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- Preoperative opioid use and its association with perioperative opioid demand and postoperative opioid independence in patients undergoing spine surgery. [Journal Article]
- Spine (Phila Pa 1976) 2014 Dec 1; 39(25):E1524-30.
Prospective cohort.To assess whether preoperative opioid use is associated with increased perioperative opioid demand and postoperative opioid independence in patients undergoing spine surgery.Previous work has demonstrated increased opioid requirements during the intraoperative and immediate postoperative period in patients with high levels of preoperative opioid use. Despite this, they remain a common agent class used for the management of pain in patients prior to spine surgery.A total of 583 patients were included. Self-reported daily opioid consumption was obtained preoperatively and converted into morphine equivalent amounts and opioid use was recorded at the 12-month postoperative time. Intraoperative and immediate postoperative opioid demand was calculated. Linear regression analyses for intraoperative and immediate postoperative opioid demand while logistic regression analyses for opioid independence at 12 months including relevant covariates such as depression and anxiety were performed.The median preoperative morphine equivalent amount for the cohort was 8.75 mg, with 55% of patients reporting some degree of opioid use. Younger age, more invasive surgery, anxiety, and primary surgery were significantly associated with increased intraoperative opioid demand (P < 0.05). Younger age, anxiety, and greater preoperative opioid use were significantly associated with increased immediate postoperative opioid demand (P < 0.05). More invasive surgery, anxiety, revision surgery, and greater preoperative opioid use were significantly associated with a decreased incidence of opioid independence at 12 months postoperatively (P < 0.01).Greater preoperative opioid use prior to undergoing spine surgery predicts increased immediate postoperative opioid demand and decreased incidence of postoperative opioid independence. Psychiatric diagnoses in those using preoperative opioids were predictors of continued opioid use at 12 months. Patients may benefit from preoperative counseling that emphasizes minimizing opioid use prior to undergoing spine surgery.2.
- ACOEM Practice Guidelines: Opioids for Treatment of Acute, Subacute, Chronic, and Postoperative Pain. [JOURNAL ARTICLE]
- J Occup Environ Med 2014 Nov 20.
The American College of Occupational and Environmental Medicine's guidelines have been updated to develop more detailed guidance for treatment of acute, subacute, chronic, and postoperative pain with opioids.Literature searches were performed using PubMed, EBSCO, Cochrane Review, and Google Scholar without publication date limits. Of 264,617 articles' titles screened and abstracts reviewed, 263 articles met inclusion criteria. Of these, a total of 157 were of high and moderate quality addressing pain treatment. Comprehensive literature reviews were accomplished with article abstraction, critiquing, grading, evidence table compilation, and guideline finalization by a multidisciplinary expert panel to develop evidence-based guidance.No quality evidence directly supports histories, physical examinations, and opioid treatment agreements, although they are thought to be important. No quality trials were identified showing superiority of opioids, compared with nonsteroidal anti-inflammatory and other medications for treatment of chronic, noncancer pain. The use of opioid-sparing treatments associated with lower doses of postoperative opioids is also associated with better long-term functional outcomes. Selective use of opioids is recommended for patients with acute and postoperative pain. Consensus recommendations also include consideration of carefully conducted trials of chronic opioid treatment for highly select patients with subacute and chronic pain and to maintenance opioid prescriptions only if documented objective functional gain(s) results. A strong and reproducible dose-response relationship identifies a recommended morphine equivalent dose limit of no more than 50 mg/day. Higher doses should be prescribed only with documented commensurately greater functional benefit(s), comprehensive monitoring for adverse effects, informed consent, and careful consideration of risk versus benefit of such treatment. Chronic opioid use should be accompanied by informed consent, a treatment agreement, tracking of functional benefits, drug screening, and attempts at tapering.
- Effect of morphine on the persistence of long-term memory in rats. [JOURNAL ARTICLE]
- Psychopharmacology (Berl) 2014 Nov 22.
Current evidence suggests that pharmacological manipulation around 12 h after training alters the persistence of long-term memory. However, no study has addressed whether opioids modulate the persistence of fear. The current study examined whether morphine alters the persistence of the memory of contextual fear conditioning.Male adult Wistar rats were injected with saline (NaCl 0.9 %, intraperitoneally (i.p.)) or morphine (3 and/or 10 mg/kg, i.p.) 6, 9, 12, or 24 h post-training and tested 2 or 7 days after training, when freezing responses were assessed. The involvement of state dependence and opioid receptors in the effect of morphine was investigated by respectively injecting naloxone (1 mg/kg, i.p.) 30 min before morphine, and morphine (10 mg/kg, i.p.) 30 min before testing.Morphine (10 mg/kg, i.p., 12 h post-training) did not alter freezing to context in animals tested 2 days after training but impaired freezing to context when testing was carried out 7 or 14 days after training. Morphine (10 mg/kg, i.p.) administration 6, 9, or 24 h post-training did not alter freezing measured 2 or 7 days after training. Pre-test morphine improved recall but did not alter the deleterious effect of 12 h post-training morphine. The deleterious effect of morphine was prevented by naloxone, indicating that opioid receptors are involved in this effect.Our findings indicate an inhibitory role for opioid receptors in memory persistence. This is relevant from both the experimental and clinical point of views, since it may have implications for the prevention of post-traumatic stress disorder (PTSD).
- Acute Generalized Exanthematous Pustulosis Caused by Dihydrocodeine Phosphate in a Patient With Psoriasis Vulgaris and a Heterozygous IL36RN Mutation. [JOURNAL ARTICLE]
- JAMA Dermatol 2014 Nov 19.
Acute generalized exanthematous pustulosis (AGEP) is a rare and severe type of drug eruption. Dihydrocodeine phosphate is a semisynthetic opioid analgesic. Recently, recessive mutations in IL36RN have been identified in generalized pustular psoriasis (GPP). To date, 4 cases of AGEP and IL36RN mutation without previous history of psoriasis vulgaris (PV) have been reported.A woman in her 60s with PV presented with diffuse erythema, nonfollicular pustules, and fever. She had been treated with dextromethorphan hydrobromide hydrate, amoxicillin hydrate, clarithromycin, dihydrocodeine phosphate, tipepidine hibenzate, and tulobuterol tape for a cough and common cold. Based on histopathologic results and a positive result in a drug provocation test with dihydrocodeine phosphate, she was diagnosed with AGEP. A heterozygous IL36RN mutation c.28C>T (p.Arg10X) was also confirmed by mutation analysis.This is the first report of dihydrocodeine phosphate-induced AGEP. In this case, helper T cells, type 17, might have been activated because of morphine and underlying PV, followed by increased production of interleukin (IL) 36. However, because of the IL36RN mutation, IL-36 signaling was uncontrolled, which might have resulted in the occurrence of AGEP. An IL36RN mutation might underlie several different pustular skin eruptions, including AGEP and GPP, and further accumulation of patient data is required.
- Morphine after tubal ligation with bupivacaine: dosage versus body weight. [Journal Article]
- JSLS 2014 Oct; 18(4)
We investigated whether there was a statistically significant difference in patient need for postoperative analgesia based on adjusted body weight between heavier and lighter women who underwent laparoscopic tubal ligation with bupivacaine injection at the skin incision.We examined 49 records of women who underwent laparoscopic tubal ligation at Oklahoma State University Medical Center between 2000 and 2005 and received an injection of bupivacaine at the surgical site during the procedure. Postsurgical morphine was measured as doses per kilogram of body weight against total body weight and as total milligrams per kilogram of body weight against total body weight. A regression was performed for each measurement.Heavier women required significantly fewer total milligrams of morphine per kilogram of body weight and fewer total doses of morphine per kilogram of body weight than lighter women (2-tailed P = .0035 and P = .0018, respectively).Our data may suggest that lipophilic bupivacaine injected at a surgical site is held in place better and works for a longer period when more fat is present.
- Detection of signals of abuse and dependence applying disproportionality analysis. [JOURNAL ARTICLE]
- Eur J Clin Pharmacol 2014 Nov 20.
Prescription drug abuse and dependence is a widespread phenomenon in many countries. The use of disproportionality measures in drug abuse surveillance is rarely performed.The aim of this study is to determine the occurrence of signals of abuse and dependence for different psychoactive drugs in real-life settings.Disproportionality analysis was realised from a database specifically constructed for the monitoring of drug abuse and dependence. This database provides information on approximately 5000 patients and 8000 consumption modalities for more than 100 distinct psychoactive medications for 2010 and 2011. Proportional reporting ratio (PRR) was computed in two population groups: subjects under an opiate maintenance treatment (OMT) versus those not under OMT, and focused on four types of behaviours: abuse and dependence, illegal acquisition, diverted route of administration and concomitant alcohol use.Among the 100 psychoactive drugs for which a signal could be detected, those presenting the highest signals were the following: flunitrazepam, clonazepam, methylphenidate, ketamine, morphine sulfate, codeine and buprenorphine.The present study shows an innovative application of disproportionality measures for drug abuse monitoring based on two cross-national, annual studies. The disproportionality analysis provided the opportunity to reveal and compare the magnitude of signals between 100 psychoactive drugs. This approach helps to compare the magnitude of abuse and dependence behaviours for a large number of drugs, and allows prioritizing actions in a context where such events are usually underreported.
- Effects of Mu Opioid Receptor Agonists in Assays of Acute Pain-Stimulated and Pain-Depressed Behavior in Rats: Role of Mu Agonist Efficacy and Noxious Stimulus Intensity. [JOURNAL ARTICLE]
- J Pharmacol Exp Ther 2014 Nov 18.
Pain is associated with stimulation of some behaviors and depression of others, and mu opioid receptor agonists are among the most widely used analgesics for treatment of pain. The present study used parallel assays of pain-stimulated and pain-depressed behavior in male Sprague-Dawley rats to compare antinociception profiles for six mu opioid analgesics that varied in efficacy at mu opioid receptors (in order from highest to lowest efficacy: methadone, fentanyl, morphine, hydrocodone, buprenorphine, nalbuphine). Intraperitonial injection of dilute lactic acid served as an acute, chemical noxious stimulus to either stimulate a stretching response or depress operant responding maintained by electrical brain stimulation in an intracranial self-stimulation (ICSS) procedure. All mu agonists blocked both stimulation of stretching and depression of ICSS produced by 1.8% lactic acid. The high-efficacy mu agonists methadone and fentanyl were more potent to block acid-induced depression of ICSS than acid-stimulated stretching, whereas lower efficacy agonists displayed similar potency across assays. All mu agonists except morphine also facilitated ICSS in the absence of the noxious stimulus at doses similar to those that blocked acid-induced depression of ICSS. The potency of the low-efficacy mu agonist nalbuphine, but not the high-efficacy mu agonist methadone, to block acid-induced depression of ICSS was significantly reduced by increasing the intensity of the noxious stimulus to 5.6% acid. These results demonstrate sensitivity of acid-induced depression of ICSS to a range of clinically effective mu opioid analgesics and reveal distinctions between opioids based on efficacy at the mu receptor.
- Safety and Tolerability of Gabapentin for Aneurysmal Subarachnoid Hemorrhage (SAH) Headache and Meningismus. [JOURNAL ARTICLE]
- Neurocrit Care 2014 Nov 18.
Headache after aneurysmal subarachnoid hemorrhage (SAH) is very common and is often described as the "worst headache imaginable." SAH-associated headache can persist for days to weeks and is traditionally treated with narcotics. However, narcotics can have significant adverse effects. We hypothesize that gabapentin (GBP), a non-narcotic neuropathic pain medication, would be safe and tolerable and would reduce narcotic requirements after SAH.We retrospectively reviewed the clinical, radiographic, and laboratory data of SAH patients at the neuroscience intensive care unit at Mayo Clinic in Jacksonville, Florida, from January 2011 through February 2013. Headache intensity was quantified by a visual analog scale score. Total opioid use per day was tabulated using an intravenous morphine equivalents scale. Cerebrospinal fluid was also reviewed when available.There were 53 SAH patients who were treated with GBP along with other analgesics for headache. Among these SAH patients, 34 (64 %) were women, with a mean age of 54 years (SD 12.3). Severe headache was observed in all SAH patients. GBP dosing was rapidly escalated within days of SAH up to a median of 1,200 mg/day, with a range of 300 mg three times a day to 900 mg three times a day. Approximately 6 % of patients treated with GBP had nausea (95 % CI 1-16 %), and only one patient (1.8 %) had to discontinue GBP.GBP appears to be relatively safe and tolerable in SAH patients with headache and may be a useful narcotic-sparing agent to prevent narcotics-associated complications, such as gastrointestinal immobility, ileus, and constipation.
- Analgesia for Early-Life Pain Prevents Deficits in Adult Anxiety and Stress in Rats. [JOURNAL ARTICLE]
- Dev Neurosci 2014 Nov 12.
Previous studies in rats have established that inflammatory pain experienced on the day of birth (P0) decreases sensitivity to acute noxious, anxiety- and stress-provoking stimuli. However, to date, the impact of early-life pain on adult responses to chronic stress is not known. Further, the ability of morphine, administered at the time of injury, to mitigate changes in adult behavioral and hormonal responses to acute or chronic stressors has not been examined. P0 male and female Sprague-Dawley rat pups were given an intraplantar injection of 1% carrageenan or handled in an identical manner in the presence or absence of morphine. As adults, rats that experienced early-life pain displayed decreased sensitivity to acute stressors, as indicated by increased time in the inner area of the Open Field, and increased latency to immobility and decreased time immobile in the Forced Swim Test (FST). An accelerated return of corticosterone to baseline was also observed. Morphine administration at the time of injury completely reversed this 'hyporesponsive' phenotype. By contrast, following 7 days of chronic variable stress, injured animals displayed a 'hyperresponsive' phenotype in that they initiated immobility and spent significantly more time immobile in the FST than controls. Responses to chronic stress were also rescued in animals that received morphine at the time of injury. These data suggest that analgesia for early-life pain prevents adult hyposensitivity to acute anxiety- and stress-provoking stimuli and increased vulnerability to chronic stress, and have important clinical implications for the management of pain in infants. © 2014 S. Karger AG, Basel.
- Analgesic Effects of Morphine in Combination with Adjuvant Drugs in Rats. [JOURNAL ARTICLE]
- Pharmacology 2014 Nov 8; 94(5-6):207-213.
Background: Morphine is co-administered with adjuvant drugs to treat pain, nausea, vomiting, dyspnoea and delirium in cancer patients. Aim of the Study: To investigate analgesic effects of morphine when co-administered with adjuvant drugs. Material and Methods: Two-month-old male Wistar rats received single morphine doses alone (0.45 and 0.9 mg/kg) or with midazolam (0.3 mg/kg), haloperidol (0.15 and 0.45 mg/kg), levomepromazine (0.35 mg/kg), metoclopramide (1.0 mg/kg), and hyoscine butylbromide (1.7 mg/kg) as single subcutaneous injections. Analgesia was measured by the tail-flick test after 15, 30, 45, 60, and 90 min of drug administration. In the case of significant analgesia enhancement, analgesic and sedative effects were explored in 3-, 5-, 6-, 8-, and 11-month-old rats. Results: Significant morphine (0.9 mg/kg) analgesia enhancement was observed 60 min after haloperidol (0.15 and 0.45 mg/kg) and hyoscine butylbromide co-administration. The addition of haloperidol to morphine significantly increased analgesia in 6-, 8- and 11-month-old rats while in the case of hyoscine butylbromide co-administration this effect was observed only in 11-month-old rats. Conclusions: Haloperidol and hyoscine butylbromide enhanced morphine analgesia. Future studies may explore the repeated administration of these drug combinations in rats and humans. © 2014 S. Karger AG, Basel.