The treatment of refractory ascites by the LeVeen shunt

JournalofHepatology, 1986;3:212-218

212

Elsevier HEP 000209

The Treatment of Refractory Ascites by the LeVeen Shunt A Multi-Centre Controlled Trial (57 Patients) P. Bories 1, D. Garcia C o m p e a n 1, H. Michel 1, M. Bourel 2, J.P. C a p r o n 3, A. G a u t h i e r 4, J. Lafon 5, V . G . L6vy 6, J.P. Pascal 7, A. Q u i n t o n 8, B. T o u m i e u x 9 and J.P. Weill 1° I Clinique des Maladies de l'Appareil Digestif, HOpital Saint-Eloi, 34059 Montpellier; 2Clinique Mddicale A, H6pital Pontchaillou, 35033 Rennes; 3Centre Hospitalier, 80030Amiens; 4HOpitalde la Conception, 13000 Marseille; 5Service de Gastroent~rologie, Centre Hospitalier, 13090 Aix en Provence; 6Service d'Hdpato-Gastroentdrologie, HOpital Saint-Antoine, 75571 Paris; 7H6pital Purpan, 31000 Toulouse; SH6pital Saint-Andr~, 33000Bordeaux; 9CHU Bretonneau, 37000 Tours; and 1°Hospices Civils, 67000 Strasbourg (France)

(Received 20 June, 1985) (Accepted 2 May, 1986)

Summary A multi-centre random trial of 57 cases of alcoholic cirrhosis with refractory ascites was carried out; 29 patients received a LeVeen shunt and 28 were treated by conventional medical therapy. The effectiveness of the LeVeen shunt in reducing ascites was good in the first month, but was not different from conventional medical therapy by the end of one year. Complications were significantly more frequent in the surgical group. Of the 29 patients fitted with a LeVeen shunt, 25 developed one or more complications. Of the 28 patients in the medical control group, only 8 developed complications. The mortality rate of the two groups also differed significantly. Twelve patients in the surgical group (41%) died in the course of the first month against only 5 (18%) in the medical control group. By the end of one year, the mortality rate of the two groups was almost identical: 23 (79%) and 21 (75%) respectively. These observations confirm the poor prognosis for refractory ascites in cases of alcoholic cirrhosis and the inadvisability of attempting to treat it by implanting a LeVeen shunt.

Introduction Refractory ascites in alcoholic cirrhosis may be defined as massive ascites which resists conventional medical therapy (i.e., alcohol withdrawal, a low sodium diet, restricted fluid intake and the administration of diuretics for 10 days to 6 weeks following ad-

mission to hospital) [1]. It usually occurs during the terminal stage of cirrhosis [2], is infrequent (4.5% of ascites cases) [1], and the mortality rate is high (40-50%), especially when accompanied by a hepatorenal syndrome [1,3]. Until 1974, the treatment for severe ascites consisted of either (a) punction (with or without reinjec-

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tion of the ascitic fluid and with or without albumin perfusion) [4-8] or (b) the implantation of a portocaval shunt [9]. The consequences of both therapeutic methods were unsatisfactory and often led to complications [9,10]. In 1974, LeVeen introduced a new device designed to drain the ascitic fluid into the jugular vein [11]. The LeVeen shunt, as it came to be known, was rapidly adopted by many surgeons [12-22]. However, the quality of the results obtained from its use have proved to be inconsistent [14]. Surgical risks are high [15] and complications frequent [16,17]. A controlled trial [13] demonstrated the superiority of the LeVeen shunt over conventional medical treatment for massive ascites, but the lack of documentation in the published report did not make it clear if the authors were dealing specifically with ascites refractory to conventional medical therapy. A new, more fully documented, controlled trial was therefore needed to allow proper assessment of the value of the LeVeen shunt in reducing refractory ascites and helping affected patients to survive.

The following Categories of patient were excluded from the trial: (1) those with digestive tract hemorrhage within the 3 months preceding the trial; (2) those with a platelet count lower than 50 000/ml, a prothrombin level lower than 25% and a euglobulin lysis time of less than 30 min; (3) patients presenting any sign of cardio-respiratory failure, systemic infection, or primary or metastatic carcinoma; (4) chylous, hemorrhagic, infected (more than 300 leucocytes/ml) or protein-rich ascites (more than 30 g/l). The following were not considered to be excluding factors: low plasma sodium, high BUN, creatinine, bilirubin or a hepatorenal syndrome. The trial was carried out in ten different hepatogastroenterology centres in different parts of France. The type of therapy to be applied was decided by random selection after all selected patients had consented to surgery. The random nature of the trial was assured as follows: 6 unmarked sealed envelopes were sent to each centre immediately before the beginning of the trial. Three indicating surgery and 3 medical therapy. One of these envelopes was allocated to each patient before being opened.

Patients and Methods

Methods The LeVeen shunt was implanted under either local or general anesthesia, according to the procedure described by LeVeen [18]: extra-peritoneal implantation in the abdominal wall, with the afferent portion of the catheter introduced into the abdominal cavity and the efferent portion tunnelled through the prethoracic cutaneous tissue to the internal jugular vein and positioned to lie in the superior vena cava. A low-sodium diet and diuretics (spironolactone 200-400 mg/day, with or without furosemide 40-80 mg/day) were prescribed for the first week after implantation. Patients were also obliged to wear an elastic abdominal band and underwent respiratory physiotherapy. Where any doubt of the permeability of the shunt existed, a radio-opaque liquid was injected into the sub-cutaneous catheter and an X-ray examination carried out. Patients in the medical control group were sub jected to a low-sodium diet and adjuvant therapy ac-

Patients Fifty-seven cirrhotic patients of all ages, both sexes, with ascites for at least 6 months, were included in the trial. In all cases, the volume of ascites exceeded 10 liters (i.e., patients' weight had increased by more than 10 kg since the onset of ascites) and was refractory to conventional medical therapy. Medical therapy was considered to be inadequate where alcohol withdrawal, bed-rest, a low sodium diet (500 mg/day), restriction of the fluid intake (800 ml/day) and the administration of diuretics over a period of 15 days after admission to hospital were unavailing. Diuretics were considered to be inoperative if no increase of diuresis took place after 15 days of increasing dosage (days 1-5: spironolactone 200 mg/day; days 6-10: spironolactone 400 mg/day; days 11-15: spironolactone 400 mg/day, furosemide 40 mg/day), or where there was a rise in blood urea nitrogen (BUN) and a fall in natremia.

P. BORIES et al.

214 cording to the facilities available at each centre. These included simple punction, punction with albumin perfusion, or punction-concentration-reinjection of ascites fluid, usually associated with the ad• ministration of diuretics (spironolactone with or without furosemide). Before the start of the trial, patients in both groups underwent a clinical examination in which body weight, measurement of the umbilical perimeter, and any sign of jaundice or hepatic encephalopathy were recorded. Hematological tests included BUN, sodium, potassium, creatinine, bilirubin, transaminases, albumin, gammaglobulin, alpha fetoprotein, RBC, WBC, a platelet count and coagulation tests. Urine analysis included the measurement of sodium and potassium.

Surveillance Clinical and laboratory observations were carried out on days 3, 7, 15 and 30, then at the end of months 2, 3, 4, 8 and 12. The effectiveness of the therapy applied was determined by the degree of reduction in the umbilical perimeter and patient weight. A reduction of more than 15 cm in the umbilical perimeter was considered to be excellent; less than 15 cm to be moderate. If there was no reduction, or if the umbilical perimeter had increased, the therapy was considered to be inadequate. The clinical and biochemical reports were collated at the end of month 1, month 12, and in the event of death. Statistics The mean laboratory values and survival rates were analyzed using the Chi 2- and Student t-tests.

Results

Fifty-seven patients were included in this trial; 29 received a LeVeen shunt and 28 were treated by conventional medical therapy. Age, sex and ascites history of the patients in both groups were similar. According to Child-Pugh's criteria, there were no cases in group A; 35 in group B (18 surgical, 17 medical), and 22 in group C (11 surgical, 11 medical). Bio-

TABLE 1 CLINICAL AND BIOCHEMICAL PROFILES OF 57 PATIENTS (mean ± SD) Operated patients (n = 29) Age (years) Sex (M/F) Aseites episodes (number) Prothrombin (%) ASAT (Nx) Bilirubin (rag/l) Albumin (g/l) Red blood cells (mill/ram3) White blood cells (mill/mm3) Platelets ( x 103/ram3) Sodium (retool/l) Creatinine (mmol/l)

Non-operated patients (n = 28)

t

59.8 16/12

NS NS

2.3 ± 1.0 61 ± 18.5 1.6 ± 0.8 29.2 ± 21.2 28.1 ± 4.5

NS NS NS NS NS

3.6±0.5

3.5±0.6

NS

6.9 + 2.7 148.6 + 72.9 127.6 + 7.3 105 + 8.1

5.9 + 2.1 157 + 66.3 130 + 6.9 96 + 4.3

NS NS NS NS

56.6 19/10 2.5 ± 59.7 ± 1.3 + 28 ± 30 ±

1.6 15.4 0.6 20.7 6

chemical data for the patients in both therapy groups concorded (see Table 1). Five patients (2 surgical, 3 medical) presented a hepatorenal syndrome, which was confirmed by a BUN greater than 7 mmol/l, plasma creatinine greater than 124 mmol/l and diuresis under 500 ml/l. Surgical patients were operated 48 h after random selection; 11 surgeons participated in the trial. Of the 28 patients in the medical control group, 16 were given a simple punction, 6 were treated by simple punction with albumin perfusion, and 6 were treated by punction-concentration-reinjection of ascites fluid. Diuretics were administered on one or more occasions in the course of the following year in 21 patients.

(1) Reduction of ascites At the end of week 1 (Table 2), reduction of ascites was excellent in 17 of the surgical cases (59%), moderate in 9 (31%) and unchanged or worse in 3 (10%). In the control group, reduction was excellent in 4 cases (14%), moderate in 12 (43%) and unchanged or worse in 12 (43%). At the end of month 1, of the 17 surviving patients in the surgical group, the elimination of ascites was excellent in 9 (31%), moderate in 4 (13.5%) and un-

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215

TABLE 2 REDUCTION OF ASCITES AFTER TREATMENT FOR 1 WEEK, 1 MONTH AND 1 YEAR IN 57 PATIENTS (excellent result = reduction of umbilical perimeter (UP) greater than 15 cm; moderate result = reduction of UP less than 15 cm and no reduction of ascites = no change or increased UP) Operated patients (n = 29)

Non-operated patients (n = 28)

Excellent

Moderate

No reduction

Excellent

Moderate

No reduction

1 week

17

9

3

4

12

12

1 month

9

4

4*

1

3

19"

1 year

3

0

3

2

1

6

*P< 0.001.

changed or worse in 4 (13.5%). The body weight decreased in all the patients except for one; the average weight decreased from 67.8 kg to 58.5 kg (P < 0.01). Of the 23 surviving patients in the medical control group, the results were excellent in one (4.8%), moderate in 3 (10%) and unchanged or worse in 19 (68%). The body weight decreased in 18 patients, increased in 6; the average weight was not significantly changed (from 70.5 kg to 67.8 kg). At the end of month 12, of the 6 surviving surgical patients, reduction was excellent in 3 (10%), but there was no reduction in the remaining 3 (10%). Of the 9 surviving patients in the medical control group, reduction was excellent in one (4%), moderate in 2 (8%) and unchanged in 6 (25%).

acute pulmonary edema (Table 3). Four patients at the control group were excluded from the trial because they had received a LeVeen shunt in the course of the year. Of the remaining 19, nine (37.5%) still survived. Of those who did not survive, the cause of death included hepatorenal syndrome, digestive tract haemorrhage and infection. Of the 4 patients in this group who had received a LeVeen shunt, only one survived. There was thus no significant difference in the survival rate at the end of month 12 between the surgical and medical control groups.

(3) Complications The complications which occurred were limited to those in the surgical group only, or were c o m m o n to

(2) Survival At the end of month 1, of the 29 patients in the surgical group, 17 (58.6%) still survived. The cause of death of the 12 who died included hepatorenal syndrome, digestive tract haemorrhage, septicaemia, disseminated intravascular coagulation, and pulmonary edema. Of the 28 patients in the medical control group, 23 (82.1%) were still alive; the cause of death of the 5 non-surviving patients included hepatorenal syndrome, digestive tract haemorrhage and septicemia (Table 3). At the end of month 12 (from the beginning of month 2 to the end of month 12), 6 surgical patients (20.6%) still survived; 11 had died. The cause of death by order of frequency was digestive tract haemorrhage, septicaemia, hepatorenal syndrome and

TABLE 3 CAUSE OF DEATH AT 1 MONTH AND 1 YEAR IN OPERATED AND NON-OPERATED PATIENTS

Hepatorenal syndrome Digestive hemorrhage Septicemia Disseminated intravascular coagulation Pulmonary edema

Total

Operated patients (n = 29)

Non-operated patients (n = 28)

1month 1year

1month 1 year

6 3 2

1 6 3

2 2 1

6 2 2

5

10

1 1 12

11

216

P. BORIES et al.

TABLE 4

Discussion

COMPLICATIONS OCCURRING IN OPERATED AND NON-OPERATED PATIENTS (1 patient can have several complications)

Leakage of ascitic fluid Obstructed shunt Jugular vein thrombosis Consumative coagulopathy Pulmonary edema Pleural effusion Umbilical hernia Digestive bleeding from (esophageal varices) Septicemia Peritonitis

Operated patients (n = 29)

Non-operated patients (n = 28)

I month 1 year

1 month 1 year

4 3 7 2

4 (3) 5

(1) Reduction of ascites (Table 5)

5 5 1 1 3 2 6 (3) 5 2

The results of this trial are discouraging. The difficulties concerning the long-term reduction of ascites, survival rates, and the frequency and severity of the surgical complications following the insertion of a LeVeen shunt have not been reported by all authors.

3 (2) 1

both groups (Table 4). Of the 29 patients in the surgical group, 25 (86%) developed one or more complications. Of the 28 patients in the medical control group, only 8 (28.5%) developed complications (P < 0.0001). Infection was more c o m m o n among patients in the surgical group. Septicemia due to Staphylococcus aureus and Enterococcus were frequently encountered during the 12 months of the trial. In the course of month 1, occlusion of the LeVeen shunt by fibrin plugs occurred in 3 patients cases. These were re-operated and the shunt removed or replaced by a new one. None of these patients survived. In a further 10 cases the shunt became occluded between the beginning of month 2 and the end of month 12, either as a result of the formation of fibrin plugs or of the appearance of thrombosis in the internal jugular vein or the superior vena cava. In these cases the shunt was removed and replaced by a new one, either homolaterally or controlaterally. Seven of these patients died before the end of month 8; the surviving 3 still had ascites. Altogether, o f the 29 patients in the surgical group, 13 (44.8%) developed an occluded valve as the result of thrombosis in the jugular vein, the brachiocephalic trunk or the superior vena cava.

Some authors report that ascites was reduced in 85-100% of patients in the course of month 1 [19,20,22], while others report a reduction in 3 0 - 6 0 % [15,22,23]. When the results at the end of month 12 are considered, some authors state that ascites was reduced in 6 7 - 7 5 % of cases [15,18], some report reduction in 4 0 - 4 4 % [21], whilst others report only 1 5 - 3 0 % [16,22,24]. To us, the most peculiar observation is the statement that in some cases ascites was reduced even when the LeVeen shunt was occluded [25].

(2) Survival rates (Table 5) Some reports give a survival rate of 9 0 - 9 4 % by the end of month 1 [19,20,22]; others give 7 0 - 8 7 % [21,23], while one mentions a more modest 59% [15]. After 12 months, the survival rates mentioned in the literature range from a high of 5 0 - 6 0 % [15,19,21,22] to a low of 32% and 35% [20,24]. For two authors [19,23], the survival rate after 2 years was only 34% and 50%.

(3) Complications In the literature, local and systemic complications were reported in 2 0 - 5 0 % of cases [13,19-24]. Of the two, local complications were the less serious and usually led to obstruction of the LeVeen shunt. On the other hand, systemic complications, especially infection, often led to death [18,26,28,31,32].

(4) The difference between the results obtained in our trial and those in the literature requires an explanation (a) The published reports (with the exception of that of Wapnick et al. [13]) were not concerned with controlled trials and no description of the patients' condition was given [13,15,22,24]. The patients in

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217

TABLE 5 PERCENT REDUCTION OF REFRACTORY ASCITES AND SURVIVAL RATE IN PATIENTS TREATED BY LEVEEN SHUNT Author(s)

Bloch et al. [23] Mouiel et al. [15] Paliard et al. [20] Franco et al. [19] Toumieux [22] Gullstrand et al. [24]

Year

1979 1980 1981 1981 1982 1982

No. of patients

Reduction of ascites 1 month 1 year (%) (%)

Survival rate 1 month (%)

23 17 16 88 25 23

46 50 85 98 88 61

85 59 94 89 92

the studies in which the longest survival rates were reported [15,23] appear to have been less seriously ill than those in our trial; it is obviously impossible to make any assessment of the effectiveness of the use of the LeVeen shunt in cases of differing gravity. (b) When considering the report of the controlled trial carried out by Wapnick et al. [13] which argues in favour of the LeVeen shunt, the following points should be remembered: Although the patients had massive ascites they did not, strictly speaking, have refractory ascites. In fact, patients were selected on the basis of the failure of a medical management consisting only of a low-sodium diet and bed-rest for 15 days, without the administration of diuretics. Control patients to whom diuretics were administered lost 10 kg in 4 weeks, which is not compatible with refractory ascites. There is no indication of the nature of the hepatic lesions affecting the patients, nor is the degree of hepatic failure indicated. No comparison on the basis of Child's classification was made. - The survival rates reported are paradoxal: 65% after 3 months and 41% after 1 year for the surgical group; 35% after 3 months and 4% after 1 year for the control group. The 3-month survival rate for controis was much lower than is usual in cases of common ascitic cirrhosis treated by diuretics (76%) [33,34]. Moreover, the 1-year survival rate for these -

-

15 75 40 67 32 17

1 year (%) 55 55 31 57 55 35

patients is lower than that in cases of untreated ascites ( 2 4 - 3 4 % ) [35,36]. This may be due to the administration of diuretics leading to a rapid loss of weight and a rise in plasma creatinine, B U N and potassium, thereby creating a precarious situation for the patients in the control group. This therapy would not lead to the same results in surgical patients. (c) The large number of surgeons who participated in our multi-centre study does not appear to have made any difference in the results for the surgical group. A questionnaire confirmed that most of the participating surgeons had carried out an average of 10 LeVeen shunt operations before the trial. The majority of the complications we encountered can therefore be considered being independent of surgical technique. The results obtained in this trial invite moderation. There is no doubt that the implanting of a LeVeen shunt leads to the drying-out of refractory ascites within the first month. However, it is usually followed by numerous complications, many of which are fatal and, after 1 year, makes no difference to the survival rate. In our opinion, considering the low survival rate, it is difficult to specify the indications for implanting a LeVeen shunt in cases of refractory ascites. The ideal solution would be to develop a temporary LeVeen type valve which could be removed without surgery.

218

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