Side Effects of hydromorphone: A Synthesis of Findings from 28 Studies

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Original Abstract of the Article

Major Research Findings

Hydromorphone is an effective pain reliever, but it can also have undesirable side effects. Research has shown that hydromorphone side effects can vary depending on the dose, route of administration, and the patient's condition. For instance, a study 16 found that patients who received hydromorphone before surgery had less blood pressure and heart rate variability during surgery, less postoperative pain intensity and morphine consumption, and higher satisfaction. However, a study 8 comparing morphine and hydromorphone concluded that, contrary to the traditional perception of healthcare professionals that hydromorphone is superior to morphine in pain control and has fewer side effects, the efficacy and side effect profiles of morphine and hydromorphone were equivalent.

A study 27 suggests the potential for developing a new type of opioid that acts on both the mu opioid receptor (MOR) and the delta opioid receptor (DOR) by modifying the chemical structure of hydromorphone, which could reduce side effects. This new opioid acts as a partial agonist at MOR and a full agonist at DOR, suggesting that it may reduce side effects such as respiratory depression. Furthermore, a study 14 suggests the potential to reduce side effects by binding hydromorphone to macromolecules, allowing for targeted drug delivery to inflamed areas of joints. This study showed that hydromorphone-bound polymers accumulated in inflamed areas of the joints in a rat model of arthritis and suppressed inflammatory pain.

Reasons for Side Effects

Hydromorphone is an opioid analgesic that exerts its analgesic effects by binding to opioid receptors in the brain. However, opioid receptors are also present in various parts of the brain, including the respiratory center, the vomiting center, and the gastrointestinal motility center, so they can also act on these parts and cause side effects. In addition, hydromorphone can act on the central nervous system, causing side effects such as decreased level of consciousness, respiratory depression, gastrointestinal symptoms, and dependence.

Common Side Effects

Gastrointestinal

Constipation is one of the most common side effects of opioids. A study 12 reported a case where constipation caused by hydromorphone led to Ogilvie syndrome (paralytic ileus) and bowel perforation. A study 11 showed that subcutaneous injection of hydromorphone in cats caused side effects such as vomiting. A study 2 reported that intravenous hydromorphone administration after surgery increased the risk of postoperative hypoxemia.

Respiratory

Hydromorphone can cause respiratory depression. A study 27 suggests that a new type of opioid that acts on both MOR and DOR may reduce side effects such as respiratory depression. A study 2 reported that intravenous hydromorphone administration after surgery increased the risk of postoperative hypoxemia.

Nervous System

Hydromorphone can cause side effects such as decreased level of consciousness, drowsiness, dizziness, headache, and hallucinations. A study 17 reported a case where hydromorphone caused hallucinations. A study 25 reported that the combined use of hydromorphone and dexmedetomidine in terminally ill cancer patients improved symptoms such as pain, agitation, sleep disturbance, anxiety, and cravings. However, dexmedetomidine can cause side effects such as hallucinations, nightmares, and psychomotor agitation.

Other

Hydromorphone can cause side effects such as dependence, tolerance, urinary retention, pruritus, and sweating. A study 3 suggests that tapentadol may have lower dependence and abuse potential than hydromorphone. A study 19 investigated side effects from long-term use of hydromorphone and diacetylmorphine.

Countermeasures for Side Effects

Constipation Countermeasures

Countermeasures for constipation include hydration, dietary fiber intake, and exercise. Laxatives can also be used if necessary. A study 12 reported that new drugs such as methylnaltrexone are effective in treating opioid-induced constipation. However, methylnaltrexone carries the risk of side effects such as bowel perforation, so caution is necessary.

Respiratory Depression Countermeasures

Countermeasures for respiratory depression include monitoring the patient's respiratory status. Oxygen administration or mechanical ventilation may be required if necessary. A study 2 suggests that the risk of hypoxemia may be reduced by administering low doses of a base infusion when administering hydromorphone intravenously.

Hallucination Countermeasures

Hallucinations may improve by reducing the dose of hydromorphone. Antipsychotics can also be used if necessary. A study 17 reported a case where hydromorphone caused hallucinations. Discontinuation of hydromorphone administration has been shown to resolve hallucinations.

Comparison Between Studies

Commonalities

Many studies have shown that hydromorphone is an effective analgesic. However, it has also been shown that it carries the risk of side effects.

Differences

Studies have reported different rates and severities of side effects from hydromorphone. This is thought to be influenced by a variety of factors such as the patient population studied, the dose and route of administration of hydromorphone, and concomitant medications.

Precautions for Application in Real Life

Hydromorphone is a potent analgesic, but it also carries the risk of dependence and respiratory depression. Therefore, it is important to use hydromorphone in appropriate doses as directed by your doctor. If you experience side effects, consult your doctor immediately. In particular, caution should be exercised in the elderly and patients with impaired liver or kidney function, as they are more susceptible to side effects. In addition, pay attention to drug interactions when using hydromorphone in combination with other drugs.

Limitations of Current Research

Many studies on hydromorphone have been conducted on a small scale, and caution is required when generalizing the results. In addition, the patient populations studied may be skewed toward patients with specific diseases, so it is unclear whether the results can be applied to other patient populations.

Future Research Directions

Further research is needed to elucidate the mechanisms of hydromorphone-induced side effects. In particular, there is hope for the development of biomarkers to predict the occurrence of side effects and the development of new drugs to reduce side effects. Furthermore, appropriate patient education and early detection and management of side effects are important for the safe use of hydromorphone. Therefore, improvements in patient education by doctors and pharmacists are required.

Conclusion

Hydromorphone is an effective analgesic, but it also carries the risk of side effects. When using hydromorphone, follow your doctor's instructions and consult your doctor immediately if you experience side effects. It is hoped that further research will elucidate the mechanisms of hydromorphone side effects and develop drugs that can reduce side effects.

Literature analysis of 28 papers
Positive Content
22
Neutral Content
3
Negative Content
3
Article Type
7
0
2
3
27
1.

Perioperative systemic nonsteroidal anti-inflammatory drugs (NSAIDs) in women undergoing breast surgery.

Author: KliftoKevin M, ElhelaliAla, PayneRachael M, CooneyCarisa M, ManahanMichele A, RossonGedge D

Inflammation reduction
Pain reduction
Bleeding complications

The use of NSAIDs for breast surgery requires careful consideration due to the potential for bleeding complications. However, NSAIDs can be effective for pain management, and further research is needed to determine the optimal risk/benefit ratio.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.
Systematic ReviewA review that systematically collects, evaluates, and integrates relevant research to answer a specific research question.

Language : English

2.

Effects of hydromorphone-based intravenous patient-controlled analgesia with and without a low basal infusion on postoperative hypoxaemia: study protocol for a randomised controlled clinical trial.

Author: MaYumei, DengZhuomin, FengXiangying, LuoJialin, MengYang, LinJingjing, MuXiaoxiao, YangXuan, NieHuang

Pain relief
Hypoxaemia
Respiratory depression

This clinical trial aims to determine if using a low basal infusion in patient-controlled intravenous analgesia (PCIA) increases the risk of postoperative hypoxemia compared to no basal infusion.

Clinical Trial ProtocolA plan for conducting a clinical trial. It describes in detail the purpose, design, methodology, and statistical considerations of the trial, ensuring the transparency and consistency of the trial.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

3.

Assessment of Tapentadol API Abuse Liability With the Researched Abuse, Diversion and Addiction-Related Surveillance System.

Author: VosburgSuzanne K, SevertsonS Geoffrey, DartRichard C, CiceroTheodore J, KurtzSteven P, ParrinoMark W, GreenJody L

Pain management
Tapentadol abuse

This study examined the abuse liability of tapentadol, a pain medication, compared to other opioids. The study found that tapentadol had a lower abuse liability than most other opioids studied.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

4.

Patient-controlled Analgesia with Target-controlled Infusion of Hydromorphone in Postoperative Pain Therapy.

Author: JeleazcovChristian, IhmsenHarald, SaariTeijo I, RohdeDoris, MellJan, FröhlichKatharina, KrajinovicLjubica, FechnerJörg, SchwildenHelmut, SchüttlerJürgen

Postoperative pain management

This study investigated the feasibility and efficacy of TCI-PCA for postoperative pain therapy with hydromorphone.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

5.

En Route Use of Analgesics in Nonintubated, Critically Ill Patients Transported by U.S. Air Force Critical Care Air Transport Teams.

Author: MoraAlejandra G, GanemVictoria J, ErvinAlicia T, MaddryJoseph K, BebartaVikhyat S

Critical Care Air Transport Teams (CCATTs) in the U.S. military use analgesics to manage acute pain in critically ill patients during evacuation from combat settings.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, U.S. Gov't, Non-P.H.S.Research funding provided by US government agencies other than the Public Health Service.

Language : English

8.

The side effects of morphine and hydromorphone patient-controlled analgesia.

Author: HongDaewha, FloodPamela, DiazGeraldine

Pain control

This study compared the efficacy and side-effect profiles of morphine and hydromorphone at concentrations producing equivalent drug effect.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.

Language : English

9.

Low-dose ketamine infusion reduces postoperative hydromorphone requirements in opioid-tolerant patients following spinal fusion: A randomised controlled trial.

Author: BoenigkKirsten, EchevarriaGhislaine C, NisimovEmmanuel, von Bergen GranellAnnelise E, CuffGermaine E, WangJing, AtchabahianArthur

Postoperative pain control
Reduced opioid use
Ketamine side effects
Opioid tolerance

This study explored the efficacy of intra-operative ketamine infusion for opioid-naïve patients after spinal fusion surgery.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.

Language : English

10.

Randomized Clinical Trial of Intravenous Acetaminophen as an Analgesic Adjunct for Older Adults With Acute Severe Pain.

Author: ChangAndrew K, BijurPolly E, AtaAshar, CampbellCaron, PearlmanScott, WhiteDeborah, ChertoffAndrew, RestivoAndrew, GallagherE John

Adding IV acetaminophen to IV hydromorphone for acute severe pain in older adults did not provide statistically or clinically superior pain relief compared to hydromorphone alone within the first hour of treatment.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Multicenter StudyResearch conducted in collaboration with multiple research institutions. It aims to collect a wide range of data and obtain more generalizable results.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, N.I.H., ExtramuralResearch funding provided by the NIH to external research institutions and researchers.

Language : English

12.

Methylnaltrexone-Associated Bowel Perforation in Postoperative Opioid-Induced Constipation and Ogilvie Syndrome: A Case Report.

Author: BlackneyKevin A, KamdarNirav V, LiuChang Amber, EdwardsDavid A

OIC treatment
Bowel perforation
OIC
Ogilvie syndrome

This case report describes a 56-year-old man who developed opioid-induced constipation (OIC) and Ogilvie syndrome following lumbar decompression surgery. Treatment with methylnaltrexone led to an acute bowel perforation, highlighting the importance of careful monitoring and understanding the risks associated with this medication.

Case ReportsIn the medical field, a report that describes in detail a unique case, an unusual medical condition, or the effect of a treatment. Provides new insights and possibilities for treatment through individual patient cases.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

13.

Cebranopadol for the Treatment of Chronic Pain.

Author: EdinoffAmber N, FlanaganChelsi J, RobertsLogan T, DiesRoss M, KatariaSaurabh, JacksonEric D, DeWittAudrey J, WengerDanielle M, CornettElyse M, KayeAdam M, KayeAlan D

Pain management
Reduced opioid side effects

Cebranopadol is a first-in-class oral drug that combines agonism of the mu and nociceptin opioid peptide (NOP) receptors, offering improved analgesia while reducing opioid side effects. It is a promising alternative to opioids for pain management, particularly in settings like the postoperative period.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

14.

The Development of a Macromolecular Analgesic for Arthritic Pain.

Author: WeberLaura, WangXiaobei, RenRongguo, WeiXin, ZhaoGang, YangJunxiao, YuanHongjiang, PangHuiling, WangHanjun, WangDong

Improved effectiveness
Reduced side effects
Reduced spinal analgesia
Safe analgesic
Targeted delivery

This study developed a novel inflammation-targeting polymeric prodrug of hydromorphone (HMP), a commonly used opioid, to reduce its addictive potential and improve its effectiveness for musculoskeletal pain. The prodrug, P-HMP, was shown to be internalized by inflammatory cells in arthritic joints, effectively alleviating pain while minimizing central nervous system effects.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, N.I.H., ExtramuralResearch funding provided by the NIH to external research institutions and researchers.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

15.

Opioid Rotation in Cancer Pain Treatment.

Author: SchusterMichael, BayerOliver, HeidFlorian, Laufenberg-FeldmannRita

Improved analgesia
Intolerable side effects

Rotating WHO level III opioid drugs is a therapeutic option for patients with chronic cancer-related pain who suffer from inadequate analgesia or intolerable side effects.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Systematic ReviewA review that systematically collects, evaluates, and integrates relevant research to answer a specific research question.

Language : English

17.

Hydromorphone-Induced Tactile Hallucinations: Rare Opioid Side Effect.

Author: KiyokawaMiki, HaningWilliam F

Hallucinosis

This case report describes a patient experiencing visual and tactile hallucinations after receiving oral hydromorphone.

Case ReportsIn the medical field, a report that describes in detail a unique case, an unusual medical condition, or the effect of a treatment. Provides new insights and possibilities for treatment through individual patient cases.

Language : English

18.

Pregabalin Did Not Improve Pain Management After Spinal Fusions.

Author: UrbanMichael K, LabibKristy M, ReidShane C, GoonAmanda K, RotundoValeria, CammisaFrank P, GirardiFederico P

Nausea
Vomiting

Pregabalin 150 mg/day did not have reduced IV narcotic usage, improved PT milestones, or reduced length of hospital stay.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

19.

Safety profile of injectable hydromorphone and diacetylmorphine for long-term severe opioid use disorder.

Author: Oviedo-JoekesEugenia, BrissetteSuzanne, MacDonaldScott, GuhDaphne, MarchandKirsten, JuthaSalima, HarrisonScott, JanmohamedAmin, ZhangDerek Z, AnisAslam H, KrauszMichael, MarshDavid C, SchechterMartin T

Reduced overdose risk
Safe opioid treatment
Opioid overdose
Somnolence

Injectable hydromorphone and diacetylmorphine were effective and safe treatments for severe opioid use disorder. Hydromorphone was associated with fewer adverse events and serious adverse events compared to diacetylmorphine. Opioid overdose events were more common in the first 30 days of treatment.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.

Language : English

21.

Long-term efficacy of OROS® hydromorphone combined with pregabalin for chronic non-cancer neuropathic pain.

Author: DauriMario, LazzariMarzia, CasaliManuela, TufaroGiuseppe, SabatoElisabetta, SabatoAlessandro Fabrizio

Neuropathic pain treatment
OROS hydromorphone efficacy
Pregabalin efficacy

Chronic neuropathic pain can be difficult to treat due to side effects and drug interactions. This study evaluated the efficacy and safety of combining OROS® hydromorphone and pregabalin in patients with chronic neuropathic pain.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

22.

Patient-Controlled Analgesia After Cardiac Surgery With Median Sternotomy: No Advantages of Hydromorphone When Compared to Morphine.

Author: WehrfritzAndreas, SengerAnne-Sophie, JustPatrick, AlbartMaximilian, MünchsmeierMichael, IhmsenHarald, SchüttlerJürgen, JeleazcovChristian

Pain relief
Nausea
Vomiting

Hydromorphone and morphine, administered as patient-controlled analgesia (PCA) for postoperative pain therapy after cardiac surgery with median sternotomy, showed no significant differences in analgesic efficacy and safety.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

23.

Case report: efficacy and tolerability of ketamine in opioid-refractory cancer pain.

Author: AminPriya, RoelandEric, AtayeeRabia

Pain relief
Reduced opioid use

This case report describes a 36-year-old female with metastatic breast cancer and opioid-refractory neuropathic pain. The patient achieved significant pain relief with weight-based intravenous ketamine and successfully transitioned to oral ketamine. This case highlights the potential effectiveness of ketamine for managing opioid-refractory cancer pain and suggests the feasibility of transitioning from intravenous to oral ketamine.

Case ReportsIn the medical field, a report that describes in detail a unique case, an unusual medical condition, or the effect of a treatment. Provides new insights and possibilities for treatment through individual patient cases.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

24.

Patient-controlled epidural analgesia or multimodal pain regimen with periarticular injection after total hip arthroplasty: a randomized, double-blind, placebo-controlled study.

Author: Jules-ElyseeKethy M, GoonAmanda K, WestrichGeoffrey H, PadgettDouglas E, MaymanDavid J, RanawatAmar S, RanawatChitranjan S, LinYi, KahnRichard L, BhagatDevan D, GoytizoloEnrique A, MaYan, ReidShane C, CurrenJodie, YaDeauJacques T

Earlier discharge
Reduced opioid consumption

This study compared the effectiveness of patient-controlled epidural analgesia (PCEA) and a multimodal pain regimen including periarticular injection (PAI) in patients undergoing total hip arthroplasty. The study found that PAI led to earlier readiness for discharge, decreased opioid consumption, and lower pain scores.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.

Language : English

25.

Long-Term Dexmedetomidine Use and Safety Profile in Palliative Care: A Case Report.

Author: Dieudonné RahmNathalie, KemichaTijani, PapasokratiLida, PautexSophie

Pain relief
Restlessness relief
Sleep improvement

Dexmedetomidine infusion, added to hydromorphone, was successfully used for two months in a patient with intractable cancer pain, restlessness, sleep disorder, anxiety, and craving symptoms. Long-term conscious sedation with IV dexmedetomidine was well tolerated, offering a potential therapeutic option for palliative patients with severe symptoms.

Case ReportsIn the medical field, a report that describes in detail a unique case, an unusual medical condition, or the effect of a treatment. Provides new insights and possibilities for treatment through individual patient cases.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

26.

Preemptive Analgesia Decreases Pain Following Anorectal Surgery: A Prospective, Randomized, Double-Blinded, Placebo-Controlled Trial.

Author: Van BackerJustin T, JordanMatthew R, LeahyDanielle T, MooreJesse S, CallasPeter, DominickTimothy, CataldoPeter A

Reduced postoperative pain
Postoperative pain

This study discusses the potential of preemptive analgesia in anorectal surgery to prevent postoperative pain and facilitate quicker patient discharge. The authors highlight the lack of research in this area despite established evidence supporting preemptive analgesia in other surgical fields.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Video-Audio MediaMedia that combines video and audio. Includes movies, TV shows, and online videos.

Language : English

27.

The Intriguing Effects of Substituents in the <i>N</i>-Phenethyl Moiety of Norhydromorphone: A Bifunctional Opioid from a Set of "Tail Wags Dog" Experiments.

Author: WangMeining, IrvinThomas C, HerdmanChristine A, HannaRamsey D, HassanSergio A, LeeYong-Sok, KaskaSophia, CrowleyRachel Saylor, PrisinzanoThomas E, WitheySarah L, ParonisCarol A, BergmanJack, InanSaadet, GellerEllen B, AdlerMartin W, KopajticTheresa A, KatzJonathan L, ChadderdonAaron M, TraynorJohn R, JacobsonArthur E, RiceKenner C

MOR/DOR agonist
No respiratory depression
Respiratory depression

A novel N-phenethyl analog of norhydromorphone (compound 2i) was found to be a potent partial agonist at the mu opioid receptor and a full agonist at the delta opioid receptor. It did not depress respiration in mice or squirrel monkeys under normal air conditions but did depress respiration under conditions of hypercapnia.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

28.

Optimal perioperative anesthesia management for gynecologic interstitial brachytherapy.

Author: NielsenAlison A, LiyanageTehani A, LeiserowitzGary S, MayadevJyoti

Improved pain management
Reduced narcotic use
Delirium
Postoperative nausea

Interstitial gynecologic brachytherapy requires a multidisciplinary effort for optimal perioperative management.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

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