Causes of hospital death in patients undergoing liver transplantation

Transcription

1 H PB 1999 Volume I, N umber, Causes of hospital death in patients undergoing liver transplantation ST Fanl, CM LOI CL Liu l, BHYong and CL Lai 3 Centre of Liver Diseases and Departments of I Surgery, Anaesthesiology and 3Medicine,The University of Hong Kong, Queen Mary Hospital, Hong Kong, China Background The hospital mortality rate of liver transplantation is about I O%.The aim of this study was to identify the major factors that predispose to these deaths. Method and results Twelve of the first 90 patients (13%) who underwent liver transplantation at this hospital died within the same admission. Univariate analysis of the preoperative and intraoperative parameters showed t hat the volume of blood Conclusions Massive bleeding during liver transplantation predisposed to severe sepsis, organ fai lure and brain infarction. Reduction of bleeding and thus of the volume of blood and blood products transfused should be the pr imary goal to improve the results of liver transplantation. Keywords liver transplant, hospital mortality rate, blood product transfusion. and blood product transfusion was the major factor related to hospital death. Introduction Liver transplantation is an ultra-major operation and probably the most difficult of all transp lant operations. The hospital mortality rate after liver transplantation has ranged from % to 16% [1-6], most series reporting a rate of about 10%. Although liver transplantation is regarded nowadays as a relatively safe operation, a hospital mortality rate of 10% is much too high, compared with other maj or liver operations for which a zero ho pita l mortality rate can be achieved [7]. The preoperative condition of the patient and nature of the transplant proced ure may be used as justification for the relatively high hospital-mortality rate, but every endeavour should be made to improve the results. In this study, the hospital deaths in our first 90 liver transplants were analysed, with a view to reducing this mortality rate in future. Patients and methods From October 1991 to February 1999, 90 liver transplants were carried out in 88 patients. The preoperative diagnoses are listed in Table 1. Two patients with hepatitis of unknown aetiology received re-transplantation. The age of the patients ranged from 7 months to 63 years. There were 55 men and 33 women. Thirty- nine patients (% ) had Table I. Preoperative diagnosis Biliary atresia Alagille syndrome Crigler- Najjar syndrome Hepatitis B cirrhosis HepatitiS C cirrhosis Alcoholic cirrhosis Cryptogenic cirrhosis Autoimmune hepatitis Recurrent pyogenic cholangitis Wilson's disease Polycystic liver Primary biliary cirrhosis Post transplant hepatitis of unknown aetiology Hepatitis B reactivation Fulminant hepatic failure Hepatitis B Drug induced Wilson's disease Cryptogenic Number II I Correspondence to: ST Fan, Deportment of Surgery, The University of Hong Kong, Queen Mary Hospita l, 10 Pokfulam Rood, Hong Kong 1999 Isis Medical Media Ltd. 85

2 ST Fon et 01. between one and four abdominal operations before liver transplantation. The status at the time of transplantation was listed according to the United Network for Organ Sharing (UNOS) criteria [8]. There were 5 patients hospitalised at the time of liver transplantation: 15 required life support, 11 were in the ICU and 6 had routine care. Others were at home, but required frequent hospital admission. The liver grafts were derived from 55 brain-stem dead donors and 35 living donors. The cadaveric grafts were implanted into 50 adults and five children (four with size reduction). For the living donor operation, left lobe grafts (n = 6) were implanted into one child and five adults, left lateral segment grafts (n = 11) were implanted into 11 children and right lobe grafts (n = 18) were implanted into 18 adults. The technique of adult-to-adult living donor liver transplantation using right lobe graft has previously been described [9]. During the transplant operation, a red-cell saver and rapid infusion system were routinely used. Veno-venous bypass was used in most adult patients. Exogenous blood transfusion was given when the red cells recovered from and returned to the patient could not alone maintain haemodynamic stability. Hospital mortality was defined as death within the same hospital admission as liver transplantation. Univariate analysis was made to define factors that were significant in differentiating between patients, with and without hospital mortality. The factors include nine preoperative (Table ) and eight intraoperative parameters (Table 3). The ratio of graft weight to estimated standard liver mass was measured. The estimated standard liver mass was calculated according to the formula devised by Urata and colleagues [10]. All continuous variables were expressed as median (range) and were compared between groups by the Mann-Whitney U test. A X Z test was used to compare discrete variables. Discriminant analysis was performed to determine the cut-off value of significant parameters (as defined by the univariate analysis) that could maximally separate patients who died from those who survived. A P value < 0.05 was taken to indicate statistical significance. Statistical calculations were made with the help of SPSS/PC plus computer software (SPSS Inc, Chicago, IL). Results Sixty-six patients developed one or more postoperative complications (Table ). Twelve patients died during the same hospital admission as liver transplantation (median 15 days, range 5-67 days), giving a hospital mortality rate of 13%. The causes of hospital death included primary graft dysfunction (n = 1), persistent graft rejection (n = 1), intracerebral bleeding (n = 3), hepatic vein stenosis (n = 1), portal vein thrombosis (n = 1), bacterial endocarditis (n = ), systemic candidiasis (n = 1), graft versus host Table. Preoperative data Hospital mortality No hospital mortality p (n = 1) (n = 78) Age 3 years 0.5 years 0.3 ( years) (7 months - 63 years) Sex M = 6, F = 6 M = 9, F = UNOS Life support ICU care 10 Routine care 6 0 At home 3 HBsAg positivity Previous abdominal surgery Platelet x 10 9 L ( ) 79.5 (11-671) 0.09 Prothrombin time (s) 1.9 ( ) 18.6 ( ) 0.7 Bilirubin (Jlmol L - I) 11.5 ( ) 99.5 (11-10) 0.55 Albumin (g L- 1 ) 8.5 (17-) 31 (-5) 0.59 Creatinine (Jlmol L -I) 88 (33-171) 78 ( ) Values are expressed as median (range). 86

3 Causes of hospital death in patients undergoing liver tronsplanation Table 3. Operation data Hospital mortality No hospital mortality p (n = 1) (n = 78) Graft cold ischaemic time (min) (6-776) 0 I (58--78) 0.79 Duration of by-pass (min) 39.5 ( ) 199 (9-500) 0.5 Warm ischaemic time (recipient) (min) 58 (3-89) 55.5 (33-100) 0.93 GW'/ESLM b ( ) ( ) 0.37 Total operation time (min) Blood transfusion (unit) Fresh frozen plasma (unit) Platelet transfusion (unit) 855 (90-110) 0 (-108) 9 (5-66) 0 (5-50) 700 (70-10) (1-3) (1-8) (0-53) Values are expressed as median (range). ' GW = Graft weight. beslm = Estimated standard liver mass. Table. Early complications Intra-abdominal bleeding Portal vein thrombosis Bile leakage Chest infection Pleural effusion Catheter sepsis Primary graft non-function Renal failure Opportunistic infection Intracerebral bleeding Cerebrovascular accident Left brachial plexus II 3 (I) I (I ) 10 5 (I) 5 (3) I Perforated duodenal ulcer Acute pancreatitis Ruptured pseudoaneurysm of hepatic artery I (I) Bacterial endocarditis () Graft versus host disease I ( I) Persistent graft rejection (I) Hepatic vein thrombosis (I) Numbers of patients dying from the complication are given in parentheses. disease (n = 1), and ruptured pseudoaneurysm of the hepatic artery (n = 1). Univariate analys is indicated that only blood transfusion volume, fresh frozen plasma infusion and platelet transfusion were significantly related to hospital mortality (Table 3). By discriminant analys is, blood replacemen t of 5.9 L was the level that could maximally separate patients who died from the survivors (p = ). Discussion In this study, the need for excessive amounts of blood and blood products was a determinant of hospital mortality. The influence of blood transfusion on surgical outcome in many types of operation is well documented. In liver surgery, excessive bleeding has been shown to be detrimental because hypotension and the manoeuvres used to control bleeding from the liver induce severe ischemic injury to the liver remnant [1 1]. In liver transplantation, consequences other than hypoxic injury to the liver are also contributory. In liver transplantation, the bleeding source is usually the tissues and organs adherent to the liver. These include Gerota's fascia, the right adrenal gland, lesser curve of stomach, duodenum and hepatic flexure of colon. The adhesions are in turn due to previous abdominal operations or infection, such as acute cholecystitis, primary bacterial p~ritonitis and sealed perforation of a duodenal ulcer. Collaterals tend to develop within and around the adhesions, division of which is likely to be associated with pro.nounced bleeding that is difficult to control. In this study the worst scenario occurred in two patients with recurrent pyogenic cholangitis, in whom pockets of pus were located within the vascular adhes ions that resulted from multiple previous abdominal operations and rupture of cholangitic liver abscesses into the peritoneal cavity. Excessive bleeding, once started, is impossible to control until the liver graft is implanted and adequate clotting factors are produced. Both patients with recurrent pyogenic cholangitis died after the operation, even though complete haemostasis was achieved. 87

4 ST Fan et 01. Apart from immunosuppression induced by blood transfusion, it is likely that bacterial contamination of the cellsaver system and introduction of bacteria into the infusion line are responsible for the high incidence of postoperative sepsis. Torrential bleeding will inevitably lead to hypotension and possibly brain infarction. It was postulated that the three patients who succumbed to intracerebral bleeding might have sustained a cerebral infarct during the transplant operation and that the infarct bled in the context of a postoperative coagulopathy. Although previous abdominal surgery is a factor that predisposes to massive intraoperative bleeding, it was not found to be a significant factor in the present series, in contradistinction to the report by Palomo Sanchez and co-workers [1]. This fact reflects the varied extent of the previous operations and the probability that in the latter part of the series a more cautious dissection was performed. However, patients with multiple abdominal operations remain at high risk. Careful dissection and prompt replacement of blood loss using the rapid infusion system are essential for success. Is it possible to avoid blood transfusion at all in liver transplantation? Unlike hepatectomy, the chance is remote, but not imposs ible. Three patients with religious objections to blood transfusion have been successfully transplanted without blood transfusion [13]. Is it possible to achieve liver transplantation with a zero hospital mortality rate? Considering the nature of the operation and the premorbid condition of the patients, particularly those in the ICU, such a target is very elusive. Nevertheless, a hospital mortality rate of only % has been reported [3] and, paradoxically, not all those who succumbed in the present series were in a critical condition before operation (Table ). With careful selection of patients, dedicated effort by anaesthetists and ICU physicians, attention from senior surgeons in every case and a large volume of liver transplants within a reasonable period [1], such a target might not be imposs ible to achieve in the future. The impact of hospital deaths on a liver transplant programme is enormous [1,15-17]. Not only is the morale of the team affected, but also the resources spent (usually in vain) are substantial. In Asian countries liver grafts are scarce. Not realizing the complexity and difficulty of the operation, patients and the community at large may express concern that grafts are unnece arily wasted. It would be an easy solution to choo e only good-risk patients for operation. Indeed, Gayow ki and colleagues [1 6] showed that patients with satisfactory biological and physiological parameters had low mortality and morbidity rates after liver transplantation. However, such a policy would deny high-risk patients the only salvage procedure. Operating on high-risk patients remains a challenge. Good results can only be obtained if the team is experienced. Fine judgment, based on individual cases and team confidence, is needed. References Moulin 0, Clement de Clety S, Reynaert M et al. Intensive care for children after orthotopic liver transplantation. Intens Care Med 1989;15:S71-. Moreno GE, Garcia GI, Gonzalez Pinto I et al. Results of orthotopic liver transplantation: a personal experience. Hepatogastroenterology 199;39: Pinson CW, Lopez RR, Benner KG et al. Initial two-year results of the Oregon Liver Transplantation Program. Am ] Surg 1991;161:606-1l. Cherqui 0, Lauzet JY, Rotman N et al. Orthotopic liver transplantation with preservation of the caval and portal flows. Technique and results in 6 cases. Transplantation 199;58: Baliga P, Merion RM, Turcotte JG et al. Preoperative risk factor assessment in liver transplantation. Surgery 199;11: 70-1 l. 6 Gilbert JR, Pascual M, Schoenfeld DA et al. Evolving trends in liver transplantation. An outcome and charge analys is. Transplantation 1999;67 : Fan ST, Lo CM, Liu CL et al. Hepatectomy for hepatocellular carcinoma: toward zero hospital deaths. Ann Surg 1999;9: Bronsther 0, Fung J], Izakis A et al. Prioritization and organ distribution for liver transplantation. ] Am Med Assoc 199; 71: Lo CM, Fan ST, Liu CL et al. Adult-to-adult living donor liver transplantation using extended right lobe grafts. Ann Surg 1997 ;6: Urata K, Kawasaki S, Matsunami H et al. Calculation of child and adult standard liver volume for liver transplantation. Hepatology 1995;1 : Belghiti J, Noun R, Malafosse R et al. Continuous versus intermittent portal triad clamping for liver resection: a controlled studies. Ann Surg 1999;9: Palomo Sanchez JC, Jimenez C, Moreno Gonzalez E et al. 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5 Causes of hospital death in patients undergoing liver tronsplanation 15 Mor E, Jennings L, Gonwa TA et al. The impact of operative bleeding on outcome in transplantation of the liver. Surg Gynecol Obstet 1993; 176: Gayowski T, Marino IR, Singh Net al. Orthotopic liver transplantation in high-risk patients: risk factors associated with mortality and infectious morbidity. Transplantation 1998;65: Sawyer RG, Pelletier SJ, Pruett TL. Increased early morbidity and mortality with acceptable long-term function in severely obese patients undergoing liver transplantation. Clin Transplant 1999;13: