Medical Pharmacology Chapter 12: Anxiolytics and Sedative-Hypnotics
Advantages for use in preoperative medication:
Absence of myocardial depressant effects
Alleviate the preoperative pain
Management of discomfort associated with invasive monitor insertion
Management of pain which may be associated with establishing regional anesthetia
Preoperative opioids may limit or eliminate the need for supplemental analgesics during the early postoperative phase
Pain experienced by lightly anesthetized patients may cause CNS changes that exacerbate pain postoperatively.
For example, in support of this hypothesis, a higher opioid concentration is required for suppression of C-fiber activation if pain has caused previous C-fiber activity
Generally, in the absence of preoperative pain there may be no compelling reason to include a narcotic for preoperative anesthetic medication.
On the other hand, opioid administration to patients experiencing preoperative pain not only relieves pain but also may induce a euphoric state.
Commonly used opioids for premedication
Most commonly used: morphine and meperidine (Demerol)
Intramuscular injection; good absorption with peak plasma levels obtained in about 45-90 minutes
IFntravenous administration: the effects occur more rapidly, usually within 20 minutes
Relative to morphine intramuscular injection yields a less predictable time to onset
One advantage of including morphine as part of preoperative medication:
Morphine tends to suppress tachycardic responses to surgical stimulation during volatile anesthetic administration
Contexts for opioid administration:
Intramuscular: appropriate for nitrous oxide-opioid anesthesia
Intravenous administration: appropriately administered immediately before induction (fentanyl (Sublimaze) is a good choice in this application)
Pain associated with regional anesthesia or associated with invasive monitoring catherization or even large intravenous lines may justify treatment with preoperative opioids.
As would be expected for many agents, dosage reduction may be required for the elderly patient.
Elderly patients may have reduced pain sensitivity that may exhibit an enhanced analgesic response to the opioid
Occasionally preoperative opioids are administered in advance of a nitrous oxide-opioid anesthesia plan -- the rationale is that previous opioid administration allows the anesthesia provider to gauge the patients ensuing intraoperative opioid response.
For postoperative pain, preoperative opioids may be employed; however, it is probably preferable to either provide administration in to recover room setting or perhaps most appropriately provide IV opioids during the emergence
Preoperative opioid administration may lower anesthetic requirements
For facemask induction, opioids may be used in combination with other agents-in this case opioid-mediated respiratory depression may decrease ventilation during spontaneous breathing which will reduce the rate of inhalational drug uptake. (the circumstance might arise if for some reason intravenous induction agents may not be used)
In this eventuality, the anesthesia provider may have to control ventilation, overcoming opioid-induced respiratory depression
Minimal cardiovascular effects are noted, except for high-dose meperidine (Demerol)
Respiratory depression: associated with reduced responsiveness to CO2 (medullary respiratory center depression)
Even low-opioid doses reduce carotid body hypoxia responsiveness; accordingly, anesthesia providers may wish to administer supplemental oxygen for those patients receiving opioids as premedication
The problem of using opioid agonist-antagonist agents, which cause reduced respiratory depression, is that they also are less effective analgesic drugs. Also, these partial agonists may cause dysphoria (instead of the more expected euphoric response), a condition and not desirable in the preoperative time frame -- or probably any other time frame
Orthostatic hypotension secondary to peripheral vascular smooth muscle relaxation:
Opioids prevent the expected compensatory peripheral vascular vasoconstriction.
This effect is in addition to opioid- promoted histamine release that tends to cause a hypotensive reaction.
The hypotensive response will be more profound in patients who are hypovolemic.
Hypotensive reactions can be avoided by ensuring that patients remained supine following opioids (and other) premedication agents.
Nausea and vomiting: These effects are frequently associated with opioid administration, possibly occurring as a result of stimulation of the medullary chemoreceptor trigger zone or vestibular apparatus stimulation leading to motion sickness.
The likelihood of nausea and vomiting may be reduced by placing the patient in a recumbent position; however, the use of opioids because of their tendency to cause nausea and vomiting perhaps should be avoided in the same-day outpatient setting or if the surgical procedure's themselves are likely to cause nausea and vomiting (i.e. some gynecological and opthalmological surgeries)
Delayed gastric emptying, which is associated with nausea symptoms, has two important consequences-(1) altered absorption rate for orally-administered agents and (2) and increased risk of pulmonary aspiration
Opioids may also cause smooth muscle constriction (biliary spasm (choledochododenal sphincter spasm, i.e. sphincter of Oddi)). Manifestation consists of an upper right quadrant pain secondary to smooth muscle constriction
Patients with biliary tract disease should perhaps not receive opioids.
Also pain associated with biliary spasm, e.g. caused by an opioid, may be difficult to distinguish from angina particularly since pain from either angina or biliary spasm would be relieved by smooth muscle relaxation due to sublingual nitroglycerin.
Opioid-induced pain, however, would be relieved by administration of a pure opioid antagonist such as naloxone (Narcan) or naltrexone (ReVia) or possibly glucagon. These drugs would not reverse true anginal pain.
Meperidine (Demerol) is less likely than morphine to cause biliary tract spasm.
Pruritis-probably secondary to histamine release;
Accordingly opioids may cause flushing and dizziness.
Since opioids are miotic agents, pinpoint pupils may occur.
Morphine:- dosage (5-15 mg, IM Route of Administration)
Well absorbed following IM administration
Time to onset: 15-30 minutes with peak effect at about 45-90 minutes with total duration of action as long as about four hours
With intravenous usage, significant, peak effects occur within about 20 minutes
Side reactions as noted for the opioid group in general, including ventilation depression; orthostatic hypotension as well as nausea and vomiting secondary to effects on the chemoreceptor trigger zone (CTZ) or on the vestibular apparatus
Reduction in GI motility
Preoperative use of morphine reduces cardioacceleration associated with surgical stimulation and volatile anesthetic agents
Meperidine (Demerol) dosage: (50-150 mg, IM Route of Administration)
Less potent compared to morphine (about 10% as potent)
Route of Administration: oral or parenteral
Single dosage effect duration: 2-4 hours with intramuscular injection providing a variable time to peak effect and duration
Elimination: mainly through hepatic metabolism
Cardiovascular effects: positive chronotropic effect secondary to antimuscarinic drug effects.
Fentanyl (Sublimaze):dosage-1-2 ug/kg intravenous for preoperative analgesia
Alternative Routes of Administration:
Oral (transmucosal) fentanyl (Sublimaze)-- 5-20 ug/kg [used in children and adults to diminish preoperative anxiety and pain)
Transmucosal fentanyl (Sublimaze) is associated with a high incidence of preoperative gastrointestinal disturbance (nausea and vomiting) typically at doses > 15 ug/kg: Therefore, transmucosal fentanyl (Sublimaze) at these dosages is not recommended for patients < 6 years of age
Fentanyl (Sublimaze) issues:
Significant respiratory (ventilation) depression
Fentanyl (Sublimaze) plus benzodiazepines may result in unwanted synergistic effects requiring close observation
Histamine release is NOT associated with fentanyl (Sublimaze)
Fentanyl (Sublimaze) administration does not cause myocardial depression
These drugs, e.g. pentazocine (Talwain), butorphanol (Stadol), nalbuphine exhibit reduced respiratory depression compared to pure opioid agonists; however, these drugs also have comparatively limited analgesic effects.
These partial agonist, given preoperatively, reduce the efficacy of pure opioid agonist given postoperatively to control postoperative pain. Partial agonist administration can in fact limit or reverse analgesia caused by the presence of the pure agonist
4Side effect incidence following preoperative opioid administration: [1 hr following dosage]-- original citation: Forest, w.H., Brown, B.W. et al.: "Subjective responses to six common preoperative medications", Anesthesiology 47:241, 1977.
Morphine (5-10 mg):
Dry mouth 80%
Slurred speech 33%
Meperidine (Demerol) (50-100 mg):
Dry mouth 85%
Slurred speech 45%
1Preoperative Medication in Basis of Anesthesia, 4th Edition, Stoelting, R.K. and Miller, R., p 119- 130, 2000)
Hobbs, W.R, Rall, T.W., and Verdoorn, T.A., Hypnotics and Sedatives; Ethanol In, Goodman and Gillman's The Pharmacologial Basis of Therapeutics,(Hardman, J.G, Limbird, L.E, Molinoff, P.B., Ruddon, R.W, and Gilman, A.G.,eds) TheMcGraw-Hill Companies, Inc., 1996, pp. 364-367.
3Sno E. White The Preoperative Visit and Premedication in Clinical Anesthesia Practice pp. 576-583 (Robert Kirby and Nikolaus Gravenstein, eds) W.B. Saunders Co., Philadelphia, 1994
4John R. Moyers and Carla M. Vincent Preoperative Medication in Clinical Anethesia, 4th edition (Paul G. Barash, Bruce. F. Cullen, Robert K. Stoelting, eds) Lippincott Williams and Wilkins, Philadelphia, PA, 2001
5Kathleen R. Rosen and David A. Rosen, "Preoperative Medication" pp. 61-70 in Principles and Procedures in Anesthesiology (Philip L. Liu, ed) J. B. Lipincott Company, Philadelphia, 1992