Ivan Kangrga

Whole-cell recordings from visualized C1 adrenergic bulbospinal neurons: ionic mechanisms underlying vasomotor tone

The membrane properties of visually identified, DiI retrogradely labeled bulbospinal neurons of the C1 adrenergic cell group were studied by whole-cell recordings in brainstem slices from 7- to 10-day-old rats. A post-hoc histochemical analysis allowed us to evaluate the electrophysiological properties of the C1 adrenergic neurons, a group of cells known to project to the sympathetic preganglionic neurons. Two types of cells were labeled: pacemaker and non-pacemaker neurons. In voltage-clamp mode, C1 pacemaker neurons exhibited a TTX-sensitive, persistent inward current that was activated between -55 and -50 mV and reached a peak between -40 and -30 mV. This current was significantly larger in the pacemaker neurons as compared to the non-pacemaker neurons and appeared to be a principal conductance driving the C1 pacemaker activity. Two other conductances modulated the frequency of pacemaker discharge: (1) an anomalous rectifier accelerated pacemaker frequency by three synergistic actions: (a) depolarizing it at rest, (b) increasing the slope of the pacemaker potentials, and (c) limiting hyperpolarizing membrane excursions; and (2) an A-type current which had two opposing actions: (a) slowing it by decreasing the slope of the pacemaker potential, and (b) accelerating it by repolarizing the fast action potential. Persistent sodium current functions as the driver potential responsible for the tonic firing pattern of the C1 bulbospinal neurons providing a cellular mechanism responsible for the descending excitatory drive imposed onto sympathetic preganglionic neurons. Thus, it may explain how C1 neurons may function to maintain vasomotor tone or modulate other autonomic functions. This study is the first attempt to analyze voltage-activated membrane conductances of RVLM neurons of known phenotype and axonal connections.

Comparison of calibrated and uncalibrated arterial pressure-based cardiac output monitors during orthotopic liver transplantation.

Arterial pressure–based cardiac output monitors (APCOs) are increasingly used as alternatives to thermodilution. Validation of these evolving technologies in high‐risk surgery is still ongoing. In liver transplantation, FloTrac‐Vigileo (Edwards Lifesciences) has limited correlation with thermodilution, whereas LiDCO Plus (LiDCO Ltd.) has not been tested intraoperatively. Our goal was to directly compare the 2 proprietary APCO algorithms as alternatives to pulmonary artery catheter thermodilution in orthotopic liver transplantation (OLT). The cardiac index (CI) was measured simultaneously in 20 OLT patients at prospectively defined surgical landmarks with the LiDCO Plus monitor (CIL) and the FloTrac‐Vigileo monitor (CIV). LiDCO Plus was calibrated according to the manufacturers instructions. FloTrac‐Vigileo did not require calibration. The reference CI was derived from pulmonary artery catheter intermittent thermodilution (CITD). CIV‐CITD bias ranged from −1.38 (95% confidence interval = −2.02 to −0.75 L/minute/m2, P = 0.02) to −2.51 L/minute/m2 (95% confidence interval = −3.36 to −1.65 L/minute/m2, P < 0.001), and CIL‐CITD bias ranged from −0.65 (95% confidence interval = −1.29 to −0.01 L/minute/m2, P = 0.047) to −1.48 L/minute/m2 (95% confidence interval = −2.37 to −0.60 L/minute/m2, P < 0.01). For both APCOs, bias to CITD was correlated with the systemic vascular resistance index, with a stronger dependence for FloTrac‐Vigileo. The capability of the APCOs for tracking changes in CITD was assessed with a 4‐quadrant plot for directional changes and with receiver operating characteristic curves for specificity and sensitivity. The performance of both APCOs was poor in detecting increases and fair in detecting decreases in CITD. In conclusion, the calibrated and uncalibrated APCOs perform differently during OLT. Although the calibrated APCO is less influenced by changes in the systemic vascular resistance, neither device can be used interchangeably with thermodilution to monitor cardiac output during liver transplantation. Liver Transpl 16:773‐782, 2010.

Whole-cell patch-clamp recordings from visualized bulbospinal neurons in the brainstem slices

The purpose of this study was to develop a method for electrophysiological characterization of retrogradely labeled bulbospinal neurons in the specific cytoarchitectonic regions in the brainstem slices. Several days after the spinal cord was injected with the carbocyanine dye, DiI, retrogradely labeled bulbospinal neurons were visualized by epifluorescence optics in the brainstem slices with the aid of a silicon intensifier tube (SIT) camera. Labeled somata were routinely seen in the caudal raphe nuclei, rostroventral medial and lateral portions of the medulla, the A5 group and in other medullary sites known to project to the spinal cord. Electrophysiological properties of the DiI-labeled neurons were assessed by whole-cell recordings using micropipettes filled with biocytin. The slices were subsequently processed for dual visualization of biocytin and serotonin or a marker for noradrenergic neurons, tyrosine hydroxylase (TH). The electrophysiological properties of bulbospinal neurons were correlated with their morphology and neurochemical content. This technique may be useful in other areas of CNS for studying morphology, neurochemical content and physiology of retrogradely labeled neurons.

Atrial Fibrillation in Patients Undergoing Liver Transplantation—A Single-Center Experience

BACKGROUND As the prevalence of atrial fibrillation rises with age and older patients increasingly receive transplants, the perioperative management of this common arrhythmia and its impact on outcomes in liver transplantation is of relevance. METHODS Retrospective review of 757 recipients of liver transplantation from January 2002 through December 2011. RESULTS Nineteen recipients (2.5%) had documented pre-transplantation atrial fibrillation. Sixteen patients underwent liver and 3 a combined liver-kidney transplantation. Three patients died within 30 days (84.2% 1-month survival) and another 3 within 1 year of transplantation (68.4% 1-year survival). Compared with patients without atrial fibrillation, the relative risk of death in the atrial fibrillation group was 5.29 at 1 month (P = .0034; 95% confidence interval [CI], 1.73-16.18) and 3.28 at 1 year (P = .0008; 95% CI, 1.63-6.59). Time to extubation and intensive care unit (ICU) and hospital readmissions were not different from the control cohort. Rapid ventricular response requiring treatment occurred in 4 patients during surgery and 7 after surgery, resulting in 3 ICU and 3 hospital readmissions. CONCLUSIONS The results suggest that patients with atrial fibrillation may be at increased risk of mortality after liver transplantation. Optimization of medical therapy may decrease ICU and hospital readmission due to rapid ventricular response.

Postreperfusion cardiac arrest and resuscitation during orthotopic liver transplantation: dynamic visualization and analysis of physiologic recordings.

ABSTRACT We recently reported on the Multi Wave Animator (MWA), a novel open-source tool with capability of recreating continuous physiologic signals from archived numerical data and presenting them as they appeared on the patient monitor. In this report, we demonstrate for the first time the power of this technology in a real clinical case, an intraoperative cardiopulmonary arrest following reperfusion of a liver transplant graft. Using the MWA, we animated hemodynamic and ventilator data acquired before, during, and after cardiac arrest and resuscitation. This report is accompanied by an online video that shows the most critical phases of the cardiac arrest and resuscitation and provides a basis for analysis and discussion. This video is extracted from a 33-min, uninterrupted video of cardiac arrest and resuscitation, which is available online. The unique strength of MWA, its capability to accurately present discrete and continuous data in a format familiar to clinicians, allowed us this rare glimpse into events leading to an intraoperative cardiac arrest. Because of the ability to recreate and replay clinical events, this tool should be of great interest to medical educators, researchers, and clinicians involved in quality assurance and patient safety.

Intraoperative transesophageal echocardiography reveals thrombotic stenosis of inferior vena cava during orthotopic liver transplantation

Transesophageal echocardiography (TEE) is increasingly being used for hemodynamic monitoring in orthotopic liver transplantation (OLT). Importantly, intraoperative TEE may provide additional critical information such as the identification of intracardiac thrombi or complications related to transjugular intrahepatic portosystemic shunts. We present a patient with postreperfusion graft congestion in whom TEE revealed hemodynamically significant thrombotic stenosis of the inferior vena cava (IVC). This finding influenced further patient management. A 34-year-old woman with a large polycystic liver (estimated volume 1⁄4 10 L; Fig. 1A,B) underwent OLT via the piggyback technique with a temporary portocaval shunt. The initial intraoperative international normalized ratio (INR) was 1.6, but thromboelastography showed an elevated maximal amplitude of 76.5 mm (normal 1⁄4 55-74 mm) that was consistent with a hypercoagulable tendency. The dissection and anhepatic stage proceeded uneventfully. Compression of the right heart by the enlarged liver was relieved after the completion of the native hepatectomy (Fig. 1C,D). After reperfusion, the surgical team reported persistent graft congestion. To determine the etiology of the congestion, we first assessed the intravascular volume status and cardiac function. TEE revealed a normal chamber size and hyperdynamic biventricular systolic function. The central venous pressure was 9 mm Hg. A possible infracardiac source of congestion was then sought. A TEE probe was redirected to visualize the IVC via a modified bicaval view. The IVC was grossly dilated and tapered acutely toward an area of marked stenosis just inferior to the right atrium (RA; Fig. 2A). Directing the probe superiorly revealed a protruding intracaval mass at the cavoatrial junction (Fig. 2B). The irregular borders were most consistent with a mural thrombus. Highly turbulent flow on color Doppler imaging was indicative of a hemodynamically significant lesion immediately superior to hepatic veins (HVs; Fig. 2C). To confirm this observation, sterile pressure tubing was passed onto the surgical field, and the pressure in the infrahepatic IVC was measured directly; this demonstrated a high pressure gradient (9 mm Hg) between the IVC and superior vena cava. On the basis of these findings, heparin anticoagulation was instituted and maintained throughout the surgery and postoperatively. We considered an endovascular intervention to relieve the IVC stenosis but abandoned this approach because of a fear of dislodging the thrombus into the right heart or covering HVs on account of their proximity to the lesion. We proceeded with anticoagulation and close follow-up. The intraoperative course was complicated by thrombosis of the hepatic artery, which necessitated takedown of the anastomosis and revision. The remainder of the surgery was uneventful. No blood products were transfused, and the patient was discharged to the intensive care unit in stable condition. On postoperative day 1, visceral Doppler sonography revealed antegrade flows and normal resistive indices in hepatic arteries, portal veins, and HVs and antegrade flow in the IVC. Hepatic and renal echogenicity was reported to be normal, and this ruled out significant liver congestion and hydronephrosis. Declining trends in transaminases and INR (from 2.3 on admission to the intensive care unit to 1.6) were consistent with improving graft function. Anticoagulation and close follow-up were continued. On postoperative day 5, repeat Doppler sonography demonstrated decreased resistive indices and blunted waveforms in hepatic arteries that were a concern for arterial thrombosis or kinking. Flows in portal veins and HVs and in the IVC were appropriately directional, but contrast venography of the IVC confirmed

High end-expiratory airway pressures caused by internal obstruction of the Draeger Apollo® scavenger system that is not detected by the workstation self-test and visual inspection.

whereby ordinal or categorical Likert scores are mapped onto a linear numerical scale. Watson also correctly points out that Likert score intervals are not necessarily equal or even certain. Fortunately, the Z-score system is based on relative performance and does not use absolute numerical cutoff scores. Although Z-scores are not diagnostic of any particular absolute level of performance, they do provide an excellent method for differentiating relative resident performance among a cohort of residents. This allows us to identify relatively poorer performers, examine the faculty-provided comments for clues as to why the scores were low and, in turn, create performance improvement strategies that often result in performance improvement, as shown in the paper in figure 9. Van Schalkwyk, Campbell, and Short are primarily concerned with misclassification of a large fraction of residents based on the statistical methodology found in the paper. In particular, they note that as the number of evaluations gets very large, precisely one-half of all residents will be confidently labeled as below average according to the approach used in the paper. They appear to express concern that more than 50% of residents could potentially be inappropriately labeled as problematic or poorly performing, which could have implications for their management and even future careers. Van Schalkwyk, Campbell, and Short appear to have interpreted “below average” as incompetent or problematic. Nowhere in the paper is this inference made. The Z-score system allows relative ordering of residents within a cohort. As correctly pointed out by these authors, the lowest-performing resident in the group may be perfectly competent. The Z-score system relates not to competence but to performance, as stated in the paper. The system correctly identifies relative performance of one resident compared with another and does so with a degree of statistical significance allowing differentiation of levels of performance. The system does not claim that the lowest-performing resident is incompetent. In fact, individual scores are meaningless per se, and it is only in the context of the comments associated with Z-scores that concerning performance attributes are identified and intervened upon. Thus there is no threshold Z-score that identifies a competent versus an incompetent resident. However, as one moves further and further below average, the likelihood of finding concerning or problematic performance gets higher and higher. This is precisely what was found in this study. For example, as mean Z-scores fall further and further below zero, the faculty increasingly checked off clinical-competency boxes relating to significant concerns with performance. This is expected if Z-scores relate to performance. As mentioned in the paper, we tended to find actionable performance concerns associated with Z-scores of about 0.5 and below. When such scores are noted, the comments associated with these scores are examined for diagnostic clues that can explain the lower-than-average performance scores. If we find actionable concerns in the comments, we create interventions, and the resident is tasked with performance improvement in the identified areas. Examples of success using this method were presented in the paper. At times, we also find residents whose average Z-scores are near 0.5 and who do not have any concerning comments related to their below-average Z-scores. Such residents are simply exhibiting performance that is below average for the cohort but is not concerning in terms of competence. Ideally, every resident would have a performance-improvement program, including those with above-average Z-scores. However, given limited resources, we focus on residents having below-average Zscores with the intent of improving their performance.

A quantitative model to predict blood use in adult orthotopic liver transplantation.

To identify preoperative predictors for the use of any blood component during and after orthotopic liver transplantation (OLT), we performed a retrospective analysis on 602 OLT patients who were randomly split into a training set (n = 482) and a validation set (n = 120). Hemoglobin and calculated MELD score were identified as independent predictors for blood use using bootstrap aggregation. A logistic regression model constructed using both variables showed comparable performance in the training and validation sets. Predictive scores can be obtained from a nomogram, and a score above -2.328 predicted transfusion of any blood component with a positive predictive value of 97% and 96% in the training and validation sets, respectively.

Atrial Laceration Caused by Removal of a Transjugular Intrahepatic Portosystemic Shunt Necessitates Emergent Cardiopulmonary Bypass during Liver Transplant: A Case Report

In situ transjugular intrahepatic portosystemic shunting (TIPS) can complicate liver transplantation. We present a case where an intraoperative attempt to remove a malpositioned TIPS resulted in atrial laceration. Massive transfusion and emergent institution of cardiopulmonary bypass allowed patient resuscitation and completion of surgery. We describe our surgical and anesthesiologic management, and discuss the absence of criteria to predict when TIPS may become adherent to the inferior vena cava or the right atrium and difficult to remove.

Combined Liver-Kidney Transplantation Complicated by Intraoperative Discovery of a Bronchobiliary Fistula

Herein, we report the case of an intraoperative diagnosis of bronchobiliary fistula during combined liver-kidney transplantation because of polycystic disease. The diagnosis necessitated changes in surgical and anesthesiologic management and in the overall medical decision-making process. Emergent isolation of the affected lung was instituted to mitigate a large air leak and ensure adequate respiratory exchange, and to enable surgical repair. The kidney transplantation procedure was delayed for a few hours, enabling hemodynamic and respiratory stabilization in the intensive care unit before conditions were deemed adequate to proceed. The posttransplantation course was complicated but eventually successful, and the patient recovered both liver and kidney function. At a later evaluation, we realized that diagnosis of bronchobiliary fistula could have been made preoperatively had the chest radiograph been interpreted correctly and had the clinicians involved had a higher degree of suspicion for this complication of polycystic liver disease.