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Intravenous Oxycodone Versus Other Intravenous Strong Opioids for Acute Postoperative Pain Control: a Systematic Review of Randomized Controlled Trials

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Intravenous Oxycodone Versus Other Intravenous Strong Opioids for Acute Postoperative Pain Control: a Systematic Review of Randomized Controlled Trials Pain Ther (2019) 8:19–39 https://doi.org/10.1007/s40122-019-0122-4 REVIEW Intravenous Oxycodone Versus Other Intravenous Strong Opioids for Acute Postoperative Pain Control: A Systematic Review of Randomized Controlled Trials Milton Raff . Anissa Belbachir . Salah El-Tallawy . Kok Yuen Ho . Eric Nagtalon . Amar Salti . Jeong-Hwa Seo . Aida Rosita Tantri . Hongwei Wang . Tianlong Wang . Kristal Cielo Buemio . Consuelo Gutierrez . Yacine Hadjiat Received: January 3, 2019 / Published online: April 19, 2019 Ó The Author(s) 2019 ABSTRACT (inclusive) that evaluated the acute postopera- tive analgesic efficacy of intravenous oxy- Introduction: Optimal pain management is codone against fentanyl, morphine, sufentanil, crucial to the postoperative recovery process. pethidine, and hydromorphone in adult We aimed to evaluate the efficacy and safety of patients (age C 18 years). Outcomes examined intravenous oxycodone with intravenous fen- included analgesic consumption, pain intensity tanyl, morphine, sufentanil, pethidine, and levels, side effects, and patient satisfaction. hydromorphone for acute postoperative pain. Results: Eleven studies were included in the Methods: A systematic literature search of review; six compared oxycodone with fentanyl, PubMed, Cochrane Library, and EMBASE data- two compared oxycodone with morphine, and bases was performed for randomized controlled three compared oxycodone with sufentanil. trials published from 2008 through 2017 There were no eligible studies comparing oxy- codone with pethidine or hydromorphone. Overall, analgesic consumption was lower with oxycodone than with fentanyl or sufentanil. Enhanced Digital Features To view enhanced digital Oxycodone exhibited better analgesic efficacy features for this article go to: https://doi.org/10.6084/ m9.figshare.7931558. than fentanyl and sufentanil, and comparable analgesic efficacy to morphine. In terms of Electronic supplementary material The online safety, there was a tendency towards more side version of this article (https://doi.org/10.1007/s40122- 019-0122-4) contains supplementary material, which is effects with oxycodone than with fentanyl, but available to authorized users. M. Raff (&) K. Y. Ho Pain Clinic, Christiaan Barnard Memorial Hospital, The Pain Clinic, Mount Alvernia Medical Centre, Cape Town, South Africa Singapore, Singapore e-mail: [email protected] E. Nagtalon A. Belbachir Department of Anesthesia, University of the East Faculte´ de me´decine, Universite´ Paris-Descartes, Ramon Magsaysay Memorial Medical Center, Poˆle d’anesthe´sie-re´animation, Hoˆpital Cochin, Quezon City, Philippines Paris, France A. Salti S. El-Tallawy Anesthesiology Institute, Sheikh Khalifa Medical Department of Anesthesia and Pain Management, City, Abu Dhabi, United Arab Emirates College of Medicine, King Khalid University Hospital, King Saud University, Riyadh, Saudi Arabia 20 Pain Ther (2019) 8:19–39 the incidence of side effects with oxycodone pain [1]. Acute postoperative pain is multi- was comparable to morphine and sufentanil. mechanistic and may consist of both nocicep- Where patient satisfaction was evaluated, tive and neuropathic pain [2]. Inadequate higher satisfaction levels were observed with postoperative pain control may impede recov- oxycodone than with sufentanil and compara- ery and delay rehabilitation, leading to poor ble satisfaction was noted when comparing outcomes [3]. Effective pain management is oxycodone with fentanyl. Patient satisfaction thus central to the postoperative recovery pro- was not evaluated in the studies comparing cess and can help improve patient comfort, oxycodone with morphine. enhance tissue healing, and promote early dis- Conclusions: Our findings suggest that intra- charge [4, 5]. venous oxycodone provides better analgesic effi- Analgesia administered by the intravenous cacy than fentanyl and sufentanil, and route is typically used in the early postoperative comparable efficacy to morphine with less adverse period when administration by the oral route is events such as sedation. No studies comparing less feasible [6]. In the case of moderately sev- intravenous oxycodone with pethidine or hydro- ere-to-severe acute postoperative pain, clinical morphone were identified in this review. Better practice guidelines recommend the use of alignment of study methodologies for future strong opioids such as oxycodone, morphine, research in this area is recommended to provide fentanyl, or hydromorphone as part of the thebestevidencebaseforameta-analysis. multimodal analgesic approach [7–12]. The Funding: Mundipharma Singapore Holding Pte strong opioids, sufentanil and pethidine, are Ltd, Singapore. less widely recommended—sufentanil due to its short duration of action and pethidine due to Keywords: Acute postoperative pain; Fentanyl; safety concerns. The unfavorable risk–benefit Hydromorphone; Morphine; Oxycodone; profile of pethidine has led to a gradual decline Pethidine; Sufentanil of its use for peri-operative analgesia in devel- oped countries [13, 14]. Many government, professional, and accreditation agencies view INTRODUCTION the use of pethidine as an indicator of poor quality of care [14]; however, pethidine is still The majority of patients who undergo surgical extensively used in regions composed largely of procedures experience acute postoperative pain, low- and middle-income countries (such as with over 80% reporting moderate-to-severe Africa, Eastern Mediterranean, and South-East Asia) [13]. Pharmacological properties vary amongst J.-H. Seo strong opioids (Table 1). Choosing between Department of Anesthesiology and Pain Medicine, Seoul National University Hospital, Seoul National these opioids is challenging when used for post- University College of Medicine, Seoul, Korea operative analgesia as there is little evidence to support the use of one opioid analgesic over A. R. Tantri Department of Anesthesiology and Intensive Care, another. Intravenous morphine is traditionally Universitas Indonesia, Dr. Ciptomangunkusumo the opioid of choice, but oxycodone is being National General Hospital, Jakarta, Indonesia increasingly utilized [15–17]. Unlike most strong opioids that act primarily through the l- H. Wang Department of Anesthesiology, Tongde Hospital of opioid receptor to induce analgesia [18, 19], Zhejiang Province, Hangzhou, Zhejiang, China oxycodone has additional agonistic effects on the j- and d-opioid receptors [20–22]; its addi- T. Wang Department of Anesthesiology, Xuanwu Hospital of tional action on the j-receptor has been sug- Capital Medical University, Beijing, China gested to be of particular significance for anti- nociception in the visceral pain system [23–26]. K. C. Buemio Á C. Gutierrez Á Y. Hadjiat Some studies also suggest that oxycodone has Mundipharma Singapore Holding Pte. Ltd., Singapore, Singapore an enhanced analgesic effect on neuropathic Pain Ther (2019) 8:19–39 21 Table 1 Pharmacological properties of oxycodone, morphine, fentanyl, sufentanil, pethidine, and hydromorphone Oxycodone Morphine Fentanyl Sufentanil Pethidine Hydromorphone [21, 22, 53–58] [59–61] [59, 61–63] [64–67] [61, 68–70] [71, 72] Absorption Tmax 6–25 min 19 min 4 min 6 min 1.2 min 20 min Distribution Plasma 45% 35–36% 84% * 90% * 58% 8–19% protein binding VD 2–3 l/kg 1–4.7 l/kg 4 l/kg 1.7–5.2 l/kg 3–5 l/kg 302.9 l Metabolism Major Noroxycodone, Morphine-3- Norfentanyl Norfentanyl Norpethidine Hydromorphone- metabolites oxymorphone glucuronide 3-glucuronide Excretion Cl 1.10 l/min 0.9–1.2 l/kg/h 0.8–1.0 ml/ 57.6 l/h 20.5 l/h 1.96 l/min min/kg T1/2 2–3.5 h 1.5–4.5 h 3.7 h 2.7 h 2–5 h 2.3 h Opioid receptor action l ??? ??? ??? ??? ??? ??? j ?? ? ? ? ? Nil d ?? ? Nil ?? ? Cl, clearance; Tmax, time to maximum plasma concentration; T1/2, half-life; VD, volume of distribution; l, mu-opioid receptor; j, kappa-opioid receptor; d, delta-opioid receptor pain [27, 28]. Furthermore, oxycodone has been sufentanil, hydromorphone, and pethidine) in reported to be faster-acting than morphine [29], the management of acute postoperative pain. and to provide longer-lasting analgesic effect when compared with fentanyl [30, 31] and morphine [32]. METHODS Given the increasing clinical use of oxy- codone for the management of acute postoper- Literature Search Strategy ative pain, further understanding is needed regarding the efficacy and safety of oxycodone A search of PubMed, Cochrane Library, and versus other strong opioids. This systematic EMBASE databases was conducted for studies review aims to summarize and synthesize the published from 2008 through 2017 that evalu- findings of recent head-to-head randomized ated the acute postoperative analgesic efficacy of controlled trials (RCTs) comparing the efficacy the parenteral oxycodone compared with mor- and safety of oxycodone with other strong phine, fentanyl, sufentanil, pethidine, or opioids (in particular, morphine, fentanyl, hydromorphone. The search terminology inclu- ded a variety of terms and medical subject 22 Pain Ther (2019) 8:19–39 headings for post-operative, analgesia, injection, RESULTS oxycodone, morphine, fentanyl, sufentanil, pethidine, hydromorphone, and RCTs. Search Study Inclusion strategies were developed specifically for each database. The full list of database-specific search Figure 1 shows the flow of the screening and queries is presented in Supplementary Table 1. evaluation process. The systematic literature The bibliographies of included articles were also search identified 450 publications. Ten studies screened for potentially relevant publications. met the eligibility criteria.
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