Opioids

In general, all opioids are suitable as analgesics in the ICU. This is particularly true in short-term ICU patients with an uncomplicated course. However, the longer the treatment lasts and the more complicated the postoperative course, the more important are the pharmacological differences between the various opioids ( Table.,2,).

Of particular relevance is the significant cumulation after prolonged administration of opioids. For example, while fentanyl presents as a short-acting opioid during anesthesia, the duration of action approaches that of morphine during prolonged continuous infusion ( T.able.3). The loss of action of fentanyl initially depends on the distribution of the drug in the body and not on elimination or metabolism. In contrast, the duration of action of sufentanil increases only slightly even after prolonged administration. Furthermore, development of tolerance seems to be less pronounced with sufentanil than with fentanyl. Whether this phenomenon is caused by the high receptor affinity of sufentanil has not been clearly demonstrated. However, the high receptor affinity and and lipophilicity are probably the reasons for the superior analgesic efficacy of sufentanil after prolonged administration of opioids. In critically ill patients the analgesic efficacy of alfentanil is often insufficient after only a few days of administration, probably because of the low affinity to the opioid receptor. Furthermore, the duration of action after prolonged administration of alfentanil (context-sensitive half-time) increases similarly to fentanyl ( T§.b.!e 3). Meperidine (pethidine) may release histamine, may result in hypotension, and has the major disadvantage that the active neurotoxic metabolite normeperidine (norpethidine) cumulates during prolonged administration.

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Table 3 Pharmacological summary of analgesic drugs

Table 3 Pharmacological summary of analgesic drugs

Piritramide has about the same duration of action as morphine, is almost free from cardiovascular side-effects, and can be used as an alternative to morphine, although it is significantly more expensive. The mixed opioid agonist-antagonist buprenorphine acts as an agonist in low dosages and as an antagonist in higher dosages. Dose increases are frequently necessary in ICU patients, and therefore mixed agonist-antagonists are only rarely useful in this setting. However, they may offer advantages in individual cases, such as patients with severe constipation. Owing to their limited analgesic power there is no role in the ICU for mixed agonists-antagonists like pentacozine, nalbuphine, or tramadol.

In general, the spectrum of opioids in the ICU should be limited to only a few drugs. Opioids with high analgesic power should be preferred. In patients with an expected short duration of treatment fentanyl can be used without problems during the immediate postoperative period. Sufentanil may have advantages in patients receiving long-term treatment because of the improved quality of analgesia, improved sedation, less tolerance, and earlier recovery. The great advantage of morphine is its unrivalled low price.

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