Medical Economic Effect of Pharmaceutical Interventions by Board-Certified Pharmacists in Palliative Pharmacy for Patients with Cancer Using Medical Narcotics in Japan: A Multicenter, Retrospective Study.

BACKGROUND: The Japanese Society for Pharmaceutical Palliative Care and Sciences specializes in pharmacology in the field of palliative medicine. More than 700 board-certified pharmacists in palliative pharmacy (BCPPP) are actively involved in palliative pharmacotherapy at various hospitals and pharmacies. The purpose of this study was to determine the economic effect of pharmaceutical interventions by BCPPPs. METHODS: This multicenter retrospective study included 27 medical centers and analyzed the medical economic effect of interventions by BCPPPs (17 pharmacists) and non-BCPPPs (24 pharmacists) on patients using medical narcotics for cancer pain in September 2021. RESULTS: The percentage of patients who received a pharmaceutical intervention and whose drug costs were reduced by pharmacist intervention was significantly higher in the BCPPP group than in the non-BCPPP group. Although there was no significant difference between the two groups in drug cost reduction per patient per month (BCPPP group: $0.89 [-$64.91 to $106.76] vs. non-BCPPP group $0.00 [-$1,828.95 to $25.82]; P = 0.730), the medical economic benefit of pharmacist intervention in avoiding or reducing adverse drug reactions was higher in the BCPPP group ($103.18 [$0.00 to $628.03]) than in the non-BCPPP group ($0.00 [$0.00 to $628.03]) (P = 0.070). The total medical economic benefit-the sum of these-was significantly higher in the BCPPP group ($88.82 [-$14.62 to $705.37]) than in the non-BCPPP group ($0.66 [-$1,200.93 to $269.61]) (P = 0.006). CONCLUSION: Pharmacological intervention for patients with cancer using medical narcotics may have a greater medical economic benefit when managed by BCPPPs than by non-certified pharmacists in Japan.

Responses to a "Typical" Morning Dose of Kratom in People Who Use Kratom Regularly: A Direct-Observation Study.

INTRODUCTION: Use of kratom has outpaced systematic study of its effects, with most studies reliant on retrospective self-report. METHODS: We aimed to assess acute effects following kratom use in adults who use regularly, and quantify alkaloids in the products, urine, and plasma. Between July and November 2022, 10 adults came to our clinic and orally self-administered their typical kratom dose; blinding procedures were not used. Physiological measures included blood pressure, respiratory rate, heart rate, pulse oximetry, temperature, and pupil diameter. Subjective outcomes included Subjective Opioid Withdrawal Scale, Addiction Research Center Inventory, and Drug Effects Questionnaire. Psychomotor performance was also assessed. RESULTS: Participants were 6 men and 4 women, mean age 41.2 years. Nine were non-Hispanic White; 1 was biracial. They had used kratom for 6.6 years (SD, 3.8 years) on average (2.0-14.1). Sessions were 190.89 minutes on average (SD, 15.10 minutes). Mean session dose was 5.16 g (median, 4.38 g; range, 1.1-10.9 g) leaf powder. Relative to baseline, physiological changes were minor. However, pupil diameter decreased (right, b = -0.70, P < 0.01; left, b = -0.73, P < 0.01) 40-80 minutes postdose and remained below baseline >160 minutes. Subjective Opioid Withdrawal Scale pre-dosing was mild (5.5 ± 3.3) and decreased postdose (b = [-4.0, -2.9], P < 0.01). Drug Effects Questionnaire "feeling effects" increased to 40/100 (SD, 30.5) within 40 minutes and remained above baseline 80 to 120 minutes (b = 19.0, P = 0.04), peaking at 72.7/100; 6 participants rated euphoria as mild on the Addiction Research Center Inventory Morphine-Benzedrine-scale. Psychomotor performance did not reliably improve or deteriorate postdosing. CONCLUSIONS: Among regular consumers, we found few clinically significant differences pre- and post-kratom dosing. Alkaloidal contents in products were within expected ranges.

Adductor Canal Nerve Block versus Intra-articular Anesthetic in Knee Arthroscopy: A Single-Blinded Prospective Randomized Trial.

Effective perioperative pain control following knee arthroscopy allows patients to reduce narcotic intake, avoid side effects of these medications, and recover more quickly. Adductor canal nerve blockade (ACB) and intra-articular injection of local anesthetic have been described as adjuvant treatments for postoperative pain control following surgery of the knee. This study directly compares the effect of each of these treatment modalities. Patients undergoing knee arthroscopy were blinded and randomized to receive either an ACB (n = 60) or intra-articular injection of local anesthetic (IAB, n = 64). Outcome measures included patient reported visual analog scale (VAS) scores at 1, 2, 4, 8, 16, 24, 36, 48 hours and 1 week and total narcotic consumption at 12, 24, and 48 hours postoperatively. Student's t-tests were used to compare unadjusted VAS scores at each time point and use of postoperative pain medication between treatment groups. Adjusted VAS scores were estimated in a multivariable general linear model with interaction of time and treatment group and other relevant covariates. There were no statistically significant differences between the two groups in terms of gender, age, body mass index, and insurance type. ACB patients had significantly higher pain scores than IAB patients at hours 1 and 2 (hour 1: 4.02 [2.99] vs. 2.59 [3.00], p = 0.009; hour 2: 3.12 [2.44] vs. 2.17 [2.62], p = 0.040). ACB patients had higher pain scores than IAB patients up to hour 16, though hours 4 to 16 were not significantly different. Adjusted covariate analyses demonstrate an additional statistically significant reduction in pain score in the IAB group at hour 4. There were no differences in narcotic consumption. Intraoperative local anesthetic and regional ACB each provides adequate pain control following knee arthroscopy, and intraoperative local anesthetic may provide enhanced pain control for up to 4 hours postoperatively. LEVEL OF EVIDENCE: : Level 1 evidence, randomized control trial.

Correlation of Patient-Reported Preoperative Narcotic Use and Postoperative Requirements in Total Joint Arthroplasty.

Preoperative narcotic use is associated with diminished outcomes and increased complications in patients undergoing primary total joint arthroplasty (TJA). The goal of this study was to compare self-reported and state database identified preoperative narcotic use and correlate it with perioperative narcotic requirements in patients undergoing primary arthroplasty. A total of 788 patients undergoing unilateral TJA from a single institution were examined using self-reported preoperative narcotic use questionnaires and were verified using the Massachusetts Prescriber Awareness Tool (MassPAT). Demographic data, perioperative morphine milligram equivalents, and postdischarge refills were recorded and analyzed. Of the total population, 16.4% of patients undergoing TJA had verified MassPAT narcotics prescriptions preoperatively. Of these patients, 55% accurately reported use to their surgeon. Patients with verified MassPAT narcotic prescriptions required more morphine milligram equivalents than patients without MassPAT prescriptions, regardless of their preoperative self-report at all time points in the study. Patients who accurately reported use required more narcotics than those who did not. Patients with MassPAT prescriptions required more postdischarge refills than patients without MassPAT prescriptions. These data suggest that state-run narcotics databases may be more useful than self-reports for identifying which patients may require more opioids both immediately postoperatively and after hospital discharge. [Orthopedics. 2024;47(1):34-39.].

Opioid Use, Disposition, and Parent Satisfaction Following Common Pediatric Surgical Procedures.

INTRODUCTION: There is wide variability in prescribing practices among providers, even for patients undergoing the same operations. Our study aims to analyze the variation in opioid prescription practices using a patient-centered approach to establish more appropriate prescribing guidelines for health care providers. METHODS: We conducted phone surveys 30 days after surgery to assess patient-reported opioid use. Over a two-year collection period, we identified patients that had undergone common outpatient pediatric surgery procedures in our 4-surgeon group. Included in the survey tool was the narcotic prescribed (if any), the amount used, and patient/family rating of pain control. RESULTS: We collected data for 189 separate procedures (88 umbilical hernias, 30 laparoscopic inguinal hernias, 2 open inguinal hernias, 41 appendectomies, 15 laparoscopic cholecystectomies, and 13 pectus bar removals). Patient age ranged from less than 1 month to 246 months. 83.5% of patients had a narcotic prescribed. The average number of doses used was 4, ranging from 0 (11.3%) to 30 (1.5%). 72.6% of families surveyed felt pain control was appropriate. However, 19.6% did feel they received too much pain medication. 10.6% reported completing their entire prescription; however, only 13.6% of families with excess narcotics reported proper disposal. CONCLUSIONS: Despite heightened awareness of the opioid epidemic, there is still a poor understanding of appropriate pain control regimens in the pediatric surgical population. We demonstrate that most patients are discharged home with excess opioids and that many families save the leftover pills/liquid. Further research and education are encouraged to limit the use of opioids in standard pediatric surgical procedures.

Trends in Management of Anal Fissures.

BACKGROUND: It is unclear how patients with anal fissures are treated in real-world settings, particularly since patients may not see colorectal surgeons. This study describes trends in treatment with medical therapies (calcium-channel blockers [CCBs], nitroglycerin [NTG], and narcotics) and surgical treatments. METHODS: Cohorts were created within the TriNetX database platform using codes for anal fissures and surgical interventions. Demographics were compared between patients that received surgical intervention within 1 year of diagnosis, CCB or NTG within 1 year (or preoperatively), or narcotics within 30 days or postoperatively vs those who did not. RESULTS: 121,213 patients were included of which 4.0% had surgical intervention. Factors associated with surgical intervention were male sex (OR 1.40), White race (OR 1.17), and Hispanic ethnicity (OR 1.11). Male patients were more likely to undergo sphincterotomy (OR 1.49). Female (OR 1.27), non-Hispanic (OR 1.34), and White patients (OR 1.41) were more likely to have chemodenervation. Regarding nonoperatively managed patients, non-Hispanic (OR .91) and White patients (OR .89) were less likely to receive CCB/NTG. Male (OR 1.21), non-Hispanic (OR 1.08), and Black patients (OR 1.20) were more likely to receive narcotics. Male patients that required surgery were more likely to be prescribed CCB/NTG preoperatively (OR 1.27). Non-Hispanic surgical patients were more likely to receive narcotics (OR 1.84). DISCUSSION: Male fissure patients were more likely to undergo surgical intervention other than chemodenervation. Differences in the rates of surgery and medical therapy (especially narcotics) between races and ethnicities require exploration to enhance the care of patients with anal fissures.

Randomized Controlled Trial Comparing Liposomal to Plain Bupivacaine in the Transversus Abdominis Plane for DIEP Flap Breast Reconstruction.

BACKGROUND: Pain control after autologous breast reconstruction is important for patient satisfaction and early recovery. Transversus abdominis plane (TAP) blocks are commonly used as part of an enhanced recovery after surgery (ERAS) pathway for breast reconstruction. It is uncertain whether liposomal bupivacaine used in TAP blocks offers additional advantages. This study aimed to compare the efficacy of liposomal bupivacaine versus plain bupivacaine for patients undergoing deep inferior epigastric perforator flap reconstruction. METHODS: This double-blinded randomized controlled trial studied patients undergoing abdominally based autologous breast reconstruction between June of 2019 and August of 2020. Subjects were randomly assigned liposomal or plain bupivacaine, performed using ultrasound-guided TAP block technique. All patients were managed according to an ERAS protocol. Primary outcomes were postoperative narcotic analgesia required, measured in oral morphine equivalents from postoperative days 1 to 7. Secondary outcomes included numeric pain scale score on postoperative days 1 to 7, nonnarcotic pain medication use, time to first narcotic use, return of bowel function, and length of stay. RESULTS: Sixty patients were enrolled: 30 received liposomal bupivacaine and 30 received plain bupivacaine. There were no significant differences in demographics, daily oral morphine equivalent narcotic use, nonnarcotic pain medication use, time to narcotic use, numeric pain scale score, time to bowel function, or length of stay. CONCLUSION: Liposomal bupivacaine does not confer advantages over plain bupivacaine when used in TAP blocks for abdominally based microvascular breast reconstruction in patients under ERAS protocols and multimodal approaches for pain control. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, I.

The I-STOP Program and Narcotic Prescriptions Following Facial Reconstructive Plastic Surgeries.

OBJECTIVES: To explore the effect of e-prescribing requirements on narcotic dispersion in New York State. Slicer Dicer was used to identify patient records based on CPT codes. METHODS: We investigated the influence of New York State e-prescribing requirements on narcotic dispersion following five common facial plastics procedures. Slicer Dicer was used to identify patient records based on CPT codes.We then looked at narcotic prescription rates following those surgeries between March 2014 and March 2018 at an academic institution. RESULTS: Overall, between March 2014 and March 2018, 76.1% of the sample received a narcotic prescription following a facial reconstructive plastic surgery. Patients who underwent rhinoplasty were most likely to receive a prescription for postoperative narcotics. The implementation of ISTOP, CPT code, use of non-narcotic adjuvant, and insurance type were each significantly associated with prescription of postoperative narcotics. Surgery time and age in years were significantly associated with prescription of postoperative narcotics. Ultimately, when controlling for the aforementioned clinical and sociodemographic variables included in the study, those who underwent surgery after the implementation of ISTOP were 42.8% less likely to receive a prescription for postoperative narcotics, aOR = 0.572, 95% CI 0.356, 0.919, p = 0.021. CONCLUSIONS: New York State's ISTOP program has succeeded in reducing the number of postoperative narcotic prescriptions following facial plastic reconstructive surgeries at this academic institution. However, opioid medications can still be utilized for postoperative analgesia when clinically appropriate. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:1208-1213, 2024.

Impact of the Russian invasion on opioid agonist therapy programs in Ukraine: A qualitative study.

BACKGROUND: Opioid Agonist Treatment (OAT) combines opioid agonist medications with counseling and therapy for a whole-patient approach to treating opioid use disorder. The war in Ukraine threatened the continuity of care and well-being of individuals receiving OAT. This study aimed to capture patients' experiences accessing OAT during the war in Ukraine to provide insights that can inform and improve the programs that serve them. METHODS: In October - November 2022, we conducted semi-structured interviews with 17 OAT patients who are peer advocates in the Ukrainian Patient Network VOLNA. All interviews were conducted virtually via Zoom, recorded, and transcribed. Through thematic analysis, we generated codes from the transcripts, iteratively using both inductive and deductive approaches. RESULTS: The qualitative interviews revealed four themes: 1) 'medication,' focusing on concerns about availability, dosage, and quality of OAT; 2) 'patient barriers,' discussing access challenges for specific patient groups, such as refugees or patients living under the occupation; 3) 'clinic-level challenges,' involving dosing adequacy, treatment continuity, patient volume, and clinician stigma, and 4) 'regulatory inflexibility,' describing uneven implementation of regulations and increased policing to receive OAT during the war. CONCLUSION: Our study emphasizes the importance of adapting OAT programs in Ukraine to better serve vulnerable patients affected by the war. The Russian invasion has severely disrupted OAT provision, increasing the risks of opioid withdrawal, overdose, and diversion. By understanding patients' experiences, treatment preferences, and barriers to care, OAT programs can provide continuity of care to those in need.

[Narcotic Use under Probation and Parole Supervision - A longitudinal Study of Risk-group-specific Recidivism under Abstinence Conditions]. / Betäubungsmittelkonsum unter Bewährungs- und Führungsaufsicht ­ Eine Langzeituntersuchung zum risikogruppenspezifischen Rückfallgeschehen unter Abstinenzauflagen.

STUDY OBJECTIVE: The aim of this long-term study was to record substance-specific prevalences of illegal use of narcotics despite court-imposed abstinence requirements. METHODS: Urine assays were obtained by a public health department on the basis of administrative assistance for the probation department of a district court. The individual and valid allocation of these urine samples was ensured using a proven marker system. After postal dispatch, laboratory chemical analyses for narcotics residues were carried out in an external laboratory via enzyme immunoassay and validation by mass spectrography in the case of positive narcotics results. On the basis of all available routine data, a pooled data set covering a total of fourteen consecutive calendar years (2006-2019) was generated digitally and evaluated anonymously. RESULTS: From a total of 380 subjects (female: 13% versus male: 87%; average age: 30.4 years), 13,500 individual narcotic substance analyses from 2,941 urine samples were available. In 2.7% of all individual analyses, at least one of eight potential narcotic substances was detected, whereby the highest overall prevalences in the sense of a relapse were found for cannabis with 3.7% and for opiates with 2.4%. In contrast, there were almost no residues for barbiturates and LSD and no positive evidence for buprenorphine and PCP. As expected, most relapses in all narcotics groups were found in the age groups from 18 to 35 years. Strikingly, more women than men violated the court abstinence order with amphetamines, while relapses with the other seven narcotics groups occurred predominantly among men. In the course of the entire observation period, the most marked fluctuations in relapse rates were found for cannabis, opiates and cocaine. CONCLUSION: The use of narcotic substances during probation and parole supervision does not appear to be a rare occurrence and has received little professional attention. Increased attention to this group-specific recidivism and more studies on this topic should help reduce this deficit.

Effects of inhaled low-concentration xenon gas on naltrexone-precipitated withdrawal symptoms in morphine-dependent mice.

BACKGROUND: Opioid withdrawal symptoms (OWS) are highly aversive and prompt unprescribed opioid use, which increases morbidity, mortality, and, among individuals being treated for opioid use disorder (OUD), recurrence. OWS are driven by sympathetic nervous system (SNS) hyperactivity that occurs when blood opioid levels wane. We tested whether brief inhalation of xenon gas, which inhibits SNS activity and is used clinically for anesthesia and diagnostic imaging, attenuates naltrexone-precipitated withdrawal-like signs in morphine-dependent mice. METHODS: Adult CD-1 mice were implanted with morphine sulfate-loaded (60 mg/ml) minipumps and maintained for 6 days to establish morphine dependence. On day 7, mice were given subcutaneous naltrexone (0.3 mg/kg) and placed in a sealed exposure chamber containing either 21% oxygen/balance nitrogen (controls) or 21% oxygen/added xenon peaking at 30%/balance nitrogen. After 10 minutes, mice were transferred to observation chambers and videorecorded for 45 minutes. Videos were scored in a blind manner for morphine withdrawal behaviors. Data were analyzed using 2-way ANOVAs testing for treatment and sex effects. RESULTS AND CONCLUSIONS: Xenon-exposed mice exhibited fewer jumps (P = 0.010) and jumping suppression was detectible within the first 10-minute video segment, but no sex differences were detected. Brief inhalation of low concentration xenon rapidly and substantially attenuated naltrexone-precipitated jumping in morphine-dependent mice, suggesting that it can inhibit OWS. If xenon effects translate to humans with OUD, xenon inhalation may be effective for reducing OWS, unprescribed opioid use, and for easing OUD treatment initiation, which could help lower excess morbidity and mortality associated with OUD.

Methadone use for acute opioid withdrawal in Tshwane shelters during the COVID-19 lockdown.

BACKGROUND: Temporary shelters were established for street-based people during the national level 5 coronavirus disease 2019 (COVID-19) lockdown. However, street-based substance users' need to access substances was not addressed, resulting in large numbers of people experiencing withdrawal. The Community Oriented Substance Use Programme (COSUP) in Tshwane provided methadone to manage opioid withdrawal. METHODS: A cross-sectional, descriptive study was conducted using the daily methadone dosing records from shelters in Tshwane between March 2020 and September 2020. RESULTS: The final analysis included 495 participants, of which 64 (12.9%) were initiated on 20 mg - 30 mg of methadone, 397 (80.2%) on 40 mg - 50 mg, and 34 (6.9%) on 60 mg - 70 mg. A total of 194 (39.2%) participants continued their initiation dose for 1-2 months, after which 126 (64.9%) had their doses increased, and 68 (35.1%) had their doses decreased. Approximately 12 (2.4%) participants were weaned off methadone after 1-3 months and 46 (9.3%) after 4-6 months. In all, 100 (20.2%) participants left the shelter prematurely and did not continue with methadone. A total of 126 (25.5%) participants continued to stay in the shelters and received methadone for 6 months, with 125 (25.3%) participants leaving the shelter with continued follow-up at a COSUP site. CONCLUSION: This study demonstrates variability in methadone dosing regimens among shelter residents. As the lockdown measures eased, many chose to leave the shelters, while others remained to receive methadone and other services. The COSUP appears to be effective during periods of increased vulnerability, since a large number of participants were successfully followed up.Contribution: Opioid dependence is a persistent, lifelong disease. It is multifaceted with complex environmental and individual determinants. This study highlighted the use of opioid substitution therapy during a period of increased vulnerability.

Detroit Interventional Pain Assessment Scale: A Pain Score and Method for Measuring and Evaluating Post-Operative Pain Management-A Prospective Study.

Background and Objectives: Orthopedic surgeons commonly prescribe opioids, surpassing all medical specialties. Our objective was to develop a pain management scale that captures medication use, patient-reported pain scores, and helps orthopedic surgeons evaluate their post-operative prescribing practice. Materials and Methods: An IRB-approved prospective study followed 502 post-operative orthopedic surgery patients over a six-month period. All patients were surveyed in an orthopedic clinic at a Level 1 US Trauma Center, during a routine follow-up. Patient pain satisfaction was assessed using the validated Interventional Pain Assessment (IPA) scale, which uses three categories: 0 (no pain), 1 (tolerable pain), and 2 (intolerable pain). Daily narcotic use was translated to morphine milligram equivalents (MMEs) using the Michigan Automated Prescription System (MAPS) narcotics registry. When patient pain satisfaction and narcotic usage were combined, this scale was called the Detroit Interventional Pain Assessment (DIPA) scale. Results: The five classes based on common prescription and usage of narcotics in this cohort include the following: A (no pain medication), B (over-the-counter medication), C (occasional use of short-acting narcotics 1-30 MMEs), D (consistent/regular use of short-acting narcotics 31-79 MMEs), and E (long-duration or stronger short-acting narcotics 80+ MMEs). Patients were most satisfied with their pain management at six weeks (80.5%) and three months (75.65%), and least satisfied at two weeks (62.5%) and six months (60.9%). Additional information displayed on the DIPA graph revealed there was a significant decrease in the percentage of patients on narcotics at two weeks (65.2%) to six months (32.6%) at p < 0.001. Conclusions: The DIPA pain scale shows the relationship between patient pain perception and opioid prescription/usage, while also tracking prescriber tendencies. Providers were able to visualize their post-operative pain management progression at each designated clinic visit with corresponding alphabetical daily MME categories. In this study, results suggest that surgeons were not effective at managing the pain of patients at two weeks post-operative, which is attributed to an inadequate number of pain pills prescribed upon discharge. Overall, the DIPA graph signaled that better pain management interventions are necessitated in periods with lower efficiency scores.

Patient Perceptions of Integrating Meditation-based Interventions in Office-based Opioid Treatment with Buprenorphine: A Mixed-methods Survey.

INTRODUCTION: Recent findings support the provision of meditation-based interventions (MBIs) in primary care. However, the acceptability of MBI among patients prescribed medications for opioid use disorder (eg, buprenorphine) in primary care remains unclear. This study assessed experiences and preferences for adopting MBI among patients prescribed buprenorphine in office-based opioid treatment (OBOT). METHODS: This 23-item, semistructured cross-sectional survey was administered by study staff to patients enrolled in OBOT (N = 72) and consisted of demographic and clinical characteristics, perceptions, experiences with MBI, and preferred strategies to access MBI to support their treatment on buprenorphine. RESULTS: Most participants reported practicing at least 1 category of MBI (90.3%) on at least a daily (39.6%) or weekly (41.7%) basis including (1) spiritual meditation (eg, centering prayer; 67.7%); (2) nonmantra meditation (eg, comfortable posture; 61.3%); (3) mindfulness meditation (eg, mindfulness-based stress reduction; 54.8%); and (4) mantra meditation (eg, transcendental meditation; 29.0%). Interest in MBI was motivated by improving one's general health and well-being (73.4%), treatment outcomes with medications for OUD (eg, buprenorphine; 60.9%), and relationships with others (60.9%). Perceived clinical benefits of MBI included reduced anxiety or depression symptoms (70.3%), pain (62.5%), illicit substance or alcohol use (60.9%), cravings for illicit substances (57.8%), and opioid-related withdrawal symptoms (51.6%). CONCLUSIONS: Findings from this study indicate high acceptability for adopting MBI among patients prescribed buprenorphine in OBOT. Further research is needed to assess the efficacy of MBI to improve clinical outcomes among patients initiating buprenorphine in OBOT.

NMDA Receptors in the Rat Paraventricular Thalamic Nucleus Reduce the Naloxone-induced Morphine Withdrawal.

BACKGROUND: NMDA receptors have a significant role in the development of opioid physical dependence. Evidence demonstrated that a drug of abuse enhances neuronal excitability in the Paraventricular Nucleus (PVT). The current research studied whether blocking NMDA receptors through the administration of MK801 in the PVT nucleus could affect the development of Morphine (Mor) dependence and hence the behavioral indices induced by morphine withdrawal in rats. METHODS: Male Wistar rats weighing 250-300 g were used. For induction of drug dependence, we injected Mor subcutaneously (s.c.) (6, 16, 26, 36, 46, 56, and 66 mg/kg, 2 ml/kg) at an interval of 24 hours for 7 days. Animals were divided into two groups in which the NMDA receptor antagonist, MK801 (20 mM in 0.1 ml), or its vehicle were applied into the PVT nucleus for 7 days before each Mor administration. On day 8, after injection of naloxone (Nal, 2.5 mg/kg, i.p.), withdrawal behaviors were checked for 25 min. RESULTS: The current results demonstrated that the blockade of the NMDA receptor in the PVT nucleus significantly increased withdrawal behaviors provoked by the application of Nal in morphinedependent (Mor-d) rats. CONCLUSION: We concluded that the NMDA receptor in the PVT nucleus changes the development of Mor dependence.

Oral versus intravenous acetaminophen for perioperative pain management in adult patients undergoing non-cardiac surgery: A quantile segmented regression analysis.

STUDY OBJECTIVE: Determine whether preferential use of perioperative enteral acetaminophen is associated with changes in perioperative pain, narcotic administration, or time to meeting criteria for post anesthesia care unit (PACU) discharge, compared to preferential parenteral administration. DESIGN: Retrospective Cohort with quantile segmented regression analysis. Groups determined by date of surgery, one year pre-initiative and one year post-initiative. SETTING: Operating room and PACU of a tertiary academic medical center. PATIENTS: Adult (age > 18 years), ASA status 1-5, non-pregnant patients undergoing non-cardiac surgery of less than six hours duration admitted to the PACU postoperatively. INTERVENTIONS: A multidisciplinary initiative to preferentially utilize enteral over parenteral acetaminophen. MEASUREMENTS: The primary outcome was narcotic consumption in the PACU. Secondary outcomes were intraoperative narcotic administration, pain score on PACU admission and discharge, and time to meeting criteria for PACU discharge. RESULTS: 24,701 patients were included in the analysis; 12,379 had surgery prior to the initiative and 12,322 after. Enteral acetaminophen administration increased preoperatively from 13.49% to 26.84%, and postoperatively from 43.16% to 51.45%, while intraoperative parenteral APAP use dropped from 43.23% to 6.81%. Quantile Segmented regression analysis after adjusting for period (pre versus postintervention), day, age, gender, inpatient status, and ASA class demonstrated a decrease in adjusted median perioperative acetaminophen dose (-175 mg P < 0.001), with no significant difference in level change of intraoperative or PACU narcotic administration. There was no significant difference in median time to meet criteria for PACU discharge, though there was a significant change in the slope, (-0.36, p = 0.007.) Median pain scores measured on a standard 0-10 numeric rating scale at PACU admission did not change, while median pain scores at PACU discharge decreased slightly (-0.24 p < 0.001). There was no change in the probability of PONV. CONCLUSION: In adult patients undergoing non-cardiac surgery of <6 h duration, preferential use of enteral rather than parenteral acetaminophen is associated with non-inferior outcomes in narcotic requirements, pain scores, time to PACU discharge, and probability of PONV when compared with routine parenteral administration. Further studies are needed to validate these findings.

Factors Associated with Inpatient Narcotic Medication Usage after Robotic-assisted Laparoscopy.

STUDY OBJECTIVE: Describe factors that contribute to an increased narcotic medication use after robotic-assisted laparoscopic (RAL) surgery. DESIGN: A retrospective cohort. SETTING: A teaching hospital. PATIENTS: All patients undergoing RAL surgery by gynecologist oncologists at St. Joseph's Hospital and Medical Center over a 3-year period. INTERVENTIONS: RAL by gynecologist oncologists. MEASUREMENTS AND MAIN RESULTS: Using retrospective chart review, patients who underwent RAL surgery from 2012 to 2015 in the division of gynecologic oncology were identified; 757 patients were eligible for inclusion in the study. Total narcotic use during the postoperative hospital stay was converted to oral morphine milligram equivalents (OME). Bivariate correlations of total OME narcotics to multiple variables were evaluated using Spearman's rho. The average age, body mass index, and length of stay were 53.76 years (17-92), 31.75 kg/m2 (17-56), and 1.56 days (range, 0-19), respectively. Increased OME correlated positively with body mass index (Spearman's rho = .077, p = .036), any intraoperative complication (Spearman's rho = .05, p = .886), any postoperative complication (Spearman's rho = .16, p <.0001), length of stay in days (Spearman's rho = .282, p <.0001), procedure time (Spearman's rho .023, p = .52), and total anesthesia time (Spearman's rho, .032). Total OME narcotics were correlated negatively with age of 65 years or older (Spearman's rho, -.144, p <.0001) and use of patient-controlled analgesia (Spearman's rho, -.185, p <.0001). CONCLUSION: Age younger than 65 years seems to be a predictor for increased requirement of total morphine equivalent medication after RAL surgery, whereas patient-controlled analgesia use had a negative association.

Efficacy and safety of tramadol in the treatment of opioid withdrawal: A meta-analysis of randomized controlled trials.

BACKGROUND: Pharmacotherapeutic options for the treatment of opioid withdrawal are limited by abuse potential, adverse effects, and lack of availability of existing drugs. The results from previous clinical trials on tramadol are contradictory and non-conclusive; hence the present meta-analysis was conducted to evaluate the efficacy and safety of tramadol in the treatment of opioid withdrawal. METHODS: Reviewers extracted data from eight relevant clinical trials after a literature search on MEDLINE/PubMed, Cochrane databases, and clinical trial registries. Quality assessment was done using the risk-of-bias assessment tool, and the random-effects model was used to estimate effect size in frequentist and Bayesian approaches. Subgroup analysis, meta-regression, and sensitivity analysis were done as applicable. PRISMA guidelines were followed in reporting findings. RESULTS: Tramadol significantly reduced opioid withdrawal scale score (SMD: -0.44; 95%CI: -0.76 to -0.13; PI: -1.54 to 0.71; p = 0.006) when all comparators were considered together in the frequentist approach but the reduction was non-significant in Bayesian approach. However, the subgroup analysis revealed no significant difference between tramadol and comparators like placebo (SMD: -1.12; 95%CI: -2.69 to 0.45) buprenorphine (SMD: -0.21; 95%CI: -0.43 to 0.01), clonidine (SMD: -0.26; 95%CI: -0.55 to 0.02) and methadone (SMD: -0.84; 95%CI: -1.78 to 0.10). Meta-regression showed non-significant associations between the SMD in opioid withdrawal score with the duration and dose of tramadol therapy. There were no significant differences in treatment retention at the end of studies between tramadol and comparators. Safety data in the individual studies were inadequate to analyze. CONCLUSION: Authors conclude that the efficacy of tramadol in reducing opioid withdrawal symptoms is not significantly different from comparators with low certainty of evidence against placebo, moderate against methadone, whereas with high certainty of evidence against buprenorphine and clonidine.

The Limit Is Zero: A Prospective Evaluation of Ketorolac in Patients Undergoing Primary Palatoplasty to Reduce Narcotic Utilization.

BACKGROUND: Patients undergoing primary palatoplasty rely on narcotics for pain control, but narcotics can lead to sedation and respiratory depression. Recent research into Enhanced Recovery After Surgery (ERAS) pathways utilizing multimodal pain therapy has yielded promising results for patients undergoing palatoplasty in terms of decreased hospital length of stay (LOS), increased oral intake, and decreased narcotic usage. Despite the potential benefit of ketorolac after palatoplasty, there is a paucity of data regarding its use. METHODS: A single-center cohort study of patients undergoing primary palatoplasty was performed using 2 cohorts: a retrospective cohort treated with our institution's prior ERAS protocol from 2016 to 2018 and a prospective group of patients who also received ketorolac (ERAS+K) postoperatively from 2020 to 2022. RESULTS: A total of 85 patients (57 ERAS and 28 ERAS+K) were included. Compared with the ERAS group, the ERAS+K cohort had significantly decreased LOS (31.8 versus 55 h, P =0.02), decreased morphine milligram equivalents administered at 24 hours (1.5 versus 2.5, P =0.003), 48 hours (0 versus 1.5, P <0.001), and total inpatient morphine milligram equivalents (1.9 versus 3.8, P =0.001). The ERAS+K group also had a significant decrease in the prescribed narcotic rate (32.1% versus 61.4%, P =0.006). No bleeding issues, blood transfusions, or reoperations were noted in either cohort. CONCLUSIONS: This study illustrates many potential benefits of using ketorolac as a pain management adjunct in combination with a multimodal pain regimen. Our results demonstrated favorable outcomes, including decreased narcotic usage and LOS as well as increased hourly oral intake, without increasing bleeding complications.