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Query: UMLS:C0027497 (nausea)
 23,468 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This placebo-controlled, double-blind crossover study assessed whether exclusive activation of peripheral opioid receptors results in significant pain reduction. To achieve opioid activity restricted to the periphery, we used a short-term (2 h) low dose infusion of morphine-6-beta-glucuronide (M6G) because M6G does not pass the blood-brain barrier during this time in amounts sufficient to induce CNS effects. The lack of central opioid effects of M6G was confirmed by a lack of change of the pupil size and absence of other opioid-related CNS effects. As a positive control, morphine was infused at a dosage that definitely produced CNS effects. This was evident by a rapid decrease of the pupil size and by other typical opioid-related side effects including nausea, vomiting, itchiness, hiccup and sedation. Three different pain models were employed to evaluate the analgesic effects: (i) cutaneous inflammatory hyperalgesia induced by briefly freezing a small skin area to -30 degrees C ('freeze lesion'); (ii) muscle hyperalgesia induced by a series of concentric and eccentric muscle contractions (DOMS model; delayed onset of muscle soreness); and (iii) pain induced by electrical current (5 Hz sinus stimuli of 0-10 mA). M6G significantly reduced cutaneous hyperalgesia in the 'freeze lesion' model as assessed with von Frey hairs. It also reduced muscle hyperalgesia in the DOMS model. Electrical pain, however, was not affected by M6G. Morphine was significantly more active in the 'freeze lesion' and DOMS model, and also significantly increased the electrical pain threshold and tolerance. Subcutaneous tissue concentrations of M6G and morphine as assessed with microdialysis were about half those of the respective plasma concentrations. The results of the study indicate that M6G has antihyperalgesic effects in inflammatory pain through activation of peripheral opioid receptors. Since this occurs at concentrations that do not cause central opioid effects, M6G might be useful as a peripheral opioid analgesic.
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PMID:Peripheral opioid analgesia in experimental human pain models. 1269 49

Morphine, the recommended drug for the management of moderate to severe cancer pain, is metabolized predominantly to the glucuronides morphine-6-glucuronide (M6G) and morphine-3-glucuronide (M3G). The quantitative clinical importance of these metabolites following the administration of oral morphine is unclear. This study investigates the relationship between plasma concentrations of morphine (M), M6G, M3G and clinical effects in patients receiving sustained release oral morphine for cancer-related pain. Peak and trough plasma concentrations of morphine and its metabolites were determined by high-performance liquid chromatography (HPLC). At corresponding time points, pain [Visual Analogue Scales (VAS), Verbal Rating Scales (VRS), Pain Relief Scores (PRS)] and toxicity (VAS and VRS) were assessed. Renal and liver function tests were performed. Forty-six patients were included in the study. There was a significant correlation between dose and both peak and trough plasma M, M6G and M3G (r > 0.60, P < 0.001 for each). Differences between peak and trough M, M6G, M3G, M+M6G, M6G:M, M3G:M and M3G:M6G were all significant (P < 0.001 for each). Pain was generally well controlled in the group, with a median VAS of 15 mm at the peak blood sampling time point. The differences between peak and trough values for VAS pain, VAS nausea and VAS drowsiness were not statistically significant (P = 0.078, 0.45 and 0.099, respectively). There were no differences in peak or trough morphine and metabolite concentrations or ratios between patients with low (< median) or high pain scores. Similarly, there was no significant relationship between high and low plasma concentrations and clinical effect. This study did not identify a simple relationship between plasma concentrations of morphine, morphine metabolites or metabolite ratios and clinical effects in patients with cancer and pain who were receiving chronic oral morphine therapy. Although overall pain control was good, there was marked interpatient variability in the dose of morphine and the plasma concentrations necessary to achieve this degree of analgesia.
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PMID:Plasma concentrations of morphine, morphine-6-glucuronide and morphine-3-glucuronide and their relationship with analgesia and side effects in patients with cancer-related pain. 1270 50

Neurolytic celiac plexus block is an established, well-developed procedure and the most accepted and applied in visceral pain; recognized by the WHO and the IASP, it is very good in palliative management of cancer pain in visceral of superior hemiabdomen. However, conventional techniques in celiac plexus have not been successful in patients with organomegaly and/or anatomic abnormalities, except when splanchnic nerve neurolytic blockade is used. On the other hand, conventional techniques in splanchnic nerves are highly associated with complications such as paraplegia, pneumothorax and liver or renal punction. For these reasons an alternative option has ben designed, termed transdiscal percutaneous approach of splanchnic nerves under tomographic control; this technique affords the option of improving accuracy and performance with minimum risks, particularly lung puncture and its consequences. Under this technique, 64 superior hemi-abdomen cancer patients initiated such a study (four without morphine treatment quit the study), 55% females and 45% males, visceral pain syndrome 65%, and mixed, 35%. Side effects were dyspnea 5%, hypotension 26.7%, nausea 31.7%, diarrhea 83.3% in which diarrhea means increased peristalsis showing adequate sympathetic inhibition via splanchnic nerves), vomiting 28.3%, punction-site pain 46.7%, aorta punction 6.7%, anal pleural punction 5%. All these incidents were dealt with by conservative treatment. Student t test showed that pain intensity in all measurements after procedure was different in comparison to basal pain intensity prior to procedure (p<0.05), emphasizing that at the 12th, 18th and 24th months, there was noticeable reduction in participants number with eight, five and four participants, respectively. Morphine intake at week 1, and 1, 2, 3, 6 and 12 months after procedure was different from basal intake prior to procedure (p<0.05) with same noticeable reduction in participant numbers at last stages. Butylhioscine intake at week 1, 1, 2, 3 and 6 months after procedure was different from basal intake prior to procedure (p<0.05). NSAIDs consumption was likely during 2 months after procedure (p<0.05). Linear regression showed that butylhioscine and morphine explained low percentage of pain intensity variance, controlling statistically that effect over pain. There were no differences in pain pathophysiology with regard to cancer type. Transdiscal percutaneous approach of splanchnic nerves guided by CAT is an alternative with minimal risks, as with lung punction, confirming that inhibiting splanchnic nerves has advantages in pain release, reducing and/or eliminating morphine consumption.
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PMID:[Transdiscal percutaneous approach of splanchnic nerves]. 1461 7

In a randomized, double-blind study, conducted in 60 patients after caesarean section, we compared epidural morphine (5 mg) with intravenous morphine patient-controlled analgesia (PCA). Efficacy of pain relief (visual analogue scale), comfort, satisfaction and side-effects were studied. In the PCA group, pain scores were higher (P < 0.005) from the third hour onward. The degree of comfort was similar. Overall satisfaction for the first 24 postoperative hours was higher in the epidural group when assessed on a graded scale from 0 to 10, but equal when assessed using qualitative terms. Haemodynamic and respiratory tolerance were identical without any episodes of respiratory depression or oxygen desaturation in either group. The epidural morphine group showed a higher incidence of pruritus requiring specific treatment (P < 0.005). Nausea was reported to be equal in the two groups. Consumption of morphine was higher in the PCA group. We conclude that epidural morphine analgesia, though of good quality, was associated with more pruritus. Morphine PCA, although producing a lesser degree of analgesia compared to epidural morphine, gave good satisfaction.
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PMID:Analgesia after caesarean section: patient-controlled intravenous morphine vs epidural morphine. 1532 Dec 87

Sustained-release morphine sulfate (SRMS) is a painkiller used in oncology. The purpose of our study was to assess its efficacy on postoperative morphine requirements in elective spine surgery. This was a placebo-controlled, randomized, double-blind study. Adults scheduled for spine surgery under general anesthesia were orally administered SRMS (30 mg) or a placebo 2 h before surgery. Primary endpoint was postoperative cumulated morphine consumption through patient-controlled analgesia (PCA) during the 12 h following extubation. Statistical analysis was performed using a sequential method, the triangular test. The study was stopped after the sixth analysis (51 patients had been included; placebo: 26, SRMS: 25). Age, weight, sex ratio, type of surgery, intra-operative sufentanil consumption, anesthesia duration and time to extubation were similar in the two groups. Morphine consumption through PCA during the 12 h following extubation was significantly lower in the SRMS group (mean +/- SD: 10.5 +/- 7.6 mg) compared with placebo group (15.6 +/- 6.0 mg, P = 0.016, sequential analysis). Corresponding unbiased median estimates were 10.6 and 15.8 mg in SRMS and placebo groups, respectively. Morphine consumption through PCA during the 24 h following extubation was also significantly lower in the SRMS group (15.9 +/- 12.7 mg) compared with the placebo group (23.8 +/- 10.9 mg, P = 0.032). Vigilance, nausea and respiratory rate 3 and 6 h after extubation were similar in the two groups. A preoperative oral administration of SRMS (30 mg) induces a 33% reduction of postoperative morphine requirements in patients scheduled for spine surgery without inducing side effects.
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PMID:Effect of preoperative oral sustained-release morphine sulfate on postoperative morphine requirements in elective spine surgery. 1554 44

Opioids are frequently associated with side effects such as nausea, vomiting, and pruritus. We hypothesized that a prophylactic, continuous small-dose naloxone infusion would reduce the incidence of opioid-induced side effects without affecting analgesia or opioid consumption. In this prospective, double-blind, randomized, controlled clinical trial, we studied 46 postoperative patients (M:F, 21:25), averaging 14 +/- 2.5 yr and 53 +/- 17 kg, at the start of morphine IV patient-controlled analgesia. Patients were randomized to either saline (control, n = 26) or naloxone 0.25 microg . kg(-1) . h(-1) (n = 20). We found that the incidence and severity of pruritus (77% versus 20%; P < 0.05) and nausea (70% versus 35%; P < 0.05) was significantly more frequent in the placebo group compared with the naloxone group. Morphine consumption (1.02 +/- 0.41 mg . kg(-1) . d(-1) versus 1.28 +/- 0.61 mg . kg(-1) . d(-1)), pain scores at rest (4 +/- 2 versus 3 +/- 2), and pain scores with coughing (6 +/- 2 versus 6 +/- 2) were not different. We conclude that, in children and adolescents, a small-dose naloxone infusion (0.25 microg . kg(-1) . h(-1)) can significantly reduce the incidence and severity of opioid-induced side effects without affecting opioid-induced analgesia. When initiating morphine IV patient-controlled analgesia for the treatment of moderate to severe pain, clinicians should strongly consider starting a concomitant small-dose naloxone infusion.
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PMID:The effects of a small-dose naloxone infusion on opioid-induced side effects and analgesia in children and adolescents treated with intravenous patient-controlled analgesia: a double-blind, prospective, randomized, controlled study. 1578 5

Morphine-6-glucuronide (M6G) appears to show equivalent analgesia to morphine but to have a superior side-effect profile in terms of reduced liability to induce nausea and vomiting and respiratory depression. The purpose of this review is to examine the evidence behind this statement and to identify the possible reasons that may contribute to the profile of M6G. The vast majority of available data supports the notion that both M6G and morphine mediate their effects by activating the micro-opioid receptor. The differences for which there is a reasonable consensus in the literature can be summarized as: (1) Morphine has a slightly higher affinity for the micro-opioid receptor than M6G, (2) M6G shows a slightly higher efficacy at the micro-opioid receptor, (3) M6G has a lower affinity for the kappa-opioid receptor than morphine, and (4) M6G has a very different absorption, distribution, metabolism, and excretion (ADME) profile from morphine. However, none of these are adequate alone to explain the clinical differences between M6G and morphine. The ADME differences are perhaps most likely to explain some of the differences but seem unlikely to be the whole story. Further work is required to examine further the profile of M6G, notably whether M6G penetrates differentially to areas of the brain involved in pain and those involved in nausea, vomiting, and respiratory control or whether micro-opioid receptors in these brain areas differ in either their regulation or pharmacology.
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PMID:Morphine-6-glucuronide: actions and mechanisms. 1595 75

Women undergoing postoperative postpartum tubal ligation (PPTL) often experience considerable pain. We hypothesized that epidural morphine, as part of a multi-modal analgesic regimen, would decrease postoperative pain and the need for systemic analgesia after PPTL. In a double-blinded study, patients were randomized to receive epidural saline or morphine 2 mg, 3 mg, or 4 mg after epidural anesthesia for PPTL. Postoperatively, ibuprofen 600 mg was administered every 6 h and patients could request acetaminophen 325 mg/hydrocodone 10 mg. The primary outcome variable was time to first request for supplemental analgesia. Verbal rating scores for pain and the incidence and severity of side effects were recorded for 24 h. Morphine group subjects requested supplemental analgesia later and received fewer doses compared with the saline group subjects. Peak cramping and incisional verbal rating scores for pain and the area under the verbal rating scores for pain x time curve for cramping pain were less after epidural morphine compared with saline, but there were no differences among morphine groups. Nausea, vomiting, and pruritus occurred more often in all morphine groups and subjects who received morphine 4 mg required treatment for these side effects more frequently than the saline or morphine 2 mg groups. In conclusion, epidural morphine 2 mg as part of a multi-modal analgesic regimen improved analgesia and decreased the need for supplemental analgesics after PPTL. The need to treat side effects with morphine 2 mg was not increased compared to a regimen of oral acetaminophen/opioid/nonsteroidal antiinflammatory analgesics.
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PMID:Postoperative epidural morphine for postpartum tubal ligation analgesia. 1655 57

Pain is a common occurrence for the hospitalized elderly, and may often be under recognized and inadequately managed. Insufficient pain management can lead to the sequelae of emotional distress and depression, delirium, anxiety, sleep disturbances, and physical disabilities, as well as increased health care costs. Effective pain management of the older adult begins with pain assessment using the proper tools. Morphine is the analgesic of choice for the older adult, and is appropriate for the postoperative period. It is important to maintain a therapeutic serum level of opioids to prevent inadequate management of the acute pain. Side effects of opioids include hypotension, nausea, mood disturbances, ileus, histamine production, and respiratory depression. The adage for pain treatment in the elderly is "start low and go slow". Paracetamol is commonly prescribed and may be the drug of choice for mild to moderate postoperative pain. Older adults may enjoy the benefits of Patient-Controlled Analgesia and Patient Controlled Epidural Analgesia in the postoperative period; however, thorough and ongoing teaching must occur to ensure understanding and compliance with the therapy. Treating post-procedure pain in the elderly patient requires an understanding of the normal changes associated with aging and the impact on medications, and multimodal analgesia can be the best approach.
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PMID:[Postoperative pain management in elderly patient]. 1759 59

In a randomised double blind prospective study, we tested the hypothesis that postoperative pain is lower in patients who receive an ProSeal LMA laryngeal mask airway compared with a tracheal tube. One hundred consecutive female patients (ASA I-II, 18-75 years) undergoing laparoscopic gynaecological surgery were divided into two equal-sized groups for airway management with the ProSeal LMA or tracheal tube. Anaesthesia management was identical for both groups and included induction of anaesthesia using propofol/fentanyl, and maintenance with propofol/remifentanil, muscle relaxation with rocuronium, positive pressure ventilation, gastric tube insertion, dexamethasone/tropisetron for anti-emetic prophylaxis, and diclofenac for pain prophylaxis. All types of postoperative pain were treated using intravenous patient-controlled analgesia (PCA) morphine. Patients and postoperative staff were unaware of the airway device used. Data were collected by a single blinded observer. We found that pain scores were lower for the ProSeal LMA at 2 h and 6 h but not at 24 h. Morphine requirements were lower for the ProSeal LMA by 30.4%, 30.6% and 23.3% at 2, 6 and 24 h, respectively. Nausea was less common with the ProSeal LMA than with the tracheal tube at 2 h and 6 h but not at 24 h. There were no differences in the frequency of vomiting, sore throat, dysphonia or dysphagia. We conclude that postoperative pain is lower for the ProSeal LMA than the tracheal tube in females undergoing gynaecological laparoscopic surgery.
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PMID:A study of airway management using the ProSeal LMA laryngeal mask airway compared with the tracheal tube on postoperative analgesia requirements following gynaecological laparoscopic surgery. 1769 18


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