Evidence of effectiveness of herbal antiinflammatory drugs in the treatment of painful osteoarthritis and chronic low back pain.

Treatment with herbal medicines is very popular in Europe. In order to get information on the evidence of effectiveness of oral herbal medicines in the treatment of pain in the joints or lower back, OVID(MEDLINE), PUBMED and COCHRANE COLLABORATION LIBRARY were searched back to 1985 for systematic reviews. The level of evidence of effectiveness was defined as strong - at least two confirmatory studies demonstrating a clinical relevant effect, moderate - one confirmatory study with a clinical relevant effect and/or multiple exploratory studies of good quality; otherwise the evidence was insufficient or conflicting in the case of inconsistent findings. Fifteen systematic reviews were identified. The evidence of effectiveness was strong for a proprietary unsaponifiable avocado soybean fraction and Harpagophytum preparations containing > 50 mg harpagoside in the daily dosage, moderate for ginger and a proprietary rose hip and seed powder, insufficient for Boswellia serrata gum resin and other herbal preparations and inconsistent for a proprietary willow bark extract. Further rigorous studies are required to confirm the usefulness of herbal medicines in the treatment of osteoarthritic complaints and chronic low back pain in order to enable acceptance of the herbal medicines into the treatment guidelines.

Effectiveness of Petasites hybridus preparations in the prophylaxis of migraine: a systematic review.

The objective of this review was to evaluate the strength of evidence of effectiveness for Petasites hybridus in the prophylaxis of migraine. Several databases and other sources were searched to identify randomised-controlled trials investigating P. hybridus preparations. Two trials totalling 293 patients (60 and 233 patients) were included in this review. Both trials investigated the proprietary Petasites root extract Petadolex. The trials were described in narrative way, taking into consideration methodological quality scores. Pooling of data was not carried out due to the heterogeneity of the results. The extract at higher dose (150 mg) showed a greater decreased frequency of migraine attacks and a greater number of responders (improvement>50%) after treatment over 3-4 months than the extract at lower dose (100 mg) and placebo. Moderate evidence of effectiveness is, thus, available for a higher than the recommended dose of the proprietary Petasites root extract Petadolex in the prophylaxis of migraine. Further rigorous studies are required to confirm effectiveness and safety in long-term use before treatment with Petasites root extract can be recommended as an alternative option in the treatment schedule for the prophylaxis of migraine.

A comparative study of oral acetylsalicyclic acid and metoprolol for the prophylactic treatment of migraine. A randomized, controlled, double-blind, parallel group phase III study.

This study was a multinational, multicentre, double-blind, active controlled phase III trial designed to investigate efficacy and safety of 300 mg acetylsalicyclic acid (ASA) (n = 135) vs. 200 mg metoprolol (n = 135) in the prophylaxis of migraine. In total 270 (51 male and 219 female) patients, aged 18-65 years, suffering between two and six migraine attacks per month were recruited. The main objective was to show equivalence with respect to efficacy, defined as a 50% reduction in the rate of migraine attacks. A run-in phase was carried out with placebo for 4 weeks, followed by a 16-week drug phase. In both treatment groups the median frequency of migraine attacks improved during the study period, from three to two in the ASA group and from three to one in the metoprolol group; 45.2% of all metoprolol patients were responders compared with 29.6% with ASA. Medication-related adverse events were less frequent in the ASA group (37) than in the metoprolol group (73). The findings from this trial show that metoprolol is superior to ASA for migraine prophylaxis but has more side-effects. Acetylsalicylic acid is better tolerated than metoprolol. Using a strict responder criterion ASA showed a responder rate comparable with the placebo rate in the literature.

[Treatment of pain with peridural administration of opioids]. / Behandlung von Schmerzen mit peridural verabreichten Opioiden.

The advantages and disadvantages associated with epidural opioids require careful selection of the opioid and its dosage. There is presently no ideal opioid available for epidural use. Comparative pharmacokinetic data help to select the appropriate epidural opioid. Morphine (provided it is given in small doses and volumes) is very appropriate for epidural pain treatment, especially for longer periods of treatment, due to excellent analgesia and very low systemic morphine concentrations. The faster onset of analgesia with epidural pethidine, alfentanil und fentanyl make these opioids recommendable. However, due to the increased risk of respiratory depression during continuous treatment, these drugs should not be given over extended periods. Epidural administration of methadone, sufentanil und buprenorphine cannot be recommended since the advantages over systemic use do not outweigh the risks. Epidural tramadol may be useful in clinical routine, if opioids are not available and supervision of the patient is not guaranteed, because tramadol is not restricted by law and has a low potential for central depressive effects. The safety of the patients should be paramount. If patients are harmed by inappropriate opioids or dose regimens this will discredit a valuable for treating postoperative pain. Postoperative epidural dosages should be as low as possible and be titrated to the patient's individual needs for analgesia. Epidural morphine treatment is an alternative to step 4 of the WHO treatment regimen for patients with intractable pain or those suffering from systemic opioid side effects. Careful selection of patients helps to increase successful treatment. If implantable devices (ports or pumps, according to the life expectancy) are employed, the intrathecal route of administration is preferable to the epidural route, as the latter has a 10 times higher morphine dose requirement.

Comparison of morphine with and without fentanyl for epidural analgesia after major abdominal surgery.

BACKGROUND AND OBJECTIVES: The study compared bolus injection of fentanyl versus morphine to supplement epidural infusion of morphine for pain relief after major abdominal surgery. METHODS: Postoperative epidural analgesia was activated by patient request for pain relief. Thirty patients were given a loading dose (random assignment, double-blind administration) of 2 mg of morphine (group M, n = 15) or 60 micrograms of fentanyl (group F/M, n = 15), along with an epidural infusion of 0.2 mg/h of morphine. Additional boluses of 0.5 mg of morphine (group M) or 25 micrograms of fentanyl (group F/M) were given according to individual need. If patients were painfree for 3 hours, the infusion rate for morphine was reduced by 50%. RESULTS: Both treatments provided similar degrees of analgesia, although onset time was shorter for the F/M group (P < .05). To obtain 24 hours of analgesia, group M needed 18.0 mg of morphine, while group F/M needed 4.7 mg of morphine and 1.48 mg of fentanyl. For group M, mean serum concentrations of morphine decreased from 18 ng/mL at 1 hour from the start of treatment to 5 ng/mL at 24 hours. For group F/M, serum morphine stayed at approximately 4 ng/mL, but serum fentanyl increased from 0.28 ng/mL at 5 minutes to about 0.8 ng/mL at 16 hours. CONCLUSIONS: When fentanyl is added continuously to epidural morphine, the resulting higher total serum levels of opioids during prolonged treatment may increase the risk of respiratory depression. Combining the two opioids for the loading dose, however, may be valuable to shorten the onset time of analgesia.

Patient-controlled epidural diamorphine for post-operative pain: verbal rating and visual analogue assessments of pain.

Twenty-two patients were studied while receiving epidural analgesia with diamorphine after major lower abdominal surgery under combined regional and general anaesthesia. Epidural PCA began when the intraoperative epidural block with bupivacaine wore off enough for the patient to request treatment. It was started with 2 mg of diamorphine and continued with a reducible background infusion that was initially set at 0.2 mg h-1 and supplemented by on-demand doses of 0.2 mg, with a lockout time of 15 min. The patients received routine post-operative monitoring and care, with pain at rest being assessed on a four-point verbal rating scale (VRS, none, mild, moderate, severe) at 5, 10, 15, 30, 45, 60, 90 and 120 min from the start of ePCA, then hourly until 24 h and then 2-hourly until 48 h. VRS on coughing and a 10 cm visual analogue score (VAS) at rest and on coughing were recorded at the same times at 4 h, then 4 hourly until 24 h and then at 48 h, at which times, blood samples were also taken to measure morphine concentrations by radioimmunoassay. Analgesia started promptly and reached a maximum at between 30 and 45 min, accompanied by maximum sedation. Thereafter clinically acceptable analgesia was maintained without undue sedation for 48 h, though pain on coughing was less well controlled than pain at rest. After the initial loading dose of diamorphine, the 95% confidence intervals (CI) for further consumption were 3.7 to 17 mg (average 9.7) in the first 24 h and 2.1 to 12.9 mg (average 6.7 mg) in the second 24 h. The plasma morphine concentrations rose to a plateau by about 15 min, with concentrations within 95% CI from 0 to 11 ng mliters-1 (average 5 ng mliters-1. The VRS and VAS pain scores were analysed by a conservative approach that treated them as ordinal data, and by a parametric approach that treated them as interval data. Both approaches conveyed broadly similar information about the post-operative analgesia.

[Treatment of postoperative pain with peridural administration of opioids]. / Die Behandlung postoperativer Schmerzen mit peridural verabreichten Opioiden.

The advantages and disadvantages associated with epidural opioids require careful selection of the opioid and its dose regimen. There is no ideal opioid available for epidural use. Comparative pharmacokinetic data help selection of the appropriate epidural opioid. Morphine (provided it is given in small doses and volumes) is very appropriate for epidural pain treatment, especially for longer periods of treatment, due to the excellent analgesia and very low systemic morphine concentrations. The faster onset of analgesia makes the epidural application of pethidine, alfentanil and fentanyl recommendable. However, due to the increased risk of respiratory depression during continuous treatment, these opioids should not be given over longer treatment periods. Epidural administration of methadon, sufentanil and buprenorphine cannot be recommended since the advantages over systemic use do not outweigh the risks. Epidural tramadol is useful in clinical routine if opioids are not available and supervision of the patient is not guaranteed, because the opioid is not restricted by law and has a low potential for central depressive effects. Nalbuphine and butorphanol should not be selected for epidural use until the benefit/risk ratio is defined. The safety of patients is paramount. If patients are harmed by inappropriate opioids or dose regimens, this will unjustly discredit a valuable treatment of postoperative pain.

[Early detection of opiate-induced respiratory depression in the postoperative phase]. / Untersuchungen zur frühzeitigen Erkennung einer opiatbedingten Atemdepression in der postoperativen Phase.

We examined in 30 patients the efficacy of regular assessments of respiratory rate (every 15 minutes) and blood gas analysis (at 30, 60, 120, 180 minutes) and continuous monitoring via pulsoximeter and capnometer in recognizing early ventilatory problems. For postoperative analgesia the patients received randomly and double-blind patient-controlled intravenous or epidural analgesia with sufentanil. Within 15 minutes after the initial intravenous bolus injection of 15 micrograms sufentanil respiratory depression occurred in 4 patients. This was alerted by the Oscar-CO2-Monitor and -Pulsoximeter. Oxygen saturation time patterns of pulsoximetry and blood gas analysis correlated significantly (p < 0.001), although the mean values of the methods differed (NS). In contrast, carbon-dioxide pressure time patterns of capnometry and blood gas analysis correlated less significantly (p < 0.01) although the mean values of the methods correlated significantly (p < 0.01). Concomittant monitoring via pulsoximeter and capnometer is therefore superior to regulary assessments of respiratory rate and blood gas analysis and potentially useful for the clinical routine.

Epidural versus subcutaneous administration of alfentanil for the management of postoperative pain.

This study was designed to compare the efficacy and serum concentrations of alfentanil given subcutaneously (SQ) or epidurally (EPID) for treatment of postoperative pain. Following abdominal surgery, patients (n = 12) were randomly assigned to receive double-blind SQ or EPID alfentanil over 24 h via the allocated route (1 mg along with 0.2 mg/h and 0.2-mg boluses on demand) and saline via the other route of administration using a patient-controlled analgesic (PCA) delivery system. Significantly less EPID alfentanil produced better quality analgesia and fewer side effects than SQ alfentanil. The fact that EPID analgesia was maintained with serum alfentanil concentrations less than those producing systemic analgesia confirms the spinal site of the EPID alfentanil action.

[Clinical use of alfentanil]. / Zum klinischen Einsatz von Alfentanil.

The fentanyl derivative alfentanil is a potent analgesic characterized by a quick onset time, short duration of action, low toxicity and short elimination time. Alfentanil is mainly used intraoperatively. In minor operations, its intravenous application is sufficient for anaesthesia. In major operations, the need for other anaesthetics can be reduced by the application of alfentanil. The best form of application is the computer-controlled infusion of alfentanil. The advantage of alfentanil over other opioids is the short recovery time of the patient. Alfentanil can also be used postoperatively for pain relief. Used intravenously after abdominal operations, it is approximately ten times more effective than morphine. Applied peridurally its analgesic effect corresponds approximately to that of morphine. Based on the lower amount of alfentanil needed, the patient-controlled application of alfentanil is superior to the use of constant infusion rates. In combination with midazolam, alfentanil can also be used for analgosedation of intensive care patients. Alfentanil is less useful for the treatment of cancer pain since it leads to greater development of tolerance than other opioids.