3,3-Dibromoflavanone, a synthetic flavonoid derivative for pain management with antidepressant-like effects and fewer side effects than those of morphine in mice.

In the pursuit of new lead compounds with fewer side effects than opioids, the novel synthetic phytochemical core, 3,3-dibromoflavanone (3,3-DBF), has emerged as a promising candidate for pain management. Acute assays demonstrated dose-dependent central and peripheral antinociceptive activity of 3,3-DBF through the µ-opioid receptor. This study aimed to explore repeated administration effects of 3,3-DBF in mice and compare them with morphine. Mice were treated with 3,3-DBF (30 mg/kg), morphine (6 mg/kg), or vehicle for 10 days, alongside single-treatment groups. Unlike morphine, 3,3-DBF demonstrated antinociceptive effects in the hot plate test without inducing tolerance. Locomotor activity and motor coordination tests (evaluated through the inverted screen and rotarod tests) revealed no significant differences between the 3,3-DBF-treated and control groups. The gastrointestinal transit assay indicated that 3,3-DBF did not induce constipation, in contrast to morphine. Furthermore, withdrawal signs assessed with the Gellert-Holtzman scale were not comparable to morphine. Additionally, 3,3-DBF exhibited antidepressant-like activity, reducing immobility time in the forced swimming and tail suspension tests, akin to imipramine. In summary, 3,3-DBF demonstrated antinociceptive effects without inducing tolerance or dependence and exhibited antidepressant properties. These findings highlight the potential of 3,3-DBF as a promising therapeutic agent for pain management and its comorbidities, offering advantages over morphine by minimizing side effects.

Intravenous Methadone versus Intrathecal Morphine as Part of an Enhanced Recovery After Cardiac Surgery Protocol on Postoperative Pain and Outcomes: A Retrospective Cohort Study.

OBJECTIVES: Evaluate the effect of intravenous (IV) methadone versus intrathecal morphine (ITM) within an Enhanced Recovery After Cardiac Surgery (ERACS) pathway on postoperative pain and outcomes (length of hospital stay and postoperative complications) after cardiac surgery. DESIGN: Retrospective cohort study. SETTING: Two tertiary academic medical institutions within the same health system. PARTICIPANTS: Eligible 289 adult patients undergoing elective cardiac surgery with an enhanced recovery pathway from January 2020 through July 2021. INTERVENTIONS: Patients were administered ITM (0.25 mg) or IV methadone (0.1 mg/kg) if ITM was contraindicated. All patients were enrolled in an ERACS pathway using current Enhanced Recovery After Surgery society guidelines. MEASUREMENTS AND MAIN RESULTS: Primary outcome measures included postoperative pain scores and opioid consumption measured as oral morphine equivalents. We analyzed patient demographics, procedural factors, intraoperative medications, and outcomes. Adjusted linear mixed models were fit to analyze associations between intervention and pain outcomes. ITM was associated with decrease in pain scores on postoperative day 0 after adjusting for clinical variables (average marginal effect, 0.49; 95% confidence interval, 0.002-0.977; p = 0.049). No difference in opioid consumption could be demonstrated between groups after adjusting for postoperative day and other variables of interest. CONCLUSIONS: ITM when compared with IV methadone was associated with a decrease in pain scores without any difference in opioid consumption after elective cardiac surgery. Methadone can be considered as a safe and effective alternative to ITM for ERACS protocols. Future large prospective studies are needed to validate this finding and further improve analgesia and safety.

Oral Clonidine-Based Strategy to Reduce Opiate Use During Cooling for Neonatal Encephalopathy: An Observational Study.

OBJECTIVE: To determine whether an enteral, clonidine-based sedation strategy (CLON) during therapeutic hypothermia (TH) for hypoxic-ischemic encephalopathy would decrease opiate use while maintaining similar short-term safety and efficacy profiles to a morphine-based strategy (MOR). STUDY DESIGN: This was a single-center, observational study conducted at a level IV neonatal intensive care unit from January 1, 2017, to October 1, 2021. From April 13, 2020, to August 13, 2020, we transitioned from MOR to CLON. Thus, patients receiving TH for hypoxic-ischemic encephalopathy were grouped to MOR (before April 13, 2020) and CLON (after August 13, 2020). We calculated the total and rescue morphine milligram equivalent/kg (primary outcome) and frequency of hemodynamic changes (secondary outcome) for both groups. RESULTS: The MOR and CLON groups (74 and 25 neonates, respectively) had similar baseline characteristics and need for rescue sedative intravenous infusion (21.6% MOR and 20% CLON). Both morphine milligram equivalent/kg and need for rescue opiates (combined bolus and infusions) were greater in MOR than CLON (P < .001). As days in TH advanced, a lower percentage of patients receiving CLON needed rescue opiates (92% on day 1 to 68% on day 3). Patients receiving MOR received a greater cumulative dose of dopamine and more frequently required a second inotrope and hydrocortisone for hypotension. MOR had a lower respiratory rate during TH (P = .01 vs CLON). CONCLUSIONS: Our CLON protocol is noninferior to MOR, maintaining perceived effectiveness and hemodynamic safety, with an apparently reduced need for opiates and inotropes.

Comparison of analgesic efficacy of tramadol, morphine and methadone in cats undergoing ovariohysterectomy.

OBJECTIVES: The aim of this study was to compare the analgesic efficacy and the effect on physiological variables and behavior of the use of tramadol, methadone and morphine as preoperative analgesia in healthy cats undergoing elective ovariohysterectomy. METHODS: Cats undergoing ovariohysterectomy were randomly assigned to receive one of the following premedication treatments intramuscularly: methadone (0.2 mg/kg; n = 10); morphine (0.2 mg/kg; n = 10); or tramadol (3 mg/kg; n = 10). Induction of anesthesia was done with propofol, and maintenance of anesthesia was done with isoflurane. Intraoperative heart rate, arterial blood pressure, respiratory rate, end-tidal isoflurane concentration and frequency of rescue analgesia (fentanyl 2.5 µg/kg) were compared between groups. Postoperative analgesia was assessed using the UNESP-Botucatu Multidimensional Composite Pain Scale, and perioperative serum glucose, cortisol concentrations and postoperative rescue analgesia were evaluated. RESULTS: Intraoperative rescue analgesia was required in 76.5% of cats at some time during surgery, and 27% of cats required postoperative rescue analgesia up to 6 h after extubation. There were no significant differences between groups with respect to intraoperative and postoperative rescue analgesia, pain scale scores and end-tidal isoflurane concentrations. In the immediate postoperative period, after extubation, most of the patients presented with hypothermia; however, 1-6 h postoperatively, hyperthermia was observed in most of the patients, and was most common in the tramadol group. CONCLUSIONS AND CLINICAL RELEVANCE: Under the conditions of this study, methadone, morphine and tramadol produced satisfactory postoperative analgesia in most of the cats undergoing ovariohysterectomy, and the effects lasted up to 6 h postoperatively. Intraoperative analgesia was not sufficient in most cases. Significant cardiovascular or respiratory effects contraindicating the use of these drugs were not found. Postanesthetic hyperthermia occurred with all opioids studied and was more frequent in the tramadol group.

Effectiveness of epidural morphine for the treatment of cancer pain in patients with gastrointestinal neoplasm-a systematic review.

One-third of cancer pain patients do not experience adequate pain relief using analgesic ladder by the World Health Organization. Interventional procedures, such as epidural morphine, have been considered. This study aimed to review the literature comparing the effects of epidural administration of morphine with the oral route. This systematic review included randomized controlled trials (RCTs) conducted with patients with gastrointestinal neoplasm. A search was conducted on PubMed, EMBASE, Web of Science, Scopus, Cochrane Library, and CINAHL databases to identify studies published up to May 2023. The retrieved study was evaluated using the Risk of Bias 2 (RoB 2) tool and qualitatively synthesized. The certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach (Prospero: CRD42021264728). Only one RCT, a crossover trial, was included in this systematic review. The study was conducted with ten participants (one withdrawal) and reported a statistically significant difference between both subcutaneous and epidural morphine solutions and oral morphine. The adverse events were not described. The included study presents some concerns of bias and low certainty of evidence on the effectiveness and security of epidural morphine administration. The available literature does not suffice to elucidate whether morphine administration via the epidural route is more effective than other routes. Further RCTs are necessary to improve the level of evidence on the effectiveness and risk-benefit of epidural morphine in the management of cancer pain in gastrointestinal neoplasm patients.

Is Acetaminophen Beneficial in Patients With Cancer Pain Who are on Strong Opioids? A Randomized Controlled Trial.

CONTEXT: Pain is common among cancer patients. The evidence recommends using strong opioids in moderate to severe cancer pain. No conclusive evidence supports the effectiveness of adding acetaminophen to patients with cancer pain who are already using this regime. OBJECTIVES: To assess the analgesic efficacy of acetaminophen in hospitalized cancer patients with moderate to severe pain receiving strong opioids. METHODS: In this randomized blinded clinical trial, hospitalized cancer patients with moderate or severe acute pain managed with strong opioids were randomized to acetaminophen or placebo. The primary outcome was pain intensity difference between baseline and 48 hours using the Visual Numeric Rating Scales (VNRS). Secondary outcomes included change in morphine equivalent daily dose (MEDD), and patients' perception of improved pain control. RESULTS: Among 112 randomized patients, 56 patients received placebo, 56 acetaminophen. Mean (standard deviation [SD]) decrease in pain intensity (VNRS) at 48 hours were 2.7 (2.5) and 2.3 (2.3), respectively (95% Confidence Interval (CI) [-0.49; 1.32]; P = 0.37). Mean (SD) change in MEDD was 13.9 (33.0) mg/day and 22.4 (57.7), respectively (95% CI [-9.24; 26.1]; P = 0.35). The proportion of patients perceiving pain control improvement after 48 hours was 82% in the placebo and 80% in the acetaminophen arms (P = 0.81). CONCLUSION: Among patients with cancer pain on strong opioid regime, acetaminophen may not improve pain control, or decrease total opioid use. These results add to the current evidence available suggesting not to use acetaminophen as an adjuvant for advanced cancer patients with moderate to severe cancer pain who are on strong opioids.

Effect of magnesium sulfate with ketamine infusions on intraoperative and postoperative analgesia in cancer breast surgeries: a randomized double-blind trial

Abstract Background Opioids are the cornerstone in managing postoperative pain; however, they have many side effects. Ketamine and Magnesium (Mg) are NMDA receptor antagonists used as adjuvant analgesics to decrease postoperative opioid consumption. Objective We assumed that adding Mg to ketamine infusion can improve the intraoperative and postoperative analgesic efficacy of ketamine infusion alone in cancer breast surgeries. Methods Ninety patients aged between 18 and 65 years and undergoing elective cancer breast surgery were included in this prospective randomized, double-blind study. Group K received ketamine 0.5 mg.kg-1 bolus then 0.12 mg.kg-1.h-1 infusion for the first 24 hours postoperatively. Group KM: received ketamine 0.5 mg.kg-1 and Mg sulfate 50 mg.kg-1, then ketamine 0.12 mg.kg-1.h-1 and Mg sulfate 8 mg.kg-1.h-1 infusions for the first 24 hours postoperative. The primary outcome was the morphine consumption in the first 24 hours postoperative, while the secondary outcomes were: intraoperative fentanyl consumption, NRS, side effects, and chronic postoperative pain. Results Group KM had less postoperative opioid consumption (14.12 ± 5.11 mg) than Group K (19.43 ± 6.8 mg). Also, Group KM had less intraoperative fentanyl consumption. Both groups were similar in postoperative NRS scores, the incidence of side effects related to opioids, and chronic neuropathic pain. Conclusion Adding Mg to ketamine infusion can safely improve intraoperative and postoperative analgesia with opioid-sparing effect in cancer breast surgery.

Randomized clinical trial comparing pericapsular nerve group (PENG) block and periarticular local anesthetic infiltration for total hip arthroplasty.

BACKGROUND: This randomized trial compared pericapsular nerve group block and periarticular local anesthetic infiltration in patients undergoing primary total hip arthroplasty. We hypothesized that, compared with pericapsular nerve group block, periarticular local anesthetic infiltration would decrease the postoperative incidence of quadriceps weakness at 3 hours fivefold (ie, from 45% to 9%). METHODS: Sixty patients undergoing primary total hip arthroplasty under spinal anesthesia were randomly allocated to receive a pericapsular nerve group block (n=30) using 20 mL of adrenalized bupivacaine 0.50%, or periarticular local anesthetic infiltration (n=30) using 60 mL of adrenalized bupivacaine 0.25%. Both groups also received 30 mg of ketorolac, either intravenously (pericapsular nerve group block) or periarticularly (periarticular local anesthetic infiltration), as well as 4 mg of intravenous dexamethasone.Postoperatively, a blinded evaluator carried out sensory assessment and motor assessment (knee extension and hip adduction) at 3, 6 and 24 hours. Furthermore, the blinded observer also recorded static and dynamic pain scores at 3, 6, 12, 18, 24, 36 and 48 hours; time to first opioid request; cumulative breakthrough morphine consumption at 24 hours and 48 hours; opioid-related side effects; ability to perform physiotherapy at 6, 24 and 48 hours; as well as length of stay. RESULTS: There were no differences in quadriceps weakness at 3 hours between pericapsular nerve group block and periarticular local anesthetic infiltration (20% vs 33%; p=0.469). Furthermore, no intergroup differences were found in terms of sensory block or motor block at other time intervals; time to first opioid request; cumulative breakthrough morphine consumption; opioid-related side effects; ability to perform physiotherapy; and length of stay. Compared with pericapsular nerve group block, periarticular local anesthetic infiltration resulted in lower static pain scores (at all measurement intervals) and dynamic pain scores (at 3 and 6 hours). CONCLUSION: For primary total hip arthroplasty, pericapsular nerve group block and periarticular local anesthetic infiltration result in comparable rates of quadriceps weakness. However, periarticular local anesthetic infiltration is associated with lower static pain scores (especially during the first 24 hours) and dynamic pain scores (first 6 hours). Further investigation is required to determine the optimal technique and local anesthetic admixture for periarticular local anesthetic infiltration. TRIAL REGISTRATION NUMBER: NCT05087862.

Modulation of the Inflammatory Response by Pre-emptive Administration of IMT504 Reduces Postoperative Pain in Rats and has Opioid-Sparing Effects.

Despite the available knowledge on underlying mechanisms and the development of several therapeutic strategies, optimal management of postoperative pain remains challenging. This preclinical study hypothesizes that, by promoting an anti-inflammatory scenario, pre-emptive administration of IMT504, a noncoding, non-CpG oligodeoxynucleotide with immune modulating properties, will reduce postincisional pain, also facilitating therapeutic opioid-sparing. Male adult Sprague-Dawley rats with unilateral hindpaw skin-muscle incision received pre-emptive (48 and 24 hours prior to surgery) or postoperative (6 hours after surgery) subcutaneous vehicle (saline) or IMT504. Various groups of rats were prepared for pain-like behavior analyses, including subgroups receiving morphine or naloxone, as well as for flow-cytometry or quantitative RT-PCR analyses of the spleen and hindpaws (for analysis of inflammatory phenotype). Compared to vehicle-treated rats, pre-emptive IMT504 significantly reduced mechanical allodynia by 6 hours after surgery, and accelerated recovery of basal responses from 72 hours after surgery and onwards. Cold allodynia was also reduced by IMT504. Postoperative administration of IMT504 resulted in similar positive effects on pain-like behavior. In IMT504-treated rats, 3 mg/kg morphine resulted in comparable blockade of mechanical allodynia as observed in vehicle-treated rats receiving 10 mg/kg morphine. IMT504 significantly increased hindpaw infiltration of mesenchymal stem cells, CD4+T and B cells, and caused upregulated or downregulated transcript expressions of interleukin-10 and interleukin-1ß, respectively. Also, IMT504 treatment targeted the spleen, with upregulated or downregulated transcript expressions, 6 hours after incision, of interleukin-10 and interleukin-1ß, respectively. Altogether, pre-emptive or postoperative IMT504 provides protection against postincisional pain, through participation of significant immunomodulatory actions, and exhibiting opioid-sparing effects. PERSPECTIVE: This preclinical study introduces the noncoding non-CpG oligodeoxynucleotide IMT504 as a novel modulator of postoperative pain and underlying inflammatory events. The opioid-sparing effects observed for IMT504 appear as a key feature that could contribute, in the future, to reducing opioid-related adverse events in patients undergoing surgical intervention.

Effect of magnesium sulfate with ketamine infusions on intraoperative and postoperative analgesia in cancer breast surgeries: a randomized double-blind trial.

BACKGROUND: Opioids are the cornerstone in managing postoperative pain; however, they have many side effects. Ketamine and Magnesium (Mg) are NMDA receptor antagonists used as adjuvant analgesics to decrease postoperative opioid consumption. OBJECTIVE: We assumed that adding Mg to ketamine infusion can improve the intraoperative and postoperative analgesic efficacy of ketamine infusion alone in cancer breast surgeries. METHODS: Ninety patients aged between 18 and 65 years and undergoing elective cancer breast surgery were included in this prospective randomized, double-blind study. Group K received ketamine 0.5.ßmg.kg...1 bolus then 0.12.ßmg.kg...1.h...1 infusion for the first 24.ßhours postoperatively. Group KM: received ketamine 0.5.ßmg.kg...1 and Mg sulfate 50.ßmg.kg...1, then ketamine 0.12.ßmg.kg...1.h...1 and Mg sulfate 8.ßmg.kg...1.h...1 infusions for the first 24.ßhours postoperative. The primary outcome was the morphine consumption in the first 24.ßhours postoperative, while the secondary outcomes were: intraoperative fentanyl consumption, NRS, side effects, and chronic postoperative pain. RESULTS: Group KM had less postoperative opioid consumption (14.12.ß...ß5.11.ßmg) than Group K (19.43.ß...ß6.8.ßmg). Also, Group KM had less intraoperative fentanyl consumption. Both groups were similar in postoperative NRS scores, the incidence of side effects related to opioids, and chronic neuropathic pain. CONCLUSION: Adding Mg to ketamine infusion can safely improve intraoperative and postoperative analgesia with opioid-sparing effect in cancer breast surgery.

Effect of Standing Intravenous Acetaminophen on Postoperative Opioid Exposure in a Pediatric Cardiac Intensive Care Unit.

This study assessed the association between standing intravenous acetaminophen and opioid exposure after cardiac surgery. Before vs after implementation of a standardized pain pathway, we report decreased opioid exposure, 0.38 milligram per kilogram of morphine equivalents [IQR 0.10-0.81] vs 0.26 milligram per kilogram of morphine equivalents [0.09-0.56] (P = .01) and increased acetaminophen exposure, 3 [2-4] vs 4 [4-5] doses (P < .001).

Randomized Clinical Trial Comparing Quadratus Lumborum Block and Intrathecal Morphine for Postcesarean Analgesia.

OBJECTIVE: To compare the efficacy of quadratus lumborum (QL) block and intrathecal morphine (M) for postcesarean delivery analgesia. METHODS: Thirty-one pregnant women with ≥ 37 weeks of gestation submitted to elective cesarean section were included in the study. They were randomly allocated to either the QL group (12.5 mg 0.5% bupivacaine for spinal anesthesia and 0.3 ml/kg 0.2% bupivacaine for QL block) or the M group (12.5 mg bupivacaine 0.5% and 100 mcg of morphine in spinal anesthesia). The visual analog scale of pain, consumption of morphine and tramadol for pain relief in 48 hours, and side effects were recorded. RESULTS: Median pain score and/or pain variation were higher in the morphine group than in the QL group (p = 0.02). There was no significant difference in the consumption of morphine or tramadol between groups over time. Side effects such as pruritus, nausea, and vomiting were observed only in the morphine group. CONCLUSION: Quadratus lumborum block and intrathecal morphine are effective for analgesia after cesarean section. Patients undergoing QL block had lower postoperative pain scores without the undesirable side effects of opioids such as nausea, vomiting, and pruritus.

OBJETIVO: Comparar a eficácia do bloqueio do quadrado lombar (QL) e da morfina intratecal (M) na analgesia pós-cesariana. MéTODOS: Trinta e uma gestantes com ≥ 37 semanas de gestação submetidas a cesariana eletiva foram incluídas no estudo. Eles foram alocados aleatoriamente no grupo QL (12,5 mg de bupivacaína a 0,5% para raquianestesia e 0,3 ml/kg de bupivacaína a 0,2% para bloqueio de QL) ou no grupo M (12,5 mg de bupivacaína a 0,5% e 100 mcg de morfina na raquianestesia). A escala visual analógica de dor, consumo de morfina e tramadol para alívio da dor em 48 horas e efeitos colaterais foram registrados. RESULTADOS: A mediana do escore de dor e/ou variação da dor foi maior no grupo morfina do que no grupo QL (p = 0,02). Não houve diferença significativa no consumo de morfina ou tramadol entre os grupos ao longo do tempo. Efeitos colaterais como prurido, náuseas e vômitos foram observados apenas no grupo morfina. CONCLUSãO: O bloqueio QL e a morfina intratecal são eficazes para analgesia após cesariana. Os pacientes submetidos ao bloqueio do QL apresentaram menores escores de dor pós-operatória sem os efeitos colaterais indesejáveis dos opioides, como náuseas, vômitos e prurido.

Efficacy of postoperative analgesia with duloxetine in posthemorrhoidectomy pain: a prospective, randomized, double-blind and placebo-controlled trial.

BACKGROUND: To evaluate the effect of duloxetine when added to a multimodal analgesia regimen on posthemorrhoidectomy pain, opioid consumption, and side effects. METHODS: Prospective, randomized, double-blind placebo-controlled trial. This study included 62 patients who underwent hemorrhoidectomy. The patients were randomly assigned to receive oral duloxetine 60 mg or placebo 2 h before and 24 h after surgery. The primary outcomes were pain intensity - measured on an 11-point visual analog pain scale - and cumulative morphine consumption at 12, 24, and 48 postoperative hours. RESULTS: Fifty-two patients completed the study (25 in the duloxetine group and 27 in the placebo group). Pain scores did not differ between duloxetine and placebo: 4.5; 3.0 - 7.0 vs. 5.0; 3.5 - 7.0, p = 0.68 at 12 h, 3.0; 2.0 - 5.0 vs. 3.0; 2.0 - 5.0, p = 0.56 at 24 h, and 2.5; 1.75 - 3.75 vs. 1.5; 0.5 - 3, p = 0.08 at 48 h. Further, cumulative morphine consumption did not differ between the duloxetine and placebo groups: 4; 1.25 - 10.75 mg vs. 7; 1.0 - 12.0 mg, p = 0.68 at 12 h, 9.5; 2.0 - 17.5 mg vs. 8.0; 4.0 - 18.0 mg; p = 0.80 at 24 h, and 11.0; 2.0 - 27.0 mg vs. 10; 4.0 - 24.0 mg, p = 0.78 at 48 h. Side effects did not differ between the groups. CONCLUSIONS: Compared with placebo, duloxetine did not decrease pain intensity or morphine consumption during the first 48 h postoperatively. TRIAL REGISTRATION: The study was retrospectively registered on the Brazilian Clinical Trials Registry (identifier: RBR-9pdgms, registration date: 08/10/2020).

Manejo del dolor posoperatorio en pacientes beneficiarios de una artroplastia total de rodilla: comparación de tres técnicas analgésica / Postoperative pail management in patients underfgoing total knee arthroplaty: comparison of three analgesic techniques

Introducción: La artroplastia total de rodilla (ATR) es un procedimiento quirúrgico muy doloroso en cirugía ortopédica, siendo muy difícil su tratamiento. El objetivo del presente estudio fue comparar 3 estrategias de analgesia post operatoria en el manejo del dolor post ATR. Pacientes y Método: se estudiaron 60 pacientes, divididos en 3 grupos. Grupo 1: Bloqueo iliofascial (BIFC), Grupo 2: Analgesia epidural continua (AEPIC) y Grupo 3: Morfina intratecal (MIT). Se evaluó el dolor post operatorio (DPO) en reposo y movimiento con escala visual análoga en las primeras 24 hrs., consumo de morfina endovenosa (MEV), incidencia de efectos adversos: prurito, náuseas y vómitos (NVPO), retención urinaria (RU). Al término del tratamiento se evaluó la satisfacción del paciente. Resultados: El DPO fue significativamente menor entre las 6 y 24 hrs. en los pacientes del Grupo 3 versus los de los Grupos 1 y 2 (p<0,01). El consumo de MEV fue menor en los pacientes del grupo 3 (p< 0,01). La incidencia de prurito post operatorio y RU fue significativamente mayor en el grupo 3 versus los grupos 1 y 2 (p< 0, 001 y p< 0,008). La hipotensión arterial fue mayor en los grupos 2 y 3 versus el grupo 1 (p< 0,05), siendo más frecuente la hipotensión moderada en el grupo 3 versus a los grupos 1 y 2 (p< 0.01). La calidad de la analgesia fue considerada superior en los pacientes del grupo 3. Conclusión: Las 3 técnicas analgésicas son útiles para el manejo del DPO de una ATR. La MIT presenta menor índice de dolor, mejor calidad de la analgesia percibida por el paciente, pero una mayor incidencia de efectos adversos en relación con el BIFC y AEPIC.

Introduction: Total knee arthroplasty (TKA) is a very painful surgical procedure in orthopedic surgery, making its treatmentvery difficult. The objective of the present study was to compare 3 postoperative analgesia strategies in the management of post TKA pain. Patients and Method: 60 patients, divided into 3 groups, were studied. Group 1: Iliofascial blockade (BIFC), Group 2: Continuous epidural analgesia (AEPIC) and Group 3: Intrathecal morphine (MIT). Postoperative pain (POD) at rest and movement was evaluated with a visual analog scale (EVA) in the first 24 hours, intravenous morphine consumption (VEM), incidence of adverse effects: pruritus, nausea and vomiting (PONV), urinary retention (UR). At the end of treatment, patient satisfaction was evaluated. Results: The DPO was significantly lower between 6 and 24 hours in the patients of Group 3 versus those of Groups 1 and 2 (p<0.01). MEV consumption was lower in patients of group 3 (p<0.01). The incidence of postoperative pruritus and UR was significantly higher in group 3 versus groups 1 and 2 (p<0.001 and p<0.008). Arterial hypotension was greater in groups 2 and 3 versus group 1 (p<0.05), with moderate hypotension being more frequent in group 3 versus groups 1 and 2 (p<0.01). The quality of analgesia was considered superior in patients in group 3. Conclusion: The three analgesic techniques are useful for managing the DPO of a TKA. MIT presents a lower pain index, better quality of analgesia perceived by the patient, but a higher incidence of adverse effects in relation to BIFC and AEPIC.

Pilot study of the effect of therapeutic photobiomodulation on postoperative pain in knee arthroplasty.

Nine participants undergoing primary TKA submitted to spinal anesthesia, sedation, ultrasound-guided obturator and Femoral nerve Block analgesia, and photobiomodulation Therapy (FBMT) were evaluated regarding postoperative pain and morphine consumption. FBMT sessions were performed in the Immediate Postoperative period (IPO) and after 24 hours. Participants received 16.7±15 mg of morphine up to the third postoperative day. At IPO, mean pain score was 4.8±3.2 and 5.6±3.5, at rest and on movement, respectively. Photo biomodulation therapy can be considered an option for mitigating pain for patients undergoing TKA.

Effects of Pharmacologic Treatment for Neonatal Abstinence Syndrome on DNA Methylation and Neurobehavior: A Prospective Cohort Study.

OBJECTIVE: To determine whether pharmacologic treatment for neonatal abstinence syndrome (NAS) is associated with changes in DNA methylation (DNAm) of the mu-opioid receptor gene (OPRM1) and improvements in neonatal neurobehavior. STUDY DESIGN: Buccal swabs were collected from 37 neonates before and after morphine treatment for NAS. Genomic DNA was extracted, and DNAm was examined at 4 cytosine-phosphate-guanine (CpG) sites within the OPRM1 gene. Assessment with the NICU Network Neurobehavioral Scales (NNNS) was also performed before and after NAS treatment. Changes in DNAm (DNAmpost-tx - DNAmpre-tx) and NNNS summary scores (NNNSpost-tx - NNNSpre-tx) were then calculated. Path analysis was used to examine associations among pharmacologic treatment (length of treatment [LOT] and total dose of morphine), changes in DNAm, and changes in NNNS summary scores. RESULTS: DNAm was significantly decreased from pretreatment to post-treatment at 1 of 4 CpG sites within the OPRM1 gene. Neonates also demonstrated decreased excitability, hypertonia, lethargy, signs of stress and abstinence, and increased quality of movement and regulation from pretreatment to post-treatment. Longer LOT and higher morphine dose were associated with greater decreases in DNAm; greater decreases in DNAm were associated with greater decreases in excitability and hypertonia on the NNNS. CONCLUSIONS: Pharmacologic treatment of NAS is associated with decreased DNAm of the OPRM1 gene and improved neonatal neurobehavior. Epigenetic changes may play a role in these changes in neonatal neurobehavior.

Comparison of the suprainguinal fascia iliaca compartment block with continuous epidural analgesia in patients undergoing hip surgeries: a retrospective study.

BACKGROUND AND OBJECTIVE: Pain control is one of the major concerns after major hip surgeries. Suprainguinal fascia iliaca compartment block (S-FICB) is an alternative analgesic technique that can be considered as an effective and less invasive method than epidural analgesia (EA). In this retrospective study, we compared postoperative analgesic efficacy of single shot ultrasound guided S-FICB and EA after major hip surgery. METHODS: We retrospectively examined 150 patients who underwent major hip surgeries and who received S-FICB or EA. Seventy-two patients submitted to EA and 78 patients who received S-FICB were included and their medical records retrospectively reviewed. Morphine consumptions, VAS scores, and side effects were recorded. Patients under antiplatelet or anticoagulant theraphy were also registered. Morphine consumption and VAS scores were the primary endpoints, succes rate and complications were the secondary endpoints of our study. P-values less than 0.05 were considered statistically significant. RESULTS: Morphine consumption was lower at the emergence in the EA group but there was no statistically significant difference between the two groups according to total opioid consumption (0 [0-0] vs 0 [0-0]; p = 0.52). There was no difference between VAS scores in the first 18 hours. Hypotension was significantly higher in the EA group (9 vs 21; p = 0.04). CONCLUSION: In conclusion, S-FICB can provide comparable analgesia with EA in the early postoperative period after hip surgery but VAS scores were found lower in the EA group than S-FICB group after 18th hour. Hypotension has occured more frequently in patients receiving EA.

Beliefs About Morphine in Palliative Care: Results From an Ecuadorian Sample.

Background: Previous research unambiguously establishes the importance of knowledge and education about opioids and pain management in medical care. This article aimed at describing the perception of the general public on the uses and the risks of morphine in palliative care in an Ecuadorian sample, where training and access to those services is limited. Methods: We used an online recruited sample of 257 participants for this cross-sectional descriptive study. Participants responded to an online self-report survey regarding morphine's effects and its relationship with addiction and death in a palliative care context. Results: Analyses indicate that there is a lack of understanding about the effectiveness of morphine and that, overall, participants did not associate morphine with death and dying. Results also show that people in health-related occupations did not differ from the general public in beliefs about the addiction and the effectiveness of morphine. However, occupation and education effects were noted for several other items, as well as whether the participants had direct experiences with palliative care as either a patient or a caregiver. Conclusions: There is still misinformation about opioids such as morphine in the general public and health professionals in Ecuador. Although personal experiences with pain control and palliative care are linked to better knowledge about opioids, education is still necessary to overcome the myths around them. Future research could address the found misconceptions to increase health literacy through education policies and interventions.

Single dose of intraoperative intravenous morphine for analgesia in children undergoing tonsillectomy: Randomized, double-blind clinical trial.

INTRODUCTION: Children undergoing tonsillectomy have severe pain in the postoperative period. One of the pharmacological options for analgesia is opioids, such as morphine. However, the risks of adverse effects, such as increased recovery time from anesthesia and respiratory depression, can limit its use. OBJECTIVES: To evaluate the use of intraoperative intravenous morphine to reduce immediate postoperative pain in children undergoing tonsillectomy. METHODS: In this double-blind randomized study, children aged 3-10 years were submitted to tonsillectomy, with or without adenoidectomy, and divided into two groups. Children in group M received 0.1 mg/kg of intravenous morphine during anesthetic induction, while those in the control group received conventional anesthesia without morphine. Postoperative pain perceptions were assessed at 30, 60, 120, 180 and 240 min after recovery from anesthesia, by the children themselves and also by their parents or guardians, using a facial pain scale. RESULTS: A total of 57 children were included, 30 in the group with morphine and 27 in the group without morphine. According to the children themselves, the postoperative pain was less at the evaluations performed at 30 min after awakening from anesthesia (p =  0.023), while according to their parents/guardians, the pain was less intense in the evaluations performed at 30 (p =  0.002), 60 (p =  0.006) and 180 min (p =  0.007) after awakening. Moreover, postoperative analgesics were less requested by children in the morphine group. No observed side effects were associated with the use of morphine. CONCLUSION: A single dose of intravenous morphine during anesthetic induction reduced the intensity of immediate postoperative pain in children undergoing tonsillectomy, without increasing the time of awakening from anesthesia and with lower consumption of rescue analgesics.

Chemical composition of Zhumeria majdae essential oil and its effects on the expression of morphine withdrawal syndrome and tolerance to the anticonvulsant effect of morphine on pentylenetetrazole-induced seizures in mice / Composição química do óleo essencial de Zhumeria majdae e seus efeitos na expressão da síndrome de abstinência de morfina e tolerância ao efeito anticonvulsivante da morfina em crises induzidas por pentilenotetrazol em camundongos

Abstract Regarding the proven anticonvulsant effect of Zhumeria majdae essential oil (ZMEO) in previous studies we were prompted to investigate the ZMEO effects on the tolerance to the anticonvulsant effects of morphine and the morphine withdrawal syndrome. Tolerance to the morphine anticonvulsant effect was induced in mice by subcutaneous injection of 2.5 mg/kg of morphine for 4 days. Subsequent doses of ZMEO (20 mg/kg) were used to study the expression and development of morphine tolerance. Clonidine was used as the standard drug to inhibit the morphine withdrawal syndrome symptoms. To study the ZMEO effect on withdrawal syndrome, mice received appropriate morphine values for 4 days and on the fifth day, 60 min before administration of naloxone. The effective dose of ZMEO was determined and the number of jumps, stands and changes in the dry stool weight, as symptoms of withdrawal syndrome were evaluated. The dose of 20 mg/kg of ZMEO decreased the tolerance in development and expression groups significantly. Counting the number of jumping, standing and defecation were assessed 30 min after morphine and 1 h after the vehicle and clonidine. The dose of 40 mg/kg ZMEO decreased all the signs of withdrawal syndrome significantly. ZMEO was analyzed by GC/MS and linalool (53.1%) and camphor (23.8%) were characterized as the main components. The results suggest that ZMEO possesses constituent(s) that have activity against tolerance to the anticonvulsant effects of morphine and the morphine withdrawal symptoms.

Resumo Em relação ao efeito anticonvulsivante comprovado do óleo essencial de Zhumeria majdae (ZMEO) em estudos anteriores, fomos instigados a investigar os efeitos do ZMEO em relação à tolerância aos efeitos anticonvulsivantes da morfina e da síndrome de abstinência de morfina. A tolerância ao efeito anticonvulsivante da morfina foi induzida em camundongos por injeção subcutânea de 2,5 mg/kg de morfina por 4 dias. Doses subsequentes de ZMEO (20 mg/kg) foram utilizadas para estudar a expressão e o desenvolvimento da tolerância à morfina. A clonidina foi usada como droga padrão para inibir os sintomas da síndrome de abstinência da morfina. Para estudar o efeito do ZMEO na síndrome de abstinência, os camundongos receberam valores apropriados de morfina por 4 dias e, no 5º dia, 60 minutos antes da administração de naloxona. A dose efetiva de ZMEO foi determinada, e o número de saltos e de permanência e as alterações no peso das fezes secas, conforme os sintomas da síndrome de abstinência, foram avaliados. A dose de 20 mg/kg de ZMEO diminuiu significativamente a tolerância nos grupos de desenvolvimento e expressão. A contagem do número de saltos, permanência e defecação foi avaliada 30 minutos após a morfina e 60 minutos após o veículo e a clonidina. A dose de 40 mg/kg de ZMEO diminuiu significativamente todos os sinais da síndrome de abstinência. O ZMEO foi analisado por GC/MS, e linalol (53,1%) e cânfora (23,8%) foram caracterizados como os principais componentes. Os resultados sugerem que o ZMEO apresenta constituintes que possuem atividade contra a tolerância aos efeitos anticonvulsivantes da morfina e aos sintomas de abstinência da morfina.