Medical Pharmacology Chapter 12:  Anxiolytics and Sedative-Hypnotics

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Preoperative Medication: Sedative Hypnotics and Other Agents and Issues Medical Pharmacology: Sedative-Hypnotic Chapter

Preoperative Medication in the Ambulatory Setting
  • 6Overview:

    • General preoperative medication objectives for the ambulatory surgical setting are similar to those for inpatient management with respect to the following goals:

      1. Anxiety control

      2. Management of postoperative pain

      3. Control/management of nausea and vomiting

      4. Attenuate aspiration risk during anesthesia induction

    • For same-day surgery attention must be paid to the choice of preanesthetic drugs such that rapid recovery is not significantly hindered

    • Typically, conventional preanesthetic medications do not influence discharge times.  

      • For instance, prior to induction the combination of 0.04 mg/kg midazolam (Versed) with 1 ug/kg fentanyl (Sublimaze) resulted in a reduction in anesthesia maintenance requirements (desflurane (Suprane)), reduced airway irritability, and reduced blood pressure increases during induction.

  • 6Anxiety control:

    • The extent to which patients may benefit from anxiolytic medication is strongly influenced by the presurgical degree of anxiety experienced by the patient.

    • Increased anxiety has been noted in females and other factors that may increase stress include:

      1. The procedure itself-for instance a "mutilating" surgery

      2. Cancer surgery

      3. The patient accompanied into the holding area by a relative or friend

      4. A first surgery

      5. Patients who have had a bad experience associated with a previous surgery

    • If the anesthesia provider it is uncertain about the level of patient anxiety, a direct and reasonable way to gain information is to simply ask the patient

    • 7Needing to remove dentures before surgery has also been associated with increased risk.  

      • Many patients may be embarrassed because they wear dentures an even cover their mouths with a blanket as they enter the operating room because of this embarrassment. 

      • Often, it is reasonable to allow the patient to leave their false teeth in place thereby reducing anxiety and exhibiting sensitivity to the patient. 

      • With contemporary anesthesia approaches it is highly unlikely that a patient will "aspirate" their dentures. Should dentures become dislodged during intubation, they can be simply removed, recognizing that at this point the patient is unconscious.

    • The reason why anxiety control is so important physiologically is that increased anxiety is likely associated with increasing circulating catecholamines which in turn may promote elevated blood pressures and other unwarranted and unnecessary adverse cardiovascular conditions.

    • For management of children, special sensitivity needs to be exhibited to ensure reduced separation anxiety from parents.  

      • This can be accomplished in part by explaining the procedure to both parties preoperatively.  Furthermore, likelihood of adverse emergence events in the child has been associated with significant preoperative anxiety.

    • Premedication may not be needed if the presurgical environment is characterized by calm parents who facilitate transfer of the child to a " warm and playful" anesthesia provider.  Partial sedation, although effective, may result in prolonged recovery.

    • The most commonly used current preanesthetic medications for production of sedation are the benzodiazepines.

      • A reduction in anxiety and children can be facilitated also by oral, transmucosal  fentanyl (Sublimaze)

  • 6Benzodiazepines:

    • Midazolam (Versed): The most commonly used preoperative benzodiazepines is midazolam (Versed), a water-soluble agent with an initial distribution half-life of about seven minutes an elimination half-life of about 2.5 hours. 

      • Elderly patients exhibit prolonged  elimination half-life (about six hours)

      • Obese patients also exhibit prolonged elimination half-life (about eight hours)

      • Metabolism:

        •  Following oral administration, about 50% of the dose undergoes hepatic first-pass metabolism  hepatic with some extrahepatic also. 

          • This observation means that about 1/2 of the midazolam (Versed) molecules are transformed by the liver into relatively inactive metabolites.

      • Dosage adjustment with age for midazolam (Versed) (IV administration): For example, to obtain adequate sedation prior to upper gastrointestinal endoscopy--

        • 20 year-old patient --0.15 mg/kg (For a 20 year-old patient, 20-40 minutes of sedation will be usually provided by a dose range of 0.07-0.15 mg/kg)

        • 60 year-old patient -- 0.1 mg/kg

        • 90 year-old patient -- 0.03 mg/kg

      • Adverse effects for midazolam (Versed):

        1. Psychomotor depression

        2. Respiratory depression

        3. Cardiovascular depression

      • 6Use of midazolam (Versed) and children:

        • Oral midazolam (Versed) is available and at a dose of 0.5 mg/kg sedation and anxiolytic effects are produced.

          • Using this dose, child-parent separation anxiety should be relieved within about 10 minutes.

        • Pre-treatment with midazolam (Versed) prior to halothane (Fluothane) administration for relatively short procedures (30 minutes) generally does not prolong the recovery time.  

          • However, when shorter-acting inhalational agents are used, such as desflurane (Suprane) or sevoflurane (Sevorane, Ultane) preceded by midazolam (Versed) administration, a prolongation recovery may occur.  

          • Importantly, this length and recovery time does not delay discharge from the hospital

        • Drug-drug interactions: 

          • Some drugs can interact with midazolam (Versed) and have the effect of prolonging sedation and intensifying sedation with the possibility of respiratory depression.  

            • Examples of these agents would be antifungal drugs such as itraconazole (Sporanox) or ketoconazole (Nizoral).

              • Itraconazole (Sporanox) is an example of an azole antifungal drug which works by inhibition of cytochrome P450 14a-demethylase, which is an important enzyme in the sterol biosynthesis pathway. 

            • Inactivation of cytochrome P450 type 3A (P450 3A4) by itraconazole (Sporanox), ketoconazole (Nizoral), cimetidine (Tagamet), and erythromycin, for example, is the basis for decreases in apparent hepatic clearance of midazolam (Versed) after IV administration.

    •  6Diazepam (Valium):

      • By oral administration, diazepam (Valium) is appropriate for managing anxiety in patients scheduled for ambulatory surgery.  Plasma levels peaked at about one-hour after dosing with notable anxiolytic effects.  Drug effects last several hours

      • Dosage and patients age:

        • There is about a 10% decrease in the required dose for each decade of patients age.

        • Elimination half lives tend to be longer in older patients, partially accounting for reduced dosing requirements; however, at equal plasma concentrations, elderly patients exhibit increased intrinsic drug sensitivity.

      • Dosage: A typical diazepam (Valium) dose would be about 2-5 mg/70 kg adult.  In the case of diazepam (Valium), active metabolites are noted (desmethyl metabolites) such that the pharmacological effect extends beyond the half-life of the parent compound.

    • 6Hemodynamic effects and benzodiazepines:

      • With appropriate dosing, midazolam (Versed) is comparable to diazepam (Valium) in terms of  relatively minor cardiovascular/respiratory effects.  Here again, however age plays a role.

        • Whereas a small blood-pressure reduction (10%) would be observed in the healthy patient, and elderly patient might experience hypotensive reaction of 20%-35%, especially in the presence of heart disease.

        • The present of other drugs in a patient's system can add to the hypotensive effects observed with benzodiazepines [coadministration of thiopental (Pentothal), fentanyl (Sublimaze) or propofol (Diprivan) along with a benzodiazepine could cause greater respiratory and hemodynamic depressive effects].

      • For midazolam (Versed), given by IV administration, a decrease in oxygen saturation may be observed during endoscopy.  

        • Generally administration of supplemental oxygen is appropriate when benzodiazepines are administered intravenously. 

        • This precaution applies not only to midazolam (Versed) used in premedication but also when used alone or with other agents for conscious sedation.

    • Fatigue and amnesia and benzodiazepines

      • Benzodiazepines may cause fatigue which could delay patient same-day discharge.

      • Usually, if the patient is not discharged on the same day as the procedure, the reason has to do with the procedure itself or with anesthesia-induced nausea as opposed to fatigue or somnolence.

      • Benzodiazepines, particularly midazolam (Versed), is associated with anterograde amnesia, that is, amnesia concerning events following benzodiazepine administration.

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  • 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, pp. 364-367 (Hardman, J.G, Limbird, L.E, Molinoff, P.B., Ruddon, R.W, and Gilman, A.G.,eds) The McGraw-Hill Companies, Inc., 1996.

  • 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, 551-565, (Paul G. Barash, Bruce. F. Cullen, Robert K. Stoelting, eds) Lippincott Williams and Wilkins, Philadelphia, PA, 2001

  • 5Gertler, R., Brown, H. C, Mitchell, D.H and Silvius, E.N Dexmedetomidine (Precedex): a novel sedative-analgesic agent, BUMC Proceedings 2001; 14:13-21

  • 6J. Lance Lichtor Anesthesia for Ambulatory Surgery in Clinical Anethesia, 4th edition, 1217-the1238, (Paul G. Barash, Bruce. F. Cullen, Robert K. Stoelting, eds) Lippincott Williams and Wilkins, Philadelphia, PA, 2001

  • 7J. S. Gravenstein, and R. R. Kirby "General Anesthesia: Induction, Maintenance, and Emergence"  in Clinical Anesthesia Practice pp.  585-596 (Robert Kirby and Nikolaus Gravenstein, eds) W.B.  Saunders Co., Philadelphia, 1994



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