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HydromorphoneAllison (Musick) RussellUniversity of Kansas Medical CenterOpioids have been used for thousands of years in the treatment of pain. Opioids, especially Morphine, have become a mainstay in the treatment of postoperative pain relief (Stoelting & Miller, 2000, p. 1618). However, the need emerged for a stronger opioid with less side effects than Morphine. Hydromorphone was created in Germany in 1924 to fill this need. It was first marketed in 1926 under the name Dilaudid (Collier, 2009). Since its introduction, Dilaudid has been widely used in the treatment of acute and chronic pain all over the world (Trescot, Datta, Lee, & Hansen, 2008).Hydromorphone is a mu-opioid receptor agonist. It is related to Morphine pharmacologically, but is approximately 5 to 10 times as potent (Miller, 2005). Opioids have three primary mechanisms of action. The first being that it inhibits calcium influx presynaptically, which results in a decreased release of neurotransmitters. The second mechanism of action is that it enhances potassium efflux from postysynaptic cells, which causes a decrease in pain transmission. This decrease in pain transmission is due to the hyperpolarization of the cell. The third mechanism is the activation of the descending inhibitory pain circuit. As an opioid, Hydromorphone acts on mu-opioid receptors in the Central Nervous system through these three mechanisms of action (Barash, Cullen, Stoelting, Chalan, Stock, & Ortega, 2013, p. 1619). Dilaudid is available in intravenous, intramuscular and oral forms. The typical intravenous/intramuscular dose is 2-7.5mg with a maximum dose of 40 mg/day. The typical oral dose for Dilaudid is 1mg every 3-4 hours (White, 2005, p.453). Dilaudid is biotransformed in the liver and has the active metabolites of dihydromorphine and dihydroisomorphine. It is excreted in the urine (Barash et al., 2013, p. 1621). The bioavailability of Dilaudid is about 24% when the immediate release tablet is used. Dilaudid has a volume distribution of 2.9 L/kg (Truven Health Analytics, 2012). Its onset is less than 15 minutes for intravenous/intramuscular administration and 30 minutes for oral administration. It peaks in 15-30 minutes for intravenous administration and lasts 2-3 hours. Oral administration peaks in 1-2 hours and lasts 4-6 hours (White, 2005, p. 453). Dilaudid is more potent than Morphine, and has proven efficacy in the treatment of postoperative and chronic pain. As with any opioid, Dilaudid does not come without side effects, but Dilaudid’s side effects are those that occur with any opioid: nausea and vomiting, sedation, pruritus, and cognitive impairment. In addition, opioid related side effects are reported as less intense with Dilaudid than with Morphine. (Barashet al., 2013, p. 1621). As with any opioid, administering too much can cause respiratory depression (Barash et al., 2013, p.1619). Because of Dilaudid’s less intense side effects and higher potency, it is a common drug to use for peri-operative and post-operative pain control. Because of Morphine’s detrimental effects on the kidneys, Dilaudid is usually the preferred opioid option for patients with acute pain and impaired kidney function. However, recent studies show that hydromorphone-3-glucuronide (the inactive metabolite) can accumulate in those with renal failure and may contribute to side effects such as neuroexcitation and cognitive impairment (Barash et al., 2013, p. 1621). In addition, opioids should be used with caution in patients with head injuries: depression of ventilation and accumulation of carbon dioxide may cause an increase in intracranial pressure (Stoelting, 2000, p. 73). Stoelting (2000) brings up an interesting point that pain relief is most prominent when opioids are administered before the painful stimulus occurs. Therefore, anesthesiology providers can consider administration of an opioid before the acute painful surgical stimulus occurs (Stoelting, 2000 p. 72).A study done in 2006 by Chang, Bijur, Meyer, Kenny, Solorzano, and Gallagher examined the difference between Morphine and Dilaudid in patients with acute pain. The study consisted of adults who presented to the Emergency Room with acute pain. Subjects were randomly assigned to receive a single dose of intravenous Morphine (0.1mg/kg) or hydromorphone (0.015mg/kg). Subjects were asked to provide a whole-integer pain score from 0-10 (0 being “no pain” and 10 being the “worst pain possible”). Pain level comparisons were then made between baseline and 30 minutes after medication administration. In addition, pain score comparisons were made at 5 minutes and 120 minutes after administration. The study also recorded any addition pain medications given after initial administration and comparisons were made of any adverse events that occurred after administration. The study found that the decrease in pain from baseline to 30 minutes was greater in the hydromorphone group (-5.5 on the numeric pain rating scale) than in the subject group that received Morphine (-4.1 on the numeric pain rating scale). Also, hydromorphone was found to be more effective in patients who initially rated their pain higher. However, there was no difference noted between the two analgesics in those patients whose baseline pain intensity was less than 10. Measured adverse effects between the two groups from baseline to 30 minutes were similar, except for pruritus which was reported significantly more in the group that received Morphine. An important clinical implication found by the study was that the physicians and nurses in the study “seemed more willing” to give a higher dose of Hydromorphone than Morphine for the same degree of pain because the actual quantity of Dilaudid is less than Morphine (Chang et al., 2006). The Chang et al. (2006) study was the first of its kind to examine the difference between Hydromorphone and Morphine pain relief in the emergency department. It is interesting to note that while Dilaudid has been around since the 1920s, Morphine, as of 2003, was the most frequently used analgesic in the emergency room. The Chang et al (2006) study illustrated that Hydromorphone is a safe alternative to Morphine, especially in light of that fact that it comes with no additional side effects than Morphine and there is no significant cost difference between the two analgesics. It is also important to note that the Chang et al. (2006) study found that Hydromorphone had a somewhat larger effect on pain than Morphine at 5 minutes after administration (Chang et al, 2006). In conclusion, Dilaudid is an effective drug for the treatment of pain. It is more potent than Morphine and has less reported side effects, making it a drug of choice for many providers. It is more pertinent to postoperative or acute pain management than intraoperative pain management, although some authors point out that giving an analgesia directly before the painful stimulus may be useful (Stoelting, 2000, p.72). Essentially, patients want effective and fast pain relief, and Dilaudid fills this role. Dilaudid has been used in practice since its introduction in the 1920s. As more studies like the Chang et al. study emerge proving Dilaudid’s efficacy, Hydromorphone will continue to be used for many years to come, perhaps one day exceeding Morphine as a first line treatment for pain.ReferencesBarash, P.G., Cullen, B.F., Stoelting, R.K., Chalan, M.K., Stock, M.C., Ortega, R. (2013). Clinical Anesthesiology (7th ed.). Philidelphia: Lippincott Williams & WilkinsChang, A.K., Bijur, P.E., Meyer, R.H., Kenny, M.K., Solorzano, C., Gallagher, E.J. (2006). Safety and efficacy of Hydromorphone as an analgesic alternative to Morphine in acute pain: a randomized clinical trial. Annals of Emergency Medicine 48(2), 164-172. Collier, M. (2009). Dilaudid: History, Uses, Side Effects, and Withdrawal. Retrieved from: , R.D. (Ed.). (2005). Acute Postoperative Pain (6th ed.). In Miller (Ed.), Miller’s Anesthesia (pp. 2729-2762)Stoelting, R.K., & Miller, R.D. (2000). Basics of Anesthesia (4th ed.). Pennsylvania: Churchill Livingstone.Trescot, A.M., Datta, S., Lee, M., & Hansen, Hans. (2008). Opioid Pharmacology. Pain Physician 2008: Opioid Special Issue (11). Retrieved from Health Analytics (2012). Micromedex (Version 1.48.0b1705) [software]. Available from , P.F. (2005). Perioperative Drug Manual (2nd ed.). Pennsylvania: Elsevier. ................
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