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Hyponatremia Impairs Early Posttransplantation Outcome in Patients With Cirrhosis Undergoing Liver Transplantation

2006; Elsevier BV; Volume: 130; Issue: 4 Linguagem: Inglês

10.1053/j.gastro.2006.02.017

1528-0012

María‐Carlota Londoño, Mónica Guevara, Antoni Rimola, Miquel Navasa, Pilar Taurá, Antoni Mas, Juan‐Carlos García‐Valdecasas, Vicente Arroyo, Pere Ginés,

Organ Transplantation Techniques and Outcomes

Background & Aims: Hyponatremia is associated with reduced survival in patients with cirrhosis awaiting liver transplantation. However, it is not known whether hyponatremia also represents a risk factor of poor outcome after transplantation. We aimed to assess the effects of hyponatremia at the time of transplantation on posttransplantation outcome in patients with cirrhosis. Methods: Two-hundred forty-one consecutive patients with cirrhosis submitted to liver transplantation during a 4-year period (January 2000–December 2003) were included in the study. The main end point was survival at 3 months after transplantation. Secondary end points were complications within the first month after transplantation. Results: Patients with hyponatremia (serum sodium lower than 130 mEq/L) had a greater incidence of neurologic disorders, renal failure, and infectious complications than patients without hyponatremia (odds ratio; 4.6, 3.4 and 2.7, respectively) within the first month after transplantation. By contrast, hyponatremia was not associated with an increased incidence of severe intra-abdominal bleeding, acute rejection, or vascular and biliary complications. Hyponatremia was an independent predictive factor of early posttransplantation survival. Three-month survival of patients with hyponatremia was 84% compared with 95% of patients without hyponatremia (P < .05). Survival was similar after 3 months. Conclusions: In patients with cirrhosis, the presence of hyponatremia is associated with a high rate of neurologic disorders, infectious complications, and renal failure during the first month after transplantation and reduced 3-month survival. In cirrhosis, hyponatremia should be considered not only a risk factor of death before transplantation but also a risk factor of impaired early posttransplantation outcome. Background & Aims: Hyponatremia is associated with reduced survival in patients with cirrhosis awaiting liver transplantation. However, it is not known whether hyponatremia also represents a risk factor of poor outcome after transplantation. We aimed to assess the effects of hyponatremia at the time of transplantation on posttransplantation outcome in patients with cirrhosis. Methods: Two-hundred forty-one consecutive patients with cirrhosis submitted to liver transplantation during a 4-year period (January 2000–December 2003) were included in the study. The main end point was survival at 3 months after transplantation. Secondary end points were complications within the first month after transplantation. Results: Patients with hyponatremia (serum sodium lower than 130 mEq/L) had a greater incidence of neurologic disorders, renal failure, and infectious complications than patients without hyponatremia (odds ratio; 4.6, 3.4 and 2.7, respectively) within the first month after transplantation. By contrast, hyponatremia was not associated with an increased incidence of severe intra-abdominal bleeding, acute rejection, or vascular and biliary complications. Hyponatremia was an independent predictive factor of early posttransplantation survival. Three-month survival of patients with hyponatremia was 84% compared with 95% of patients without hyponatremia (P < .05). Survival was similar after 3 months. Conclusions: In patients with cirrhosis, the presence of hyponatremia is associated with a high rate of neurologic disorders, infectious complications, and renal failure during the first month after transplantation and reduced 3-month survival. In cirrhosis, hyponatremia should be considered not only a risk factor of death before transplantation but also a risk factor of impaired early posttransplantation outcome. Hyponatremia is a common feature of patients with advanced cirrhosis.1Ginès P. Berl T. Bernardi M. Bichet D.G. Hamon G. Jimenez W. Liard J.F. Martin P.Y. Schrier R.W. Hyponatremia in cirrhosis from pathogenesis to treatment.Hepatology. 1998; 28: 851-864Crossref PubMed Scopus (241) Google Scholar The development of hyponatremia is related to an impairment of the renal capacity to excrete solute-free water, which causes retention of water in an amount disproportionate to that of sodium retained. This results in a decrease in serum sodium levels despite the existence of increased renal sodium reabsorption and high total body sodium content.1Ginès P. Berl T. Bernardi M. Bichet D.G. Hamon G. Jimenez W. Liard J.F. Martin P.Y. Schrier R.W. Hyponatremia in cirrhosis from pathogenesis to treatment.Hepatology. 1998; 28: 851-864Crossref PubMed Scopus (241) Google Scholar, 2Ishikawa S. Schrier R.W. Pathogenesis of hyponatremia the role of arginine vasopressin.in: Ginès P. Arroyo V. Rodés J. Schrier R.W. Ascites and renal dysfunction in liver disease. Blackwell Publishing, Oxford, UK2005: 305Crossref Scopus (1) Google Scholar For this reason, this condition is usually referred to as dilutional hyponatremia. Several mechanisms are known to participate in the impairment of solute-free water excretion in cirrhosis and the subsequent development of hyponatremia, including a reduced delivery of filtrate to the distal nephron, impaired renal prostaglandin synthesis, and hypersecretion of arginine vasopressin (the antidiuretic hormone). Among them, the increased plasma levels of arginine vasopressin, which are secondary to a nonosmotic hypersecretion of the hormone from the neurohypophysis, appear to be the most important.1Ginès P. Berl T. Bernardi M. Bichet D.G. Hamon G. Jimenez W. Liard J.F. Martin P.Y. Schrier R.W. Hyponatremia in cirrhosis from pathogenesis to treatment.Hepatology. 1998; 28: 851-864Crossref PubMed Scopus (241) Google Scholar, 2Ishikawa S. Schrier R.W. Pathogenesis of hyponatremia the role of arginine vasopressin.in: Ginès P. Arroyo V. Rodés J. Schrier R.W. Ascites and renal dysfunction in liver disease. Blackwell Publishing, Oxford, UK2005: 305Crossref Scopus (1) Google Scholar It has been known for years that the impairment in solute-free water excretion and hyponatremia are important prognostic markers in the general population of patients with cirrhosis.3Hecker R. Sherlock S. Electrolyte and circulatory changes in terminal liver failure.Lancet. 1956; 271: 1121-1125Abstract PubMed Scopus (134) Google Scholar, 4Arroyo V. Rodes J. Gutierrez-Lizarraga M.A. Revert L. Prognostic value of spontaneous hyponatremia in cirrhosis with ascites.Am J Dig Dis. 1976; 21: 249-256Crossref PubMed Scopus (163) Google Scholar, 5Llach J. Ginès P. Arroyo V. Rimola A. Tito L. Badalamenti S. Jimenez W. Gaya J. Rivera F. Rodés J. Prognostic value of arterial pressure, endogenous vasoactive systems, and renal function in cirrhotic patients admitted to the hospital for the treatment of ascites.Gastroenterology. 1988; 94: 482-487Abstract PubMed Google Scholar, 6Fernandez-Esparrach G. Sanchez-Fueyo A. Gines P. Uriz J. Quinto L. Ventura P.J. Cardenas A. Guevara M. Sort P. Jimenez W. Bataller R. Arroyo V. Rodés J. A prognostic model for predicting survival in cirrhosis with ascites.J Hepatol. 2001; 34: 46-52Abstract Full Text Full Text PDF PubMed Scopus (215) Google Scholar In addition, several recent studies in patients with cirrhosis awaiting liver transplantation have extended these observations by showing that patients with hyponatremia are at high risk of early death before transplantation and that the prognostic value of low serum sodium concentration is independent of the severity of cirrhosis, as assessed by model for end-stage liver disease (MELD) score.7Heuman D.M. Abou-Assi S.G. Habib A. Williams L.M. Stravitz R.T. Sanyal A.J. Fisher R.A. Mihas A.A. Persistent ascites and low serum sodium identify patients with cirrhosis and low MELD scores who are at high risk for early death.Hepatology. 2004; 40: 802-810Crossref PubMed Scopus (425) Google Scholar, 8Biggins S.W. Rodriguez H.J. Bacchetti P. Bass N.M. Roberts J.P. Terrault N.A. Serum sodium predicts mortality in patients listed for liver transplantation.Hepatology. 2005; 41: 32-39Crossref PubMed Scopus (313) Google Scholar, 9Ruf A.E. Kremers W.K. Chavez L.L. Descalzi V.I. Podesta L.G. Villamil F.G. Addition of serum sodium into the MELD score predicts waiting list mortality better than MELD alone.Liver Transpl. 2005; 11: 336-343Crossref PubMed Scopus (339) Google Scholar Nevertheless, despite this growing interest in the relationship between hyponatremia and liver transplantation, to our knowledge there is no information as to whether the presence of hyponatremia before transplantation may influence posttransplantation outcome. Therefore, the current study was designed to investigate whether pretransplantation hyponatremia may affect morbidity and/or mortality after transplantation. The current investigation is a single-center retrospective cohort study of 241 consecutive adult patients with cirrhosis submitted to liver transplantation at the Hospital Clínic of Barcelona during a 4-year period (January 2000–December 2003). Seventy other patients undergoing transplantation also at our center during this period of time were excluded from the study because of retransplantation (n = 24), liver diseases other than cirrhosis (acute liver failure [n = 19], familial amyloidotic polyneuropathy [n = 13], polycystic liver disease [n = 4], and hemangioendothelioma and idiopathic portal hypertension [1 patient each]), and combined liver-kidney transplantation (n = 8). Complications of cirrhosis before transplantation were managed according to preestablished protocols as follows. Moderate ascites was treated with low-sodium diet and diuretics, and large ascites was treated with paracentesis plus albumin, followed by low-sodium diet and diuretics, as described in detail elsewhere.10Ginès P. Cardenas A. Arroyo V. Rodés J. Management of cirrhosis and ascites.N Engl J Med. 2004; 350: 1646-1654Crossref PubMed Scopus (649) Google Scholar Hyponatremia was managed with fluid restriction (1000 mL/day), except for those patients with severe hyponatremia (serum sodium <120 mEq/L) (n = 3), who were treated with hypertonic saline. The administration of hypertonic saline is not a standard therapy for dilutional hyponatremia in cirrhosis because its effects on sodium concentration are inconsistent and is associated with rapid accumulation of ascites and edema.11Moore K.P. Wong F. Ginès P. Bernardi M. Ochs A. Salerno F. Angeli P. Porayko M. Moreau R. Garcia-Tsao G. Jimenez W. Planas R. Arroyo V. The management of ascites in cirrhosis report on the consensus conference of the International Ascites Club.Hepatology. 2003; 38: 258-266Crossref PubMed Scopus (672) Google Scholar, 12Ginès P. Arroyo V. Rodés J. Ascites, hepatorenal syndrome and spontaneous bacterial peritonitis.in: McDonald J. Burroughs A. Feagan B.G. Evidence based-gastroenterology and hepatology. Blackwell Publishing, Oxford, UK2005: 487Google Scholar Nevertheless, in the absence of effective alternative therapies, this treatment was used in patients with severe hyponatremia in an attempt to improve serum concentration before transplantation and reduce the risk of central pontine myelinolysis (CPM) related to rapid increases in serum sodium after transplantation.13Wszolek Z.K. McComb R.D. Pfeiffer R.F. Steg R.E. Wood R.P. Shaw Jr, B.W. Markin R.S. Pontine and extrapontine myelinolysis following liver transplantation. Relationship to serum sodium.Transplantation. 1989; 48: 1006-1012Crossref PubMed Scopus (117) Google Scholar Of the 3 patients with severe hyponatremia treated with hypertonic saline, serum sodium concentration did not change significantly in 2 (from 116 and 115 mEq/L before treatment to 118 and 114 mEq/L after treatment, respectively) and increased markedly in 1 (from 112 mEq/L to 131 mEq/L). All of these 3 patients were alive 1 year after transplantation. Hepatorenal syndrome (HRS) in patients awaiting liver transplantation was treated according to following criteria: patients with type 1 HRS and those with type 2 HRS with serum creatinine greater than 2 mg/dL (174 μmol/L) received terlipressin and albumin.14Ginès P. Guevara M. Arroyo V. Rodés J. Hepatorenal syndrome.Lancet. 2003; 362: 1819-1827Abstract Full Text Full Text PDF PubMed Scopus (489) Google Scholar Patients with HRS type 2 with serum creatinine equal to or lower than 2 mg/dL (174 μmol/L) were not treated with terlipressin and albumin because the information on the efficacy of treatment in this group of patients was very limited at the time of the study.14Ginès P. Guevara M. Arroyo V. Rodés J. Hepatorenal syndrome.Lancet. 2003; 362: 1819-1827Abstract Full Text Full Text PDF PubMed Scopus (489) Google Scholar Of the 241 patients included in the study, 14 patients had HRS before transplantation, and 2 of them met criteria for treatment. One patient had type 1 HRS and underwent transplantation after 3 days of therapy while renal function was improving (serum creatinine decreased from 6.7 mg/dL to 3.6 mg/dL), whereas the other patient had type 2 HRS and recovered from HRS with serum creatinine decreasing from 2.1 mg/dL to 1.0 mg/dL. Spontaneous bacterial peritonitis was treated with ceftriaxone plus intravenous albumin followed by norfloxacin to prevent recurrence, and the other complications of cirrhosis were managed with conventional therapy.10Ginès P. Cardenas A. Arroyo V. Rodés J. Management of cirrhosis and ascites.N Engl J Med. 2004; 350: 1646-1654Crossref PubMed Scopus (649) Google Scholar, 15Cardenas A. Ginès P. Management of complications of cirrhosis in patients awaiting liver transplantation.J Hepatol. 2005; 42: S124-S133Abstract Full Text Full Text PDF PubMed Scopus (67) Google Scholar According to the transplantation protocol in our center, all patients were seen by an experienced hepatologist immediately before transplantation. Preoperative routine workout included a complete medical history, with particular emphasis on the possible events occurring the preceding days, physical examination; electrocardiogram; chest x-ray; and blood samples measuring liver and renal function tests, serum electrolytes, blood cell count, urine sediment, and coagulation parameters. Biochemical parameters measured immediately before transplantation were those used to evaluate the effect of liver and renal function on patient’s outcome after transplantation. In patients with ascites, a diagnostic paracentesis was performed for cell count and culture. Patients were then transferred to the surgical room in which liver transplantation was performed. In all patients, transplantation was performed using the piggyback technique.16Gonzalez F.X. Garcia-Valdecasas J.C. Grande L. Pacheco J.L. Cugat E. Fuster J. Lacy A.M. Taura P. Lopez-Boado M.A. Rimola A. Visa J. Vena cava vascular reconstruction during orthotopic liver transplantation a comparative study.Liver Transpl Surg. 1998; 4: 133-140Crossref PubMed Scopus (36) Google Scholar After surgery, patients were transferred to the intensive care unit for continued care. Standard liver and renal function tests were measured twice a day during the first 2 days and daily thereafter, unless otherwise indicated. Stable patients were transferred to a standard ward in which blood samples were routinely obtained at least twice a week to measure blood cell count, liver and renal function tests, serum electrolytes, and coagulation parameters. After discharge from the hospital, patients were followed in the outpatient clinic every month during the first 3 months and every 2–3 months during the first year, or more frequently if clinically indicated. Standard immunosuppression in our center consisted of the administration of prednisone and tacrolimus. Prednisone was given at decreasing doses from 200 mg/day the first day to 20 mg/day at day 6 after transplantation. This dose was maintained until 1 month after transplantation. If there were no signs of rejection, prednisone was tapered progressively and stopped within 6–12 months after transplantation. Tacrolimus was started the first day after transplantation at a dose of 0.1 mg/kg/day and then adjusted to maintain blood levels between 8 and 15 ng/mL within the first 3 months. The dose of tacrolimus was then adjusted to achieve target blood levels of 7–12 ng/mL during months 4 to 12 and 5 to 10 ng/mL thereafter. Patients with diabetes mellitus before transplantation were treated with cyclosporine instead of tacrolimus, at an initial dose of 10 mg/kg per day to achieve trough blood levels between 150 and 300 ng/mL during the first 3 months, 100–200 ng/mL from months 4 to 12, and 50–150 ng/mL thereafter. In patients with serum creatinine levels equal to or greater than 1.5 mg/dL before transplantation or immediately after transplantation, the initiation of tacrolimus or cyclosporine administration was delayed until a reduction in serum creatinine concentration was observed. In the meantime, patients were treated with prednisone, at identical doses as described previously, and mycophenolate mofetil at a dose of 1 g/12 hours. In patients developing renal failure after transplantation, the doses of tacrolimus or cyclosporine were reduced or the drugs temporarily withdrawn. In patients in whom these drugs were withdrawn, mycophenolate mofetil was given until renal function recovered. The primary end point of this study was survival at 3 months after transplantation. Secondary end points were the development of complications, including early severe intra-abdominal bleeding and renal failure, neurologic disorders, infectious complications, acute rejection, and biliary and vascular complications during the first month after transplantation. Severe intra-abdominal bleeding was defined as the presence of abdominal hemorrhage requiring reintervention for bleeding control within the first 48 hours after surgery, elimination of intra-abdominal hematomas, and/or removal of gauzes used for packing during the surgical procedure. Renal failure was defined as an increase in serum creatinine concentration of greater than 50% of the immediate pretransplantation value to a final value greater than 2 mg/dL (174 μmol/L). Neurologic disorders were defined as the development of signs or symptoms of abnormal neurologic function and were classified as severe, which included coma, seizures, and/or CPM, and nonsevere (all other abnormalities of neurologic function).17Bronster D.J. Emre S. Boccagni P. Sheiner P.A. Schwartz M.E. Miller C.M. Central nervous system complications in liver transplant recipients—incidence, timing, and long-term follow-up.Clin Transplant. 2000; 14: 1-7Crossref PubMed Scopus (178) Google Scholar Infectious complications were defined by the presence of systemic or local signs of infection together with positive cultures and/or compatible radiologic findings requiring intravenous administration of antimicrobial agents. Acute rejection was diagnosed on the basis of Banff criteria.18Ormonde D.G. de Boer W.B. Kierath A. Bell R. Shilkin K.B. House A.K. Jeffrey G.P. Reed W.D. Banff schema for grading liver allograft rejection utility in clinical practice.Liver Transpl Surg. 1999; 5: 261-268Crossref PubMed Scopus (90) Google Scholar Biliary complications were defined as the presence of biliary strictures or bile leaks diagnosed by imaging techniques. Vascular complications were defined as the development of thrombosis or stenosis of hepatic artery or portal vein diagnosed by doppler ultrasound and angiography. Patients receiving a liver from a living donor (n = 35) were excluded from the analysis of biliary and vascular complications because this population has an increased risk of surgical complications compared with patients receiving a liver from a cadaveric donor.19Olthoff K.M. Merion R.M. Ghobrial R.M. Abecassis M.M. Fair J.H. Fisher R.A. Freise C.E. Kam I. Pruett T.L. Everhart J.E. Hulbert-Shearon T.E. Gillespie B.W. Emond J.C. A2ALL Study GroupOutcomes of 385 adult-to-adult living donor liver transplant recipients. A report from the A2ALL consortion.Ann Surg. 2005; 242: 314-325PubMed Google Scholar Finally, hyponatremia was defined as serum sodium concentration lower than 130 mEq/L according to the definition of the International Ascites Club.1Ginès P. Berl T. Bernardi M. Bichet D.G. Hamon G. Jimenez W. Liard J.F. Martin P.Y. Schrier R.W. Hyponatremia in cirrhosis from pathogenesis to treatment.Hepatology. 1998; 28: 851-864Crossref PubMed Scopus (241) Google Scholar Clinical and analytical variables were analyzed as possible predictors of survival in a univariate analysis, and survival curves (Kaplan–Meier method) were compared with the log-rank test. A multivariate analysis of survival was performed using a Cox regression method. Comparisons of variables between groups of patients were made using the nonparametric Mann–Whitney test for continuous data and the χ2 test or Fisher test for categorical data. Statistical analysis was performed using the SPSS 10 for Windows (SPSS Inc., Chicago, IL). Results are expressed as mean ± SD. P < .05 was considered statistically significant. The study population includes 241 consecutive adult patients with cirrhosis undergoing liver transplantation during a 4-year period, from January 2000 to December 2003. Two hundred six out of the 241 patients included in the study (85%) received a liver from a cadaveric donor, whereas the remaining 35 patients (15%) received a graft from a living donor. Demographic, clinical, and biochemical data of patients included in the study at time of transplantation are shown in Table 1.Table 1Demographic and Clinical Data and Liver and Renal Function Tests at Time of Transplantation in the 241 Patients Included in StudyAge (y)55 ± 9 (24–69)Sex Male152 (63%) Female89 (37%)Etiology of cirrhosis, No. patients Hepatitis C135 (56%) Alcohol46 (19%) OtheraHepatitis B (18 patients; 7%), hepatitis C and alcohol (13 patients; 5%), chronic cholestatic liver diseases (11 patients; 5%), and other (18 patients; 7%).60 (25%)Ascites162 (67%)Hepatic encephalopathy, No. patients Past history82 (34%) At transplantation15 (6%)Renal failure,bAs defined by serum creatinine greater than 1.5 mg/dL (133 μmol/L). Causes of renal failure were hepatorenal syndrome in 14 (type I in 1 and type II in 13) and chronic, nonfunctional renal diseases in 5 patients. No. patients19 (8%)Serum bilirubin (mg/dL)2.8 ± 3.5 (0.3–30)Prothrombin time Ratio (%)65 (26–100) INRcInternational normalized ratio was calculated according to the following formula: (prothrombin time of patient/control prothrombin time)ISI, ISI being the International Sensitivity Index for thromboplastins.1.5 ± 0.3 (1–3.3)Albumin (g/L)32 ± 6 (18–47)Serum creatinine (mg/dL)1.0 ± 0.3 (0.4–3.6)Serum sodium (mEq/L)136 ± 5 (114–146)MELD score17 ± 6 (6–40)Child-Pugh score8 ± 2 (5–13)NOTE. Values are mean ± SD (ranges).a Hepatitis B (18 patients; 7%), hepatitis C and alcohol (13 patients; 5%), chronic cholestatic liver diseases (11 patients; 5%), and other (18 patients; 7%).b As defined by serum creatinine greater than 1.5 mg/dL (133 μmol/L). Causes of renal failure were hepatorenal syndrome in 14 (type I in 1 and type II in 13) and chronic, nonfunctional renal diseases in 5 patients.c International normalized ratio was calculated according to the following formula: (prothrombin time of patient/control prothrombin time)ISI, ISI being the International Sensitivity Index for thromboplastins. Open table in a new tab NOTE. Values are mean ± SD (ranges). Nineteen of the 241 patients (8%) had hyponatremia at the time of transplantation. Patients with hyponatremia at transplantation had been hyponatremic for a mean period of 106 days (range, 12–237days). Table 2 shows the comparison of demographic and clinical data and liver and renal function tests in patients with and without hyponatremia at transplantation. Patients with hyponatremia had greater frequency of ascites and encephalopathy, more marked impairment of liver function tests, and higher MELD and Child–Pugh scores, compared with values in patients without hyponatremia. The frequency of HRS was similar in patients with and without hyponatremia (5% and 6%, respectively; P = ns).Table 2Demographic and Clinical Data and Liver and Renal Function Tests at Time of Transplantation According to Presence or Absence of HyponatremiaVariableHyponatremia (n = 19)No hyponatremia (n = 222)P valueAge (y)52 ± 13 (24–65)55 ± 9 (24–69)nsSex Male9 (47%)143 (64%)ns Female10 (53%)79 (36%)nsEtiology of cirrhosis, No. patientsns Hepatitis C11 (58%)124 (56%) Alcohol4 (21%)42 (19%) Other4 (21%)56 (25%)Ascites, No. patients19 (100%)143 (64%)<.01DiureticsaPatients being treated with diuretics at the time of transplantation. Number of patients12 (63%)119 (54%)ns Furosemide (mg/day)80 ± 69 (40–160)45 ± 23 (20–160)ns Spironolactone (mg/day)167 ± 121 (100–400)105 ± 42 (25–300)nsHepatorenal syndrome, No. patients1 (5%)13 (6%)nsHepatic encephalopathy, No. patients Past history9 (47%)73 (33%)ns At transplantation4 (21%)11 (5%).01Serum bilirubin (mg/dL)7.5 ± 7.5 (0.6–30)2.4 ± 2.6 (0.3–29)<.01Prothrombin time Ratio (%)55 ± 22 (26–98)66 ± 16 (32–100).02 INR1.7 ± 0.5 (1–2.6)1.5 ± 0.3 (1–3.3)nsAlbumin (g/L)28 ± 5 (22–41)33 ± 6 (18–47)<.01Serum creatinine (mg/dL)1.2 ± 0.6 (0.4–3.6)1.0 ± 0.3 (0.4–2.7)nsSerum sodium (mEq/L)125 ± 4 (114–129)138 ± 3 (130–146)<.01MELD score20 ± 7 (9–40)17 ± 5 (6–30).04Child-Pugh score10 ± 2 (6–13)8 ± 2 (5–13)<.01NOTE. Values are mean ± SD (ranges).a Patients being treated with diuretics at the time of transplantation. Open table in a new tab NOTE. Values are mean ± SD (ranges). One hundred twenty-seven of the 241 patients (53%) developed at least 1 major complication during the 30-day postoperative period. Overall, the most common complication was acute rejection in 52 patients (21%). In all patients, acute rejection resolved after the administration of steroid boluses and/or adjustment of doses of baseline immunosuppressive agents. Forty-six patients (18% of the whole series) developed infectious complications: 15 (33%) had pneumonia, 9 (20%) biliary tract infection, 7 (15%) urinary tract infection, 7 (15%) intraabominal infection, 5 (11%) catheter-related sepsis, and 3 (7%) sepsis of unknown origin. Resolution of the infection was obtained in 34 of the 46 patients (74%). In the remaining 12 patients, infection did not resolve and contributed to the death of the patients. Thirty-nine of the 241 patients (16%) developed renal failure within the 30-day postoperative period. Peak serum creatinine in these patients was 3.7 mg/dL (range, 2.1–9.1 mg/dL), and the median time to reach the peak value was 8 days. Nine of the 39 patients (23%) with renal failure required renal replacement therapy. No patient required long-term hemodyalisis. Patients who developed renal failure after transplantation did not have higher levels of immunosuppressive agents (tacrolimus or cyclosporine) throughout the 30-day postoperative period compared with those patients who did not develop renal failure. Thirty-two of the 241 (13%) patients included in the study developed neurologic disorders within the 30-day postoperative period. Median time to the development of neurologic disorders was 10 days (range, 2–29 days). Twenty-nine of the 32 patients (91%) developed altered mental status without focal motor disorders, associated with seizures in 4 patients, in the absence of significant lesions in cerebral computerized tomography (CT) or magnetic resonance imaging (MRI); 2 patients developed CPM and 1 patient cerebral hemorrhage. Serum sodium concentrations before and immediately after transplantation in the 2 patients who developed CPM were 146 mEq/L and 124 mEq/L vs 142 mEq/L and 140 mEq/L, respectively. In all patients, neurologic function recovered completely, except for the patient with cerebral hemorrhage and 1 of the 2 patients with CPM, who died 38 and 103 days after transplantation, respectively. This latter patient died from hepatic artery thrombosis when symptoms because of CPM were improving. There were no significant differences between patients who did and did not develop neurologic complications with respect to the blood levels of immunosuppressive agents (tacrolimus or cyclosporine) obtained throughout the 30-day postoperative period. Twenty-five of the 241 patients (10%) had severe intra-abdominal bleeding. The average number of packed red blood cells transfused in these 25 patients was 19, compared with only 5 in the remaining 216 patients (P < .0001). Resolution of the intra-abdominal bleeding was obtained in 23 patients. Persistent bleeding contributed to death in the remaining 2 patients. Finally, out of the 206 patients receiving a liver from a cadaveric donor, 7 patients (3%) developed biliary complications, and 11 patients (5%) developed vascular complications during the 30-day postoperative period. To assess whether the presence of hyponatremia before transplantation was associated with an increased risk of complications after transplantation, patients were divided according to the presence or absence of hyponatremia at transplantation, and the rate of complications between the 2 groups was compared. As shown in Table 3, patients with hyponatremia had a greater risk of developing complications after transplantation than patients without hyponatremia, the difference being at the level of significance. When complications were analyzed individually, patients with hyponatremia had a significantly greater frequency of neurologic disorders, renal failure, and infectious complications. Severe neurologic disorders were also more frequent in patients with hyponatremia as compared with patients without hyponatremia (21% and 5%, respectively; P = .003). By contrast, the presence of hyponatremia was not associated with an increased risk of severe intra-abdominal bleeding, acute rejection, and biliary or vascular complications. Figure 1 shows the cumulative probability of de