Administration Of Opioid Analgesics Research Articles

Early Administration of Intravenous Hydration and Opioid Analgesics Is Correlated with Decreased Admission Rates during Vaso-Occlusive Episodes in Sickle Cell Disease.

Background: Painful vaso-occlusive episodes (VOEs) are the hallmark of sickle cell disease (SCD) and account for frequent visits to the emergency department (ED) or urgent care (UC). Currently, the early administration of analgesics is recommended as initial management; however, there is a need for further understanding of the effect of prompt analgesics and hydration during VOEs. The objective of this study is to analyze the factors associated with the rate of hospital admission in the setting of time to intravenous (IV) analgesics and hydration. Method: This retrospective single-institution study reviewed adult and pediatric patients with SCD who presented with VOEs from January 2018 to August 2023. Results: Of 303 patient encounters, the rates of admission for the overall group, the subgroup which received IV hydration within 60 min of arrival, and the subgroup which received both IV analgesics and hydration within 60 min were 51.8%, 25.6% (RR = 0.46), and 18.2% (RR = 0.33), respectively. Further, factors such as gender and the use of hydroxyurea were found to be significantly associated with the rate of admission. Conclusions: This signifies the importance of standardizing the management of VOEs through the timely administration of IV analgesics and hydration in both adult and pediatric ED/UC.

Abstract 7496: The piritramide-based perioperative analgesia can affect the cancer dissemination in colorectal cancer patients

Abstract Introduction: Colorectal cancer (CRC) stands as a prominent contributor to global cancer-related mortality. Post-surgical management of CRC patients often involves the administration of opioid analgesics. These analgesics operate through opioid and cannabinoid receptors, pathways implicated in tumor progression and metastasis, potentially impacting patient survival adversely. This investigation delves into the influence of piritramide and morphine on cancer dissemination, encompassing in vitro and in vivo assessments, cytotoxicity analyses, and elucidation of their mode of action. Methods: The presence of circulating tumor cells (CTCs) in the blood of 131 CRC patients was quantitatively assessed using the real-time polymerase chain reaction (qPCR) method. Cytotoxic effects of morphine and piritramide were evaluated via colony-forming assays (CFA) utilizing HCT116 and HT29 cell lines. The impact of piritramide and morphine on opioid receptor activity was gauged through transfected reporter cell lines and fluorescence imaging plater reader (FLIPR) calcium assays. In vivo models involving subcutaneous and intrasplenic administration in SCID and BALB mice, respectively, utilizing HCT116 and HT29 cell lines, were conducted. Morphological profiling, employing the cell painting assay, facilitated high-content image-based analysis on both cell lines. Results: Perioperative analgesia with piritramide exhibited a tendency towards longer time to recurrence (TTR) survival in CRC patients (HR=1.8, p=0.104). Conversely, morphine-treated patients demonstrated a twofold increase in TTR events (HR=4.7, p=0.011). Piritramide, but not morphine, significantly inhibited colony growth in HCT116 and HT-29 cell lines in the CFA, consistent with cytotoxicity test results. Functional assays revealed agonistic effects of both piritramide and morphine on opioid receptor kappa 1 (OPRK1) and mu 1 (OPRM1), with piritramide exhibiting greater potency as an OPRK1 agonist. In the SCID mice model, subcutaneous application of HT29 cell lines resulted in significantly reduced tumor growth in piritramide-treated mice. In the intrasplenic model utilizing BALB mice, mice treated with piritramide exhibited diminished tumor growth and a reduction in both the number and size of metastases. Comparative analysis with reference compounds revealed a distinct phenotypic profile of piritramide affecting the endoplasmic reticulum. Conclusion: Piritramide, as opposed to morphine, demonstrated cytotoxic effects on both in vitro and in vivo CRC cell lines, resulting in reduced tumor growth and dissemination. Perioperative analgesia with piritramide exhibited potential in improving time to recurrence survival in CRC patients. Acknowledgement: This study received support from the European Union - Next Generation EU (LX22NPO5102) and Palacky University Olomouc (LF 2023_006). Citation Format: Josef Srovnal, Emil Berta, Monika Vidlarova, Alona Rehulkova, Katerina Jecmenova, Miroslav Popper, Alzbeta Srovnalova, Petr Prasil, Pavel Skalicky, Tomas Gabrhelik, Jan Maca, Pavel Michalek, Marian Hajduch. The piritramide-based perioperative analgesia can affect the cancer dissemination in colorectal cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7496.

Trends in pain undertreatment among lung cancer patients at the EOL: Analysis of urban city medical insurance data in China.

Cancer-related pain is one of the common priority symptoms in advanced lung cancer patients at the end-of-life (EOL). Alleviating pain is undoubtedly a critical component of palliative care in lung cancer. Our study was initiated to examined trends in opioid prescription-level outcomes as potential indicators of undertreated pain in China. This study used data on 1330 patients diagnosed with lung cancer of urban city medical insurance in China who died between 2014 and 2017. Opioid prescription-level outcomes were determined by annual trends of the proportion of patients filling an opioid prescription, the total dose of opioids filled by decedents, and morphine milligram equivalents per day (MMED) at the EOL (defined as the 60 days before death). We further analyzed monthly changes in the number of opioid prescriptions filled, MMED, and mean daily dose of opioids per prescription (MDDP) of the last 60 days of life by year at death and age, respectively. A total of 959 patients with exact dates of death were included, with 432 cases (45.06%; 95% CI: 44.36%-45.77%) receiving at least one opioid prescription at the EOL. The declining trends were shown in the proportion of patients filling any opioid prescription, the total dose of opioids filled by decedents and MMED, with an annual decrease of 0.341% (p = 0.01), 104.23 mg (p = 0.011) and 2.84 mg (p = 0.014), respectively. Within the 31-60 days to the 0-30 days of life, the MMED declined 6.08 mg (95% CI: -7.14 to -5.03; p = 0.000351), while the number of opioid prescriptions rose 0.66 (95% CI: 0.160-1.16; p = 0.025). Like the MMED, the MDDP fell 4.11 mg (95% CI: -5.86 to -2.37; p = 0.005) within the last month before death compared to the previous month. Terminal lung cancer populations in urban China have experienced reduced access to opioids at the EOL. The clinicians did not prescribe a satisfactory dose of opioids per prescription, while the patients suffered increasing pain in the last 30 days of life. Sufficient opioid analgesic administration should be advocated for lung cancer patients during the EOL period.

The Adequacy of Anesthesia Guidance for Vitreoretinal Surgeries with Preemptive Paracetamol/Metamizole.

Despite the possibility of postoperative pain occurrence, in some patients, vitreoretinal surgeries (VRSs) require performance of general anesthesia (GA). The administration of intraoperative intravenous rescue opioid analgesics (IROA) during GA constitutes a risk of perioperative adverse events. The Adequacy of Anesthesia (AoA) concept consists of an entropy electroencephalogram to guide the depth of GA and surgical pleth index (SPI) to optimize the titration of IROA. Preemptive analgesia (PA) using cyclooxygenase-3 (COX-3) inhibitors is added to GA to minimize the demand for IROA and reduce postoperative pain. The current analysis evaluated the advantage of PA using COX-3 inhibitors added to GA with AoA-guided administration of IROA on the rate of postoperative pain and hemodynamic stability in patients undergoing VRS. A total of 165 patients undergoing VRS were randomly allocated to receive either GA with AoA-guided IROA administration with intravenous paracetamol/metamizole or with preemptive paracetamol or metamizole. Preemptive paracetamol resulted in a reduction in the IROA requirement; both preemptive metamizole/paracetamol resulted in a reduced rate of postoperative pain as compared to metamizole alone. We recommend using intraoperative AOA-guided IROA administration during VRS to ensure hemodynamic stability alongside PA using both paracetamol/metamizole to reduce postoperative pain.

Is the psoas compartment block effective in eliminating pain in children after hip surgery?

BACKGROUND: Hip joint surgery is a highly traumatic surgical intervention. Currently, the anesthesia service in the clinic of H. Turner National Medical Research Center uses either prolonged epidural block with catheter placement in the lumbar spine at the LIII–LIV level or prolonged intravenous analgesia as the main method of pain syndrome treatment after hip joint surgery. Moreover, the potential of prolonged psoas compartment block has not been considered until recently.
 AIM: To evaluate the effectiveness of prolonged psoas compartment block for pain control in the early postoperative period after hip surgery in comparison with traditional methods of pain control.
 MATERIALS AND METHODS: This study analyzed the results of postoperative analgesia in 14 children after 15 surgeries in the hip joint, including 3 patients with prolonged psoas compartment block, 9 with prolonged epidural block, and 3 who received postoperative analgesia with systemic analgesics. One patient with bilateral congenital hip joint dislocation was anesthetized with prolonged psoas compartment block after the first operation for the first time and with prolonged epidural block after the second similar operation but on the other leg for the second time. Analgesia efficacy was assessed using the Wong–Baker scale, FLACC behavioral scale, and visual analog scale.
 RESULTS: All three patients with prolonged psoas compartment block required an addition of butorphanol tartrate (tramal) for good analgesia. Additional administration of opioid analgesics was not needed when a prolonged epidural block was initiated.
 CONCLUSIONS: Due to the continued need for additional administration of butorphanol tartrate, when prolonged epidural block was available, the use of prolonged psoas compartment block in children for pain relief in the early postoperative period after hip surgery was not considered appropriate.

Case report of ultrasound-assisted nerve blockade of fascial plane by erector spine block in acute pancreatitis

Introduction. Pain in the intensive care unit is a common problem in patients with acute pancreatitis of various etiologies. Given the severity of the pain syndrome, as well as the low effectiveness of nonsteroidal anti-inflammatory drugs or antispasmodic therapy, it is often necessary to resort to the administration of opioid analgesics or epidural analgesia. Each of these pain management methods has certain disadvantages and contraindications, which makes it urgent to search for a safe and effective method of relieving pain in patients with pancreatitis or pancreonecrosis.Goal. To determine the effectiveness blockade of the nerves of the fascial space of the muscles’ erector spine in acute pancreatitis. Clinical observation. Patient X., 58 years old, was arrived to the emergency department of the V.M. Buyanov State Clinical Hospital with severe pain in the epigastric region (10 points out of 10 on the visual-analog scale).Conclusions. ESPB in a patient with acute biliary pancreatitis complicated by pancreonecrosis allowed to control pain syndrome quickly and safely. Further randomized clinical trials will allow to implement and optimize the technique, improving the clinical outcome.

Effects of Adding Intrathecal Epinephrine to Spinal Anesthesia on Anesthesia-Related Cesarean Delivery Outcomes: Should We Reconsider Its Use?

Intrathecal epinephrine is used to increase the duration of spinal anesthesia for amenable surgical procedures anticipated to require additional time; however, in the ambulatory setting, it is associated with a prolonged time to post-anesthesia care unit (PACU) discharge. The current study's authors hypothesized that adding intrathecal epinephrine to spinal anesthesia for cesarean delivery would be associated with a dose-dependent prolonged post-anesthesia unit length of stay. A single-center, retrospective study of patients undergoing repeat cesarean delivery under spinal anesthesia from 2011 to 2015 was conducted. Patients received spinal bupivacaine 12 mg, morphine 150 mcg, and fentanyl 15 mcg with no-epinephrine, 100 mcg, or 200 mcg of epinephrine. The primary outcome was recovery room length of stay. Secondary outcomes were surgical duration, intraoperative vasopressor use, perioperative opioids, and antiemetic use. Data were analyzed for 1,362 patients. Median recovery room stay was 123 min (interquartile range, 100 to 150) and was not different among groups. More women receiving epinephrine 200 mcg had ≥2 prior cesarean deliveries compared with no-epinephrine or 100 mcg. No significant differences in surgical duration or intraoperative opioids were identified among the groups. Median intraoperative vasopressor use was increased by 225 mcg of phenylephrine equivalents (99% CI, 25 mcg to 430 mcg) in the 100 mcg group and 250 mcg of phenylephrine equivalents in the 200 mcg group (99% CI, 75 mcg to 500 mcg) compared to no-epinephrine (P<0.001). Recovery room antiemetic and opioid analgesic administration were not different among groups. Based on the results of this study, the addition of intrathecal epinephrine for women undergoing cesarean delivery increases intraoperative vasopressor use but does not prolong PACU length of stay, reduce intraoperative opioids, or increase antiemetic requirements postoperatively. The current study also demonstrated that surgical duration times were not different among the no-epinephrine, 100 mcg, and 200 mcg epinephrine groups.

Особливості управління болем у вагітних та породіль

Purpose - to evaluate the efficacy and adverse side effects (if any) of intravenous infusion of 1000 mg paracetamol as a method of pain relief in labour during the active phase of labour and in the postoperative period after caesarean section. Materials and methods. 43 pregnant women in the first stage of labor with active labor were studied. The selection criteria were healthy low-risk first-term mothers; aged 18-35 years; with spontaneous onset of labor at 37-40 weeks of pregnancy; the first period of labor with the opening of the cervix by 3-5 cm; one live fruit; main presentation Infulgan inf. solution was chosen as a paracetamol preparation 10 mg/ml per 100 ml. Multimodal anesthesia with a combination of the drugs Infulgan (paracetamol) and Keydex (dexketoprofen) was performed for postoperative analgesia. The pain intensity indicator was determined using the visual analog scale (VAS) - a method of subjective pain assessment. The patient marked a point on a non-graduated ruler 10 cm long, which corresponds to the degree of severity of pain. During the dynamic evaluation of changes in pain intensity, they were considered objective and significant if the true VAS value differed from the previous one by more than 1.3 cm. The comparison group consisted of 20 pregnant women in the 1st stage of labor who did not receive anesthesia at their own request. Also, a study of the effectiveness of complex multimodal anesthesia (Infulgan (paracetamol) and Keydex (dexketoprofen)) was conducted in 5 (11.6%) women in labor after delivery by caesarean section. Results. The use of intravenous paracetamol injection for analgesia during labor is an effective analgesia. There was an initial but significant decrease in the VAS score 30 minutes after Infulgan administration and a statistically significant decrease in pain after 2, 3 and 4 hours compared with the VAS score before treatment. In the group of women who did not undergo analgesia, the intensity of the pain syndrome steadily increased. In the postoperative period, after caesarean section, women underwent combined analgesia with the use of Infulgan (paracetamol) drugs as the basic component of multimodal analgesia and Keydex (dexketoprofen) as a necessary step of multimodal analgesia. The above-mentioned combination of drugs allows for Step-Up analgesia - step-by-step pain therapy. Infulgan was administered in 1 vial (1000 mg) every 6 hours by intravenous injection, and Keydex - in 1 ampoule every 8 hours by intramuscular injection. The addition of Keydex (dexketoprofen) to the analgesia provided an adequate analgesic effect and did not require the administration of opioid analgesics in the postoperative period. Conclusions. Intravenous paracetamol is an effective non-opioid drug for the relief of labor pain without any significant side effects for mother and fetus. The absence of any maternal side effects (sedation, respiratory depression, delayed gastric emptying, nausea and vomiting) or neonatal side effects (respiratory depression and decreased Apgar scores) associated with opioids allows us to recommend Infulgan for the relief of labor pain. The step-by-step Step-Up pain therapy in the postoperative period allows you to reduce the doses of each of the analgesics and reduce the frequency and side effects of the drugs. The use of Infulgan and Keydex as a method of pain management by means of Step-Up analgesia in the postoperative period in parturient women showed high efficiency, adequate tolerability and patient’s satisfaction. The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of all participating institutions. The informed consent of the patient was obtained for conducting the studies. No conflict of interests was declared by the authors.

Sex-Based Inequality of Opioid and Psychotropic Drug Administration After Cardiac Surgery

To determine the association of sex with the inpatient administration of opioid analgesia and psychotropic drugs after cardiac surgery.

Safety implications of concomitant administration of antidepressants and opioid analgesics in surgical patients

ABSTRACT Background Commonly prescribed antidepressants (paroxetine, fluoxetine, duloxetine, bupropion) inhibit bioconversion of several prodrug opioid medications to their active metabolite, potentially decreasing analgesic effect. There is a paucity of studies assessing the risk-benefit of concomitant administration of antidepressants and opioids. Research design and methods Observational study of adult patients taking antidepressants prior to scheduled surgery using 2017–2019 electronic medical record data to assess perioperative use of opioids and to determine the incidence and risk factors for developing postoperative delirium. We conducted a generalized linear regression with the Gamma log-link to assess the association between use of antidepressants and opioids and a logistic regression to assess the association between antidepressants use and the likelihood of developing postoperative delirium. Results After controlling for patient demographic and clinical characteristics, and postoperative pain, use of inhibiting antidepressants was associated with 1.67 times greater use of opioids per hospitalization day (p = 0.00154), a two-fold increase in the risk for developing postoperative delirium (p = 0.0224), and an estimated average of four additional days of hospitalization (p < 0.00001) compared to use of non-inhibiting antidepressants. Conclusions Careful consideration to drug-drug interactions and risk of related adverse events remains critical in the safe and optimal management of postoperative pain in patients taking concomitantly antidepressants.

Racial Disparities in Opioid Analgesia Administration Among Adult Emergency Department Patients with Abdominal Pain.

Racial disparities in pain management have been reported among emergency department (ED) patients. In this study we evaluated the association between patients' self-identified race/ethnicity and the administration of opioid analgesia among ED patients with abdominal pain, the most common chief complaint for ED presentations in the United States. This was a retrospective cohort study of adult (age ≥18 years) patients who presented to the ED of a single center with abdominal pain from January 1, 2019-December 31, 2020. We collected demographic and clinical information, including patients' race and ethnicity, from the electronic health record. The primary outcome was the ED administration of any opioid analgesic (binary). Secondary outcomes included the administration of non-opioid analgesia (binary) and administration of any analgesia (binary). We used logistic regression models to estimate odds ratios (OR) of the association between a patient's race/ethnicity and analgesia administration. Covariates included age, sex, initial pain score, Emergency Severity Index, and ED visits in the prior 30 days. Subgroup analyses were performed in non-pregnant patients, those who underwent any imaging study, were admitted to the hospital, and who underwent surgery within 24 hours of ED arrival. We studied 7,367 patients: 45% (3,314) were non-Hispanic (NH) White; 28% (2,092) were Hispanic/Latinx; 19% (1,384) were NH Black, and 8% (577) were Asian. Overall, 44% (3,207) of patients received opioid analgesia. In multivariable regression models, non-White patients were less likely to receive opioid analgesia compared with White patients (OR 0.73, 95% CI 0.65-0.83 for Hispanic/Latinx patients; OR 0.62, 95% CI 0.54-0.72 for Black patients; and OR 0.64, 95% CI 0.52-0.78 for Asian patients). Black patients were also less likely to receive non-opioid analgesia, and Black and Hispanic/Latinx patients were less likely than White patients to receive any analgesia. The associations were similar across subgroups; however, the association was attenuated among patients who underwent surgery within 24 hours of ED arrival. Hispanic/Latinx, Black, and Asian patients were significantly less likely to receive opioid analgesia than White patients when presenting to the ED with abdominal pain. Black patients were also less likely than White patients to receive non-opioid analgesia.

Spinal orexin A attenuates opioid-induced mechanical hypersensitivity in the rat.

BackgroundRepeated administration of opioid analgesics for pain treatment can produce paradoxical hyperalgesia via peripheral and/or central mechanisms. Thus, this study investigated whether spinally (centrally) administered orexin A attenuates opioid-induced hyperalgesia (OIH).Methods[D-Ala2, N-Me-Phe4, Gly5-ol]-enkephalin (DAMGO), a selective µ-opioid receptor agonist, was used to induce mechanical hypersensitivity and was administered intradermally (4 times, 1-hour intervals) on the rat hind paw dorsum. To determine whether post- or pretreatments with spinal orexin A, dynorphin A, and anti-dynorphin A were effective in OIH, the drugs were injected through an intrathecal catheter whose tip was positioned dorsally at the L3 segment of the spinal cord (5 µg for all). Mechanical hypersensitivity was assessed using von Frey monofilaments.ResultsRepeated intradermal injections of DAMGO resulted in mechanical hypersensitivity in rats, lasting more than 8 days. Although the first intrathecal treatment of orexin A on the 6th day after DAMGO exposure did not show any significant effect on the mechanical threshold, the second (on the 8th day) significantly attenuated the DAMGO-induced mechanical hypersensitivity, which disappeared when the type 1 orexin receptor (OX1R) was blocked. However, intrathecal administration of dynorphin or an anti-dynorphin antibody (dynorphin antagonists) had no effect on DAMGO-induced hypersensitivity. Lastly, pretreatment with orexin A, dynorphin, or anti-dynorphin did not prevent DAMGO-induced mechanical hypersensitivity.ConclusionsSpinal orexin A attenuates mechanical hyperalgesia induced by repetitive intradermal injections of DAMGO through OX1R. These data suggest that OIH can be potentially treated by activating the orexin A-OX1R pathway in the spinal dorsal horn.

Postoperative Analgesia Management Evaluation in the Postanesthesia Unit: An Exploratory Analysis Based on Patient and Surgery Characteristics

Purpose:Several methods have been proposed for postoperative pain management, including administration of opioid analgesics, epidural analgesia, and perineural and infiltrative techniques; however, data are lacking on the relationship between pain intensity, patients’ age and gender, and surgery duration. Design: Prospective, observational, single-center study. Methods: The study included patients greater than or equal to 18 years old who underwent surgery with different anesthesia types, grouped according to the American Society of Anesthesiologists’ physical status classification score. The McGill Pain Questionnaire was used to assess postoperative pain intensity. The postoperative pain evaluation was performed in the first 5 minutes on entering the postanesthesia care unit (PACU), and at 30 minutes and 24 hours after the operation. Results: Our results showed a significant negative relationship between pain intensity as assessed at 5 and 30 minutes postoperatively and age. Postoperative pain intensity at 24 hours was significantly lower after low-risk surgeries lasting up to 1 hour; pain intensity was also significantly lower at 30 minutes following epidural anesthesia. When nonsteroidal anti-inflammatory drugs were not administered in the PACU, pain intensity was significantly lower at 5 minutes, 30 minutes, and 3 hours. Conclusions: Postoperative analgesic administration should be conducted in accordance with age and surgery type. Additionally, epidural anesthesia can reduce the immediate postoperative pain intensity.

NORMAL INDICATORS OF OXIDATIVE STRESS AND THE DYNAMICS OF THEIR CHANGES AT DIFFERENT TERMS OF EXPERIMENTAL OPIOID INFLUENCE

In the modern world, there are a large number of exogenous factors that contribute to the emergence of disorders associated with changes in biochemical data. One of these factors is the long-term usage of the opioid analgesics for therapeutic purposes, as well, as the use of opioid drugs without medical indications by people belonging to the category of drug addicts. More often, doctors of various specialties are faced with the problem of treating various nosology in people with opioid addiction. The process of correction of the main pathology makes it diffi cult due to the consequences arising from the chronic use of opioid drugs. The aim of the study is to fi nd out the dynamics of changes in the oxidative stress indicators of the blood of rats under normal conditions and during subchronic and chronic experimental opioid exposure. Material and methods. The research material was sexually mature, purebred male rats in the amount of 38 animals, weighing 160.0-270.0 g, aged 4.5-7.5 months. The animals were injected with nalbuphine intramuscularly, once a day at one time (10-11 am) per 70 days. The initial dose of nalbuphine during the fi rst 2 weeks was 0.212 mg/kg, the next 2 weeks (II-IV weeks) – 0.225 mg/kg, the next (IV-VI weeks) – 0.252 mg/kg, the next (VI-VIII weeks) – 0.260 mg/kg, and during (VIII-X weeks) – 0.283 mg/kg. Thus, conditions for chronic opioid exposure were created. Research results and their discussion. As a result of our experimental study, the eff ect of an opioid analgesic on the indicators of oxidative stress in the blood of rats, at the end of the 2nd week, we observed an unreliable increase in malondialdehyde and diene conjugates with a signifi cant decrease in the ceruloplasmin indicator. At the end of the 6th week administration of opioid analgesics, we observed a steady and continued growth of malondialdehyde and diene conjugates and a further decrease in ceruloplasmin. All indicators had a statistically proven diff erence compared with the control group. The animals of the experimental group, after 10 weeks of experimental opioid exposure have shown that all indicators continued the previously identifi ed dynamics and reached their maximum value of the diff erence compared to the control group. Conclusions. The conducted studies make it possible to clarify the peculiarities of changes in the oxidative stress indicators of the blood of rats in the subchronic and chronic periods of experimental opioid exposure.

Inpatient administration of opioids and risk for post-operative ileus in older adults.

Post-operative ileus (POI) is a common and potentially serious complication after surgery. We assessed the incidence and identified predictors of POI in older surgical patients. A retrospective observational study. University of California-San Francisco electronic medical record data. Opioid-naïve, noncancer patients, aged 65 and older, who underwent elective surgery in the period 2017-2019. Administration of opioid analgesics per day of hospitalization in opioid naïve patients. Incidence of POI and likelihood of developing POI. In the study period, 3 percent of opioid naïve patients developed POI. Patients with POI used on average 197.1 oral morphine equivalents (OMEs) per day of hospitalization compared to 82.5 OME in patients without POI (p = 0.013). Yet, there were not statistically significant differences in post-operative pain scores between patients with and without POI. General surgery (p = 0.0031), length of surgery (p = 0.0031), and hospital length of stay (p < 0.0001) were significant predictors of the risk for developing POI. Adjusted inpatient administration of more than 90 OME per day of hospitalization was associated with a four times greater risk for developing POI (p = 0.016). Developing POI was associated with 6.5 (95 percent confidence interval: 5.2-7.8) additional days of hospitalization among patients who developed POI compared to patients who did not develop POI (p < 0.0001). Adjusted inpatient administration of more than 90 OME significantly increased the risk for developing POI in opioid-naïve older patients. Developing POI after surgery significantly increased the hospital length of stay. Optimizing inpatient administration of opioids may prevent opioid use-related POI and longer hospitalizations.

Rabbits (Oryctolagus cuniculus) as a Model System for Longitudinal Experimental Opioid Treatments: Implications for Orthopedic and Biomedical Research

Due to the high prevalence of opioid prescription following orthopedic procedures, there is a growing need to establish an animal model system to evaluate the effects of opioids on bone remodeling. Rabbits have been employed as model organisms in orthopedic research as they exhibit well-defined cortical bone remodeling similar to humans. Existing research in rabbits has been limited to modes of opioid administration that are short-acting and require repeated application. Here, we present data from a proof-of-principle longitudinal study employing two opioid analgesic administration routes (subcutaneous injection and transdermal patch) to evaluate the efficacy of studying chronic opioid exposure in a rabbit model. Skeletally mature male New Zealand White rabbits (Oryctolagus cuniculus) were divided into three groups of seven animals: morphine, fentanyl, and control. Experimental treatments were conducted for eight weeks. Preparation of the skin at the fentanyl patch site and subsequent patch removal presented experimental difficulties including consistent skin erythema. Though noninvasive, the patches further caused acute stress in fentanyl animals. We conclude that though transdermal fentanyl patches may be preferred in an acute clinical setting, this method is not feasible as a means of long-term pain relief or opioid delivery in a laboratory context.

Analysis of Predictive Factors for Diarrhea after the Administration of Naldemedine.

Naldemedine (NAL), a peripherally acting μ-opioid receptor antagonist, is effective for opioid-induced constipation (OIC). However, diarrhea is the most common adverse event. We investigated the incidence of NAL-induced diarrhea in patients who started NAL at Nagasaki University Hospital between June 2017 and March 2019. Predictors of NAL-induced diarrhea were analyzed using a multivariate logistic regression model. Two hundred and forty-two patients were included in the present study, and NAL-induced diarrhea was observed in 17.8% (43 patients). The results of multiple logistic regression analyses identified the administration of opioid analgesics for 8 d or longer before the initiation of NAL (odds ratio (OR): 2.20, 95% confidence interval (95% CI): 1.04-4.64, p = 0.039), the combination of a laxative (OR: 2.22, 95%CI: 1.03-4.81, p = 0.042), and the combination of CYP3A4 inhibitors (strong/moderate) (OR: 2.80, 95%CI: 1.02-7.67, p = 0.045) as risk factors. Therefore, the development of diarrhea needs to be considered in patients with these risk factors. Furthermore, diarrhea may be controlled by the initiation of NAL within 7 d of opioid analgesics and, where possible, the discontinuation of or change in the combination of moderate or strong CYP3A4 inhibitors.

Long-Term Analgesia following a Single Application of Fentanyl Transdermal Solution in Pigs

Introduction: In animal research, obtaining efficient and constant pain control is regulatory but challenging. The gold standard pain management consists of opioid analgesic administration, such as buprenorphine or fentanyl extended-release patches. However, as in all drugs with a short half-life time, repeated buprenorphine administrations are needed, leading to multiple injections that affect the research protocol. On the other hand, fentanyl patch efficacy is discussed in some species. These elements highlight the need of an optimal formulation of analgesic drugs for laboratory animals. In this study, we investigated how Recuvyra®, a fentanyl transdermal solution (FTS), validated in dog perioperative pain management, could provide sustained analgesia after a single topical administration in pigs in a surgical context. Methods: A total of 11 minipigs were used in this study. As a preliminary experiment, two different doses were tested as a single application on five pigs: two pigs at full dose (2.6 mg/kg) and three pigs at half dose (1.3 mg/kg). Plasma fentanyl dosages were performed during 4 consecutive days, using liquid chromatography with tandem mass spectrometry detection. The efficacy of FTS was then evaluated in a perioperative period. Six minipigs benefited from a surgical intervention comprising a laparotomy. The FTS was blotted on the skin in a single application 20 min before the surgical incision and plasma fentanyl dosages, clinical examination (body weight, food intake, heart rate, and body temperature) and pain assessment were performed for 7 consecutive days. Results: During the preliminary experiment, all fentanyl concentrations reached the minimum effective concentration (MEC) extrapolated in pigs (fentanylemia ≥0.2 ng/mL) throughout the 4 days. The half dose was chosen for the next step of the study. After the surgical intervention, all plasma fentanyl concentrations remained above the MEC up to 7 days post administration. Pig clinical examinations and pain evaluations showed efficient and constant pain control at the half dose, and few adverse events were observed. Discussion and Conclusion: This study confirms the pharmacological and clinical efficacy of FTS at 1.3 mg/kg in pigs throughout at least 7 postoperative days following laparotomy. The clinical analgesic effect of FTS appears more efficient and well-tolerated than the one observed with repeated injections of buprenorphine. This analgesic drug formulation could be universally used in animal research to provide optimal perioperative pain management and long-term analgesia.

Observational, Retrospective Evaluation of a New Nurse-Initiated Emergency Department Pain Management Protocol

BackgroundTriage nurses are important in pain management and in early relief of pain among patients admitted to the emergency department (ED). AimsTo assess a new nurse-initiated pain management protocol, without the requirement for medical prescription, wich was implemented in October 2016 for patients with moderate or severe pain in the ED. It allows the administration of oral acetaminophen and oral oxycodone chlorydrate during the first evaluation of the patient by a nurse and eliminates the use of codeine or tramadol. MethodsWe conducted a comparative, single-center, retrospective study that looked at the outcomes of a new nursing protocol for patients aged ≥16 years with moderate to severe pain. The primary outcome was the percentage of increase of analgesics delivered by the nurse. ResultsA total of 756 patients were included: 377 before and 379 after protocol implementation. Oral analgesic use on admission increased from 44.3% to 57.8% (p < .001), and from 50.2% to 76.6% among patients with severe pain (p < .001). Strong opioid analgesic administration increased from 2.1% to 41.2%. This increase was also observed among those with moderate pain (1.4% to 13.3%; p < .001) and those with severe pain (2.6% to 62.6%; p < .001). Analgesic prescriptions added by the clinician decreased from 28.6% to 21.4% (p = .028). ConclusionsWe observed an increase in analgesic administration after the implementation of a new nurse-initiated pain treatment protocol, especially an increase in oral opioid analgesics, for patients with moderate to severe pain.

Postoperative pain management in obstetrics and gynecology

The efficiency and quality of postoperative pain management may be considered unsatisfactory in Europe, as well as in the United States. Notwithstanding our better understanding of the physiology of pain and the development of new analgesia procedures, the improvement in satisfaction of patients has not be enhanced to the same degree. Obstetrics and gynecology are no exception to this statement. In fact, obstetrics and gynecology are surgical departments in which patients experience the greatest severity of postoperative pain. Current concepts of postoperative pain management are largely based on the administration of systemic non-opioid and opioid analgesics, supplemented with regional analgesia procedures and/or peripheral nerve blockades and, in some cases, the administration of other pain-relieving pharmaceutical agents. Based on the existing body of evidence, it would be appropriate to develop procedure-related concepts of analgesia. The concepts are based on the special circumstances of the respective department, and the scheme of analgesia is aligned to the respective interventions. Generally, however, a surgeon’s individual experience in dealing with the procedures and substances could be more significant than the theoretical advantages demonstrated in preceding investigations.