Effect of cardiac output changes on exhaled carbon dioxide in newborn piglets.

INTRODUCTION: International neonatal resuscitation guidelines recommend that correct tube placement should be confirmed by clinical assessment and exhaled CO2 detection. Absence of exhaled CO2 after intubation suggests oesophageal intubation, non-aerated lungs, low tidal volume delivery, or low cardiac output. The relationship between changes in cardiac output and exhaled CO2 in neonates is unknown. The aim of the study was to determine if changes in cardiac output affect exhaled carbon dioxide in a porcine model of neonatal resuscitation. METHOD: Term piglets (n=5) aged 3-4 days were anesthetised, intubated, instrumented and exposed to normocapnic hypoxia. Exhaled CO2 was continuously measured using a flow sensor (Respironics NM3(®)). Pulmonary artery blood flow, a surrogate for cardiac output was measured using an ultrasonic flow probe (Transonic(®)). A semi-quantitative CO2-detector (Pedi-Cap(®)) was placed between the tracheal tube and flow sensor to assess colour change at changing levels of cardiac output. RESULTS: Median (IQR) pulmonary artery blood flow significantly decreased from 177 (147-177)mL/kg/min at baseline to 4 (3-26)mL/kg/min during hypoxia (p=0.02). Exhaled CO2 remained similar throughout the experiment, 47 (41-47)mmHg at baseline vs. 40 (38-41)mmHg at the end of the hypoxia (p=1.00). Additionally, at each time point, colour change at the Pedi-Cap(®) was observed. CONCLUSION: A significant decrease in cardiac output was not associated with changes in exhaled CO2 or failure to achieve a Pedi-Cap(®) colour change.

Portal vein thrombosis is a potentially preventable complication in clinical islet transplantation.

Percutaneous transhepatic portal access avoids surgery but is rarely associated with bleeding or portal venous thrombosis (PVT). We herein report our large, single-center experience of percutaneous islet implantation and evaluate risk factors of PVT and graft function. Prospective data were collected on 268 intraportal islet transplants (122 subjects). A portal venous Doppler ultrasound was obtained on Days 1 and 7 posttransplant. Therapeutic heparinization, complete ablation of the portal catheter tract with Avitene paste and limiting packed cell volume (PCV) to <5 mL completely prevented any portal thrombosis in the most recent 101 islet transplant procedures over the past 5 years. In the previous cumulative experience, partial thrombosis did not affect islet function. Standard liver volume correlated negatively (r =-0.257, p < 0.001) and PCV correlated positively with portal pressure rise (r = 0.463, p < 0.001). Overall, partial portal thrombosis occurred after 10 procedures (overall incidence 3.7%, most recent 101 patient incidence 0%). There were no cases of complete thrombosis and no patient developed sequelae of portal hypertension. In conclusion, portal thrombosis is a preventable complication in clinical islet transplantation, provided therapeutic anticoagulation is maintained and PCV is limited to <5 mL.

Imaging evaluation of potential donors in living-donor liver transplantation.

Liver transplants, originally obtained from deceased donors, can now be harvested from living donors as well. This technique, called living-donor liver transplantation (LDLT), provides an effective alternative means of liver transplantation and is a method of expanding the donor pool in light of the demand and supply imbalance for organ transplants. Imaging plays an important role in LDLT programmes by providing robust evaluation of potential donors to ensure that only anatomically suitable donors with no significant co-existing pathology are selected and that crucial information that allows detailed preoperative planning is available. Imaging evaluation helps to improve the outcome of LDLT for both donors and recipients, by improving the chances of graft survival and reducing the postoperative complication rate. In this review, we describe the history of LDLT and discuss in detail the application of imaging in donor assessment with emphasis on use of modern computed tomography (CT) and magnetic resonance imaging (MRI) techniques.

High risk of sensitization after failed islet transplantation.

Human Leukocyte Antigen (HLA) antibodies posttransplant have been associated with an increased risk of early graft failure in kidney transplants. Whether this also applies to islet transplantation is not clear. To achieve insulin independence after islet transplants multiple donor infusions may be required. Hence, islet transplant recipients are at risk of sensitization after transplantation. Islet transplant recipients were screened for HLA antibodies posttransplant by flow-based methods. A total of 98 patients were studied. Twenty-nine patients (31%) developed de novo donor specific antibodies (DSA) posttransplant. Twenty-three patients developed DSA while on immunosuppression (IS). Among recipients who have discontinued IS, 10/14 (71%) are broadly sensitized with panel reactive antibody (PRA) >or=50%. The risk of becoming broadly sensitized after transplant was 11/69 (16%) if the recipient was unsensitized prior to transplant. The majority of these antibodies have persisted over time. Appearance of HLA antibodies posttransplant is concerning, and the incidence rises abruptly in subjects weaned completely from IS. This may negatively impact the ability of these individuals to undergo further islet, pancreas or kidney transplantation and should be discussed upfront during evaluation of candidates for islet transplantation.

Prevention of bleeding after islet transplantation: lessons learned from a multivariate analysis of 132 cases at a single institution.

Islet transplantation is being offered increasingly for selected patients with unstable type 1 diabetes. Percutaneous transhepatic portal access avoids a need for surgery, but is associated with potential risk of bleeding. Between 1999 and 2005, we performed 132 percutaneous transhepatic islet transplants in 67 patients. We encountered bleeding in 18/132 cases (13.6%). In univariate analysis, the risk of bleeding in the absence of effective track ablation was associated with an increasing number of procedures (2nd and 3rd procedures with an odds ratio (OR) of 9.5 and 20.9, respectively), platelets count <150,000 (OR 4.4), elevated portal pressure (OR 1.1 per mm Hg rise), heparin dose > or =45 U/kg (OR 9.8) and pre-transplant aspirin (81 mg per day) (OR 2.6, p = 0.05). A multivariate analysis further confirmed the cumulative transplant procedure number (p < 0.001) and heparin dose > or =45 U/kg (p = 0.02) as independent risk factors for bleeding. Effective mechanical sealing of the intrahepatic portal catheter tract with thrombostatic coils and tissue fibrin glue completely prevented bleeding in all subsequent procedures (n = 26, p = 0.02). We conclude that bleeding after percutaneous islet implantation is an avoidable complication provided the intraparenchymal liver tract is sealed effectively.

Curative resection by superior hepatectomy for advanced hepatoblastoma facilitated by the presence of a large inferior right hepatic vein.

BACKGROUND: Despite the success of neoadjuvant chemotherapy some patients with hepatoblastoma remain unresectable due to the proximity of important vascular structures. We report an unconventional surgical resection via a superior hepatectomy in a 16-month-old infant with hepatoblastoma. CASE OUTLINE: Staging CT scan revealed extensive replacement of the superior portion of the liver with complete occlusion of the three hepatic veins, and with extension into the inferior vena cava and right atrium. Following chemotherapy the tumour was confined to the superior portion of the liver with obstruction of the right, middle and left hepatic veins, but with a large patent inferior hepatic vein draining the inferior liver segments. Superior hepatectomy was performed without complication. DISCUSSION: Complete surgical resection offers the only chance of cure for patients with hepatoblastoma. This case illustrates that careful preoperative planning facilitated aggressive surgical clearance with superior hepatectomy for curative resection of an otherwise non-resectable tumour.

Portal venous and enteric exocrine drainage versus systemic venous and bladder exocrine drainage of pancreas grafts: clinical outcome of 40 consecutive transplant recipients.

OBJECTIVE: To test the hypothesis that pancreas transplantation using the more physiologic method of portal venous-enteric (PE) drainage could be performed without compromising patient and graft outcome, compared with the standard method of systemic venous-bladder (SB) drainage. METHODS: Between November 1995 and November 1998, the authors prospectively followed up 20 consecutive patients with SB drainage followed by 20 consecutive patients with PE drainage. All patients underwent simultaneous pancreas-kidney transplantation, and all were immunosuppressed with antilymphocyte serum, cyclosporin, azathioprine, and steroids. RESULTS: The actuarial patient survival rate at 1 year was 95% in the SB group and 100% in the PE group. Death-censored kidney graft survival was 100% in both groups; pancreas graft survival was 95% in the SB group and 100% in the PE group. The mean initial hospital stay was 15 days for both groups. However, during the first 6 months after transplantation, the SB group required more medical day-unit visits, mostly for treatment of metabolic acidosis and dehydration. The incidence of urinary tract infections was similar in both groups. The incidence of cytomegalovirus infections was significantly less in the PE group. The incidence of acute rejection was 37% in the SB group and 15% in the PE group. Mean serum creatinine levels 6 months after transplantation were significantly lower in the PE group than in the SB group. Glycemic control was excellent in both groups, but fasting serum insulin levels were significantly lower in the PE group. CONCLUSIONS: The PE method of pancreas transplantation can be performed with excellent patient and graft outcomes.

Hepatitis C-related cirrhosis: a predictor of diabetes after liver transplantation.

Hepatitis C virus (HCV) infection has recently been suggested to be a risk factor for the development of diabetes mellitus. The aim of our study was to investigate whether the prevalence of diabetes is increased among liver transplant recipients infected with HCV. We compared the prevalence of diabetes among 278 liver transplant recipients whose original cause of liver failure was HCV infection (110 patients), hepatitis B virus infection (HBV; 53 patients), and cholestatic liver disease (CLD; 115 patients). The pretransplantation prevalence of diabetes was higher in the HCV group (29%) compared with the HBV (6%) and CLD (4%) groups (P <.001). The prevalence of diabetes remained higher in the HCV group 1 year after transplantation: 37%, 10%, and 5% in the HCV, HBV, and CLD groups, respectively (P <.001). The cumulative steroid dose during the first year of transplantation was significantly lower in the HCV group compared with the CLD group. Multivariate analysis revealed that HCV-related liver failure (P =.002), pretransplantation diabetes (P <.0001), and male sex (P =.019) were independent predictors of the presence of diabetes 1 year after transplantation. The high prevalence of diabetes persisted in the HCV group, with 41% diabetic at 5 years. The majority of patients with diabetes mellitus (89%) required insulin therapy after transplantation. Patient and graft survival rates were similar among patients with and without diabetes. In conclusion, our study shows that there is a high prevalence of diabetes among liver transplant recipients infected with HCV both before and after transplantation.

Innominate artery interposition graft simplifies the portal venous drainage method of pancreas transplantation.

Pancreas transplantation utilizing portal venous and enteric exocrine drainage has potential benefits over the standard systemic venous and bladder exocrine drainage method. Unfortunately, technical difficulties are often experienced with the arterial anastomosis after the portal venous anastomosis is completed. We have found that the addition of an innominate artery interposition graft has greatly simplified the procedure.

Temporal effects of prolonged hypoxaemia and reoxygenation on systemic, pulmonary and mesenteric perfusions in newborn piglets.

OBJECTIVE: Temporal effects of prolonged hypoxaemia and reoxygenation, on the systemic pulmonary and mesenteric circulations in newborn piglets, were investigated. METHODS: Two groups [control (n = 5), hypoxaemic (n = 7)] of 1-3 day old anaesthetised piglets were instrumented with ultrasound flow probes placed to measure cardiac, hepatic arterial flow and portal venous flow indices, and catheters inserted for measurements of systemic and pulmonary arterial pressures. Hypoxaemia with arterial oxygen saturation 40-50% was maintained for 3 h, followed by reoxygenation with 100% inspired oxygen. RESULTS: Cardiac index was transiently elevated at 30-60 min of hypoxaemia (23% increase from baseline 158 +/- 39 ml/kg/min), along with increases in stroke volume but not heart rate. A significant decrease in systemic vascular resistance after 30 min of hypoxaemia was followed by hypotension at 180 min of hypoxaemia. Progressive pulmonary hypertension with significant vasoconstriction was found after 30 min of hypoxaemia. The hypoxaemic mesenteric vasoconstriction was transient with a 37% decrease in portal venous flow index at 15 min of hypoxaemia (29 +/- 12 vs. 46 +/- 18 ml/kg/min of baseline, p < 0.05). The hepatic arterial to total hepatic oxygen delivery ratio increased significantly during hypoxaemia. In contrast to the significant increase in systemic oxygen extraction throughout hypoxaemia, elevation in mesenteric oxygen extraction decreased after 30 min of hypoxaemia associated with modest decreases in oxygen consumption. Following reoxygenation, the pulmonary hypertension was partially reversed. Cardiac index decreased further (130 +/- 39 ml/kg/min) with reduced stroke volume, persistent systemic hypotension and decreased systemic oxygen delivery. CONCLUSIONS: We demonstrated differential temporal changes in systemic, pulmonary and mesenteric circulatory responses during prolonged hypoxaemia. Cautions need to be taken upon reoxygenation because the neonates are at risk of developing myocardial stunning, persistent pulmonary hypertension and necrotising enterocolitis.

Effects of a continuous epinephrine infusion on regional blood flow in awake newborn piglets.

OBJECTIVE: To determine the effects of a continuous epinephrine infusion on renal and mesenteric blood flow in both healthy newborn piglets and animals subjected to hemorrhagic shock. METHODS: Superior mesenteric artery (SMA) and left renal artery ultrasonic flow probes were implanted into 16 1- to 3-day-old piglets. Two days later, the effects of epinephrine on SMA and renal blood flow, mean arterial pressure (MAP) and central venous pressure were measured in conscious, non-sedated normovolemic piglets. Epinephrine doses of 0.2, 0.4, 0.8, 1.6 and 3.2 microg/kg.min were used in random order. Piglets were subsequently hemorrhaged (20 ml/kg) to mild hypotension and again received epinephrine infusion in the same doses. RESULTS: Doses of epinephrine less than 3.2 microg/kg.min had no significant effects on renal or mesenteric arterial flow. At 3.2 microg/kg.min of epinephrine during normovolemia, there was a significant decrease in SMA blood flow (34% [SD 42], p < 0.05) and increase in SMA vascular resistance (147% [SD 114], p < 0.05). Similar results were shown during hypovolemia, SMA flow decreased by 32% (SD 33), and SMA vascular resistance increased by 220.3% (SD 177). At 3.2 microg/kg.min renal artery flow decreased by 43% (SD 21) during normovolemia and a similar decrease occurred during hypovolemia, 37% (SD 31). Renal vascular resistance increased by about 200% at this dose (normovolemia 211% [SD 185], hypovolemia 186% [SD 150], p < 0.01). Low-to-moderate dose epinephrine caused no significant change in SMA or renal blood flow. During hypovolemia low dose epinephrine infusion was associated with a trend to increased SMA blood flow. CONCLUSION: Low-dose epinephrine does not cause vasoconstriction in the renal or mesenteric circulations during normovolemia or hypovolemia. High doses of epinephrine above 1.6 microg/kg.min may cause renal or mesenteric ischemia, in either the normovolemic or hypovolemic neonate.

Systemic, pulmonary and mesenteric perfusion and oxygenation effects of dopamine and epinephrine.

The response of the systemic, pulmonary, hepatic and portal circulations to infusion of dopamine and epinephrine was studied in newborn piglets 1 to 3 d of age. Anesthetized animals were instrumented to measure cardiac index (CI), hepatic arterial flow, and portal venous blood flow. Catheters were inserted for measurement of systemic arterial pressure (SAP), pulmonary arterial pressure (PAP), and for sampling of arterial, portal venous, and mixed venous oxygen saturations and plasma lactate levels. Systemic, pulmonary and mesenteric vascular resistance indices (SVRI, PVRI, MVRI), and systemic and mesenteric oxygen extraction were calculated. Dopamine and epinephrine were infused in doses of 2, 10, 32 microg/kg/min and 0.2, 1.0, 3.2 microg/kg/min respectively, given in random order. Significant increases in SAP, PAP, and CI were demonstrated with 32 microg/kg/min of dopamine and the two higher doses (1.0 and 3.2 microg/kg/min) of epinephrine. There were no significant changes in SVRI and PVRI with dopamine infusions. Epinephrine at 3.2 microg/kg/min significantly elevated SVRI and PVRI. The SAP/PAP ratio was decreased with 32 microg/kg/min of dopamine whereas epinephrine did not affect the ratio. Dopamine had no significant effect on hepatic arterial flow, portal venous flow, or mesenteric vascular resistance. Epinephrine infusion at 3.2 microg/kg/min decreased portal venous blood flow, total hepatic blood flow, and hepatic oxygen delivery with an increase in calculated mesenteric vascular resistance. Systemic and mesenteric oxygen extraction were not affected by dopamine or epinephrine infusions. Plasma lactate levels were significantly elevated with epinephrine infusion 3.2 microg/kg/min. The differential responses of dopamine and epinephrine on pulmonary and mesenteric circulations may be significant in the pathophysiology and management of persistent fetal circulation and necrotizing enterocolitis.