Efficacy and safety of opioid analgesics for pain and palliative care for adults indexed on World Health Organizations Essential Medicines List : master's thesis

Uvod: Morfin, hidromorofon, oksikodon i kodein su opioidni analgetici navedeni u Osnovnoj listi lijekova Svjetske zdravstvene organizacije za liječenje boli i palijativnu skrb odraslih. Cilj ovog istraživanja bio je analizirati dokaze o djelotvornosti i sigurnosti tih analgetika za liječenje boli i palijativnu skrb u odraslih iz sustavnih pregleda s meta-analizom. Metode: Pretražene su četiri bibliografske baze podataka: baze Embase i MEDLINE putem OVID-a te baze Cochrane Database of Systematic Reviews (CDSR) i Database of Reviews of Effects (DARE) putem sučelja The Cochrane Library. Bibliografski zapisi izvedeni su iz svih bibliografskih baza podatka u računalni program EndNote, gdje je zatim provedeno brisanje duplikata, najprije računalno, a zatim i ručno ako je nakon računalnog uklanjanja duplikata ostalo još primjera duplih radova. Uključeni su radovi u čijim je naslovima i/ili sažetcima bilo navedeno da se radi o sustavnim pregledima i/ili meta-analizama, ili su navedene pretraživane bibliografske baze. Procjena metodološke kvalitete sustavnih pregleda je analizirana uz pomoć AMSTAR ljestvice. Rezultati: U istraživanje je uključeno 35 sustavnih pregleda. Objavljeni su u vremenskom razdoblju od 2000. do 2015. godine. Dokazana je djelotvornost morfina za osteoartritis, postoperativnu bol kod artroskopije koljena, karcinomsku bol, kroničnu nekarcinomsku bol, kroničnu karcinomsku i nekarcinomsku bol, akutnu abdominalnu bol, bol nakon carskog reza, postduralnu punkcijsku glavobolju i postoperativnu bol. Također je najveća incidencija nuspojava, kao što su mučnina, povraćanje, konstipacija, retencija urina, vrtoglavica, pospanost, respiratorna depresija i pruritus, bila vezana uz primjenu morfina. Za hidromorfon je dokazana djelotvornost u različitim modelima boli (akutna i kronična bol), a incidencija nuspojava nije se značajno razlikovala od one uzrokovane primjenom morfina. Djelotvornost oksikodona u bolnoj perifernoj dijabetičkoj neuropatiji je upitna, a u dozi 300 mg pokazao je i statistički značajno veći relativni rizik za nuspojave u odnosu na druge aktivne komparatore. Kodein nije pokazao bolji učinak u ublažavanju postoperativne boli u usporedbi s paracetamolom, NSAID te njihovim kombinacijama s kodeinom, osobito kod stomatoloških zahvata, a incidencija nuspojava nakon njegove primjene bila je značajno veća u usporedbi s placebom Kvaliteta pronađenih dokaza je procijenjena kao srednja. Zaključak: Dokazi o djelotvornosti i sigurnosti morfina, hidromorfona, oksikodona i kodeina u kroničnoj boli i u prevenciji postoperativne boli, boli nakon carskog reza i postduralne punkcijske glavobolje pokazuju opravdanost primjene tih lijekova za navedene indikacije. Njihova primjena u postoperativnoj boli kod stomatoloških zahvata, neuropatskoj boli i za ublažavanje simptoma dispneje povezane s karcinomom u palijativnoj skrbi je upitna. Osnovnu listu lijekova SZO trebalo bi revidirati na način da se navedu indikacije za koja stanja su navedeni opioidni analgetici dokazano djelotvorni.Introduction: Morphine, hidromorofon, oxycodone and codeine are opioid analgesics listed in the World Health Organization Model Lists of Essential Medicines (WHO EML) for relieving pain and palliative care in adults. The aim of this study was to analyze evidence from systematic reviews with meta-analysis on efficacy and safety of those analgesics for pain and palliative care in adults. Methods: Four databases were searched: MEDLINE, EMBASE, CDSR and DARE. Bibliographic records are derived from all databases in a computer program EndNote. After independent duplicate screening of bibliographic records and removing duplicate works, we included systematic reviews containing at least one meta-analysis on pain and safety of studied medicines. Methodological quality of included systematic reviews was analysed using the AMSTAR scale. Results: There were 35 systematic reviews included, published from 2000 till 2015. The efficacy of morphine was proven for osteoarthritis, postoperative pain after knee arthroscopy, cancer pain, chronic non-carcinoma pain, chronic cancer and non-carcinoma pain, acute abdominal pain, pain after cesarean section, postdural puncture headache and postoperative pain. Moreover, high number of side effects was reported as a result of taking morphine, such as nausea, vomiting, constipation, urinary retention, dizziness, drowsiness, respiratory depression and pruritus. For hydromorphone, the efficacy was proven in various models of pain (acute and chronic pain), and incidence of side effects was not significantly different from those induced by morphine. The efficacy of oxycodone in painful peripheral diabetic neuropathy is questionable. In the dose 300 mg oxycodone showed significantly higher relative risk of side effects compared to other medicines. When it comes to treatment of postoperative pain, particularly in dental surgery, codeine did not show better effect when compared to acetaminophen, NSAIDs, and their combination with codeine. The incidence of side effects as a result of taking codeine was significantly higher compared to placebo. Quality of evidence from included systematic reviews was moderate. Conclusion: Evidence from systematic reviews about efficacy and safety of morphine, hydromorphone, oxycodone and codeine as a therapy for chronic pain and for preventing postoperative pain, pain after cesarean section and postdural puncture headache is of satisfactory quality and their use in the majority of analysed indications is justified. The role of these analgesics for managing neuropathic pain and postoperative pain in dental procedures, as well as their role in palliative care for relieving symptoms of dyspnea is unclear due to lack of evidence of efficacy from systematic reviews. The WHO EML should be revised in order to specify the indications for which these analgesics have been proven as effective