no vegetations by ECHO
Preexisting Defect
Blood Culture Isolates
Treatment and Outcome
Small VSD
Haemophilus influenzae type €3
6 wk IV ceftriaxone; vegetation resolved by ECHO; VSD closed 1 year later
No congenital heart defect
Coagulase-positive Staphylococcus aureus
6 wk IV oxacillin; vegetation resolved by ECHO; patient recovered
Remote postop for IAA (tube graft) and VSD (closure) Double-inlet single left ventricle with d-transposition; PS
Haemophilus influenzae type €3
6 wk IV ceftriaxone; ECHO remained normal; patient recovered 6 wk IV penicillin; vegetations resolved on ECHO; successful modified Fontan 1 y later
Tricuspid atresia with PS; postop systemic-to-PA shunt
Coagulase-negative Staphylococcus aureus
a-Hemolytic Streptococcus
6 wk IV vancomycin; ECHO remained normal; awaiting Fontan procedure
ECHO = echocardiography; IAA = interrupted aortic arch; iESR = increased erythrocyte sedimentation rate; VSD = ventricular septal defect. pulmonary atresia; PS = pulmonary stenosis;
in conjunction with complete courses of antibiotic therapy targeted at specific organisms when known. Fifteen patients have known follow-up from the time of their operation to the present. In general, patients with a central venous line in place, in whom bacteremia developed, underwent catheter removal. Furthermore, venous access was maintained
Fig 1. (A)Apical preoperative echocardiogram showing echogenic mass (arrow) attached to septal leaflet of the tricuspid valve. ( B ) Postoperative echocardiogram showing absence of previously visualized mass related to septal leaflet of tricuspid valve. (LA = left atrium; LV = left ventricle; RA = right atrium; RV = right ventricle.)
IV = intravenous;
PA
=
through a peripheral site when possible. When required, new central lines were placed through a different site and antibiotics were continued. Adherence to this protocol cleared nearly all cases of central line sepsis. However, endocarditis did develop in 5 patients, presumably related to central venous lines. Their special circumstances are addressed elsewhere in this report.
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Ann Thorac Surg 1992;54:75560
Results Nineteen operations in 16 patients were performed for the treatment of endocarditis, as shown in Table 2. Three patients required a second operation. One had initial aortic valve replacement and pericardial exclusion of a subannular abscess. Persistent sepsis and a newly formed right ventricular vegetation resulted in the second operation for debridement. The patient died of arrhythmias and cardiac failure. The second patient with an unoperated ventricular septal defect had development of right ventricular and tricuspid vegetations and underwent debridement. Continued sepsis resulted in a second operation to debride recurrent vegetations on the tricuspid valve and pericardial ventricular septal defect closure. This was followed by complete recovery. Congestive failure developed in the third patient after aortic valve replacement for sepsis and was complicated by a left ventricular-to-right atrial fistula. The aortic valve was re-replaced and the fistula closed with pericardium and Dacron, which was followed by complete recovery [12]. Nine patients (56%) had previously identifiable cardiac disease. Six of these had previously undergone some type of corrective procedure. The other 3 of these had small unoperated ventricular septal defects (2) and preexisting rheumatic heart disease (1).Endocarditis developed in 5 patients (31%) as a result of indwelling central venous Table 2. Operations for Endocarditis No. of Operationsa
Procedure Resection of vegetation (a) Vegetation resection, VSD closure with pericardium (second operation for 1 of the patients in a) Aortic valve replacement (No. 17 Bjork-Shiley valve) (b) Aortic valve replacement (No. 19 Bjork-Shiley valve) and closure of left ventricular-to-right atrial fistula (second operation after b) Aortic valve replacement (No. 19 St. Jude valve) and pericardial exclusion of subannular abscess (c) Resection of right ventricular vegetation and debridement of outflow tract (second operation after c) Mitral valve replacement (No. 27 CarpentierEdwards porcine valve) Tricuspid valve replacement (No. 1 StarrEdwards, No. 27 Carpentier-Edwards porcine valve) Closure of VSD Excision of vegetation and septal leaflet of tricuspid valve, reconstruction with pericardium Excision of vegetation from tricuspid valve and portion of papillary muscle Removal of torn Eustachian valve and debridement of vegetations ~~
a
~
~
Nineteen operahons were performed in 16 pahents
VSD
=
ventricular septal defect.
7 1
1
1 1
2 1 1
757
Table 3. Organisms Isolated From 16 Patients Who Underwent Operation for Endocarditis Number
% Total
Gram-negative organisms (Escherichia coli,
3 2 2 1 2
19 12.5 12.5 6 12.5
None recovered
2 4
12.5 25
0rg an ism -
Staphylococcus aureus Staphylococcus epidermidis Haemophilus influenzae Streptococcus pneumoniae Klebsiella) Candida species
catheterization. Four of these were treated by removal of infected thrombus from the superior vena cava or right atrium only, and the other required a tricuspid valvuloplasty using pericardium for reconstruction. The remaining 2 patients had normal cardiac anatomy, but endocarditis developed from a remote extracardiac source. One of these was from a pneumococcal pneumonia, and the other from dental caries. The organisms obtained by blood cultures or specimen cultures are listed in Table 3. No single organism was predominant. Four patients failed to grow an organism on culture but did have endocarditis based on clinical and operative findings. There were four operative deaths in this series resulting in a 25% mortality (70% confidence limits, 13%to 40%). The only late death occurred 9 months after tricuspid valve replacement in a 16-year-old patient who died of congestive failure due to underlying cardiac disease (31% overall mortality; 70% confidence limits, 18% to 47%). Autopsy showed the prosthetic porcine valve to be intact, and there was no evidence of endocarditis. Three of the four perioperative deaths occurred in patients less than 2 years of age. Operative mortality rate in this age group was 43% compared with 11% in patients 2 years of age or older. Although the difference is striking, statistical significance was not achieved due to the small number of patients in the study. No single infecting organism or type of operation affected operative mortality.
Comment The association of infective endocarditis and congenital heart disease has been well described [l,2, 4-71. Surgical treatment for endocarditis in children was initiated in 1940 by Touroff and Vesell[13], who reported successful recovery of a patient with endocarditis and patent ductus arteriosus after ligation. In 1961 Kay and associates [14] reported the cure of an adult patient with Candida endocarditis by ventricular septal defect closure and partial tricuspid valve excision. Four years later, Zakrzewski and Keith [2) described successful treatment of staphylococcal endocarditis after removal of the infected pledgets that were used to anchor the sutures after ventricular septal defect closure. Other authors have outlined guidelines and indications for surgical therapy in pediatric patients with endocarditis [5, 61. The patients in our series under-
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Ann Thorac Surg 1992;5475560
Table 4. Five Patients Requiring Resection of Vegetation Resulting From Central Venous Catheters Operation
Type of Catheter
Duration of Catheter Placement
1
3 wk
ECMO cannulas
6 d, 4 d
2
6 wk
1.9F Silastic
15 d
Candida albicans
3
8 wk
1.9F Silastic
20 d
S epidermidis
4
4 mo
2.8F Silastic
13 d
E coli, Klebsiella
5
15 wk
2.7F Broviac
Patient No.
Age at
x2
6 wk
Organism
Circumstances
S epidermidis & group B Streptococcus
Candida tropicalis
ECMO x 10 days; catheter change on day 6 for clots in circuit 28-wk gestation, NEC, laparotomy ~ 2 gram; negative sepsis 27-wk gestation, hyaline membrane disease, hydrocephalus, parenteral nutrition 28-wk gestation, NEC, laparotomy; gramnegative sepsis Acute lymphocytic leukemia,
Outcome Recovery Died of MSOF
Recovery
Died of MSOF Recovery
chemotherapy, leukopenia ECMO
=
extracorporeal membrane oxygenation;
MSOF = multisystem organ failure;
went operations for indications that include: (1)persistent endocarditis and sepsis uncontrolled by antibiotic therapy, (2) threatened, embolized, or recurrent systemic embolization of vegetative material, and (3) cardiac decompensation, severe congestive heart failure, and cardiac arrhythmias due to myocardial structural damage. The overall mortality in our series was 31%. One death occurred 9 months after tricuspid valve replacement in a 16-year-old boy. At autopsy the valve was without evidence of defect or infection and did not contribute to the patient’s death. Of the four operative deaths, three occurred in patients less than 2 years of age. Johnson and Rhodes [l] have reported on the grave prognosis of children less than 2 years of age with endocarditis. Two of our patients were premature neonates with severe infections, and the third was a child with complex congenital heart lesions who had already undergone two previous corrective procedures. Half of the patients operated on for endocarditis in Schollin and associates’ series died [6]. Schollin and associates note that surgical treatment may be necessary in a ”few cases,” and that it would be wise to consider operative intervention earlier as opposed to a last desperate effort, which is associated with a high operative mortality. Of the 9 patients greater than 2 years of age operated on for endocarditis in our series, there was only one death for an operative mortality rate of 11%. This trend toward a better outcome reflects a philosophy of early operative intervention for infection or heart failure when it becomes apparent that medical management alone will not be successful. The spectrum of infective organisms included staphylococcal species as well as pneumococcal, gram-negative rods, and fungal species. This is similar to that found by other authors [l,3, 5 , 7, 101 who report staphylococcal or streptococcal species as those most frequently encountered. One-fourth of our operated patients had negative blood cultures. This is higher than that reported in other
NEC
=
necrotizing enterocolitis.
series, which range from 3% to 13% [l, 3, 7, lo]. These cases of endocarditis were diagnosed based on clinical, echocardiographic, and operative findings, and all patients had received lengthy courses of antibiotics before operative intervention. Five patients (34%)with otherwise normal hearts had development of endocarditis as a complication of central line sepsis. These cases are outlined in Table 4. One patient, a 15-week-oldgirl with leukemia, had a long-term implantable catheter in place for chemotherapy administration. While she was immunocompromised as a result of chemotherapy, fungal endocarditis developed, which did not resolve after catheter removal and amphotericin-B therapy. She made a complete recovery after vegetation excision. Another patient was a neonate with group B Streptococcus sepsis, who required extracorporeal membrane oxygenation for 10 days. The extracorporeal membrane oxygenator venous cannula had to be changed on day 6 due to clots in the circuit. This cannula manipulation is not common, but probably played a role in the development of this patient’s endocarditis. This patient also did well after operative removal of his vegetation. The remaining three catheter-related infections were in premature neonates, who had soft Silastic (Ethicon, Somerville, NJ) catheters placed through basilic arm veins. All had other complications of prematurity including necrotizing enterocolitis, hyaline membrane disease, or hydrocephalus. Despite catheter removal and antibiotic therapy, endocarditis with vegetations developed. Two of these patients died postoperatively of sepsis and multisystem organ failure due to gram-negative and fungal organisms. The presence of a central venous catheter may have contributed to, but was not primarily responsible for, their septic condition. In the third patient, endocarditis was due to Staphylococcus epidermidis, probably related to the central line itself. Operative excision of the vegetation was required and this patient recovered. The two
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Ann Thorac Surg 1992;54:75560
fatalities in this group were in patients whose sepsis was primarily either abdominal or pulmonary, and removal of their vegetations did not resolve the focus of infection. Endocarditis due to central line sepsis has not been noted frequently in other series [3, 51, but accounted for one-third of the cases in ours. With the advent of neonatal and pediatric intensive care units, central venous catheterization for the delivery of fluids, medications, and nutrition has become more commonplace. This problem is certain to be encountered more frequently as the use of central lines in very young infants continues to grow [15-171. Intracardiac vegetations associated with active infection represent a serious management problem due to persistent sepsis, myocardial structural damage, and threat of embolization. Appropriate antibiotic therapy may control the septic episode and even result in vegetation resolution, as was the case in 3 of our medically treated patients (see Table 1). Under these circumstances, the threat of embolization after sepsis resolution must be weighed against the morbidity and mortality of an open heart procedure to remove the vegetation. The decision to operate is much easier when intracardiac vegetations are associated with persistent sepsis despite antibiotic therapy. A conservative operation, such as the excision of vegetations alone, may be all that is required to effect sterilization of the bloodstream. We performed seven such procedures for ongoing sepsis with demonstrable vegetations by echocardiogram (see Fig l) that were unresponsive to antibiotic therapy alone. Karl and associates [4] reported 3 patients requiring vegetation excision who failed medical therapy. Vegetations form through the deposition of platelets and fibrin on injured vascular endothelium. Endocarditis ensues when circulating bacteria colonize a thrombotic vegetation. Growth of the vegetation continues through further deposition of platelets and fibrin, isolating the bacteria from neutrophils and antibiotics in the bloodstream. This phenomenon of protecting bacteria from phagocytosis has been termed a “zone of agranulocytosis” [3] and is one reason why a long duration of intravenous antibiotics is indicated for the eradication of organisms on infected vegetations. Operative debridement of vegetations results in nearcomplete eradication of the infected focus in the bloodstream, allowing antibiotics and phagocytosis to complete the sterilization process. Patients with persistent sepsis, candidemia, systemic emboli, and vegetations demonstrated by echocardiography should be considered candidates for vegetation excision. Larger operations are frequently needed to properly clear the focus of infection and correct any associated hemodynamic problems. These may range from valve replacement to more complex reconstructive procedures. Several reports in the adult literature have showed that, although not desirable, it is possible to replace infected cardiac valves in the presence of bacteremia as long as adequate debridement of the valvular annulus is performed [18-201. In general, we prefer to implant pros-
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thetic heart valves for infective endocarditis unless other pressing indications call for a porcine or homograft valve. In our series, 5 patients had six valve replacements, of which four were prosthetic and two were porcine. Five of the native valves grew various microorganisms. There was one death, in a 10-year-oldboy who, after aortic valve replacement with debridement of a subannular abscess, required a second operation for debridement of a right ventricular vegetation. Valve cultures were positive for S auyeus, although he died of persistent congestive failure and cardiac arrhythmias rather than sepsis. The remaining patients all cleared their bacteremias after valve replacement. These data support the published conclusions that valve replacement or other reconstructive procedures are safe and efficacious in patients with ongoing bacteremia from a cardiac source [19, 201. A selected number of cases involving valvular lesions may be treated with a more conservative resection and reconstruction rather than total valve replacement. Yee and Ullyot [21] reported good results in treating rightsided lesions in adults by partial valve resection and or defect repair using a pericardial patch. Initial insufficiency after valvuloplasty on right-sided valves is well tolerated and usually improves over time. We obtained good results in 1 patient who underwent excision of vegetation and the septal leaflet of the tricuspid valve, using pericardium for reconstruction. Two other patients had excisions of chorda or portions of papillary muscle of the tricuspid valve with good results. We used pericardium as an autologous tissue patch for valvular reconstruction and additionally for closure of ventricular septal defects, closure of an intracardiac fistula, and for the exclusion of a subannular abscess cavity from the left ventricle. In summary, we report our experience with operative procedures used to treat endocarditis in children. Early operation before the onset of major hemodynamic problems should be practiced. Conservative resection of vegetations or valvuloplasty may provide adequate treatment. Pericardium provides an autologous tissue patch that is useful for repair of intracardiac and valvular defects.
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