Thiamineinduced

Figure III-9. Effects of high doses of vitamin B1 (thiamine) used for anesthesia where only an opioid is needed for analgesia

During use of all these different techniques it became obvious that a potent opioid is a mandatory part in an anesthetic regimen, because an intensive nociceptive barrage, which needs to be blocked sufficiently, always accompanies operation. In addition, opioids do not have any detrimental effects on organ function while at the same time protecting the organism from stress-related consequences. Such demands are reflected in the therapeutic margin of safety (Table III-1), which mirrors the ratio of a dose necessary to induce analgesia and the dose resulting in cardiovascular depression.

The therapeutic margin of safety is of clinical significance because any side effects arising from the cardiovascular system are minimal. Also, preclinical as well as clinical data suggest that with higher affinity and stereoselectivity of an opioid to the receptor site, there is an increase of therapeutic safety [16, 17, 18, 19].

In summary, there are several reasons why an opioid should be incorporated into the anesthetic routine:

1. Volatile anesthetics and especially barbiturates, when given in high concentrations, depress the cardiovascular system (narrow therapeutic index).

2. Neuroleptic agents such as droperidol, but also sedatives (i.e., diazepam, midazolam) are not able to block nociceptive afferents.

3. The surgical procedure per se is a painful process. It therefore is only rational to administer agents, which selectively inhibit the increase in nociceptive afferents.

Table III-1. Therapeutic margin of safety of different opioids when compared to other intravenous and/or volatile anesthetic agents. With higher receptor selectivity of the opioid, there is an increase in therapeutic safety

Anesthetic/analgesic compound

Therapeutic margin of safety (LD50/ED50)

Halothane

Enflurane

Isoflurane

Tramadol

Pentazocine

Thiopental sodium

Pethidine

Methohexital

Ketamine

Methadone

Meptazinol

Etomidate

Phenoperidine

Butorphanol

Morphine

Lofentanil

Fentanyl

Nalbuphine

Alfentanil

Buprenorphine

Carfentanil

Sufentanil

Remifentanil

70-90 112

270-400 1034 1080 7933 10.000 26.716 33.000

4. Potent opioids are characterized by a wide therapeutic margin of safety.

5. Opioids are given intravenously. They represent the cornerstone in total intravenous anesthesia (TIVA).

6. Ecologically opioids are superior to volatile agents, as they do not pollute the environment.

7. Selective antagonists can reverse the effects of opioids.

8. There is an abundant knowledge on opioid action and their specific receptor sites within the central nervous system.

9. Opioids do not depress internal organ function.

10. Malignant hyperthermia, contrary to volatile anesthesia, is not induced by opioids.

11. There is less postoperative pain after an opioid-based anesthesia when compared to a volatile anesthetic regimen.

12. Use of opioids for anesthesia results in a beneficial cost/benefit.

The aim of modern anesthesia is to induce analgesia, unconsciousness and muscle relaxation with agents having a selective profile, which do not depress the cardiovascular and induce stabilization within the autonomic nervous system during operation. Present knowledge suggests that only opioids, when given alone or in combination with other anesthetics, are able to sufficiently fulfill such demands.

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