Systemic Naloxone Infusion May Trigger Spasticity in Patients With Spinal Cord Injury: Case Series

Abstract

Background/Objective: Three patients with spinal cord injury (SCI) and 3 able-bodied (AB) patients were infused with naloxone during a study to examine their neuroendocrine function. An unanticipated side effect occurred during the naloxone infusion. All 3 patients with SCI, but none of the AB patients, experienced profoundly increased spasticity during the naloxone infusion. Our report describes this side effect, which has potential implications for the clinical treatment or scientific evaluation of individuals with SCI.

Methods: All patients were in good general health and medication free for 11 days or longer before the study. Each patient was placed on a 30-hour protocol to analyze pulsatile release of gonadotropins. Physiologic saline was intravenously infused on day 1 to serve as a control period for naloxone infusion on day 2.

Results: AB patients experienced no muscle spasm activity or any other side effects at any time during the study. In contrast, all 3 patients with SCI experienced a profoundly increased frequency and duration of spasticity in muscles innervated by the nerve roots caudal to their level of injury. In all 3 patients with SCI, spasticity increased only during the period of naloxone infusion. Within 1 hour of stopping naloxone, spasticity returned to baseline levels.

Conclusions: Naloxone infusion produced a differential effect on the muscle activity of men with SCI compared to AB men with intact spinal circuits. Consistent with previous studies, the results of this study indicate a relationship between opioid neuromodulation and spasticity after SCI.     

Pilot study of fetal brain development and morphometry in prenatal opioid exposure and smoking on fetal MRI

PurposeThe purpose of this study was to assess for any differences in brain maturation, structure and morphometry in fetuses exposed to opioids in utero, compared to non-opioid exposed fetuses on fetal MRI.MethodsWe performed a prospective study in pregnant women using opioids and healthy pregnant women without prenatal opioid use. We evaluated brain maturation, structure, and morphometry on second or third trimester fetal MRI and assessed group differences.Results28 pregnant women were enrolled, 12 with opioid exposure (average gestational age 33.67, range 28–39 w), 9 of whom also smoked, and 16 without opioid exposure (average gestational age 32.53, range 27–38 w). There was a significant difference in the anteroposterior diameter of the fetal cerebellar vermis in the opioid exposed fetuses compared to non-opioid exposed fetuses (p = 0.004). There were no significant differences in brain biparietal diameter, fronto-occipital diameter, transverse cerebellar diameter and anteroposterior dimension of the pons in opioid exposed fetuses compared to non-opioid exposed fetuses. There were no abnormalities in brain maturation and no major brain structural abnormalities in the opioid exposed fetuses.ConclusionSmaller fetal anteroposterior cerebellar vermian dimension was associated with in utero opioid exposure. There were no abnormalities in brain maturation or major structural abnormalities in fetuses exposed to opioids.     

术前焦虑对腹腔镜下子宫切除患者术后疼痛及阿片类药物用量的影响

目的评价术前焦虑状态对腹腔镜下子宫切除患者术后疼痛及围手术期阿片类药物用量的影响。方法选择南方医科大学珠江医院妇产科2014年11月~2015年8月择期行腹腔镜下子宫切除术患者40例,年龄18~65岁,ASAⅠ或Ⅱ级,术前1d行状态焦虑量表(SAI)评估。按照SAI评分将患者分为低焦虑组(L组,SAI≤37,n=18)和高焦虑组(H组,SAI37,n=22)。记录患者麻醉时间、术中瑞芬太尼用量、从停用瑞芬太尼到首次给予舒芬太尼的时间(首剂时间);记录术后1h(T_1)、2h(T_2)、4h(T_3)、6h(T_4)、24h(T_5)及48h(T_6)患者舒芬太尼用量、PCIA按压次数、视觉模拟量表(VAS)评分和术后48h内不良反应的发生情况。结果术后各时点H组舒芬太尼用量明显大于L组(P0.05);H组舒芬太尼首剂时间[(9.1±6.5)min]明显短于L组[(15.8±11.9)min](P0.05);术后各时点两组VAS评分差异无统计学意义;T_5时H组PCIA按压次数明显多于L组(P0.05);术后48h内两组恶心呕吐发生率差异无统计学意义,且均无呼吸抑制、皮肤瘙痒及尿潴留发生。结论术前高焦虑状态可增加术后疼痛感知,术后需要更多的阿片类药物。     

Stimulus-evoked opioid inhibition in guinea-pig longitudinal muscle-myenteric plexus strip is modulated by NMDA receptors

Longitudinal muscle-myenteric plexus (LMMP) strips of the guinea-pig ileum were used to investigate the stimulus-evoked endogenous opioid inhibition and its modulation by ionotropic glutamate receptors. Regular cholinergic twitch responses evoked by a short 3-s-field stimulation in intervals of 80s were found reduced after an interposed period of prolonged 40-s-field stimulation. In the presence of a peptidase-inhibitor-cocktail, the cholinergic twitch response following the period of prolonged stimulation was even further reduced as compared to normal Tyrode solution without peptidase inhibitors. In both instances, the impairment of the cholinergic twitch response was completely abolished by naloxone thus demonstrating its opioidergic nature. This endogenous inhibitory opioid effect was significantly mitigated by the NMDA-receptor antagonist MK-801, but not by the AMPA/kainate receptor antagonist CNQX. These results demonstrate by functional experiments that there is a significant opioid-mediated inhibition in guinea-pig LMMP preparations evoked by a prolonged electrical stimulation, and that an NMDA antagonist can mitigate the opioid inhibition.     

我国门诊癌症患者阿片类镇痛药使用的现状研究

摘 要 目的：分析我国门诊癌症患者阿片类镇痛药的使用情况。方法：从医院处方分析合作项目数据库中随机提取我国5个城市89家医院门诊癌痛患者2016年中40 d的使用阿片类镇痛药处方数据,对其用药频度（DDDs）及限定日费用（DDC）、总费用等指标进行分析。 结果：共纳入13 803例患者的阿片类镇痛药处方,其中男8 522例,患者年龄分布在3~96岁。按照阿片类镇痛药使用人次由多到少的顺序排列依次为羟考酮及其复方制剂、曲马多及其复方制剂、可待因及其复方制剂、吗啡和芬太尼。羟考酮及其复方制剂的处方总金额和DDDs均最高。口服是最主要的给药途径,人次占比和金额占比分别为86.6%和83.3%。结论：阿片类镇痛药使用的基本面比较合理,但是在部分药品使用方面与国外情况有所区别,其合理性需要通过处方点评等方法进行进一步研究。     

Impact of intra-operative dexamethasone after scheduled cesarean delivery: a retrospective study

BackgroundDexamethasone is an effective analgesic and anti-emetic in patients undergoing many surgical procedures but its effects on pain after cesarean delivery are poorly studied. The aim of this study was to evaluate if routine intra-operative administration of dexamethasone improved analgesia and decreased postoperative nausea and vomiting after scheduled cesarean delivery.MethodsElectronic medical record data for scheduled cesarean deliveries performed under neuraxial anesthesia, before and after a practice change that introduced the routine use of intravenous dexamethasone 4 mg, were obtained. Patients were analyzed based on whether they received routine care (n=182) or also received dexamethasone (n=187). The primary outcome was time to first opioid use. Secondary outcomes included postoperative opioid consumption, pain scores, incidence and treatment of postoperative nausea and vomiting, satisfaction and length of stay.ResultsThere was no significant difference between groups in median time to first postoperative opioid administration (15.8 [3.4–48.0] h routine care vs 14.7 [3.2–38.8] h routine care plus dexamethasone, P=0.08). There were no significant differences in any secondary outcomes.ConclusionsThis impact study involving more than 360 patients suggests that routine administration of intra-operative intravenous dexamethasone 4 mg does not provide additional analgesic benefit after scheduled cesarean delivery, in the context of a multimodal postoperative analgesic regimen. Studies are required to determine if a larger dose or repeated administration influence postoperative analgesia or side effects, or whether certain subsets of patients may benefit.     

The effects of preoperative chronic opioid use in total hip arthroplasty

BackgroundPerioperative opioid use is becoming an increasingly concerning topic in total joint arthroplasty (TJA). The current study aims to add to the paucity of prior studies that have detailed perioperative opioid use patterns and the effects of preoperative chronic opioid use among a cohort of total hip arthroplasty (THA) patients.MethodsA retrospective analysis of 256 consecutive patients who underwent a THA at our institution between February 2016 and June 2016 was performed. Two cohorts were compared: patients deemed 1) preoperative chronic opioid users, and 2) non-chronic users. Variables compared included baseline characteristics, quality metrics, and patients’ opioid use histories 3 months prior to surgery and 6 months following surgery.ResultsOf the 256 patients, 54 (21.1%) patients were identified as preoperative chronic opioid users. Baseline characteristics including age, gender, BMI, and ASA scores were similar between both cohorts. Discharge disposition, value-based purchasing (VBP) costs, length of stay (LOS), emergency room visits, and postoperative office visits were similar between the two cohorts. Readmission rates (30-day, 90-day, and 6-month) were significantly higher (p < 0.05) in the chronic opioid users cohort. By the 6-month postoperative time period, chronic opioid users were consuming approximately 100-times the morphine equivalents than non-chronic users.ConclusionsThe current study demonstrates that a substantial proportion of preoperative chronic opioid users continue to consume large amounts of opioids up to 6-months following THA surgery. Furthermore, preoperative chronic use is significantly associated with poorer quality outcomes, specifically with respect to readmission rates.Level of evidenceLevel II, Prognostic Study.     

Parenting under the influence: The effects of opioids,alcohol and cocaine on mother–child interaction

Nearly 20% of adults receiving treatment for a substance use disorder live with their minor children (Stanger et al., 1999) and women in drug use treatment are twice as likely as men to have children in their household (Wechsberg et al., 1998). Parental drug use impacts the family through reduced family resources such as money and food, and researchers consistently note parenting deficits among substance users (Solis, Shadur, Burns, & Hussong, 2012). Little is known about differences in parenting and mother–child interaction among mothers with different drugs of choice or among mothers of older children, between 8 and 16 years. This study reports the findings from a sample of treatment seeking opioid, alcohol and cocaine using mothers and their 8–16-year-old child. Findings from a mother–child observational task and self-reported parenting measure indicated less undermining autonomy and higher mother maternal acceptance among opioid compared to alcohol addicted mothers. African American mothers were observed to have fewer negative interactional behaviors than Whites and both African American mothers and children self-reported higher firm control and maternal acceptance. Overall, mothers appeared to struggle with effective discipline with older versus younger children. Findings offer useful information to clinicians seeking to effectively tailor their interventions to women and children who present with different drugs of abuse, race/culture and developmental stage of child.     

Methadone maintenance treatment may improve completion rates and delay opioid relapse for opioid dependent individuals under community corrections supervision

Aims

Several studies have demonstrated the importance of agonist therapies such as methadone and buprenorphine for preventing relapse for individuals being released from jail or prison to the community. No studies have examined the impact of methadone for increasing the completion of community supervision requirements and preventing opioid relapse for individuals under community corrections supervision. This observational study compared the community corrections completion rate and opioid relapse rate of individuals receiving methadone maintenance therapy (MMT) to individuals who did not.

Methods

Of the 2931 individuals enrolled under criminal justice supervision in the community, Treatment Accountability for Safer Communities (TASC), and who met criteria for opioid dependence, 329 (11%) individuals reported receiving MMT in the community.

Results

The majority of participants were White (79.8%) and male (63.5%), with a mean age of 31.33 years (SD = 9.18), and were under supervision for 10.4 months (SD = 9.1). MMT participants were less likely to fail out of supervision compared to individuals not in MMT (39.0% vs. 52.9%, p < 0.001), and had a lower rate of relapse (32.9%) and longer time to relapse (average days = 89.7, SD = 158.9) compared to the relapse rate (55.9%) and time to relapse (average days = 60.5, SD = 117.9) of those not on MMT.

Conclusions

While the observational nature of this study prevents causal inferences, these results suggest that utilization of MMT in community corrections may increase the likelihood of completing supervision requirements and delay time to opioid relapse. Providing agonist therapies to opioid dependent individuals under supervision appears to be a critical strategy in this important population.