Background:Antibiotic resistance is a threat to public health driven in part by widespread antibiotic administration. Days of antibiotic spectrum coverage (DASC) is a novel metric to quantify both duration and breadth of antibiotic exposure that has not previously been used as an endpoint in a clinical trial. We calculated DASC using data from the Ceftriaxone to Prevent Pneumonia and Inflammation after Cardiac Arrest (PROTECT) trial to determine the association of ceftriaxone prophylaxis with DASC and with the acquisition of antibiotic resistance genes (ARGs). Methods:PROTECT randomized out-of-hospital cardiac arrest subjects to ceftriaxone or placebo for 3 days. ARGs were measured from rectal swabs collected at Days 0, 3 and 7 post randomization. DASC was calculated for each subject and compared using a two-sided Mann-Whitney U-test. Correlations between DASC and new ARGs, antibiotic-free days (AFD) and days of therapy (DOT) were tested using Kendall's tau-alpha. Results:PROTECT enrolled 52 subjects, 26 per treatment group, and treatment groups were similar at baseline. Median DASC scores were lower in the ceftriaxone group (19.5; IQR: 0, 43) compared with placebo (53; IQR: 16, 81). We found no correlation between DASC and new ARGs at either timepoint, or between DASC and AFD. DASC was correlated with DOT. Conclusions:DASC post intervention was lower in the ceftriaxone group, representing less antibiotic exposure following the intervention. There was no correlation between new ARGs and DASC. Further study is needed to understand the relationship between antibiotic prophylaxis, subsequent antibiotic exposure and resistome changes in the critically ill.

Introduction: Amantadine, an effective neurostimulant for traumatic brain injury, has limited data supporting its use for other acute brain injuries (ABI). This pragmatic study evaluated amantadine for nontraumatic ABI monitored in the ICU with the Coma Recovery Scale-Revised (CRS-R). Methods: This prospective open-label cohort study developed a protocol to treat impaired consciousness after ABI with amantadine, assessing participants with CRS-R as 0-100 Rasch units, monitoring feasibility, safety, and effectiveness. Results: 40 patients (age 64 [52-73] years, 25 [62%] female) were included during this protocol development phase: 13 ischemic stroke, 10 intracerebral hemorrhage, 7 subarachnoid hemorrhage, 4 hypoxic-ischemic encephalopathy, 3 other ABI. The median baseline CRS-R was 11 (IQR 7-16), including 16 meeting criteria for Disorder of Consciousness. Among 30 participants with an adequate amantadine treatment trial, 27 (90%) responded, with disposition to home (1,4%), skilled nursing facility (6,22%), acute inpatient rehabilitation (15,56%), or withdrawal of life support (5,18%). Pre- versus post-treatment CRS-R increased for responders by 8 (6-11), equivalent to 26 (15-45) Rasch units. Among 10 untreated or inadequate trial patients, 3 (30%) were discharged to rehab, 7 (70%) had support withdrawn. Conclusions: It is feasible to measure responsiveness to amantadine using the CRS-R for ICU patients with ABI.

AIM:To evaluate the impact of adding early processed quantitative EEG biomarkers to health record data for early neurological risk stratification after cardiac arrest using machine learning. METHODS:Data available during ICU admission after return of spontaneous circulation (ROSC) were collected from comatose patients, including the processed EEG metrics suppression ratio (SR) and bispectral index (BIS). Clinical data included demographics, Charlson Comorbidity Index, cardiac arrest and resuscitation details, admission vital signs, and initial laboratory results. Primary outcome was poor Cerebral Performance Category score (CPC 3-5). Six machine learning models were developed to predict hospital discharge and 6-month long-term outcome with clinical data alone, EEG (BIS-SR) data alone, and combined clinical and EEG data. Two additional operating points (high specificity for poor outcome and for good outcome) were also calculated. Feature importance was analyzed to identify the most predictive variables. RESULTS:Among 913 patients, the median age was 59 years, most were male (69%), and 44% had an initial shockable rhythm. Poor outcome was observed in 70% at discharge and 72% at long-term assessment. The best-performing models for combined 6-h EEG and clinical data revealed AUC 0.88 (0.87-0.90) for poor long-term outcome and 0.86 (0.84-0.87) for poor discharge outcome. Combining the processed EEG and clinical data significantly improved the AUC compared to either data set alone (p < 0.001). CONCLUSION:The combination of early processed EEG and clinical data were best able to stratify neurological risk early after cardiac arrest using machine learning algorithms, but external validation is needed.

BACKGROUND:Antibiotic prophylaxis following out-of-hospital cardiac arrest (OHCA) reduces early-onset pneumonia. However, it has an uncertain impact on mortality and noninfectious outcomes, with ongoing concerns about the subsequent development of antibiotic resistance. RESEARCH QUESTION:Does prophylactic ceftriaxone reduce the incidence of early-onset pneumonia without increasing the acquisition of antibiotic resistance genes after OHCA? STUDY DESIGN AND METHODS:Comatose survivors of OHCA treated with targeted temperature management without a clinical diagnosis of pneumonia at admission were randomized to receive ceftriaxone 2 g or matching placebo every 12 hours for 3 days. The primary outcome was early-onset pneumonia occurring ≤ 4 days following intubation confirmed by masked adjudicators. Abundance of antibiotic resistance genes recovered from rectal swabs before and after study drug administration were analyzed with metagenomic sequencing. RESULTS:A total of 411 participants were screened; 53 (13%) were randomized to treatment, and 1 participant withdrew, leaving 26 in each group in the final analysis. Early-onset pneumonia was diagnosed in 10 (38%) participants receiving ceftriaxone and 18 (69%) participants receiving placebo (risk ratio, 0.57; 95% CI, 0.21-1.001; P = .05). Open-label antibiotics were administered to 14 (54%) participants receiving ceftriaxone and 22 (85%) receiving placebo (risk ratio, 0.64; 95% CI, 0.43-0.94); most of the antibiotics were broad-spectrum agents (93% and 100%, respectively). After adjusting for differences in abundance of antibiotic resistance genes prior to study drug administration, participants randomized to receive ceftriaxone acquired significantly fewer antibiotic resistance genes to frequently used antibiotics in the ICU compared with those randomized to receive placebo (incidence risk ratio, 0.30; 95% CI, 0.13-0.70). Serious adverse drug effects were not reported in either treatment group. INTERPRETATION:This trial was inconclusive regarding the impact of ceftriaxone prophylaxis on reducing the incidence of early-onset pneumonia following OHCA. However, ceftriaxone was associated with less frequent administration of open-label antibiotics and reduced acquisition of antibiotic resistance genes to frequently used antibiotics in the ICU. CLINICAL TRIAL REGISTRATION:ClinicalTrials.gov; No.: NCT04999592; URL: www. CLINICALTRIALS:gov.

Introduction:Delirium affects nearly half of hospitalized older adults and is associated with prolonged hospitalization, dementia, and death. The behavioral manifestations of delirium are generally managed with antipsychotics, but there is growing interest in alternative medical therapy, including guanfacine. Methods:This retrospective cohort study included patients ≥65 years of age admitted to Maine Medical Center between January 2021 and April 2023 and treated with guanfacine for delirium management on a non-ICU unit. Effectiveness outcomes included antipsychotic use and dose as well as a change in positive delirium screen after guanfacine initiation. Safety outcomes included incidence of hypotension, bradycardia, or transfer to ICU. Results:A total of 56 patients who received at least 1 dose of guanfacine were evaluated, and 38 patients (68%) with complete data for days -1 to +2 were included in the effectiveness analysis. Before guanfacine initiation, 22/38 patients (58%) were receiving an antipsychotic medication, compared with 18/38 (47%) after guanfacine initiation (p = 0.86). Patients received a median (interquartile range) 6.4 (3.3 to 16) olanzapine equivalents (OE) before guanfacine was initiated and 4.2 (1.7 to 10.0) OE after guanfacine (absolute difference 2.2 OE; relative difference, 34 %; p = 0.8). All 56 patients were included in the safety analysis; 21 (38%) experienced hypotension, and of these, 7 (33%) patients required intervention. Twenty-three (41%) experienced bradycardia while on guanfacine, resulting in 1 patient being transferred to the ICU. Discussion:Upon initiation of guanfacine, patients with delirium had a reduction in daily antipsychotic exposure and a decrease in positive delirium screens. However, guanfacine was associated with hypotension and bradycardia.

Objective:Systematically examine the literature describing midodrine to treat shock and to summarize current administration and dosing strategies. Data sources:Structured literature search conducted in MEDLINE (PubMed) from inception through May 10, 2023. Study Selection and Data Extraction:Abstracts and full texts were assessed for inclusion by two blinded, independent reviewers. English-language publications describing use of midodrine in adult patients with shock were included. Data were extracted by two blinded, independent abstractors using a standardized extraction tool. Quality assessments were completed by paired reviewers using JBI methodology. Data Synthesis:Fifteen of 698 (2%) screened manuscripts were included with 1,714 patients with a variety of shock types. Seven studies (47%) were retrospective, two (13%) prospective observational, and six (40%) randomized controlled studies. Midodrine was initiated to facilitate intravenous vasopressor (IVP) weaning in most (11, 73%) studies; only two (13%) reported IVP weaning protocol use. Starting doses were 10 mg every 8 hours (4, 27%) or three times a day (3, 20%), 20 mg every 8 hours (2, 13%); six studies (40%) did not report initial midodrine dosing. A midodrine titration protocol was reported in 6 (40%) studies. Thirteen (87%) studies evaluated for bradycardia, identified in 6 (46%) studies among 204 patients; only one (0.5%) patient required midodrine discontinuation. Three (20%) studies reported on hypertension with an incidence of 7-11%. Four (27%) studies assessed for ischemia; 5/1128 (0.4%) patients experienced mesenteric ischemia requiring midodrine discontinuation. Relevance to Patient care and Clinical Practice:This review explores the pragmatic details involved in initiating, titrating, and weaning midodrine for the bedside clinician and identifies rates of adverse events and complications. Conclusions:Published literature describing midodrine use for shock is heterogeneous and comprised primarily of low or very low quality data. Future controlled trials addressing the shortcomings identified in this systematic review are warranted.

BACKGROUND:Critically ill patients may be overexposed to valproate because altered protein binding leads to a disproportionate free valproate fraction. The Fraser equation was derived and internally validated to estimate critically ill patients' free valproate concentrations, but it requires external validation. METHODS:Adult intensive care unit (ICU) patients at two academic centers with concurrently measured free and total valproate concentrations were included. Free valproate concentrations were estimated using the Fraser equation which includes total valproate, albumin and BUN concentration, and whether the patient received propofol or aspirin. The primary outcome was Fraser equation performance, assessed using Bland-Altman methods. Comparative performance against estimates from the Doré equation (an alternative predictive equation), therapeutic concordance using a target free valproate range of 5-15 mg/L, and equation improvements were explored. RESULTS:Overall, 315 patients and 556 free-total valproate concentration pairs were included. The mean (±SD) age was 58 (±17) years and 90 (29%) patients were on valproate prior to hospital admission. The Fraser equation estimated free valproate concentrations were correlated with measured concentrations (r = 0.728) with a negative bias (mean bias -2.77 mg/L, 95% LOA -18.9, 13.4). The Fraser equation increasingly underestimated measured concentrations as measured concentrations increased. 71% of Fraser equation estimates were therapeutically concordant (e.g., estimate and measured both within reference range) compared to 61.9% of Doré estimates (p = 0.001). Fraser equation modifications led to minor performance improvements but did not overcome worsening underestimation with higher measured free valproate concentrations. CONCLUSION:The Fraser equation was moderately accurate and corresponded with an appropriate interpretation for 71% of free valproate concentrations. Worse underestimation with higher measured free valproate concentrations suggests direct measurement of free valproate concentrations is warranted. While the Fraser equation could complement therapeutic decision making at centers where direct free valproate measurements are unavailable or slow to return, its accuracy is currently insufficient to replace direct measurement.

Objectives:To describe the dosing strategy, safety, and effectiveness of amantadine in patients admitted to inpatient rehabilitation after stroke. Design:Retrospective, single-center, cohort study. Setting:Ninety-bed, inpatient rehabilitation hospital. Participants:Twenty-eight patients (N=28) with amantadine started in a neuro-intensive care unit after stroke and continued after transfer to rehabilitation; the median age was 67 years and 61% were men. Interventions:Oral amantadine. Main Outcome Measures:Amantadine prescribing practices, adverse drug effects, and changes in recovery trajectory relative to dose changes. Results:This cohort included 14 adult patients with intracerebral hemorrhage, 10 with subarachnoid hemorrhage, and 4 with acute ischemic stroke. The most common admitting amantadine dose was 100 mg twice daily. Inpatient rehabilitation lasted 27 (24-35) days, and amantadine was discontinued during rehabilitation in 6 patients (21%). Amantadine was prescribed to 22 patients (79%) at discharge from rehabilitation, most commonly 100 mg daily or twice daily, and was continued for 105 (39-510) days after admission to rehabilitation among the 17 patients with this data available. Twenty-one potential adverse events were identified among 16 (57%) patients, including confusion or delirium, sleeplessness, agitation, fatigue or lethargy, and spasticity; 8 of these (38%) occurred after reductions in amantadine dose. Conclusions:Amantadine dosing was highly variable during inpatient rehabilitation, with trends for longer dosing after acute ischemic stroke and shorter for subarachnoid hemorrhage. Amantadine appeared well tolerated during and after inpatient rehabilitation, and most (22/28) patients were prescribed amantadine at discharge. Strategies to guide long-term use of amantadine after acute stroke require further prospective study.

Valproate has a narrow therapeutic index and unpredictable protein binding, and critically ill patients may experience unexpectedly elevated free concentrations. We sought to identify the clinical consequences and determinants of disproportionate free valproate concentration elevation in critically ill adults. This was a retrospective observational cohort study conducted at two academic medical centers from December 2015 to December 2023. Adult patients admitted to an intensive care unit who were receiving valproate and had concurrent total and free valproate concentrations measured were eligible for inclusion. We examined whether valproate concentrations were independently associated with adverse effects (AEs), including thrombocytopenia, hepatotoxicity, hyperammonemia, and pancreatic injury. Secondarily, determinants of disproportionate free valproate elevation, defined as a free valproate concentration that was greater than expected and out of proportion to the total concentration (e.g., free valproate above reference range but total valproate below reference range), were also identified. A total of 311 patients (mean age 58 [SD ± 17] years, 36

Riker, Richard1; Schlichting, Erica2; Seder, David2; Sorcher, Mary3; Gagnon, David4; May, Teresa2 Author Information

Chemokines, a family of chemotactic cytokines, mediate leukocyte migration to and entrance into inflamed tissue, contributing to the intensity of local inflammation. We performed an analysis of chemokine and immune cell responses to cardiac arrest (CA). Forty-two patients resuscitated from cardiac arrest were analyzed, and twenty-two patients who underwent coronary artery bypass grafting (CABG) surgery were enrolled. Quantitative antibody array, chemokines, and endotoxin quantification were performed using the patients blood. Analysis of CCL23 production in neutrophils obtained from CA patients and injected into immunodeficient mice after CA and cardiopulmonary resuscitation (CPR) were done using flow cytometry. The levels of CCL2, CCL4, and CCL23 are increased in CA patients. Temporal dynamics were different for each chemokine, with early increases in CCL2 and CCL4, followed by a delayed elevation in CCL23 at forty-eight hours after CA. A high level of CCL23 was associated with an increased number of neutrophils, neuron-specific enolase (NSE), worse cerebral performance category (CPC) score, and higher mortality. To investigate the role of neutrophil activation locally in injured brain tissue, we used a mouse model of CA/CPR. CCL23 production was increased in human neutrophils that infiltrated mouse brains compared to those in the peripheral circulation. It is known that an early intense inflammatory response (within hours) is associated with poor outcomes after CA. Our data indicate that late activation of neutrophils in brain tissue may also promote ongoing injury via the production of CCL23 and impair recovery after cardiac arrest.

Background and Objectives: Valproate has wide pharmacokinetic variability and a narrow therapeutic index. Its protein binding is unpredictable, particularly among critically ill patients who may experience unexpectedly elevated free concentrations. We sought to identify the clinical consequences and determinants of occult free valproate toxicity in critically ill adults. Methods: We conducted a multicenter retrospective cohort study of adult patients admitted to an intensive care unit (ICU) who were receiving valproate and had concurrent total and free valproate concentrations measured. We examined whether valproate concentrations were independently associated with adverse drug effects (ADEs) including thrombocytopenia, hepatotoxicity, hyperammonemia, and pancreatic injury. Determinants of occult toxicity were also identified using logistic mixed-effects models, adjusting for age, weight, albumin, propofol and aspirin use, and blood urea nitrogen (BUN). Occult toxicity was defined as a free valproate concentration that was discordant with total concentration (e.g., supratherapeutic free concentration associated with therapeutic total concentration). Results: 311 unique patients (mean age 58 [±17] years, 36% female, 31% non-white, and 29% on valproate prior to admission) with 550 concurrent free and total valproate concentration pairs met inclusion criteria. The median (IQR) total valproate concentration was 46 mcg/mL (34-63) and the median free valproate concentration was 17 mcg/ml (11-23); median free fraction was 35% (25-63%). Eighty-four percent of total valproate concentrations represented occult free toxicity; a therapeutic total with a supratherapeutic free valproate concentration was the most common pattern (32% of concentration pairs). Each 2.5 mcg/mL increase in free valproate concentration was associated with thrombocytopenia (adjusted unit odds 1.15, 95% CI 1.05-1.26) and hepatotoxicity (adjusted unit odds 1.11, 95% CI 1.05-1.18). Albumin concentration (adjusted odds; aOR 0.17, 95% CI 0.08-0.36), BUN (aOR 1.36, 95% CI 1.09-1.70), and propofol exposure (aOR 3.06, 95% CI 1.38-6.79) were associated with occult toxicity. Conclusion: Free valproate concentrations should be measured in critically ill patients because it is associated with ADEs and is often underrepresented by total concentrations. Most critically ill patients are at risk, especially those with hypoalbuminemia, uremia, and lipid exposure.### Competing Interest StatementA.J. Webb has received consulting fees from Acasti Pharma Inc. D.J. Gagnon is a clinical specialist in neurosciences for Lexicomp and is supported by NIGMS grant 1P20GM139745. C.S. Brown has received consulting fees from Trevena Pharmceuticals and grant funding from Astra Zeneca. R.R. Riker is supported by NIH-NIGMS grant 1P20GM139745. S.F. Zafar is supported by NIH-NINDS grants (1R01NS131347, 5K23NS114201, 1R01AG082693, and 1R21NS137117). E.S Rosenthal has received consulting fees from UCB, Inc. and Ceribell, Inc. and is supported by DoD grants (W81XWH-18-DMRDP-PTCRA) and NIH-NINDS and NIH-OD grants (R01NS117904, K23NS105950, R01NS113541, U54NS100064, OT2OD032701).### Funding StatementD.J. Gagnon is supported by NIGMS grant 1P20GM139745. R.R. Riker is supported by NIH-NIGMS grant 1P20GM139745. S.F. Zafar is supported by NIH-NINDS grants (1R01NS131347, 5K23NS114201, 1R01AG082693, and 1R21NS137117). E.S Rosenthal is supported by DoD grants (W81XWH-18-DMRDP-PTCRA) and NIH-NINDS and NIH-OD grants (R01NS117904, K23NS105950, R01NS113541, U54NS100064, OT2OD032701).### Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:The study was deemed exempt by the Massachusetts General Brigham Institutional Review Board and the need for informed consent was waived (2023P000131).I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.YesAnonymized data not published within this article will be made available upon reasonable request from any qualified investigator after completion of a data use agreement.

Torr, Haley; Armstrong, Kaitlin; Sedar, David B.; Riker, Richard R.; Gagnon, David Author Information

Background: The prescribing information for parenteral midazolam contains a Boxed Warning stating its use may precipitate respiratory arrest, and its safety in non-intensive care unit (ICU) nursing units has been understudied. Objective: To characterize the safety of intermittent midazolam injections in patients admitted to non-ICU nursing units relative to lorazepam injections. Methods: This single-center, retrospective, matched-cohort study included patients ≥18 years of age who received intermittent midazolam in non-ICU nursing units. Midazolam administrations were matched 1:1 to lorazepam administrations. Safety outcomes included hypotension, bradycardia, bradypnea, and escalation in level of nursing unit care or oxygen requirement. Results: A total of 94 midazolam administrations were matched to lorazepam administrations. Demographic data were similar between groups. Midazolam was more commonly given intravenously (95.7% vs 85.1%, P = 0.02) and in an intermediate care nursing unit (31.9% vs 14.9%, P = 0.009). The lorazepam cohort had significantly fewer concomitant respiratory depressants administered, and there were no differences in the use of beta-blockers or antihypertensives. There were no differences in the incidence of hypotension (1.1% vs 2.1%, P = 1), bradycardia (5.3% vs 2.1%, P = 0.44), bradypnea (1.1% vs 0%, P = 1), escalation in level of care (2.1% vs 2.1%, P = 1), or escalation in oxygen requirement (5.3% vs 3.2%, P = 0.72). Conclusion and Relevance: The administration of parenteral midazolam in non-ICU nursing units resulted in a similar incidence of hypotension, bradycardia, bradypnea, escalation in oxygen requirement, and escalation in level of care compared with lorazepam. These results suggest that midazolam may have a similar safety profile to lorazepam, supporting its use in non-ICU nursing units.

The removal of the X-waiver in the Mainstreaming Addiction Treatment (MAT) Act of 2023 has substantial implications for buprenorphine prescribing as one of the options to treat opioid use disorder. The purpose of this commentary is to discuss the unanswered questions regarding buprenorphine in the intensive care unit (ICU) including how the passage of the MAT Act will affect ICU providers, which patients should receive buprenorphine, what is the most appropriate route of administration and dose of buprenorphine, what medications interact with buprenorphine, and how can transitions of care be optimized for these patients.

Objective We hypothesized that the administration of amantadine would increase awakening of comatose patients resuscitated from cardiac arrest. Methods We performed a prospective, randomized, controlled pilot trial, randomizing subjects to amantadine 100 mg twice daily or placebo for up to 7 days. The study drug was administered between 72 and 120 hours after resuscitation and patients with absent N20 cortical responses, early cerebral edema, or ongoing malignant electroencephalography patterns were excluded. Our primary outcome was awakening, defined as following two-step commands, within 28 days of cardiac arrest. Secondary outcomes included length of stay, awakening, time to awakening, and neurologic outcome measured by Cerebral Performance Category at hospital discharge. We compared the proportion of subjects awakening and hospital survival using Fisher exact tests and time to awakening and hospital length of stay using Wilcoxon rank sum tests. Results After 2 years, we stopped the study due to slow enrollment and lapse of funding. We enrolled 14 subjects (12% of goal enrollment), seven in the amantadine group and seven in the placebo group. The proportion of patients who awakened within 28 days after cardiac arrest did not differ between amantadine (n=2, 28.6%) and placebo groups (n=3, 42.9%; P>0.99). There were no differences in secondary outcomes. Study medication was stopped in three subjects (21.4%). Adverse events included a recurrence of seizures (n=2; 14.3%), both of which occurred in the placebo group. Conclusion We could not determine the effect of amantadine on awakening in comatose survivors of cardiac arrest due to small sample size.

Objective: This study aimed to determine whether there is a difference in pain scores and opioid consumption after elective surgery in patients maintained on methadone or buprenorphine for opioid use disorder (OUD). Additionally, we investigated the impact of continuing or discontinuing methadone or buprenorphine on post-operative pain outcomes. Design: A single-center retrospective cohort study. Setting: Tertiary care medical center. Patients and participants: Adults aged 18 years or older with OUD maintained on buprenorphine or methadone who underwent elective surgery between January 1, 2017, and January 1, 2021. Interventions: Patients were identified through electronic medical records, and demographic and clinical data were collected. Main outcome measures: The primary outcome was opioid consumption at 24 hours post-operatively, measured in milligram morphine equivalents. The secondary outcome was opioid consumption and pain scores up to 72 hours postoperatively, assessed using a numeric rating scale. Results: This study included 366 patients (64 percent on buprenorphine and 36 percent on methadone). Opioid utilization significantly increased when buprenorphine was not administered post-operatively. Both groups exhibited comparable total opioid consumption during the post-operative period. In the buprenorphine cohort, pain scores differed significantly based on the receipt of medications for OUD post-operatively. Conclusions: This study reinforces existing evidence supporting the continuation of medications for opioid use disorder, specifically buprenorphine and methadone, during the perioperative period. Dissemination of guideline recommendations is essential to ensure optimal post-operative pain management for this patient population.