Tools
Morphine
Indications
FDA-approved usage of morphine sulfate includes moderate to severe pain that may be acute or chronic. Most commonly used in pain management, morphine provides significant relief to patients afflicted with pain.[1] Clinical situations that benefit significantly by medicating with morphine include management of palliative/end-of-life care, active cancer treatment, and vaso-occlusive pain during sickle cell crisis. Morphine is widely used off-label for almost any condition that causes pain. In the emergency department, morphine is given for musculoskeletal pain, abdominal pain, chest pain, arthritis, and even headaches when patients fail to respond to first and second-line agents.[2] Morphine is rarely used for procedural sedation. However, for small procedures, physicians will sometimes combine a low dose of morphine with a low dose of benzodiazepine-like lorazepam.
Patients that are actively having acute coronary syndrome are often given morphine in the emergency setting before going to the cath lab. Morphine to relieve pain during a myocardial infarction (MI) has been in use since the early 1900s. In 2005, an observational study raised some concerns, but there are very few effective alternatives. Morphine is a potent opioid; it decreases pain, which in turn leads to a decrease in the activation of the autonomic nervous system. These are desirable effects when a patient is having an MI. Additionally, morphine has hemodynamic side effects that can be beneficial during an MI.[3]
Morphine can decrease heart rate, blood pressure, and venous return. Morphine can also stimulate local histamine-mediated processes.[4] In theory, the combination of these can reduce myocardial oxygen demand.
Mechanism of Action
Register For Free And Read The Full Article
Search engine and full access to all medical articles- 10 free questions in your specialty
- Free CME/CE Activities
- Free daily question in your email
- Save favorite articles to your dashboard
- Emails offering discounts
Learn more about a Subscription to StatPearls Point-of-Care
Mechanism of Action
Morphine is considered the classic opioid analgesic with which other painkillers are compared. Like other medications in this class, morphine has an affinity for delta, kappa, and mu-opioid receptors.[5] This drug produces most of its analgesic effects by binding to the mu-opioid receptor within the central nervous system (CNS) and the peripheral nervous system (PNS).[6] The net effect of morphine is the activation of descending inhibitory pathways of the CNS as well as inhibition of the nociceptive afferent neurons of the PNS, which leads to an overall reduction of the nociceptive transmission.
Administration
Morphine administration can occur through various vehicles. Its administration is most often via the following routes: orally (PO), intravenously (IV), epidural, and intrathecal. Oral formulations are available in both immediate and extended-release for the treatment of acute and chronic pain. Pain that is more severe and not well controlled may be manageable with single or continuous doses of IV, epidural, and intrathecal formulations.[2] Infusion dosing can vary significantly between patients and largely depends on how naive or tolerant they are to opiates. It is interesting to point out that IV morphine formulation is also commonly given intramuscularly (IM). Morphine is also available as a suppository.[7] Morphine is widely used and abused. As a result of this, people have found ways to insufflate (snort) the medication.[8] Morphine is also available as an oral solution and can be administered sublingually. Sublingual morphine is very popular in palliative care.
Adverse Effects
Among the more common unwanted effects of morphine use is constipation. This effect occurs via stimulation of mu-opioid receptors on the myenteric plexus, which in turn inhibits gastric emptying and reduces peristalsis. Other common side effects include central nervous system depression, nausea, vomiting, and urinary retention. Respiratory depression is among the more serious adverse reactions with opiate use that is especially important to monitor in the postoperative patient population.[9] Other reported side effects include lightheadedness, sedation, and dizziness. Patients often report nausea and vomiting, which is why in many emergency departments, morphine administration is with an antiemetic such as ondansetron.[10] Other effects include euphoria, dysphoria, agitation, dry mouth, anorexia, and biliary tract spasm, which is why some physicians will avoid morphine when patients present with right upper quadrant pain and they suspect possible biliary tract pathology. Morphine can also affect the cardiovascular system and reportedly can cause flushing, bradycardia, hypotension, and syncope. It is also important to note that patients can experience pruritis, urticaria, edema, and other skin rashes.
Contraindications
Morphine is an extremely beneficial medication when used appropriately. However, in certain situations, this medication may be strongly contraindicated. Extreme caution is necessary with severe respiratory depression and asthma exacerbation cases since morphine can further decrease the respiratory drive. Additionally, morphine should be avoided in cases of previous hypersensitivity reaction and immediately discontinued in the presence of an active reaction.[11] Caution is also necessary with the concurrent use of monoamine oxidase inhibitors (MAOIs) as these medications have an additive effect with morphine. This combination can then trigger severe hypotension, serotonin syndrome, or increase respiratory depression in patients. GI obstruction is another important contraindication.[1] It is also considered by many as a contraindication to provide opioids to individuals that have a history of substance misuse, especially if a patient has had a history of abusing opioids. Although this is a very controversial topic, most clinicians would agree that pain requires management.[12] However, most will agree and acknowledge that there are alternatives to opioid analgesics.
Monitoring
The efficacy and therapeutic index of morphine are assessable with a combination of subjective and objective findings. Controlling pain, which is usually the first symptom evaluated in patients, is the ultimate goal of morphine use. Other essential parameters requiring monitoring include mental status, blood pressure, respiratory drive, and misuse/overuse.[2] Although it may seem intuitive, it is also important to monitor what other medications a patient is taking. This list includes but is not limited to prescription medications. All patients taking morphine should understand the need to avoid any other substances that could lead to respiratory depression.[13] These medications include but are not limited to alcohol, additional opioids, benzodiazepines, and barbiturates. Patients can become apneic at lower doses if combining morphine with any of these substances.
Toxicity
Morphine can potentially be a lethal medication when not used properly.[14] It causes a host of symptoms related to depression of the CNS. Severe respiratory depression is the most feared complication of morphine in cases of overdose. Immediate injection of naloxone is required to reverse the effects of morphine.
Enhancing Healthcare Team Outcomes
Ordering and administering morphine requires an interprofessional team of healthcare professionals, including clinicians, mid-level practitioners, nurses, and pharmacists.[15] However, patients may be transferred throughout the hospital while under the effects of these medications. Morphine use, monitoring, and administration can utilize many resources, including laboratory technologists, pharmacists, and nurses/nursing assistants. Without proper training and careful monitoring, often starting in the emergency department, patients can develop serious side effects and have adverse reactions to morphine. The clinician is responsible for coordinating the care, which includes the following:
- Ordering the drug
- Monitoring the patient for signs and symptoms of respiratory depression[16]
- Administering the drug
- Consulting with the pharmacist about the use of morphine with other medications that can cause respiratory depression.
- Consulting with a specialist if an overdose or allergic reaction occurs.
- Consulting with the radiology if a patient has received morphine prior to imaging
- Consulting with the cardiologist if using morphine in a STEMI[17]
References
Hosseininejad SM, Mohammadian Amiri M, Bozorgi F, Montazar SH, Firouzian A, Moosazadeh M, Goli Khatir I, Shahbakhti N, Darvishi-Khezri H. Does co-treatment with ultra-low-dose naloxone and morphine provide better analgesia in renal colic patients? The American journal of emergency medicine. 2019 Jun:37(6):1025-1032. doi: 10.1016/j.ajem.2018.08.038. Epub 2018 Aug 16 [PubMed PMID: 30121157]
Barut GA, Tunç M, Şahin Ş, Ulus F, Sazak H. Effects of epidural morphine and levobupivacaine combination before incision and after incision and in the postoperative period on thoracotomy pain and stress response. Turkish journal of medical sciences. 2018 Aug 16:48(4):716-723. doi: 10.3906/sag-1706-106. Epub 2018 Aug 16 [PubMed PMID: 30119145]
El Shora HA, El Beleehy AA, Abdelwahab AA, Ali GA, Omran TE, Hassan EA, Arafat AA. Bilateral Paravertebral Block versus Thoracic Epidural Analgesia for Pain Control Post-Cardiac Surgery: A Randomized Controlled Trial. The Thoracic and cardiovascular surgeon. 2020 Aug:68(5):410-416. doi: 10.1055/s-0038-1668496. Epub 2018 Aug 16 [PubMed PMID: 30114712]
Level 1 (high-level) evidenceSchauer SG, Naylor JF, Maddry JK, Hinojosa-Laborde C, April MD. Trends in Prehospital Analgesia Administration by US Forces From 2007 Through 2016. Prehospital emergency care. 2019 Mar-Apr:23(2):271-276. doi: 10.1080/10903127.2018.1489022. Epub 2018 Aug 17 [PubMed PMID: 30118637]
Haghjooy-Javanmard S, Ghasemi A, Laher I, Zarrin B, Dana N, Vaseghi G. Influence of morphine on TLR4/ NF-kB signaling pathway of MCF-7 cells. Bratislavske lekarske listy. 2018:119(4):229-233. doi: 10.4149/BLL_2018_043. Epub [PubMed PMID: 30113863]
Leite Junior JB, de Mello Bastos JM, Samuels RI, Carey RJ, Carrera MP. Reversal of morphine conditioned behavior by an anti-dopaminergic post-trial drug treatment during re-consolidation. Behavioural brain research. 2019 Feb 1:359():771-782. doi: 10.1016/j.bbr.2018.08.009. Epub 2018 Aug 13 [PubMed PMID: 30114434]
Anghelescu DL, Guo A, Morgan KJ, Frett M, Prajapati H, Gold R, Federico SM. Pain Outcomes After Celiac Plexus Block in Children and Young Adults with Cancer. Journal of adolescent and young adult oncology. 2018 Dec:7(6):666-672. doi: 10.1089/jayao.2018.0035. Epub 2018 Aug 16 [PubMed PMID: 30113244]
Hess SR, Lahaye LA, Waligora AC, Sima AP, Jiranek WA, Golladay GJ. Safety and side-effect profile of intrathecal morphine in a diverse patient population undergoing total knee and hip arthroplasty. European journal of orthopaedic surgery & traumatology : orthopedie traumatologie. 2019 Jan:29(1):125-129. doi: 10.1007/s00590-018-2293-9. Epub 2018 Aug 13 [PubMed PMID: 30105593]
Gomtsian L, Bannister K, Eyde N, Robles D, Dickenson AH, Porreca F, Navratilova E. Morphine effects within the rodent anterior cingulate cortex and rostral ventromedial medulla reveal separable modulation of affective and sensory qualities of acute or chronic pain. Pain. 2018 Dec:159(12):2512-2521. doi: 10.1097/j.pain.0000000000001355. Epub [PubMed PMID: 30086115]
Han L, Su Y, Xiong H, Niu X, Dang S, Du K, Li Q, Liu J, Zhang P, Li S. Oxycodone versus sufentanil in adult patient-controlled intravenous analgesia after abdominal surgery: A prospective, randomized, double-blinded, multiple-center clinical trial. Medicine. 2018 Aug:97(31):e11552. doi: 10.1097/MD.0000000000011552. Epub [PubMed PMID: 30075523]
Level 1 (high-level) evidenceKim M, Custodio RJ, Botanas CJ, de la Peña JB, Sayson LV, Abiero A, Ryoo ZY, Cheong JH, Kim HJ. The circadian gene, Per2, influences methamphetamine sensitization and reward through the dopaminergic system in the striatum of mice. Addiction biology. 2019 Sep:24(5):946-957. doi: 10.1111/adb.12663. Epub 2018 Aug 9 [PubMed PMID: 30091820]
Davis MP, Pasternak G, Behm B. Treating Chronic Pain: An Overview of Clinical Studies Centered on the Buprenorphine Option. Drugs. 2018 Aug:78(12):1211-1228. doi: 10.1007/s40265-018-0953-z. Epub [PubMed PMID: 30051169]
Level 3 (low-level) evidenceBriggs SB, Hafenbreidel M, Young EJ, Rumbaugh G, Miller CA. The role of nonmuscle myosin II in polydrug memories and memory reconsolidation. Learning & memory (Cold Spring Harbor, N.Y.). 2018 Sep:25(9):391-398. doi: 10.1101/lm.046763.117. Epub 2018 Aug 16 [PubMed PMID: 30115760]
Kim K, Zheng F, Zhan CG. Oligomerization and Catalytic Parameters of Human UDP-Glucuronosyltransferase 1A10: Expression and Characterization of the Recombinant Protein. Drug metabolism and disposition: the biological fate of chemicals. 2018 Oct:46(10):1446-1452. doi: 10.1124/dmd.118.082495. Epub 2018 Aug 15 [PubMed PMID: 30111624]
Gushgari AJ, Driver EM, Steele JC, Halden RU. Tracking narcotics consumption at a Southwestern U.S. university campus by wastewater-based epidemiology. Journal of hazardous materials. 2018 Oct 5:359():437-444. doi: 10.1016/j.jhazmat.2018.07.073. Epub 2018 Jul 24 [PubMed PMID: 30059885]
Planelles B, Margarit C, Ajo R, Sastre Y, Muriel J, Inda MD, Esteban MD, Peiró AM. Health benefits of an adverse events reporting system for chronic pain patients using long-term opioids. Acta anaesthesiologica Scandinavica. 2019 Feb:63(2):248-258. doi: 10.1111/aas.13243. Epub 2018 Aug 14 [PubMed PMID: 30109708]
Manchikanti L, Sanapati J, Benyamin RM, Atluri S, Kaye AD, Hirsch JA. Reframing the Prevention Strategies of the Opioid Crisis: Focusing on Prescription Opioids, Fentanyl, and Heroin Epidemic. Pain physician. 2018 Jul:21(4):309-326 [PubMed PMID: 30045589]