Haloperidol versus haloperidol plus ondansetron for the prophylaxis of postoperative nausea and vomiting after ophthalmologic surgery.

INTRODUCTION: In this prospective, randomized, and double-blinded study we investigated the efficacy of haloperidol (10 microg/kg) and the combination of haloperidol (10 microg/kg) with ondansetron (0.1 mg/kg) for the prophylaxis of postoperative nausea and vomiting (PONV) after ophthalmologic surgery. METHODS: 60 patients (ASA status 1-3) with risk factors for PONV (female, non-smoker, motion sickness or PONV in history, opioids for postoperative analgesia) undergoing retinal or strabismus surgery were included into the study and randomised to the haloperidol group (H-Group) or the haloperidol-ondansetron group (H/O-Group). 20 min before the end of anaesthesia the study medication was given. Nausea, vomiting, pain scores, and adverse events were assessed postoperatively over 24 h. RESULTS: The incidence of PONV was lower for the H/O-Group (23 vs. 57% for the H-Group). Especially the incidence of vomiting was reduced for the H/O-Group (7 vs. 27% in the H-Group). No significant differences could be detected regarding adverse events. CONCLUSION: The single use of haloperidol for the prophylaxis of PONV is doubtful. Better results were obtained with the combination therapy of haloperidol with ondansetron, especially for vomiting.

Local anesthetics differentially inhibit sympathetic neuron-mediated and C fiber-mediated synovial neurogenic plasma extravasation.

UNLABELLED: Local anesthetics are used for local irrigation after many types of operations. However, recent evidence of toxic effects of local anesthetics at large concentrations during continuous administration suggests an advantage of using decreased local anesthetic concentrations for irrigation solutions. In this study, we determined whether smaller concentrations of local anesthetics may maintain an antiinflammatory and, therefore, analgesic effect without the risk of possible toxicity. Lidocaine and bupivacaine were studied for their ability to inhibit both components of neurogenic inflammation-C fiber-mediated and sympathetic postganglionic neuron (SPGN)-mediated inflammation-in the rat knee joint. Intraarticular lidocaine 0.02% reduced 5-hydroxytryptamine (5-HT)-induced (SPGN-mediated) plasma extravasation (PE) by 35%, and further decreases were obtained by perfusing larger concentrations of lidocaine. Intraarticular bupivacaine 0.025% inhibited 5-HT-induced PE by 60%, and a 95% inhibition was obtained with bupivacaine 0.05%. Larger local anesthetic concentrations were necessary to inhibit C fiber-mediated PE than those required to inhibit SPGN-mediated PE. Lidocaine 0.4% was required to reduce mustard oil-induced PE by 60%. Lidocaine 2% inhibited mustard oil-induced PE to baseline levels. Bupivacaine 0.1% was required for an 80% reduction of PE. Bupivacaine 0.25% inhibited mustard oil-induced PE to baseline levels. Our results demonstrate differential effects of local anesthetics on SPGN- and C fiber-mediated PE but confirm the concept of using smaller concentrations of local anesthetics to achieve inhibition of postoperative inflammation. IMPLICATIONS: Local anesthetic wound irrigation is often used to treat postoperative surgical pain. Large concentrations of local anesthetics are usually used, and these concentrations may have possible neurotoxic and myotoxic effects. Our results demonstrate antiinflammatory effects of lidocaine and bupivacaine at concentrations smaller than used clinically.

5-HT7 receptors are involved in mediating 5-HT-induced activation of rat primary afferent neurons.

The purpose of this study was to determine whether the 5-hydroxytryptamine7 (5-HT7) receptor is expressed by nociceptor-like neurons in the rat PNS and whether 5-HT activates these nociceptors via the 5-HT7 receptor subtype. Using a polyclonal antibody and the method of immunofluorescence staining, we demonstrated that the 5-HT7 receptor appears predominately on "nociceptor-like" neurons of the rat lumbar dorsal root ganglia. Using immunocytochemical methods, we showed that the immunoreactivity of the 5-HT7 receptor antibody complex is localized in the superficial layers of the spinal cord dorsal horn, which corresponds with laminae I, IIouter and IIinner. Furthermore, we demonstrated that noxious stimulation produced by knee injection of 5-HT or a 5-HT7 agonist dose-dependently increases c-Fos production of the rat spinal cord dorsal horn. This effect was significantly inhibited by the preinjection of a 5-HT7 antagonist. We conclude that the 5-HT7 receptor is expressed by rat primary afferent nociceptors which terminate in the superficial layers of the spinal cord dorsal horn and that the 5-HT7 receptor subtype is involved in nociceptor activation by 5-HT.

Involvement of endogenous opioid systems in nociceptin-induced spinal antinociception in rats.

The present study investigates the involvement of opioid receptors in the antinociceptive effects of nociceptin in the spinal cord of the rat. Intrathecal administrations of 5 and 10 nmol of nociceptin significantly increase the withdraw response latencies to noxious thermal and mechanical stimulations. This nociceptin-induced antinociceptive effect is significantly attenuated by intrathecal injection of (Nphe(1))nociceptin(1-13)-NH(2), a selective antagonist of the nociceptin receptor (opioid receptor-like receptor ORL1), indicating an ORL1 receptor-mediated mechanism. This antinociceptive effect is also significantly attenuated by intrathecal injections of naloxone (a nonselective opioid receptor antagonist), naltrindole (a selective delta-opioid receptor antagonist), and beta-funaltrexamine (a selective mu-opioid receptor antagonist) in a dose-dependent manner, but not by the selective kappa-opioid receptor antagonist norbinaltorphimine. Since it is unlikely that nociceptin acts by direct binding to opioid receptors, these results suggest a possible interaction between the nociceptin/ORL1 and opioid systems in the dorsal horn of the rat spinal cord.

Symptoms during cancer pain treatment following WHO-guidelines: a longitudinal follow-up study of symptom prevalence, severity and etiology.

Most patients with advanced cancer develop diverse symptoms that can limit the efficacy of pain treatment and undermine their quality of life. The present study surveys symptom prevalence, etiology and severity in 593 cancer patients treated by a pain service. Non-opioid analgesics, opioids and adjuvants were administered following the WHO-guidelines for cancer pain relief. Other symptoms were systematically treated by appropriate adjuvant drugs. Pain and symptom severity was measured daily by patient self-assessment; the physicians of the pain service assessed symptom etiology and the severity of confusion, coma and gastrointestinal obstruction at each visit. The patients were treated for an average period of 51 days. Efficacy of pain treatment was good in 70%, satisfactory in 16% and inadequate in 14% of patients. The initial treatment caused a significant reduction in the average number of symptoms from four to three. Prevalence and severity of anorexia, impaired activity, confusion, mood changes, insomnia, constipation, dyspepsia, dyspnoea, coughing, dysphagia and urinary symptoms were significantly reduced, those of sedation, other neuropsychiatric symptoms and dry mouth were significantly increased and those of coma, vertigo, diarrhea, nausea, vomiting, intestinal obstruction, erythema, pruritus and sweating remained unchanged. The most frequent symptoms were impaired activity (74% of days), mood changes (22%), constipation (23%), nausea (23%) and dry mouth (20%). The highest severity scores were associated with impaired activity, sedation, coma, intestinal obstruction, dysphagia and urinary symptoms. Of all 23 symptoms, only constipation, erythema and dry mouth were assessed as being most frequently caused by the analgesic regimen. In conclusion, the high prevalence and severity of many symptoms in far advanced cancer can be reduced, if pain treatment is combined with systematic symptom control. Nevertheless, general, neuropsychiatric and gastrointestinal symptoms are experienced during a major part of treatment time and pain relief was inadequate in 14% of patients. Cancer pain management has to be embedded in a frame of palliative care, taking all the possibilities of symptom management into consideration.