Tapentadol is a centrally acting analgesic with a dual mechanism of action of mu receptor agonism and norepinephrine reuptake inhibition. Tapentadol immediate-release is approved by the US Food and Drug Administration for the management of moderate-to-severe acute pain. It was developed to decrease the intolerability issue associated with opioids. Tapentadol extended-release has a 12-hour duration of effect, and has recently been evaluated for pain in patients with chronic osteoarthritis, low back pain, and pain associated with diabetic peripheral neuropathy. Tapentadol extended-release was found to provide safe and highly effective analgesia for the treatment of chronic pain conditions, including moderate-to-severe chronic osteoarthritis pain and low back pain. Initial trials demonstrating efficacy in neuropathic pain suggest that tapentadol has comparable analgesic effectiveness and better gastrointestinal tolerability than opioid comparators, and demonstrates effectiveness in settings of inflammatory, somatic, and neuropathic pain. Gastrointestinal intolerance and central nervous system effects were the major adverse events noted. Tapentadol will need to be rigorously tested in chronic neuropathic pain, cancer-related pain, and cancer-related neuropathic pain.

Poorly controlled acute and chronic pain can increase morbidity, impair quality of life and prolong disability. Over 80 percent of post surgical patients report moderate to severe uncontrolled postoperative pain. Over-reliance on potent opioid agonists can lead to several opioid related side effects such as gastrointestinal intolerability, respiratory depression and cognitive impairment. A recently approved dual acting central analgesic tapentadol may offer improved tolerability over traditional opioid agonists while having multimodal opioid and nonopioid analgesic benefits. Tapentadol, classified by the US Food and Drug Administration as a class 2 opioid, is currently marketed in the United States as immediate release (IR) NUCYNTA® for moderate to severe acute pain in tablets of 50 mg, 75 mg, and 100 mg, and as extended release (ER) NUCYNTA ER® for the treatment of chronic moderate to severe pain in tablets of 50 mg, 100 mg, 150 mg, 200 mg, and 250 mg. Tapentadol is a low affinity mu opioid receptor agonist and a norepinephrine reuptake inhibitor. Tapentadol has no active metabolites and this property makes it useful in patients with hepatic and renal failure. Clinical trials with tapentadol IR showed that there was improved gastrointestinal tolerability and similar pain relief as compared to oxycodone IR. Tapentadol ER allows for twice daily dosing. Clinical trials showed that tapentadol ER could effectively relieve moderate to severe chronic pain and was associated with significantly fewer gastrointestinal adverse effects as compared to oxycodone controlled release. Tapentadol ER is indicated and has Food and Drug Administration approval for the treatment of chronic painful diabetic neuropathy. The most common side effects of tapentadol are nausea (30%), vomiting (18%), dizziness (24%), and somnolence (15%). Tapentadol, due to its potential synergistic effects on norepinephrine levels, is contraindicated in patients who have taken monoamine oxidase inhibitors within the last 14 days. Caution has to be exercised with the use of tapentadol IR and tapentadol ER in the presence of other central nervous system depressants such as neuroleptics, opioids, illicit drugs, muscle relaxants, sedatives, and anxiolytics.

Objective This literature review summarizes evidence on the safety and efficacy of intraarticular hyaluronic acid (IAHA) preparations approved in the United States for the treatment of osteoarthritis of the knee. Design A systematic literature search was performed in PubMed, Ovid MEDLINE, and SCOPUS databases. Only studies in which clinical outcomes of individual IAHA preparations alone could be assessed when compared to placebo, no treatment, other standard knee osteoarthritis treatments, and IAHA head-to-head studies were selected. Results One hundred nine articles meeting our inclusion criteria were identified, including 59 randomized and 50 observational studies. Hylan G-F 20 has been the most extensively studied preparation, with consistent results confirming efficacy in placebo-controlled studies. Efficacy is also consistently reported for Supartz, Monovisc, and Euflexxa, but not for Hyalgan, Orthovisc, and Durolane. In the head-to-head trials, high-molecular-weight (MW) Hylan G-F 20 was consistently superior to low MW sodium hyaluronate preparations (Hyalgan, Supartz) up to 20 weeks, whereas one study reported that Durolane was noninferior to Supartz. Head-to-head trials comparing high versus medium MW preparations all used Hylan G-F 20 as the high MW preparation. Of the IAHA preparations with strong evidence of efficacy in placebo-controlled studies, Euflexxa was found to be noninferior to Hylan G-F 20. There are no direct comparisons to Monovisc. One additional IAHA preparation (ie, Synovial), which has not been assessed in placebo-controlled studies, was also noninferior to Hylan G-F 20. Conclusion IAHA efficacy varies widely across preparations. High-quality studies are required to assess and compare the safety and efficacy of IAHA preparations.

Objective: Inferior and limited analgesic options/techniques during living donor hepatectomy surgery can result in pain and risks of morbidity, opioid-related adverse events (AEs), predisposition to the development of chronic pain and concerns of potential narcotic abuse. Traditional analgesia uses unimodal intravenous opioids that can cause significant side effects. Ketamine provides analgesia and may be opioid sparing, but use in living-donor hepatectomy has not been studied. Methods: Following human investigation committee approval and informed written consent, 47 liver donor patients over a 5-year period scheduled for surgery were categorized into one of three groups: 24 patients received no ketamine (Group 1), 9 received only intraoperative ketamine (Group 2) and 14 patients received intraoperative plus postoperative ketamine (Group 3). Subjects had access to opioid patient-controlled analgesia (PCA). Chart reviews (including operating room and intensive care unit) were collected and analysed for morphine consumption, pain-intensity scores, opioid-sparing effects, AEs of analgesics and for evidence of ketamine side effects on donor hepatectomy patients. Results: There were no differences in patient demographics. Living donor hepatectomy patients receiving intraoperative ketamine that was continued postoperatively consumed fewer morphine-equivalents and had lower median pain scores than subjects from the other two groups. Ileus occurred in those not receiving ketamine, pruritus was lowest in Group 3, and there was no evidence or reports of ketamine-associated AEs. Conclusion: Perioperative ketamine for donor hepatectomy patients could safely provide improved analgesia and be opioid sparing when compared to PCA opioids alone, and there is no evidence of ketamine-related AEs at the dose and delivery methods described here during partial liver donation surgery. Keywords: Living-donor liver transplantation, ketamine, perioperative analgesia Amaç: Canlı donörlü hepatektomi ameliyatı sırasında uygulanan inferior ve sınırlı analjezi seçenekleri/teknikleri ağrıya ve morbidite riskine, opioide bağlı yan etkilere, kronik ağrı gelişimi eğilimine ve potansiyel narkotik bağımlılığına neden olabilirler. Geleneksel analjezi uygulamasında, önemli yan etkilere neden olabilen unimodal intravenöz opioidler kullanılmaktadır. Ketamin analjezi sağlar ve opioid tüketimini azaltabilir. Ancak canlı donörlü hepatektomide kullanımı hakkında henüz çalışma yapılmamıştır. Yöntemler: İnsan araştırmaları etik kurulu onayı ve yazılı bilgilendirilmiş hasta onam formu alındıktan sonra, 5 yıllık bir süreçte ameliyat olması planlanan 47 canlı donör hastası 3 gruba ayrıldı. 24 hastaya hiç ketamin verilmedi (Grup 1); 9 hastaya sadece intraoperatif ketamin verildi (Grup 2); ve 14 hastaya intraoperatif ve postoperatif ketamine uygulandı (Grup 3). Denekler hasta kontrollü opioid analjezisi kullandılar. Hastaların tıbbi kayıtları toplandı (ameliyathane ve yoğun bakım ünitesinden) ve morfin kullanımı, ağrı-yoğunluk skorları, opioid tüketiminin azaltıc...