Medical Pharmacology Chapter 12: Anxiolytics and Sedative-Hypnotics
1Occasional use for preoperative medication due to sedative and antiemetic characteristics.
For example meperidine (Demerol) + promethazine (Pherergan) produces additive sedation without enhancing the likelihood of nausea/vomiting or respiratory depression.
Purpose of premedication -- prevention of intraoperative allergic reactions for those patients who have a history of chronic atopy (predisposition towards hypersensitivity reactions) or who will be undergoing a procedure associated with allergic reaction such as a radiographic studies requiring the use of a dye.
For these applications diphenhydramine (Benadryl) [0.5-1 mg/kg orally) may be combined with H2 receptor antagonist (blocker). An example of an H2 receptor antagonist would be cimetidine (Tagamet) [4-6 mg/kg].
The combination of an H1 blocker (diphenhydramine (Benadryl)) and the H2 antagonist (cimetidine (Tagamet)) reduces the likelihood of physiological responses to endogenous histamine release.
An additional agent, a steroid such as prednisone (Deltasone) (50 mg orally every six hours for the 24-hour period preceding the surgical procedure) may be helpful in combination with the above antihistamines.
Despite the use of these agents preoperatively, allergic reactions may still occur and may have to be managed intraoperatively
Other applications for histamine receptor blockers: reduction of gastric acid secretion
Mechanism: blockade of histamine-receptor mediated gastric acid secretion by selective, competitive inhibition; as a consequence gastric pH increases
No reliable effect on gastric fluid volume or emptying time
Probably appropriate as premedication for patients with aspiration pneumonia risk. Routine use is probably not appropriate.
Patient groups probably at increased pulmonary aspiration risk:
Morbidly obese patients
Patients with esophageal reflux symptoms
"Difficult airway" patients
For patients undergoing elective surgery, costs associated with preventing a single serious pulmonary aspiration complication may preclude routine use of H2 blockers (this conclusion follows from the very low likelihood of pulmonary aspiration and and serious morbidity in this patient group)-- also note that these drugs would not be expected to be 100% effective anyway.
Several doses are likely more effective for increasing gastric pH compared to single preoperative dose
Important reminder: Use of medications, such as H2 receptor antagonists, to reduce aspiration risk is much less important than proper anesthetic technique which ensures for the correct placement of cuffed tracheal tubes
Cimetidine (Tagamet), reduces acid secretion responses to histamine, caffeine, hypoglycemia, gastrin
Route of Administration: oral or parenteral
Dosage: 150-300 mg (obese patients may require larger doses)
Such administration (oral) 60-90 min preceding surgery increases gastric acid pH to > 2.5 in most patients; however gastric fluid volume is not significantly altered.
Recall that in adults: possibly, relatively high-risk of pulmonary complications if aspiration volume when gastric fluid volume is > 25 ml with a pH < 2.5.
Concerning neonatal effects:
Probably limited since, although cimetidine (Tagamet) crosses placental barrier, studies resolved no difference between use of 30 ml of antacid 1-3 hours prior to the surgery and cimetidine (Tagamet) (300 mg) 1-3 hours before the procedure, with respect to neonatal neurobehavorial scores
Duration of action: 3-4 hours
Prominent side effect: inhibition of hepatic mixed-function oxidase enzyme system (cytochrome P450 system): consequence-
Half-life prolongation for drugs including diazepam (Valium), theophylline, propranolol (Inderal), lidocaine (Xylocaine)
Serious cardiovascular side effects may occur following rapid IV administration particularly in critically ill patients (these effects include arrhythmias, hypotension, and cardiac arrests)
Ranitidine (Zantac), six times as potent as cimetadine in inhibiting gastric acid secretion
Ranitidine (Zantac) compared to cimetidine (Tagamet):
Increased relative potency is reflected in a lower dosage range (50-200 mg)
Oral: 50-200 mg
Parenteral: 50-100 mg (gastric fluid pH will increase within about our)
Duration of action: may last as long as 9 hr, suggesting that for very long cases premedication with ranitidine (Zantac) may reduce aspiration pneumonia is risk during emergence/tracheal tube extubation
Side effects: probably fewer CNS or cardiovascular side effects compared to cimetidine (Tagamet);smaller inhibitory effect on cytochrome P450 system than observed with cimetidine (Tagamet)
Generally similar to cimetidine (Tagamet) and ranitidine (Zantac)however with a longer elimination half-life
Dosage: (oral) 40 mg administered 1.5-3 hours preoperatively is likely effective in increasing gastric pH
Nizatidine (Axid): similar to the above agents in that 150-300 mg (oral) given about two hours before the procedure will increase preoperative gastric pH.
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, pp 551-565, 2001
5Michael Ross and Susan Dufel "Torticollis" emedicine, http://www.emedicine.com/emerg/topic597.htm