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1.
Analgesia, Opioids, and Other Drug Use During Pregnancy and Neonatal Abstinence Syndrome.
Jones, HE, Kraft, WK
Clinics in perinatology. 2019;(2):349-366
Abstract
When opioid misuse rises in the United States, pregnant women and their neonates are affected. This article summarizes the use of Food and Drug Administration-approved products, including methadone, buprenorphine, and the combination formulation of buprenorphine and naloxone to treat adult opioid use disorder during the perinatal period. All labels include pregnancy, neonatal, and lactation information and note the accepted use of these medications during the perinatal period if the benefits outweigh the risks. A summary of the neonatal abstinence syndrome definition, its assessment tools, treatment approaches, and future genetic directions are provided.
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2.
Analgesic efficacy of ketorolac associated with a tramadol/acetaminophen combination after third molar surgery - a randomized, triple-blind clinical trial.
Martins, LD, Rezende, M, Loguercio, AD, Bortoluzzi, MC, Reis, A
Medicina oral, patologia oral y cirugia bucal. 2019;(1):e96-e102
Abstract
BACKGROUND This study compared the efficacy of ketorolac alone versus its combination with tramadol/acetaminophen for pain control after mandibular third molar surgery. MATERIAL AND METHODS A randomized, triple-blind clinical trial was carried out with 52 patients divided into 2 groups: Group K+T+A (1 tablet of Ketorolac 10 mg plus and 1 capsule of Tramadol 37.5 mg/acetaminophen 325 mg) and Group K (1 tablet of Ketorolac 10 mg plus and 1 placebo capsule). The treatments were given 1 h before the surgery and was repeated 4 times per day, for 48 h. The difference in postoperative pain was assessed by 4 primary end-points: pain intensity (VAS 100mm, for 48 h), rescue medication, overall assessment and adverse effects. RESULTS Significant differences in pain intensity were observed in the different times (p < 0.05). The comparison of groups in each time showed significant differences only of 9 h, with lower level of pain intensity for group K+T+A (p = 0.005). The need of analgesics was higher in Group K (p < 0.001), the need of antiemetic were greater in Group K+T+A (p < 0.0001). No significant difference between groups were observed in overall assessment. The adverse effects was higher in Group K+T+A. CONCLUSIONS The current study showed that both ketorolac and the combination of ketorolac plus tramadol/acetaminophen showed good control of pain after the extraction of the lower third molars. Although the combination group showed lower pain at 9 h, the difference is small and not clinically relevant.
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3.
Intravenous vs Oral Acetaminophen for Analgesia After Cesarean Delivery: A Randomized Trial.
Wilson, SH, Wolf, BJ, Robinson, SM, Nelson, C, Hebbar, L
Pain medicine (Malden, Mass.). 2019;(8):1584-1591
Abstract
OBJECTIVE Examination of postoperative analgesia with intravenous and oral acetaminophen. DESIGN Prospective, three-arm, nonblinded, randomized clinical trial. SETTING A single academic medical center. SUBJECTS Parturients scheduled for elective cesarean delivery. METHODS This trial randomized 141 parturients to receive intravenous acetaminophen (1 g every eight hours, three doses), oral acetaminophen (1 g every eight hours, three doses), or no acetaminophen. All patients received a standardized neuraxial anesthetic with intrathecal opioids and scheduled postoperative ketorolac. The primary outcome, 24-hour opioid consumption, was evaluated using the Kruskal-Wallace test and Tukey-Kramer adjustment for multiple comparisons. Secondary outcomes included 48-hour opioid consumption, first opioid rescue, pain scores, patient satisfaction, times to ambulation and discharge, and side effects. RESULTS Over 18 months, 141 parturients with similar demographic variables completed the study. Median (interquartile range) opioid consumption in intravenous morphine milligram equivalents at 24 hours was 0 (5), 0 (7), and 5 (7) for the intravenous, oral, and no groups, respectively, and differed between groups (global P = 0.017). Opioid consumption and other secondary outcomes did not differ between the intravenous vs oral or oral vs no groups. Opioid consumption was reduced at 24 hours with intravenous vs no acetaminophen (P = 0.015). Patients receiving no acetaminophen had 5.8 times the odds of consuming opioids (P = 0.036), consumed 40% more opioids controlling for time (P = 0.041), and had higher pain scores with ambulation (P = 0.004) compared with the intravenous group. CONCLUSIONS Intravenous acetaminophen did not reduce 24-hour opioid consumption or other outcomes compared with oral acetaminophen. Intravenous acetaminophen did decrease opioid consumption and pain scores compared with no acetaminophen.
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4.
Genomewide Gene-by-Sex Interaction Scans Identify ADGRV1 for Sex Differences in Opioid Dependent African Americans.
Yang, BZ, Zhou, H, Cheng, Z, Kranzler, HR, Gelernter, J
Scientific reports. 2019;(1):18070
Abstract
Sex differences in opioid dependence (OD) are genetically influenced. We conducted genomewide gene-by-sex interaction scans for the DSM-IV diagnosis of OD in 8,387 African-American (AA) or European-American subjects (43.6% women; 4,715 OD subjects). Among AAs, 9 SNPs were genome-wide significant at ADGRV1 (adhesion G-protein-coupled receptor V1, lead-SNP rs2366929*(C/T), p = 1.5 × 10-9) for sex-different risk of OD, with the rs2366929*C-allele increasing OD risk only for men. The top co-expressions in brain were between ADGRV1 and GRIK2 in substantia nigra and medullary inferior olivary nucleus, and between ADGRV1 and EFHC2 in frontal cortex and putamen. Significant sex-differential ADGRV1 expression from GTEx was detected in breast (Bonferroni-corrected-p < 0.002) and in heart (p < 0.0125), with nominal significance identified in brain, thyroid, lung, and stomach (p < 0.05). ADGRV1 co-expression and disease-enrichment analysis identifying the top 10 diseases showed strikingly sexually dimorphic risks. The enrichment and transcriptome analyses provided convergent support that ADGRV1 exerts a sex-different effect on OD risk. This is the first study to identify genetic variants contributing to sex differences in OD. It shows that ADGRV1 contributes to OD risk only in AA men, a finding that warrants further study.
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5.
Opioids Preconditioning Upon Renal Function and Ischemia-Reperfusion Injury: A Narrative Review.
Palomino, J, Echavarria, R, Franco-Acevedo, A, Moreno-Carranza, B, Melo, Z
Medicina (Kaunas, Lithuania). 2019;(9)
Abstract
Kidneys have an important role in regulating water volume, blood pressure, secretion of hormones and acid-base and electrolyte balance. Kidney dysfunction derived from acute injury can, under certain conditions, progress to chronic kidney disease. In the late stages of kidney disease, treatment is limited to replacement therapy: Dialysis and transplantation. After renal transplant, grafts suffer from activation of immune cells and generation of oxidant molecules. Anesthetic preconditioning has emerged as a promising strategy to ameliorate ischemia reperfusion injury. This review compiles some significant aspects of renal physiology and discusses current understanding of the effects of anesthetic preconditioning upon renal function and ischemia reperfusion injury, focusing on opioids and its properties ameliorating renal injury. According to the available evidence, opioid preconditioning appears to reduce inflammation and reactive oxygen species generation after ischemia reperfusion. Therefore, opioid preconditioning represents a promising strategy to reduce renal ischemia reperfusion injury and, its application on current clinical practice could be beneficial in events such as acute renal injury and kidney transplantation.
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6.
Opioid-Induced Foregut Dysfunction.
Patel, D, Callaway, J, Vaezi, M
The American journal of gastroenterology. 2019;(11):1716-1725
Abstract
The impact of opioid use on the lower gastrointestinal tract is well described, but recent opioid crisis has caused increased awareness of the detrimental effects of these drugs on esophageal and gastroduodenal motility. Opioid use has been associated with increased incidence of spastic esophageal motility disorders and gastroduodenal dysfunction. Opioid receptors are present with high abundance in the myenteric and submucosal plexus of the enteric nervous system. Activation of these receptors leads to suppressed excitability of the inhibitory musculomotor neurons and unchecked tonic contraction of the autogenic musculature (such as the lower esophageal sphincter and the pylorus).
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7.
Risk Factors Associated with the Occurrence of Neonatal Opioid Withdrawal Syndrome: A Review.
Kelty, E, Preen, DB
CNS drugs. 2019;(11):1113-1120
Abstract
In a number of countries, the prevalence of neonatal opioid withdrawal syndrome (NOWS) is increasing. While NOWS is ultimately the result of opioid exposure in utero, a wide range of risk factors have been associated with the prevalence of NOWS, extending beyond just drug exposure. This article reviews the available literature on factors associated with the incidence of NOWS in opioid-exposed neonates. A range of risk factors have been associated with NOWS, including features of neonatal drug exposure, maternal and neonatal characteristics, aspects of labor and delivery, and genetics. Increased length of gestation and higher birth weight were consistently associated with an increased risk of NOWS, while breast feeding and 'rooming-in' were associated with a reduced risk of NOWS. Additionally, several genetic factors have also been associated with NOWS severity. There is conflicting evidence on the association between NOWS and other risk factors including opioid dose, neonate sex, and the use of some medications during pregnancy. This may be in part attributable to differences in how NOWS is diagnosed and the variety of methodologies across studies. While a large number of risk factors associated with NOWS are non-modifiable, encouraging pregnant women to reduce other drug use (including smoking), breast feed their child, and the judicious use of medications during pregnancy may help reduce the prevalence of NOWS. The presence or absence of NOWS in an opioid-exposed neonate is associated with a wide range of factors. Some of these modifiable risk factors may be potential targets for the primary prevention of NOWS.
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8.
Efficacy of pethidine, ketorolac, and lidocaine gel as analgesics for pain control in shockwave lithotripsy: A single-blinded randomized controlled trial.
Hashem, A, Ghobrial, FK, Elbaset, MA, Atwa, AM, Fadallah, M, Laymon, M, El-Assmy, A, Sheir, KZ, Abol-Enein, H
Investigative and clinical urology. 2019;(4):251-257
Abstract
PURPOSE To compare the safety and efficacy of xylocaine gel and ketorolac as opioid-sparing analgesia compared with pethidine for shock wave lithotripsy (SWL) pain. MATERIALS AND METHODS A single-blinded randomized controlled trial (RCT) was performed in 132 patients with renal and upper ureteral stones amenable to treatment with SWL. The first patient group received intravenous (IV) pethidine and placebo gel; the second group received IV ketorolac plus placebo gel; the third group received lidocaine gel locally plus normal saline IV. Stone disintegration was classified as none (no change from basal by kidney, ureter, bladder X-ray or ultrasound [US] imaging), partial (fragmented and >4-mm residual fragments), and complete (≤4-mm residual fragments). Stone disintegration was assessed by kidney-ureter-bladder X-ray and US imaging. Pain was evaluated by use of the Numeric Pain Rating Scale (NPRS). RESULTS The NPRS scores were highest in the xylocaine group at 10, 20, and 30 minutes (p=0.0001) with no significant difference between the ketorolac and pethidine groups, except at 10 minutes (p=0.03) and a near significant difference at 30 minutes (p=0.054) in favor of ketorolac. Results for stone disintegration (none, partial, and complete, respectively) were as follows: 25 (50.0%), 23 (46.0%), and 2 (4.0%) for pethidine; 19 (35.8%), 23 (43.4%), and 11 (20.8%) for ketorolac; and 26 (89.7%), 3 (10.3%), and 0 (0.0%) for lidocaine (p=0.008). CONCLUSIONS Ketorolac is a safe and more effective alternative to morphine derivatives for SWL analgesia. Lidocaine gel should not be used as mono-analgesia for SWL.
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9.
Intravenous Patient-controlled Analgesia Versus Thoracic Epidural Analgesia After Open Liver Surgery: A Prospective, Randomized, Controlled, Noninferiority Trial.
Hausken, J, Fretland, ÅA, Edwin, B, Andersen, MH, Dagenborg, VJ, Bjørnelv, GMW, Kristiansen, R, Røysland, K, Kvarstein, G, Tønnessen, TI
Annals of surgery. 2019;(2):193-199
Abstract
OBJECTIVE We conducted a randomized, controlled, noninferiority trial to investigate if intravenous, multimodal, patient-controlled analgesia (IV-PCA) could be noninferior to multimodal thoracic epidural analgesia (TEA) in patients undergoing open liver surgery. SUMMARY BACKGROUND DATA The increasing use of minimally invasive techniques and fast track protocols have questioned the position of epidural analgesia as the optimal method of pain management after abdominal surgery. METHODS Patients operated with open liver resection between February 2012 and February 2016 were randomly assigned to receive either IV-PCA enhanced with ketorolac/diclofenac (IV-PCA, n = 66) or TEA (n = 77) within an enhanced recovery after surgery protocol. Noninferiority would be declared if the mean pain score on the numeric rating scale (NRS) for postoperative days (PODs) 0 to 5 in the IV-PCA group was no worse than the mean pain score in the TEA group by a margin of <1 point on an 11-point scale (0-10). RESULTS The primary endpoint, mean NRS pain score was 1.7 in the IV-PCA group and 1.6 in the TEA group, establishing noninferiority. Pain scores were lower in the TEA group on PODs 0 and 1, but higher or equal on PODs 2 and 5. Postoperative hospital stay was significantly shorter for patients in the IV-PCA group (74 vs 104 h, P < 0.001). The total opioid consumption during the first 3 days was significantly lower in the IV-PCA group. CONCLUSIONS IV-PCA was noninferior to TEA for the treatment of postoperative pain in patients undergoing open liver resection.
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10.
Pharmacotherapeutic options for complex regional pain syndrome.
Iolascon, G, Moretti, A
Expert opinion on pharmacotherapy. 2019;(11):1377-1386
Abstract
INTRODUCTION Complex regional pain syndromes (CRPS) are rare painful conditions characterized by considerable variability in possible triggering factors, usually traumatic, and in the clinical scenario. The limited knowledge of the pathophysiological mechanisms has led to countless treatment attempts with multiple conservative and surgical options that act by different mechanisms of action. AREAS COVERED In this narrative review, the authors discuss key points about CRPS definitions, diagnostic criteria and pitfalls, pathophysiological hypotheses, and treatment strategies with particular reference to pharmacotherapy. The article was based on a literature search using PubMed while the available guidelines for the management of CRPS were also examined. EXPERT OPINION According to the quality of evidence, pharmacological interventions for CRPS seem to be more effective all the more so when they act on peripheral mechanisms, particularly on nociceptive pain, and when applied early in the disease, while reliable evidence about central mechanisms of chronic pain in CRPS is lacking. In our opinion, drug therapy should be preferred as early as possible, particularly in warm forms of CRPS to prevent significant functional limitation, psychological distress, and social and economic fallout.