Nursing Pharmacology Chapter 12:  Anxiolytics and Sedative-Hypnotics

• ³Midazolam (Versed) & diazepam (Valium) comparisons:

  • Pharmacokinetic issues:

    • Midazolam (Versed): short half-life (1-4 hours); diazepam (Valium), including active metabolites: long half-life 20-100 hours

    • In elderly patients, diazepam (Valium) half-life may be extended to several days (midazolam (Versed) half-life may be extended by eight hours)

  •  Diazepam (Valium) metabolites: oxazepam which is Serax and desmethyldiazepam are active

  •  Weak midazolam (Versed) metabolites suggest that in the outpatient setting, midazolam (Versed) would be preferred.  Quicker recovery &  greater amnesia have been found with midazolam (Versed).

  •  Midazolam (Versed) in combination with opioids: cautious use in view of possible respiratory depression leading to inadequate oxygenation.  Nalbuphine (0.2 mg/kg) & midazolam (Versed) (0.09 mg/kg) may be the most appropriate combination in order to minimize respiratory complications at least in patients undergoing minor oral surgery

•   Pediatric uses of  Midazolam (Versed)³:

  • Oral midazolam (Versed) (0.5 mg/kg) is useful in preventing "facemask phobia"

  • Following oral administration (midazolam (Versed), 0.5 mg/kg) the child is typically easily separated from parents and willing to accept monitoring and facemask

  • At a midazolam (Versed) dosage of 0.75 mg/kg, most pediatric patients {90%} undergo induction without crying or combative behavior

  • At these dosages, midazolam (Versed) effects last <  1 hour and do not appear to prolong recovery

  • Midazolam (Versed) administration (occasionally in combination with atropine, e.g.) can be facilitated by mixing with cherry syrup or with a melted popsicle.

  •  Special circumstances:

    •  In pediatric patients with congenital heart disease, midazolam (Versed) may improve oxyhemoglobin saturation in most cases; however in some children with cyanotic heart disease (3 of 17 tested) desaturation may occur with a reduction of greater than 10%.  

      • Accordingly,  pulse oximetry monitoring is essential.

  • Children with a compromised airway: midazolam (Versed) premedication would not be advised because apnea following midazolam (Versed) administration may be associated with an inability to mask ventilate.

    • Crying itself (which may be made less likely by midazolam (Versed) administration) can worsen airway obstruction in the presence of, for example, epiglottitis or laryngeal papillomatosis, a condition of multiple papilloma grows on the larynx caused by a viral infection-this condition occurs with approximately equal frequency and children and adults.  

    Laryngeal papillomatosis, Epiglottitis

 

• Intranasal midazolam (Versed) administration (0.2 mg/kg)

  • Less patient cooperation required (appropriate for combative children)

  • Quicker onset compared to oral Route of Administration

  • Occasionally (rare), midazolam (Versed) made evoked a hyperexcitability reaction-some anesthesia providers may wish to employ midazolam (Versed) only with relatively uncooperative patients

• ³Lorazepam (Ativan)

  • Overview

    • No active metabolites; short half-life (approximately 15 hours)

    • Half-life not influenced by patient age

  • Pharmacokinetic/metabolism characteristics

    • Reduced, compared to diazepam (Valium), rate of CNS access secondary to relatively less lipophilicity

    • Onset of action for both diazepam (Valium) & lorazepam (Ativan) is similar, about 30-60 minutes

    • CNS effects e.g. psychomotor impairment, may be observed for 12 hours following the single lorazepam (Ativan) dose

    • Metabolism:

      • Glucuronidation (conjugation) followed by renal excretion

      • Glucuronidation reactions tend to be less susceptible to effects of aging or hepatic disease, i.e. typically no significant change in half-life as a function of age or liver dysfunction

  • Comparing lorazepam (Ativan) and diazepam (Valium):

    • Dosage -- 2 mg orally of lorazepam (Ativan) is about equal to 10 mg oral diazepam (Valium)

    • Sedation following a single 2 mg dose less about five hours

    • At higher dosages, such as 5 mg, anterograde amnestic effects may last up to about eight hours

    • Disorientation following the 5 mg dose may last as long as 17 hours; this finding suggests that the upper dosage limit for lorazepam (Ativan) perhaps should be 4 mg

    • Diazepam (Valium) --

      • At the 10 mg level: typically no amnesia

      • At the 20 mg level, about 30% of patients exhibit amnesia {4 mg of lorazepam (Ativan) (oral) results in an amnesia frequency of > 70%}

  • Lorazepam (Ativan) uses:

    • Appropriate for patients undergoing major surgical procedures which will be followed by intensive care unit monitoring

    • Advantage for seriously ill (critically ill) patients include:

      • Absence of myocardial depression or vascular smooth muscle relaxation even at doses above 9 mg 

    • Concerning typical premedication in patients with heart disease, sedative and anxiolytic action of flurazepam (Dalmane) (orally administered; 0.06 mg/kg, administered 90 minutes prior surgery) was comparably effective to a more traditional premedication regimen consisting of intramuscular morphine (0.1 mg/kg) combined with scopolamine.

     

References

• 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 & 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 & 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