Editorial

A Perspective on Emergency Portacaval Shunt

The paper by Orloff and colleagues in this issue of HEPATOLOGY (1) reports the long-term follow-up of a prospective randomized clinical trial comparing emer- gency portacaval shunt (EPCS) with medical man- agement followed by elective shunt surgery in patients with acute variceal bleeding. In evaluating this study, we need to address several issues.

The Patient Population. When this study first ap- peared in abstract form in 1986, a commentary in “Hepatology Elsewhere” by Harold Conn raised per- tinent questions on the “all-comers” inclusion and the possibility of “referral bias” (2). Careful analysis of the Orloff paper confirms that their population does not include all comers with acute variceal bleeding managed by the authors. The study group of 43 patients in this trial represents a relatively small subset of their total patient population. In the same time interval for this study (1978-19831, the authors report a consecutive all- comers series of 84 patients with acute variceal bleeding, all of whom were managed with emergency portacaval shunt (3) . The study population reported in the Orloff paper was selected such that all were men managed exclusively at the San Diego Veterans Administration Hospital and were 95% alcoholic. Figure 1 summarizes the reported experience by this group of investigators from the University of California, San Diego, Medical Center from the initiation of Dr. Orloffs program in 1963 to his latest publication in 1992 (3-5). Any center conducting randomized controlled trials has potential constraint on patient entry dictated by factors such as referral and practice patterns, and patient compliance. These must be clearly defined; in and of themselves they do not necessarily lessen the importance of this type of clinical trial.

The Study Design. This trial was designed to compare EPCS, a management method with which the investi- gators have considerable experience and expertise, to conventional^' medical management, a management method in which the authors have expressed little confidence (4). The authors are to be commended for the excellent results obtained in patients randomized to surgery. However, a major concern in the study design is the adequacy of medical management. Emergency medical therapy comprised resuscitation from bleeding,

HEPATT(ILI.WY 1994;20: 1090- LO91 See related article on page 863. Address reprint requests to: J. Michael Henderson, M.D., The Cleveland

Copyright C 1994 by the American Association for the Study of Liver Clinic Foundation, 9500 Euclid Ave.. Cleveland, OH 44195.

Diseases. 0270-9139194 $3.00 t o :w/59013

intravenous pitressin and balloon tamponade. Surpris- ingly, tamponade controlled bleeding in only 10 of 22 patients, whereas in most other series control ofboth the initial bleeding and episodes of rebleeding by tamponade was closer to 90% (6, 7). The “medical” regimen used in this study is clearly deficient by today’s standards. Even in the early 1980s many centers were using emergency sclerotherapy as the standard of care in management of acute variceal bleeding. The authors do address this issue but had excluded sclerotherapy because it was still in its infancy when their study was designed. Unfortu- nately, this omission greatly weakens the impact of this study; it has been shown that sclerotherapy con- trols acute bleeding in 70% to 90% of patients ( 8 ) and has significantly improved the management of acute bleeding in most centers over the past decade. The authors indicate that their current prospective ran- domized trial of emergency portacaval shunt vs. emer- gency sclerotherapy is proceeding.

Impact of Other Therapies. Patients in both limbs of this trial received other significant therapies, based pri- marily on the methods that had evolved over the last 30 years in the authors’ management of patients under- going emergency shunt surgery. The paper defines in detail the use of pitressin in the evaluation phase, neo- mycin and magnesium sulfate by nasogastric tube, enemas to clear the blood from the bowel, aggressive correction of hypokalemic alkalosis and digitalization of patients with cardiac output exceeding 6 L/min. Intra- venous antibiotics were utilized for 3 days. This detailed management regimen has evolved as optimal for their care of the operative patient but was not modified in any way for the medical group. Most of the therapies in this regimen are logical and reflect appropriate care of the patient with cirrhosis and variceal bleeding. An ex- ception may be the digitalization of all patients with hyperdynamic circulation: No data have been published in support of this approach. Do these therapies affect outcome? Certainly they were equivalently applied in the two populations and probably are not major factors in overall survival in this study.

Other Studies. In viewing the outcome of this study the reader should also consider the outcome of Dr. Or- loff‘s overall experience (Fig. 1). In 1978, the operative mortality for EPCS dropped dramatically from 42% before that year to 17% for subsequent years. The treatment strategy for patients with acute variceal hemorrhage did not appear to change at this time point. In the serial publications related to their overall series, the authors never adequately address the changes that led to the dramatic improvement in operative mortality in the late 1970s. Other reported trials of EPCS were

1090

HEPATOLOGY Vol. 20, No. 4, 1994 HENDERSON AND GRACE 1091

1963 1970 1980 1990 Reference: D 1 I I I

5. 1 1 422 patients -1 4. I-' 180 patients -1 3.

5.

H Child's A - 13% B - 69% 84 patients C - 18%

Survival: 30d - 58% Child's A - 11% 5yr - 38% B - 43%

C - 46% Survival: 30d - 83%

5yr - 72% - 94 patients

Child's C - 100% Survival: 30d - 80%

5yr - 64%

FIG. 1. Summary of reported experience with emergency portacaval shunt from University of California, San Diego Medical Center, 1963- 1992.

conducted at a time equivalent to the initial experience of this group. Malt and his coworkers (9) documented an operative mortality of approximately 50%, with a sig- nificantly poorer survival in Child class C patients. More recently, Cello and associates (10) reported an operative mortality of 58% in Child class C patients at a study time equivalent to the most recently reported consecutive series of Child class C patients by Orloff et al. (5). It is apparent that other centers have been unable to produce the good results reported by the San Diego group.

Finally, a question must be raised about the apparent delay in publication of the definitive paper on this trial. The statistical difference in survival between the two therapeutic approaches occurred in the first month after randomization, and results have not changed from those in the abstract published in 1986. Patients were entered in this study between 1978 and 1983; randomization was stopped at that time because there was such a clear difference between the two therapeutic approaches. Has the delay in publication of this definitive paper been because the authors or their peers have had concerns about the applicability of this study? It is important for the readers of HEPATOLOGY to critically evaluate the design, execution and analysis of this study. The conclusions drawn would be strengthened if the results of the San Diego study could be confirmed by another center using a similar study design for the surgical approach and medical management more in keeping with current standards.

J. MICHAEL HENDERSON, M.D. Department of General Surgery The Cleveland Clinic Foundation Cleveland, Ohio

NORMAN D. GRACE, M.D. Division of Gastroenterology Faulkner Hospital and Tufts University Medical School Boston, Massachusetts

REFERENCES 1. Orloff MJ (other authors of current paper obscured on my copy).

Prospective randomized trial of emergency portacaval shunt and emergency medical therapy in unselected cirrhotic patients with bleeding varices. HEPATOLOGY 1994;20:863-872.

2. Conn HO. Emergency portacaval anastomosis (EPCA): the long- awaited trial. HEPATOLOGY 1986;6: 1058-60.

3. Bell RH, Miyai K, Orloff MJ. Outcome in cirrhotic patients with acute alcoholic hepatitis after emergency portacaval shunt for bleeding esophageal varices. Am J Surg 1984;147:78-84.

4. Orloff MJ, Bell RH. Long-term survival after emergency porta- caval shunting for bleeding varices in patients with alcoholic cirrhosis. Am J Surg 1986;151:176-183.

5. Orloff MJ, Orloff MS, Ranbotti M, Girard B. Is portal systemic shunt worthwhile in Child's Class C cirrhosis? Long-term results of emergency shunt in 94 patients with bleeding varices. Ann Surg

6. Haddock G, Garden OJ, McKee RF, et al. Esophageal tamponade in the management of acute variceal hemorrhage. Dig Dis Sci

7. Hunt PS, Korman MG, Hansky J, Parkin WG. An 8 year prospective experience with balloon tamponade in emergency control of bleeding esophageal varices. Dig Dis Sci 1982;27:

8. Grace ND. Management of portal hypertension. The Gastroenter-

9. Malt RA, Abbott W, Warshaw A, et al. Randomized trial of emergency mesocaval and portacaval shunts for bleeding esoph- ageal varices. Am J Surg 1978;135:584-589.

10. Cello JP, Grendall JH, Crass RA, et al. Endoscopic sclerotherapy versus portacaval shunt in patients with severe cirrhosis and acute variceal hemorrhage. N Engl J Med 1987;316:11-15.

1992;216:256-268.

1989;34:913-918.

413-416.

ologist 1993;1:39-58.