Variation in Intraoperative Opioid Administration by Patient, Clinician, and Hospital Contribution.

Importance: The opioid crisis has led to scrutiny of opioid exposures before and after surgical procedures. However, the extent of intraoperative opioid variation and the sources and contributing factors associated with it are unclear. Objective: To analyze attributable variance of intraoperative opioid administration for patient-, clinician-, and hospital-level factors across surgical and analgesic categories. Design, Setting, and Participants: This cohort study was conducted using electronic health record data collected from a national quality collaborative database. The cohort consisted of 1 011 268 surgical procedures at 46 hospitals across the US involving 2911 anesthesiologists, 2291 surgeons, and 8 surgical and 4 analgesic categories. Patients without ambulatory opioid prescriptions or use history undergoing an elective surgical procedure between January 1, 2014, and September 11, 2020, were included. Data were analyzed from January 2022 to July 2023. Main Outcomes and Measures: The rate of intraoperative opioid administration as a continuous measure of oral morphine equivalents (OMEs) normalized to patient weight and case duration was assessed. Attributable variance was estimated in a hierarchical structure using patient, clinician, and hospital levels and adjusted intraclass correlations (ICCs). Results: Among 1 011 268 surgical procedures (mean [SD] age of patients, 55.9 [16.2] years; 604 057 surgical procedures among females [59.7%]), the mean (SD) rate of intraoperative opioid administration was 0.3 [0.2] OME/kg/h. Together, clinician and hospital levels contributed to 20% or more of variability in intraoperative opioid administration across all analgesic and surgical categories (adjusting for surgical or analgesic category, ICCs ranged from 0.57-0.79 for the patient, 0.04-0.22 for the anesthesiologist, and 0.09-0.26 for the hospital, with the lowest ICC combination 0.21 for anesthesiologist and hosptial [0.12 for the anesthesiologist and 0.09 for the hospital for opioid only]). Comparing the 95th and fifth percentiles of opioid administration, variation was 3.3-fold among anesthesiologists (surgical category range, 2.7-fold to 7.7-fold), 4.3-fold among surgeons (surgical category range, 3.4-fold to 8.0-fold), and 2.2-fold among hospitals (surgical category range, 2.2-fold to 4.3-fold). When adjusted for patient and surgical characteristics, mean (square error mean) administration was highest for cardiac surgical procedures (0.54 [0.56-0.52 OME/kg/h]) and lowest for orthopedic knee surgical procedures (0.19 [0.17-0.21 OME/kg/h]). Peripheral and neuraxial analgesic techniques were associated with reduced administration in orthopedic hip (51.6% [95% CI, 51.4%-51.8%] and 60.7% [95% CI, 60.5%-60.9%] reductions, respectively) and knee (48.3% [95% CI, 48.0%-48.5%] and 60.9% [95% CI, 60.7%-61.1%] reductions, respectively) surgical procedures, but reduction was less substantial in other surgical categories (mean [SD] reduction, 13.3% [8.8%] for peripheral and 17.6% [9.9%] for neuraxial techniques). Conclusions and Relevance: In this cohort study, clinician-, hospital-, and patient-level factors had important contributions to substantial variation of opioid administrations during surgical procedures. These findings suggest the need for a broadened focus across multiple factors when developing and implementing opioid-reducing strategies in collaborative quality-improvement programs.

Association of adherence to individual components of Society of Thoracic Surgeons cardiac surgery antibiotic guidelines and postoperative infections.

OBJECTIVES: The study objectives were to measure the association among the 4 components of Society of Thoracic Surgeons antibiotic guidelines and postoperative complications in a cohort of patients undergoing valve or coronary artery bypass grafting requiring cardiopulmonary bypass. METHODS: In this retrospective observational study, adult patients undergoing coronary revascularization or valvular surgery who received a Surgical Care Improvement Project-compliant antibiotic from January 1, 2016, to April 1, 2021, at a single, tertiary care hospital were included. The primary exposures were adherence to the 4 individual components of Society of Thoracic Surgeons antibiotic best practice guidelines. The association of each component and a combined metric was tested in its association with the primary outcome of postoperative infection as determined by Society of Thoracic Surgeons data abstractors, controlling for several known confounders. RESULTS: Of the 2829 included patients, 1084 (38.3%) received care that was nonadherent to at least 1 aspect of Society of Thoracic Surgeons antibiotic guidelines. The incidence of nonadherence to the 4 individual components was 223 (7.9%) for timing of first dose, 639 (22.6%) for antibiotic choice, 164 (5.8%) for weight-based dose adjustment, and 192 (6.8%) for intraoperative redosing. In adjusted analyses, failure to adhere to first dose timing guidelines was directly associated with Society of Thoracic Surgeons-adjudicated postoperative infection (odds ratio, 1.9; 95% confidence interval, 1.1-3.3; P = .02). Failure of weight-adjusted dosing was associated with both postoperative sepsis (odds ratio, 6.9; 95% confidence interval, 2.5-8.5; P < .01) and 30-day mortality (odds ratio, 4.3; 95% confidence interval, 1.7-11.4; P < .01). No other significant associations among the 4 Society of Thoracic Surgeons metrics individually or as a combination were observed with postoperative infection, sepsis, or 30-day mortality. CONCLUSIONS: Nonadherence to Society of Thoracic Surgeons antibiotic best practices is common. Failure of antibiotic timing and weight-adjusted dosing is associated with odds of postoperative infection, sepsis, and mortality after cardiac surgery.

Pressure-Regulated Ventilator Splitting for Disaster Relief: Design, Testing, and Clinical Experience.

The coronavirus disease 2019 (COVID-19) pandemic has revealed that even the best-resourced hospitals may lack sufficient ventilators to support patients under surge conditions. During a pandemic or mass trauma, an affordable, low-maintenance, off-the-shelf device that would allow health care teams to rapidly expand their ventilator capacity could prove lifesaving, but only if it can be safely integrated into a complex and rapidly changing clinical environment. Here, we define an approach to safe ventilator sharing that prioritizes predictable and independent care of patients sharing a ventilator. Subsequently, we detail the design and testing of a ventilator-splitting circuit that follows this approach and describe our clinical experience with this circuit during the COVID-19 pandemic. This circuit was able to provide individualized and titratable ventilatory support with individualized positive end-expiratory pressure (PEEP) to 2 critically ill patients at the same time, while insulating each patient from changes in the other's condition. We share insights from our experience using this technology in the intensive care unit and outline recommendations for future clinical applications.

Brain Iron Distribution after Multiple Doses of Ultra-small Superparamagnetic Iron Oxide Particles in Rats.

The purpose of this study is to determine the effects of high cumulative doses of ultra-small paramagnetic iron oxide (USPIO) used in neuroimaging studies. We intravenously administered 8 mg/kg of 2 USPIO compounds daily for 4 wk to male Sprague-Dawley rats (Crl:SD). Multiecho gradient-echo MRI, serum iron levels, and histology were performed at the end of dosing and after a 7-d washout period. R2* maps and quantitative susceptibility maps (QSM) were generated from multiecho gradient-echo data. R2* maps and QSM showed iron accumulation in brain ventricles on MR images acquired at the 4- and 5-wk time points. Estimates from QSM data showed ventricular iron concentration was equal to or higher than serum iron concentration. Histologic analysis revealed choroid plexus hemosiderosis and midbrain vacuolation, without iron deposition in brain parenchyma. Serum iron levels increased with administration of both compounds, and a 7-d washout period effectively reduced serum iron levels of one but not both of the compounds. High cumulative doses from multiple, frequent administrations of USPIO can lead to iron deposition in brain ventricles, resulting in persistent signal loss on T2*-weighted images. Techniques such as QSM are helpful in quantifying iron biodistribution in this situation.

Whole-agent selectivity within the macaque face-processing system.

The primate brain contains a set of face-selective areas, which are thought to extract the rich social information that faces provide, such as emotional state and personal identity. The nature of this information raises a fundamental question about these face-selective areas: Do they respond to a face purely because of its visual attributes, or because the face embodies a larger social agent? Here, we used functional magnetic resonance imaging to determine whether the macaque face patch system exhibits a whole-agent response above and beyond its responses to individually presented faces and bodies. We found a systematic development of whole-agent preference through the face patches, from subadditive integration of face and body responses in posterior face patches to superadditive integration in anterior face patches. Superadditivity was not observed for faces atop nonbody objects, implying categorical specificity of face-body interaction. Furthermore, superadditivity was robust to visual degradation of facial detail, suggesting whole-agent selectivity does not require prior face recognition. In contrast, even the body patches immediately adjacent to anterior face areas did not exhibit superadditivity. This asymmetry between face- and body-processing systems may explain why observers attribute bodies' social signals to faces, and not vice versa. The development of whole-agent selectivity from posterior to anterior face patches, in concert with the recently described development of natural motion selectivity from ventral to dorsal face patches, identifies a single face patch, AF (anterior fundus), as a likely link between the analysis of facial shape and semantic inferences about other agents.

Contrasting specializations for facial motion within the macaque face-processing system.

Facial motion transmits rich and ethologically vital information, but how the brain interprets this complex signal is poorly understood. Facial form is analyzed by anatomically distinct face patches in the macaque brain, and facial motion activates these patches and surrounding areas. Yet, it is not known whether facial motion is processed by its own distinct and specialized neural machinery, and if so, what that machinery's organization might be. To address these questions, we used fMRI to monitor the brain activity of macaque monkeys while they viewed low- and high-level motion and form stimuli. We found that, beyond classical motion areas and the known face patch system, moving faces recruited a heretofore unrecognized face patch. Although all face patches displayed distinctive selectivity for face motion over object motion, only two face patches preferred naturally moving faces, while three others preferred randomized, rapidly varying sequences of facial form. This functional divide was anatomically specific, segregating dorsal from ventral face patches, thereby revealing a new organizational principle of the macaque face-processing system.

Alert response to motion onset in the retina.

Previous studies have shown that motion onset is very effective at capturing attention and is more salient than smooth motion. Here, we find that this salience ranking is present already in the firing rate of retinal ganglion cells. By stimulating the retina with a bar that appears, stays still, and then starts moving, we demonstrate that a subset of salamander retinal ganglion cells, fast OFF cells, responds significantly more strongly to motion onset than to smooth motion. We refer to this phenomenon as an alert response to motion onset. We develop a computational model that predicts the time-varying firing rate of ganglion cells responding to the appearance, onset, and smooth motion of a bar. This model, termed the adaptive cascade model, consists of a ganglion cell that receives input from a layer of bipolar cells, represented by individual rectified subunits. Additionally, both the bipolar and ganglion cells have separate contrast gain control mechanisms. This model captured the responses to our different motion stimuli over a wide range of contrasts, speeds, and locations. The alert response to motion onset, together with its computational model, introduces a new mechanism of sophisticated motion processing that occurs early in the visual system.

Topographic enhancement mapping of the cancer-associated breast stroma using breast MRI.

In animal and laboratory models, cancer-associated stroma, or elements of the supporting tissue surrounding a primary tumor, has been shown to be necessary for tumor evolution and progression. However, little is understood or studied regarding the properties of intact stroma in human cancer in vivo. In addition, for breast cancer patients, the optimal volume of local tissue to treat surrounding a primary tumor is not clear. Here, we performed an interdisciplinary study of normal-appearing breast tissue using breast magnetic resonance imaging (MRI), correlative histology and array comparative genomic hybridization to identify a cancer-associated stroma in humans. Using a novel technique for segmenting breast fibroglandular tissue, quantifiable topographic percent enhancement mapping of the stroma surrounding invasive breast cancer was found to be significantly elevated within 2 cm of the tumor edge. This region was also found to harbor increased microvessel density, and genomic changes that were closely associated with host normal breast tissue. These findings indicate that a cancer-associated stroma may be identified and characterized in human breast cancer using non-invasive imaging techniques. Identification of a cancer-associated stroma may be further developed to help guide local therapy to reduce recurrence and morbidity in breast cancer patients.

Synchronized firing among retinal ganglion cells signals motion reversal.

We show that when a moving object suddenly reverses direction, there is a brief, synchronous burst of firing within a population of retinal ganglion cells. This burst can be driven by either the leading or trailing edge of the object. The latency is constant for movement at different speeds, objects of different size, and bright versus dark contrasts. The same ganglion cells that signal a motion reversal also respond to smooth motion. We show that the brain can build a pure reversal detector using only a linear filter that reads out synchrony from a group of ganglion cells. These results indicate that not only can the retina anticipate the location of a smoothly moving object, but that it can also signal violations in its own prediction. We show that the reversal response cannot be explained by models of the classical receptive field and suggest that nonlinear receptive field subunits may be responsible.