Caring for the Amish: What Every Anesthesiologist Should Know.

The Amish are a relatively isolated group with cultural and religious customs that differ significantly from the mainstream American population. Functioning as tight-knit communities with strong conservative Christian beliefs, the Amish maintain a culture based on intentional separateness from the outside world. Key aspects of Amish life include distinct clothing and behaviors, a unique language, an agrarian lifestyle, limited formal education, nonviolence/nonaggression, and a general lack of modern technology, as exemplified by the use of the traditional horse-and-buggy. The Amish have distinct health care practices, beliefs, and goals, and because of differing genetics and lifestyle, also have a distinct constellation of health and disease characteristics. This article reviews the core beliefs, community and lifestyle, health care beliefs and practices, and health characteristics of this unique and medically challenging population. Generalizable strategies for providing culturally competent care for any such ethnically, socially, or medically unique community are presented.

Effect of cold perfusion and perfluorocarbons on liver graft ischemia in a donation after cardiac death model.

BACKGROUND: Effects of two perfluorocarbon (PFC) formulations (perfluorodecalin emulsion and perfluorodecalin liquid) on the quality of liver graft preservation, in a donation after cardiac death (DCD) rat model, were investigated. The significance of continuous graft perfusion during cold preservation was also explored. MATERIALS AND METHODS: DCD model: 30 min after cardiopulmonary arrest was initiated, livers were excised and flushed with cold University of Wisconsin (UW) solution (± PFC) and preserved in the same solution for 8 h. The study groups were preserved as follows: group 1: no perfusion; group 2: perfusion with UW; group 3: PFC was administered before cardiac arrest and the liver was perfused with UW alone; and groups 4 and 5: perfused with UW + 1 of two PFCs. In a baseline group used only for comparison of gene expression, livers were quick-frozen after cardiac arrest. Microarrays were used to analyze liver messenger RNA transcripts. Histopathologic, immunohistochemical, and ADP/ATP ratio evaluations were performed to assess the quality of graft preservation. RESULTS: Significant decreases in downregulation and increases in upregulation of hepatic genes (relative to baseline) were demonstrated in all perfusion groups. This trend was most pronounced in the PFC groups. Lower fat content and ADP/ATP ratio and a reduction in Caspase 3 activation were found in all perfusion groups. CONCLUSION: Hypothermic perfusion of rat DCD liver grafts with oxygenated UW solution (± PFC) produced superior preservation compared with nonperfusion storage. The observed changes in expression of hepatic genes may represent a protective effect in the DCD model.

Nociceptin receptor signaling in sympathetic neurons from septic rats.

BACKGROUND: The endogenous opioid peptide, nociception (Noc), contributes to the regulation of systemic blood pressure and regional blood flow. Recent clinical and animal studies have reported that Noc and its receptor (nociceptin/orphanin FQ [NOP]) are involved in inflammation and sepsis. The purpose of the present study was to examine the modulation of Ca(2+) channels by Noc in acutely isolated stellate ganglion (SG) neurons from control and septic rats. MATERIALS AND METHODS: Sepsis was induced in male Sprague-Dawley rats via cecal ligation and puncture. SG neurons were isolated 24 and 72 h after sepsis induction. Thereafter, the concentration-response relationships for the Noc-stimulated NOP receptor Ca(2+) current inhibition were determined using the whole-cell patch clamp technique. In addition, the Noc precursor (prepronociceptin [PNOC]) and NOP receptor messenger RNA (mRNA) levels were determined by quantitative real-time polymerase chain reaction, and PNOC protein levels were measured by Western blot analysis. RESULTS: Comparison of the Noc concentration-response relationships in SG neurons from control and septic rats 24 h after sepsis revealed similar potency and efficacy. Moreover, 72 h after sepsis, neurons from control and septic rats exhibited an increased potency compared with both groups at the 24-h time point--an effect that was more pronounced in neurons from septic rats. PNOC mRNA levels were significantly greater in SG neurons isolated from septic rats compared with control neurons, but NOP receptor mRNA levels remained unchanged during the 72-h period. CONCLUSIONS: Our study demonstrates the cecal ligation and puncture model-induced temporal upregulation of components within the NOP receptor signaling pathway in rat sympathetic neurons. As SG neurons provide the main sympathetic input to the heart, an increased Noc release and potency during sepsis may compromise cardiovascular function.

Computational model for nanocarrier binding to endothelium validated using in vivo, in vitro, and atomic force microscopy experiments.

A computational methodology based on Metropolis Monte Carlo (MC) and the weighted histogram analysis method (WHAM) has been developed to calculate the absolute binding free energy between functionalized nanocarriers (NC) and endothelial cell (EC) surfaces. The calculated NC binding free energy landscapes yield binding affinities that agree quantitatively when directly compared against analogous measurements of specific antibody-coated NCs (100 nm in diameter) to intracellular adhesion molecule-1 (ICAM-1) expressing EC surface in in vitro cell-culture experiments. The effect of antibody surface coverage (σ(s)) of NC on binding simulations reveals a threshold σ(s) value below which the NC binding affinities reduce drastically and drop lower than that of single anti-ICAM-1 molecule to ICAM-1. The model suggests that the dominant effect of changing σ(s) around the threshold is through a change in multivalent interactions; however, the loss in translational and rotational entropies are also important. Consideration of shear flow and glycocalyx does not alter the computed threshold of antibody surface coverage. The computed trend describing the effect of σ(s) on NC binding agrees remarkably well with experimental results of in vivo targeting of the anti-ICAM-1 coated NCs to pulmonary endothelium in mice. Model results are further validated through close agreement between computed NC rupture-force distribution and measured values in atomic force microscopy (AFM) experiments. The three-way quantitative agreement with AFM, in vitro (cell-culture), and in vivo experiments establishes the mechanical, thermodynamic, and physiological consistency of our model. Hence, our computational protocol represents a quantitative and predictive approach for model-driven design and optimization of functionalized nanocarriers in targeted vascular drug delivery.

Efficacy of Infrared Vein Visualization versus Standard Technique for Peripheral Venous Cannulation in Infant and Toddler Populations: A Randomized Study.

Establishing intravenous (IV) access in younger patient populations via the traditional cannulation technique for procedures requiring anesthesia is often challenging. Infrared (IR) vein visualization is a modality that aids venous cannulation; however, few reports of this technique exist in the infant and toddler population. The primary aim of this study was to compare the efficacy of IR vein visualization to the standard cannulation technique for obtaining peripheral IV access in infant and toddler populations. Following Institutional Review Board (IRB) approval and written informed consent, children were randomly assigned to either a standard cannulation technique group or an IR vein visualization device group for venous cannulation. The primary outcome variable was the success rate of IV cannulation, and the secondary variables were the total number of attempts and the time to successful cannulation. No difference was noted between either group for first-attempt success rate (standard versus IR: 61.25% vs. 54.4%; p = 0.4) or time to establish IV cannulation (standard versus IR: median [interquartile range], 40 s [24-120] vs. 53 s [26-106]; p = 0.55). The anesthesiologist's grading of the anticipated difficulty of IV cannulation was a significant predictor of cannulation success (p = 0.0016). Our study demonstrated no significant benefit in utilizing the IR vein visualization device in terms of the overall success rate, number of attempts, and time to establish successful IV cannulation when compared to the standard technique. However, in difficult IV access situations, this device proved to be a valuable rescue adjunct.

New Serotonin-Norepinephrine Reuptake Inhibitors and Their Anesthetic and Analgesic Considerations.

Serotonin-norepinephrine reuptake inhibitors (SNRIs) inhibit the presynaptic neuronal uptake of serotonin and norepinephrine and prolong the effects of the monoamines in the synaptic cleft within the central nervous system, leading to increased postsynaptic receptor activation and neuronal activities. Serotonin-norepinephrine reuptake inhibitors can have multiple clinical indications, including as the first-line agents for the management of depression and anxiety, and as analgesics in the treatment of chronic pain. The effects of reuptake inhibition of norepinephrine and serotonin are often dose-dependent and agent-dependent. There are five FDA-approved serotonin-norepinephrine reuptake inhibitors (desvenlafaxine, duloxetine, levomilnacipran, milnacipran and sibutramine) currently being marketed in the United States. As the COVID-19 pandemic significantly increased the incidence and prevalence of anxiety and depression across the country, there are significantly increased prescriptions of these medications perioperatively. Thus, anesthesiologists are more likely than ever to have patients administered with these agents and scheduled for elective or emergency surgical procedures. A thorough understanding of these commonly prescribed serotonin-norepinephrine reuptake inhibitors and their interactions with commonly utilized anesthetic agents is paramount. There are two potentially increased risks related to the continuation of SNRIs through the perioperative period: intraoperative bleeding and serotonin syndrome. SNRIs have some off-label uses, more new indications, and ever-increasing new applications in perioperative practice. This article aims to review the commonly prescribed serotonin-norepinephrine reuptake inhibitors and the current clinical evidence regarding their considerations in perioperative anesthesia and analgesia.

Recovery Characteristics in Neonates Following General Anesthesia: A Retrospective Chart Review.

Introduction Preterm babies increasingly survive the neonatal period as a result of advanced care practices. Accordingly, anesthesiologists are likely to encounter these patients with greater frequency. Ex-premature infants and term neonates are known to have an increased risk of post-operative apneas following surgery and anaesthesia. Methods Following approval from the Institutional Review Board, we performed a retrospective chart review of neonates 0-28 days of age who underwent general anaesthesia procedures over two years. Data collected included age days, sex, weight, gestational age, American Society of Anaesthesiologists (ASA) physical status, type of anaesthetic (general/regional/spinal), airway management, surgical procedure, intraoperative adverse events, duration of anaesthesia, medications administered, post-operative recovery location, the occurrence of apneic events, medical co-morbidities, duration of post anaesthesia care unit (PACU) admission, a requirement for neonatal intensive care unit (NICU) admission, and duration of hospital admission. Results A total of 239 charts were reviewed from January 1, 2015, to December 31, 2016. Ninety-five cases were excluded for required postoperative mechanical ventilation. For the remaining 144 cases, the mean age was 12.8 days, 65% male, 35% female, mean gestational age 38.6 weeks, mean post-menstrual age 40.5 weeks, mean ASA status 3.5, and mean weight 3.46 kg. Post-operative apnea was observed in two neonates (1.4%). Risk factors for postoperative apnea included lower gestational age at birth (median 37.5 vs. 39.1 weeks, p=0.26), lower post-menstrual age (median 38.5 vs. 41.0 weeks, p=0.18), and lower weight (median 2.8 vs. 3.5kg, p=0.27), respectively. ASA classification, preoperative anaemia, and known pathology were all significant risk factors for apnea (p<0.05). Significant factors from the bivariate analysis were preoperative anaemia, known pathology, age, duration of anaesthesia, weight, intraoperative fentanyl, and amount of neuromuscular blocker. Age and preoperative anaemia were significant predictors for recovery location. The odds of going to PACU vs NICU/PICU for post-operative recovery were 7.4 times greater for every two weeks greater age (95% CI=(2.80-19.31), p<0.001).  Conclusion This study corroborates previous findings of predictive risk factors for post-anaesthesia apnea in preterm and term neonates. Previously reported risk factors, including low gestational/post-menstrual age, lower weight, and intraoperative narcotic use, were likely contributors to one of the apneic events in our study. A larger sample size is warranted to confirm a valid predictive model. Standardized universal guidelines would be useful in eliminating local variation in PACU monitoring and discharge criteria in this vulnerable age group.

Transglottic high frequency jet ventilation for management of laryngeal fracture associated with air bag deployment injury.

Blunt laryngeal trauma is an uncommon injury associated with high prehospital mortality. Conventional airway management consists of awake tracheostomy. A case of laryngeal trauma associated with air bag deployment managed with tubeless suspension laryngoscopy with high frequency transglottic jet ventilation is presented. The advantages of this technique in the management of patients who are not good candidates for awake tracheostomy are discussed.

Ultrasonic imaging of tumor angiogenesis using contrast microbubbles targeted via the tumor-binding peptide arginine-arginine-leucine.

Endothelial cells (EC) of angiogenic tumor vasculature are characterized by altered expression of molecular markers on their surface. Numerous peptides have been identified that specifically bind tumor angiogenic endothelium, including the tripeptide arginine-arginine-leucine (RRL). We hypothesized that ultrasound contrast microbubbles (MB) targeted via linkage with RRL would specifically adhere to tumor angiogenic endothelium versus normal myocardium, and that this selective adhesion could be detected ultrasonically. Microbubbles were conjugated to cyclic peptides containing either RRL (RRL-MB) or a glycine control sequence (control-MB). As measured in a parallel plate flow chamber, in vitro adhesion of RRL-MBs was three times greater to cultured tumor-derived ECs than to normal ECs (P < 0.01), demonstrating selective binding of RRL-MBs to tumor endothelium. Mice bearing s.c. Clone C or PC3 tumors were given i.v. injections of fluorescent RRL to show in vivo localization to tumor vasculature or were ultrasonically imaged following i.v. injections of targeted contrast MBs. Ultrasound images showed strong RRL-MB contrast enhancement within the tumors but not the control tissue myocardium. Control-MBs caused minimal enhancement in either tissue. Quantitative acoustic videointensity was significantly greater for the tumors than the hearts (5 +/- 1 versus 0.5 +/- 1 intensity units; P = 0.001). These data show that ultrasound contrast MBs targeted to tumor vasculature via RRL preferentially adhere to tumor versus normal vasculature and that this selective adherence can be detected with ultrasound. Targeted microbubbles may thus offer a noninvasive contrast-enhanced ultrasound imaging technique for the functional imaging of tumor neovascularization, and may have further implications for therapeutic tumor targeting.

Ultrasound imaging of acute cardiac transplant rejection with microbubbles targeted to intercellular adhesion molecule-1.

BACKGROUND: Noninvasive techniques for detecting acute cardiac transplant rejection are limited. We hypothesized that ultrasound contrast microbubbles targeted to the endothelial cell (EC) inflammatory marker intercellular adhesion molecule-1 (ICAM-1) would selectively bind to rejecting versus nonrejecting myocardium and that myocardial contrast echocardiography can therefore detect acute rejection. METHODS AND RESULTS: Lipid-based microbubbles were conjugated to anti-rat ICAM-1 (MBICAM) or isotype control antibody (MBControl). In vitro MBICAM adhesion to cultured rat ECs, as assessed in a parallel plate flow apparatus, was greater to inflammatory versus normal ECs (11+/-3 versus 3+/-2 microbubbles/EC, P<0.005). In vivo abdominal heterotopic heart transplantation was performed in rats (rejection group: Brown Norway to Lewis strain; control group: Lewis to Lewis or Brown Norway to Brown Norway). Triggered myocardial contrast echocardiography was performed during intravenous MBICAM or MBControl (2.5x10(6)) injection on postoperative day 5. Myocardial videointensity from adhered MBICAM was significantly higher in rejecting (n=8) versus control (n=7) rats (10+/-4 versus 1+/-4 U, P=0.01). Postmortem histology showed normal myocardium in control rats, whereas allograft myocardium demonstrated grade III to IV rejection and strong immunohistochemical ICAM-1 staining. CONCLUSIONS: Preferential adherence of ICAM-1-targeted microbubbles to rejecting versus nonrejecting rat cardiac transplant myocardium can be detected ultrasonically. Targeted microbubbles may thus offer a noninvasive ultrasound imaging technique for the detection of acute cardiac transplant rejection and other processes characterized by endothelial dysfunction.

Modulation of voltage-gated Ca2+ channels by G protein-coupled receptors in celiac-mesenteric ganglion neurons of septic rats.

Septic shock, the most severe complication associated with sepsis, is manifested by tissue hypoperfusion due, in part, to cardiovascular and autonomic dysfunction. In many cases, the splanchnic circulation becomes vasoplegic. The celiac-superior mesenteric ganglion (CSMG) sympathetic neurons provide the main autonomic input to these vessels. We used the cecal ligation puncture (CLP) model, which closely mimics the hemodynamic and metabolic disturbances observed in septic patients, to examine the properties and modulation of Ca2+ channels by G protein-coupled receptors in acutely dissociated rat CSMG neurons. Voltage-clamp studies 48 hr post-sepsis revealed that the Ca2+ current density in CMSG neurons from septic rats was significantly lower than those isolated from sham control rats. This reduction coincided with a significant increase in membrane surface area and a negligible increase in Ca2+ current amplitude. Possible explanations for these findings include either cell swelling or neurite outgrowth enhancement of CSMG neurons from septic rats. Additionally, a significant rightward shift of the concentration-response relationship for the norepinephrine (NE)-mediated Ca2+ current inhibition was observed in CSMG neurons from septic rats. Testing for the presence of opioid receptor subtypes in CSMG neurons, showed that mu opioid receptors were present in ~70% of CSMG, while NOP opioid receptors were found in all CSMG neurons tested. The pharmacological profile for both opioid receptor subtypes was not significantly affected by sepsis. Further, the Ca2+ current modulation by propionate, an agonist for the free fatty acid receptors GPR41 and GPR43, was not altered by sepsis. Overall, our findings suggest that CSMG function is affected by sepsis via changes in cell size and α2-adrenergic receptor-mediated Ca2+ channel modulation.

Fully automated common carotid artery and internal jugular vein identification and tracking using B-mode ultrasound.

We describe a fully automated ultrasound analysis system that tracks and identifies the common carotid artery (CCA) and the internal jugular vein (IJV). Our goal is to prevent inadvertent damage to the CCA when targeting the IJV for catheterization. The automated system starts by identifying and fitting ellipses to all the regions that look like major arteries or veins throughout each B-mode ultrasound image frame. The spokes ellipse algorithm described in this paper tracks these putative vessels and calculates their characteristics, which are then weighted and summed to identify the vessels. The optimum subset of characteristics and their weights were determined from a training set of 38 subjects, whose necks were scanned with a portable 10 MHz ultrasound system at 10 frames per second. Stepwise linear discriminant analysis (LDA) narrowed the characteristics to the five that best distinguish between the CCA and IJV. A paired version of Fisher's LDA was used to calculate the weights for each of the five parameters. Leave-one-out validation studies showed that the system could track and identify the CCA and IJV with 100% accuracy in this dataset.

Targeted ultrasound contrast agents: in vitro assessment of endothelial dysfunction and multi-targeting to ICAM-1 and sialyl Lewisx.

An ultrasound-based molecular imaging technique capable of detecting endothelial cell markers of inflammation may allow early, non-invasive assessment of vascular disease. Clinical application of targeted, acoustically-active microbubbles requires optimization of microbubble-endothelial adhesion strength to maximize image signal-to-noise ratio, as well as the ability to discern the degree of inflammation along a continuum of dysfunction. Accordingly, we hypothesized that adhesion of intercellular adhesion molecule-1 (ICAM-1)-targeted microbubbles is dependent on the degree of endothelial inflammation, and that microbubbles multi-targeted to both ICAM-1 (via anti-ICAM-1 antibodies) and selectins (via sialyl Lewisx) demonstrate greater adhesion strength than microbubbles targeted to either inflammatory marker alone. In a radial flow chamber, microbubbles were perfused across endothelial cells activated with interleukin-1beta to four different levels of inflammation, as assessed by quantitative ICAM-1 expression. ICAM-1-targeted microbubble adhesion strength increased with increasing degree of inflammation, with a relationship that was both positive and linear (r > 0.99). Microbubble adhesion strength was significantly higher for the multi-targeted microbubbles than either of the single-targeted microbubbles. These data thus demonstrate that multi-targeting of contrast microbubbles may offer improved adhesion characteristics, allowing for greater sensitivity to inflammation. Furthermore, the adhesion strength of targeted microbubbles is linearly dependent on the degree of inflammation, suggesting that targeted ultrasound imaging may offer differentiation between various degrees of endothelial dysfunction, and thus detect not only the presence, but also the severity of inflammatory disease processes.

Modulating targeted adhesion of an ultrasound contrast agent to dysfunctional endothelium.

The early stages of atherosclerosis are characterized by increased endothelial cell (EC) surface expression of leukocyte adhesion molecules (LAMs). Ultrasound detection of acoustically active LAM-targeted microbubbles might provide a means to noninvasively assess the functional status of the endothelium. Toward this end, a lipid-based perfluorobutane-filled microbubble was synthesized with various densities of anti-ICAM-1 monoclonal antibodies conjugated to the bubble shell. We hypothesized that modulating the surface antibody density would permit regulation of the adhesion characteristics of the microbubbles, and that microbubble adhesion would be dependent on local wall shear rate. Coverslips of cultured human coronary artery ECs were exposed to microbubbles with various surface antibody densities (1%, 5%, 10%, 50%, 75%, and 100% of maximum coverage) at various wall shear rates (100, 175, 250, 350, and 500 s-1) in a parallel plate perfusion chamber. ECs were either normal or activated by interleukin-1 beta to overexpress ICAM-1. Adhesion was greater to activated vs. normal ECs (p < 0.001), increased with increasing surface antibody density (p < 0.01), and decreased with increasing wall shear rate (p = 0.02). We conclude that shell antibody density and wall shear rate are critical parameters controlling differential microbubble adhesion. This phenomenon might ultimately permit imaging of clinically relevant LAM expression in vivo.