Case Report Use of Early Inhaled Nitric Oxide Therapy in Fat Embolism Syndrome to Prevent Right Heart Failure

Fat embolism syndrome (FES) is a life-threatening condition in which multiorgan dysfunction manifests 48-72 hours after long bone or pelvis fractures. Right ventricular (RV) failure, especially in the setting of pulmonary hypertension, is a frequent feature of FES. We report our experience treating 2 young, previously healthy trauma patients who developed severe hypoxemia in the setting of FES. Neither patient had evidence of RV dysfunction on echocardiogram. The patients were treated with inhaled nitric oxide (NO), and their oxygenation significantly improved over the subsequent few days. Neither patient developed any cardiovascular compromise. Patients with FES that have severe hypoxemia and evidence of adult respiratory distress syndrome (ARDS) are likely at risk for developing RV failure. We recommend that these patients with FES and severe refractory hypoxemia should be treated with inhaled NO therapy prior to the onset of RV dysfunction

Novel use of an exchange catheter to facilitate intubation with an Aintree catheter in a tall patient with a predicted difficult airway: a case report

<p>Abstract</p> <p>Introduction</p> <p>The Aintree intubating catheter (Cook^®Medical Inc., Bloomington, IN, USA) has been shown to successfully facilitate difficult intubations when other methods have failed. The Aintree intubating catheter (Cook^®Medical Inc., Bloomington, IN, USA) has a fixed length of 56 cm, and it has been suggested in the literature that it may be too short for safe use in patients who are tall.</p> <p>Case presentation</p> <p>We present the case of a 32-year-old, 180 cm tall Caucasian woman with a predicted difficult airway who presented to our facility for an emergency cesarean section. After several failed intubation attempts via direct laryngoscopy, an airway was established with a laryngeal mask airway. After delivery of a healthy baby, our patient's condition necessitated tracheal intubation. A fiber-optic bronchoscope loaded with an Aintree intubating catheter (Cook^®Medical Inc., Bloomington, IN, USA) was passed through the laryngeal mask airway into the trachea until just above the carina, but was too short to safely allow for the passage of an endotracheal tube.</p> <p>Conclusions</p> <p>We present a novel technique in which the Aintree intubating catheter (Cook^®Medical Inc., Bloomington, IN, USA) was replaced with a longer (100 cm) exchange catheter, over which an endotracheal tube was passed successfully into the trachea.</p

The Role of Branched-Chain Amino Acids in Glutamate Metabolism and Seizure Modulation in a Rat Model of Mesial Temporal Lobe Epilepsy

Elevations in extracellular glutamate in the brain are implicated in the pathogenesis of several neurological conditions, including mesial temporal lobe epilepsy. The underlying mechanisms of this elevation are not completely understood, however, and there are no effective methods that reduce the elevation or limit its neurotoxic effects. Glutamate is normally cleared from the extracellular space and replenished in axon terminals by a series of compartmentalized processes collectively known as the glutamate-glutamine cycle. A critical step of the cycle is the conversion of glutamate to glutamine by the astrocyte-specific enzyme glutamine synthetase. In several neurological conditions including mesial temporal lobe epilepsy, studies have demonstrated that glutamine synthetase activity is pathologically low. Because glutamine synthetase is thought to be critical for glutamate metabolism, its deficiency has been postulated as a possible mechanism for the increased glutamate observed in the extracellular fluid of the epileptogenic areas of the brain. The branched-chain amino acids valine, leucine, and isoleucine are thought to contribute to de novo synthesis of glutamate in the brain by transferring an amino nitrogen to the tricarboxylic acid intermediate alpha-ketoglutarate. The branched-chain amino acids have gained increasing attention in recent years for the important roles they play in cell signaling, immune modulation, protein metabolism, and glutamate synthesis. It was previously unknown, however, if increasing peripheral branched-chain amino acids concentrations can increase extracellular glutamate concentrations in the brain during physiological or in pathological conditions, particularly when glutamate metabolism is perturbed (i.e. in glutamine synthetase deficiency). Moreover, the effects of branched-chain amino acids on seizures and neuronal viability were unknown. The objective of this thesis was to use state of-the-art methods in microdialysis, isotope tracing, mass spectrometry and video-intracranial electroencephalogram recordings to study the metabolism and functional effects of branched-chain amino acids and glutamate in naïve and glutamine synthetase-inhibited, epileptic rats. The central hypothesis was that increased extracellular concentrations of branched-chain amino acids in the brain, in combination with alterations in enzymatic processes of glutamate metabolism, are key pathogenic features that result in brain glutamate excess and seizures in mesial temporal lobe epilepsy. To achieve the objective of this thesis, we pursued 3 specific aims. In Aim 1, we determined the effects of intravenous branched-chain amino acid administration on brain extracellular fluid concentrations of glutamate and glutamine in naïve rats. We found that the administration of a high-dose bolus of branched-chain amino acids significantly increased the concentrations of branched-chain amino acids and glutamine in the extracellular compartment of the brain. Glutamate concentrations transiently increased, but the elevation was not statistically significant. In Aim 2, we determined the effects of intravenous isotope-labeled leucine administration on brain extracellular fluid concentrations of glutamate and glutamine in glutamine synthetase-inhibited rats. We found that glutamine synthetase-inhibited rats, like normal rats, were remarkably efficient in handling glutamate. Moreover, we demonstrated that leucine influx across the blood brain barrier is highly dependent on glutamine levels in the extracellular fluid of the brain. In Aim 3, we investigated the effects of chronic oral branched-chain amino acid supplementation on spontaneous and induced seizures, and neuron loss in glutamine synthetase-inhibited epileptic rats. We found that the branched-chain amino acid supplementation was ineffective in reducing the frequency and severity of spontaneous seizures, but increased the threshold to pentylenetetrazole-induced seizures. Furthermore, chronic branched-chain amino acid supplementation resulted in increased loss of hippocampal hilar neurons. Future studies will explore the impact of glutamine and leucine dysregulation in the brain on cell signaling and immune modulation, which may play an important role in epilepsy as well as other disorders. We will also further explore the mechanisms underlying the branched-chain amino acid-induced neuron loss

Case Report Use of Early Inhaled Nitric Oxide Therapy in Fat Embolism Syndrome to Prevent Right Heart Failure

Copyright © 2014 Evgeni Brotfain et al.This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Fat embolism syndrome (FES) is a life-threatening condition in which multiorgan dysfunction manifests 48–72 hours after long bone or pelvis fractures. Right ventricular (RV) failure, especially in the setting of pulmonary hypertension, is a frequent feature of FES.We report our experience treating 2 young, previously healthy trauma patients who developed severe hypoxemia in the setting of FES. Neither patient had evidence of RV dysfunction on echocardiogram. The patients were treated with inhaled nitric oxide (NO), and their oxygenation significantly improved over the subsequent few days. Neither patient developed any cardiovascular compromise. Patients with FES that have severe hypoxemia and evidence of adult respiratory distress syndrome (ARDS) are likely at risk for developing RV failure. We recommend that these patients with FES and severe refractory hypoxemia should be treated with inhaled NO therapy prior to the onset of RV dysfunction. 1

Neuroprotective effects of intravenous anesthetics: a new critical perspective.

Perioperative cerebral damage can result in various clinical sequela ranging from minor neurocognitive deficits to catastrophic neurological morbidity with permanent impairment and death. The goal of neuroprotective treatments is to reduce the clinical effects of cerebral damage through two major mechanisms: increased tolerance of neurological tissue to ischemia and changes in intra-cellular responses to energy supply deprivation. In this review, we present the clinical evidence of intravenous anesthetics on perioperative neuroprotection, and we also provide a critical perspective for future studies. The neuroprotective efficacy of the intravenous anesthetics thiopental, propofol and etomidate is unproven. Lidocaine may be neuroprotective in non-diabetic patients who have undergoing cardiac surgery with cardiopulmonary bypass (CBP) or with a 48-hour infusion, but conclusive data are lacking. There are several limitations of clinical studies that evaluate postoperative cognitive dysfunction (POCD), including difficulties in identifying patients at high-risk and a lack of consensus for defining the "gold-standard" neuropsychological testing. Although a battery of neurocognitive tests remains the primary method for diagnosing POCD, recent evidence suggests a role for novel biomarkers and neuroimaging to preemptively identify patients more susceptible to cognitive decline in the perioperative period. Current evidence, while inconclusive, suggest that intravenous anesthetics may be both neuroprotective and neurotoxic in the perioperative period. A critical analysis on data recorded from randomized control trials (RCTs) is essential in identifying patients who may benefit or be harmed by a particular anesthetic. RCTs will also contribute to defining methodologies for future studies on the neuroprotective effects of intravenous anesthetics

Establishment of an animal model of depression contagion

BackgroundDepression is a common and important cause of morbidity, and results in a significant economic burden. Recent human studies have demonstrated that that depression is contagious, and depression in family and friends might cumulatively increase the likelihood that a person will exhibit depressive behaviors. The mechanisms underlying contagion depression are poorly understood, and there are currently no animal models for this condition.MethodsRats were divided into 3 groups: depression group, contagion group, and control group. After induction of depression by 5 weeks of chronic unpredictable stress, rats from the contagion group were housed with the depressed rats (1 naïve rat with 2 depressed rats) for 5 weeks. Rats were then subjected to sucrose preference, open field, and forced swim tests.ResultsThe sucrose preference was significantly reduced in the depressed rats (p&lt;0.01) and contagion depression rats (p&lt;0.01). Climbing time during forced swim test was reduced in the depression and contagion depression groups (p&lt;0.001), whereas immobility time was significantly prolonged in only the depression group (p&lt;0.001). Rats in both the depression (p&lt;0.05) and depression contagion group (p&lt;0.005) had decreased total travel distance and decreased mean velocity in the open field test, whereas the time spent in the central part was significantly shorter in only the depression group (p&lt;0.001).ConclusionsIn this study, for the first time we demonstrated depression contagion in an animal model. A reliable animal model may help better understand the underlying mechanisms of contagion depression, and may allow for future investigations of the studying therapeutic modalities

Extracorporeal methods of blood glutamate scavenging: a novel therapeutic modality

Pathologically elevated glutamate concentrations in the brain's extracellular fluid are associated with several acute and chronic brain insults. Studies have demonstrated that by decreasing the concentration of glutamate in the blood, thereby increasing the concentration gradient between the brain and the blood, the rate of brain-to-blood glutamate efflux can be increased. Blood glutamate scavengers, pyruvate and oxaloacetate have shown great promise in providing neuroprotection in many animal models of acute brain insults. However, glutamate scavengers' potential systemic toxicity, side effects and pharmacokinetic properties may limit their use in clinical practice. In contrast, extracorporeal methods of blood glutamate reduction, in which glutamate is filtered from the blood and eliminated, may be an advantageous adjunct in treating acute brain insults. Here, we review the current evidence for the glutamate-lowering effects of hemodialysis, peritoneal dialysis and hemofiltration. The evidence reviewed here highlights the need for clinical trials

Association between Hypophosphatemia and Cardiac Arrhythmias in the Early Stage of Sepsis: Could Phosphorus Replacement Treatment Reduce the Incidence of Arrhythmias?

It is well known that new-onset arrhythmias are common in septic patients. It is thought that hypophosphatemia in the early stages of sepsis may contribute to the development of new arrhythmias. In this study, we hypothesized that intravenous (IV) phosphorus replacement may reduce the incidence of arrhythmias in critically ill patients. 34 adult septic patients with hypophosphatemia admitted to the general intensive care unit were treated with IV phosphorus replacement per ICU protocol, and the incidence of new arrhythmias were compared with 16 patients from previously published data. IV phosphorus replacement was associated with a significantly reduced incidence of arrhythmias (38% vs. 63%, p=0.04). There were no differences in observed mortality between subgroups, which may be due to the small sample size. This study demonstrated that IV phosphorus replacement might be effective in reducing the incidence of new arrhythmias in septic patients