nificantly increased during a permanent oxycodone treatment. However, the plasma concentration can be increased in patients suffering from renal and liver insufficiency.

It can be administered in non-retarded (onset of action takes place after 15 to 25 minutes, action time 4 to 6 hours) and retarded (onset of action takes place after 60 minutes, action time 8 to 12 hours) form and is also available as parenterally injectable solution (rapid onset of action within 2 to 5 minutes, action time 4 hours). 2 mg orally administered oxycodone equals 1 mg parenterally administered oxycodone. However, due to individually different responses, a careful dosage titration is essential.

L-Methadone

L-Methadone is a μ-receptor agonist with low addiction potential and a 2 to 3-fold higher potency than morphine. It is not suitable for acute pain management as its action time is relatively long and not clearly predictable. Apart from that there is a high risk of accumulation, particularly in the presence of liver insufficiency.

In addition to its action at the opioid receptors, methadone has also antagonistic properties at the NMDA receptors. During a permanent opioid treatment with tolerance development, a rotation to methadone can improve analgesia.

In a patient (TBSA 55%) with chronic neuropathic pain after wound healing, the rotation to methadone could reduce the pain by 70% and improve the quality of life significantly [47].

Remifentanil

Remifentanil is an ultra short-acting, very well controllable opioid. Its potency is 200-fold higher than morphine. It is used intraoperatively during sedoanalgesia and in the intensive care unit (see IX. intensive care patients/6.2. analgesia). In single cases remifentanil is used with adequate monitoring for the treatment of burn pain in patients not receiving artificial respiration.

Other analgesics

Ketamine (see also intensive care unit and analgosedation)

Ketamine is used during sedoanalgesia in the intensive care unit and in the treatment of opioid-induced hyperalgesia and opioid tolerance as well as in chronic pain.

Literature provides numerous studies concerning the supplementation of an opioid therapy with ketamine in low, subanesthetic doses [48]. Psychomimetic side effects have only been reported in single cases.

Repeated surgical interventions as well as opioid therapy cause the activation of NMDA receptors. The effect of opioids is reduced due to a sensitization of the NMDA receptors through opioid induced hyperalgesia and opioid tolerance [49]. The application of NMDA receptor antagonists can lessen or inhibit these antinociceptive effects [50].

Weinbroum et al. showed that administering 250 μg/kg Ketamine in postoperative ineffectiveness of strong opioids could sufficiently relieve the pain [51].

Furthermore, an intraoperative intravenous administration of ketamine can reduce the postoperative demand for opioids and the opioid-induced side effects [52]. This effect should be taken advantage of after painful interventions with high demand for opioids (e. g. debridements in burn patients). Single studies show that a perioperative intravenous administration of ketamine can reduce the incidence of postoperative chronic pain [53, 54].

When administered for sedation during painful procedures stationary, ketamine is also effective and secure in children with burn trauma. An analysis of 347 sedations with administering ketamine according to a strict protocol and adequate monitoring showed a very low number (10i. e. 2.9%) of complications that required interventions like oxygenation or volume substitution [55].

Compared to the racemate ketamine the analgesic potency of S(+)-ketamine is twice as high and has fewer psychomimetic side effects. Thus, when administering S(+)-ketamine half of the dosage of the racemate is sufficient.

Anticonvulsants (Gabapentin and Pregabalin)

Gabapentin is important in numerous clinical settings: initially is was developed as an anticonvulsant for the treatment of epileptic partial seizures. However, nowadays gabapentin is a commonly used drug in the treatment of neuropathic pain of various causes. Additionally, several clinical studies have shown its effectiveness in the treatment of anxiety disorder [56–58]. Gabapentin also reduces the postoperative need for opioids and the opioid-induced side effects [59]. It is assumed that gabapentin has an antihyperalgetic component [60].

The exact mechanism of action remains unknown. The 2- -subunits of the voltage-dependent calcium channel were identified as binding spots. By inhibiting the calcium influx, the release of substance P, glutamate and calcitonin gene related peptide (CGRP) is suppressed.

In clinically relevant concentrations gabapentin does not bind to other receptors in the brain. In several in vitro test systems gabapentin decreased partially the effect on the glutamate agonist N-methyl- D-aspartic acid, however only in concentrations over 100 μg, which cannot be achieved in vivo.

Gabapentin does not bind to plasma proteins. There is no evidence of metabolism and it is only renally excreted. The dosage of gabapentin should thus be determined depending on the renal function of the patient (e. g. dependent on creatinine clearance).

To avoid side effects it is recommended to find the correct dosage by titrating: initially 300 mg once daily and after that depending on reaction and tolerance increase of the daily dosage in steps of 300 mg every second to third day until a maximum dosage of 3 600 mg daily is reached. In children of 6 years and older the initial daily total dosage is 10 mg/kg/day to 15 mg/kg/day dependent on the dosage of the onset therapy. The maximum daily dosage should be administered in three single doses as in adults. Dosages up to 40 mg/kg have proven well tolerated in clinical studies.

The usage of gabapentin in the management of burn injuries is still not sufficiently evaluated. A small study with burn patients (mean total burned surface area 25%) showed that gabapentin could reduce significantly the opioid consumption and pain

intensity. From day 3 to day 24 after the burn accident patients were administered 2 400 mg gabapentin in 3 single doses [61].

The neuropathic component of burn pain is often misinterpreted and has not been evaluated very extensively so far. Gabapentin could be administered successfully in a case series of 6 patients, who developed burning (neuropathic) pain in the area of the burned skin or the donor sites for skin grafting within 1 to 7 days after the burn accident [5].

Furthermore, a study in 35 children (6 months to 15 years of age) with severe itching of the healing burns showed that gabapentin could improve the symptoms significantly within 24 hours [62].

Pregabalin is a structure-related anticonvulsant and has the same mechanism of action as gabapentin. However, its pharmacological properties are better (oral bioavailability independent of the dosage, linear dose-effect relation). The initial dose is 150 mg in 2 single doses, the daily maximum dosage is 600 mg.

Antidepressants with analgesic effects

Depression and pain are very often closely related and show several similarities in their psychopathology and pharmacology. A dysfunction of ascending and descending serotonergic and noradrenergic tracts not only can cause depressive syndromes but also maintain the pain syndromes.

Thus, antidepressants are a very important part of the multimodal general treatment of burn patients [63]. A study group from Texas showed that an early administration of antidepressants in children with burn trauma could treat acute stress reactions successfully [64]. An intensifying effect of descending and ascending serotonergic and noradrenergic tracts by antidepressants can inhibit the pain signals from the body’s periphery and the intestines. The analgesic effect occurs mostly with a time lag of several days up to 3 weeks. Currently, the literature does not provide any studies concerning the analgesic effects of antidepressants in burn patients.

Tricyclic antidepressant (TCA) as for example amitryptiline: For a long time the use of TCA was the golden standard in the coanalgesia with antidepressants. A downside of TCA is the high potential for anticholinergic side effects. Apart from