Advanced endoscopic gastrointestinal techniques for the bariatric patient: implications for the anesthesia provider.

PURPOSE OF REVIEW: The incidence of obesity and the use of endoscopy have risen concurrently throughout the 21st century. Bariatric patients may present to the endoscopy suite for primary treatments as well as preoperatively and postoperatively from bariatric surgery. However, over the past 10 years, endoscopic bariatric and metabolic therapies (EBMTs) have emerged as viable alternatives to more invasive surgical approaches for weight loss. RECENT FINDINGS: The United States Food and Drug Administration (FDA) has approved several different gastric EBMTs including aspiration therapy, intragastric balloons, and endoscopic suturing. Other small intestine EBMTs including duodenal mucosal resurfacing, endoluminal magnetic partial jejunal diversion, and Duodenal-Jejunal Bypass Liner are not yet FDA approved, but are actively being investigated. SUMMARY: Obesity causes anatomic and physiologic changes to every aspect of the human body. All EBMTs have specific nuances with important implications for the anesthesiologist. By considering both patient and procedural factors, the anesthesiologist will be able to perform a safe and effective anesthetic.

Defining a Taxonomy of Intracranial Hypertension: Is ICP More Than Just a Number?

Intracranial pressure (ICP) monitoring and control is a cornerstone of neuroanesthesia and neurocritical care. However, because elevated ICP can be due to multiple pathophysiological processes, its interpretation is not straightforward. We propose a formal taxonomy of intracranial hypertension, which defines ICP elevations into 3 major pathophysiological subsets: increased cerebral blood volume, masses and edema, and hydrocephalus. (1) Increased cerebral blood volume increases ICP and arises secondary to arterial or venous hypervolemia. Arterial hypervolemia is produced by autoregulated or dysregulated vasodilation, both of which are importantly and disparately affected by systemic blood pressure. Dysregulated vasodilation tends to be worsened by arterial hypertension. In contrast, autoregulated vasodilation contributes to intracranial hypertension during decreases in cerebral perfusion pressure that occur within the normal range of cerebral autoregulation. Venous hypervolemia is produced by Starling resistor outflow obstruction, venous occlusion, and very high extracranial venous pressure. Starling resistor outflow obstruction tends to arise when cerebrospinal fluid pressure causes venous compression to thus increase tissue pressure and worsen tissue edema (and ICP elevation), producing a positive feedback ICP cycle. (2) Masses and edema are conditions that increase brain tissue volume and ICP, causing both vascular compression and decrease in cerebral perfusion pressure leading to oligemia. Brain edema is either vasogenic or cytotoxic, each with disparate causes and often linked to cerebral blood flow or blood volume abnormalities. Masses may arise from hematoma or neoplasia. (3) Hydrocephalus can also increase ICP, and is either communicating or noncommunicating. Further research is warranted to ascertain whether ICP therapy should be tailored to these physiological subsets of intracranial hypertension.

A behavioral and molecular analysis of ketamine in zebrafish.

Ketamine exerts powerful anesthetic, psychotic, and antidepressant effects in both healthy volunteers and clinically depressed patients. Although ketamine targets particular glutamate receptors, there is a dearth of evidence for additional, alternative molecular substrates for the behavioral actions of this N-methyl-D-aspartate (NMDA) receptor antagonist drug. Here, we provide behavioral and molecular evidence for the actions of ketamine using a new vertebrate model for psychiatric disorders: the zebrafish. Subanesthetic doses of ketamine produced a variety of abnormal behaviors in zebrafish that were qualitatively analogous to those previously measured in humans and rodents treated with drugs that produce transient psychosis. In addition, we revealed that the transcription factor Phox2b is a molecular substrate for the actions of ketamine, particularly during periods of hypoxic stress. Finally, we also show that SIRT1, a histone deacetylase widely recognized for its link to cell survival is also affected by hypoxia crises. These results establish a relevant assay system in which the effects of psychotomimetic drugs can rapidly be assessed, and provide a plausible and novel neuronal mechanism through which ketamine affects critical sensory circuits that monitor breathing behavior.

Distribution analysis of deacetylase SIRT1 in rodent and human nervous systems.

Sirtuins function with other biogenic molecules to promote adaptation to caloric restriction in a broad spectrum of eukaryotic species. Sirtuin pathways also converge in the mammalian brain where they appear to protect neurons from nutrient stress. However, few anatomical studies on sirtuins (e.g., SIRT1) are available, particularly those detailing the spatial distribution and subcellular localization pattern of SIRT1 in the brain parenchyma. Here, we report the characterization of a panel of SIRT1-specific antibodies within rodent (i.e., rat and mouse) and human central nervous systems. Immunocytochemical and Western blot analyses indicate that the subcellular localization of SIRT1 is predominantly nuclear throughout the rodent brain and spinal cord. A similar subcellular distribution pattern of SIRT1 was detected in human central nervous system material. SIRT1 is ubiquitously present in areas of the brain especially susceptible to age-related neurodegenerative states (e.g., the prefrontal cortex, hippocampus and basal ganglia). Further, we show no apparent species-specific differences in the subcellular localization pattern of rodent versus human SIRT1. Finally, we identify the chemical phenotype of SIRT1-containing neurons in a number of brain sites that are strongly compromised by aging. These data provide additional and important anatomical findings for the role of SIRT1 in the mammalian brain and suggest that SIRT1 pathways are broadly distributed in neurons most susceptible to senescence injury. Activating endogenous sirtuin pathways may, therefore, offer a therapeutic approach to delay and/or treat human age-related diseases.

Expression profile of Bag 1 in the postmortem brain.

Bag 1 is a protein intimately involved in signaling pathways that regulate cell survival. Here we examined the expression profile of Bag 1 in the brain to consider issues associated with the sampling of anti-apoptotic proteins in a rat model of the human postmortem process. Following a 4h postmortem interval, we analyzed the hippocampus of rats maintained at 24 or 4 degrees C storage temperatures using immunocytochemical and Western blotting techniques. Remarkably, postmortem tissue (up to 4h) showed a significant and prominent up-regulation of Bag 1 in CA1 and CA3 subfields of the hippocampal formation. Over-expression of Bag 1, however, could only be traced down to a storage temperature of 24 degrees C. These data suggest that storage temperatures, but not postmortem intervals, significantly affect the expression profile and cellular stability of Bag 1 proteins.