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- Transversus Abdominis Plane Block Reduces Morphine Consumption in the Early Postoperative Period following Microsurgical Abdominal Tissue Breast Reconstruction: A Double-Blind, Placebo-Controlled, Randomized Trial. [JOURNAL ARTICLE]
- Plast Reconstr Surg 2014 Nov; 134(5):870-878.
The analgesic efficacy of the transversus abdominis plane peripheral nerve block following abdominal tissue breast reconstruction has not been studied in a randomized controlled trial.The authors conducted a double-blind, placebo-controlled, 1:1 allocation, two-arm parallel group, superiority design, randomized controlled trial in patients undergoing microsurgical abdominally based breast reconstruction. Intraoperatively, epidural catheters were inserted under direct vision through the triangle of Petit on both sides of the abdomen into the transversus abdominis plane just before rectus fascial closure. Patients received either bupivacaine (study group) or saline (placebo group) through the catheters for 2 postoperative days. All patients received hydromorphone by means of a patient-controlled analgesic pump. The primary outcome was the difference in the parenteral opioid consumption on each postoperative day between the groups. The secondary outcome measures included the following: total in-hospital opioid; antinausea medication; pain, nausea, and sedation scores; Quality of Recovery Score; time to ambulation; and hospital stay duration.Between September of 2011 and June of 2013, 93 patients were enrolled: 49 received bupivacaine and 44 received saline. There were 11 postoperative complications (13 percent); none were related to the catheter. Primary outcomes were completed by 85 of 93 patients (91.3 percent); the mean parenteral morphine consumption was significantly reduced on postoperative day 1 in the bupivacaine group (20.7 ± 20.1 mg) compared with 30.0 ± 19.1 mg in the control group (p = 0.02). There were no significant differences in secondary outcomes.Following abdominally based breast reconstruction, transversus abdominis plane peripheral nerve block is safe and significantly reduces morphine consumption in the early postoperative period.Therapeutic, II.
- [Opioids can modulate the immune system.] [JOURNAL ARTICLE]
- Ugeskr Laeger 2014 Jan 27; 176(5A)
Opioids can modulate and suppress the immune system through central mediated mechanisms. Morphine increases replication and spread of HIV-1. Evidence suggests that morphine can also enhance growth and spread of some cancer diagnoses like breast-, prostate- and non-small cell lung cancer. The mechanisms behind the effects of morphine are mainly mediated by inhibiting apoptosis of cancer cells and by stimulation of angiogenesis. Some other opioid agonists seem to be depleted from these effects. Prospective studies are needed to clarify the immunosuppressive effects of opioids in cancer pain management.
- Comparing the effects of morphine sulfate and diclofenac suppositories on postoperative pain in coronary artery bypass graft patients. [Journal Article]
- Anesth Pain Med 2014 Oct; 4(4):e19423.
Simple and efficient way of pain management after Coronary Artery Bypass Graft (CABG) surgery is an important aspect of patients' care.This study aimed to compare the effects of morphine and diclofenac suppositories on postoperative pain management.In this double-blinded clinical trial study, 120 patients aged 30-65 years old, undergone CABG, were equally divided into two groups of A (morphine) and B (diclofenac). All patients were anesthetized with intravenous fentanyl 10 μg/kg, etomidate 0.2 mg/kg and cisatracurium 0.2 mg/kg. Anesthesia was maintained with oxygen 50% and air 50%, propofol 50 μg/kg/min, fentanyl 1-2 μg/kg/h and atracurium 0.6 mg/kg/h. Analgesics were administered after the operation at intensive care unit (ICU) and Visual Analogue Score (VAS) was evaluated in both groups in 4-hour intervals after extubation for 24 hours. After extubation in case of VAS > 3, morphine suppository 10 mg (group A) or diclofenac suppository 50 mg (group B) was administered for patients.No significant statistical relationship was found between the two groups regarding gender, age, BMI, paracetamol consumption, length of operation time, cardiopulmonary bypass pump (CPB) time, and stay time at ICU (P Value ≥ 0.05). Total dosage of used morphine was 22 ± 8.3 mg in each patient and total dosage of used diclofenac was 94 ± 32.01 mg. Average variation of VAS at measured intervals was significant (P Value ≤ 0.0001), but these variations were not significantly different when comparing the two groups (P Value = 0.023).Both morphine and diclofenac suppositories reduced pain significantly and similarly after CABG surgery.
- The Contribution of Gi/o Protein to Opioid Antinociception in an Oxaliplatin-Induced Neuropathy Rat Model. [JOURNAL ARTICLE]
- J Pharmacol Sci 2014 Oct 25.
Oxaliplatin is a chemotherapeutic agent that induces chronic refractory neuropathy. To determine whether opioids effectively relieve this chronic neuropathy, we investigated the efficacies of morphine, oxycodone, and fentanyl, and the mechanisms underlying opioid antinociception, in oxaliplatin-induced neuropathy in rats. Rats exhibited significant mechanical allodynia following 2 weeks of chronic oxaliplatin administration. Within the range of doses that did not induce sedation and/or muscle rigidity, morphine (3 mg/kg, subcutaneously, s.c.) and oxycodone (0.3 - 0.56 mg/kg, s.c.) completely reversed oxaliplatin-induced mechanical allodynia, whereas fentanyl (0.017 - 0.03 mg/kg, s.c.) showed partial antinociception. The antinociception of the optimal doses of morphine and oxycodone were completely inhibited by pertussis toxin (PTX; 0.5 μg/rat, i.c.v.), a Gi/o protein inhibitor, while the partial effect of fentanyl was not affected in the oxaliplatin model. In the [(35)S]-GTPγS binding assay, activation of μ-opioid receptor by fentanyl, but not by morphine or oxycodone, in the mediodorsal thalamus was significantly reduced in oxaliplatin-treated rats. These results indicate that the lower antinociceptive potency of fentanyl in the oxaliplatin model might in part result from the loss of PTX-sensitive Gi/o protein activation, and the degree of Gi/o protein activation might be related to the potency of antinociception by opioids in this model.
- Morphine and codeine in oral fluid after controlled poppy seed administration. [JOURNAL ARTICLE]
- Drug Test Anal 2014 Oct 24.
Opiates are an important drug class in drug testing programmes. Ingestion of poppy seeds containing morphine and codeine can yield positive opiate tests and mislead result interpretation in forensic and clinical settings. Multiple publications evaluated urine opiate concentrations following poppy seed ingestion, but only two addressed oral fluid (OF) results; neither provided the ingested morphine and codeine dosage. We administered two 45 g raw poppy seed doses, each containing 15.7 mg morphine and 3.1 mg codeine, 8 h apart to 17 healthy adults. All OF specimens were screened by on-site OF immunoassay Draeger DrugTest 5000, and confirmed with OF collected with Oral-Eze® device and quantified by liquid chromatography-tandem mass spectrometry (1 µg/L morphine and codeine limits of quantification). Specimens (n = 459) were collected before and up to 32 h after the first dose. All specimens screened positive 0.5 h after dosing and remained positive for 0.5-13 h at Draeger 20 µg/L morphine cut-off. Maximum OF morphine and codeine concentrations (Cmax ) were 177 and 32.6 µg/L, with times to Cmax (Tmax ) of 0.5-1 h and 0.5-2.5 h post-dose, respectively. Windows of detection after the second dose extended at least 24 h for morphine and to 18 h for codeine. After both doses, the last morphine positive OF result was 1 h with 40 µg/L 2004 proposed US Substance Abuse and Mental Health Services Administration cut-off, and 0.5 h with 95 µg/L cut-off, recently recommended by the Driving under the Influence of Drugs and Medicines project. Positive OF morphine results are possible 0.5-1 h after ingestion of 15.7 mg of morphine in raw poppy seeds, depending on the cut-off employed. Copyright © 2014 John Wiley & Sons, Ltd.
- Epigenetic Modification in Neuropathic Pain. [JOURNAL ARTICLE]
- Curr Pharm Des 2014 Oct 27.
Neuropathic pain is characterized by complicated combination of positive (e.g., hyperalgesia and allodynia) and negative (e.g., hypoesthesia and hypoalgesia) symptoms, and is often refractory to conventional pharmacological agents, including morphine. Although the molecular mechanisms for positive symptoms are extensively studied, those for negative symptoms are poorly understood. There is convincing evidence that altered gene expression within peripheral and central nervous systems is a key mechanism for neuropathic pain; however, its transcriptional mechanisms are poorly understood. Epigenetic modifications, such as DNA methylation and histone modifications (e.g., acetylation, methylation, and phosphorylation), are known to cause stable gene expression via chromatin remodeling. These mechanisms have a role not only in the determination of developmental cell fates, but also in the physiological and pathological processes in nervous system. Moreover, epigenetic therapies using epigenetic modifying compounds are progressively advanced in the treatments of diverse diseases, including cancer and neurological diseases. Importantly, there is emerging evidence that a variety of genes undergo epigenetic regulation via DNA methylation and histone modifications within peripheral and central nervous systems, thereby contributing to the alterations in both pain sensitivity and pharmacological efficacy in neuropathic pain. In this review, we will highlight the epigenetic gene regulation underlying neuropathic pain, especially focusing on the negative symptoms. Moreover, we will discuss whether epigenetic mechanisms can serve as a potential target to treat neuropathic pain.
- Ultrasound guided bilateral cervical plexus block reduces postoperative opioid consumption following thyroid surgery. [JOURNAL ARTICLE]
- J Clin Monit Comput 2014 Oct 26.
Thyroid surgery may cause severe postoperative pain and discomfort for patients. Superficial cervical plexus block (SCPB) is one of the regional anesthesia techniques that can provide postoperative analgesia for thyroid surgery. The purpose of this study was to evaluate analgesic effect of ultrasound (US) guided SCPB in patients undergoing thyroid surgery. Fifty ASA I-II patients, aged 20-60, were included in this single blinded study. In a randomized and prospective manner patients were allocated to either SCPB or control group. Bilateral SCPB was performed preoperatively under US guidance using 10 ml 0.25 % bupivacaine for each side. Postoperative analgesia was provided with patient-controlled analgesia method with morphine intravenous. Primary outcome measure was postoperative opioid consumption and analyzed using Mann-Whitney U test. Secondary outcome measures were comparison of opioid side effects like nausea and vomiting and analyzed using Chi square test. VAS scores for pain at postoperative 1st, 6th, 12th, and 24th h were similar in SCPB and control groups (Median VAS values were 2.5, 3, 2, 0 and 3.5, 3, 2, 0 respectively). Postoperative morphine consumption was lower in SCPB group compared to control group at postoperative 6th, 12th, and 24th h (Median doses of morphine consumption were 4, 8, 9 and 5, 9, 11 mg respectively) (P < 0.05). Eight patients in the control group and six patients in the SCBP group had vomiting. Seven patients in the SCPB and none in the control group had hoarseness. Our study has shown that US guided SCPB has a significant analgesic effect in patients undergoing thyroid surgery. Further studies are required to search for the optimal LA dose during US guided SCPB.
- Differential Expressions of the Alternatively Spliced Variant mRNAs of the µ Opioid Receptor Gene, OPRM1, in Brain Regions of Four Inbred Mouse Strains. [Journal Article]
- PLoS One 2014; 9(10):e111267.
The µ opioid receptor gene, OPRM1, undergoes extensive alternative pre-mRNA splicing in rodents and humans, with dozens of alternatively spliced variants of the OPRM1 gene. The present studies establish a SYBR green quantitative PCR (qPCR) assay to more accurately quantify mouse OPRM1 splice variant mRNAs. Using these qPCR assays, we examined the expression of OPRM1 splice variant mRNAs in selected brain regions of four inbred mouse strains displaying differences in µ opioid-induced tolerance and physical dependence: C56BL/6J, 129P3/J, SJL/J and SWR/J. The complete mRNA expression profiles of the OPRM1 splice variants reveal marked differences of the variant mRNA expression among the brain regions in each mouse strain, suggesting region-specific alternative splicing of the OPRM1 gene. The expression of many variants was also strain-specific, implying a genetic influence on OPRM1 alternative splicing. The expression levels of a number of the variant mRNAs in certain brain regions appear to correlate with strain sensitivities to morphine analgesia, tolerance and physical dependence in four mouse strains.
- The Opioid Rotation Ratio of Hydrocodone to Strong Opioids in Cancer Patients. [JOURNAL ARTICLE]
- Oncologist 2014 Oct 23.
Cancer pain management guidelines recommend initial treatment with intermediate-strength analgesics such as hydrocodone and subsequent escalation to stronger opioids such as morphine. There are no published studies on the process of opioid rotation (OR) from hydrocodone to strong opioids in cancer patients. Our aim was to determine the opioid rotation ratio (ORR) of hydrocodone to morphine equivalent daily dose (MEDD) in cancer outpatients.We reviewed the records of consecutive patient visits at our supportive care center in 2011-2012 for OR from hydrocodone to stronger opioids. Data regarding demographics, Edmonton Symptom Assessment Scale (ESAS), and MEDD were collected from patients who returned for follow-up within 6 weeks. Linear regression analysis was used to estimate the ORR between hydrocodone and MEDD. Successful OR was defined as 2-point or 30% reduction in the pain score and continuation of the new opioid at follow-up.Overall, 170 patients underwent OR from hydrocodone to stronger opioid. The median age was 59 years, and 81% had advanced cancer. The median time between OR and follow-up was 21 days. We found 53% had a successful OR with significant improvement in the ESAS pain and symptom distress scores. In 100 patients with complete OR and no worsening of pain at follow-up, the median ORR from hydrocodone to MEDD was 1.5 (quintiles 1-3: 0.9-2). The ORR was associated with hydrocodone dose (r = -.52; p < .0001) and was lower in patients receiving ≥40 mg of hydrocodone per day (p < .0001). The median ORR of hydrocodone to morphine was 1.5 (n = 44) and hydrocodone to oxycodone was 0.9 (n = 24).The median ORR from hydrocodone to MEDD was 1.5 and varied according to hydrocodone dose.
- Oral Morphine Weaning for Neonatal Abstinence Syndrome at Home Compared with In-Hospital: An Observational Cohort Study. [JOURNAL ARTICLE]
- Paediatr Drugs 2014 Oct 24.
The objective of this observational study was to evaluate the safety and effectiveness of discharging stabilized neonates to complete their oral morphine weaning at home.This retrospective cohort study evaluated neonates treated with oral morphine at two hospitals in London, Ontario, Canada. Neonates who completed their morphine wean in hospital were compared with neonates who completed their morphine wean following discharge from hospital (at home).There were 80 neonates treated with oral morphine at two hospitals from 2006 to 2010. The majority (65 %, 52/80) of neonates completed their morphine weaning after hospital discharge and were significantly less likely to return to hospital for further withdrawal treatment (1/52 vs 4/28, p < 0.05). Neonates who were treated at home remained on morphine for more days (32 vs 19 days, p < 0.01).We present the first North American cohort of neonates weaned with morphine at home for neonatal abstinence syndrome (NAS). We found that more days on oral morphine resulted in fewer returns to hospital for continued withdrawal management. There was no evidence of increased effectiveness, measured by the number of returns to hospital for further NAS management with in-hospital weaning. The estimated cost savings of continued weaning upon discharge was approximately $11,000 per patient (Canadian dollars). While further prospective research is necessary, in some cases morphine weaning at home may present a safe and cost-effective strategy for NAS management.