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Parenteral routes for opioid administration in cancer pain management

  • Sebastiano Mercadante
    Correspondence
    Anesthesia and Intensive Care and Pain Relief and Palliative Care Unit, La Maddalena Cancer Center, Via San Lorenzo 312, 901456 Palermo, Italy. Tel.: +39 0916806521; fax: +39 0916806110.
    Affiliations
    Anesthesia and Intensive Care and Pain Relief and Palliative Care Unit, La Maddalena Cancer Center, Palermo, Italy
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      Oral opioid administration is preferable in most cancer patients with pain. However, while the oral route is not available for different reasons, an alternative route of administration is often necessary in many clinical circumstances ⦋1⦌. The parenteral routes of administration consist in the intravenous (IV) and subcutaneous route (SC). Parenteral opioids have been used in different clinical situations. The aim of this short review is to provide an overview of the use of parenteral opioids for cancer pain management.
      • 1.
        Characteristics of SC and IV route. SC administration is easy and can be effectively used in some settings, such as hospices, nursing homes, or home care. However, patients with generalized edema or poor peripheral circulation, patients who develop erythema, soreness, or abscesses, and those with coagulation disorders are unfitted for SC route. Although IV administration may require some supervision, it has consistent advantages. IV route also facilitates hydration, and may provide an immediate treatment for emergencies [
        • Mercadante S.
        Intravenous morphine for management of cancer pain.
        ].
      • 2.
        Efficacy. Parenteral opioids are considered a good alternative to oral opioids and were recommended for patients candidates to spinal analgesia [
        • Caraceni A.
        • Hanks G.
        • Kaasa S.
        • et al.
        Use of opioid analgesics in the treatment of cancer pain: evidence-based recommendations from the EAPC..
        ]. In advanced cancer patients who failed with oral or transdermal opioids, the use of parenteral opioids provided optimal pain with no relevant adverse effects in most patients. Constipation and the need for laxatives occurred more frequently when patients were given morphine parenterally [
        • Mazumdar A.
        • Mishra S.
        • Bhatnagar S.
        • et al.
        Intravenous morphine can avoid distressing constipation associated with oral morphine: a retrospective analysis of our experience in 11 patients in the palliative care in-patient unit.
        ], and analgesia was similar to that obtained with epidural morphine [
        • Kalso E.
        • Heiskanen T.
        • Rantio M.
        • et al.
        Epidural and subcutaneous morphine in the management of cancer pain: a double-blind cross-over study.
        ].
        SC-IV comparison studies. Both routes were feasible, effective, and safe. While efficacy seems to be similar, the rapidity of effect seems to be in favor of IV route. Patients who receive higher doses of morphine may need higher doses of SC morphine in comparison with IV route, as high volume infusions may limit SC absorption [
        • Nelson K.
        • Glare P.
        • Walsh D.
        • et al.
        A prospective, within-patient, crossover study of continuous intravenous and subcutaneous morphine for chronic cancer pain.
        ]. In a randomized trial comparing SC and IV morphine dose titration in patients with uncontrolled cancer pain, boluses of morphine were calculated on the basis of the previous oral dose and given every 5 min or 30 min, with IV and SC, respectively. An improvement in pain intensity was observed with both routes with mean morphine IV and SC doses of about 18 mg and 56 mg, respectively. SC morphine titration required more time and higher doses than IV titration, although no differences were observed 24 h after [
        • Elsner F.
        • Radbruch L.
        • Loick G.
        • et al.
        Intravenous versus subcutaneous morphine titration in patients with persisting exacerbation of cancer pain.
        ]. These findings suggest that IV morphine titration allows a timely analgesic activity.
      • 3.
        Breakthrough pain. Breakthrough cancer pain is a transitory peak in pain intensity, occurring spontaneously, or in relation to a specific trigger, in patients with otherwise stable background pain. Supplemental dosing of an opioid is the main treatment suggested to manage breakthrough pain. In patients who are highly tolerant to opioids, IV route may be an option for their refractory pain condition. IV patient-controlled analgesia (IV-PCA) technique has been proposed to provide timely, safe, and useful analgesia for patients with severe breakthrough pain. This technique, however, is not easily applicable in the setting of palliative care because of the costs and complexity [
        • Mercadante S.
        Intravenous morphine for management of cancer pain.
        ]. IV morphine has been effectively used for treating breakthrough pain by using doses proportional to the opioid basal regimen, according to the level of patient’ opioid tolerance [
        • Mercadante S.
        • Intravaia G.
        • Villari P.
        • et al.
        Intravenous morphine for breakthrough (episodic) pain in an acute palliative care unit: a confirmatory study.
        ]. In a comparison study with oral transmucosal fentanyl citrate, both drugs were equally safe and effective, but IV morphine had a shorter onset than fentanyl [
        • Mercadante S.
        • Villari P.
        • Ferrera P.
        • et al.
        Transmucosal fentanyl vs intravenous morphine in doses proportional to basal opioid regimen for episodic breakthrough pain.
        ]. Fentanyl, other than being more potent than morphine, is able to achieve a faster peak effects after IV administration.
      • 5.
        Dose titration studies. Most patients with cancer have moderate pain intensities and require simple titration schedules with oral opioids [
        • Caraceni A.
        • Hanks G.
        • Kaasa S.
        • et al.
        Use of opioid analgesics in the treatment of cancer pain: evidence-based recommendations from the EAPC..
        ]. However, the presence of severe pain intensity requires aggressive dosing that is not feasible with standard methods of oral opioid titration, that can take several days to achieve an effective dose. Rapid titration with IV morphine has been found to provide fast and efficient pain relief in cancer patients with severe excruciating pain. With IV morphine, the analgesic effect can be appreciated in a shorter time and dosing can be rapidly changed according to the clinical response. In advanced cancer patients with severe pain, boluses of IV morphine were given until the initial signs of significant analgesia were detected or severe adverse effects occurred. Effective analgesia was achieved in less than 10 min, using mean doses of 8.5 mg of IV morphine [
        • Mercadante S.
        • Villari P.
        • Ferrera P.
        • et al.
        Rapid titration with intravenous morphine for severe cancer pain and immediate oral conversion.
        ]. The use of IV methadone by patient-controlled analgesia could be an attractive method for the management of severe cancer pain and may offer some advantages over high-dose IV morphine.
      • 5.
        Risk for developing respiratory depression. Respiratory depression is one of the more feared adverse effect of opioids. Observational studies in cancer patients treated with morphine did not show significant respiratory changes, even in the elderly or with high doses [
        • Mercadante S.
        Intravenous morphine for management of cancer pain.
        ]. These observations suggest that the rapid administration of even consistent doses of opioids has a low potential of respiratory depression when a careful dose titration is done by experienced professionals, due to a protective effect of opioid tolerance. Indeed, pain relief may indirectly reduce dyspnea due to chest involvement, facilitating breathing.
      • 6.
        Conversion studies Some patients may require to change the route of administration because they are no longer able to swallow oral medications. An oral-to-IV relative potency ratio of 1:2 to 1:3 in patients with cancer pain receiving chronic morphine treatment has been commonly used [
        • Caraceni A.
        • Hanks G.
        • Kaasa S.
        • et al.
        Use of opioid analgesics in the treatment of cancer pain: evidence-based recommendations from the EAPC..
        ]. This assumption was supported by pharmacokinetic and clinical studies [
        • Mercadante S.
        Opioid metabolism and clinical aspects.
        ].
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      References

        • Caraceni A.
        • Hanks G.
        • Kaasa S.
        • et al.
        Use of opioid analgesics in the treatment of cancer pain: evidence-based recommendations from the EAPC..
        Lancet Oncol. 2012; 13: e58-68
        • Mercadante S.
        Intravenous morphine for management of cancer pain.
        Lancet Oncol. 2010; 11: 484-489
        • Mazumdar A.
        • Mishra S.
        • Bhatnagar S.
        • et al.
        Intravenous morphine can avoid distressing constipation associated with oral morphine: a retrospective analysis of our experience in 11 patients in the palliative care in-patient unit.
        Am J Hosp Palliat Care. 2008; 25: 282-284
        • Kalso E.
        • Heiskanen T.
        • Rantio M.
        • et al.
        Epidural and subcutaneous morphine in the management of cancer pain: a double-blind cross-over study.
        Pain. 1996; 67: 443-449
        • Nelson K.
        • Glare P.
        • Walsh D.
        • et al.
        A prospective, within-patient, crossover study of continuous intravenous and subcutaneous morphine for chronic cancer pain.
        J Pain Symptom Manage. 1997; 13: 262-267
        • Elsner F.
        • Radbruch L.
        • Loick G.
        • et al.
        Intravenous versus subcutaneous morphine titration in patients with persisting exacerbation of cancer pain.
        J Palliat Med. 2005; 8: 743-750
        • Mercadante S.
        • Intravaia G.
        • Villari P.
        • et al.
        Intravenous morphine for breakthrough (episodic) pain in an acute palliative care unit: a confirmatory study.
        J Pain Symptom Manage. 2008; 35: 307-313
        • Mercadante S.
        • Villari P.
        • Ferrera P.
        • et al.
        Transmucosal fentanyl vs intravenous morphine in doses proportional to basal opioid regimen for episodic breakthrough pain.
        Br J Cancer. 2007; 96: 1828-1833
        • Mercadante S.
        • Villari P.
        • Ferrera P.
        • et al.
        Rapid titration with intravenous morphine for severe cancer pain and immediate oral conversion.
        Cancer. 2002; 95: 203-208
        • Mercadante S.
        Opioid metabolism and clinical aspects.
        Eur J Pharmacol. 2015; 769: 71-78