Opioid Dose Research Articles

Optimizing burn wound procedural pain control, efficiency, and satisfaction through integrated nurse and physician education

Herein, we report the results of a quality improvement project (QI). Following a review of the burn unit practices, a nursing-led, physician supported educational intervention regarding optimal timing, dosage, and indication for medications used during hydrotherapy, including midazolam and opioids, was implemented. We hypothesized that such intervention would support improvement in both nurse and patient satisfaction with pain control management. Patients undergoing hydrotherapy were surveyed. Demographics, opioid dose prescribed (oral morphine equivalents), midazolam use, timing of administration, and adverse events were collected. Patient pain scores (1−10) before and after hydrotherapy and patient and nurse satisfaction scores (1−10) after hydrotherapy were collected. The pre- and post-education populations were compared. P < 0.05 was considered significant. Post-education, administration of opioids (59.1% v. 0%, p < 0.001) and midazolam (59.1% vs. 10.4%; p < 0.001) prior to hydrotherapy significantly improved, leading to fewer patients requiring rescue opioids during hydrotherapy (25% vs. 74%, p < 0.001). Hydrotherapy duration significantly decreased post-education (19 [13.3–30] min vs. 32 [18–43] min, p = 0.003). Nurses’ ratings of their patient’s pain control (9 [7.3–10] vs. 7.5 [6–9], p = 0.004) and ease of procedure (10 [9,10] vs. 9 [7.8–10], p = 0.037) significantly improved. Patients’ pain management satisfaction rating did not change, but the number of subjects rating their pain management as excellent tended to increase (36.4% vs. 20%, p = 0.077). Nursing led, physician supported, education can improve medication administration prior to and during hydrotherapy, increasing the ease of the procedure as well as staff satisfaction.

Ultrasound-guided medial branch of the superior laryngeal nerve block to reduce peri-operative opioids dosage and accelerate patient recovery.

To explore whether the medial branch block of superior laryngeal nerve can reduce the stress response of patients undergoing intubation and further reduce the dosage of opioids. 80 patients undergoing gynecological laparoscopic surgery were selected, and randomly divided into 4 groups. All patients in the experimental groups received bilateral internal branch of superior laryngeal nerve block and transversus abdominis plane block. But the dosage of sufentanil used for anesthesia induction in the group A, B, and C was 0.4, 0.2, and 0μg/kg, respectively. Group D do not underwent supralaryngeal nerve block and the dosage of sufentanil was 0.4μg/kg. The heart rate (HR) and mean arterial pressure(MAP) were recorded at the time of entering the operating room(T1), before intubation after induction(T2), immediately after intubation(T3), 5min after intubation(T4), before extubation(T5), immediately after extubation(T6), 5min after extubation(T7). We also recorded the stay time in the recovery room, the number of cases of postoperative sore throat, the number of cases of nausea and vomiting, the first intestinal exhaust time, the length of hospital stay after operation. The HR of group A, C and D at T3 was significantly higher than that at T2(P < 0.01), while the HR of group B had no significant change. The HR of group A, C and D at T4 was lower than that at T3(P < 0.01), while the HR of group B had no obvious change. The HR of group C and D at T3 was significantly higher than that at T1 (P < 0.01). The MAP of group A and D at T4 was significantly lower than that at T1 (P<0.001). The first postoperative intestinal exhaust time in group A, B and C was significantly shorter than that in group D. The length of hospital stay after operation in group B and C was shorter than that in group D. Ultrasound-guided superior laryngeal nerve block combined with 0.2μg/kg sufentanil can reduce the intubation reaction, have better hemodynamic stability, reduce the first postoperative intestinal exhaust time and postoperative hospital stay, thereby accelerating the postoperative recovery of patients.

Simplified Pain Management Including Fentanyl TTS in PACU Patients With Hip Fracture Surgery to Improve Patients’ Well-Being: A Double-Blind Randomized Trial

Adequate pain management is eminently relevant for elderly and more vulnerable patients with hip fractures in the setting of pre and postoperative pain. This study compares postoperative hip fracture patients treated with standard pain management with a variety of medications or an approach with only one option in each medication category (nonopioid: acetaminophen; opioid: fentanyl TTS 12,5 mcg/hour; rescue medication: piritramide) to simplify the treatment algorithm for nurses and improve patient well-being. Double-blind randomized controlled trial. The sample was cognitively intact patients (N = 141) with hip fractures in a tertiary university hospital. Administration of fentanyl12mcg/hourtransdermal therapeutic system was administered by the nurses in the postanesthesia care unit (PACU) to address basal wound pain to improve patientwell-beingand patient treatment inthe PACU for24hours to bettercontrolfor early complications. Well-being was equally increased in both groups in comparison to our preintervention data from 35.7% to over 60% and did not differ significantly between the intervention and control group. No statistically significant differences in numeric rating scale scores, rescue opioid dosage (piritramide i.v.) or in complications were present. This one-size-fits-all simplified pain management approach did not improve patient well-being or any other outcome but highlighted the importance of adequate pain management and a sufficient nurse-to-patient ratio.

Patterns of Opioid Prescriptions in the Veterans Health Administration for Patients With Chronic Low-Back Pain After the Onset of the COVID-19 Pandemic: A Retrospective Cohort Analysis

The COVID-19 pandemic led to severe disruptions in health care and a relaxation of rules surrounding opioid prescribing—changes which led to concerns about increased reliance on opioids for chronic pain and a resurgence of opioid-related harms. Although some studies found that opioid prescriptions increased in the first 6 months of the pandemic, we know little about the longer-term effects of the pandemic on opioid prescriptions. Further, despite the prevalence of pain in veterans, we know little about patterns of opioid prescriptions in the Veterans Health Administration (VA) associated with the pandemic. Using a retrospective cohort of VA patients with chronic low-back pain, we examined the proportion of patients with an opioid prescription and mean morphine milligram equivalents over a 3-year period—1 year prior to and 2 years after the pandemic’s onset. Analyses revealed that both measures fell during the entire observation period. The largest decrease in the odds of filling an opioid prescription occurred in the first quarter of the pandemic, but this downward trend continued throughout the observation period, albeit at a slower pace. Clinically meaningful differences in opioid prescriptions and dose over time did not emerge based on patient race or rurality; however, differences emerged between female and male veterans, with decreases in opioid prescriptions slowing more markedly for women after the pandemic onset. These findings suggest that the pandemic was not associated with short- or long-term increases in opioid prescriptions or doses in the VA. PerspectiveThis article examines opioid prescribing over a 3-year period—1 year prior to and 2 years after the onset of the COVID-19 pandemic—for VA patients with chronic low-back pain. Results indicate that, despite disruptions to health care, opioid prescriptions and doses decreased over the entire observation period.

Symptoms and Prognoses of Patients With Breast Cancer and Malignant Wounds in Palliative Care Units: The Multicenter, Prospective, Observational EASED Study.

This study sought to investigate the symptoms and prognoses of patients with breast cancer and malignant wounds in the palliative care unit setting. This study was a sub-group analysis of a multicenter, prospective, observational study. Patients admitted to 23 palliative care units in Japan between January and December 2017 were enrolled. Data of patients with breast cancer were extracted. We compared demographic characteristics, symptoms, and prognoses by breast cancer malignant wound status. The primary outcome was overall survival. Secondary outcomes included Palliative Prognostic Index (PPI) score, malignant wound characteristics, and symptom burden. Of 1896 patients, 131 (6.9%) had breast cancer. In this cohort, 44 (33.6%) patients had malignant wounds. Most malignant wounds (88%) were on the back and chest. Malignant wounds were associated with skin redness, erosion, necrosis, or fistula. Symptoms included bleeding, exudate, odor, and pain. Twenty-eight patients (63.6%) needed dressing changes and 14 (31.8%) patients experienced bleeding. None died due to bleeding. In the malignant wounds group, 32 (72.8%) patients had used an opioid dose equivalent to 38mg of oral morphine daily, compared to 25mg by 57 (65.5%) patients in the non-malignant wounds group (P = .26). Median PPI scores at hospital admission were 4.5 vs 6.5 (P = .08). Median survival was 23 vs 21days (P = .48). Patients with malignant wounds had a distinct symptom burden profile and tended to use a higher dose of opioids. The effect of malignant wounds on survival was unclear.

Pediatric ultrasound-guided dorsal penile nerve block and sedation in spontaneous breathing: a prospective observational study.

Worldwide, one of the most common surgical procedures in the pediatric population is circumcision. There is no consent on the best anesthesiologic approach. This study aimed to investigate ultrasound-guided dorsal penile nerve block (DPNB) plus sedation in spontaneous breathing as a time-saving, safe, effective, and opioid-sparing technique. The primary outcome was the assessment of the time from the end of surgery and the discharge to the post-anesthesia care unit. Secondary outcomes were to evaluate the cumulative dosages of opioids, differences in pain levels between the two groups, and complications at the awakening, 4 h and 72 h after surgery, respectively. This was a prospective study with a retrospective control group, approved by the Friuli-Venezia Giulia Ethics Committee. Children in the intervention group received an ultrasound-guided DPNB under sedation and spontaneous breathing. With the probe positioned transversally at the base of the penis using an in-plane approach with a modified technique, local anesthetic was injected under the deep fascia of the penis. We recruited 70 children who underwent circumcision at the University Hospital of Udine, Italy, from 1 January 2016 to 1 October 2021: 35 children in the ultrasound-guided DPNB group and 35 children in the control group. Children who received ultrasound-guided DPNB had a statistically significant lower time to discharge from the operating room, did not require mechanical ventilation, maintained spontaneous breathing at all times, received fewer opioids, had lower mean intraoperative arterial pressures, and lower pain levels immediately after surgery. Ultrasound-guided DPNB associated with sedation and spontaneous breathing is a time-saving, opioid-sparing, safe, and effective strategy for the management of intraoperative and postoperative pain in children undergoing circumcision.Clinical trial registration: ClinicalTrial.gov (NCT04475458, 17 July 2020).

Examining the benefit of a higher maintenance dose of extended-release buprenorphine in opioid-injecting participants treated for opioid use disorder

BackgroundBUP-XR (SUBLOCADE®) is the first buprenorphine extended-release subcutaneous injection approved in the USA for monthly treatment of moderate-to-severe opioid use disorder (OUD). Among patients with OUD, those who inject or use high doses of opioids likely require higher doses of buprenorphine to maximize treatment efficacy. The objective of this analysis was to compare the efficacy and safety of 100-mg versus 300-mg maintenance doses of BUP-XR in OUD patients who inject opioids.MethodsThis was a secondary analysis of a randomized, double-blind, placebo-controlled study in which adults with moderate or severe OUD received monthly injections of BUP-XR (2 × 300-mg doses, then 4 × 100-mg or 300-mg maintenance doses) or placebo for 24 weeks. Abstinence was defined as opioid-negative urine drug screens combined with negative self-reports collected weekly. Each participant’s percentage abstinence was calculated after the first, second, and third maintenance doses in opioid-injecting and non-injecting participants. The proportion of participants achieving opioid abstinence in each group was also calculated weekly. Treatment retention rate following the first maintenance dose was estimated for opioid-injecting participants with Kaplan–Meier method. Risk-adjusted comparisons were made via inverse propensity weighting using propensity scores. Buprenorphine plasma concentration–time profiles were compared between injecting and non-injecting participants. The percentages of participants reporting treatment-emergent adverse events were compared between maintenance dose groups within injecting and non-injecting participants separately.ResultsBUP-XR 100-mg and 300-mg maintenance doses were equally effective in non-injecting participants. However, in opioid-injecting participants, the 300-mg maintenance dose delivered clinically meaningful improvements over the 100-mg maintenance dose for treatment retention and opioid abstinence. Exposure–response analyses confirmed that injecting participants would require higher buprenorphine plasma concentrations compared to non-injecting opioid participants to achieve similar efficacy in terms of opioid abstinence. Importantly, both 100- and 300-mg maintenance doses had comparable safety profiles, including hepatic safety events.ConclusionsThese analyses show clear benefits of the 300-mg maintenance dose in injecting participants, while no additional benefit was observed in non-injecting participants relative to the 100-mg maintenance dose. This is an important finding as opioid-injecting participants represent a high-risk and difficult-to-treat population. Optimal buprenorphine dosing in this population might facilitate harm reduction by improving abstinence and treatment retention.Trial registration: ClinicalTrials.gov, NCT02357901.

Risk Factors for Self-Harm Ideation Among Persons Treated With Opioids for Chronic Low Back Pain.

Chronic pain is a significant health concern that adversely affects all aspects of life, including emotional well-being. Opioids are prescribed for the management of refractory, severe chronic pain, although they have been associated with adverse effects, including addiction and overdose. The aim of this study was to examine factors that predict thoughts of self-harm among adults with chronic pain who are prescribed opioids. Seven hundred sixty-five (N=765) persons with opioid-treated chronic lower back pain completed the Current Opioid Misuse Measure (COMM) and other validated questionnaires as part of a larger study. Response to 1 question from the COMM ("How often have you seriously thought about hurting yourself?") was used to assess suicide risk on a 5-point scale (0=never; 4=very often). Participants were categorized into 3 groups according to their responses to the self-harm question: never (N=628; 82.1%), seldom or sometimes (N=74; 9.7%), and often or very often (N=63; 8.2%). Multivariate adjusted odds ratio (aOR) analyses indicated that reports of alcohol or drug overuse within the past month (aOR=1.41,[95% CI 1.11-1.78]), posttraumatic stress (PTSD; aOR=1.24,[1.07 to 1.44]), pain catastrophizing (aOR=1.03,[1.01 to 1.05]), not loving oneself (aOR=0.99,[.98-1.00]) and poor perceived mental health (aOR=0.94,[.92 to 97]) were most associated with thoughts of self-harm. Importantly, the ideation frequency of self-harm was highest among individuals treated with higher daily doses of opioids. These results support the need for continued monitoring of adults treated with opioids for chronic pain, particularly among those on high-dose opioids who present with increased negative affect and concerns of substance misuse.

Relationship Between Pain and Delirium in Critically Ill Adults.

Although opioids are frequently used to treat pain, and are an important risk for ICU delirium, the association between ICU pain itself and delirium remains unclear. We sought to evaluate the relationship between ICU pain and delirium. Prospective cohort study. A 32-bed academic medical-surgical ICU. Critically ill adults (n = 4,064) admitted greater than or equal to 24 hours without a condition hampering delirium assessment. None. Daily mental status was classified as arousable without delirium, delirium, or unarousable. Pain was assessed six times daily in arousable patients using a 0-10 Numeric Rating Scale (NRS) or the Critical Care Pain Observation Tool (CPOT); daily peak pain score was categorized as no (NRS = 0/CPOT = 0), mild (NRS = 1-3/CPOT = 1-2), moderate (NRS = 4-6/CPOT = 3-4), or severe (NRS = 7-10/CPOT = 5-8) pain. To address missingness, a Multiple Imputation by Chained Equations approach that used available daily pain severity and 19 pain predictors was used to generate 25 complete datasets. Using a first-order Markov model with a multinomial logistic regression analysis, that controlled for 11 baseline/daily delirium risk factors and considered the competing risks of unarousability and ICU discharge/death, the association between peak daily pain and next-day delirium in each complete dataset was evaluated. Among 14,013 ICU days (contributed by 4,064 adults), delirium occurred on 2,749 (19.6%). After pain severity imputation on 1,818 ICU days, mild, moderate, and severe pain were detected on 2,712 (34.1%), 1,682 (21.1%), and 894 (11.2%) of the no-delirium days, respectively, and 992 (36.1%), 513 (18.6%), and 27 (10.1%) of delirium days (p = 0.01). The presence of any pain (mild, moderate, or severe) was not associated with a transition from awake without delirium to delirium (aOR 0.96; 95% CI, 0.76-1.21). This association was similar when days with only mild, moderate, or severe pain were considered. All results were stable after controlling for daily opioid dose. After controlling for multiple delirium risk factors, including daily opioid use, pain may not be a risk factor for delirium in the ICU. Future prospective research is required.

The Enhanced Recovery After Surgery protocol for the surgical management of craniosynostosis: Lausanne experience.

Over the past decade, the Enhanced Recovery After Surgery (ERAS) program has demonstrated its effectiveness and efficiency in improving postoperative care and enhancing recovery across various surgical fields. Preliminary results of ERAS protocol implementation in craniosynostosis surgery are presented. An ERAS protocol was developed and implemented for cranial pediatric neurosurgery, focusing on craniosynostosis repair. The study incorporated a pre-ERAS group consisting of a consecutive series of patients who underwent craniosynostosis repair surgery prior to the implementation of the ERAS protocol; the results were compared with a consecutive group of patients who had been prospectively collected since the introduction of the ERAS for craniosynostosis protocol. The safety, feasibility, and efficiency of the ERAS protocol in pediatric neurosurgery was evaluated, through the collection of clinical data from the pre-, intra-, and postoperative phase. Surgery-related complications were evaluated according to the Clavien-Dindo classification. Costs of the stays were obtained using a microcosting approach. A total of 35 pre-ERAS patients and 10 ERAS patients were included. Scaphocephaly was the most common pathology in both groups. The overall compliance with the pre-, intra-, and postoperative criteria significantly increased-from 35.5%, 64.4%, and 54.7%, respectively, in each phase to 94%, 90%, and 84% (p < 0.001). The authors noticed a reduction in the average opioid dose used per patient in the ERAS group (p = 0.004), and they observed a trend toward a decreased mean length of stay from 5.2 days in the pre-ERAS group to 4.6 days in the ERAS group, without an increase of the rate of readmission within 30 days of surgery. The rate of complications decreased but this difference was not statistically significant. The hospital costs lowered significantly: from 21,958 Confederatio Helvetica Francs (CHF) in the pre-ERAS group to 18,936 CHF in the ERAS group (p = 0.02). The ERAS protocol represents a safe and cost-effective tool for the perioperative management of craniosynostosis. It showed its positive impact on the analgesia provided and on the reduction of in-hospital costs for these patients. ERAS protocols may thus be interesting options in the pediatric neurosurgical field.

Association between Acute Pain Scores in Children with Sickle Cell Disease and Emergency Department Disposition and Return Visit Rates

Introduction Reducing pain through prompt administration of pain medication in the emergency department (ED) is a primary driver of national guidelines for sickle cell disease (SCD), yet there are few data on how pain scores and changes in pain scores are associated with both the disposition at the initial visit and the likelihood of a return visit. In this study, we analyzed acute pain scores from ED visits for children with uncomplicated SCD pain crisis to determine the relationships between pain scores and disposition (admission or discharge) or occurrence of a return ED visit. Objectives For children with uncomplicated SCD pain crises, we aimed to determine (1) the association between initial pain score, last pain score, change in pain scores and the disposition of index ED visits, and (2) the association between these pain score values, number of parenteral opioid doses in the ED, whether an opioid prescription was provided at discharge, and an ED return visit within 14 days. Methods This is a multicenter retrospective cohort study of acute pain scores of ED visits by children for uncomplicated SCD pain crises. It was conducted using electronic health care data from the Pediatric Emergency Care Applied Research Network (PECARN) Registry across 7 sites (Lurie Children's, Children's Hospital of Philadelphia, Cincinnati Children's Hospital, Children's National Medical Center, Children's Colorado, Children's Wisconsin, and Nationwide Children's). Index ED visits were defined as uncomplicated pain crises with no preceding ED visits within 14 days between 01/2017 - 11/2021. We collected the following ED pain scores: initial, last, and change in scores (initial minus last) as measured by a numeric rating scale (0-10). For analyses related to disposition, we modeled the relationship between the three pain scores and hospital disposition adjusting for age, sex and uncomplicated pain crisis visit admission rate. For analyses related to return visits, we utilized the same predictor variables and added both the number of parenteral opioid doses administered in the ED and whether or not a prescription for an opioid was given at discharge. For all analyses, adjustment for site was made using generalized estimating equations with an exchangeable correlation structure to account for clustering within site. Modified Poisson regression was used to identify associations. SAS software version 9.4 was used for all statistical analyses. Results A total of 4,985 index visits for uncomplicated SCD pain crisis were included; 52% resulted in hospitalization. Overall, 39% of the children were &amp;lt;12 years old, 54% were female, and 96% were Black. Eligible index ED visits per site varied from 157 to 1855. The overall ED median (IQR) initial pain score was 8.0 (6.0-10).The median last pain score was 5.0 (2.0-8.0); median change in ED pain score was 2.0 (0.0-5.0). In univariate analyses, higher initial and last pain scores and a smaller change in pain scores were all associated with higher hospitalization rates. Adjusted rate ratios (95% CI) from multivariable models showed last pain score was the best predictor of admission 1.16 (1.12, 1.19), with change in pain score no longer significant 0.98 (0.96, 1.00). Examining percent of children hospitalized by last pain score shows over 80% of children with a last pain score of 7 or higher were hospitalized, compared to less than 40% if 4 or lower (Figure 1). 29% of the 2,377 visits that were originally discharged to home had a return visit within 14 days. None of the included pain scores from the initial visit (initial, last, or change) were associated with having a return visit within 14 days. However, both an increased number of ED opioid doses and failure to receive a prescription for an opioid at discharge were associated with increased return visits. Figure 2 shows the ED opioid doses and prescription for opioid combination and their respective return visit rates, with a high of 36% for ≥ 3 doses of ED opioid doses and no prescription and a low of 22% if 1 opioid given and a prescription at discharge. Conclusions: We found that for a child with SCD presenting to the ED with an uncomplicated pain crisis, the last ED pain score was a better predictor of hospitalization than initial or change in pain score. None of those pain scores predicted a return visit after discharge; however, fewer opioid doses in the ED and receipt of an opioid prescription at discharge were associated with fewer return visits.

Delayed Management of Sickle Cell Disease Vaso-Occlusive Episodes and the Impact on Prolonged Hospitalizations at a Single Academic Center

Introduction: Sickle Cell Disease (SCD) affects nearly 100,000 people in the United States (Centers for Disease Control and Prevention, 2023). Vaso-occlusive episode (VOE) is the most common reason for hospitalization in SCD. Many providers are unfamiliar with the pain management timing and dosages required to adequately treat these episodes (Jang et al., J Transl Med 2021). Nationally, areas with comprehensive sickle cell centers have shown decreased hospital utilization, fewer VOEs, and improved quality of life (Oyedeji et al. JAMA 2020). Even in areas without a comprehensive center, implementing individualized pain care plans for SCD has reduced admission rates of high-utilizing patients while not impacting their pain rating scores (Welch-Coltrane et al. Pain Medicine 2021). Our academic hospital, Oregon Health and Science University (OHSU), lacks a comprehensive SCD center and VOE treatment plans are not easily accessible for these patients. We conducted a retrospective analysis on a cohort of patients with SCD to investigate the factors influencing the length of emergency department (ED) and hospital stays for VOE. We aim to identify if implementing individualized pain plans via a standardized template within the electronic health record (EHR) for these patients will decrease hospital admission, length of stay and time to ED discharge. We also aim to integrate individualized pain plans into the EHR that would allow for direct exposure to the care team by creating plans that are easily accessible, reviewed, and routinely utilized for clinical decision-making. Methods: We performed a preliminary retrospective analysis of encounters (n=107) from 2008-2023 at OHSU, where the primary diagnosis was either a VOE or an equivalent diagnosis. Based on data demonstrating earlier maximum opioid doses leading to shortened hospital stays in frequent pain patients, we recorded the timing of the first opioid and morphine milliequivalents per hour in the first 24 hours (Payne et al. Pediatr Blood Cancer 2018). Additionally, we recorded the length of stay, admission rates, time to first IV fluid, and the type of IV fluid used. We performed a linear regression analysis on the collected data with the dependent variable as the length of stay across the independent variables of time to first opioid, time to first intravenous fluid, and morphine milliequivalents per hour during the first 24 hours after presentation. Results: Eighteen patients accounted for the 107 analyzed encounters. Thirteen patients (72%) had Hgb-SS disease, 2 (11%) had Hgb-SC disease, and 3 (17%) had Hgb-S-beta thalassemia. Sixty-two admissions (58%) were ED discharges, and 45 (42%) were ED to hospital admissions. The length of stay and time to the first opioid positively correlated with p=0.005 (Figure 1a). The length of stay and time to first intravenous fluid administration was also positively correlated with p=0.01. The length of stay and morphine milliequivalents per hour in the first 24 hours were negatively correlated with p&amp;lt;0.0001 (Figure 1b). Conclusions: Longer time to administration of opioids and intravenous fluids correlated with a longer length of stay in both the ED and the hospital. Additionally, lower morphine milliequivalents in the first 24 hours of presentation were associated with a prolonged hospital stay at our institution. We hypothesize that these three factors are secondary to delays in care and inappropriate initial treatment of VOE. To address these factors, we aim to implement standardized pain plans in the EHR of our institution. Implementation of individualized pain plans, particularly in the ED, has led to the earlier initiation of opioids (Della-Moretta et al. Ann Emerg Med 2020). We anticipate similar effectiveness for timely and appropriate fluid administration and adequate opioid dosing. We plan to continue retrospective analysis and compare this data to VOE encounters post-implementation. By implementing individualized plans that are integrated within the EHR and efficiently utilized by the care team, we hope to improve VOE management at our institution with decreased length of stay, less ED to hospital admissions, and improved patient satisfaction.

Identifying Inflammatory and Immune Markers Associated with Vasoocclusive Crisis in Patients with Sickle Cell Disease

Background: Sickle cell disease (SCD) is an inherited disorder that can cause a range of clinical complications, featured by unpredictable and recurrent acute painful episodes associated with vasoocclusive crises (VOCs). Individuals with SCD experience frequent VOCs and require high doses of opioids for pain control. Thus far, studies on biomarkers associated with VOCs in SCD are very limited and the known markers are hardly considered as critical end points in studying VOCs in SCD. This study aimed to comprehensively analyze immune and inflammatory characteristics of patients with SCD to understand the disease-specific pathogenesis and develop targeted diagnostic and therapeutic strategies related to VOCs. Methods: The study cohort consisted of 40 patients with SCD aged 14-73 years (23 female, 58%), recruited for an ongoing clinical trial (ClinicalTrials.gov Identifier: NCT05045820). Twenty-three ethnicity-, age- and gender-matched pain-free participants were also enrolled as healthy controls (HCs) (Table 1). Multiplex immunoassays were used to profile 80 inflammatory cytokines/chemokines/growth factors and 18 autoantibodies in plasma samples from patients with SCD and the matched HCs. Peripheral blood mononuclear cells were used to profile immune cells. Statistical analysis was performed using GraphPad Prism with Mann-Whitney test, χ 2 test, and Spearman's correlation. P &amp;lt; 0.05 was considered statistically significant. Results: Patients with SCD exhibited significantly higher plasma levels of 34 analytes, including 12 pro-inflammatory/anti-inflammatory cytokines (IFN-γ, IL-1α, IL-2, IL-8, IL-9, IL-18, TNF-α, TNF-β, IL-4, IL-5, IL-6, and TSLP), 10 chemokines (CCL21, CCL23, Eotaxin-2, Gal-3, GRO-α, IP-10, MCP-2, MIP-1α, MIP-1β, and MIP-3α), 8 growth factors (bNGF, G-CSF, GM-CSF, HGF, IL-7, IL-20, IL-34, and LIF), 2 effectors (granzymes A and B), and 2 soluble receptors (PTX3, TREM-1). Higher activation levels of B cells, CD4 T cells, CD8 T cells, and MAIT cells were seen in patients with SCD. Autoantibody profiles were also altered in patients with SCD, with elevated levels of antibodies against SSA/Ro60, Ribosomal P, Myeloperoxidase, and PM/Scl-100. Levels of cytokines/chemokines/growth factors were correlated with time interval between blood draw and occurrence of VOCs. Four soluble factors (Eotaxin-2, GRO-α, IL-6, and LIF) were positively associated with time interval after VOCs, while two factors (IL-18 and granzyme A) showed negative associations with time interval, suggesting that the altered inflammatory mediators were associated with the occurrence of VOC events. Conclusion: Our results provide novel and comprehensive understanding of the immune and inflammatory dysregulation in patients with SCD and their relationship with occurrence of VOCs, offering insights into potential SCD-specific biomarkers for further investigation.

SNAP: Implementation of Supportive Non-Invasive Ventilation for Acute Chest Syndrome Prevention in Adults with Sickle Cell Disease

Introduction Acute chest syndrome (ACS) is the 2 nd most common cause of hospitalization and a major cause of mortality in sickle cell disease (SCD). ACS commonly occurs during a hospitalization for a vaso-occlusive crisis (VOC) when the combination of chest wall pain and intravenous opioids may lead to hypoventilation and atelectasis. Incentive spirometry may prevent ACS by encouraging patients to take deep breaths to reduce atelectasis and improve oxygenation, but requires active participation by an awake patient. Non-invasive bi-level positive airway pressure [BiPAP] provides positive pressure breaths via a mask to improve ventilation and prevent atelectasis during sleep. Hospitalized pediatric SCD patients who were at risk for ACS have used nocturnal BiPAP for ACS prevention on the Boston Medical Center (BMC) general pediatric unit since February 2017. In January 2023, BMC instituted the use of nocturnal BiPAP in hospitalized adult patients with SCD who are at high risk for ACS. Methods This is a prospective observational cohort study to examine the safety, acceptability, and tolerability of BiPAP in high-risk adult patients with SCD hospitalized with a VOC. Criteria for increased ACS risk included: 1) Oxygen saturation &amp;lt; 94% on room air at presentation; 2) History of pulmonary hypertension diagnosed by right heart catheterization; 3) Known obstructive sleep apnea (OSA) not currently treated with positive airway pressure; 4) Prior severe ACS requiring invasive or non-invasive ventilation, high-flow oxygen, and/or exchange transfusion; or 5) History of fat emboli syndrome. Exclusion criteria were: 1) OSA being treated with outpatient positive airway pressure, 2) Surgery within the last 30 days, 3) Direct admission to the intensive care unit (ICU). Manual chart extraction was used to collect patient demographic data, medical history, symptoms, vital signs, chest radiography, laboratory data, indications for BiPAP use, and acceptability and use of BiPAP. Results BiPAP was offered during 38 hospitalizations to 25 individual patients (14 (56%) female) between February and July 2023. The mean age was 35.8 years (SD 10.2); 16 (64%) were HbSS, 8 (32%) HbSC and 1 (4%) HbS-β 0. Nineteen patients (76%) were using &amp;gt;1 SCD-modifying therapy; 16 (64%) reported hydroxyurea use. ACS was present on admission in 7 hospitalizations. Patients agreed to try BiPAP in 22/38 hospitalizations (58%) and BiPAP was used for 1 night in 3 hospitalizations, 2 nights in 3 hospitalizations and more than 2 nights in 7 hospitalizations. In 9/22 hospitalizations, attempts at BiPAP use were unsuccessful. Of the 38 hospitalizations in which BiPAP was offered, 3 patients who did not use BiPAP were transferred to the ICU, 2 for ACS and 1 for ketamine infusion for pain that was refractory to high doses of opioids. Three episodes of ACS developed after admission to the hospital: 2 when BiPAP use had not been attempted and 1 when BiPAP was used for 6 days. Blood transfusions were administered during 7 hospitalizations; 5 of which BiPAP was not used. No deaths occurred during this study period. No adverse events were directly attributable to this novel use of BiPAP for ACS prevention. In the 22 encounters where BiPAP use was attempted, four patients noted difficulties with the continuous airflow and feeling suffocated, one reported lightheadedness. One patient who used BiPAP developed oral pain related to periodontal disease. Conclusion Medically stable, adult hospitalized patients with SCD and VOC were willing to try BiPAP to prevent the development of ACS. In 13/22 (59%) BiPAP was tolerated for &amp;gt;1 one night with no adverse events noted. Future directions include optimizing implementation and studying the efficacy of this intervention.

Knowing the Dose to Control the Dose: Optimizing Patient-Controlled Analgesia in Adults with Sickle Cell Disease (SCD)

Introduction: Acute painful episodes are the most common cause of hospitalization in SCD. Intravenous (IV) opioids are the analgesic of choice to treat pain requiring hospitalization in adults. On-demand IV opioid dosing can be either via a patient-controlled analgesia (PCA) pump or via intermittent nurse bolus. Advantages of PCA include better analgesia accessibility and relative independence from staff. However, significant variability exists in PCA management. A multicenter, randomized-controlled trial of PCA strategies in SCD was terminated early due to slow accrual, stemming from barriers such as suboptimal communication between inpatient teams. Additional limitations with PCA include technological limitations and incomplete charting through a manual process. We initiated a quality improvement project to understand patterns of PCA use in patients hospitalized for SCD pain crises at our institution. Methods: We performed a retrospective manual chart review on all adult patients diagnosed with SCD pain crises admitted to the University of Cincinnati Medical Center (UCMC) from October 1 through December 31, 2022. Inpatient data collected included reason for admission, length of stay, and documentation of inpatient opioid usage in daily clinical notes. Hospitalizations requiring intensive care admission for severe complications were excluded. Outpatient data collected included demographics and outpatient opioid prescriptions via the state prescription drug monitoring database. The study was approved by the UCMC IRB. Results: Fifteen patients were admitted to UCMC a total of 24 times for SCD pain crises during the 3-month period. The patients ranged in age from 21 years to 73 years (median age 33 years, interquartile range (IQR) 19.5 years) and the majority (11/15) were women. Disease-modifying therapies prescribed included hydroxyurea (8/15, 53%), chronic transfusions (2/15, 13%), chronic transfusions plus hydroxyurea (1/15), voxelotor (1/15), no disease-modifying therapy (2/15). Nine patients were prescribed daily outpatient opioids that included an oral long-acting opioid plus an oral short-acting opioid. Out of the 24 hospitalizations, 11 were for an uncomplicated pain crisis, 10 were complicated by mild acute chest syndrome (mild hypoxia and/or abnormal chest imaging), and 3 patients experienced other treatable complications (2 with Staphylococcus epidermidis bacteremia, 1 with deep venous thrombosis). Five patients were admitted two or more times. Two patients, admitted a total of 5 times, were maintained on nurse-administered IV bolus opioids during their admissions, in addition to oral opioids. The remainder of the patients were treated with a hydromorphone PCA pump with on-demand bolus dosing only, in addition to home long-acting oral opioids when applicable. Two patients were ultimately transitioned from PCA onto nurse-administered bolus IV opioids, due to failure to achieve adequate analgesia with PCA. In 9 out of the 19 admissions using a PCA, daily MME or the equivalent was charted in at least one progress note (47%). The median LOS in the subgroup in which PCA use was charted at least once was 7 (IQR 3.5) days. In the 10 admissions on a PCA in which daily MME was never charted (53%), the median LOS was 11 (IQR 6.25) days. Among patients not receiving outpatient opioids, daily MMEs from the PCA in the first few days of hospitalization (when recorded) ranged from 24 to 520 (median 178, IQR 241) MME. In patients who had daily chronic pain on outpatient opioid therapy, daily inpatient MME from PCA ranged from 360 to 1020 (median 545, IQR 418) MME. In patients with multiple admissions during the study period, the recorded daily opioid use was about two times that in the single admission group (median 673, IQR 500 MME in the multiple admissions group; vs median 329, IQR 351 MME in the single admission group). Conclusions: Our data suggest that length of stay is shortened by ~4 days when clinicians quantify daily opioid use for patients on PCA. In addition, patients with frequent admissions tend to have higher inpatient daily opioid use. This hints that readmission may be partly driven by mild withdrawal when on outpatient opioids at lower MME. A major barrier to data collection was inconsistent documentation of daily opioid use. The next step in our quality improvement project is an educational curriculum on inpatient opioid management for residents and hospitalists.

Rates and risk factors for persistent opioid use after cardiothoracic surgery: A cohort study

BackgroundThis study’s aim was to estimate potential risk factors for persistent opioid use after cardiothoracic surgery. MethodsThis study included participants in the McGill University Health Centre clinical trial (2014 to 2016). Provincial medical services, prescription claims, and medical charts data were linked. Persistent opioid use was defined as an initial peri-operative opioid dispensation followed by an opioid dispensation between 91 and 180 days postdischarge. Multivariable Cox Proportional Hazards models were used to assess factors associated with persistent opioid use. ResultsA cohort of 815 patients (mean age: 68.9 [standard deviation = 8.9]) was assembled, of which 8.2% became persistent opioid users. Factors such as higher Charlson Comorbidity Index (adjusted hazard ratio: 3.4, 95% confidence interval: 1.1–10.6), history of diabetes (adjusted hazard ratio: 2.1, 95% confidence interval: 1.3–3.4), substance and alcohol abuse (adjusted hazard ratio: 16.3, 95% confidence interval: 5.3–49.5), and radiotherapy (adjusted hazard ratio: 2.4, 95% confidence interval: 1.5–4.1) were associated with a higher hazard of persistent opioid use. Previous opioid use (adjusted hazard ratio: 1.7, 95% CI: 1.0–2.8), daily peri-operative opioid dose (adjusted hazard ratio: 2.3, 95% confidence interval: 1.5–3.7), having an opioid dispensation 30 days pre-admission (adjusted hazard ratio: 1.7, 95% confidence interval: 1.0–2.8), and pre-admission analgesic use (adjusted hazard ratio: 1.7, 95% confidence interval: 1.0–2.8), were also associated with an increased hazard of persistent use. Being prescribed multimodal analgesia at discharge (adjusted hazard ratio: 0.54, 95% confidence interval: 0.32–0.92) was associated with a 46% decreased hazard of developing persistent opioid use. ConclusionMultiple patient- and medication-related characteristics were associated with an increased hazard of persistent opioid use.

Mu-Opioid Receptor 1 and C-Reactive Protein Single Nucleotide Polymorphisms as Biomarkers of Pain Intensity and Opioid Consumption.

Children constitute a special group in pain therapy. Single nucleotide polymorphisms that are associated with differences in postoperative, inflammatory pain perception and opioid requirement are the A118G SNP in the mu-opioid receptor 1 (OPRM1) gene and the rs1205 CRP. This study aimed to determine connection between OPRM1 and rs1205 CRP SNPs in pediatric patients postoperatively and pain intensity, the opioid dose needed to control pain after scoliosis correction, and other clinical aspects. Genotypes of rs1205 CRP and OPRM1 polymorphisms in a sample of 31 patients were specified, and statistical analysis was performed in terms of age, genotype frequency, pain assessment, sufentanil flow, post-anesthesia care unit stay, and the use of coanalgesics. The frequency of A/A and A/G genotypes in the OPRM1 gene was in line with 1000Genomes data for the European population. Patients from the AG group of OPRM1 SNP more frequently required coanalgesics for adequate pain control; however, it was of weak statistical significance. Other parameters measured in the study were not statistically significant in relation to OPRM1 and CRP polymorphisms. The effect of SNPs on postoperative pain management and opioid therapy in children was not confirmed by this study. An expansion of the study sample and other opioid-related SNPs is required.

Perioperative Opioid Use and Dosage Trajectories Vary Depending on Pain Outcome Classification and Bodily Pain in Patients who Catastrophize About Their Pain: A Secondary Analysis of a Randomized Trial in Knee Arthroplasty

Opioid use and dosage following knee arthroplasty (KA) has not been reported for subgroups with persistent moderate pain versus rapidly improving mild pain, externally validated from prior work. We determined if opioid use and dosage varied for persons classified into these externally validated subgroups. A secondary purpose determined if bodily pain scores are associated with the outcome subgroup. This was a secondary analysis of a prospective no-effect randomized clinical trial conducted on 384 participants with pain catastrophizing and scheduled for KA. Data were collected preoperatively and at 2-, 6-, and 12-month following surgery. Two-piece latent class growth curve analyses applied previously validated pain outcomes to determine subgroup outcome trajectories for the proportion of opioid users and oral morphine equivalent (OME) dosages. Substantial trajectory separation was found for opioid use and OME. Specifically, the average OME dosage for the persistent moderate pain subgroup was more than double that for the other outcome subgroup. The average preoperative opioid daily OME dosage for 170 patients reporting opioid use was 24.94 (95% [confidence interval] CI = 20.52, 29.38). Bodily pain was consistently higher for the persistent moderate pain subgroup compared to the other subgroup. Outcome subgroups in patients with pain catastrophizing demonstrated substantial differences in opioid use and dosage and were predicted by high pain catastrophizing, more bodily pain, and changes in bodily pain over time. The persistent moderate pain subgroup is at greater risk of opioid use and greater opioid dosages and should be targeted for preoperative screening and interventions to reduce opioid use and potential opioid misuse. PerspectiveMore frequent and higher opioid dosage following KA was found for the persistent moderate pain subgroup compared to the other subgroup. Patients with persistent pain had worse catastrophizing, contralateral and ipsilateral lower extremity pain, low back pain, and whole body pain compared to the rapidly improving mild pain subgroup.

Adjunctive tonic motor activation enables opioid reduction for refractory restless legs syndrome: a prospective, open-label, single-arm clinical trial

BackgroundThere is a large population of restless legs syndrome (RLS) patients who are refractory to medication. Whereas experts recommend off-label opioids as an effective long-term treatment for refractory RLS, reducing opioid dose could substantially reduce side effects and risks. Tonic motor activation (TOMAC) is a nonpharmacological therapeutic device indicated for refractory RLS. Here, we investigated if TOMAC could enable opioid dose reduction for refractory RLS.MethodsThis prospective, open-label, single-arm clinical trial [NCT04698343] enrolled 20 adults taking ≤ 60 morphine milligram equivalents (MMEs) per day for refractory RLS. Participants self-administered 30-min TOMAC sessions bilaterally over the peroneal nerve when RLS symptoms presented. During TOMAC treatment, opioid dose was reduced iteratively every 2–3 weeks until Clinician Global Impression of Improvement (CGI-I) score relative to baseline exceeded 5. Primary endpoint was percent of participants who successfully reduced opioid dose ≥ 20% with CGI-I ≤ 5. Secondary endpoints included mean successful percent opioid dose reduction with CGI-I ≤ 5.ResultsOn average, participants were refractory to 3.2 medications (SD 1.6) and were taking a stable dose of opioids for 5.3 years (SD 3.9). Seventy percent of participants (70%, 14 of 20) successfully reduced opioid dose ≥ 20% with CGI-I ≤ 5. Mean percent opioid dose reduction with CGI-I ≤ 5 was 29.9% (SD 23.7%, n = 20) from 39.0 to 26.8 MME per day. Mean CGI-I score at the reduced dose was 4.0 (SD 1.4), indicating no change to RLS severity.ConclusionsFor refractory RLS, TOMAC enabled substantial opioid dose reduction without increased RLS symptoms. These results suggest that TOMAC has the potential to reduce the risk profile associated with opioid therapy for refractory RLS.Trial registrationClinicalTrials.gov trial number NCT04698343 registered on January 6, 2021.

Opioid dose risk, clinician and patient characteristics, and adherence to opioid prescribing recommendations in chronic non-cancer pain.

This study aims to assess associations between morphine-equivalent daily dose (MEDD) of opioids, clinician and patient characteristics, and prescriber adherence to guidelines for long-term opioid therapy (LTOT) in chronic noncancer pain (CNCP) and to elucidate potential relationships associated with increased-risk opioid prescribing. Retrospective cross-sectional study. Academic health system's 33 primary care clinics. Adults (≥18 years old) prescribed LTOT (10 + outpatient prescriptions in the past year) for CNCP. Electronic health record data on prescribed opioids (for MEDD), clinician/patient characteristics, and adherence rates to LTOT guideline-concordant recommendations. A total of 2,738 patients were eligible, 61.6 percent Lower, 15.7 percent Moderate, and 22.7 percent Higher Risk MEDD (<50, 50-89, and ≥90 mg/day, respectively). Higher MEDD correlated (p < 0.001) with Medicare insurance, current cigarette smoking, higher pain intensity and interference scores, and the presence of opioid use disorder diagnoses. Male clinicians more frequently prescribed (p < 0.001) and male patients were more likely to be prescribed (p < 0.001) higher MEDD compared to their female counterparts. Higher Risk MEDD was associated with higher coprescribed benzodiazepines (p = 0.015), lower depression screening (p = 0.048), urine drug testing (p = 0.003), comparable active treatment agreement (p = 0.189), opioid misuse risk screening (p = 0.619), and prescription drug monitoring checks (p = 0.203). This study documented that higher MEDD was associated with risks of worse health outcomes without improved adherence to opioid prescribing guideline recommendations. Enhanced clinician awareness of factors associated with MEDD has the potential to mitigate LTOT risks and improve overall patient care.