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Nonopioid, Multimodal Analgesia as First-line Therapy After Otolaryngology Operations: Primer on Nonsteroidal Anti-inflammatory Drugs (NSAIDs).
Cramer, JD, Barnett, ML, Anne, S, Bateman, BT, Rosenfeld, RM, Tunkel, DE, Brenner, MJ
Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery. 2021;(4):712-719
Abstract
OBJECTIVE To offer pragmatic, evidence-informed advice on nonsteroidal anti-inflammatory drugs (NSAIDs) as first-line therapy after surgery. This companion to the American Academy of Otolaryngology-Head & Neck Surgery (AAO-HNS) clinical practice guideline (CPG), "Opioid Prescribing for Analgesia After Common Otolaryngology Operations," presents data on potency, bleeding risk, and adverse effects for ibuprofen, naproxen, ketorolac, meloxicam, and celecoxib. DATA SOURCES National Guidelines Clearinghouse, CMA Infobase, National Library of Guidelines, NICE, SIGN, New Zealand Guidelines Group, Australian National Health and Medical, Research Council, TRIP database, PubMed, Guidelines International Network, Cochrane Library, EMBASE, CINAHL, BIOSIS Previews, ISI Web of Science, AHRQ, and HSTAT. REVIEW METHODS AAO-HNS opioid CPG literature search strategy, supplemented by PubMed/MEDLINE searches on NSAIDs, emphasizing systematic reviews and randomized controlled trials. CONCLUSION NSAIDs provide highly effective analgesia for postoperative pain, particularly when combined with acetaminophen. Inconsistent use of nonopioid regimens arises from common misconceptions that NSAIDs are less potent analgesics than opioids and have an unacceptable risk of bleeding. To the contrary, multimodal analgesia (combining 500 mg acetaminophen and 200 mg ibuprofen) is significantly more effective analgesia than opioid regimens (15 mg oxycodone with acetaminophen). Furthermore, selective cyclooxygenase-2 inhibition reliably circumvents antiplatelet effects. IMPLICATIONS FOR PRACTICE The combination of NSAIDs and acetaminophen provides more effective postoperative pain control with greater safety than opioid-based regimens. The AAO-HNS opioid prescribing CPG therefore prioritizes multimodal, nonopioid analgesia as first-line therapy, recommending that opioids be reserved for severe or refractory pain. This state-of-the-art review provides strategies for safely incorporating NSAIDs into acute postoperative pain regimens.
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2.
Opioid Management in CKD.
Lu, E, Schell, JO, Koncicki, HM
American journal of kidney diseases : the official journal of the National Kidney Foundation. 2021;(5):786-795
Abstract
Patients with chronic kidney disease (CKD) experience a high pain and symptom burden. Concurrently, opioid prescription and use in patients with CKD continues to increase, leading to concern for opioid-related risks. Nephrologists increasingly face challenging clinical situations requiring further evaluation and treatment of pain, for which opioid use may be indicated. However, nephrologists are not commonly trained in pain management and may find it difficult to compile the necessary information and tools to effectively assess and treat potentially multidimensional pain. In these situations, they may benefit from using an evidence-based stepwise approach proposed in this article. We address current approaches to opioid use for pain management in CKD and offer a stepwise approach to individualized opioid assessment, focusing on kidney-specific concerns. This includes thorough evaluation of the pain experience, opioid use history, and treatment goals. We subsequently discuss considerations when initiating opioid therapy, strategies to reduce opioid-related risks, and recommended best practices for opioid stewardship in CKD. Using this sequential approach to opioid management, nephrologists can thereby gain a broad overview of key patient considerations, the foundation for understanding implications of opioid use, and a patient-tailored plan for opioid therapy.
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Impact of Preoperative Acetaminophen and Carbohydrate Loading on Pain and Functional Status in Patients Undergoing Mohs Micrographic Surgery for Nonmelanoma Skin Cancers.
Aleisa, A, Naccarato, L, Gramz, M, Patel, J, Nguyen, B
Dermatologic surgery : official publication for American Society for Dermatologic Surgery [et al.]. 2020;(7):863-867
Abstract
BACKGROUND Preoperative acetaminophen and carbohydrate loading has been shown to improve the functional recovery of surgical patients. OBJECTIVE To determine the effects of preoperative acetaminophen and carbohydrates on functional outcomes and the use of pain medications after surgery in patients undergoing Mohs Micrographic Surgery (MMS) for nonmelanoma skin cancer (NMSC). MATERIALS AND METHODS One hundred patients treated with MMS for NMSC at an academic center were randomized into a control group receiving standard preoperative care or an intervention group receiving acetaminophen and carbohydrate drinks immediately before surgery. Patients rated levels of pain, thirst, hunger, anxiety, and fatigue on the day of surgery on a scale of 0 to 100, and reported through a phone interview the use of pain medications within 48 hours of surgery. RESULTS There was no significant difference between intervention and control groups in maximum pain score on the day of surgery; maximum pain score 48 hours after surgery; use of nonopioid pain medications; and use of opioids. However, the intervention group had lower anxiety levels during and at the end of surgery. CONCLUSION Patients undergoing MMS for NMSC reported very low levels of pain during and after surgery. Preoperative acetaminophen and carbohydrate loading had no impact on pain levels or the use of pain medications but did reduce levels of anxiety.
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4.
Efficacy of non-opioid analgesics to control postoperative pain: a network meta-analysis.
Carter, JA, Black, LK, Sharma, D, Bhagnani, T, Jahr, JS
BMC anesthesiology. 2020;(1):272
Abstract
BACKGROUND The aim of this network meta-analysis (NMA) was to evaluate the safety and efficacy of intravenous (IV) Meloxicam 30 mg (MIV), an investigational non-steroidal anti-inflammatory drug (NSAID), and certain other IV non-opioid analgesics for moderate-severe acute postoperative pain. METHODS We searched PubMed and CENTRAL for Randomized Controlled Trials (RCT) (years 2000-2019, adult human subjects) of IV non-opioid analgesics (IV NSAIDs or IV Acetaminophen) used to treat acute pain after abdominal, hysterectomy, bunionectomy or orthopedic procedures. A Bayesian NMA was conducted in R to rank treatments based on the standardized mean differences in sum of pain intensity difference from baseline up to 24 h postoperatively (sum of pain intensity difference: SPID 24). The probability and the cumulative probability of rank for each treatment were calculated, and the surface under the cumulative ranking curve (SUCRA) was applied to distinguish treatments on the basis of their outcomes such that higher SUCRA values indicate better outcomes. The study protocol was prospectively registered with by PROSPERO (CRD42019117360). RESULTS Out of 2313 screened studies, 27 studies with 36 comparative observations were included, producing a treatment network that included the four non-opioid IV pain medications of interest (MIV, ketorolac, acetaminophen, and ibuprofen). MIV was associated with the largest SPID 24 for all procedure categories and comparators. The SUCRA ranking table indicated that MIV had the highest probability for the most effective treatment for abdominal (89.5%), bunionectomy (100%), and hysterectomy (99.8%). MIV was associated with significantly less MME utilization versus all comparators for abdominal procedures, hysterectomy, and versus acetaminophen in orthopedic procedures. Elsewhere MME utilization outcomes for MIV were largely equivalent or nominally better than other comparators. Odds of ORADEs were significantly higher for all comparators vs MIV for orthopedic (gastrointestinal) and hysterectomy (respiratory). CONCLUSIONS MIV 30 mg may provide better pain reduction with similar or better safety compared to other approved IV non-opioid analgesics. Caution is warranted in interpreting these results as all comparisons involving MIV were indirect.
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Whole-Course Application of Dexmedetomidine Combined with Ketorolac in Nonnarcotic Postoperative Analgesia for Patients with Lung Cancer Undergoing Thoracoscopic Surgery: A Randomized Control Trial.
Miao, Z, Wu, P, Wang, J, Zhou, FC, Lin, Y, Lu, XY, Lv, R, Hou, QH, Wen, QP
Pain physician. 2020;(2):E185-E193
Abstract
BACKGROUND Opioid-based postoperative analgesia provides adequate analgesia with much adverse effects and immunosuppression. Dexmedetomidine and ketorolac have properties of opioid-sparing, antiinflammation, and immune protection. OBJECTIVES To investigate the efficacy and safety of whole-course application of dexmedetomidine combined with ketorolac in nonnarcotic postoperative analgesia and its effect on inflammatory response and immune function in thoracoscopic surgery of lung cancer. STUDY DESIGN Double-blind, randomized control trial. SETTING The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China. METHODS Sixty patients scheduled for thoracoscopic surgery were enrolled and randomly divided into 2 groups to receive a combination of intraoperative usage of dexmedetomidine and postoperative patient-controlled intravenous analgesia of dexmedetomidine 0.1 µg/kg/h and ketorolac 3 mg/kg (DEX group) or only postoperative patient-controlled intravenous analgesia of sufentanil 1.5 µg/kg and ketorolac 3 mg/kg (SUF group) for 48 hours. Vital signs, postoperative Visual Analog Scale (VAS) score, Ramsay sedation score, patient-controlled analgesia pressing times, consumption of sufentanil and rescue drug, and complications were compared between the 2 groups. The levels of inflammatory factors and immune function were also compared. RESULTS A significant reduction in median blood pressures and heart rates within 48 hours after surgery and perioperative consumption of sufentanil were observed in the DEX group compared with the SUF group (P < 0.05). No statistically significant difference was found in VAS scores, patient-controlled analgesia pressing times, and rescue drug consumption between the 2 groups (P > 0.05). The incidence of nausea was significantly lower in the DEX group compared with the SUF group (P < 0.05). A significant decrease of interleukin (IL)-1 beta, IL-6, tumor necrosis factor (TNF)-alpha, and increased CD4+ and CD4+/CD8+ were observed in the DEX group compared with the SUF group at 24 and 48 hours after surgery (P < 0.05). There was no difference in the levels of CD8+ and natural killer cells between the 2 groups (P > 0.05). LIMITATIONS This study was limited by its sample size. CONCLUSIONS Whole-course application of dexmedetomidine combined with ketorolac in nonnarcotic postoperative analgesia provided adequate and safe postoperative analgesia, reduced sufentanil consumption, analgesia-related complications, alleviated inflammatory response, and immunosuppression compared with sufentanil-based analgesia in thoracoscopic surgery. KEY WORDS Dexmedetomidine, ketorolac, sufentanil, thoracoscopic surgery, postoperative analgesic, patient-controlled analgesia, inflammatory response, immune function.
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Opioid Use and Misuse in Pregnancy.
Shatil, B, Landau, R
Clinics in perinatology. 2020;(4):769-777
Abstract
The rate of pregnant women with an opioid use disorder has risen drastically in the past 20 years, paralleling that in the general population. Pregnancies associated with opioid use, abuse, or dependence have significantly higher rates of complications, such as neonatal opioid withdrawal syndrome, intrauterine growth restriction, neural tube defects, stillbirth, increased maternal mortality, greater postpartum pain, and longer inpatient stays. Patient education about the risks and benefits of multimodal analgesia and empowering shared decision making may help curb the opioid epidemic. Tailoring pain management to individual needs might be the solution to the problem.
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Predictors of Nabiximols (Sativex®) discontinuation over long-term follow-up: a real-life study.
Carotenuto, A, Costabile, T, De Lucia, M, Moccia, M, Falco, F, Petruzzo, M, De Angelis, M, Russo, CV, Saccà, F, Lanzillo, R, et al
Journal of neurology. 2020;(6):1737-1743
Abstract
Nabiximols is an effective treatment for spasticity in MS. However, treatment discontinuation over-time might occur and predictors of sustained treatment persistence over long-term follow-up in real-world settings are highly needed. We aim at evaluating baseline predictors of treatment persistence on Nabiximols. This is a retrospective real-world study including MS patients treated with Nabiximols. At baseline (Nabiximols prescription), we evaluated disability using the EDSS, and cognitive function using the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS). Nabiximols discontinuation was evaluated after 4 weeks of treatment ("titration phase''), and over the follow-up ("treatment phase"). We included 396 MS patients (228 females and 168 males). After 4 weeks (titration phase), 266 MS patients (67.2%) were considered persistent on treatment, while 130 patients dropped out. After 19 ± 21 months (treatment phase), 136 out of 266 MS patients (51.1%) were still on treatment, whereas 130 patients dropped at follow-up. Higher EDSS and cognitive impairment predicted treatment discontinuation at follow-up (p = 0.04 and p = 0.005, respectively). In conclusion, higher physical and cognitive disability predicted Nabiximols treatment discontinuation over 2 years in MS patients suffering from spasticity. Nabiximols should be started earlier to decrease the likelihood of treatment discontinuation over time.
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Early acetaminophen-protein adducts predict hepatotoxicity following overdose (ATOM-5).
Chiew, AL, James, LP, Isbister, GK, Pickering, JW, McArdle, K, Chan, BSH, Buckley, NA
Journal of hepatology. 2020;(3):450-462
Abstract
BACKGROUND & AIMS Acetaminophen-protein adducts are specific biomarkers of toxic acetaminophen (paracetamol) metabolite exposure. In patients with hepatotoxicity (alanine aminotransferase [ALT] >1,000 U/L), an adduct concentration ≥1.0 nmol/ml is sensitive and specific for identifying cases secondary to acetaminophen. Our aim was to characterise acetaminophen-protein adduct concentrations in patients following acetaminophen overdose and determine if they predict toxicity. METHODS We performed a multicentre prospective observational study, recruiting patients 14 years of age or older with acetaminophen overdose regardless of intent or formulation. Three serum samples were obtained within the first 24 h of presentation and analysed for acetaminophen-protein adducts. Acetaminophen-protein adduct concentrations were compared to ALT and other indicators of toxicity. RESULTS Of the 240 patients who participated, 204 (85%) presented following acute ingestions, with a median ingested dose of 20 g (IQR 10-40), and 228 (95%) were treated with intravenous acetylcysteine at a median time of 6 h (IQR 3.5-10.5) post-ingestion. Thirty-six (15%) patients developed hepatotoxicity, of whom 22 had an ALT ≤1,000 U/L at the time of initial acetaminophen-protein adduct measurement. Those who developed hepatotoxicity had a higher initial acetaminophen-protein adduct concentration compared to those who did not, 1.63 nmol/ml (IQR 0.76-2.02, n = 22) vs. 0.26 nmol/ml (IQR 0.15-0.41; n = 204; p <0.0001), respectively. The AUROC for hepatotoxicity was 0.98 (95% CI 0.96-1.00; n = 226; p <0.0001) with acetaminophen-protein adduct concentration and 0.89 (95% CI 0.82-0.96; n = 219; p <0.0001) with ALT. An acetaminophen-protein adduct concentration of 0.58 nmol/ml was 100% sensitive and 91% specific for identifying patients with an initial ALT ≤1,000 U/L who would develop hepatotoxicity. Adding acetaminophen-protein adduct concentrations to risk prediction models improved prediction of hepatotoxicity to a level similar to that obtained by more complex models. CONCLUSION Acetaminophen-protein adduct concentration on presentation predicted which patients with acetaminophen overdose subsequently developed hepatotoxicity, regardless of time of ingestion. An adduct threshold of 0.58 nmol/L was required for optimal prediction. LAY SUMMARY Acetaminophen poisoning is one of the most common causes of liver injury. This study examined a new biomarker of acetaminophen toxicity, which measures the amount of toxic metabolite exposure called acetaminophen-protein adduct. We found that those who developed liver injury had a higher initial level of acetaminophen-protein adducts than those who did not. CLINICAL TRIAL REGISTRATION Australian Toxicology Monitoring (ATOM) Study-Australian Paracetamol Project: ACTRN12612001240831 (ANZCTR) Date of registration: 23/11/2012.
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Pain Management After Surgical Tonsillectomy: Is There a Favorable Analgesic?
Jotić, A, Savić Vujović, K, Milovanović, J, Vujović, A, Radin, Z, Milić, N, Vučković, S, Medić, B, Prostran, M
Ear, nose, & throat journal. 2019;(6):356-361
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Abstract
The aim of this study was to examine how ibuprofen and paracetamol prevent pain after cold-steel extracapsular tonsillectomy in children. Also, we examined the relation between age, gender, nausea, postoperative bleeding, antibiotic use, type of diet, and postoperative pain intensity and the type of administered analgesic. A prospective study was conducted on 147 children (95 males and 52 females, aged 7-17 years) who underwent tonsillectomy in the Clinical-Hospital Center "Dragiša Mišović" from January 1 to June 30, 2016. The degree of pain was measured using a visual analog scale (VAS). We did not observe any significant differences in postoperative nausea, hospitalization rate postoperative bleeding, and antibiotic use between the paracetamol and ibuprofen groups. A test of within-patient effects showed that VAS scores changed significantly during the postoperative follow-up period (P = .00), but there were no significant differences between the groups (P = .778). After 12 hours, 29.3% of the patients on paracetamol and 21.8% on ibuprofen were transferred to a soft diet; after 24 hours, 84.8% of the paracetamol group and 85.5% of the ibuprofen group were on a soft diet (χ2 test, P < .05). There was a statistically significant correlation between VAS scores measured 4 hours after the surgery and the time of transference to the soft diet (Spearman ρ test, P < .001). The transfer to soft and normal diets was not significantly different between the 2 groups as assessed by the VAS scores (Pearson χ2 test, P = .565).There is still no consensus on the most effective postoperative pain-control regiment after tonsillectomy. This study showed that satisfactory pain management was achieved equally with both paracetamol and ibuprofen.
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N-acetylcysteine prevents glutathione decrease and does not interfere with paracetamol antinociceptive effect at therapeutic dosage: a randomized double-blind controlled trial in healthy subjects.
Pickering, G, Macian, N, Papet, I, Dualé, C, Coudert, C, Pereira, B
Fundamental & clinical pharmacology. 2019;(3):303-311
Abstract
Paracetamol (APAP) may lead to hepatic changes even at therapeutic dosages. Glutathione (GSH) plays a pivotal role in APAP metabolism as it allows the detoxification of a toxic metabolite. N-Acetylcysteine (NAC) is APAP antidote, is also largely used as a mucoactive drug and is often associated with APAP. This study aims at evaluating if 1- NAC modifies APAP pain efficacy and 2- NAC prevents glutathione depletion with APAP at therapeutic doses. This double-blind randomized controlled study (NCT02206178) was carried out in 24 healthy volunteers. APAP was given for 4 days (1 g ×4 daily) with NAC or with placebo. Thermal pain tests, whole blood GSH, and hepatic enzymes (ASAT, ALAT) were measured before (D0) and after (D4) oral APAP-NAC or APAP-placebo intake. anova for repeated measures adapted to cross-overdesign was performed and a two-tailed type I error was fixed at 5%. The primary endpoint was the area under the curve (0-240 min) of pain intensity (Numerical Scale) after thermal pain stimulation using Pathway-Medoc® . APAP antinociceptive effect was similar in both groups. GSH was maintained to its baseline value in the APAP/NAC group but diminished in the APAP/placebo group (P = 0.033). This study shows for the first time that APAP antinociceptive effectiveness is not influenced by NAC. It also shows that the effect of APAP at therapeutic dosage on GSH may be counteracted by NAC. These issues are particularly important for patients as APAP is often prescribed for years as a first-line pain treatment and further trials in patients are now warranted.