Opioide in der Behandlung von Tumorschmerzen bei Kindern und Jugendlichen
Opioids take effect by way of binding to specific receptors both in the central nervous system and, as shown by recent investigations, in the peripheral areas. The different preparations available have a largely identical spectrum of activity and comparable side-effects. There are, however, differences in the intensity of action and in how pronounced the various side-effects are.
As in other age groups, opioids should be administered to children in the form of sustained release preparations and not “as needed” but regularly according to a predetermined time-schedule.
Partial agonists (e.g. buprenorphine) must not be given with absolute agonists (codeine, dihydrocodeine, tramadol, morphine or methadone).
If the effect of a strong agonist (morphine or methadone) is too small there is little sense in changing to a partial agonist; it is preferable to give a higher dose of the agonist.
For moderately severe pain in children and young people, the most suitable of the mild opioids available are tramadol (Tramai) and dihydrocodeine (DHC 60 Mundipharma). Tramadol is given orally every 4–6 h as tablets or drops, a single dose being 0.5–2.0 mg/kg body weight. Dihydrocodeine (using sustained release tablets) can be dosed at 1–2 mg/kg body weight every 8–12 h. If adequate pain relief cannot be achieved with such weak opioids, the strong opioid of choice is morphine, for children too. Even following oral administration it is a powerful analgesic. Initially, morphine is given by the oral route in the form of an aqueous solution (single doses of 0.2–0.5 mg/kg body weight) every 4 h or in the form of sustained release tablets (MST Mundipharma) in single doses of 0.5–1.0 mg/kg body weight every 8–12 h. If oral administration is impossible morphine suppositories can be considered (MSR Mundipharma). The initial dose in this case is 0.2–0.5 mg/kg body weight every 4 h.
The long duration of action (8–12 h) of using sustained release tablets of morphine is a decisive advantage in therapy. For this reason the tablets should not be divided, and especially not be reduced to powder. This would largely destroy the sustained release effect, and in isolated cases undesirably high plasma levels of morphine could occur in the short term, which could not easily be estimated in advance.
As the therapy progresses, the dose of morphine required must then be individually determined for each patient with reference to the degree of pain relief achieved. There is no fixed maximum dose for morphine — even for use in children — (in contrast to the non-narcotic analgetics and weak opioids), and in severe cases several hundred milligrams of morphine per day may be necessary for adequate pain relief even in children.
Other strong opioids that can be used in children are buprenorphine (Temgesic) and methadone (L-Polamidon). The efficacy of buprenorphine is limited by the so-called ceiling effect — beyond a certain point further dose increases no longer bring about any enhancement of the analgesic effect. In the case of methadone the half-life is several times longer than the duration of effect, so that there is a real danger of cumulation. Children treated with methadone must therefore be carefully monitored. If necessary, either the dose must be reduced or the interval between doses must be extended.
If a sufficiently effective oral therapy is not possible (e.g. in the terminal stage or in the presence of extremely severe vomiting and/or obstinate constipation), long-term subcutaneous or intravenous infusion of morphine is an alternative. This is started with 0.05–0.1 mg/kg body weight per hour, or with one third to one half of the daily dose hitherto given by mouth. If morphine has very pronounced side-effects piritramide or fentanyl can be tried as alternatives.
The side-effects most frequently encountered with opioids are obstinate constipation, nausea and vomiting. These should be consistently treated from the start with laxatives (e.g. lactulose) and antiemetics (e.g. haloperidol). Refractory pruritis with morphine can occasionally make it necessary to switch to a different analgesic or to a different route of administration.
At first, tiredness and slight sedation are frequent. Opioids do not, however, lead to a lasting impairment of intellectual ability. On the contrary, the freedom from pain achieved with highly dosed opioids is the only thing that makes it possible for the children to return to nursery school or school in many cases. Except for very young infants, children’s reactions to opioids are no more intense than those of adults.
The new research results obtained in recent years on systematic pain therapy — particularly with morphine in children and young people — must be even more intensely integrated into day-to-day clinical practice than has hitherto been the case. It is of crucial importance that the unfounded but still widespread fear of opioids will be reduced.
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