Opioid Dose Research Articles

Pain Assessment Following Opioid Administration in Aneurysmal Subarachnoid Hemorrhage Associated Headache

Background: Headache is a debilitating complication following an aneurysmal subarachnoid hemorrhage (aSAH). Despite its impact on morbidity and quality of life, limited evidence characterizes the effectiveness of opioids. Objective: The aim of this study was to evaluate opioid associated reduction in pain scores in patients with aSAH-associated headache. Methods: This is a retrospective study of adult patients with an aSAH, Hunt and Hess grades I – III, admitted to a neurosciences intensive care unit. Descriptive and inferential statistics were used to characterize headache treatment strategies and opioid associated reduction in pain scores. Results: Opioids were used in up to 97.6% of patients for the management of aSAH-associated headache. Median reduction in pain after opioid administration was −1 (IQR: -3-0). Correlation between opioid dose and change in pain scores was negligible (rs = .01). Overall, 68.8% of patients were discharged on an opioid analgesic with predictive factors being severe headache (OR 2.52; 1.04 – 6.14) and oral morphine milligram equivalents ≥60 mg per day during the hospital stay (OR 3.02; 1.22 – 7.47). Conclusions: Opioids were associated with a small reduction in pain when assessed via the NRS. An increased opioid dose did not correlate with a greater reduction in assessed pain scores. A high percentage of patients remained on opioids throughout hospitalization and were eventually discharged on an opioid. The impact of discharge opioid prescriptions and risk of opioid persistence creates a cause for concern. It is imperative that we seek improved pain management strategies for aSAH-associated headache.

Perioperative Management of Opioid-Tolerant Patients: A Comprehensive Guide

The perioperative management of opioid-tolerant patients presents significant challenges, necessitating a tailored approach to pain management and the prevention of opioid-related complications. This review discusses the essential aspects of preoperative assessment, intraoperative strategies, and postoperative care for opioid-tolerant patients. Emphasis is placed on the continuation of baseline opioid therapy, the use of multimodal analgesia, and the importance of individualized opioid dosing to achieve effective pain control while minimizing the risk of withdrawal, respiratory depression, and opioid-induced hyperalgesia. The role of a multidisciplinary team in optimizing patient outcomes and the necessity of thorough discharge planning and follow-up are also highlighted. By addressing these critical factors, healthcare providers can ensure safe and effective perioperative care for opioid-tolerant patients.

FLT3 signaling inhibition abrogates opioid tolerance and hyperalgesia while preserving analgesia

Navigating the duality of opioids’ potent analgesia and side effects, including tolerance and hyperalgesia, is a significant challenge in chronic pain management, often prompting hazardous dose escalation to maintain analgesic effects. The peripheral mu-opioid receptor (MOR) is known to mediate these contradictory effects. Here, we show that the fms-like tyrosine kinase receptor 3 (FLT3) in peripheral somatosensory neurons drives morphine tolerance and hyperalgesia in a male rodent model. We found that chronic morphine treatment increases FLT3 and MOR co-expression, and that inhibiting FLT3 represses MOR-induced hyperactivation of the cyclic adenosine monophosphate (cAMP) signaling pathway, mitigating maladaptive excitatory processes engaged after chronic morphine treatment. Furthermore, in postsurgical or inflammatory models of chronic pain, co-administering morphine with a FLT3-specific inhibitor not only prevents or suppresses tolerance and hyperalgesia but also potentiates the analgesic efficacy of morphine, without aggravating other morphine-induced adverse effects. Our findings suggest that pairing morphine with FLT3 inhibitors could become a promising avenue for chronic pain management to safely harness the power of opioids, without the risk of dose escalation. By enhancing morphine analgesic potency through FLT3 inhibition, this approach could minimize opioid dosage, thereby curtailing the risk of addiction and other opioid-related side effects.

Low-dose add-on methadone for cancer pain management: a retrospective analysis of 102 Japanese patients.

Methadone was introduced in 2013 for the treatment of intractable cancer pain in Japan and is indicated for patients receiving opioid doses ≧60mg/day as an oral morphine equivalent. Low-dose (≦10mg/day) add-on methadone to prior opioids has been reported from European countries to successfully relieve various types of intractable cancer pain; however, there are few reports of such use in Japan. The aim of this study was to analyze more than a hundred cases with low-dose add-on methadone to treat intractable pain in Japanese cancer patients. All cases in which 5 or 10mg/day of methadone was added to prior opioids by the Palliative Care Team or Division of Palliative Medicine in our hospital during the period between April 2016 and September 2023 were extracted and analyzed retrospectively on electrical medical charts. A total of 102 cases were extracted with a male-to-female ratio of60:42, and the age (mean±SD) was 62.8±14.7years old. Methadone was introduced in an inpatient setting to 86 patients. The major pathologies that caused intractable pain were spinal metastases in 48, pelvis or pelvic floor lesions in 29 and pleural and/or chest wall lesions in 16. The most common mechanism of pain was the mixture of somatic and neuropathic components. The major opioids administered prior to methadone included tapentadol in 46 patients, hydromorphone in 36 and oxycodone in 19. The dose of the prior opioids [median, (interquartile range: IQR)] was 97, (62.8-167.3) (range: 15-1313) mg/day of oral morphine equivalent. Radiotherapy, chemotherapy and nerve blocks were performed as concomitant therapies in 48, 22 and 11 patients, respectively (with some overlap). The number of rescue doses [median (IQR)] was significantly decreased from three (two to five) on the day before methadone to one (zero to four) after seven days from methadone initiation. The side effects leading to discontinuation of methadone were drowsiness in three cases, nausea in three cases and dizziness in one case (with some overlap). Compared with complete switching from other opioids, low-dose add-on methadone can reduce the possibility of major dose discrepancies and can be quickly adjusted by combined opioid reduction/increase. Low-dose add-on methadone can be an effective and safe method for intractable cancer pain.

The Power of a Good Word: Enhancing the Efficacy of Analgesics in Clinical Settings

Introduction: Communication between medical staff and patients about treatment efficacy elicits expectations of benefit and improves treatment outcomes. While demonstrated in multiple studies via different research methodologies, uniform communication protocols have not been adopted in clinical practice. Here, we summarize the results of two sister studies aimed at bridging this gap. Methods: Women undergoing C-section (study 1, randomized controlled trial) and patients undergoing general or otolaryngologic surgeries (study 2, control group design) were recruited and assigned to the “regular communication” (RC) or “enhanced communication” (EC) arms. The EC arm received positive information about treatment, while the RC arm received no such information. In both studies, the primary outcome was change in pain intensity; in study 2, an additional outcome was morphine consumption. Results: Eighty women successfully completed study 1, and 102 patients successfully completed study 2. In both studies, significant time*group interactions were observed (p < 0.001). The analgesic effect was virtually twice as large in the EC arm compared to the RC arm. In study 2, in the last two timepoints of assessment, participants in the EC arm also consumed fewer doses of opioids than participants in the RC arm (p < 0.001). No significant differences were found in vital signs. Conclusions: We provide ecological evidence that positive information about treatment significantly decreases pain and opioid consumption during routine clinical care. This study and others could encourage healthcare providers to harness the powerful effects of patients’ expectations of benefit to improve analgesics outcomes and, potentially, the outcomes of other symptoms.

Optimizing pediatric tonsillectomy outcomes with an opioid sparing anesthesia protocol: Learning and continuously improving with real-world data.

This quality improvement initiative is a continued pursuit to optimize outcomes by iteratively improving our opioid sparing anesthesia protocol for tonsillectomy with or without adenoidectomy at our pediatric ambulatory surgical center through data driven Plan-Do-Study-Act cycles. From 1/2015 through 12/2023, our standardized tonsillectomy protocol underwent nine procedure-specific perioperative Plan-Do-Study-Act cycles, three procedure-specific postoperative prescription Plan-Do-Study-Act cycles, and four general ambulatory surgical center enhanced recovery Plan-Do-Study-Act cycles. We analyzed data from the medical record using statistical process control charts. The primary outcome measure was the percent of patients requiring intravenous opioid in the post anesthesia care unit. Secondary outcomes included maximum post anesthesia care unit pain score, the percent of patients requiring treatment for nausea and/or vomiting in the post anesthesia care unit, and the number of postoperative opioid prescription dosages. Balancing measures were average post anesthesia care unit length of stay, percent of patients with prolonged Post Anesthesia Care Unit length of stay (>120 min), and 30-day reoperation rate. A total of 5654 tonsillectomy with or without adenoidectomy cases were performed at our ambulatory surgical center from 2015 to 2023. The incidence of intravenous opioid administered in the post anesthesia care unit initially rose with opioid free anesthesia launch, but subsequently decreased below the target of 10%. Maximum post anesthesia care unit pain scores rose from mean 3.6 to 4.5, but subsequently returned to the baseline of 3.5, while the incidence of postoperative nausea and/or vomiting improved. The average post anesthesia care unit length of stay increased by 10 min with opioid free anesthesia; however, prolonged post anesthesia care unit stay and 30-day reoperation rates were unchanged. The continued refinement of our opioid sparing anesthesia protocol has led to reduced perioperative and home opioid use, stable maximum post anesthesia care unit pain scores, and improved postoperative nausea and vomiting rates, with only a slight increase in mean post anesthesia care unit length of stay.

Intraoperative Non-Opiate Anesthesia for Patients Undergoing Arthroscopic Temporomandibular Joint Surgery: A Randomized Controlled Trial.

Pain intensity after temporomandibular joint (TMJ) surgery is often underestimated, and inadequate pain control may relate to poor recovery quality, increased opioid consumption, and longer hospital stay. This trial aims to evaluate whether non-opiate anesthesia provides a promising option of pain management for patients undergoing TMJ surgery. Sixty patients receiving TMJ surgery were randomly assigned to either the control group or the non-opiate group. Non-opiate anesthesia used lidocaine, dexmedetomidine, and ketamine infusion therapy for pain management. The primary outcome was the highest documented pain score while in the post-anesthesia care unit (PACU). Secondary outcomes included perioperative opioid consumption, utilization, dosage, and timing of rescue analgesia in the PACU, incidence of postoperative nausea and vomiting in the PACU and at home, pain satisfaction levels, occurrence of opioid-related adverse effects, duration of PACU and hospital stays, and total consumption of oxycodone-acetaminophen tablets at 24 and 48hours post-surgery. Patients were predominantly female (88.3%) and had a median age of 37.5 [IQR 26.0, 52.5] years. There were no significant differences observed in the highest documented pain scores (mean difference [MD] -0.36 points, 95% CI: -1.84, 1.12, p = 0.63), postoperative oxycodone-acetaminophen consumption (MD 6.68 mg, 95% CI: -2.48, 15.84, p = 0.15), pain satisfaction (odds ratio [OR] 0.81, 95% CI: 0.23, 2.81, p = 0.74), time to PACU discharge (hazard ratio [HR] 1.24, 95% CI: 0.67, 2.30, p = 0.49) or time to hospital discharge (HR 1.48, 95% CI: 0.80, 2.75, p = 0.21) between the two groups. Similarly, no significant difference was observed in time to rescue analgesia, calculated in minutes from the end of surgery (HR 1.69, 95% CI: 0.79, 3.61, p = 0.18). Non-opiate anesthesia for pain management shows a similar postoperative analgesia effect, compared to opioid-based anesthesia, in patients undergoing arthroscopic TMJ surgery.

Perioperative pain management for cardiac surgery.

Acute postsurgical pain after cardiac surgery is challenging to treat. Adverse effects related to the high dose opioids which have traditionally been used perioperatively in cardiac surgery have led to the adoption of alternative analgesic strategies. This review aims to highlight current evidence-based approaches to managing pain after cardiac surgery. Current evidence and international guidelines support the use of multimodal analgesics for managing perioperative pain after cardiac surgery. Regional anaesthesia in the form of fascial plane blocks, such as the erector spinae plane and parasternal intercostal plane blocks, are effective and safe techniques for anticoagulated cardiac surgery patients. Transitional pain services are multidisciplinary programmes that bridge the gap between inpatient and outpatient care for these patients. This paper reviews advancements in perioperative pain management for cardiac surgery patients, emphasising the shift from high-dose opioids to multimodal analgesia and regional anaesthetic techniques, and highlighting the role of multidisciplinary transitional pain services.

Interventions to reduce opioid use for patients with chronic non-cancer pain in primary care settings: A systematic review and meta-analysis.

This systematic review and meta-analysis aimed to assess interventions to reduce opioid use for patients with chronic non-cancer pain (CNCP) versus usual care or active controls in primary care settings. In this registered study (PROSPERO: CRD42022338458), we searched MEDLINE, Embase PsycInfo, CINAHL, and Cochrane Library from inception to December 28th 2021, and updated on Dec 14th 2023 for randomized controlled trials (RCTs) and cohort studies with no restrictions. Methodological quality was assessed using the Cochrane Risk of Bias tool for RCTs and Newcastle Ottawa Scale for cohort studies. Primary outcomes included mean reduction in morphine equivalent daily dose (reported as mean differences [MDs] mg/day; 95% confidence intervals [95%CIs]) and/or opioid cessation proportion. Secondary outcomes were mean changes in pain severity (reported as standardized mean difference [SMDs]; 95%CIs) and (serious) adverse events. Meta-analyses were performed using random-effects models. We identified 3,826 records, of which five RCTs (953 participants) and five cohort studies (901 participants) were included. Overall, opioid dosage was significantly reduced in intervention groups compared to controls (MD: -28.63 mg/day, 95%CI: -39.77 to -17.49; I2 = 31.25%; eight studies). Subgroup analyses revealed significant opioid dose reductions with mindfulness (MD: -29.36 mg/day 95%CI: -40.55 to -18.17; I2 = 0.00%; two trials) and CBT-based multimodalities (MD: -41.68 mg/day; 95%CI: -58.47 to -24.89; I2 = 0.00%; two cohort studies), respectively, compared to usual care. No significant differences were observed in opioid cessation (Odds ratio: 1.10, 95%CI: -0.48 to 2.67, I2 = 58.59%; two trials) or pain severity (SMD: -0.13, 95%CI: -0.37 to 0.11; I2 = 33.51%; three trials). Adverse events were infrequently examined, with withdrawal symptoms commonly reported. The studied interventions were effective in reducing opioid dosage for people with CNCP in primary care. They highlighted the importance of multidisciplinary collaboration. Large-scale RCTs measuring the long-term effects and cost of these interventions are needed before their implementation.

Experience of using multimodal opioid-saving anesthesia in children: single-center prospective randomized study

BACKGROUND: In the protocols of rapid recovery after surgery, it is recommended to avoid long-term administration and/ or high doses of opioids in order to reduce the severity of their adverse reactions in the postoperative period. In this regard, opioid-sparing anesthesia (OSA) may become a promising approach to the treatment of cancer patients. AIM. To evaluate the effectiveness of multimodal OSA in the scheme "dexmedetomidine+ketamine (in subanesthetic doses)+lidocaine (intravenous infusion)" in pediatric oncosurgery. MATERIALS AND METHODS: A single-center prospective randomized study involved 40 children aged 12 to 18 years. Patients were divided into 2 groups depending on the method of anesthesia: in group I (n=20), combined endotracheal anesthesia with opioids was performed, in group II (n=20) — multimodal OCA based on intravenous infusion of lidocaine, dexmedetomidine and subanesthetic doses of ketamine. The patients underwent extended operations in the head and neck area in the volume of thyroidectomy with fascial-sheath lymph dissection and excision of the central tissue of the neck from 2 sides. RESULTS: With stable intraoperative hemodynamic parameters, the median total intraoperative need for analgesics in group II was: for lidocaine— 351 (289.6; 418.5) mg (which is 1.75mg/kg per hour), for dexmedetomidine— 88.2 (38.5; 119.7) µg, for ketamine — 21.6 (17.4; 27.3mg. In group I, the median total intraoperative need for fentanyl was 273.7 (406; 240.9)µg. In addition, in group I, the median amount required for postoperative analgesia of the synthetic opioid analgesic tramadol was 419 (365.6; 479)mg (which is 7.8mg/kg; p=0.01). In group II, the median amount of lidocaine required for postoperative analgesia (1 mg/kg per hour) turned out to be 1377.3 (735.7; 1894)mg, while additional tramadol administration at a dose of 57.3 (28.5; 107.7)mg was required in only 7(35%) patients. CONCLUSION: Multimodal OSA based on dexmedetomidine, lidocaine, ketamine and sevoflurane is an effective and safe method of anesthesia in children from 12 to 18 years old, which is not inferior to opioid analgesics in the treatment of perioperative pain during surgical interventions on the thyroid and parathyroid glands in cancer patients, and also reduces the number of adverse reactions characteristic of opioids.

Pharmacological treatment of pain, dyspnea, death rattle, fever, nausea, and vomiting in the last days of life in older people: A systematic review.

Evidence based guidelines for treatment of physical symptoms during the last days of life in older people are not available. We wanted to synthesize the existing evidence on the pharmacological treatment of pain, dyspnea, death rattle, fever, nausea, and vomiting during the last days of life in older people to develop recommendations that can help guide clinical practice. A systematic review was conducted (PROSPERO #CRD42023406100) and reported in accordance with PRISMA guidelines. MEDLINE and EMBASE were searched from inception till March 2023, together with national and international guideline databases. Four predominantly descriptive studies on opioid use were included for the treatment of pain and four for dyspnea, without clear evidence for the choice of one specific opioid, nor a specific opioid dose. For death rattle, five randomized controlled trials and two retrospective studies were included. These provide evidence for the prophylactic treatment of death rattle with hyoscine butylbromide. For fever, nausea, and vomiting, no articles met the inclusion criteria. Limited evidence exists to guide the pharmacological treatment of pain, dyspnea, death rattle, fever, nausea, and vomiting in the last days of life of older people. Other than the use of opioids for treatment of pain and dyspnea and prophylactic administration of hyoscine butylbromide to decrease the likelihood of developing death rattle, no specific recommendations can be formulated for use in clinical practice. This demonstrates the challenging nature of research in the last days of life of older people, despite its pressing need.

Effects of Intraoperative Opioid Use and a Combined Anesthesia Protocol in Patients Undergoing Radical Cystectomy for Urothelial Carcinoma of the Bladder—A Single-Center Experience

Background: An increased intraoperative opioid dose seems to lead to worse outcomes in several types of cancer. We assessed the effect of intraoperatively administered opioids as well as the type of anesthesia on survival, recurrence rates and major perioperative outcomes in patients who underwent radical cystectomy (RC) for urothelial carcinoma of the urinary bladder. Methods: We included patients who underwent open RC at our center between 2015 and 2022. The role of the type and dosage of intraoperative opioid agents, such as remifentanil, sufentanil and morphine milligram equivalents (MME), as well as the type of anesthesia (intravenous only versus intravenous/epidural), was assessed regarding perioperative and long-term outcomes after RC. Results: A total of 508 patients with a median age of 73 years (IQR: 64–78) were included. Overall, 92 (18%) patients received intravenous anesthesia, whereas 416 (82%) received combined anesthesia. At a median follow-up of 270 days (IQR: 98–808), 108 (21%) deaths and 106 (21%) recurrences occurred. Combined anesthesia was associated with better survival (HR:0.63, 95% CI: 0.4–0.97, p = 0.037) and lower intensive care unit admission rates (OR: 0.49, 95% CI: 0.31–0.77, p = 0.002) in the univariate analysis (unadjusted). The type and dosage of intraoperative opioid agents did not affect long-term survival and recurrence rates, as well as major perioperative outcomes. Nevertheless, the findings of our study were limited by its single-center, retrospective design. Conclusion: The use of intraoperative opioids was not associated with worse outcomes in our cohort, while the use of additional epidural anesthesia seems to be beneficial in terms of overall survival and intensive care unit admissions. Nevertheless, further research is mandatory to validate the safety of opioids in patients undergoing RC.

A COMPARISON OF EFFICACY OF EPIDURAL BUTORPHANOL AND FENTANYL FOR POST-OPERATIVE PAIN ANALGESIA IN LOWER ABDOMINAL AND LOWER LIMB SURGERIES UNDER EPIDURAL ANESTHESIA: A PROSPECTIVE RANDOMIZED DOUBLE-BLINDED STUDY

Objective: Lower doses of epidural opioids can achieve post-operative analgesia for infraumbilical surgeries. A study was conducted to compare the efficacy of epidural butorphanol and fentanyl for post-operative analgesia, onset, duration, and side effects in infraumbilical surgeries. Methods: A study was conducted on 80 adult patients, both male and female, aged between 20 and 60 years, having American Society of Anesthesiologists Physical Status I and II, who were undergoing lower abdominal and lower limb surgeries under epidural anesthesia. The patients were randomly divided into two groups: Group A and Group B. Both groups were given injections of bupivacaine 20 mL of 0.5% epidurally. In the post-operative period, when the patient’s Visual Analog Scale score was more than 4, Group A was administered butorphanol 2 mg followed by top-up doses of 0.5 mg, and Group B was administered fentanyl 50 μg followed by top-up doses of 15 μg, which were diluted to 10 mL in normal saline. Along with cardiorespiratory parameters, the study also noted onset, duration, quality of analgesia, and the number of epidural doses in 24 h. The statistical analysis was done using Student’s t-test and two-tailed Fisher’s exact test or Chi-square (χ2) test, and a significant value of p&lt;0.05 was considered. Results: In comparing the post-operative analgesia between both groups, it was found that Group B had significant early onset of analgesia (2.600±0.4557 vs. 6.087±0.7501), shorter duration of analgesia (200.08±26.257 vs. 366.25±42.829), a higher number of epidural doses administered (3.75±1.171 vs. 2.98±0.733), lower quality of analgesia (2.55±0.504 vs. 3.18±0.636), and a greater incidence of vomiting (30.0% vs. 2.5%) when compared to group A. Conclusion: Superior analgesia with higher sedation can be achieved through epidural butorphanol, while fentanyl has a quicker onset of analgesia but a higher tendency for vomiting. Our conclusion is that both options, fentanyl and epidural butorphanol, are safe and effective for achieving post-operative pain relief.

The opioid industry's use of scientific evidence to advance claims about prescription opioid safety and effectiveness

Abstract It is widely recognized that pharmaceutical marketing contributed to the ongoing US opioid epidemic, but less is understood about how the opioid industry used scientific evidence to generate product demand, shape opioid regulation, and change clinician behavior. In this qualitative study, we characterize select scientific articles used by industry to support safety and effectiveness claims and use a novel database, the Opioid Industry Documents Archive, to determine notable elements of industry and non-industry documents citing the scientific articles to advance each claim. We found that 15 scientific articles were collectively mentioned in 3666 documents supporting 5 common, inaccurate claims: opioids are effective for treatment of chronic, non-cancer pain; opioids are “rarely” addictive; “pseudo-addiction” is due to inadequate pain management; no opioid dose is too high; and screening tools can identify those at risk of developing addiction. The articles contributed to the eventual normalization of these claims by symbolically associating the claims with scientific evidence, building credibility, expanding and diversifying audiences and the parties asserting the claims, and obfuscating conflicts of interest. These findings have implications for regulators of industry products and corporate activity and can inform efforts to prevent similar public health crises.

Phenotypes based on respiratory drive and effort to identify the risk factors when P0.1 fails to estimate ∆PES in ventilated children.

Monitoring respiratory effort and drive during mechanical ventilation is needed to deliver lung and diaphragm protection. Esophageal pressure (∆PES) is the gold standard measure of respiratory effort but is not routinely available. Airway occlusion pressure in the first 100ms of the breath (P0.1) is a readily available surrogate for both respiratory effort and drive but is only modestly correlated with ∆PES in children. We sought to identify risk factors for P0.1 over or underestimating ∆PES in ventilated children. Secondary analysis of physiological data from children and young adults enrolled in a randomized controlled trial testing lung and diaphragm protective ventilation in pediatric acute respiratory distress syndrome (PARDS) (NCT03266016). ∆PES (∆PES-REAL), P0.1 and predicted ∆PES (∆PES-PRED = 5.91*P0.1) were measured daily to identify phenotypes based upon the level of respiratory effort and drive: one passive (no spontaneous breathing), three where ∆PES-REAL and ∆PES-PRED were aligned (low, normal, and high effort and drive), two where ∆PES-REAL and ∆PES-PRED were mismatched (high underestimated effort, and overestimated effort). Logistic regression models were used to identify factors associated with each mismatch phenotype (High underestimated effort, or overestimated effort) as compared to all other spontaneous breathing phenotypes. We analyzed 953 patient days (222 patients). ∆PES-REAL and ∆PES-PRED were aligned in 536 (77%) of the active patient days. High underestimated effort (n = 119 (12%)) was associated with higher airway resistance (adjusted OR 5.62 (95%CI 2.58, 12.26) per log unit increase, p < 0.001), higher tidal volume (adjusted OR 1.53 (95%CI 1.04, 2.24) per cubic unit increase, p = 0.03), higher opioid use (adjusted OR 2.4 (95%CI 1.12, 5.13, p = 0.024), and lower set ventilator rate (adjusted OR 0.96 (95%CI 0.93, 0.99), p = 0.005). Overestimated effort was rare (n = 37 (4%)) and associated with higher alveolar dead space (adjusted OR 1.05 (95%CI 1.01, 1.09), p = 0.007) and lower respiratory resistance (adjusted OR 0.32 (95%CI 0.13, 0.81), p = 0.017). In patients with PARDS, P0.1 commonly underestimated high respiratory effort particularly with high airway resistance, high tidal volume, and high doses of opioids. Future studies are needed to investigate the impact of measures of respiratory effort, drive, and the presence of a mismatch phenotype on clinical outcome. NCT03266016; August 23, 2017.

A retrospective study of duloxetine for phantom limb pain post lower‐limb amputation

AbstractBackgroundPhantom limb pain (PLP) refers to the painful sensory perception of a missing limb after amputation, which can have physical and psychological impacts.AimTo determine the effectiveness of duloxetine for pain management in PLP by the reduction of opioid doses and other neuropathic analgesics when introduced into multimodal pain management strategies in the subacute rehabilitation setting.MethodThis was a retrospective observational case‐matched cohort study of patients who were admitted to a geriatric and rehabilitation unit at a tertiary Australian hospital from January 2005–December 2017 with PLP after lower‐limb amputation. Patients were included if they had a new amputation and experienced PLP. The primary outcome was a difference in oxycodone dose equivalents at discharge between the two cohorts. Univariable analysis was used to compare groups. Ethical approval was granted by the Metro South Low Negligible Risk Ethics Committee (Reference no: LNR/2018/QMS/47370) and the study conforms with the National statement on ethical conduct in human research.ResultsThirty patients from the duloxetine treatment cohort and 57 patients from the non‐duloxetine cohort were identified. Participants were predominantly male (81%) and had a median age of 63 years (interquartile range = 10.7). Both populations showed a similar rate of opioid dose reduction comparing doses at admission with those at discharge. There were no significant differences in absolute oxycodone equivalent doses at the two observed check points: admission and discharge.ConclusionThis study demonstrated that opioid consumption in post‐surgical lower‐limb amputees reporting PLP was not significantly different between populations that used and did not use duloxetine. Future research should evaluate the efficacy of duloxetine in PLP pain management using a multisite prospective study design.

Opioid tapering and discontinuation for head and neck cancer (HNC) survivors.

366 Background: Older HNC survivors often experience post-treatment pain, and they fill opioid prescriptions more often than similar cancer-free adults for the first 5 years after HNC diagnosis. To better understand whether ongoing opioid use is likely explained by continued opioid prescribing from the time of cancer treatment, we aimed to quantify the extent to which opioids prescribed near the end of treatment are reduced in dose (tapered) and discontinued after treatment completion. Methods: Using linked Surveillance, Epidemiology, and End Results (SEER) registry and Medicare claims data, we identified adults age &gt;65 diagnosed 2014-2017 with stage I-III HNC with ≥6 months treatment-free follow-up prior to censoring at further treatment, new cancer, hospice, 3 months prior to death, or end 2019. We evaluated the presence of a new or ongoing opioid prescription 2 weeks following treatment completion (baseline) and calculated daily baseline dose in morphine milligram equivalents (MME). Among those with an opioid prescription (“on opioids”) at baseline, we described cross-sectional metrics of opioid receipt and dose every 30 days: proportion of survivors on opioids (who were also on opioids the prior month), initial and current dose of opioids for those currently on opioids, and proportion of survivors on opioids whose dose declined ≥50% from baseline. Results: Among 5135 HNC survivors, 894 were on opioids at baseline (average daily dose 44 MME). By 1 month, 29% of survivors on opioids at baseline (N=260) had a current opioid fill, and 7% had an opioid dose &lt;50% of the baseline dose. Discontinuation of opioids increased each month; median daily dose each month ranged from 44 MME at 30 days to 60 MME at 180 days. Those who remained on opioids over 6 months had the highest opioid dose than those who discontinued earlier (median 45 MME at 90 days; Table). Conclusions: About 1 in 6 HNC survivors had an opioid prescription filled at the end of cancer treatment, and opioids were generally discontinued within a few months. Given the low median dose at baseline, the limited evidence of tapering likely results from low initial opioid doses rather than a failure to taper from long-term or high-dose use. Opioid use among older treatment-free HNC survivors that is apparent years after treatment completion is unlikely to result from inadequate tapering. Instead, it may be due to new or worsening cancer-related pain, as well as to non-cancer pain. Dose reduction and discontinuation (N=894). Days after baseline Off opioids On opioids Starting dose in MME among those on opioids Current dose in MME among those on opioids Tapered to &lt;50% starting dose N (%) N (%) Median (IQR) Median (IQR) N (%) 30 634 (71) 260 (29) 53 (30, 80) 44 (29, 60) 61 (7) 60 772 (86) 122 (14) 45 (30, 67.5) 44 (29, 60) 15 (2) 90 820 (92) 74 (8) 58 (30, 90) 45 (29, 60) 7 (1) 120 838 (94) 56 (6) 60 (30, 90) 45 (25, 60) 7 (1) 150 849 (95) 45 (5) 56 (30, 65) 48 (29, 60) 2 (&lt;1) 180 856 (96) 38 (4) 51 (30, 65) 60 (30, 90) 1 (&lt;1)

Clinical Trial Study Protocol: A Prospective Blinded, Randomized, Controlled Clinical Trial Protocol to Assess the Efficacy of Ultrasound-Guided Transversus Abdominis Plane Block on Postoperative Analgesia and Recovery Quality in Laparoscopic Donor Hepatectomy.

Liver transplantation is considered an effective treatment for end-stage liver disease. Laparoscopic donor hepatectomy (LDH) has become a new standard procedure. And it is important to minimize the pain of the donor. Good postoperative analgesia can reduce the occurrence of postoperative complications and promote the early recovery of the donor. Ultrasound-guided transversus abdominis plane (TAP) block can provide effective analgesia for liver donors and reduce postoperative opioid consumption. This study aims to use ultrasound-guided TAP block for LDH to improve postoperative analgesia for donors while reducing opioid consumption and improving patient rehabilitation quality. This study is a prospective blinded, randomized, controlled clinical trial with a concealed allocation of patients (living liver donors) scheduled to receive laparoscopic partial hepatectomy 1:1 to receive local infiltration anesthesia or TAP block. This study will recruit a total of 80 patients. The primary outcome is the dosage of opioids within 24hours after surgery. This trial has been approved by the Institutional Review Board of Beijing Friendship Hospital of China Capital University. This trial study protocol was approved on 8 May 2023. The trial will start recruiting patients after being registered on the Chinese Clinical Trial Registry. ChiCTR2300071694.

The effects of opioid tapering on select endocrine measures in men and women with head and neck cancer-a longitudinal 12-month study.

Opioid treatment may affect endocrine measures in humans either through centrally or peripherally mediated mechanisms. There is a general lack of longitudinal studies examining endocrine measures in opioid-treated patients. To longitudinally follow the levels of select endocrine measures in men and women with head and neck cancer for 1 year, who after having completed radiotherapy began tapering opioids. This was a prospective, longitudinal, observational study. Testosterone and estradiol were measured in men and women, respectively. Follicle-stimulating hormone (FSH), luteinizing hormone (LH), dehydroepiandrosterone sulfate (DHEAS), and prolactin were measured in both sexes. Women were grouped based on if premenopausal or postmenopausal. Samples were collected when opioid tapering started and at 1, 3, 6, and 12 months after tapering start. Daily opioid doses at the same time points were registered. Twenty-five men and 12 women were followed for 12 months. In men, testosterone levels increased significantly during the first month after opioid tapering started (P < 0.001). Levels of testosterone, FSH, DHEAS, and prolactin changed significantly in men during the study period. A moderate correlation between opioid dose reduction and testosterone level increase in men aged ≤60 years was found (r s = -0.577, 95% CI -0.854 to -0.044, P = 0.039). In postmenopausal women (n = 10), levels of FSH and LH changed significantly during the study period. Previously known effects of opioids on endocrine measures in humans seem to be reversible as select endocrine measures changed significantly in men and postmenopausal women after opioid tapering was initiated.

A Framework for a New Paradigm of Opioid Drug Tapering Using Adjunct Drugs.

The misuse of and dependency on prescription opioids represents a significant crisis at the national level, impacting not only the health of the public but also the societal and economic well-being. There is a critical need for strategies to reduce the dosage of prescribed opioids to limit opioid-associated adverse effects and lower the risk of addiction development in patients experiencing chronic pain. Opioid-sparing medications, when co-administered with opioids, enable a reduced opioid dose without loss of efficacy. This suggests the potential for using opioid adjunct drugs in opioid tapering, whereby opioid doses are lowered incrementally in a systematic manner to improve a patient's safety profile or quality of life. The objective of this report is two-fold: 1) to illustrate the potential for adjunct drugs in opioid tapering, and 2) to describe the steps needed to be taken to develop a framework for the use of adjunct drugs in opioid tapering. This can provide the impetus for further investigation into opioid tapering and the development of improved clinical care. The proposed project implements knowledge synthesis methods to develop the framework for a new paradigm of opioid drug tapering that incorporates opioid dosage reductions with adjunct drugs. Framework development is organized into three major phases: 1) Adjunct drug characterization, 2) Assessment of the opioid-sparing effect, and 3) Usability of data for clinicians. The knowledge gained from this project can provide a foundation for improved analgesia protocols for opioids and adjunctive drug therapy.