Fentanyl in a pectin gel treating breakthrough pain in vertebral compression fracture due to multiple myeloma: A descriptive study of three cases.

Breakthrough pain (BTP) currently represents a challenge for health professionals dedicated to the treatment of pain. In this descriptive 1-year follow-up study on three patients with BTP from vertebral crush, in the context of multiple myeloma, the authors have observed the great either efficacy or tolerability profile of fentanyl pectin nasal spray. The most relevant findings in this study were better adherence to treatment compared to previously opioids and also great personal satisfaction. Because of common pathophysiological mechanism for noncancerous pain of bone origin, these good results could open the door to investigation of the use of this drug in this patient's group.

Treatment of failed back surgery syndrome in a forty-three-year-old man with high-dose oxycodone/naloxone.

INTRODUCTION: Failed back surgery syndrome (FBSS) is an increasing cause of chronic pain in most countries. This poses high costs to both patients and National Health Organizations. CASE PRESENTATION: In this report, multimodal pain management based on daily high-dose oxycodone/naloxone (OXN 180/90 mg) led to reduced patient's pain score and improved quality of life. CONCLUSIONS: Oxycodone/naloxone can be a good alternative for the management of FBSS when other interventional or pharmacologic strategies have failed. In this case report, higher doses than those recommended as a maximum daily ceiling (80/40 mg) were safely used in one selected patient with noncancer severe pain.

Current evidence for spinal opioid selection in postoperative pain.

BACKGROUND: Spinal opioid administration is an excellent option to separate the desirable analgesic effects of opioids from their expected dose-limiting side effects to improve postoperative analgesia. Therefore, physicians must better identify either specific opioids or adequate doses and routes of administration that result in a mainly spinal site of action rather than a cerebral analgesic one. METHODS: The purpose of this topical review is to describe current available clinical evidence to determine what opioids reach high enough concentrations to produce spinally selective analgesia when given by epidural or intrathecal routes and also to make recommendations regarding their rational and safety use for the best management of postoperative pain. To this end, a search of Medline/Embase was conducted to identify all articles published up to December 2013 on this topic. RESULTS: Recent advances in spinal opioid bioavailability, based on both animals and humans trials support the theory that spinal opioid bioavailability is inversely proportional to the drug lipid solubility, which is higher in hydrophilic opioids like morphine, diamorphine and hydromorphone than lipophilic ones like alfentanil, fentanyl and sufentanil. CONCLUSIONS: Results obtained from meta-analyses of RTCs is considered to be the 'highest' level and support their use. However, it's a fact that meta-analyses based on studies about treatment of postoperative pain should explore clinical surgery heterogeneity to improve patient's outcome. This observation forces physicians to use of a specific procedure surgical-based practical guideline. A vigilance protocol is also needed to achieve a good postoperative analgesia in terms of efficacy and security.

Spinal opioid bioavailability in postoperative pain.

Opioids have been used for spinal analgesia for more than a century, and their injection epidurally and intrathecally has a key role in the control of postoperative pain. Since the discovery of the endogenous opioid system, 3 decades ago, their use has become more generalized in obstetric analgesia, the management of chronic pain, and acute postoperative pain. To use opioids effectively for this type of analgesia, it is important to understand the pharmacokinetics and clinical pharmacology of these drugs, specifically those that produce analgesia by an intrinsic spinal mechanism. Evidence from animal and human experiments indicates that hydrophilic opioids (such as hydromorphone and morphine) bind more strongly to specific receptors within the dorsal horn of the spinal cord than lipophilic opioids (such as alfentanil, fentanyl, and sufentanil). This can be understood by considering the spinal cord selectivity and bioavailability of these opioids. This difference is attributable to differences in the pharmacokinetic and pharmacodynamic properties of the 2 groups. It is more difficult for lipophilic opioids to reach and remain at sufficiently high concentrations at the site of action due to their sequestration in epidural fat and rapid plasma clearance from both epidural and intrathecal spaces, resulting in analgesia with a limited spread and duration, as well as the appearance of early supraspinal side effects. In contrast, morphine has very different properties, including greater spinal bioavailability and therefore administered neuraxially, it is suitable choice for the treatment of acute postoperative pain. However, when using morphine, a greater incidence of adverse effects can be expected, and it requires careful patient selection.

A review of epidural and intrathecal opioids used in the management of postoperative pain.

Opioids are the most potent centrally acting analgesic drugs for the treatment of pain. For the past years, since the discovery of spinal opioid receptors, the use of spinal opioids has been adopted in clinical practice in the hope of producing intense segmental analgesia that was devoid of the dose-limiting side effects associated with systemic opioid administration. Experimental studies have demonstrated that after their perispinal administration, liposolubility is inversely proportional to their spinal selectivity, which is higher for the most water-soluble drug, morphine, than for other more lipophilic drugs, such as fentanyl and sufentanil. Clinical trials have shown that epidural morphine in the form of extended-release liposome injections gives good analgesia for a period of 48 hours, with no need for epidural catheterization. Conversely, fentanyl is the most appropriate opioid in ambulatory surgery and seems to have the strongest effect at the spinal cord administered epidurally as a bolus and supraspinally using continuous epidural infusion. Epidural methadone and hydromorphone are suitable alternatives for analgesia in the postoperative period, given that they have intermediate pharmacokinetic characteristics with respect to the two aforementioned groups of opioids. All opioids administered intrathecally will produce some degree of spinally mediated analgesia. The main differences are related to their duration of action, rate of clearance, and the pathways by which the drugs reach their receptors in the brain. In general, lipophilic opioids produce short-term analgesia (1-4 hours), which is very useful for immediate postoperative pain. However, morphine produces intense analgesia for up to 24 hours with doses as low as 100 µg.