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Query: UMLS:C0344307 (analgesia)
 28,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Breakthrough pain is normally severe in intensity and has a rapid onset. The availability of supplemental doses of opioids (rescue medication) in addition to the continuous analgesic medication is the main treatment suggested to manage these pain flares. The intravenous (i.v.) route may provide analgesia fast enough, but has never been assessed in clinical studies. The aim of this open-label study was to verify the safety and effectiveness of an i.v. dose equal to one-fifth the calculated equianalgesic total daily dose in advanced cancer patients with episodic pain. A consecutive sample of 48 cancer patients treated with oral morphine, who reported an acceptable basal analgesia and reported episodic pains, were selected for the study. The intravenous dose of morphine was one-fifth of the oral daily dose, converted into an i.v. dose using an equianalgesic ratio of 1/3 (i.v./oral). Written orders were given and intravenous morphine (i.v.-M) was administered by nurses. For each episode, pain intensity and opioid-related symptoms were recorded at the start (T0), after achieving maximum pain relief (T1), and one hour after (T2). In five patients, blood samples were taken at the time intervals described for measuring plasma concentrations of morphine and related glucuronated metabolites. One hundred seventy-one breakthrough pains were recorded during admission. In 162 episodes, a reduction of pain intensity of more than 33% was obtained within a mean of 17.7 minutes, from a mean intensity of 7.9 (on a 0-10 numeric scale) to 3. One hundred thirty-six episodes had more than a 50% pain intensity decrease after the i.v.-M within a mean of 16.6 minutes, from a pain intensity of 7.9 to 2.6. No differences in age, sex, pain mechanism, and time of events were found. There was a trend but no statistically significant differences between the groups receiving different basal doses and time to reach the maximum effect. Twenty episodes in ten patients required an additional dose within 2 hours. Adverse effects were uncommon and were significantly related to the basal dose, and as a consequence, with the i.v.-M dose. Morphine concentration significantly increased at the time of pain intensity reduction, and then decreased. These observations suggest that i.v.-M at a dose equivalent to 20% of the basal oral dosage is safe and effective in the majority of patients experiencing pain exacerbation. This treatment is inexpensive and can be used at little risk to patients.
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PMID:Safety and effectiveness of intravenous morphine for episodic (breakthrough) pain using a fixed ratio with the oral daily morphine dose. 1505 Jun 63

A 2.8-year-old female patient (11.6 kg) was admitted to the hospital for uncontrolled pain and swelling in the left leg relating to a metastatic neuroblastoma. Initially, her pain was managed with oral morphine 2 mg (approx. 0.2 mg/kg) every 4 hours. Because she was quite somnolent but still in significant pain, analgesia was then changed to methadone 1 mg orally every 6 hours (approximately 0.1 mg/kg/dose) and was eventually increased over 36 hours to 2 mg every 6 hours (approximately 0.2 mg/kg/dose). She received oral methadone 0.6 mg (approximately 0.05 mg/kg) every 4 hours as needed for breakthrough pain. She continued to have severe pain and experienced side effects, including respiratory depression, sedation, visual hallucinations, and vomiting. An intravenous ketamine infusion was started at 100 microg/kg/hour. Regular opioid administration was ceased, but she was given intravenous morphine 0.5 to 0.75 mg for breakthrough pain. She required only zero to three doses of breakthrough morphine per day, initially. After starting the ketamine infusion, her pain control improved and her symptoms of opioid toxicity abated. She was more alert and able to partake in limited activities. As a result of pain from progressive disease, the ketamine infusion was increased to 200 microg/kg/hour after 6 days with positive results. Her condition continued to deteriorate. An intravenous morphine infusion was initiated 2 weeks after starting the ketamine infusion and was eventually increased to 50 microg/kg/hour. One week later, she died with reasonable pain control. This case illustrates the use of ketamine as an effective analgesic in an adjuvant setting in a pediatric patient with advanced poorly controlled cancer pain. Ketamine not only eased the child's suffering while preserving life but also improved her quality of life by maintaining the child's ability to communicate and engage in activities.
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PMID:Intravenous ketamine infusion as an adjuvant to morphine in a 2-year-old with severe cancer pain from metastatic neuroblastoma. 1545 42

Fentanyl, a surgical analgesic and general anaesthetic, is a lipophilic short-acting synthetic opioid, having a selective potent effect on mu receptors. The transdermal therapeutic fentanyl-system (TTS-F) allows for a continued and sustained titratable amount of fentanyl to be delivered without the inconvenience of the typical 24-h administration of other analgesics. Although incidences of respiratory depression led to TTS-F being contraindicated for postoperative analgesia, it is currently undergoing Phase III trials for nociceptive, neuropathic and chronic moderate to severe pain in a variety of settings. It demonstrates a slow pharmacokinetic profile and incidences of breakthrough pain may still require rapid analgesia, for which intravenous and bolus administration of rapid acting opioids remain 'gold standard' However, TTS-F is finding uses for chronic pain of cancer origin where it offers a solution for step 3-pain (WHO) management on the WHO analgesic ladder. More recent data indicates that TTS-F is not only effective for neuropathic but also nociceptive non-cancer and cancer pain alike. This review presents an overview of the synthesis, delivery, pharmacokinetics, toxicity and clinical pharmacology of the transdermal delivery of fentanyl.
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PMID:Transdermal therapeutic fentanyl-system (TTS-F). 1552 5

In this randomized, controlled, dose-ranging study, we evaluated the analgesic efficacy of a novel single-dose extended-release epidural morphine (Depodur) in patients undergoing lower abdominal surgery. Five-hundred-forty-one patients were randomly assigned to one of six epidural treatments administered approximately 30 min before surgery. The 6 treatments were 5 mg of standard epidural morphine sulfate (MS) (active comparator); 5 mg of single-dose extended-release epidural morphine (EREM) (dose control); and 10, 15, 20, and 25 mg of single-dose EREM. The main study objective was to assess the efficacy of single-dose EREM 10, 15, 20, or 25 mg versus single-dose EREM 5 mg for the management of postoperative pain. This was done by plotting a linear dose-response relationship to assess postoperative IV patient-controlled analgesia (PCA) fentanyl consumption for breakthrough pain for 48 h after surgery. Secondary safety and efficacy analyses compared the 10-, 15-, 20-, and 25-mg single-dose EREM groups with the 5-mg single-dose EREM group and compared each single-dose EREM group with 5 mg of MS. As shown by the dose-response relationship, there was a dose-related reduction in the use of postoperative IV fentanyl through 48 h (estimated slope, -22.2; P = 0.0002). Patients treated with 10, 20, and 25 mg of single-dose EREM used significantly less IV fentanyl (mean +/- sd: 995 +/- 987 microg, P = 0.0446; 972 +/- 982 microg, P = 0.0221; and 683 +/- 620 microg, P < 0.0001, respectively) through 48 h after surgery compared with the 5-mg single-dose EREM group (1218 +/- 894 microg). At 48 h postdose, significantly more single-dose EREM patients (13%) than MS patients (2%) had required no IV fentanyl (P < 0.01). Although all treatment groups had access to PCA fentanyl and there was more frequent PCA fentanyl use in the MS group, patients in the single-dose EREM 15, 20, and 25 mg groups reported significantly lower pain-intensity scores and greater satisfaction with their pain relief. Overall, single-dose EREM was well tolerated, with 97% of adverse events rated as mild to moderate. As expected, the adverse events reported were consistent with those of other epidural opioids (i.e., nausea, vomiting, pruritus, and hypotension). In conclusion, this controlled study demonstrated that single-dose EREM can provide up to 48 h of postoperative analgesia, but supplementation for breakthrough pain is still required in most patients. Within the context of this study, the side effect profile of single-dose EREM was acceptable and predictable.
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PMID:A comparison of Depodur, a novel, single-dose extended-release epidural morphine, with standard epidural morphine for pain relief after lower abdominal surgery. 1578 24

Although clonidine has been shown to increase the duration of local anesthetic action and prolong postoperative analgesia when included in single-injection nerve blocks, the only controlled investigation of the efficacy of this practice to improve analgesia for continuous perineural local anesthetic infusion failed to discern any clinically relevant benefits. For this study, we used a larger dose of clonidine in an attempt to improve analgesia. Patients (n = 20) undergoing moderately painful orthopedic surgery of the shoulder received an interscalene brachial plexus block (40 mL of mepivacaine 1.5%, epinephrine 2.5 microg/mL, and clonidine 50 microg) and a perineural catheter before surgery. After surgery, ropivacaine 0.2% or ropivacaine 0.2% plus clonidine 2 microg/mL was delivered via the catheter for 3 days (basal rate, 5 mL/h; patient-controlled bolus, 5 mL; lockout, 1 h). Investigators and patients were blind to random group assignment. The primary outcome variable was designated as the most intense pain during the day after surgery. Secondary end-points included additional pain scores, patient-controlled bolus doses, oral analgesic use, sleep quality, and catheter- or infusion-related complications. There were no statistically significant differences between groups for any of the variables investigated. We conclude that adding clonidine 2 microg/mL to a ropivacaine interscalene perineural infusion does not decrease breakthrough pain intensity the day after surgery. For the additional end-points, our negative findings are only suggestive of a lack of effect and require further study for verification.
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PMID:Clonidine added to a continuous interscalene ropivacaine perineural infusion to improve postoperative analgesia: a randomized, double-blind, controlled study. 1578 40

The physiochemical characteristics of the potent synthetic opioid agonist fentanyl make it ideal for noninvasive transmucosal delivery. Studies of oral transmucosal fentanyl citrate (OTFC), a candied matrix formulation administered orally as a palatable lozenge on a stick, have investigated and determined this analgesic's pharmacokinetics and pharmacodynamics in a number of clinical settings, including premedication before surgery, acute analgesia for painful medical procedures, and, most recently, for the control of breakthrough cancer pain. The onset to meaningful pain relief in patients with acute pain from surgery or breakthrough pain from cancer is between 5 and 10 minutes after initiating OTFC use, equivalent to intravenous morphine. Analgesic dose equivalency studies suggest that OTFC is, on average, about 10 times more potent than morphine, although, in randomized, controlled, and blinded studies, many patients who were using relatively high doses of opioid anlagesics on an around the- clock schedule for control of cancer pain reported that even a low dose of OTFC (i.e., 200 microg) provided adequate relief from breakthrough pain. Side effects from OTFC are similar in character and frequency to other opioids, including sedation, nausea, and pruritus. These effects appear to wane rapidly with repeated use of this medication. To date there have been no reported serious adverse events in any of the population groups studied or treated with OTFC.
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PMID:A review of oral transmucosal fentanyl citrate: potent, rapid and noninvasive opioid analgesia. 1585 72

Patient-controlled epidural analgesia (PCEA) is used to maintain epidural analgesia following initial intrathecal analgesia. This trial investigated whether a continuous background infusion with PCEA provides superior analgesia to PCEA alone among patients who received combined spinal-epidural (CSE) analgesia during labour Eighty parturients were randomized to either PCEA alone (PCEA) or PCEA with a background infusion of ropivacaine 0.15% with sufentanil 0.75 microg/ml at 2 ml/h (PCEA + CEI). PCEA settings were a bolus of 4 ml of the same analgesic solution with a lockout interval of 15 minutes. Significantly more patients in the PCEA group required at least one anaesthetist intervention for breakthrough pain (27 [71%] vs 10 [25%] in the PCEA + CEI group, P<0.05). Consumption of local anaesthetic (excluding manually administered boluses) was similar between the groups. If anaesthetist-administered boluses were included, more local anaesthetic was consumed by the PCEA group (47.1 +/- 19.4 mg vs 35.6 +/- 12.0 mg in the PCEA + CEI group, P<0.05). We conclude that PCEA with a background infusion provides effective analgesia with less anaesthetist workload and reduced local anaesthetic consumption as compared with PCEA without a background infusion.
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PMID:Patient-controlled epidural analgesia following combined spinal-epidural analgesia in labour: the effects of adding a continuous epidural infusion. 1611 82

Control and abolition of pain during and after surgical procedures is crucial point in the practice of anaesthesiology. In the last years the concept of multimodal analgesia (the use of different analgesic and techniques to relieve pain), has developed and non-steroidal anti-inflammatory drugs (NSAIDs) have a major role in it, because they have an opioid sparing effect. Moreover, they are very effective on somatic and breakthrough pain. NSAIDs can be divided functionally in four classes: salicylates, acetaminophen, non-specific inhibitors (i.e. ibuprofen, ketorolac, etc.) and cyclooxygenase2-inhibitors (coxibs). The target of action of these drugs is the different isozymes of the Prostaglandin G/H synthase, called Cyclooxygenases (COX). At least three different types of COX have been identified, which are probably organ specific. These isozymes play a crucial role in the developing of the inflammatory cascade, and in the genesis of various pain mediators released from tissue injury. Their most important side effects affect mainly gastrointestinal system, the kidney and the coagulation system. Less important are the effects on the liver and the immunologic system (asthma). The analgesic nephropathy and the coagulopathy must be taken into account in the surgical patient, for the possibility of increase perioperative morbidity. Very recently the newest class of coxibs, although they reduce g.i. bleeding and coagulopathy, have proved to increase the risk of cardiovascular accidents both in long term therapy than postoperatively in cardiac surgical patients. Many data are needed, but in patients at high risk of cardiac disease other NSAIDs should be considered.
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PMID:Analgesia in PACU: nonsteroidal anti-inflammatory drugs. 1630 56

Patients who experience a poor response to different systemic opioid trials (oral and intravenous) are candidates for spinal treatment. Breakthrough pain occurring in this group of patients is challenging for physicians. This phenomenon has never been described in this context and the treatment is quite difficult, as patients already demonstrated a poor response to systemic opioids. We report a preliminary experience of alternative methods, including the intrathecal injection of local anesthetic boluses as needed, or alternatively, the use of sublingual ketamine. Twelve consecutive patients with advanced cancer and pain were selected for intrathecal treatment after receiving different trials with systemic opioids. During intrathecal therapy, pain flares not responding to high doses of intravenous morphine were treated with intrathecal boluses of local anesthetics titrated to achieve the best balance between analgesia and adverse effects, or with sublingual ketamine (25 mg), according to their preference. Pain and symptoms were recorded for each episode of breakthrough pain during hospital admission. Effective pain control was achieved in all the episodes treated within 10 minutes with either method, without relevant complications. A mean volume of 0.6 mL of levobupivacaine (LB) 0.25% (1.5 mg) was effective within a few minutes and was well tolerated in patients receiving a continuous intrathecal infusion of a combination of morphine and LB in different doses. Similarly, ketamine in doses of 25 mg sublingually was effective and relatively well tolerated. Despite the difficult clinical situation of these patients, these approaches controlled almost all breakthrough pain events previously unresponsive to relatively high doses of intravenous opioids. These intensive treatments should be reserved for a very selected population and initiated in an appropriate setting with frequent monitoring facilities and skilled nursing.
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PMID:Alternative treatments of breakthrough pain in patients receiving spinal analgesics for cancer pain. 1631 Jun 22

In pediatric oncology, optimal pain control is still a challenge. A structured pain history and the regular scoring of pain intensity using age-adapted measuring tools are hallmarks of optimal pain control. Psychological measures are as important as drug therapy in the prophylaxis or control of pain, especially when performing invasive procedures. Pain control is oriented toward the WHO multistep therapeutic schedule. On no account should the pediatric patient have to climb up the "analgesic ladder" - strong pain requires the primary use of strong opioids. Give opioids preferably by the oral route and by the clock - short-acting opioids should be used to treat breakthrough pain. Alternatives are i.v. infusion, patient-controlled analgesia, and transdermal applications. Constipation is the adverse effect most often seen with (oral) opioid therapy. Adverse effects should be anticipated, and prophylactic treatment should be given consistently. The assistance of pediatric nurses is of the utmost importance in pediatric pain control. Nurses deliver the basis for rational and effective pain control by scoring pain intensity and documenting drug administration as well as adverse effects. The nurses' task is also to prepare the patient for and monitor the patient during painful procedures. It is the responsibility of both nurse and doctor to guarantee emergency intervention during sedation whenever needed. In our guideline we comment on drug selection and dosage, pain measurement tools, and documentation tools for the purpose of pain control. Those tools may be easily integrated into daily routine.
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PMID:[Practical pain control in pediatric oncology. Recommendations of the German Society of Pediatric Oncology and Hematology, the German Association for the Study of Pain, the German Society of Palliative Care, and the Vodafone Institute of Children's Pain Therapy and Palliative Care]. 1642 8


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