Benzodiazepines produce anterograde amnesia in addition to anxiolysis with minimal sedative effects. Note that benzodiazepines may interfere with the release of cortisol during stressful situations [Kay et. al. Anesth Analg 79: 501, 1994; Arvat et. al. J Endocrinol Invest 25: 735, 2002]. Opiates were initially thought to be an important component of preemptive analgesia, but it turns out that they may sensitize patients to pain [Chu et. al. Clin J Pain 24: 479, 2008].
Clonidine may provide preemptive analgesia, at least when given epidurally.
|Relative Contraindications to Depressant Premedication|
|Newborn (< 1 year of age)|
|Decreased level of consciousness|
|Severe pulmonary disease|
Antihistamines are occasionally used for their sedative and anti-emetic properties, however beware as promethazine now carries an FDA warning re: apnea and death in children. Diphenhydramine (25-50 mg PO) can be given as prophylaxis for allergic reactions (atopy, dye studies), and should be administered in conjunction with an H2-antagonist (ex. famotidine). Prednisone 50 mg PO may also be added
Clonidine, in addition to possibly providing preemptive analgesia when given epidurally, can decrease the incidence of MI [Quintin et. al. Anesth Analg 83: 687, 1996], while also decreasing MAC (in one study, 56 children were randomized to 4 ucg/kg 100 min prior to sevo induction vs. no clonidine, and MAC was reduced from 2.00% to 1.33% [Nishina et. al. Paediatr Anaesth 16: 834, 2006]). Possible side effects of clonidine include bradycardia and dry mouth.
Popular antiemetics include ondansetron, dexamethasone, droperidol, metoclopramide, and perphenazine. Disadvantages of routine use include cost and possible orthostatic hypotension
Anticholinergics should not be administered routinely, but rather to produce an antisialogogue effect, sedation/amnesia, or prevent reflex bradycardia. Scopolamine has outstanding antisialogogue properties and produces sedation. Glycopyrrolate (quatenary amine) produces slightly less antisialogogue effect but does not produce sedation as it can’t cross the BBB. Atropine is the worst in terms of secretions, and also crosses the BBB. Atropine and scopolamine can produce a central anticholinergic syndrome, which can only be treated with physostigmine, 1-2 mg IV (neostigmine and pyridostigmine do not pass into the CNS). Only atropine can reliably produce an increase in heart rate (in fact, the most common cardiac response to IM glyco or scopolamine is bradycardia, presumably due to a weak cholinergic agonist effect)
Routine use of H2 blockers is not recommended [Warner et. al. Anesthesiology 90: 896, 1999] but may be a consideration in patients at risk for aspiration (morbidly obese, parturients, GERD, anticipated difficult airway). In elective surgeries, the risk of aspiration is low enough that the cost of routine H2 blockers is not justified [Warner et. al. Anesthesiology 78: 56, 1993]. Furthermore, these drugs do not always work [White PF Anesth Analg 65: 963, 1986] and do not alter the pH of fluid already present.
Antacids given 15-30 minutes prior to surgery are, by contrast, nearly 100% effective at raising gastric pH to > 2.5. Nonparticulate antacids such as sodium citrate are key as they do not cause pulmonary complications if aspirated. The theoretical tradeoff for sodium citrate is that gastric volume is actually increased, however data from rats showed that 0.3 cc/kg of aspirate with pH < 1.0 carried a mortality rate of 90%, whereas 1-2 cc/kg of aspirate with a pH > 1.8 carried a mortality rate of 14% [James et. al. Anesth Analg 63: 665, 1984]. Thus, antacids should never be withheld based on volume.
Metoclopramide (or cisapride) may be considered as well, although erythromycin may be a better pro-motility agent, as it is an antibiotic as well. It may be particularly useful for emergency cases, and in one case study 100 mg IV 80 minutes before surgery (with 30 cc sodium citrate 30 minutes prior) led to complete gastric emptying (EGD confirmed) in a 56 kg boy [Kopp et. al. Anesthesiology 87: 703, 1997]. Reglan begins working within 1-3 minutes, but may be attenuated by anticholinergics, opioids, or antacids.
Keep in mind that complete gastric emptying is an impossibility. Solid food can take up to 12 hours, whereas clear liquids have a 50% emptying time of 12-20 minutes. Fears that ingestion of clear fluids within 2 hours of induction will increase gastric volume significantly are probably unfounded [Warner et. al. Anesthesiology 90: 896, 1999]. It is acceptable to administer medications with up to 150 cc of water one hour prior to induction. Preoperative (1600 – 2400 the day before) oral nutrition with 800 cc of a carbohydrate-rich beverage does not appear to increase gastric fluid volume or acidity and may reduce insulin resistance postoperatively [Hausel et. al. Br J Surg 92: 415, 2005]. Aspiration occurs in only 1:3200 anesthetics but is associated with 10-30% of all anesthesia-related deaths [Pisegna et. al. J Clin Gastro 39: 10, 2005].