Pain management after burn trauma

en from the wound during the numerous therapeutical measures and thus limit their efficacy.

Modified WHO pain ladder (see Fig. 1)

Depending on pain intensity and pain history the application of the (modified) WHO pain ladder can be recommended: Therapy starts either on stage 1 and is increased until sufficient analgetics are administered or already begins on a higher stage, which is often necessary in burn injuries.

Non-opioids (Table 1)

It is recommended to apply basic treatment with non-opioids. Side effects and possible complications as mentioned below should always be considered.

Non-opioids reduce the opioid requirement by 20% to 30% [22]. NSAID can reduce the side effects caused by opioids significantly [23]. By blocking the cyclooxygenasis or blocking the development of PG E2, a stimulation of the NMDA-receptor-NO system with development of an opioid tolerance and opioidinduced hyperalgesia can be reduced [24, 25].

Step I	Step II	Step III
		Strong opioids
	Weak/Moderate	Morphine
	opioids	Hydromorphone
	Tramadol	Fentanyl
Non-opiod	Pethidine	Oxycodon
analgesics		Methadon
NSAID, Coxibe
Metamizole
Paracetamol	+ Step 1	+Step 1

Ketamin, anticonvulsants, antidepressants

Treatment without medication

Regional anesthetic

Fig. 1. Modified WHO pain ladder

Paracetamol should be administered carefully if the patient suffers from chronic alcoholism or chronic malnutrition as in these cases the reserves of hepatic glutathione are low. Paracetamol can be administered enterally, parenterally or rectally. The benefits of an intravenous administration is a rapid invasion of the active ingredients into the central nervous system. Compared to an oral administration, an intra-

Paracetamol

Paracetamol is part of the non-acidic antipyretic analgesics. The exact mechanism of the analgentic and antipyretic effects has not been fully investigated yet. However, central and peripheral points of action might play a role in the efficacy of paracetamol. Influences to the serotonergic system have already been verified [26].

The maximum daily dose for adults of normal weight is 4 000 mg, maximum dose for children is 60 mg/kgBW. Daily doses of paracetamol above 100 mg/kgBW (6g to 8g daily) are hepatoxic. It has to be considered though that the administration of the normal daily dose can also cause liver cell necrosis and liver failure in case of pre-existing liver disorders and/or glutathione deficiency. N-acetycysteine is an efficient antidote and should be administered within 10 hours after the overdosage if possible.

A contra-indication for administering paracetamol is the presence of severe liver insufficiency.

Table 1. Pharmacological data of non-opioids

Active	HL (h)	Ad-	Single dose	Daily
Ingred-		minis-	in adults	maximum
ient		tration	(mg)	dose (mg)
Diclo-		p. o.,
fenac	1–2	i. v.	50–75	150
Ibu-
profen	1,5–2,5	p. o.	200–800	2400
Lorn-		p. o.,
oxicam	3–4	i. v.	8	16
Paraceta-
mol	1,5–2,5	p. o.	500–1000	4000
		i. v.	1000	4000
Metami-
zole	2–4	p. o.	500–1000	4000
		i. v.	1000–2500	5000
Celecoxib	11	p. o.	100–200	400
Pare-
coxib	~ 22	i. v.	40	80

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venous administration takes effect faster and more effectively [27]. The analgesic effect of paracetamol administered intravenously occurs within 5 to 10 minutes and generally persists for 4 to 6 hours.

Among all non-opioids only paracetamol can be administered safely during pregnancy and lactation period.

Metamizole

Metamizole belongs to the non-acidic antipyretic analgesics. It is one of the most efficient non-opioids and additionally has a spasmolytic effect.

The exact mechanism of metamizole is still unknown. Basically it is assumed that it has a central effect. An additional peripheral analgesic effect by inhibiting the prostaglandinesynthesis is described for pyrazolonederivates [28].

Metamizole does not combine in acidic tissue, does not have any pharmacologically active metabolites and is mostly egested renally. Compared to NSAID, the benefit of metamizole is few interaction with the thrombocyte function. Metamizole can be administered enterally, parenterally, intramuscularly, and rectally. Contrary to most of the NSAID, metamizole can be administered in any form to children of 3 months and older. A single dose for an adult is between 1g and 2.5g with a daily maximum dose of 5g. In children it is recommended to administer 10 mg/kg/BW to 25 mg/kgBW orally or rectally and 10 mg/kgBW to 15 mg/kgBW intravenously every 4 to 6 hours.

The risk of agranulocytosis is described controversially, with incidences of 1 : 1,000,000 [29] to 1 : 1,451 in Sweden [30]. The risk of an agranulocytosis during a permanent therapy with metamizole can be minimized by regular blood counts. A rapid infusion of metamizole can cause severe hypotonia due to anaphylactoid reactions.

Non-steroidal antirheumatics (NSAID)

NSAID have analgesic, antipyretic and antiphlogistic effects. They are nonselective inhibitors of the enzyme cyclooxygenasis, which plays a key role in the prostaglandine synthesis. They are bound with more than 90% to plasmaproteins and enrich in tissue that has been altered by inflammation.

The mechanism relevant for an analgesic therapy mightbetheriseintheexcitationthresholdofnociceptors after inhibition of the prostaglandine synthesis. The anatomic area of action of the substances has not been fully explained yet, however central and peripheral points of action have been described so far.

NSAID have numerous side-effects. When administered only for a short-time, renal disorders and disorders in the thrombocyte function are most commonly observed. The risk of post-surgical bleeding under therapy with non-opioids is discussed controversially. The bleeding time is increased by approximately 30% under the administration of NSAID. Thus, due to the inhibition of the thrombocyte aggregation, NSAID should only be administered when there is no more need for a bleeding intensive necrosectomy.

In a long-term administration, gastric, cardiac and renal effects are most commonly observed.

Diclofenac: Approved for short-term administration (max. 2 weeks). No recommendation for children younger than 14 years. However, the administration is very common in numerous countries due to lack of alternatives. Dosage: 50 mg to 150 mg daily in 2 or 3 single doses.

Lornoxicam: Not recommended for children and teenagers younger than 18 years. No special dosage instructions for older patients. Dosage: 8 mg to 16 mg daily in 2 or 3 single doses.

Ibuprofen: Ibuprofen does not have many sideeffects. It shows the lowest ulcerogenic potency of all NSAID. As syrup approved for children and infants from the age of 6 months.

Selective cyclooxygenasis-2-inhibitors

The discovery of at least 2 cyclooxygenasis-isoen- zymes has lead to the development of a cyclogen- asis-2 selective group of analgesics, which differs from the other NSAID particularly because of their missing thrombocyte function disorder and the significantly reduced gastro-intestinal side-effects.

However, numerous large-scale randomized studies showed a cardiovascular toxicity [31–33]. According to the recommendation of the European Medicines Agency, selective cyclooxygenase-2-in- hibitors are contra-indicated in the presence of clinically diagnosed coronary heart disorders, clinic-

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