W. Hewitt

Clinical experience with a porcine hepatocyte-based liver support system.

The only clinically proven effective treatment of fulminant hepatic failure (FHF) is orthotopic liver transplant (OLT). However, many patients die before an organ becomes available. Thus, there is a need for development of an extracorporeal liver support system to “bridge” these patients either to OLT or spontaneous recovery. We developed a bioartificial liver (BAL) based on plasma perfusion through a circuit of a hollow-fiber cartridge seeded with matrix-anchored porcine hepatocytes to treat patients with severe acute liver failure. Two groups of patients were studied. Group 1 (n = 12): patients with FHF. All patients were successfully “bridged” to OLT. “Bridge” time to OLT was 21-96 hr (mean: 39.3 hr). All patients were discharged neurologically intact. Reversal of decerebration was noted in all 11 deep stage 4 coma patients. There was reduction in intracranial pressure (ICP mmHg, 18.2 ± 2.2 to 8.5 ± 1.2; p<0.004) and increase in cerebral perfusion pressure (CPP mmHg, 71.1 ± 4.0 to 84.7 ± 2.6; p<0.006). Laboratory values pre- and post- BAL treatment: glucose (mg/dl) 122 ± 11 to 183 ± 21, p<0.002; ammonia (μmol/l) 155.6 ± 13.2 to 121.6 ± 9.5, p<0.02; total bilirubin (mg/dl) 21.6 ± 2.8 to 18.2 ± 2.2, p<0.001; PT (sec) 23.2 ± 1.7 to 21.9 ± 1.0, p<0.3. Group II (n=8): patients with chronic liver failure experiencing acute exacerbation. Two patients survived and later underwent OLT. Six patients (not OLT candidates) died 1-14 days after last BAL treatment. Laboratory values pre- and post-treatment: ammonia (μmol/l) 201 ± 47 to 143 ± 25, p<0.06; total bilirubin (mg/dl) 22.8 ± 5.2 to 19.5 ± 4.4, p<0.01; PT (sec) 22.5 ± 2.0 to 21.8 ± 1.1, p<0.6. Conclusion: our clinical experience with the BAL suggests that it may serve as “bridge” to OLT in patients with FHF primarily by reversing intracranial hypertension, but it is not a substitute for OLT in patients with end-stage liver disease who are non-transplant candidates.

Intracranial pressure: Effects of pneumoperitoneum in a large-animal model

AbstractBackground: The effects of pneumoperitoneum on intracranial pressure (ICP) have received relatively little attention. This study was undertaken to investigate the changes in ICP occurring as a result of increased intraabdominal pressure (IAP) and positioning in animals with normal and elevated ICP. Method: Five pigs (average weight 60 lb) were studied. A subarachnoid screw was placed for ICP monitoring. End tidal CO2 was monitored. Ventilation was performed to keep PCO2 between 30 and 50 mmHg. Measurements of arterial blood gases, mean arterial blood pressure, and ICP were recorded at four different levels of intraabdominal pressure (IAP 0, 8, 16, and 24 mmHg), both in the supine and Trendelenburg positions. A Foley catheter was introduced into the subarachnoid space to elevate the intracranial pressure, and the same measurements were performed. Results: There was a significant and linear increase in ICP with increased IAP and Trendelenburg position. The combination of increased IAP of 16 mmHg and Trendelenburg position increased ICP 150% over control levels. Conclusions: Patient positioning and level of IAP should be taken into consideration when performing laparoscopy on patients with head trauma, cerebral aneurysms, and other conditions associated with increased ICP.

Transplantation of hepatocytes for prevention of intracranial hypertension in pigs with ischemic liver failure.

Intracranial hypertension leading to brain stem herniation is a major cause of death in fulminant hepatic failure (FHF). Mannitol, barbiturates, and hyperventilation have been used to treat brain swelling, but most patients are either refractory to medical management or cannot be treated because of concurrent medical problems or side effects. In this study, we examined whether allogeneic hepatocellular transplantation may prevent development of intracranial hypertension in pigs with experimentally induced liver failure. Of the two preparations tested--total hepatectomy (n = 47), and liver devascularization (n = 16)--only pigs with liver ischemia developed brain edema provided, however, that animals were maintained normothermic throughout the postoperative period. This model was then used in transplantation studies, in which six pigs received intrasplenic injection of allogeneic hepatocytes (2.5 x 10(9) cells/pig) and 3 days later acute liver failure was induced. In both models (anhepatic state, liver devascularization), pigs allowed to become hypothermic had significantly longer survival compared to those maintained normothermic. Normothermic pigs with liver ischemia had, at all time points studied, ICP greater than 20 mmHg. Pigs that received hepatocellular transplants had ICP below 15 mmHg until death; at the same time, cerebral perfusion pressure (CPP) in transplanted pigs was consistently higher than in controls (45 +/- 11 mmHg vs. 16 +/- 18 mmHg; p < 0.05). Spleens of transplanted pigs contained clusters of viable hepatocytes (hematoxylin-eosin, CAM 5.2). It was concluded that removal of the liver does not result in intracranial hypertension; hypothermia prolongs survival time in both anhepatic pigs and pigs with liver devascularization, and intrasplenic transplantation of allogeneic hepatocytes prevents development of intracranial hypertension in pigs with acute ischemic liver failure.

Should HIV status alter indications for hemorrhoidectomy

PURPOSE: There is a widespread belief that performing hemorrhoidectomy on a patient infected with human immunodeficiency virus (HIV) is an invitation for disaster. Aim of this study was to compare morbidity of hemorrhoidectomy in HIV-positive (HIV+) with HIV-negative (HIV−) patients. METHODS: Charts of 27 HIV+ and 30 HIV−male patients less than age 50 years who underwent hemorrhoidectomy were reviewed. RESULTS: Mean age of the 57 study group patients was 38 years. Open hemorrhoidectomy was performed in 26 patients (46 percent), and a closed technique was used in 31 patients (54 percent). HIV+ and HIV−patient groups were well matched to all preoperative and intraoperative variables. Mean T-cell helper count in the HIV+ patient group was 301 (range, 9–1,040) cells/Μl. There were no deaths, and complications were seen in 15 patients (26 percent). There was no difference in overall complication rates between HIV+ and HIV−patient groups. Urinary retention was seen in ten patients (18 percent), three of whom were HIV+ (11 percent)vs.seven of whom were HIV -(23 percent) (P=not significant). Although no patient required reoperation for bleeding, postoperative hemorrhage was seen in three patients (1 HIV+, 2 HIV -). None of the patients developed fecal incontinence. Mean time to complete wound healing was 6.8 (range, 4−12) weeks for HIV+ patientsvs.6.6 (range, 4–14) weeks for HIV−patients (P=not significant). CONCLUSIONS: These data suggest that HIV status of a patient should not alter indications for surgical management of hemorrhoidal disease.