151 Surgeon Variation in Perioperative Opioid Prescribing and Medium- or Long-term Opioid Utilization after Total Knee Arthroplasty: A Cross-sectional Analysis
The hypothesis tested in this database study was that patients who received care from surgeons whose patients were in the upper quartile of opioid utilization in the immediate perioperative period were more likely to fill opioid prescriptions in the medium- and long-term postoperative periods compared to patients who did not receive treatment from such surgeons. Administrative claims data for 604,093 Medicare fee-for-service patients with an average age of 74 yr undergoing total knee arthroplasty between 2011 and 2016 were analyzed to characterize variation in perioperative opioid utilization among the 7,141 orthopedic surgeons who treated them. Patients cared for by surgeons whose patients were more likely to fill opioid prescriptions in the immediate perioperative period had slightly higher rates of filling opioid prescriptions in the 8 to 90 days after surgery and slightly lower rates in the 91 to 365 days after surgery compared to patients cared for by surgeons with a lower propensity to prescribe opioids in the perioperative setting. Although these differences were statistically significant, they were of small clinical significance. See the accompanying Editorial on page 131.
187 Isoelectric Electroencephalography in Infants and Toddlers during Anesthesia for Surgery: An International Observational Study
Increased doses of propofol and sevoflurane lead to an initial increase in electroencephalography (EEG) amplitude and progressively decreased frequency, until isoelectric EEG occurs, indicating an electrically inactive neocortex. The hypothesis that the prevalence of isoelectric events would be common in infants and toddlers undergoing routine surgeries worldwide and associated with certain anesthetic practices and intraoperative hypotension was tested in 649 patients in a 15-center prospective observational cross-sectional study. Isoelectric events occurred in 32% of patients worldwide with large variation across sites. Isoelectric events were more common during preincision and surgical maintenance and were associated with younger age (0 to 3 months), use of endotracheal tube, use of propofol instead of a muscle relaxant for intubation, and higher expired sevoflurane concentrations during preincision and surgical maintenance. Isoelectric events were associated with intraoperative hypotension in patients of all ages. In post hoc analysis, higher-than-average prevalence sites had higher expired sevoflurane concentrations and higher proportions of patients with hypotension during surgical maintenance.
232 Coagulopathy Underlying Rotational Thromboelastometry Derangements in Trauma Patients: A Prospective Observational Multicenter Study
Viscoelastic hemostatic assays such as rotational thromboelastometry are point-of-care whole blood coagulation tests that are able to rapidly assess the full scope of the coagulation cascade and provide parameters that reflect in vitro initiation of coagulation, clot propagation, and fibrinolysis. The hypothesis that rotational thromboelastometry derangements reflect specific clinically relevant in vivo coagulation deficiencies associated with adverse outcome was tested in a secondary analysis of a prospective cohort study of 1,828 patients presenting with full trauma team activation in six European trauma centers between 2008 and 2016. A deranged rotational thromboelastometry profile was present in 732 patients (40%). In the group with an isolated clotting time prolongation, coagulation factor concentrations and outcomes were similar to those of patients with normal profiles. In contrast, other rotational thromboelastometry derangements reflected a decrease in fibrinogen and factor V concentrations and a combination of EXTEM and FIBTEM clot amplitude after 5 min derangements represented fibrinolysis, even when lysis at 30 min was normal.
176 Gas Phase Diffusion Does Not Limit Lung Volatile Anesthetic Uptake Rate
Inefficiency of gas uptake and elimination in the lung is reflected by development of partial pressure gradients between expired alveolar (end-tidal) gas and arterial blood. These arise mainly from variation of alveolar ventilation–perfusion ratios across the lung, but longitudinal partial pressure gradients down the respiratory tree due to diffusion limitation may possibly also contribute, especially for larger molecules such as volatile anesthetics. The hypothesis that the end-tidal–to–arterial partial pressure gradient for desflurane would be larger than that for N2O was tested in 17 patients inhaling a mixture of desflurane and N2O, which have similar effective blood–gas partition coefficients but a fourfold difference in molecular weight. Raw measurements of end-tidal–to–arterial partial pressure gradients, relative to inspired concentration, were smaller for desflurane. After adjustment for the higher rate of lung gas uptake for desflurane at the time of measurement, no difference in end-tidal–to–arterial partial pressure gradients was found.
243 Estimates of Probabilities of Successful Development of Pain Medications: An Analysis of Pharmaceutical Clinical Development Programs from 2000 to 2020
Despite the prevalence and societal costs of pain in the United States, investment in pain medication development is low, due in part to poor understanding of the probability of successful development of such medications. This study examined outcomes and parameters of 469 pain pharmaceutical development programs of 399 unique active pharmaceutical ingredients between 2000 and 2020. The development of new pain medications with high abuse potential decreased since the peak of the opioid epidemic around 2010, while the number of development programs for low abuse potential pain medications increased. The probability of successful development programs was 27.8% for high abuse potential compounds and 4.7% for low abuse potential compounds. The probability of successful development of a treatment for nociceptive pain was 13.3% and that for a treatment of neuropathic pain was 7.1%. The development of pain medications in large phase 3 safety and efficacy trials took an average of 30 months. See the accompanying Editorial on page 134.
201 Expert Consensus Regarding Core Outcomes for Enhanced Recovery after Cesarean Delivery Studies: A Delphi Study
The absence of consensus regarding how to assess the effect of enhanced recovery after cesarean delivery protocols affects interpretation and synthesis of research related to it, slowing the progress and standardization of clinical care. This international expert and patient stakeholder consensus study used Delphi methodology to develop a standardized enhanced recovery after cesarean delivery core outcome set based on consensus. The modified Delphi methodology included two rounds of electronic questionnaires followed by a final roundtable discussion and ratification round. Thirty-two stakeholders from seven countries across four continents participated in Round 1, 31 in Round 2, and 26 in Round 3. Stakeholders were presented with 98 perioperative outcomes that were reported in a systematic review of enhanced recovery after cesarean delivery implementation studies in Round 1. Fifteen outcomes met the criteria for inclusion in the final core outcome set that could be applied in future research and implementation studies evaluating the effect of enhanced recovery after cesarean delivery protocols.
212 Isoflurane Disrupts Postsynaptic Density-95 Protein Interactions Causing Neuronal Synapse Loss and Cognitive Impairment in Juvenile Mice via Canonical NO-mediated Protein Kinase-G Signaling
The hippocampus is the main region for learning and memory and has been implicated in the amnestic and delayed cognitive effects of anesthetics. The authors hypothesized that activation of protein kinase-G by the components of nitric oxide signaling pathway constitutes a mechanism that prevents loss of early dendritic spines and synapses in neurons and cognitive impairment in mice in response to disruption of PDZ2 domain of the postsynaptic density-95 (PSD-95) protein by isoflurane. Exposure of neonatal mice to 1.5% isoflurane for 4 h markedly disrupted the interactions between N-methyl-d-aspartate receptor (NMDAR) NR2A/2B subunits and the PSD-95 protein in the hippocampus. Neonatal isoflurane or synaptic PSD-95 PDZ2 disruption impaired recognition memory in both male and female mice at 5 weeks and loss of early dendritic spines and synapses in vitro without inducing significant neuronal death. Introduction of a nitric oxide donor or cyclic guanosine monophosphate analog in vitro prevented loss in early dendritic spines and synapses. Introducing soluble guanyl cyclase activator YC-1 at the time of isoflurane exposure prevented the loss in object recognition memory.
252 Emerging Paradigms in the Prevention of Surgical Site Infection: The Patient Microbiome and Antimicrobial Resistance (Clinical Focus Review)
Healthcare-associated infection is the most common overall class of postoperative complication measured by the American College of Surgeons National Surgical Quality Improvement Program, driven largely by surgical site infection. The inability of traditional infection prevention measures to reduce the present rate of surgical site infection has led to a reexamination of its causes, yielding new conceptual models of pathogenesis that have important clinical implications. The emerging model of surgical site infection, including both the ways in which the patient microbiome may contribute to it and the changing landscape of antimicrobial resistance, introduces new complexities and opportunities for the field of perioperative medicine now and in the future. This Clinical Focus Review summarizes new scientific evidence on the pathogenesis of surgical site infection and reviews the evolution of approaches to its prevention from a hospital-centered to a patient-centered model of pathogenesis and from aseptic to medical approaches to prevention.