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Complications of TPN catheter-induced vena caval thrombosis in children less than one year of age
Complications of T P N Catheter-Induced Vena Caval Thrombosis in Children Less Than One Year of Age By Daniel L. Mollitt and E Stevers Golladay
L i t t l e Rock, Arkansas 9 Recent large series have reported a 5% to 10% incidence of major venous thrombosis associated w i t h central indwelling total parenteral nutrition (TPN) catheters. Previous authors suggested that this was well tolerated by children and resulted in f e w clinically important sequelae. Our experience differs significantly and forms the basis of this report. Between 1979 and 1981, 117 Broviac TPN catheters (Evermed, Medina, Washington) w e r e placed in children less than 1 year of age. Catheters w e r e introduced into the superior vena cava (SVC) by w a y of a common facial vein cutdown. Catheter position was confirmed radiographically in the operating room. Eight infants (7%) subsequently developed superior vena caval thrombosis. All presented w i t h edema of the head and neck associated with facial plethora, chemosis, and prominent cutaneous venous pattern. In five of the eight children the clinical signs resolved spontaneously following catheter removal and there w e r e no apparent sequelae. The remaining three (38%), however, suffered significant morbidity. T w o developed intracardiac extension of their thrombus. The first child suffered extensive pulmonary embolization. In the second child, the thrombus prolapsed through the tricuspid valve inciting congestive heart failure. This thrombus subsequently became infected, necessitating urgent cardiotomy. The third infant developed bilateral chyIothoraces due to pulmonary lymphangiectasia associated w i t h SVC thrombosis. These proved unresponsive to medical or surgical management and resulted in the death of this newborn. Although the majority of infants developing catheter-induced central venous thrombosis respond t o catheter removal and suffer no subsequent ill effects, these children are at risk for major complications. These complications can be associated w i t h not only significant morbidity but w i t h mortality as well. The generalization that such thrombosis is well tolerated in the infant is unwarranted.
From the Departments of Surgery and Pediatrics, Arkansas Children's Hospital and University of Arkansas for Medical Sciences, Little Rock, Ark. Presented before the 31 st Annual Meeting of the Surgical Section of the American Academy of Pediatrics, New York, New York, October 23-24, 1982. Address reprint requests to Daniel L. Mollitt, MD, Arkansas Children's Hospital, 804 Wolfe Street, Little Rock, AR 72201. 9 1983 by Grune & Stratton, Inc. 0022-3468/83/1804~025/$01.00/0
462
INDEX WORDS: Parenteral alimentation; central venous catheter; vena caval thrombosis; SVC syndrome.
O T A L P A R E N T E R A L N U T R I T I O N has
T proven to be an effective means of nutritional support in the neonate and infant. Complications are related to metabolic alterations induced by the infusate, sepsis, and mechanical difficulties secondary to the intravenous cannula. The development of a cuffed silastic catheter of appropriate size, and of a standard operative approach, has reduced the adverse consequences of long-term indwelling central venous lines. Although an almost universal incidence of clot formation was found in a series in which venograms were routinely performed, recent large series report a 5% to 10% incidence of catheterinduced central venous thrombosis, t-3 O t h e r reports suggested that this complication was well tolerated in children and resulted in few clinically important sequelae, 4 but our experience differs significantly from this and forms the basis for this report. MATERIALS A N D METHODS
Between 1978 and 1981, 117 catheters were placed in children less than 1 year of age at Arkansas Children's Hospital. The catheters were placed in all instances for purposes of total parenteral nutrition (TPN). The majority were introduced into the superior vena cava by way of a common facial vein cutdown. An occasional infant underwent placement into the inferior vena cava by way of the saphenous vein as a secondary procedure. All cutdowns were performed in the operating room. Pediatric Broviac parenteral alimentation catheters were employed and tunneled through the subcutaneous tissue to the site of the venotomy. Catheters were placed at the junction of the superior vena cava and right atrium as confirmed by intraoperative roentgenograms. Each patient was then begun on a standard schedule of gradually increasing parenteral nutrition culminating in a final glucose solution concentration of 20% and amino acid concentration of 2% at 150 mL/kg/d (114 cal/kg/d) which has an osmolality of 1695 m0sm and a pH of 5.7. Eight patients (7%) subsequently developed superior vena caval thrombosis. All presented with edema of the head or neck associated with facial plethora, chemosis, and a prominent cutaneous venous pattern. Each patient was treated with
Journal of Pediatric Surgery, Vol. 18, No. 4 (August), 1983
TPN-INDUCEO CAVAL THROMBOSIS IN INFANTS prompt removal of the catheter. In five of the eight, the clinical signs resolved quickly and there were no apparent sequelae. The remaining three infants, however, suffered significant morbidity despite catheter removal. CASE REPORTS Case 1 A 700 g, premature female infant was transferred on the 18th day of life for management of neonatal necrotizing enterocolitis. The medical management initiated included placement of a central venous catheter. On the fourth postoperative day, deterioration in her clinical course prompted removal of the catheter and subsequent abdominal explore-
463 tion and segmental ileal resection. Four days later, she was returned to the operating room and the central venous line was replaced. After 21 days of TPN, she was noted to have clinical evidence of superior vena caval thrombosis and the catheter was removed. Within 24 hours, she developed respiratory distress associated with bilateral lymphangiectasia and pleural effusions. (Fig. 1A). Radionucleotide lymphangiogram demonstrated occlusion of the thoracic duct and retrograde filling of the pulmonary lymphatics. A venogram showed almost complete occlusion of the superior vena cava. (Fig. 1B). Bilateral chylothoraces proved unresponsive to both medical and surgical therapy and resulted in the death of this infant. Case 2 A premature male infant was transferred at 6 hours of age with a diagnosis of omphalocele and Beckwith-Wiedemann syndrome. He underwent primary closure of the abdominal wall defect and placement of a central venous catheter shortly after arrival. On the 14th postoperative day, he developed staphylococcal sepsis and the central line was removed. Despite appropriate antibiotic coverage, he remained septic with evidence of increasing cardiomegaly, respiratory distress, hepatic enlargement, and cardiac failure. Echocardiography, and then angiocardiography, demonstrated a tricuspid vegetation associated with a large right atrial mass prolapsing through the valve (Fig. 2). Cardiotomy was performed and the septic right atrial thrombus was removed. He was discharged 31/2 months after admission. Case 3 A premature female infant with gastroschisis underwent staged closure and central line placement shortly after birth. She developed necrotizing enterocolitis late in her course and required multiple small-bowel resections resulting in "short gut" syndrome. She was maintained on TPN but had accidental dislodgement of one catheter. A second catheter was placed on the contralateral side and removed at 4 months of age due to superior vena cave} thrombosis. She had continued inability to tolerate enteral nutrition, and a third line was placed utilizing the saphenous vein for access to the inferior vena cava. She developed gradually increasing respiratory insufficiency over the next several months. Evaluation documented thrombosis of the vena cava with propagation into the right atrium and calcification of a right atrial thrombus (Fig. 3A). A lung scan (Fig. 3B) and pulmonary arteriogram showed almost no pulmonary flow (Fig. 3C). She was begun on continuous heparin infusion but continued to deteriorate and ultimately succumbed to respiratory insufficiency and sepsis. DISCUSSION
Fig. 1. (A) Chest radiograph of a 21-day-old, 700 g infant with diffuse bilateral infiltrates associated with pulmonary lymphangiectasia. (B) Venogram of the same neonate demonstrating obliteration of the superior vena cava.
Vena caval thrombosis, once largely secondary to n e o p l a s t i c d i s e a s e , h a s i n c r e a s i n g l y b e e n reported as a complication of use of indwelling c e n t r a l c a t h e t e r s in t h e p e d i a t r i c a g e g r o u p , l : A n inclusive series through 1949 showed only four children with SVC syndrome) Since that time,
464
MOLLITr AND GOLLADAY
Fig. 2.
Lateral and anterioposterior angiocardiograms in which a right atrial t h r o m b u s is s h o w n (arrow).
however, 175 additional cases have been reported and 27 of these are secondary to TPN. ~ The incidence of catheter-induced SVC thrombosis in children is 5% to 10% and has been infrequently associated with any apparent sequelae in previously reported series. 4'6'7Morbidity and mortality have, however, been reported. Scattered case presentations have documented the association of catheter-induced central venous thrombosis with hydrocephalus, pulmonary lymphangiectasia, chylothorax, pulmonary embolus, endocarditis, and cardiac dysfunction. 8 10 The majority of these have been in children less than 1 year of age. The newborn and infant are at greatest risk for both TPN-induced thrombosis and thrombotic complications. Vascular thrombosis is the result of stasis, hypercoagulability, and/or endothelial disruption. Hypercoagulability has not been identified as an etiologic factor in catheter-induced thrombosis. Stasis may play a role in low-flow states such as dehydration, cardiac failure, and hyperviscosity. Catheter-related endothelial disruption can certainly incite thrombosis, but a major contributing factor is direct endothelial injury secondary to the hyperosmolar infusate. The incidence of caval thrombosis following central venous lines placed for pressure monitoring is significantly less than those utilized for TPN. ~ In
the small-caliber vessels of the neonate, proper dilution of the infusate and precise positioning is mandatory. Catheter migration or improper placement was present in 70% of the previously reported pediatric cases of TPN-related central venous thrombosis. ~ There is a minimal distance between the confluence of the innominate veins and the right atrium in the infant, and even slight migration can result in incorrect placement. Minor migration also occurs as the result of growth alone. Prolonged exposure of the central venous system to an indwelling catheter and T P N infusion also enhances the probability of thrombosis. In a series reported by Fonkalsrud and co-workers, 4 central catheters in children who developed thrombosis were in place twice as long as those without complications. Central venous occlusion may be suspected first on the basis of difficulty with infusion or inability to withdraw or flush the catheter. Attempts at flushing are associated with discomfort. Signs of increased venous pressure include proptosis, plethora, chemosis, swelling of the head and neck, axillary adenopathy, and cyanosis of the upper body. Symptoms are increased by a horizontal position or bending forward. Signs of cutaneous collateralization are a prominent venous pattern about the head, neck, and anterior chest. Respiratory symptoms include a
TPN-INDUCED CAVAL THROMBOSIS IN INFANTS
465
Fig. 3. (A) Lateral chest radiograph with calcified right atrial thrombus (arrow). (B) Pulmonary perfusion scan w i t h flow essentially limited to the lower lobes bilaterally. (C) Pulmonary angiogram performed by way of the azygos vein demonstrates marked reduction in pulmonary blood f l o w due to repeated embolization.
hoarse cry, stridor, dyspnea, and airway occlusions. ~2 Neurologic symptoms including headache, irritability, disturbed consciousness, nausea, dizziness, lethargy, and distorted vision may be present in the older child but are difficult to evaluate in the newborn. Confirmation of clinical suspicion is obtained through radiographic means. Plain roentgenographic findings of catheter migration or a widened mediastinum are frequently seen. Contrast injection will confirm central occlusion and collateralization. Ultrasonography of the vena cava
can localize a thrombus and assess the cardiac valves for the presence of vegetations. Lymphangiograms may demonstrate retrograde lymphatic flow into the lungs secondary to central venous occlusion. 8 Complications are secondary to increased venous pressure, propagation a n d / o r clot disruption, and superimposed infection. The increased venous pressure accompanying central venous thrombosis leads to the accumulation of tissue fluid and dilation of patent collaterals. This, in turn, results in the characteristic facial edema
466
MOLLITT AND GOLLADAY
and plethora. Similarly, this increased pressure, when transmitted intracranially, overcomes the venous osmotic pressure and interferes with cerebrospinal fluid dynamics. Fluid is produced in excess of absorption and, when this occurs in early childhood, will result in ventricular dilatation and enlargement of the head. Although this is usually unaccompanied by neurologic sequelae, ventricular shunting has been required for control in isolated casesJ ~ Propagation of caval thrombosis has been demonstrated to occur both proximally and distally. With involvement of both subclavian vessels, there may be occlusion of the thoracic and right lymphatic ducts with resultant stasis within the pleural and pulmonary lymphatics. Interstitial pulmonary edema and chylothorax then result (case I). As noted by K r a m m e r and associates, chylothorax may be the only manifestation of superior vena caval thrombosis in the neonate.14 This complication is intractable to the usual forms of management and may require partial pleurectomyJ 5 Propagation of the thrombus into the right atrium will interfere with valvular competence resulting in tricuspid insufficiency (case 2) and predispose to clot disruption with resultant pulmonary embolization (case 3). Thrombosis can result from catheter-related septic thrombophlebitis or the thrombus may become infected secondarily. The organisms most frequently involved are Staphylococcus and CandidaJ 6-~8 The usual manifestations of SVC syndrome may then be accompanied by murmur, severe respiratory insufficiency, or signs of overwhelming sepsis. Candida infection is often associated with disseminated intravascu-
lar coagulopathy secondary to fungal coagulase and/or exposure of subendothelial collagen by the direct action of the microorganism. 17 This manifestation of candidal infection is associated with a poor response to therapy and with high mortality. Regardless of the immediate sequelae, thrombophlebitis of the vena cava severely limits further access in children with long-term parenteral nutritional needs. I f thrombosis occurs, immediate withdrawal of the catheter and elevation of the head and neck are the important facets of therapy. Culture of the withdrawn catheter tip should be performed to rule out associated sepsis. I f there is clinical evidence of infection, antibiotic coverage should be initiated prior to culture results. Systemic anticoagulation has not been employed routinely but m a y be necessary in cases of pulmonary embolism. Specific complications can require operative intervention. Progressive hydrocephalus secondary to central venous occlusion can be controlled with ventricular shunting procedures. Cardiotomy with thrombectomy may be necessary for removal of septic thrombi or vegetations. Chylothorax may require tube thoracostomy or pleurectomy. Central venous thrombosis will continue to complicate the management of critically ill newborns with indwelling catheters, Although the majority of these can be successfully managed by catheter removal, complications secondary to such thrombosis will continue to occur. These complications can be associated not only with significant morbidity but also with mortality as well. The generalization that such thrombosis is well tolerated in the infant is unwarranted.
REFERENCES
1. Janin Y, Becker J, Wise L, et al: Superior vena cava syndrome in childhood and adolescence: A review of the literature and report of three cases. J Pediatr Surg 17:290-295, 1982 2. Padberg FT, Jr, Ruggiero J, Blackburn GL, et al: Central venous catheterization for parenteral nutrition. Ann Surg 193:264-270, 1981 3. Fliegel CP, Signer E, Stahl M, et al: Thrombotic complications of long term intravenous alimentation in infants. Ann Radiol 19:15-22, 1976 4. Fonkalsrud EW, Ament ME, Berquist WE, et al: Occlusion of the vena cava in infants receivingcentral venous hyperalimentation. Surg GynecolObstet 154:189-192, 1982 5. Mclntyre FT, Sykes EM, Jr: Obstruction of the superior vena cava: A review of the literature and report of two personal cases. Ann Intern Med 30:925-960, 1949
6, Vain NE, Georgeson KE, Cha CC, et al: Central parenteral alimentation in newborn infants: A new technique for catheter placement. J Pediatr 93:864-866, 1978 7. Groff DB: Complications of intravenous hyperalimentation in newborns and infants. J Pediatr Surg 4:460-463, 1969 8. Seibert J J, Golladay ES, Keller C: Chylotborax secondary to superior vena caval obstruction. Pediatr Radiol 12:1-3, 1982 9. Joshi VV, Wang NS: Repeated pulmonaryembolismin an infant. Am J Dis Child 125:257-259, 1973 10. Hooper R: Hydrocephalus and obstruction of the superior vena cava in infancy. Pediatrics 28:792-799, 1961 11. Effmann EL, Ablow RC, Touloukian RJ, et al: Radiographic aspects of total parenteral nutrition during infancy. Radiology 127:195-201, 1978
TPN-INDUCED CAVAL THROMBOSIS IN INFANTS
12. D'Angio GJ, Mitus A, Evans AE: The superior mediastinal syndrome in children with cancer. Am J Roentgenol Radiol Therap Nuclear Med 93:537-544, 1965 13. Seibert J J, Weinstein MM, Erenherg A: Catheterrelated complications of total parenteral nutrition in infants. Pediatr Radiol 4:233-237, 1976 14. Krammer SS, Taylor GA, Garfinkel D J, et al: Lethal chylothoraces due to superior vena cava thrombosis in infants. Am J Roentgenol 137:559-562, 1981 15. Curci MR, Dibbins AW: Bilateral chylothorax in a newborn. J Pediatr Surg 15:663, 1980
467
16. Wiley EL, Hutchins GM: Superior vena cava syndrome secondary to Candida thrombophlebitis complicating parenteral alimentation. J Pediatr 91:977-979, 1977 17. Prochazka JV, Lucas RN, Beauchamp CJ, et al: Systemic Candidiasis with disseminated intravascular coagulation. Amer J Dis Child 122:255-256, 1971 18. Wigger H J, Bransilver BR, Blank WA: Thromboses due to catheterization in infants and children. J Pediatr 76:1-11, 1970
L i t t l e Rock, Arkansas 9 Recent large series have reported a 5% to 10% incidence of major venous thrombosis associated w i t h central indwelling total parenteral nutrition (TPN) catheters. Previous authors suggested that this was well tolerated by children and resulted in f e w clinically important sequelae. Our experience differs significantly and forms the basis of this report. Between 1979 and 1981, 117 Broviac TPN catheters (Evermed, Medina, Washington) w e r e placed in children less than 1 year of age. Catheters w e r e introduced into the superior vena cava (SVC) by w a y of a common facial vein cutdown. Catheter position was confirmed radiographically in the operating room. Eight infants (7%) subsequently developed superior vena caval thrombosis. All presented w i t h edema of the head and neck associated with facial plethora, chemosis, and prominent cutaneous venous pattern. In five of the eight children the clinical signs resolved spontaneously following catheter removal and there w e r e no apparent sequelae. The remaining three (38%), however, suffered significant morbidity. T w o developed intracardiac extension of their thrombus. The first child suffered extensive pulmonary embolization. In the second child, the thrombus prolapsed through the tricuspid valve inciting congestive heart failure. This thrombus subsequently became infected, necessitating urgent cardiotomy. The third infant developed bilateral chyIothoraces due to pulmonary lymphangiectasia associated w i t h SVC thrombosis. These proved unresponsive to medical or surgical management and resulted in the death of this newborn. Although the majority of infants developing catheter-induced central venous thrombosis respond t o catheter removal and suffer no subsequent ill effects, these children are at risk for major complications. These complications can be associated w i t h not only significant morbidity but w i t h mortality as well. The generalization that such thrombosis is well tolerated in the infant is unwarranted.
From the Departments of Surgery and Pediatrics, Arkansas Children's Hospital and University of Arkansas for Medical Sciences, Little Rock, Ark. Presented before the 31 st Annual Meeting of the Surgical Section of the American Academy of Pediatrics, New York, New York, October 23-24, 1982. Address reprint requests to Daniel L. Mollitt, MD, Arkansas Children's Hospital, 804 Wolfe Street, Little Rock, AR 72201. 9 1983 by Grune & Stratton, Inc. 0022-3468/83/1804~025/$01.00/0
462
INDEX WORDS: Parenteral alimentation; central venous catheter; vena caval thrombosis; SVC syndrome.
O T A L P A R E N T E R A L N U T R I T I O N has
T proven to be an effective means of nutritional support in the neonate and infant. Complications are related to metabolic alterations induced by the infusate, sepsis, and mechanical difficulties secondary to the intravenous cannula. The development of a cuffed silastic catheter of appropriate size, and of a standard operative approach, has reduced the adverse consequences of long-term indwelling central venous lines. Although an almost universal incidence of clot formation was found in a series in which venograms were routinely performed, recent large series report a 5% to 10% incidence of catheterinduced central venous thrombosis, t-3 O t h e r reports suggested that this complication was well tolerated in children and resulted in few clinically important sequelae, 4 but our experience differs significantly from this and forms the basis for this report. MATERIALS A N D METHODS
Between 1978 and 1981, 117 catheters were placed in children less than 1 year of age at Arkansas Children's Hospital. The catheters were placed in all instances for purposes of total parenteral nutrition (TPN). The majority were introduced into the superior vena cava by way of a common facial vein cutdown. An occasional infant underwent placement into the inferior vena cava by way of the saphenous vein as a secondary procedure. All cutdowns were performed in the operating room. Pediatric Broviac parenteral alimentation catheters were employed and tunneled through the subcutaneous tissue to the site of the venotomy. Catheters were placed at the junction of the superior vena cava and right atrium as confirmed by intraoperative roentgenograms. Each patient was then begun on a standard schedule of gradually increasing parenteral nutrition culminating in a final glucose solution concentration of 20% and amino acid concentration of 2% at 150 mL/kg/d (114 cal/kg/d) which has an osmolality of 1695 m0sm and a pH of 5.7. Eight patients (7%) subsequently developed superior vena caval thrombosis. All presented with edema of the head or neck associated with facial plethora, chemosis, and a prominent cutaneous venous pattern. Each patient was treated with
Journal of Pediatric Surgery, Vol. 18, No. 4 (August), 1983
TPN-INDUCEO CAVAL THROMBOSIS IN INFANTS prompt removal of the catheter. In five of the eight, the clinical signs resolved quickly and there were no apparent sequelae. The remaining three infants, however, suffered significant morbidity despite catheter removal. CASE REPORTS Case 1 A 700 g, premature female infant was transferred on the 18th day of life for management of neonatal necrotizing enterocolitis. The medical management initiated included placement of a central venous catheter. On the fourth postoperative day, deterioration in her clinical course prompted removal of the catheter and subsequent abdominal explore-
463 tion and segmental ileal resection. Four days later, she was returned to the operating room and the central venous line was replaced. After 21 days of TPN, she was noted to have clinical evidence of superior vena caval thrombosis and the catheter was removed. Within 24 hours, she developed respiratory distress associated with bilateral lymphangiectasia and pleural effusions. (Fig. 1A). Radionucleotide lymphangiogram demonstrated occlusion of the thoracic duct and retrograde filling of the pulmonary lymphatics. A venogram showed almost complete occlusion of the superior vena cava. (Fig. 1B). Bilateral chylothoraces proved unresponsive to both medical and surgical therapy and resulted in the death of this infant. Case 2 A premature male infant was transferred at 6 hours of age with a diagnosis of omphalocele and Beckwith-Wiedemann syndrome. He underwent primary closure of the abdominal wall defect and placement of a central venous catheter shortly after arrival. On the 14th postoperative day, he developed staphylococcal sepsis and the central line was removed. Despite appropriate antibiotic coverage, he remained septic with evidence of increasing cardiomegaly, respiratory distress, hepatic enlargement, and cardiac failure. Echocardiography, and then angiocardiography, demonstrated a tricuspid vegetation associated with a large right atrial mass prolapsing through the valve (Fig. 2). Cardiotomy was performed and the septic right atrial thrombus was removed. He was discharged 31/2 months after admission. Case 3 A premature female infant with gastroschisis underwent staged closure and central line placement shortly after birth. She developed necrotizing enterocolitis late in her course and required multiple small-bowel resections resulting in "short gut" syndrome. She was maintained on TPN but had accidental dislodgement of one catheter. A second catheter was placed on the contralateral side and removed at 4 months of age due to superior vena cave} thrombosis. She had continued inability to tolerate enteral nutrition, and a third line was placed utilizing the saphenous vein for access to the inferior vena cava. She developed gradually increasing respiratory insufficiency over the next several months. Evaluation documented thrombosis of the vena cava with propagation into the right atrium and calcification of a right atrial thrombus (Fig. 3A). A lung scan (Fig. 3B) and pulmonary arteriogram showed almost no pulmonary flow (Fig. 3C). She was begun on continuous heparin infusion but continued to deteriorate and ultimately succumbed to respiratory insufficiency and sepsis. DISCUSSION
Fig. 1. (A) Chest radiograph of a 21-day-old, 700 g infant with diffuse bilateral infiltrates associated with pulmonary lymphangiectasia. (B) Venogram of the same neonate demonstrating obliteration of the superior vena cava.
Vena caval thrombosis, once largely secondary to n e o p l a s t i c d i s e a s e , h a s i n c r e a s i n g l y b e e n reported as a complication of use of indwelling c e n t r a l c a t h e t e r s in t h e p e d i a t r i c a g e g r o u p , l : A n inclusive series through 1949 showed only four children with SVC syndrome) Since that time,
464
MOLLITr AND GOLLADAY
Fig. 2.
Lateral and anterioposterior angiocardiograms in which a right atrial t h r o m b u s is s h o w n (arrow).
however, 175 additional cases have been reported and 27 of these are secondary to TPN. ~ The incidence of catheter-induced SVC thrombosis in children is 5% to 10% and has been infrequently associated with any apparent sequelae in previously reported series. 4'6'7Morbidity and mortality have, however, been reported. Scattered case presentations have documented the association of catheter-induced central venous thrombosis with hydrocephalus, pulmonary lymphangiectasia, chylothorax, pulmonary embolus, endocarditis, and cardiac dysfunction. 8 10 The majority of these have been in children less than 1 year of age. The newborn and infant are at greatest risk for both TPN-induced thrombosis and thrombotic complications. Vascular thrombosis is the result of stasis, hypercoagulability, and/or endothelial disruption. Hypercoagulability has not been identified as an etiologic factor in catheter-induced thrombosis. Stasis may play a role in low-flow states such as dehydration, cardiac failure, and hyperviscosity. Catheter-related endothelial disruption can certainly incite thrombosis, but a major contributing factor is direct endothelial injury secondary to the hyperosmolar infusate. The incidence of caval thrombosis following central venous lines placed for pressure monitoring is significantly less than those utilized for TPN. ~ In
the small-caliber vessels of the neonate, proper dilution of the infusate and precise positioning is mandatory. Catheter migration or improper placement was present in 70% of the previously reported pediatric cases of TPN-related central venous thrombosis. ~ There is a minimal distance between the confluence of the innominate veins and the right atrium in the infant, and even slight migration can result in incorrect placement. Minor migration also occurs as the result of growth alone. Prolonged exposure of the central venous system to an indwelling catheter and T P N infusion also enhances the probability of thrombosis. In a series reported by Fonkalsrud and co-workers, 4 central catheters in children who developed thrombosis were in place twice as long as those without complications. Central venous occlusion may be suspected first on the basis of difficulty with infusion or inability to withdraw or flush the catheter. Attempts at flushing are associated with discomfort. Signs of increased venous pressure include proptosis, plethora, chemosis, swelling of the head and neck, axillary adenopathy, and cyanosis of the upper body. Symptoms are increased by a horizontal position or bending forward. Signs of cutaneous collateralization are a prominent venous pattern about the head, neck, and anterior chest. Respiratory symptoms include a
TPN-INDUCED CAVAL THROMBOSIS IN INFANTS
465
Fig. 3. (A) Lateral chest radiograph with calcified right atrial thrombus (arrow). (B) Pulmonary perfusion scan w i t h flow essentially limited to the lower lobes bilaterally. (C) Pulmonary angiogram performed by way of the azygos vein demonstrates marked reduction in pulmonary blood f l o w due to repeated embolization.
hoarse cry, stridor, dyspnea, and airway occlusions. ~2 Neurologic symptoms including headache, irritability, disturbed consciousness, nausea, dizziness, lethargy, and distorted vision may be present in the older child but are difficult to evaluate in the newborn. Confirmation of clinical suspicion is obtained through radiographic means. Plain roentgenographic findings of catheter migration or a widened mediastinum are frequently seen. Contrast injection will confirm central occlusion and collateralization. Ultrasonography of the vena cava
can localize a thrombus and assess the cardiac valves for the presence of vegetations. Lymphangiograms may demonstrate retrograde lymphatic flow into the lungs secondary to central venous occlusion. 8 Complications are secondary to increased venous pressure, propagation a n d / o r clot disruption, and superimposed infection. The increased venous pressure accompanying central venous thrombosis leads to the accumulation of tissue fluid and dilation of patent collaterals. This, in turn, results in the characteristic facial edema
466
MOLLITT AND GOLLADAY
and plethora. Similarly, this increased pressure, when transmitted intracranially, overcomes the venous osmotic pressure and interferes with cerebrospinal fluid dynamics. Fluid is produced in excess of absorption and, when this occurs in early childhood, will result in ventricular dilatation and enlargement of the head. Although this is usually unaccompanied by neurologic sequelae, ventricular shunting has been required for control in isolated casesJ ~ Propagation of caval thrombosis has been demonstrated to occur both proximally and distally. With involvement of both subclavian vessels, there may be occlusion of the thoracic and right lymphatic ducts with resultant stasis within the pleural and pulmonary lymphatics. Interstitial pulmonary edema and chylothorax then result (case I). As noted by K r a m m e r and associates, chylothorax may be the only manifestation of superior vena caval thrombosis in the neonate.14 This complication is intractable to the usual forms of management and may require partial pleurectomyJ 5 Propagation of the thrombus into the right atrium will interfere with valvular competence resulting in tricuspid insufficiency (case 2) and predispose to clot disruption with resultant pulmonary embolization (case 3). Thrombosis can result from catheter-related septic thrombophlebitis or the thrombus may become infected secondarily. The organisms most frequently involved are Staphylococcus and CandidaJ 6-~8 The usual manifestations of SVC syndrome may then be accompanied by murmur, severe respiratory insufficiency, or signs of overwhelming sepsis. Candida infection is often associated with disseminated intravascu-
lar coagulopathy secondary to fungal coagulase and/or exposure of subendothelial collagen by the direct action of the microorganism. 17 This manifestation of candidal infection is associated with a poor response to therapy and with high mortality. Regardless of the immediate sequelae, thrombophlebitis of the vena cava severely limits further access in children with long-term parenteral nutritional needs. I f thrombosis occurs, immediate withdrawal of the catheter and elevation of the head and neck are the important facets of therapy. Culture of the withdrawn catheter tip should be performed to rule out associated sepsis. I f there is clinical evidence of infection, antibiotic coverage should be initiated prior to culture results. Systemic anticoagulation has not been employed routinely but m a y be necessary in cases of pulmonary embolism. Specific complications can require operative intervention. Progressive hydrocephalus secondary to central venous occlusion can be controlled with ventricular shunting procedures. Cardiotomy with thrombectomy may be necessary for removal of septic thrombi or vegetations. Chylothorax may require tube thoracostomy or pleurectomy. Central venous thrombosis will continue to complicate the management of critically ill newborns with indwelling catheters, Although the majority of these can be successfully managed by catheter removal, complications secondary to such thrombosis will continue to occur. These complications can be associated not only with significant morbidity but also with mortality as well. The generalization that such thrombosis is well tolerated in the infant is unwarranted.
REFERENCES
1. Janin Y, Becker J, Wise L, et al: Superior vena cava syndrome in childhood and adolescence: A review of the literature and report of three cases. J Pediatr Surg 17:290-295, 1982 2. Padberg FT, Jr, Ruggiero J, Blackburn GL, et al: Central venous catheterization for parenteral nutrition. Ann Surg 193:264-270, 1981 3. Fliegel CP, Signer E, Stahl M, et al: Thrombotic complications of long term intravenous alimentation in infants. Ann Radiol 19:15-22, 1976 4. Fonkalsrud EW, Ament ME, Berquist WE, et al: Occlusion of the vena cava in infants receivingcentral venous hyperalimentation. Surg GynecolObstet 154:189-192, 1982 5. Mclntyre FT, Sykes EM, Jr: Obstruction of the superior vena cava: A review of the literature and report of two personal cases. Ann Intern Med 30:925-960, 1949
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