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Vol. 14,No. 1 Printed in U.S.A.

JOURNAL OF PARENTERAL AND ENTERAL NUTRITION Copyright 0 1990 by the American Society for Parenteral and Enteral Nutrition

Thrombosis of the Superior Vena Cava Due to a Central Catheter for Total Parenteral Nutrition SALVATORE BELCASTRO, M.D., ANTONIOSUSA,M.D., LINAPAVANELLI, M.D., AURELIAGUBERTI,M.D., AND COSIMETTA BUCCOLIERO M.D. From the Departments of Surgery and Anesthesiology, University of Ferrara, Ferrara, Italy

ABSTRACT. Total parenteral nutrition (TPN) today is a fundamental procedure in the treatment of critically ill patients, especially if they have serious gastrointestinal diseases. However, use of the central venous catheter is connected with a very important morbidity. At the “Istituto di Patologia Chirurgica” and at the “Intensive Care Unit” of the University of Ferrara, we analyzed 59 cases of deaths from different diseases, on whom a postmortem examination had been performed. Twenty-seven patients had had no central venous catheter:

none of them presented thrombosis of the central veins. Thirtytwo patients had had a central venous catheter for TPN: five of them presented thrombosis of the central veins at the postmortem examination. Except for one case who had thrombosis connected with a carcinoma of the right main bronchus, four cases (12.9%)presented thrombosis due to the central venous catheter. The subclavian vein seems to be more commonly connected with thrombosis than the jugular vein. (Journal of Parenteral and Enteral Nutrition 14:31-33, 1990)

Total parenteral nutrition (TPN) today is a therapeutically fundamental procedure in the treatment of critically ill patients. The abundance of research and written material on this subject has taken into consideration almost all the clinical and metabolic aspects linked with TPN, including the problems that T P N may itself create. A great number of papers reported complications connected with the technique of cannulation of a central vein and with sepsis caused by the catheter itself. The mechanical damaging effect of the catheter on the endothelium of the central vein is less frequently reported. These complications can be severe enough to increase the mortality risk of the patients. The purpose of this report is to evaluate the morbidity connected with the presence of a central venous catheter. We have done a retrospective analysis of all deaths from January 1, 1981 to December 31, 1985 a t the “Istituto di Patologia Chirurgica” and a t the “Intensive Care Unit” of the University of Ferrara on whom a postmortem examination had been carried out.

cases had had the catheter placed first in the JV and then in the SV for a mean time of 8.8 days (from 3-17 days); (d) Three patients had had a long catheter introduced through a brachial vein for a mean time of 6 days. The four subgroups were quite homogeneous, that is to say there was no significant difference in their average mean cannulation time which was between 8.6 and 9.3 days (if we exclude the subgroup “d” because the number of cases was too small) Twenty-six of 31 patients (83%) had undergone therapy with subcutaneous calcium Heparine 15,000 units/day, without any significant difference of distribution among the four subgroups. All of the catheters were made of Uretane Polivinil (Cavafix, Certo SD-Braun). Only in the cases where the brachial vein was cannulated, was an Abbot Drum Cartridge Catheter used. The last hematologic data obtained before death showed a slight hemoconcentration (mean hematocrit 46%, mean Hb 16 g/dl), whereas coagulation tests did not show any significant pathological changes with the exception of two who died of septic shock and had a disseminated intravascular coagulation (DIC). T P N was administered with a balanced solution of dexMATERIALS AND METHODS trose, lipids, and amino acids according to the classical Fifty-nine cases of deaths from different diseases were procedure with 30 to 40 cal/Kg/day and a ratio of caloexamined. Two main groups were recognized (Table I): rieslnitrogen of 100 to 150/1. In all the cases the postGroup A-27 patients did not have a catheter. Group B, mortem examination involved the investigation of the 32 patients, with a mean age of 64 years (range 32-87), head, neck, subclavian veins and thorax, and the area of 21 men and 11women, had had a central venous catheter the inferior vena cava (IVC) while in none of the cases was the calf area examined. for TPN from 1to 60 days. In group B four subgroups were recognized (Table 11): Group A (a) Twelve critically ill patients had had a catheter in At necropsy they showed normal central veins. Two the subclavian vein (SV). The mean cannulation time patients had died of pulmonary embolism (7.4%), the was 8.6 days (from 1-25 days). (b) Twelve cases had had source of which was discovered in the femoral and iliac the catheter inserted in the jugular vein (JV). The mean cannulation time was 9.3 days (from 2-60 days). (c) Four veins. RESULTS

Received for publication, June 30, 1988. Accepted for publication, February 20, 1989. Reprint requests: Salvatore Belcastro, MD, Via della Fornace n.4, 44100 Ferrara, Italy. 31

Group B Five of those a t necropsy showed thrombosis in the central veins. One was immediately excluded from the

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BELCASTRO ET AL

TABLEI Fiftv-eight oostmortem examinations' Group A t Group BS N. 27 Cases N. 31 Cases Thrombosis N. 0 Thrombosis 4 (12.9%) 2 (7.4%) Pulm. Emb. 4 (12.9%) Pulm. Emb. N. * One postmortem examination was excluded because the thrombosis was due to a bronchogenic carcinoma. t Group A, cases without any central catheter. $ Group B, cases with a central venous catheter.

Distribution Subgroup

(a) (b) (c) (d)

of

TABLEI1 the patients of group B according to the cannulated veins for TPN

Cannulated veins

No,

SV JV JV+SV Brachial v.

Thrombosis observed

(%)

12

2

16.6

12

0

2 2

4

1 1

0 0

3

Pulmonary embolism

(%Ig)

16.6 16.6 25.0 33.3

analysis on account of the fact that the superior vena cava was involved in a lung tumor. In the other four, however, the postmortem showed signs of thrombosis in connection with the presence of a venous catheter (12.9%) (Table I): two had thrombosis of the right atrium (RA) and the superior vena cava (SVC) and the subclavian vein (SV); one had thrombosis only of the RA; and one thrombosis of the right innominate (IV) and the SV. In two of those four cases the cause of death was a pulmonary embolism (6.5%). Out of the whole of group B four patients died of pulmonary embolism (12.9%). In two of those the source was not found, The latter two had had a catheter inserted in the internal jugular vein (JV) for a long period of time. In the necropsy, lesions of the wall of the JV were not found. In none of these patients was thrombosis clinically diagnosed apart from the neoplastic case. Subgroup (a). Two cases of thrombosis of the central cannulated veins were found. Both patients (65 and 77 years old, respectively) died from pulmonary embolism. At necropsy the source of the embolism was discovered in the cannulated veins. Both patients had been operated on for stones in the common biliary duct. The cannulation time was, respectively, 5 and 7 days and they had had one inserted catheter each. Subgroup (b). Two patients died from pulmonary embolism among this subgroup. They had one and three catheters inserted for 4 and 11days, respectively. At the postmortem examination neither thrombosis on the cannulated side nor any source of the embolism was found. Subgroup (c). One patient who had the catheter inserted for 9 days showed signs of thrombosis. He had two catheters, one in the JV and one in the contralateral SV. Thrombosis occurred at the side where the SV was cannulated. No pulmonary embolism occurred in this subgroup. Subgroup (d). One of those cases had thrombosis. Three of the four cases with thrombosis of the central vein underwent therapy with calcium heparin (75%). DISCUSSION

Thrombosis of the central veins connected with T P N seems to be a rather important complication. In OUT

Vol. 14, No. 1

series we discovered thrombosis in 12.9% of cases. Some authors report an incidence of obstruction of the SVC of 15% following the use of central venous catheter over lengthy periods of time,' others as much as 26%.2 However, the statistical comparison between the cases without any central catheters and those who had a central venous catheter inserted for TPN, showed no statistically significant value because the groups were not numerous enough. In spite of that, we believe that the thrombosis observed is connected with the cannulation of the veins. Also our data seem to suggest a higher incidence of thrombosis when the SV or peripheral brachial vein is used in TPN. Although we still had no statistical significant value in this analysis, for peripheral veins the high frequency of thrombophlebitis connected with a long catheter inserted is p r ~ v e dFor . ~ central veins it has not yet been proved that there is a different incidence of thrombosis between the JV and the SV. Two of the deceased had died of pulmonary embolism and had had the central venous catheter in the JV. At the postmortem the source of the embolism was not discovered in the areas examined. Furthermore, the lack of information in connection with the calf area renders the above data of rather limited value. We think that the JV might be the source of embolism. An embolism which comes from the JV might not leave traces on the wall of this vessel. In the iliofemoral and popliteal veins, thrombosis leaves permanent marks on the valves themselves. In the superior caval system these signs are clearly evident on the valves when thrombosis has occurred in the brachial or the subclavian veins. The JVs often do not have cuspided valves, but do have one or two rudimentary valves that take the form of circular endothelial bulges at the confluence of the subclavian vein and the innominate vein. For this reason we think that an embolism that might form in the JV does not leave marks on the endothelial wall. Perhaps the valves themselves in the SV could be considered as a factor which might favor the development of small thrombus related with the mechanical action of the catheter on the cuspidal valves. Every respiratory cycle causes opening and closing of the valves, which experience some small trauma from the catheter. This explanation identifies the cause of thrombosis as one connected to the mechanical action of the catheter and explains the great ease with which a brachial vein cannulated with a catheter might cause thrombosis (the cannulated segment is very long and has many valves inside). However, thrombosis may also occur in the right atrium." Often the tip of the catheter reaches as far as the right atrium. It could create a continuous microtrauma which, operating against the cardiac wall, damages the endothelium causing inflammation which in turn encourages the development of thrombosis. Critically ill patients can also develop disturbances of cardiac rhythm. Thus, we have all the factors necessary for the formation of thrombus in the atrium: microtrauma, inflammation of the endothelium, the slowing down of the velocity of blood flow due to the arrhythmias. The mechanical action in the small vessels is certainly more important. The incidence of thrombosis of the SVC in children receiving T P N is reported between 7 and Janin et alg in 1982 reviewed the literature on thrombosis of the SVC in children. In 175 cases, about 70% had had

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JanuarylFebruary 1990

33

THROMBOSIS OF THE SUPERIOR VENA CAVA

iatrogenic thrombosis: in 50.8% of children, thrombosis was secondary to cardiac operations; in 15.4%to catheterization of SVC for TPN; in 3.5% to catheterization of SVC for monitoring and fluid admini~tration.~ The association of thrombosis in the SVC and infection of the catheter is rather frequent.'-'' According to Ryan et all5, 23% of the postmortems studied that were receiving T P N showed signs of thrombosis in the SVC and 8.8%had an infected catheter." The hypothesis that infection of the catheter is a strong thrombogenic factor does not, however, contradict the mechanical factor. Small clots on the cuspidal serve as an ideal breeding ground for germs. The passage of germs from the skin along the catheter is not difficult. Perhaps infection from Candida is even easier.l23l3 All the patients underwent antibiotic treatment of a wide-spectrum type and all had a weakened defense system.13In our series, however, not one cultured tip of the catheters developed pathogenic bacteria. The hyperosmolar infusions can themselves be the cause of irritation of the endothelium and therefore factors contributing to thrombosis, especially if the solution goes directly towards the same point for a long period of time. The negative effects of infusion are more evident in ~ h i l d r e n We . ~ think that this factor, though not negligible, is perhaps less important than the mechanical factor. Indeed, in patients fitted with pace-makers there is a high incidence of thrombosis of the SV and of the SVC. In these cases there is no infusion, but the endothelium is subjected to continuous microtrauma by the wire string. We are unable at present to judge to what extent the incidence of thrombosis is linked to the material with which catheters are made. Some authors report a significantly different incidence of thrombosis when catheters ~ ~ ~ catheters are are made of silicon or p 0 1 y v i n y l . l ~Silicon less thrombogenic than polyvinyl catheters. In all the cases examined in this series, catheters made of polyvinyl silicated urethane were used. The incidence of thrombosis that we have reported resembles the incidence of thrombosis reported with sylastic catheters.14 Mean cannulation time plays an important role in thrombogenesis; in this series it was of about 9 days, considering that the central venous catheter was changed with a reasonable frequency. CONCLUSION

For critically ill patients, especially those with serious gastroenteric disease, we cannot manage without TPN, which is part of the therapeutic procedure. A retrospective analysis of our case studies allows us to pinpoint the

problem of thrombosis connected with the cannulation of a central vein. We found no negligible incidence of thrombosis of the central cannulated veins for TPN. The incidence of thrombosis of the SV seems to be more frequent than the JV, although we found some pulmonary embolism in patients who had the catheter inserted in the JV. Because we do not have statistical proof, on this point we must wait for further experience.

REFERENCES

1. Axelsson K, Efsen F Phlebography in long-term catheterization of the subclavian vein. A retrospective study in patients with severe gastrointestinal disorders. Scand J Gastroenterol13:933-938, 1978 2. Belcastro S, Pavanelli L, Guberti A, et al: Le superinfezioni da candida nei decorsi postoperatori complicati. Giorn. Chir. 5423426,1984 3. Bozzetti F, Scarpa D, Terno G, et al: Subclavian venous thrombosis due to indwelling catheters: A prospective study of 52 patients. JPEN 7:560-562,1983 4. Broviac JW, Cole J J , Scribner BH: A silicon rubber stria1 catheter for prolonged parenteral alimentation. Surg Gynecol Obstet. 136:602-606,1973 5. Fischer JE: Nutrizione totale per via parenterale. Verduci Editore, Roma, 1980, p. 55 6. Giuffrida DJ, Bryan-Brown CW, Lumb PD, Kwun KB, et al: Central vs. peripheral venous catheters in critically ill patients. Chest 90:806-809, 1986 7. Graham L Jr, Gumbiner CH: Right atrial thrombus and superior vena cava syndrome in a child. Pediatrics 73:225-229, 1984 8. Jacobs MB, Yeager M: Thrombotic and infectious complications of Hickman-Broviac catheters. Arch Intern Med 144:1597-1599, 1984 9. 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 17290-295,1982 10. Malmvall B, Alestig K, Dottor 0,e t al: Septicemia in patients with central venous catheters. Acta Chir Scand 149:155-159, 1980 11. Mollitt DL, Golladay SS: Complications of TPN catheter-induced vena caval thrombosis in children less than 1year of age. J Pediatr Surg 18462-467,1983 12. Mulvihill SJ, Fonkalsrud EW: Complications of superior versus inferior vena cava occlusion in infants receiving central total parenteral nutrition. J Pediatr Surg 19:752-757, 1984 13. Parish JM, Marschke RF Jr, Dines DE, et al: Etiologic considerations in superior vena cava syndrome. Mayo Clin Proc 56407-413, 1981 14. Ratcliffe FM: Suppurative thrombosis of the superior vena cava: A lethal complication of central venous catheters. Int Care Med 11:265-266,1985 15. Ryan JA, Abel RM, Abbott M, et al: Catheter complications in total parenteral nutrition: A prospective study of 200 consecutive patients. N Engl J Med 290:757-761, 1974

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