Readmission to the intensive care unit after liver transplantation.

OBJECTIVE: We undertook this study to understand the factors at our transplant center that contribute to patients' return to the ICU after their liver transplant and their initial discharge from that unit. Patients who, after liver transplantation, fail discharge from the Intensive Care Unit (ICU) and must be readmitted to that unit may well utilize many more resources than those patients who are well enough to stay out of the ICU. DESIGN: A retrospective review of a prospectively maintained liver transplant research database followed by a retrospective review of (a subgroup) patient charts and contemporaneous controls. SETTING: A large metropolitan tertiary care center and adult liver transplant center. PATIENTS: A total of 1,197 consecutive adult patients who underwent their initial liver transplantation from 1984 to 1996. INTERVENTION: Readmission to the intensive care unit after adult liver transplantation and discharge from that unit. MAIN RESULTS: Only recipient age, pretransplant synthetic function labs (protime and albumin), bilirubin levels, and intraoperative blood product requirements could be statistically linked to the group requiring ICU readmission. The primary etiology for ICU readmission was cardiopulmonary deterioration. Readmission was associated with significantly lower patient and graft survivals. A detailed review of 23 patients transplanted from October 1994 to June 1996 was made, with special emphasis on cardiopulmonary status (hemodynamics, respiratory variables, and chest radiograph findings). This subgroup was compared with 30 temporally matched controls who were not readmitted to the ICU. Intravascular fluid overload and lower inspiratory capacity were significant factors related to ICU readmission. Readmitted patients had a longer hospitalization with higher hospital charges than the control group. CONCLUSIONS: We conclude that the most important means of preventing ICU readmission in liver transplantation patients is to optimize cardiopulmonary function and status. Close monitoring of fluid balance to avoid hypervolemia is essential. Readmitted patients have a greater resource utilization and have lower survival rates.

Oral transmucosal fentanyl citrate as an additional premedicant for adult cardiac surgery patients.

OBJECTIVE: To investigate the efficacy of a combination of midazolam and oral transmucosal fentanyl citrate (OTFC) as a preoperative medication for adult cardiac surgery patients compared with the use of midazolam alone. DESIGN: A randomized, prospective study. SETTING: University teaching hospital. PARTICIPANTS: Patients scheduled for elective coronary artery bypass surgery. INTERVENTIONS: All patients were given 50 micrograms/kg of midazolam intramuscularly in their rooms. Group I received 300 micrograms of OTFC Oralet (Anesta Corp, Salt Lake City, UT) if they weighed less than 70 kg and 400 micrograms of OTFC Oralet if they weighed more than 70 kg. Group II received a placebo Oralet. A radial artery catheter, two internal jugular venous catheters, and a pulmonary artery catheter inserted through one of the internal jugular catheters were placed in each study patient. Fentanyl was administered intravenously as a rescue drug. MEASUREMENTS AND MAIN RESULTS: Ninety percent of midazolam/OTFC patients reported feeling no pain during catheter placement, compared with 50% of midazolam/placebo patients. Fifty percent of the placebo group required fentanyl supplement of 50 micrograms intravenously because of complaints of pain, compared with 10% of the OTFC group. The midazolam/OTFC group scored approximately 20% better than the placebo group in the independent observer score of patient analgesia and the anesthesiologist rating for ease of invasive catheter placement. No myocardial ischemic events were noted in either group as determined by electrocardiogram. All patients found the Oralet mode of delivery very acceptable. CONCLUSIONS: The OTFC Oralet provides effective analgesia and sedation when combined with midazolam for invasive catheter placement in adult cardiac surgery patients. The OTFC Oralet with its gradual onset lessens the possibility of overmedicating with fentanyl, and it offers a very acceptable mode of delivery for a preemptive analgesic.

Severe pulmonary hypertension in liver transplant candidates.

Advanced liver disease with portal hypertension may be associated with pulmonary hypertension. A review of 1,205 consecutive liver transplant patients was made to assess the incidence and severity of pulmonary hypertension in patients with end-stage liver disease. Postoperative data were reviewed to determine if outcome was influenced and, in patients with severe pulmonary hypertension, whether pulmonary hypertension was reversed after transplantation. The hemodynamic data of 5 patients who were found to have severe pulmonary hypertension before transplantation and did not receive transplants were also reviewed. The incidence of pulmonary hypertension in the patients who received transplants was 8.5% (n = 102; mean pulmonary artery pressure, > 25 mmHg). The incidence of mild pulmonary hypertension was 6.72% (n = 81; systolic pulmonary artery pressure, 30 to 44 mmHg); that of moderate pulmonary hypertension was 1.16% (n = 14; systolic pulmonary artery pressure, 45 to 59 mmHg); and that of severe pulmonary hypertension was 0.58% (n = 7; systolic pulmonary artery pressure, > 60 mmHg). Mild and moderate pulmonary hypertension did not influence the outcome of the procedure. Severe pulmonary hypertension was associated with mortality rates of 42% at 9 months posttransplantation and 71% at 36 months posttransplantation. Only 2 of 7 patients with severe pulmonary hypertension have survived liver transplantation with a good quality of life. The remaining 5 patients continued to deteriorate with progressive right heart failure with no evidence of amelioration of the pulmonary hypertension. This experience supports the view that in most patients who have severe pulmonary hypertension associated with advanced liver disease, it is caused by fixed pathological changes in the pulmonary vasculature, is not reversible with liver transplantation, and is associated with a very high perioperative mortality rate.

Continuous small-dose tranexamic acid reduces fibrinolysis but not transfusion requirements during orthotopic liver transplantation.

Tranexamic acid (TA) is a synthetic drug that inhibits fibrinolysis. It has been administered to decrease the use of blood products during cardiac surgery and orthotopic liver transplantation when infused in larger doses. A small-dose infusion of aprotinin causes a reduction in fibrinolysis and blood product requirement during orthotopic liver transplantation without apparent risk of intravascular thrombosis. This prospective study was designed to investigate whether a small-dose infusion of TA would be equally effective in reducing fibrinolysis and blood product transfusions during orthotopic liver transplantation. A double-blind, controlled study was undertaken to compare the efficacy of a small-dose TA infusion with that of a placebo. Thirty-two consecutive patients were randomized either to the TA group (n = 16), which received an intravenous infusion of 2 mg x kg(-1) x h(-1), or to the control group (n = 16), which received an identical volume of normal saline. Coagulation values were measured, a field rating was made by the surgeon, and a thromboelastogram was produced at four predetermined intervals throughout the case-before TA infusion was started, after portal vein ligation, 10 min after reperfusion, and at the end of surgery. Intraoperative transfusion requirements were recorded during the procedure and for the first 24 h postoperatively. A record was kept of any intraoperative epsilon-aminocaproic acid administered for uncontrolled fibrinolysis. The thromboelastogram clot lysis index was significant for lysis in the control group during both the anhepatic and the neohepatic phases (P < 0.01 and P < 0.05, respectively) when compared with the TA group. Fibrin degradation products were significantly increased (>20 microg/mL) in the control group at reperfusion (P < 0.03) and at the end of surgery (P < 0.01). D-dimers were also significantly increased (>1 mg/L) in the control group at the end of surgery (P < 0.04). Nine of the 16 control patients versus 3 of the 16 TA patients required epsilon-aminocaproic acid rescue for fibrinolysis. There were no other significant differences between groups. Transfusion requirements during surgery and for the first 24 h postoperatively did not differ significantly between the two groups. We conclude that the use of small-dose TA reduces fibrinolysis but not transfusion requirements during orthotopic liver transplantation.

Pharmacokinetics of rocuronium during the three stages of liver transplantation.

BACKGROUND: Little is known about the influence of liver transplantation on the pharmacokinetics of most anesthetic drugs. The authors determined the pharmacokinetics of rocuronium during liver transplantation and examined whether variability in pharmacokinetics could explain variability in recovery of neuromuscular function. METHODS: Twenty patients undergoing liver transplantation were given rocuronium, 600 microg/kg, after induction of anesthesia and again after perfusion of the transplanted liver. Plasma was sampled to determine rocuronium concentrations. Pharmacokinetic models were fit to rocuronium concentrations versus time data using a mixed-effects population approach. Various models permitted changes in clearance (Cl) or central compartment volume to account for changes in hepatic function and circulatory status during the paleohepatic, anhepatic, and neohepatic periods. Time to initial recovery of four twitches of the orbicularis oculi was determined. RESULTS: During the paleohepatic and anhepatic periods, the typical value of Cl was 2.47 ml x kg(-1) x min(-1) and was not influenced by the magnitude of preexisting liver disease (as evidenced by prothrombin time, bilirubin, serum albumin, alanine transaminase [ALT], and aspartate transaminase [AST]). During the neohepatic period, the typical value of Cl varied as a function of the duration of warm ischemia of the hepatic allograft and was 2.72 ml x kg(-1) x min(-1) for a patient with an average 60-min period of warm ischemia; time to neuromuscular recovery varied as a function of Cl. CONCLUSIONS: Despite prolonged hypothermic ischemia, the newly transplanted liver eliminates rocuronium as well as the diseased native liver (and comparably with historical control values). However, some patients had decreased rocuronium Cl during the neohepatic period, apparently a result of prolonged graft warm ischemia. The authors' finding of preservation of hepatic drug elimination in the hepatic allograft is consistent with limited data for other drugs evaluated during anesthesia.

Duration of rocuronium-induced neuromuscular block during liver transplantation: a predictor of primary allograft function.

The prolongation of vecuronium-induced neuromuscular block has been reported as a predictor of hepatic allograft dysfunction. This study investigates the duration of action of rocuronium, which also relies on hepatic clearance, to examine whether it also is prolonged with allograft dysfunction. Fifty-seven patients undergoing orthotopic liver transplant were given rocuronium (0.6 mg/kg) prior to allograft placement and the recovery of contraction of the orbicularis oculi muscle to a 2-Hz train-of-four stimulus was recorded. Fifteen minutes after reperfusion of the allograft, rocuronium (0.6 mg/kg) was administered and the time to recovery of muscle contraction to a train-of-four stimulus (train-of-four time) was again recorded. The patients were divided into two groups according to posttransplant liver function. Group I consisted of 50 patients with immediate normal liver function. Group II contained 7 patients with primary dysfunctional livers. Primary dysfunction was determined by peak serum aspartate aminotransferase and alanine aminotransferase levels > 2000 U/L, and prothrombin time > 16 s. The train-of-four time in Group II was prolonged compared with Group I (P < 0.05). Immediate graft function testing using the recovery time from rocuronium of > 150 min has a positive predictive value of 100% and a negative predictive value of 96%. The sensitivity and specificity is 71% and 100%, respectively. Receiver operating characteristic analysis supports this conclusion.

Nitric oxide does not reverse pulmonary hypertension associated with end-stage liver disease: a preliminary report.

Pulmonary hypertension is a well known, though uncommon complication of end-stage liver disease (ESLD). Patients with severe pulmonary hypertension and ESLD undergoing orthotopic liver transplantation (OLT) may develop right ventricular failure and death. This study investigates the reversibility of pulmonary hypertension by the inhalation of nitric oxide in patients under evaluation for OLT. Ten patients with ESLD who were discovered to have moderate to severe pulmonary hypertension were administered nitric oxide via face mask in concentrations ranging from 0 to 80 ppm. Inhaled nitric oxide is a potent pulmonary vasodilator without apparent systemic effects. Nitric oxide had no demonstrable effect on mean pulmonary artery pressure (PAP) (37 vs. 37 mm Hg), transpulmonary gradient (TPG) (26 vs. 26 mm Hg), or pulmonary vascular resistance (PVR) (295 vs. 288 dynes x sec x cm (-5)). Two patients were discovered to have an elevated pulmonary artery occlusion pressure (PAOP) on baseline readings. The cause of pulmonary hypertension in these two patients was secondary to volume overload as a result of hepato-renal syndrome rather than primary pulmonary arteriolar pathology and was responsive to diuresis or dialysis but not to nitric oxide therapy. In conclusion nitric oxide does not reverse pulmonary hypertension associated with ESLD.