0, no change; +, increased; ++, more increased; +++, most increased; -, decreased; —, more decreased;---, most decreased.

0, no change; +, increased; ++, more increased; +++, most increased; -, decreased; —, more decreased;---, most decreased.

minimal change in blood pressure and systemic vascular resistance. Therefore, coadministration of diazepam and nitrous oxide is not associated with significant decreases in cardiovascular function (39); thus, it is employed in patients for whom such concerns may be justified.

4.3. Opioids

Opioids are analgesics commonly administered as adjuncts to anesthesia. Opioids currently used in clinical practice include fentanyl, morphine, meperidine, sufentanil, and remifentanil (Table 5). All opioids exert their effect by interacting with opioid receptors (mu1? mu2, kappa, or delta) (Table 6); they are adjuncts to help blunt sympathetic responses to noxious stimuli. Overall, opioids cause minimal changes in cardiac output and blood pressure. Yet, opioids will generally cause bradycardia by increasing vagal tone.

Typically, at very high doses, opioids may have the following effects on hemodynamics: inhibition of the autonomic nervous system, direct myocardial depression, and/or induced histamine release. More specifically, one in vitro study of human atrial myocardium found that fentanyl, remifentanil, and sufentanil did not modify inotropic effects; alfentanil caused negative inotropy by affecting calcium regulation (40). However, it has also been reported that opioids such as fentanyl may depress rat myocardial contractility by affecting calcium regulation (41). Finally, it is considered that morphine may cause decreases in mean arterial pressures by causing histamine release and bradycardia.

Table 5

Opioid Agonists Commonly Used in Clinical Practice

Heart rate

Blood pressure

System vascular resistance

Contractility Histamine







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