The effects of drainage tube on pain and functional recovery after unicompartmental knee arthroplasty / Efeitos do tubo de drenagem na dor e recuperação funcional após artroplastia unicompartimental do joelho

ABSTRACT Objective: The objective of this study was to evaluate the impact of drainage tube placement on postoperative pain, recovery, and opioid consumption within a 72-hour period following unicompartmental knee arthroplasty (UKA). Methods: Patients with medial knee osteoarthritis who underwent UKA from January 2019 to August 2020 were enrolled in the study and divided into two groups based on whether they received a drain postoperatively. Results: The drainage group had significantly lower VAS scores on day 1, day 2, and day 3, in addition to significantly smaller changes in the circumference of the knee joint within 3 days postoperatively (P <0.05). The ROM in the drainage group significantly increased at 3 days and 1 month post-surgery, with a statistically significant difference in morphine consumption between the two groups at 3 days (P<0.05). The incidence of postoperative nausea and vomiting (5 cases) and wound bleeding (1 case) was lower in the drainage group compared to the non-drainage group (P<0.05). Conclusions: The placement of a drainage tube in UKA may reduce the swelling of knee joint and pain, which not only reduces the use of Opioid but also facilitates early functional activities of the knee joint. Level of Evidence III; Retrospective Comparative Study.

RESUMO Objetivo: O objetivo deste estudo foi avaliar o impacto da implantação do tubo de drenagem na dor pós-operatória, na recuperação e no consumo de opioides em um período de 72 horas após a artroplastia unicompartimental do joelho (UKA). Métodos: Pacientes com osteoartrite medial do joelho submetidos à UKA de janeiro de 2019 a agosto de 2020 foram incluídos no estudo e divididos em dois grupos com base no fato de terem ou não recebido um dreno no pós-operatório. Resultados: O grupo de drenagem apresentou escores EVA significativamente menores no dia 1, no dia 2 e no dia 3, além de alterações significativamente menores na circunferência da articulação do joelho em 3 dias de pós-operatório (P <0,05). A ADM no grupo de drenagem aumentou significativamente em 3 dias e 1 mês após a cirurgia, com uma diferença estatisticamente significativa no consumo de morfina entre os dois grupos em 3 dias (P<0,05). A incidência de náuseas e vômitos no pós-operatório(5 casos) e sangramento da ferida (1 caso) foi menor no grupo de drenagem em comparação com o grupo sem drenagem (P<0,05). Conclusão: A utilização de tubo de drenagem na UKA pode reduzir o edema articular do joelho e a dor, reduzindo o uso de opioides e facilitando as atividades funcionais iniciais da articulação do joelho. Nível de Evidência III; Estudo Comparativo Retrospectivo.

Morfina/ketamina versus morfina en el control del dolor postoperatorio de cirugía renal electiva / Morphine/ketamine versus morphine in postoperative pain control for elective renal surgery

Resumen: Introducción: el dolor agudo postoperatorio demora la recuperación funcional del paciente. Objetivo: evaluar utilidad de la ketamina asociada a morfina administrados en bolos intravenosos en el control del dolor agudo postoperatorio de pacientes sometidos a cirugía renal electiva. Material y métodos: realizamos estudio doble ciego en pacientes con dolor postoperatorio moderado-severo sometidos a cirugía renal electiva. Se conformaron dos grupos: grupo MK administramos morfina 0.05 mg/kg más ketamina 0.2 mg/kg y grupo M morfina 0.05 mg/kg más solución salina a 0.9%. Pacientes con dolor de intensidad moderada-severa según escala analógica visual recibieron dosis de morfina cada 20 minutos hasta lograr dolor ligero, registrándose el consumo total de morfina por paciente. La tensión arterial, frecuencia cardíaca y respiratoria, saturación de oxígeno y efectos adversos fueron evaluados con la misma periodicidad. Resultados: el grupo MK mostró menor intensidad del dolor con disminución significativa del consumo de morfina. Ambos grupos resultaron ser similares en cuanto a cifras de tensión arterial, frecuencia cardíaca, frecuencia respiratoria y saturación de oxígeno. Las náuseas y vómitos fueron los efectos adversos de mayor prevalencia, siendo superiores en el grupo morfina. Conclusiones: la asociación morfina-ketamina resultó útil en el control del dolor moderado-severo en pacientes sometidos a cirugía renal electiva.

Abstract: Introduction: acute postoperative pain delays the patient's functional recovery. Objective: to evaluate the utility of ketamine associated with morphine administered in intravenous boluses in the control of acute postoperative pain in patients undergoing elective renal surgery. Material and methods: we conducted a double-blind study in patients with moderate-severe postoperative pain undergoing elective renal surgery. Two groups were formed: group MK administered 0.05 mg/kg morphine plus 0.2 mg/kg ketamine and group M 0.05 mg/kg morphine plus 0.9% saline solution. Patients with pain of moderate-severe intensity according to the visual analogue scale received doses of morphine every 20 minutes until achieving light pain, recording the total consumption of morphine per patient. Blood pressure, heart and respiratory rates, oxygen saturation, and adverse effects were evaluated with the same periodicity. Results: MK group showed lower pain intensity with a significant decrease in morphine consumption. Both groups turned out to be similar in terms of blood pressure, heart rate, respiratory rate and oxygen saturation Figures. Nausea and vomiting were the most prevalent adverse effects, being higher in the morphine group. Conclusions: the morphine-ketamine association was useful in the control of moderate-severe pain in patients undergoing elective renal surgery.

Comparison of two analysis methods of opioid consumption sum in medical institutions / 中国药房

OBJECTIVE To compare the similarities and differences of the two methods in analyzing the use of opioids in third grade class A medical institutions and provide a reference for the management of opioids in medical institutions. METHODS Two methods， Defined Daily Dose （DDD） and Oral Morphine Equivalent （OME）， were used to count the opioid prescription data of five comprehensive medical institutions of third grade class A （named H1-H5） in Shanxi province in 2020， calculate consumption sum of opioid， annual per capita consumption sum， patient cost burden and drug consumption sum ratio， compare the index results presented by the two analysis methods， and explore the application scenarios of the advantages of each of the two evaluation methods. RESULTS The ranking of consumption sum of opioid and patient cost burden calculated by the two methods was the same in the five sample medical institutions， but the ranking of per capita consumption sum was different. Taking the 5 medical institutions as a whole， the top 4 rankings of consumption sum ratio for each species of opioid compared by both methods were the same， i. e. remifentanil＞sufentanil＞oxycodone＞morphine. The ratio of remifentanil was close to 50%. When comparing the ranking of consumption sum ratio in each medical institution， the ranking calculated by the two methods was different for those medical institutions except for H1 medical institutions. The consumption sum ratio of fentanyl calculated by DDD method was significantly higher than that of OME method； whereas consumption sum ratio of remifentanil calculated by OME method was significantly higher than that of DDD method. Perioperative patients had the highest consumption sum ratio， about 50%. The consumption sum ratio of critically ill patients in H3 jwsydey@163.com medical institutions and inpatient patients with cancer pain and other patients in H5 medical institutions calculated by DDD method was significantly higher than that by OME method. There were differences in the order of cost burden of different types of patients calculated by two methods. CONCLUSIONS DDD method can accurately reflect the dosage of opioid drugs and facilitate the monitoring and management of the dosage； OME method can more reflect the analgesic effect and compare the cost burden of patients.

Refractory Diarrhea Associated with Carcinoid Syndrome Improved after Opioid Switching from Fentanyl to Morphine

Background: In the case of refractory diarrhea that cannot be treated with loperamide only, drugs such as octreotide and serotonin receptor antagonists are generally recommended. We have reported a case of refractory diarrhea associated with carcinoid syndrome in which symptoms improved only with opioid switching, without octreotide. Case: We experienced a case of a 28-year-old female with cervical cancer. She was diagnosed with recurrence after cervical cancer surgery and presented with pain and diarrhea. Her diarrhea did not improve sufficiently after taking loperamide. She was admitted to the palliative care hospital for symptom control due to persistent diarrhea and right lower extremity pain associated with bone metastasis. We diagnosed the cause of her diarrhea as carcinoid syndrome by some laboratory examination. For pain management, we switched opioids from transdermal fentanyl to continuous subcutaneous infusion of morphine. It resulted in pain relief and improvement in the frequency of diarrhea, and she was able to be discharged home. Conclusion: In cases of refractory diarrhea and in patients who need opioids, there is one option to use morphine. If it is effective, it may simply resolve both pain and diarrhea and reduce the use of multiple medications.

The effectiveness of erector spina plane, quadratus lumborum blocks, and intrathecal morphine for analgesia after cesarean: a randomized study

SUMMARY OBJECTIVE: This prospective randomized study was conducted at Ataturk University Medical Faculty Hospital, Department of Anesthesia and Reanimation, from June 2022 to May 2023. The aim of this study was to compare the effectiveness of ultrasound-guided erector spinae plane block, quadratus lumborum block, and intrathecal morphine to decrease postoperative pain after cesarean section. METHODS: Sixty-term pregnant women who were scheduled for elective cesarean sections with spinal anesthesia were included. Patients were randomly divided into three groups (n=20 for each group): Group 1: Patients were administered intrathecal morphine during spinal anesthesia; Group 2: Patients performed bilateral erector spinae plane block postoperatively; and Group 3: Patients performed bilateral quadratus lumborum block postoperatively. In the postpartum care unit, patients received intravenous Patient-Controlled Analgesia. The Patient-Controlled Analgesia devices were set to administer an intravenous bolus of 25 μg fentanyl, with a lockout interval of 10 min. Opioid consumption and maximum pain score in the 24 postoperative hours were recorded. RESULTS: Patients in Group 1 had a longer time to first analgesic requirement compared to Group 2 (p=0.017). Opioid consumption and resting and moving visual analog score scores in the first 24 h postoperatively were similar between groups. CONCLUSION: All three methods, including intrathecal morphine, erector spinae plane block, and quadratus lumborum block, are efficacious and comparable in providing postoperative analgesia after cesarean under spinal anesthesia.

Morphine promotes migration and lung metastasis of mouse melanoma cells

Abstract Background Morphine is an analgesic agent used for cancer pain management. There have been recent concerns that the immunosuppressant properties of morphine can also promote cancer metastasis. Morphine is an agonist for toll like receptor 4 (TLR4) that has a dual role in cancer development. The promotor or inhibitor role of morphine in cancer progression remains controversial. We investigated the effects of morphine on migration and metastasis of melanoma cells through TLR4 activation. Methods Mouse melanoma cells (B16F10) were treated with only morphine (0, 0.1, 1, and 10 μM) or in combination with a TLR4 inhibitor (morphine10 μM +CLI-095 1μM) for either 12 or 24 hours. Migration of cells was analyzed by transwell migration assays. Twenty C57BL/6 male mice were inoculated with B16F10 cells via the left ventricle of the heart and then randomly divided into two groups (n = 10 each) that received either morphine (10 mg.kg−1, sub-q) or PBS injection for 21 days (control group). Animals were euthanized and their lungs removed for evaluation of metastatic nodules. Results Morphine (0.1, 1, and 10 μM) increased cell migration after 12 hours (p < 0.001) and after 24 hours of treatment with morphine (10 μM) (p < 0.001). Treatment with CLI-095 suppressed migration compared to cells treated with morphine alone (p < 0.001). Metastatic nodules in the morphine-treated group (64 nodules) were significantly higher than in the control group (40 nodules) (p < 0.05). Conclusion Morphine increases the migration and metastasis of mouse melanoma cells by activating TLR4.

Ketamine pour la gestion de la douleur post hystérectomie au CHU Professeur Zafisaona Gabriel Mahajanga Madagascar / Ketamine for the management of post-hysterectomy pain at the Professor Zafisaona Gabriel University Hospital, Mahajanga, Madagascar

Une analgésie multimodale est incontournable pour la prise en charge de la douleur post opératoire. L'objectif de notre étude était de montrer l'intérêt de l'utilisation de la kétamine, avec son effet analgésique, parmi les différentes molécules disponibles. Méthodes : Il s'agit d'une étude prospective monocentrique en simple aveugle de 31 cas d'hystérectomie programmée sur une période de 6 mois (mai­octobre 2016) divisée en deux groupes soumis au même protocole anesthésique : un groupe recevant de la kétamine en bolus suivi d'une perfusion continue peropératoire et sur les premières 24 heures et un groupe contrôle sans kétamine. En période post opératoire les deux groupes bénéficient d'une analgésie multimodale. L'analyse statistique a été faite par le test de Student. Résultats : Les scores de douleur diffèrent peu en moyenne sur les 24 heures de surveillance, tandis qu'une épargne morphinique importante est notée dans le groupe kétamine de l'ordre de 50% avec une valeur de p<0,001 fortement significative. A côté nous n'avons constaté aucun effet indésirable notable. Conclusion : L'adjonction de kétamine même de brève durée dans la prise en charge de la douleur post opératoire a permis de baisser considérablement la consommation morphinique

Analysis of constipation status and influencing factors in patients with lung cancer during postoperative hospitalization / 中国胸心血管外科临床杂志

@#Objective     To investigate the current status of constipation during postoperative hospitalization and the factors associated with moderate to severe constipation at discharge in lung cancer patients. Methods     Lung cancer patients who underwent surgery in 6 tertiary hospitals in Sichuan Province from November 2017 to January 2020 were enrolled. The MD Anderson Symptom Scale-Lung Cancer Module was used to collect postoperative constipation scores. Unconditional logistic stepwise regression was used to analyze the related influencing factors for moderate to severe constipation on the day of discharge. Results     Finally 337 patients were collected. There were 171 males and 166 females, with an average age of 55.0±10.3 years. Constipation scores of lung cancer patients increased from postoperative day 1 to day 3, and showed a decreasing trend from day 3 to day 7. Moderate to severe constipation was present in 68 (20.2%) patients at discharge. The postoperative hospital stay (OR=0.743, P<0.001) and the dose of morphine used during postoperative hospitalization (OR=1.002, P=0.015) were influencing factors for moderate to severe constipation at discharge in lung cancer patients. Conclusion    Lung cancer patients have the most severe constipation on postoperative day 3. Moderate to severe constipation at discharge is associated with the postoperative hospital stay and the dose of morphine used during postoperative hospitalization.

Role of circTmeff-1 in morphine addiction memory of mice / 中国药理学与毒理学杂志

In addition to the essential pharmacologi-cal effects of opioids,situational cues associated with drug addiction memory are key triggers for drug seeking.CircRNAs,an emerging hotspot regulator in crown genet-ics-play an important role in central nervous system-relat-ed diseases.However,the internal mediating mechanism of circRNA in the field of drug reward and addiction mem-ory remains unknown.Here,we trained mice on a condi-tional place preference(CPP)model and collected nucle-us accumbens(NAc)tissues from day 1(T0)and day 8(T1)for high-throughput RNA sequencing.qRT-PCR revealed that circTmeff-1 was highly expressed in the NAc core but not in the NAc shell,suggesting that it plays a role in addiction memory formation.Meanwhile,the reverse regulation of circTmeff-1 by adeno-associated viruses could both inhibit the formation of addiction mem-ory in the NAc core or shell.Subsequently,the GO and KEGG analyses indicated 21 that circTmeff-1 might regu-late the addiction memory via the MAPK and AMPK path-ways.These findings suggest that circTmeff-1 in NAc plays a crucial role in morphine-dependent memory for-mation.

Randomized Clinical Trial Comparing Quadratus Lumborum Block and Intrathecal Morphine for Postcesarean Analgesia / Ensaio Clínico Randomizado Comparando Bloqueio do Quadrado Lombar e Morfina Intratecal Para Analgesia Pós-cesariana

Abstract 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.

Resumo 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.

Epidural morphine for chronic pain in a patient with peripheral neuropathy and DRESS syndrome. Case report / Morfina peridural para tratamento de dor crônica em paciente com polineuropatia periférica e síndrome DRESS. Relato de caso

ABSTRACT BACKGROUND AND OBJECTIVES: Peripheral neuropathy is a rare condition with many etiologies. Common symptoms are numbness, paresthesia, weakness and neuropathic pain. Treatment consists in frst-line agents such as anticonvulsants and some antidepressants. Te aim of this study was to report a case of chronic pain refractory to several therapies in a patient with absolute contraindication to the use of all anticonvulsants and antidepressants drugs. CASE REPORT: Female patient, a 40-year-old treated for trigeminal neuralgia with decompression that developed chronic occipital pain refractory to radiofrequency and onset of transient and bilateral T4 sensory and motor polyneuropathy after viral meningitis. In addition, she showed a severe pharmacodermy (Drug Rash with Eosinophilia and Systemic Symptoms- DRESS Syndrome) after using carbamazepine and other anticonvulsants, as well as allergy to all analgesics and opioids except morphine. Epidural puncture with insertion of a catheter was performed aiming at a 5-day test through intermittent epidural morphine bolus to assess the possibility of morphine pump implantation. CONCLUSION: The test was successful and the patient referred to the neurosurgery team. At the 6-month follow-up after the insertion of the morphine intrathecal pump, the strategy has proven to be efective in controlling pain secondary to polyneuropathy.

RESUMO JUSTIFICATIVA E OBJETIVOS: Neuropatia periférica é uma condição rara, de etiologia multifatorial. Dormência, parestesia, redução de força muscular e dor neuropática são sintomas comuns. O tratamento consiste em uso de anticonvulsivantes e antidepressivos. O objetivo deste estudo foi relatar o caso de dor crônica refratária a diversas terapias de uma paciente com contraindicação absoluta para uso de todos os fármacos anticonvulsivantes e antidepressivos. RELATO DO CASO: Paciente do sexo feminino, 40 anos, com história de neuralgia do trigêmeo abordada previamente com cirurgia, com cefaleia occipital crônica refratária à radiofrequência e polineuropatia bilateral T4 sensorial e motora após meningite viral. No curso do tratamento, apresentou grave farmacodermia (Drug Rash with Eosinophilia and Systemic Symptoms - Síndrome DRESS) após o uso de carbamazepina e outros anticonvulsivantes, além de reação alérgica a todos analgésicos e opioides, exceto morfina. Optou-se por analgesia teste por via peridural, durante 5 dias, com bolus intermitentes e diários de morfina para avaliação de possibilidade de implante de bomba de morfina. CONCLUSÃO: O teste foi considerado bem-sucedido e a paciente encaminhada para neurocirurgia. No seguimento de 6 meses após implante de bomba por via subaracnoidea, esta estratégia se mostrou eficaz no controle da dor secundária à polineuropatia.

Anestesia espinal con bupivacaína más morfina en cirugía de urgencia de fractura intertrocantérica de cadera / Spinal anesthesia with bupivacaine plus morphine in urgent intertrochanteric hip fracture surgery

Introducción: La fractura de cadera en el anciano es una entidad frecuente y tiene gran incidencia en el mundo y en Cuba por el envejecimiento. Objetivo: Evaluar la eficacia de la anestesia espinal con bupivacaína más morfina en la cirugía de fractura intertrocantérica de cadera. Métodos: Se realizó un estudio clínico, experimental, no aleatorizado, prospectivo y de corte longitudinal en el Hospital Universitario Faustino Pérez Hernández de Matanzas de octubre de 2017 a octubre de 2019. El universo estuvo conformado por todos los pacientes quirúrgicos con fractura de cadera del hospital. La muestra se realizó por muestreo intencional, por 120 pacientes elegidos a criterio de los investigadores. Grupo control (B): Anestesia subaracnoidea con bupivacaína 0,5 por ciento 10 mg. Grupo estudio (M): Anestesia subaracnoidea con bupivacaína 0,5 por ciento 7 mg más 0,2 mg de morfina. Cada grupo estuvo integrado por 60 pacientes. Las variables analizadas fueron las siguientes: grupos de edades, género, estado físico, nivel de punción, tiempo de inicio del bloqueo motor, hipotensión arterial, uso de vasopresores y complicaciones secundarias a la técnica anestésica. Resultados: Predominó grupo de 84 y 90 años, género femenino y ASA III. La punción lumbar se realizó entre L3-L4. El tiempo de inicio del bloqueo motor fue 1,3 veces menor en el grupo M. Prevaleció la hipotensión arterial en el grupo B; y uso de vasopresores en ambos grupos. Predominó el prurito, grupo M, y la bradicardia, grupo B como complicaciones. Conclusiones: La asociación bupivacaína/morfina en anestesia espinal en adulto mayor para fractura de cadera proporciona mejores resultados sin complicaciones mayores(AU),

Introduction: Hip fracture in the elderly patient is a frequent entity with a high incidence worldwide and in Cuba due to aging. Objective: To assess the efficacy of spinal anesthesia with bupivacaine plus morphine in intertrochanteric hip fracture surgery. Methods: A clinical, experimental, nonrandomized, prospective, prospective and longitudinal study was carried out in Faustino Pérez Hernández University Hospital of Matanzas, from October 2017 to October 2019. The universe consisted of all surgical patients with hip fracture attended in the hospital. The sample was made by purposive sampling, consisting of 120 patients chosen at the discretion of the researchers. The control group (B) was administered subarachnoid anesthesia with 10 mg of bupivacaine 0.5 percent. The study group (M) was administered subarachnoid anesthesia with 7 mg of bupivacaine 0.5 percent. plus 0.2 mg of morphine. Each group consisted of 60 patients. The following variables were analyzed: age groups, gender, physical condition, puncture level, motor block onset time, arterial hypotension, use of vasopressors, and complications secondary to the anesthetic technique. Results: The predominant age group was 84 and 90 years old, together with female gender and ASA III. Lumbar puncture was performed between L3 and L4. The motor block onset time was 1.3 times shorter in the M group. Arterial hypotension prevailed in the B group; apart from the use of vasopressors in both groups. As complications, there was a predominance of pruritus in the M group and bradycardia in the B group. Conclusions: The association bupivacaine/morphine in spinal anesthesia for hip fracture among elderly adults provides better outcomes without major complications(AU)

Morphine counteracts the effects of paclitaxel in triple-negative breast cancer cells

Background & objectives: Several studies have provided evidence that opioids may play a role in cancer recurrence and metastasis. Multiple research data indicate that morphine can act as a proliferative or suppressive agent on tumour cells depending on the applied concentration. Therefore, this study was aimed to investigate whether the presence of clinically relevant concentrations of morphine has any effect on the efficacy of paclitaxel, a widely used chemotherapeutic drug, on the viability and apoptosis of human triple-negative breast cancer cell line. Methods: MDA.MB.231 cells were treated with paclitaxel in the presence or absence of morphine and examined for cell proliferation by the MTT assay. In addition, the effect of morphine on paclitaxel- induced apoptosis was investigated by flow cytometric assay and by the ratio of Bax/Bcl-2 mRNA expression levels with quantitative real-time (qRT)-PCR. Results: Morphine significantly increased the proliferation of breast cancer cells at low concentrations (0.1-2.5 ?M) but higher concentrations showed cytotoxic effect. Pre-treatment with 0.1 or 1 ?M of morphine decreased the paclitaxel-induced cytotoxicity, the proportion of apoptotic cell, and the ratio of Bax/Bcl-2 mRNA expressions. Interpretation & conclusions: Our data suggest that morphine promotes breast cancer cell viability at clinically relevant plasma concentrations and reduces the apoptotic effect of paclitaxel. This interaction may be very important in clinical settings; however, more studies are needed to explore the plausible mechanisms of interaction and to correlate such findings through in vivo animal studies as well as clinically.

Preclinical evaluation of analgesic activity of hydroalcoholic extract of Costus pictus leaves in Wistar albino rats

Background: Pain is the most common symptom in various pathological conditions requiring appropriate treatment with analgesics. Use of analgesics is limited by various adverse drug effects. The present study was aimed to evaluate the analgesic activity of hydroalcoholic extract of Costus pictus leaves in Wistar albino rats. Aim and Objective: The objective of this study is to evaluate the analgesic activity of hydroalcoholic extract of C. pictus leaves in Wistar albino rats. Materials and Methods: The study was conducted on 30 Wistar albino rats and was divided into five groups each of six rats. Group-I (Sterile water-equivalent volume/po), Group-II Morphine (5 mg/kg/ip), Group-III CPHAE (200 mg/kg/po), Group-IV CPHAE (400 mg/kg/po), and Group-V Diclofenac (12.5 mg/kg/po). All the rats were administered respective drugs before starting of 30 min of experiment. Central analgesic (Tail clip and hot plate) and peripheral analgesic (Writhing test) methods were used to evaluate the analgesic activity. The data were recorded and analyzed with SPSS software. Results: Group-II, III, IV and V showed significant analgesic activity compared to Group-I in both central and peripheral animal models. Group-II showed significant effect compared to Group-III and IV in the central analgesic activity. Group-V showed significant effect compared to Group-III and IV in peripheral analgesic activity. Group-IV showed significant effect compared to Group-III. Conclusion: High dose of (400 mg/kg) C. pictus plant extract showed significant analgesic activity in the central and peripheral animal models compared to low dose.

Administración prolongada de morfina intratecal por bomba de infusión implantada, en un caso de dolor crónico no oncológico / Prolonged administration of intratecal morphine by infusion pump implanted in a case of non-oncological chronic pain / Administração prolongada de morfina intratecal por bomba de infusão implantada, em caso de dor crônica não oncológica

Introducción: Se describe la evolución de un paciente que recibe morfina intratecal mediante una bomba de infusión, que le fuera implantada hace 14 años para tratamiento de su dolor lumbar crónico post-laminectomía. Material y método: Requería la administración de 60 mg/día de morfina subcutánea que le provocaban efectos secundarios que no toleraba, y múltiples internaciones para control del dolor. Se le implantó una bomba de infusión continua (Isomed) conectada a un catéter subaracnoideo, que libera 1 ml/día, y requiere ser llenada cada 60 días. Resultados: Se observó una disminución del dolor promedio de 50% al año, y de 75% a los 6 y 14 años. Requirió un aumento progresivo de las dosis de llenado, que pasaron de 30 mg de morfina (0.5 mg/día) al inicio, a 40 mg de morfina (0.66 mg /día) al año, a 70 mg de morfina (1.16 mg/día) a los 6 años, a 140 mg (2.33 mg/día) a los 14 años. No se registraron complicaciones médicas graves. Mantuvo constipación y sudoración durante todo el período, e instaló un hipogonadismo secundario con trastornos de la libido y de la erección que fueron corregidos con la administración de testosterona. No requirió más internaciones por dolor. No se observaron complicaciones relacionadas con el funcionamiento o llenado de la bomba, ni vinculadas al catéter. El paciente manifestó estar satisfecho con el implante. Discusión: A pesar del aumento de las dosis de llenado, expresión del desarrollo de tolerancia, las dosis de morfina/día requeridas son francamente inferiores al límite recomendado. Conclusiones: El balance del riesgo-beneficio del implante resultó positivo, considerando el mejor control del dolor logrado, las menores dosis de morfina utilizadas, así como la ausencia de complicaciones graves y de internaciones para control del dolor.

Introduction: The evolution of a patient receiving intrathecal morphine through an infusion pump that was implanted 14 years ago for the treatment of chronic post-laminectomy low back pain is described. Material and method: It required the administration of 60 mg / day of subcutaneous morphine that caused side effects that did not tolerate, and multiple hospitalizations for pain control. He was implanted with a continuous infusion pump (Isomed) connected to a subarachnoid catheter, which releases 1 ml / day, and needs to be filled every 60 days. Results: An average pain decrease of 50% per year, and 75% at 6 and 12 years was observed. It required a progressive increase in filling doses, which went from 30 mg of morphine (0.5 mg / day) at the beginning, to 40 mg of morphine (0.66 mg / day at the first year, to 70 mg of morphine (1.16 mg / day) at the sixth year, at 140 mg (2.33 mg / day) at the fourteen year. No serious medical complications were recorded, he maintained constipation and sweating throughout the period, and installed secondary hypogonadism with libido and erection disorders, that were corrected with the administration of testosterone. No further hospitalizations were required due to pain. No complications were observed related to the operation or filling of the pump or linked to the catheter. The patient stated that he was satisfied with the implant. Discussion: Despite the increase in filling doses, expression of tolerance development, the required morphine / day doses are frankly below the recommended limit. Conclusions: The risk-benefit balance of the implant was positive, considering the best pain control, the lowest doses used, the absence of serious complications, and the lack of hospitalizations for pain control.

Introdução: Descreve-se a evolução de um paciente que recebeu morfina intratecal através de uma bomba de infusão, implantada há 14 anos para o tratamento de lombalgia crônica pós-laminectomia. Material e método: Necessitou de administração de 60 mg/dia de morfina por via subcutânea, que provocou efeitos colaterais intolerantes, e múltiplas internações para controle da dor. Foi implantada uma bomba de infusão contínua (Isomed) conectada a um cateter subaracnóideo, que libera 1 ml/dia, necessitando de reenchimento a cada 60 dias. Resultados: Observou-se redução média da dor de 50% em um ano e 75% em 6 e 14 anos. Foi necessário um aumento progressivo das doses de enchimento, que passaram de 30 mg de morfina (0,5 mg/dia) no início, para 40 mg de morfina (0,66 mg/dia) por ano, para 70 mg de morfina (1,16 mg/dia) dia) aos 6 anos, para 140 mg (2,33 mg/dia) aos 14 anos. Não foram registradas complicações médicas graves. Manteve constipação e sudorese durante todo o período e desenvolveu hipogonadismo secundário com distúrbios de libido e ereção que foram corrigidos com administração de testosterona. Ele não necessitou de mais hospitalizações por dor. Não foram observadas complicações relacionadas à operação ou enchimento da bomba, ou relacionadas ao cateter. O paciente afirmou estar satisfeito com o implante. Discussão: Apesar do aumento das doses de enchimento, expressão do desenvolvimento da tolerância, as doses necessárias de morfina/dia são francamente inferiores ao limite recomendado. Conclusões: A relação risco-benefício do implante foi positiva, considerando o melhor controle da dor alcançado, as menores doses de morfina utilizadas, bem como a ausência de complicações graves e internações para controle da dor.

Single dose of intraoperative intravenous morphine for analgesia in children undergoing tonsillectomy: Randomized, double-blind clinical trial / Dose única de morfina endovenosa intraoperatória para analgesia de crianças submetidas à amigdalectomia: ensaio clínico randomizado duplo cego

Abstract 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.

Resumo Introdução Crianças submetidas a amigdalectomias apresentam dor intensa no pós-operatório. Uma das opções farmacológicas de analgesia são os opioides, como a morfina. No entanto, os riscos de efeitos adversos, como aumento do tempo de recuperação da anestesia e depressão respiratória, podem limitar o seu uso. Objetivos Avaliar o uso de morfina endovenosa intraoperatória na redução da dor pós-operatória imediata de crianças submetidas a amigdalectomia. Método Neste estudo cego randomizado, crianças de 3 a 10 anos foram submetidas a amigdalectomia, com ou sem adenoidectomia, e divididas em dois grupos. As crianças do grupo M receberam 0,1 mg.kg-1 de morfina endovenosa na indução anestésica, enquanto as do grupo controle receberam anestesia convencional sem morfina. As percepções de dor no pós-operatório foram avaliadas aos 30, 60, 120, 180 e 240 min após a recuperação da anestesia, pelas próprias crianças e também pelos seus pais ou responsáveis, com uma escala de dor pela face. Resultados Foram incluídas 57 crianças, 30 no grupo com morfina e 27 no grupo sem morfina. De acordo com as próprias crianças, a dor pós-operatória foi menor durante as avaliações feitas aos 30 minutos após o despertar da anestesia (p = 0,023), enquanto segundo seus pais/responsáveis a dor foi menos intensa nas avaliações feitas aos 30 (p = 0,002), 60 (p = 0,006) e 180 minutos (p = 0,007) após o despertar. Além disto, analgésicos no pós-operatório foram menos solicitados pelas crianças do grupo da morfina. Não foram observados efeitos colaterais associados ao uso da morfina. Conclusão Uma dose única de morfina endovenosa durante a indução anestésica reduziu a intensidade da dor pós-operatória imediata de crianças submetidas a amigdalectomia, sem aumento do tempo de despertar da anestesia e com menor consumo de analgésicos de resgate.

Efficacy and safety of hydromorphone for postoperative analgesia in children / 中国小儿急救医学

Objective:To investigate the efficacy and safety of hydromorphone for postoperative analgesia in children with congenital heart disease, and provide a suitable reference dose for postoperative analgesia in children.Methods:Using a prospective study, 157 patients with congenital heart disease(ASA Ⅱ- Ⅳ) admitted to pediatric intensive care unit at Children′s Hospital of Chongqing Medical University from November 2019 to November 2021 were randomly divided into five groups.Low-dose hydromorphone group (H1 group, 30 cases): hydromorphone dose ≥2 and <3 μg/(kg·h), hydromorphone medium-dose group (H2 group, 30 cases): hydromorphone dose ≥3 and <4 μg/(kg·h), high-dose hydromorphone group (H3 group, 31 cases): hydromorphone dose ≥4 and ≤5 μg/(kg·h), sufentanil group (S group, 36 cases): the dose of sufentanil was 0.08 μg/(kg·h), morphine group (M group, 30 cases): the dose of morphine was 20 μg/(kg·h). The five groups of children received midazolam 2 μg/(kg·min) intravenously at the same time as sedative therapy.Pain score and sedation score were scored at 1 h, 4 h, 8 h, 12 h, and 24 h after operation.Heart rate, mean arterial pressure, blood glucose, lactate, and serum cortisol levels were also monitored and detected, and the occurrence of adverse reactions, the number of cases requiring additional analgesic and sedative drugs, as well as the duration of mechanical ventilation were compared.Results:(1) There were no significant differences regarding the age, body weight, cardiopulmonary bypass time, pediatric critical illness score and ASA score among five groups (all P>0.05). (2) There was no significant difference in the levels of respiration, heart rate, blood sugar, lactate and serum cortisol among five groups after operation.There was no significant difference in preoperative mean arterial pressure among the groups, but there was significant difference in the postoperative mean arterial pressure among the groups at 4 h and 8 h( P<0.05). (3) The analgesic satisfaction of H1 group, H2 group and H3 group at 1 h, 4 h, 12 h and 24 h after operation was significantly higher than that in M group ( P<0.05). There was no significant difference in analgesic satisfaction among H1 group, H2 group and H3 group at each time point.(4) The sedation satisfaction of H1 group, H2 group and H3 group at 4 h and 24 h after operation was significantly higher than that in M group ( P<0.05). There was no significant difference in sedation satisfaction among H1 group, H2 group and H3 group at each time point.(5) There was no significant difference in postoperative analgesia satisfaction and sedation satisfaction between H1 group, H2 group, H3 group and S group.(6) Children in H1 group[1(0, 2)], H2 group[1(0, 2)], H3 group[1(0, 2)] had fewer additional doses within 24 hours than that in M group[2(2, 3)]( P<0.05), and fewer children in H1 group, H2 group and H3 group had been given analgesic sedatives than that in M group ( P<0.05); The extubation time was shortest in H2 group and S group[H2 group(88.3±2.9) h, S group(85.9±3.0) h]. (7) There were no adverse reactions in H1 group, H2 group, H3 group and S group, and there were two cases of apnea in M group. Conclusion:The analgesic effect of hydromorphone in children with congenital heart disease after surgery is better than that of morphine, and the effect of hydromorphone is comparable to that of sufentanil.Hydromorphone 3-4 μg/(kg·h)+ midazolam 2 μg/(kg·min) can achieve satisfactory analgesic and sedative effects in children after congenital heart surgery, with few adverse reactions, safe and reliable, which is an excellent choice for postoperative analgesia and sedation in children.

Insulin replacement prevents the acquisition but not the expression of morphine-induced conditioned place preference in streptozotocin-induced diabetic rats

Abstract Insulin receptors have distributed in all brain regions, including the nucleus Accumbens (NAc), and where is implicated in the reward properties of drugs. It is well known that insulin signaling can regulate dopamine release. Therefore, in the present study, we tried to examine the effect of insulin replacement on the acquisition and expression of morphine-induced conditioned place preference (CPP) in diabetic rats. Forty-eight male Wistar rats were divided into two non-diabetic (Naïve) and diabetic groups rendered by a single injection of streptozotocin (STZ). These groups separately received insulin (10U/kg) or saline (1 ml/kg) one hour prior to morphine administration (5mg/kg;s.c.) during conditioning days (acquisition phase) or post-conditioning day (expression phase) in the CPP paradigm. In this paradigm, conditioning score (CS) and locomotion activity were recorded by Ethovision. The STZ-induced diabetic rats displayed higher CS compared to naïve rats (P<0.05). This effect was abolished in all diabetic rats that received insulin during conditioning days but not the expression phase. This study has provided evidence that insulin plays a modulatory role in morphine-induced CPP, and insulin replacement during the acquisition phase could reduce the rewarding properties of morphine in diabetes conditions through a possible modulating effect on dopamine release in the NAc region

Comparative study on analgesic effect of tetrodotoxin in four acute pain models / 药学实践杂志

Objective To evaluate the analgesic effect of tetrodotoxin (TTX) in four types of acute pain models and provide experimental support for its rational application. Methods Mice or rats were intramuscularly pretreated with morphine (1 mg/kg) or TTX (0, 0.5, 1, 2, 4 and 8 μg/kg) 40 min before acetic acid writhing test, formalin stimulation test, hot plate test or tail flick test. Pain response or pain threshold were recorded, and inhibition rate was calculated during the tests. The arachidonic acid of serum was determined by Elisa. Results Significant analgesic effects were observed with morphine in all four acute pain models. TTX dose-dependently reduced the number of writhing induced by acetic acid and inhibited the pain response induced by formalin during phase I and phase II, with the highest inhibition rate of more than 80.00% in two pain models. TTX showed analgesic effect in tail flick test and hot plate test, with the highest inhibition rate of 25.00% and 19.79%, respectively. Both acetic acid and formalin increased arachidonic acid in animal serum, but TTX had no significant inhibitory effect on the releasing of arachidonic acid. Conclusion TTX showed significant analgesic effect in the chemical stimulation pain models induced by acetic acid and formalin, but limited analgesic effect was observed on the physical stimulation pain model induced by heat (hot plate and hot water). TTX may produce analgesic effect by blocking the inflammatory mediators mediating pain response.

Clinical efficacy comparison between hydromorphone and morphine subcutaneous injection analgesia for cancer outbreak pain / 肿瘤研究与临床

Objective:To explore the clinical effects and adverse reactions of hydromorphone versus morphine subcutaneous injection analgesia for cancer outbreak pain.Methods:A total of 98 patients with cancer outbreak pain admitted to Xuzhou Central Hospital were selected. According to the random number table method, the patients were divided into the observation group (receiving subcutaneous injection of hydromorphone for analgesia) and the control group (receiving subcutaneous injection of morphine for analgesia), 49 cases in each group. The numerical rating scale (NRS) scores and quality of life (QOL) scores, pain relief effects, serum β-endorphin, substance P, 5-hydroxytryptamine levels and the incidence of adverse reactions were compared between the two groups.Results:The NRS scores of the two groups after treatment were decreased compared with those before treatment (all P < 0.05); and the NRS score of the observation group was lower than that of the control group after treatment [(2.4±0.4) scores vs. (3.2±0.5) scores, t = 8.69, P < 0.001]; the QOL scores of the two groups after treatment were higher than those before treatment (all P < 0.05); and there were no statistically significant difference in QOL scores after treatment between the two groups [(46±7) scores vs. (43±7) scores, t = 1.62, P = 0.109]. The total effective rate of pain relief of the observation group was higher than that of the control group [93.88% (46/49) vs.79.59% (39/49), χ2 = 4.35, P = 0.037]. The serum β-endorphin, substance P, 5-hydroxytryptamine levels of the two groups after treatment were decreased compared with those before treatment (all P < 0.05). β-endorphin, substance P and 5-hydroxytryptamine of the observation group were lower than those of the control group after treatment[β-endorphin: (85±15) ng/L vs. (98±17) ng/L, substance P: (2.1±0.3) μg/ml vs. (2.4±0.4) μg/ml, 5-hydroxytryptamine: (0.31±0.05) ng/L vs.(0.38±0.06) ng/L; t values were 3.75, 3.63, 6.27, all P < 0.05). Compared with the control group, the incidence of adverse reactions like skin pruritus, nausea and vomiting of the observation group were lower (all P < 0.05). Conclusions:Compared with subcutaneous injection of morphine for analgesia, hydromorphone can better alleviate the pain of patients with cancer outbreak pain, decrease the level of pain mediators, and reduce the incidence of skin pruritus, nausea and vomiting.