Invasive Fungal Infections in Low-Risk Liver Transplant Recipients: A Multi-Center Prospective Observational Study

Prevention of invasive fungal infections (IFIs) in orthotopic liver transplant (OLT) recipients utilizing postoperative systemic antifungal prophylaxis, typically with fluconazole, is justified among those at high risk for IFI. Use of postoperative antifungal prophylaxis for low-risk OLT recipients is widely practiced but not universally accepted nor supported by data. We conducted a prospective observational study among 200 OLT recipients who were at low risk for IFI and did not receive postoperative antifungal prophylaxis. Patients were considered low risk if they had /=units of 40 blood products or return to the operating room for intra-abdominal bleeding; return to the operating room for anastomotic leak or vascular insufficiency; preoperative serum creatinine of >/=2 mg/dL; and perioperative Candida colonization. Patients were followed 100 d post-transplantation for evidence of IFI. Of 193 eligible patients, 7 (4%) developed an IFI. Three (2%) IFIs were due to Candida spp. and potentially preventable by standard fluconazole prophylaxis. Three patients developed invasive aspergillosis; one developed late onset disseminated cryptococcosis. Liver transplant recipients at low risk for IFI can be identified utilizing pre-determined criteria, and post-transplantation antifungal prophylaxis can be routinely withheld in these patients.     

Intramuscular Injection of Sevoflurane Detects Malignant Hyperthermia Predisposition in Susceptible Pigs

Background: The authors hypothesized that intramuscular sevoflurane injection allows diagnostic differentiation between malignant hyperthermia-susceptible (MHS) and -nonsusceptible (MHN) pigs by measurement of intramuscular lactate and carbon dioxide partial pressure (Pco2), and that dantrolene reduces the sevoflurane-induced Pco2 increase.

Methods: With approval of the local animal care committee, microdialysis probes with attached microtubing for sevoflurane injection were placed in the adductor muscles of nine MHS and six MHN pigs, and Pco2 probes with microtubing were positioned in the triceps muscle of eight MHS and six MHN pigs. After equilibration, sevoflurane boluses at different concentrations and a sevoflurane-dantrolene bolus were injected synchronously. Lactate, pyruvate, and glucose as well as Pco2 were measured spectrophotometrically, and the rate of Pco2 increase was calculated.

Results: Intramuscular sevoflurane injection increased local lactate and Pco2 dose dependently, and significantly higher in MHS than in MHN pigs. Measurement of the rate of Pco2 increase allowed a distinct differentiation between single MHS and MHN pigs. No significant increase in Pco2 was found with sevoflurane and dantrolene.     

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In Vivo Molecular Imaging Characterizes Pulmonary Gene Expression During Experimental Lung Transplantation

Experimental gene therapy is a promising strategy to prevent ischemia-reperfusion (I/R) injury and allograft rejection after lung transplantation, and methods will eventually be needed to characterize pulmonary transgene expression in vivo in humans. Therefore, we studied positron emission tomography (PET) as a means of performing in vivo molecular imaging in rodent models of lung transplantation. Rats were transfected endotracheally with adenovirus encoding a fusion gene of a mutant Herpes simplex virus-1 thymidine kinase and the green fluorescent protein gene (the former serving as an imaging reporter gene). Twenty-four hours after transfection, lungs were transplanted in groups representing normal transplantation, I/R injury and acute allograft rejection. Imaging was obtained either 24 h after transplantation to study reperfusion injury or 4 days after transplantation to study graft rejection. After imaging, lungs were excised and analyzed for thymidine kinase activity. Imaging detected transgene expression in transplanted lungs even in the presence of acute rejection or I/R injury. The PET imaging signal correlated with in vitro lung tissue assays of thymidine kinase activity (r(2) = 0.534). Thus, noninvasive molecular imaging with PET is a feasible, sensitive and quantitative method for characterizing pulmonary transgene expression in experimental lung transplantation.     

Computer-assisted analysis of wall motion of the right ventricle in a normal patient sample and diagnosis of right heart infarction using transesophageal echocardiography

Using 2D and M-Mode transesophageal short axis cross sections, right ventricular systolic wall motion was quantified in 15 normal patients. A further group of 39 patients with right ventricular infarction was investigated. In the normal group fractional shortening of the septum was -19.6% (-45 to 8%), that of the lateral wall 51.6% (37 to 73%), of the posterior wall 33.9% (5 to 50%) and of the anterior wall 42.7% (18 to 57%). Right ventricular infarction (RVI) was associated in 33 patients with posterior left ventricular infarction (85%) and in three patients with anterior infarction. In two cases only an isolated RVI was found. Right ventricular dilation occurred in 24 patients (61%). Hemodynamic criteria were fulfilled in eleven out of 21 patients (53%). RVI was confirmed in one patient by surgery and in ten patients by autopsy. Recognition of regional wall motion abnormalities by transesophageal echocardiography permits an accurate bedside identification of RVI. 2D and M-Mode registration of the short axis improves RVI assessment. Wall motion analyses offer the possibility to determine the extent of right ventricular infarction.     

Evaluation of Seldinger Technique Emergency Cricothyroidotomy versus Standard Surgical Cricothyroidotomy in 200 Cadavers

Background: Percutaneous cricothyroidotomy is a lifesaving procedure for airway obstruction in trauma victims who need airway establishment and cannot be intubated or in whom intubation has failed.

Methods: The purpose of this study was to examine whether there is a training effect using Seldinger technique emergency cricothyroidotomy (group 1; Arndt Emergency Cricothyroidotomy Catheter Set; Cook Critical Care, Bloomington, IN) versus standard surgical cricothyroidotomy (group 2). Twenty emergency physicians performed five cricothyroidotomies with each method in a total of 200 human cadavers, comparing efficacy and safety (speed, success rate, and injuries).

Results: Seven attempts in group 1 and six in group 2 had to be aborted. Time intervals from the start of the procedure to location of the cricothyroid membrane were not significantly different between the groups. However, time to tracheal puncture (P < 0.01) and time to first ventilation (P < 0.001) were significantly longer in group 2. No time effect could be observed in both groups. The airway was accurately placed into the trachea through the cricothyroid membrane in 88.2% (82 of 93) of the cadavers in group 1 and in 84.0% (79 of 94) in group 2 (not significant). No injuries were observed in group 1, whereas there were six punctures of the thyroid vessels in group 2 (P < 0.05).     

Diffusion limitation and limitation by chemical reactions during alveolar-capillary transfer of oxygen-labeled CO2

A major difficulty in the measurement of carbon dioxide diffusing capacity is the development of significant CO2 back pressure within the capillary. The use of oxygen-labeled CO2 limits this back pressure due to rapid dilution of the label into the water pool by isotopic exchange. We demonstrated the use of C16O18O to measure DCO2 (Schuster, 1985). A major question from that study is whether the isotope measures a true membrane diffusing capacity or is limited by back reaction. In this study we examine the diffusing capacity of doubly 18O-labeled carbon dioxide, C18O2, a species in which the kinetics of isotopic exchange in pulmonary blood is higher than that of C16O18O. Eighteen single breath experiments were performed on two resting male subjects whose CO2-transfer-kinetics was previously studied with C16O18O (Schuster, 1985). Following expiration to residual volume the subjects inspired a gas mixture containing 20% O2 and 1.5-2.6% C18O2. After holding their breath for 0.4-17 sec they exhaled into a tube and the end-expired gas was analysed by mass spectrometry. The time course of the C18O2 disappearance from alveolar gas showed a biexponential characteristic as that which had been measured with C16O18O, but C18O2 disappeared faster. The mean value of the diffusing capacity of C18O2 amounts to 1102 ml mmHg-1 X min-1. It is 228 +/- 163 ml mmHg-1 X min-1 greater than that of C16O18O. This significant difference suggests that: DC16O18O is limited in part by isotopic exchange reactions; the observed DC18O2 may be taken as a new lower limit for DMCO2, higher than values established from other techniques; the decarboxylation of bicarbonate in red cells is not a rate limiting step for CO2 exchange.