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Background Due to the life-threatening consequences that a failed tracheal intubation entails, many efforts have been made to identify specific patient features, which may predict difficulty during tracheal intubation. In addition, debate exists as to whether or not video-assisted laryngoscopy (VAL) should replace direct laryngoscopy and if airway practitioners will lose their skills associated with direct laryngoscopy, now that VAL use has increased in clinical practice. Aim This study was designed to determine the first attempt success rate of tracheal intubation with the McGRATH™ MAC laryngoscope using direct visualization in patients with known difficult airways, as well as exploring the possibility of identifying a particular direct Cormack-Lehane (C-L) grade view where indirect (video) visualization can be most beneficial during laryngoscopy and intubation. Methods Following IRB/ethical board approval and written informed consent, 100 adult patients (age > 18 years) with an ASA status I-III and a BMI 2 who met ≥ 2 of the following inclusion criteria: Mallampatti class: III-IV, reduced mouth opening 40 cm for females, > 43 cm for males), thyromental distance Results Out of the 94 patients that were included in the data analysis, 72 (76.6%) were successfully intubated via direct laryngoscopy and 16 (17%) were successfully intubated via indirect (video) laryngoscopy on the first attempt with the McGRATH™ MAC ( P = 0.59). This translates to an overall first-attempt success rate of 96.15% (n = 88). Six patients required a second attempt for tracheal intubation, in which indirect (video) laryngoscopy was then performed, representing an 83% second attempt success rate (n = 5; 5.3%). One patient (1.1%) required a third intubation attempt and an alternative device was used to secure the airway (n = 1; Table 1). The most common initial C-L grade view during the first attempt was a 2b (28.7%), which accounted for 36.1% of the 72 patients that were successfully intubated via direct laryngoscopy (n = 26). A noticeable C-L grade view improvement was observed with the use of the McGRATH™ MAC using the indirect view. Thus, the most common initial indirect C-L grade view during the first attempt was a 1 (54.3%), which accounted for 65.3% of the 72 patients that were successfully intubated via direct laryngoscopy (n = 47). Conclusion The McGRATH™ MAC is a versatile laryngoscope that allows both direct and indirect (video) laryngoscopy to be performed, simultaneously if needed, with a favorable chance of successful intubation during the first attempt. VAL with the McGRATH™ MAC exhibited an enhanced glottic view and served as a successful rescue airway device during inadequate glottic visualization and/or unsuccessful tracheal intubation, after failing with the same device when direct laryngoscopy was performed.

Given potential disparity and limited allocation of deceased donor kidneys for transplantation, a new federal kidney allocation system was implemented in 2014. Donor organ function and estimated recipient survival in this system has implications for perioperative management of kidney transplant recipients. Early analysis suggests that many of the anticipated goals are being attained. For anesthesiologists, implications of increased dialysis duration and burdens of end-stage renal disease include increased cardiopulmonary disease, challenging fluid, hemodynamic management, and central vein access. With no recent evidence to guide anesthesia care within this new system, we describe the kidney allocation system, summarize initial data, and briefly review organ systems of interest to anesthesiologists. As additional invasive and echocardiographic monitoring may be indicated, one consideration may be development of a dedicated anesthesiology team experienced in management and monitoring of complex patients, in a similar manner as has been done for liver transplant recipients.

Resuscitative endovascular balloon occlusion of the aorta (REBOA) is an endovascular technique that allows for temporary occlusion of the aorta in patients with severe, life-threatening, trauma-induced noncompressible hemorrhage arising below the diaphragm. REBOA utilizes a transfemoral balloon catheter inserted in a retrograde fashion into the aorta to provide inflow control and support blood pressure until definitive hemostasis can be achieved. Initial retrospective and registry clinical data in the trauma surgical literature demonstrate improvement in systolic blood pressure with balloon inflation and improved survival compared to open aortic cross-clamping via resuscitative thoracotomy. However, there are no significant reports of anesthetic implications and perioperative management in this challenging cohort. In this narrative, we review the principles, technique, and logistics of REBOA deployment, as well as initial clinical outcome data from our level-1 American College of Surgeons-verified trauma center. For anesthesiologists who may not yet be familiar with REBOA, we make several suggestions and recommendations for intraoperative management based on extrapolation from these initial surgical-based reports, opinions from a team with increasing experience, and translated experience from emergency aortic vascular surgical procedures. Further prospective data will be necessary to conclusively guide anesthetic management, especially as potential complications and implications for global organ function, including cerebral and renal, are recognized and described.

Rat is commonly used for pharmacokinetic screening during pharmaceutical lead optimization. To handle the large number of compounds, rats with a single jugular vein cannulation are commonly utilized for intravenous pharmacokinetic studies, where the same cannula is used both for dose administration and blood sampling. We demonstrate that the single cannula method is not suitable for all compounds, especially for high logP compounds. We propose an alternative dual cannulation technique in which two cannulas are placed in the same jugular vein, thus avoiding an additional surgery. Compounds were administered orally or via intravenous infusion to compare PK parameters, including bioavailability, using both procedures. For itraconazole and amiodarone, known to bind to the cannula, the measured plasma exposures were substantially higher in the single cannulated rats than those from dual cannulated rats. Area under the plasma concentration time curve differed by 79% and 74% for itraconazole and amiodarone, respectively. When compared to the single cannulation approach, clearance, volume of distribution and bioavailability determined by dual cannulation were 39%, 60% and 38% higher for itraconazole, and 46%, 34% and 42% higher for amiodarone, respectively. In contrast, all pharmacokinetic parameters were similar between single and dual-cannulated rats for the hydrophilic compound atenolol. Based on these results, we recommend the use of dual cannulated rats for intravenous pharmacokinetic studies when testing a series of hydrophobic compounds that may be prone to non-specific binding to the cannula. If single cannulated model is selected for pharmacokinetic screening, we recommend a bridging study with dual cannulated rats with representative compounds of a given chemical series.

Study Objective To assess reliability and reproducibility of a recently instituted anesthesiology resident applicant interview scoring system at our own institution. Design Retrospective evaluation of 2 years of interview data with a newly implemented scoring system using randomly assigned interviewing faculty. Setting Interview scoring evaluations were completed as standard practice in a large academic anesthesiology department. Subjects All anesthesiology resident applicants interviewed over the 2013/14 and 2014/15 seasons by a stable cohort of faculty interviewers. Data collection blinded for both interviewers and interviewees. Interventions None for purposes of study – collation of blinded data already used as standard practice during interview process and analysis. Measurements None specific to study. Main Results Good inter-rater faculty reliability of interview scoring (day-of) and excellent inter-faculty reliability of application review (pre-interview). Conclusions Development of a department-specific interview scoring system including many elements beyond traditional standardized tests shows good-excellent reliability of faculty scoring of both the interview itself (including non-technical skills) and the application resume.

We describe the design, synthesis and pharmacokinetic (PK) evaluation of a series of amino acid-based prodrugs of the HIV-1 protease inhibitor atazanavir (1) derivatized on the pharmacophoric secondary alcohol using a (carbonyl)oxyalkyl linker. Prodrugs of 1 incorporating simple (carbonyl)oxyalkyl-based linkers and a primary amine in the promoiety were found to exhibit low chemical stability. However, chemical stability was improved by modifying the primary amine moiety to a tertiary amine, resulting in a 2-fold enhancement of exposure in rats following oral dosing compared to dosing of the parent drug 1. Further refinement of the linker resulted in the discovery of 22 as a prodrug that delivered the parent 1 to rat plasma with a 5-fold higher AUC and 67-fold higher C24 when compared to oral administration of the parent drug. The PK profile of 22 indicated that plasma levels of this prodrug were higher than that of the parent, providing a more sustained release of 1 in vivo.

After a hiatus of several decades, the concept of cold whole blood (WB) is being reintroduced into acute clinical trauma care in the United States. Initial implementation experience and data grew from military medical applications, followed by more recent development and data acquisition in civilian institutions. Anesthesiologists, especially those who work in acute trauma facilities, are likely to be presented with patients either receiving WB from the emergency department or may have WB as a therapeutic option in massive transfusion situations. In this focused review, we briefly discuss the historical concept of WB and describe the characteristics of WB, including storage, blood group compatibility, and theoretical hemolytic risks. We summarize relevant recent retrospective military and preliminary civilian efficacy as well as safety data related to WB transfusion, and describe our experience with the initial implementation of WB transfusion at our level 1 trauma hospital. Suggestions and collective published experience from other centers as well as ours may be useful to those investigating such a program. The role of WB as a significant therapeutic option in civilian trauma awaits further prospective validation.

HIV-1 protease inhibitors (PIs), which include atazanavir (ATV, 1), remain important medicines to treat HIV-1 infection. However, they are characterized by poor oral bioavailability and a need for boosting with a pharmacokinetic enhancer, which results in additional drug-drug interactions that are sometimes difficult to manage. We investigated a chemo-activated, acyl migration-based prodrug design approach to improve the pharmacokinetic profile of 1 but failed to obtain improved oral bioavailability over dosing the parent drug in rats. This strategy was refined by conjugating the amine with a promoiety designed to undergo bio-activation, as a means of modulating the subsequent chemo-activation. This culminated in a lead prodrug that (1) yielded substantially better oral drug delivery of 1 when compared to the parent itself, the simple acyl migration-based prodrug, and the corresponding simple l-Val prodrug, (2) acted as a depot which resulted in a sustained release of the parent drug in vivo, and (3) offered the benefit of mitigating the pH-dependent absorption associated with 1, thereby potentially reducing the risk of decreased bioavailability with concurrent use of stomach-acid-reducing drugs.

Perioperative organ injury has a significant impact on surgical outcomes and presents a leading cause of death in the United States. Recent research has pointed out an important role of hypoxia signaling in the protection from organ injury, including for example myocardial infarction, acute respiratory distress syndrome, acute kidney, or gut injury. Hypoxia induces the stabilization of hypoxia-inducible factors (HIFs), thereby leading to the induction of HIF target genes, which facilitates adaptive responses to low oxygen. In this review, we focus on current therapeutic strategies targeting hypoxia signaling in various organ injury models and emphasize potential clinical approaches to integrate these findings into the care of surgical patients. Conceptually, there are 2 options to target the HIF pathway for organ protection. First, drugs became recently available that promote the stabilization of HIFs, most prominently via inhibition of prolyl hydroxylase. These compounds are currently trialed in patients, for example, for anemia treatment or prevention of ischemia and reperfusion injury. Second, HIF target genes (such as adenosine receptors) could be activated directly. We hope that some of these approaches may lead to novel pharmacologic strategies to prevent or treat organ injury in surgical patients.

We report dramatic changes in bilateral cerebral tissue oxygenation in a patient undergoing an orthotopic liver transplant coincident with clamping and subsequent restoration of flow through the inferior vena cava. Although hemodynamic stability was maintained with low-dose vasopressor support, cardiac output was decreased, suggesting preload dependence of the measured cerebral oxygenation. Further investigation is warranted in patients with end-stage liver disease and interruption of venous return.

The role of uptake transporter (organic anion–transporting polypeptide [Oatp]) in the disposition of a P-glycoprotein (P-gp) substrate (digoxin) at the barriers of central nervous system, namely, the blood-brain barrier (BBB), blood-spinal cord barrier (BSCB), and brain-cerebrospinal fluid barrier (BCSFB), was studied using rat as a preclinical species. In vivo chemical inhibition of P-gp and Oatp was achieved using elacridar and rifampicin, respectively. Our findings show that (1) digoxin had a low brain-to-plasma concentration ratio (B/P) (0.07) in rat; (2) in the presence of elacridar, the B/P of digoxin increased by about 12-fold; (3) rifampicin administration alone did not change the digoxin B/P significantly when compared with digoxin B/P alone; (4) rifampicin administration along with elacridar resulted only in 6-fold increase in the B/P of digoxin; (5) similar fold changes and trends were seen with the spinal cord-to-plasma concentration ratio of digoxin, indicating the similarity between BBB and the BSCB; and (6) unlike BBB and BSCB, the presence of rifampicin further increased the cerebrospinal fluid-to-plasma concentration ratio (CSF/P) for digoxin, suggesting a differential orientation of the uptake transporters at the BCSFB (CSF to blood) compared with the BBB (blood to brain). The observations for digoxin uptake, at least at the BBB and the BSCB, advocate the importance of uptake transporters (Oatps). However, the activity of such uptake transporters became evident only after inhibition of the efflux transporter (P-gp).