A controlled comparison of continuous intraarterial and intravenous infusions of vasopressin in hemorrhage from esophageal varices.

Infusions of intraarterial vasopressin (IAV) into the superior mesenteric artery have been shown to be effective in controlling hemorrhage from esophagogastric varices. Intravenous infusions of vasopressin (IVV), which can be initiated rapidly and require less sophisticated equipment and personnel, have also been reported to control variceal hemorrhage. We undertook a controlled clinical trial to compare these two routes of administration. Twenty-two cirrhotic patients with massive hemorrhage from varices were randomized to receive either IVV or IAV. Intraarterial vasopressin was begun at 0.1 U/min and increased progressively as needed to 0.2, 0.3, 0.4, and 0.5 U/min. Intravenous vasopressin was begun at 0.3 U/min and increased progressively as needed to 0.6, 0.9, 1.2, and 1.5 U/min. Hemorrhage was controlled in 5 of 10 episodes (50%) with IVV and in 6 of 12 episodes (50%) with IAV. Seven of the ten episodes treated with IVV (70%) ended fatally compared with 9 of 12 treated with IAV (75%). Side-effects and complications occurred with similar frequency in the two groups. The two routes of administration are equal in effects, side-effects, and complications. We recommend that IVV, which can be administered more easily, be given a brief therapeutic trial early in the management of hemorrhage from varices.     

Pharmacokinetic-hemodynamic interactions between vasopressin and nitroglycerin: comparison between intravenous and cutaneous routes of nitrate delivery

Addition of nitroglycerin (NTG) improves the hemodynamic response to vasopressin and may thus be useful in the treatment of gastrointestinal hemorrhage. We studied in the rat the influence of vasopressin on the disposition of a constant intravenous infusion of NTG and the cutaneous absorption of NTG ointment. The effect of NTG on the pharmacokinetics of vasopressin was also determined. Animals were divided into four groups: control, NTG, vasopressin and vasopressin + NTG. Infusions (or ointments) were maintained for 70 min; cardiac output and regional blood flows were determined with the microsphere technique. Both intravenous and cutaneous NTG resulted in similar hemodynamic responses. Vasopressin caused generalized vasoconstriction, while the addition of NTG reversed the deleterious systemic hemodynamic effects of vasopressin. Addition of vasopressin to NTG did not alter NTG systemic clearance nor did NTG affect vasopressin clearance. Of note, the systemic clearance of NTG was directly correlated with the cardiac output (r = 0.804), supporting a model of NTG distribution where blood vessels and/or extrahepatic tissues are the site of elimination of the drug. The marked reduction in skin blood flow by vasopressin did not decrease the steady-state plasma concentration of NTG nor the estimated cutaneous absorption rate of NTG ointment, indicating that cutaneous blood flow is not an important determinant in the absorption of NTG ointment. The skin is an appropriate route of delivery for NTG when combined with vasopressin.     

Risk prediction for chronic kidney disease progression using heterogeneous electronic health record data and time series analysis

Background As adoption of electronic health records continues to increase, there is an opportunity to incorporate clinical documentation as well as laboratory values and demographics into risk prediction modeling.Objective The authors develop a risk prediction model for chronic kidney disease (CKD) progression from stage III to stage IV that includes longitudinal data and features drawn from clinical documentation.Methods The study cohort consisted of 2908 primary-care clinic patients who had at least three visits prior to January 1, 2013 and developed CKD stage III during their documented history. Development and validation cohorts were randomly selected from this cohort and the study datasets included longitudinal inpatient and outpatient data from these populations. Time series analysis (Kalman filter) and survival analysis (Cox proportional hazards) were combined to produce a range of risk models. These models were evaluated using concordance, a discriminatory statistic.Results A risk model incorporating longitudinal data on clinical documentation and laboratory test results (concordance 0.849) predicts progression from state III CKD to stage IV CKD more accurately when compared to a similar model without laboratory test results (concordance 0.733, P<.001), a model that only considers the most recent laboratory test results (concordance 0.819, P < .031) and a model based on estimated glomerular filtration rate (concordance 0.779, P < .001).Conclusions A risk prediction model that takes longitudinal laboratory test results and clinical documentation into consideration can predict CKD progression from stage III to stage IV more accurately than three models that do not take all of these variables into consideration.     

Experimental models of hepatic encephalopathy: ISHEN guidelines

Objectives of the International Society for Hepatic Encephalopathy and Nitrogen Metabolism Commission were to identify well‐characterized animal models of hepatic encephalopathy (HE) and to highlight areas of animal modelling of the disorder that are in need of development. Features essential to HE modelling were identified. The best‐characterized animal models of HE in acute liver failure, the so‐called Type A HE, were found to be the hepatic devascularized rat and the rat with thioacetamide‐induced toxic liver injury. In case of chronic liver failure, surgical models in the rat involving end‐to‐side portacaval anastomosis or bile duct ligation were considered to best model minimal/mild (Type B) HE. Unfortunately, at this time, there are no satisfactory animal models of Type C HE resulting from end‐stage alcoholic liver disease or viral hepatitis, the most common aetiologies encountered in patients. The commission highlighted the urgent need for such models and of improved models of HE in chronic liver failure in general as well as a need for models of post‐transplant neuropsychiatric disorders. Studies of HE pathophysiology at the cellular and molecular level continue to benefit from in vitro and or ex vivo models involving brain slices or exposure of cultured cells (principally cultured astrocytes) to toxins such as ammonia, manganese and pro‐inflammatory cytokines. More attention could be paid in the future to in vitro models involving the neurovascular unit, microglia and neuronal co‐cultures in relation to HE pathogenesis.     

Therapeutic Hypothermia for Acute Liver Failure: Toward a Randomized,Controlled Trial in Patients with Advanced Hepatic Encephalopathy

Acute liver failure (ALF), the abrupt loss of liver function in a patient without previous liver disease, remains a highly mortal condition. Patients with ALF often succumb to their liver injury after the development of cerebral edema, resulting in intracranial hypertension and brain herniation. While the management of cerebral edema in ALF always includes the administration of osmotically active agents, osmotherapy often reduces intracranial pressure (ICP) insufficiently, such that herniation may be delayed but not prevented. Therapeutic hypothermia, the intentional reduction of body core temperature, has been increasingly used to treat cerebral edema in patients with traumatic and hypoxic brain injury. Data in animal models of ALF also suggest that hypothermia is effective in the prevention and treatment of cerebral edema, and case reports in humans have suggested that hypothermia is an effective bridge to orthotopic liver transplantation. A randomized, controlled trial comparing the management of ALF patients under normothermic and hypothermic conditions is a logical extension of these preliminary observations. Herein, we consider the many difficulties which will be encountered in the design of such a trial in patients with ALF at high risk of developing cerebral edema. The authors wish to dedicate this work to our friend, teacher, and colleague, Dr. Andres Blei, who inspired the work as part of his life-long study of hepatic encephalopathy and acute liver failure. We also wish to acknowledge the thoughtful input of Drs. Fin Larsen, Julia Wendon, Nick Murphy, and William Bernal.     

Hemodynamic evaluation before liver transplantation: insights into the portal hypertensive syndrome

The cardiac hemodynamics of patients awaiting liver transplantation is complex. Coronary atherosclerosis, a hyperdynamic circulatory state and cirrhotic cardiomyopathy are present to a variable degree in this population. In this contribution to the Symposium on Portal Hypertension, we expand on our published experience with coronary angiography and cardiac hemodynamics at the time of evaluation of candidacy for liver transplantation in a cohort of 161 patients. Although we confirmed the relation of systemic hemodynamics with the degree of liver failure, we noted a higher prevalence of high output heart failure, defined as an increased left ventricular end-diastolic pressure in the setting of an elevated cardiac output, most notably in patients classified as Child C. Most patients with high pulmonary artery pressure also exhibited evidence of elevated left ventricle filling pressures. A low systemic vascular resistance, a marker of arterial vasodilatation, was similar in the presence of atherosclerosis, a condition where impaired vasorelaxation occurs as a result of endothelial dysfunction. The high prevalence of coronary artery disease in this series supports the observations that atherosclerosis is a major issue in the current population with cirrhosis awaiting liver transplantation. A lower sensitivity of noninvasive screening tools for the detection of coronary atherosclerosis is likely the result of the interaction of the hyperdynamic circulation with the performance of these tests.     

New clinical observations in hemangiomas.

Much research in endothelial biology is aimed at developing methods to stimulate productive angiogenesis or inhibit unwanted angiogeneseis. Hemangiomas provide a model for endothelial proliferation and involution. This article is intended to update the reader with new information regarding hemangiomas of infancy, the most common tumor of childhood. Topics such as possible origin, management issues, and psychosocial stresses are addressed. This field is constantly changing, but an effort has been made to include most of the recently reported articles. Our hope is that this information will enable physicians caring for patients with hemangiomas to better address the concerns of their patients and families.     

Treatment of Stomal Variceal Hemorrhage with TIPS: Case Report and Review of the Literature

We report a case in which recurrent hemorrhage from stomal varices was successfully treated by placement of a TIPS in a patient with prior colectomy for inflammatory bowel disease. Although several treatment options have been reported for this entity we believe that TIPS offers minimally invasive and definitive treatment.     

Etiology and management of fulminant hepatic failure

Fulminant hepatic failure (FHF) remains a rare but devastating disease. Viruses and drug-induced hepatotoxicity are the most common causes of the syndrome, but the relevance of each differs depending on the geographic area. In a large proportion of patients no cause for FHF can be identified. Good intensive care is critical for patient survival. Orthotopic liver transplantation (OLT) remains a definitive therapeutic option. Prognostic indices have helped to optimize patient selection and timing for performance of OLT. However, the accuracy of these prognostic indices decreases when they are applied to different populations, probably because of regional differences in etiology and peculiar native host factors. More accurate prognostic criteria and new therapeutic alternatives to OLT are required.     

Splenic infarction due to concomitant hereditary spherocytosis and sickle cell trait

Concomitant hereditary spherocytosis and sickle cell trait, although extremely rare, could potentially lead to splenic sequestration or infarction. We report here the first case of splenic infarction in a child with hereditary spherocytosis and sickle cell trait while flying on a commercial aircraft. The presence of hypoxia, hemoconcentrated erythrocytes, and sickle hemoglobin created the perfect environment for clinical sequelae.