Investigation of intraoperative dosing patterns of neuromuscular blocking agents.

There is a growing body of literature documenting the use of deep neuromuscular block (NMB) during surgery. Traditional definitions of depth of NMB rely on train-of-four assessment, which can be less reliable in retrospective studies. The goal of our study was to investigate the real-world practice pattern of dosing of neuromuscular blocking agents (NMBA), utilizing the amount of NMBA used during the course of a case, adjusted for patient weight and case duration, as a surrogate measure of depth of NMB. We also aimed to identify case factors associated with larger NMBA doses. In this retrospective observational analysis of our anesthesia information management system, we analyzed all general endotracheal anesthesia cases from 2012 to 2015 in which an intermediate-acting NMBA was used. Cases using a long-acting NMBA or only succinylcholine were excluded. The expected duration of the case was calculated based on the cumulative dose of NMB used, normalized to the patient's ideal body weight and the ED95 of the drug. If the expected duration of the case was greater than the actual case duration documented in the case record, it was classified as higher dosing (HD). If the expected duration was equal to or less than the actual duration, it was considered predicted dosing (PD). Categorical comparisons between HD and PD groups were made for various patient, procedural, and provider factors. 72,684 cases were included in the final analysis, of which 46,358, or 64% of cases, used HD. Cases with patients who were morbidly obese, younger than 65 years, and who were lower ASA Physical Status classification (I or II) used more HD as opposed to PD. Cases that were non-open, used total intravenous anesthesia, emergent cases, or used non-rapid sequence anesthesia induction had higher rates of HD than their matched counterparts. All results were statistically significant. HD was more common in cases that documented train-of-four and used the reversal agent neostigmine. Approximately two-thirds of general endotracheal anesthesia cases using an intermediate-acting NMBA used HD. Cases with higher rates of HD may be those that are traditionally technically complex or emergent, would benefit from greater paralysis, or do not use adjunctive medications for muscle relaxation. Age greater than 65 years was shown to have lower rates of HD, likely due to provider awareness of age-related changes in pharmacokinetics and pharmacodynamics. Intraoperative monitoring and NMB antagonism with neostigmine were used more frequently with HD.

Syndecan-1 regulates cell migration and fibronectin fibril assembly.

Corneal scarring is a major cause of blindness worldwide and can result from the deposition of abnormal amounts of collagen fibers lacking the correct size and spacing required to produce a clear cornea. Collagen fiber formation requires a preformed fibronectin (FN) matrix. We demonstrate that the loss of syndecan1 (sdc1) in corneal stromal cells (CSC) impacts cell migration rates, the sizes and composition of focal and fibrillar adhesions, the activation of integrins, and the assembly of fibronectin into fibrils. Integrin and fibronectin expression are not altered on sdc1-null CSCs. Cell adhesion, spreading, and migration studies using low compared to high concentrations of FN and collagen I (CNI) or vitronectin (VN) with and without activation of integrins by manganese chloride show that the impact of sdc1 depletion on integrin activation varies depending on the integrin-mediated activity evaluated. Differences in FN fibrillogenesis and migration in sdc1-null CSCs are reversed by addition of manganese chloride but cell spreading differences remain. To determine if our findings on sdc1 were specific to the cornea, we compared the phenotypes of sdc1-null dermal fibroblasts with those of CSCs. We found that without sdc1, both cell types migrate faster; however, cell-type-specific differences in FN expression and its assembly into fibrils exist between these two cell types. Together, our data demonstrate that sdc1 functions to regulate integrin activity in multiple cell types. Loss of sdc1-mediated integrin function results in cell-type specific differences in matrix assembly. A better understanding of how different cell types regulate FN fibril formation via syndecans and integrins will lead to better treatments for scarring and fibrosis.

The safety and efficacy of open bedside tracheotomy: A retrospective analysis of 1000 patients.

OBJECTIVES: To evaluate the safety/efficacy of performing open bedside tracheotomy (OBT) in intensive care unit (ICU) patients and identify predictive factors for outcomes. METHODS: This is a retrospective cohort study. We identified 1000 consecutive patients undergoing OBT at a single university hospital starting from August 1, 2007. Complication rate, 30-day mortality, decannulation rate, time to surgery (TTS) from initial consult, and ICU length of stay were analyzed. Multivariate analysis was performed to identify predictors of complication rate, 30-day mortality, and decannulation rate. RESULTS: Mean TTS was 1.80 days. Major complication rate was 1%. No intraoperative deaths were caused by tracheotomy although two deaths resulted from late tracheotomy-related complications. Thirty-day mortality was 26.6%. The only significant predictor for overall complications was mild chronic hepatitis (OR = 2.355). Predictors for 30-day mortality included platelet count <50,000 (OR = 2.125) and vasopressor use (OR = 3.51). Each additional year of age was associated with decreased decannulation rate (OR = 0.972). CONCLUSIONS: This study demonstrates the safety and efficacy of starting an OBT program in a highly comorbid population without strict selection criteria. Safety of OBT was supported by minimal major complication rates and no intraoperative tracheotomy-related deaths in our cohort. These complication rates were comparable to, or lower than, published studies of open and percutaneous techniques. Predictive factors for decannulation, complication, and mortality were identified to help determine which patients would benefit from OBT. LEVEL OF EVIDENCE: 4 Laryngoscope, 130:1263-1269, 2020.