Leo Fabian: A Life of Accomplishment.

Leo Fabian played a role in many anesthesia firsts: the first halothane anesthetics in the United States, the first American electrical anesthetic, the first lung allotransplant, and the first heart xenotransplant. As was common for men of his generation, Fabian's first taste of medicine came during World War II, as a pharmacist's mate aboard the U.S.S. Bountiful. Afterward, he pursued his medical education before joining Dr. C. Ronald Stephen and the anesthesiology department at Duke. There he helped to create one of the first inhalers for halothane, the Fabian Newton Stephen (F-N-S) Fluothane Vaporizer. Fabian left Duke for the University of Mississippi Medical Center, where he consistently worked with the chair of surgery, Dr. James Hardy. Together they performed the first American electrical anesthetic, the first lung allotransplant, and the first heart xenotransplant. By the end of his time at Mississippi, Fabian and Hardy had several philosophical disagreements, and Fabian ultimately left for Washington University in St. Louis, where he rejoined Dr. Stephen. He served as Stephen's right-hand man and would oversee the department when Stephen was away. Fabian spent the final years of his career as chair of the department before his own health forced him to step down.

Adenotonsillectomy and postoperative respiratory adverse events: A retrospective study.

OBJECTIVES: Postoperative respiratory adverse events (PRAEs) are known complications following adenotonsillectomy (AT). Clinical data at a single institution were reviewed to investigate the factors that may contribute to PRAEs in the postanesthesia care unit (PACU). The relationship between PRAEs in the PACU and escalation of care, defined as either an unplanned admission for outpatient surgery or unplanned pediatric intensive care unit (PICU) admission, was investigated. METHODS: The perioperative records for all patients who underwent AT from 2016 to 2018 were reviewed. The surgical procedure was performed at both the main campus and the ambulatory surgery center in accordance with the institutional obstructive sleep apnea (OSA) guidelines. Patient characteristics and intraoperative medications were compared. Categorical variables were summarized as counts with percentages and compared using chi-square tests or Fisher's exact tests. Continuous variables were summarized as medians with interquartile ranges and compared using rank-sum tests. Multivariable logistic regression was performed to evaluate the association of intraoperative dosing with the occurrence of PRAEs. RESULTS: The study cohort included 6110 patients. Ninety-three patients (2%) experienced PRAEs in the PACU. Of these 93 patients, 14 (15%) resulted in an escalation of care, nearly all of which were unplanned PICU admissions. PRAEs tended to occur in younger patients, non-Hispanic black patients, and those with a higher American Society of Anesthesiologists (ASA) status. CONCLUSIONS: PRAEs are infrequent after AT at a tertiary institution with OSA guidelines in place. However, when PRAEs do occur, escalation of care may be required. Risk factors include age, ethnic background, and ASA physical status. LEVEL OF EVIDENCE: III.

Pre-medication before dental procedures: A randomized controlled study comparing intranasal dexmedetomidine with oral midazolam.

BACKGROUND: This study aimed to determine if intranasal dexmedetomidine is a superior pre-medication to oral midazolam in older, difficult children. METHODS: This was conducted as a prospective, single-blind randomized control trial in a tertiary care center. Seventy-five children, age >5 years and weight >20 kg, who needed general anesthesia for dental procedures were randomly assigned to be pre-medicated with either oral midazolam at a dose of 0.5 mg/kg (max 15 mg) or intranasal dexmedetomidine at a dose of 2 mcg/kg (max 100 mcg). The primary outcome studied was the patients' level of sedation when separated from their parents, which was assessed using a 5-point University of Michigan Sedation Scale. Secondary outcome studied was the level of anxiolysis assessed by the acceptance of mask induction using a 4-point scale. All assessments were made by one research person blinded to the study drug. RESULTS: The two groups were similar in age, sex, weight, pre-anesthetic behavior, time from pre-medication to anesthesia induction, and surgical time. A significantly higher proportion of patients who received dexmedetomidine had satisfactory sedation at separation from parents (69.4% vs 40.5%, P = .03) compared to those who received midazolam. There were no significant differences in the rate of acceptance of mask induction (80.6% vs 78.4%, P = 1.00). Intranasal dexmedetomidine was tolerated well when administered using a mucosal atomizer and without any clinically significant effect on heart rate or systolic blood pressure. CONCLUSIONS: Intranasal dexmedetomidine provides higher success rate in sedation and parental separation compared to oral midazolam, in older, difficult children.

Sorting of ß1-adrenergic receptors is mediated by pathways that are either dependent on or independent of type I PDZ, protein kinase A (PKA), and SAP97.

The ß1-adrenergic receptor (ß1-AR) is a target for treatment of major cardiovascular diseases, such as heart failure and hypertension. Recycling of agonist-internalized ß1-AR is dependent on type I PSD-95/DLG/ZO1 (PDZ) in the C-tail of the ß1-AR and on protein kinase A (PKA) activity (Gardner, L. A., Naren, A. P., and Bahouth, S. W. (2007) J. Biol. Chem. 282, 5085-5099). We explored the effects of point mutations in the PDZ and in the activity of PKA on recycling of the ß1-AR and its binding to the PDZ-binding protein SAP97. These studies indicated that ß1-AR recycling was inhibited by PKA inhibitors and by mutations in the PDZ that interfered with SAP97 binding. The trafficking effects of short sequences differing in PDZ and SAP97 binding were examined using chimeric mutant ß1-AR. ß1-AR chimera containing the type I PDZ of the ß2-adrenergic receptor that does not bind to SAP97 failed to recycle except when serine 312 was mutated to aspartic acid. ß1-AR chimera with type I PDZ sequences from the C-tails of aquaporin-2 or GluR1 recycled in a SAP97- and PKA-dependent manner. Non-PDZ ß1-AR chimera derived from µ-opioid, dopamine 1, or GluR2 receptors promoted rapid recycling of chimeric ß1-AR in a SAP97- and PKA-independent manner. Moreover, the nature of the residue at position -3 in the PDZ regulated whether the ß1-AR was internalized alone or in complex with SAP97. These results indicate that divergent pathways were involved in trafficking the ß1-AR and provide a roadmap for its trafficking via type I PDZs versus non-PDZs.