Preoperative Medication: Sedative Hypnotics and Other Agents and Issues

return to main menu 1Antihistamines: Overview: 1Occasional use for preoperative medication due to sedative & antiemetic characteristics.  For example meperidine (Demerol) + promethazine (Pherergan) produces additive sedation without enhancing the likelihood of nausea/vomiting or respiratory depression. Specific applications: 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: Parturients 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 & 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 Specific medications: 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, & cardiac arrests} Ranitidine (Zantac), six times as potent as cimetadine in inhibiting gastric acid secretion Ranitidine (Zantac) compared to cimetidine (Tagamet): Longer acting increased relative potency is reflected in a lower dosage range (50-200 mg) Dosage: 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) Famotidine (Pepcid) 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 4Antacids:  Overview: Antacids are exceedingly effective in increasing gastric fluid pH to > 2.5 when administered 15-30 minutes prior to anesthesia induction An important factor in the affects the antacid efficacy is simply the extent of patient movement-with increased movement promoting more complete antacid mixing with the gastric fluid Concerns associated with inhalation of gastric fluid containing antacids: If aspiration does occur and gastric fluid containing antacid particulates is inhaled a possible significant inflammatory reaction may ensue which can cause significant pulmonary dysfunction.   This possibility is an argument in favor of nonparticulate antacids such as sodium citrate (0.3 M) which also is effective in raising gastric fluid pH to  > 2.5 without producing significant pulmonary complication should inhalation of fluids occur.  Pulmonary complications can include pulmonary edema and arterial hypoxemia. Special advantages of antacids compared to H2 receptor blockers:  Administration of an antacid immediately increases gastric pH, without the lag time associated with histamine receptor blockers.  The antacids, however, may increase gastric fluid volume, although this effect should not be interpreted as to discourage antacid use and is more likely to occur after repeated doses (such as during labor) and especially if opioids have been given which themselves delay the gastric emptying As noted earlier for the receptor blockers, antacids need not be routinely used, but rather used for those selected patients who appear to have a higher risk for pulmonary aspiration. 3Rationale: A large percentage of patients will exhibit gastric fluid volumes > 0.4 ml/kg  with a pH < 2.5 {about 3/4 of pediatric patients and about half of adult out-patients qualify} However the likelihood of aspiration turns out to be very low.   In one study of about 40,000 anesthetic procedures in children, aspiration was noted only four times {2 occasions intraoperatively and two occasions postoperatively}.  [Tiret, L., Nivoche, Y, Hatton, F, et al:  Complications related to anesthesia in infants and children:  a prospective surbey of 40,240 anaesthetics.  Br J. Anaesth 1988:  61: 263] In a separate study involving retrospective assessment of 185,000 procedures, 83 aspiration occurrences were noted resulting in an incidence rate of about 1 in 2000.  [Olsson, GL, Hallen, B.  Pharmacological evacuationof the stomach with metoclopramide.  Acta Anesth Scand, 1982; 26, 417] For most of these cases (68 out of 83), other factors which would be expected to delay gastric emptying were noted. Therefore, an approach that involves routine premedication to avoid aspiration pneumonitis is difficult to support; however identification of risk factors IS important. 3Risk factors for aspiration pneumonitis-- causative factors for gastric emptying delay: Elevated intracranial pressure Obesity Gastritis or ulcer history Emergency abdominal surgery Pregnancy Emergency surgery Pain/stress Elective upper abdominal surgery 3Patients who should receive aspiration prophylaxis: (Table 34-6) Anticipated challenging airway intubation Emergency surgical patients Trauma patients Patients exhibiting reduced level of consciousness which may be caused by head trauma or drug overdosage Intestinal obstruction Elevated intracranial pressure due to mass effects or edema Impaired laryngeal reflexes which could be caused by Shy-Drager syndrome (autonomic data), amyotrophic lateral sclerosis (Lou Gehrig's disease), vocal cord paralysis, stroke, bulbar palsy  Bulbar palsy: bulbar refers to the lower brain stem, i.e. cranial nerves 7-12; palsy refers to weakness -- Therefore bulbar palsy refers to weakness of muscles controlled by cranial nerves 7-12.   Manifestations could include difficulty in speaking, swallowing, coughing as well as difficulty with facial expressions.  Bulbar palsy, therefore, may be manifestation of a number of diseases including Lou Gehrig's disease, stroke, or inflammatory disease. Obesity Ulcer disease including previous surgeries such as partial  gastrectomy or vagotomy the latter of which  would lead to gastroparesis due to the absence of cholinergic tone following nerve section.  Hiatal hernia and reflux  hiatal hernia -- definition: A hiatal hernia could be defined as a condition in which a portion of the stomach pushes through the diaphragm into the chest cavity. This condition is relatively common affecting about 15% of the population (U.S.)  Reflux and hiatal hernias-- The size of the hiatal hernia predicts the likelihood of symptoms.  For large hernias the symptoms are almost always associated with gastro-esophageal reflux disease or GERD GERD occurs because the hernia itself interferes with the lower esophageal sphincter which usually prevents gastric acid from refluxing into the esophagus.  GERD can occur in the absence of a hernia. Gastric acid typically does not reflux into the esophagus for a couple of reasons  (1) because the diaphragm muscle wraps around the region of the lower esophageal sphincter.  Therefore both the diaphragmatic muscle and the lower esophageal muscle contribute to blocking regurgitation.  In the presence of a hiatal hernia, says the lower esophageal sphincter is no longer in the region the diaphragm, the diaphragmatic pressure component is lost, making regurgitation more likely.  he second reason (2) is that normally the esophagus enters the stomach at an angle, a fairly sharp angle, with a thin piece of tissue at this location forming a "valve".  When the stomach protrudes through the diaphragm in hiatal hernia, the sharpness of the angle between the esophagus and stomach is significantly reduced with the concurrent reduction in the ability of the valve to prevent regurgitation. Pregnancy Upper abdominal surgery Abdominal ascites/tumor 3Gastric paresis (paralysis) caused by other sources including dialysis or diabetes 3Choice of agents for prophylaxis of expected aspiration: For trauma patients, sodium citrate (30 ml-raises the pH of gastric fluid already present); ranitidine (Zantac) by IV administration at a dosage of 50 mg; metoclopramide (Reglan), 20 mg by IV administration to facilitate gastric emptying.  For preparation of elective surgery patients who have a difficult airway: Ranitidine (Zantac) orally administered at a dosage of 150 mg at 7 p.m. and in the morning of surgery; metoclopramide (Reglan) at a dosage of 20 mg administered orally in the morning of surgery;  glycopyrrolate (Robinul),0.2 mg by IV administration to reduce secretions in support of fiberoptic bronchoscopy Proton pump inhibitors: Overview: Parietal cells H+ ion secretion depends on a H+,K+-ATPase pump-- promoting H+ K+ exchange H+,K+-ATPase located in apical membraneto and tubulovesicular apparatus of parietal cells Luminal surface of the membrane enzyme: exposed to gastric luminal acid Specific drugs: Omeprazole (Prilosec) Dosage (adult): Intravenous dosage is 40 mg administered 30 minutes prior to induction The oral dose range is between 40 and 80 mg administered between 2 and 4 hours before the procedure Mechanism of action: Omeprazole (Prilosec) and lansoprazole (Prevacid) bind "irreversibly" to the proton pump.  This action result in an extended duration of action, since new protein must be synthesized to reestablish proton secretion function. Duration of action: The effect on gastric pH may be as long as 24 hours with variable effects on gastric volume (omeprazole (Prilosec)) 1Antiemetic drugs: Overview and rationale-- Antiemetic agents are included in anesthetic premedication with the objective decreasing postoperative nausea and vomiting incidence. Factors that tend to increase patients risk for developing postoperative nausea and vomiting: Females Previous history of postoperative nausea History motion sickness Use of general rather than regional anesthesia Opioid (e.g. morphine, meperidine (Demerol)) administration Opthalmological or gynecologic surgeries Orthopedic shoulder surgery Prophylactic use of antiemetic agents decrease the likelihood of postoperative nausea vomiting; however, little outcome difference has been documented based on whether the patient receives prophylactic medication or medication only if nausea and vomiting symptoms occur. Drugs used for prophylaxis against postoperative nausea and vomiting: Serotonin antagonists such as: ondansetron (Zofran), tropisetron, granisetron (Kytril),dolasetron (Anzemet) Butyrophenones class antipsychotic drugs: droperidol (Inapsine) Gastrointestinal prokinetic agents: metoclopramide (Reglan) Phenothiazine class antipsychotic drugs: perphenazine (Trilafon) Administration protocols: often given near the end of the surgical procedure by IV Route of Administration Arguments against prophylactic antiemetic use: Increased cost -- at the present particularly for the serotonin antagonist drug class Possibility of dysphoria/sedation should butyrophenones be used Orthostatic hypotension (a side effect of phenothiazine-type agents because of their alpha-1 adrenergic receptor blocking properties) A percentage of patients will vomit independent of whether antiemetic drug prophylaxis is used 3More about metoclopramide (Reglan): Dosage and Route of Administration: Oral: 90-120 minutes preoperatively the dosage of 0.2 mg/kg IV administration: onset occurs within 3  minutes (compared to a time to onset of about 20 minutes following oral dosage) In emergent circumstances, oral dosing is still appropriate and clinically effective, since gastric contents will be decreased within 15 minutes In the trauma setting, metoclopramide (Reglan) has been found more effective in emptying child's stomach compared to waiting 6-8 hours. Contraindications to metoclopramide (Reglan) administration-note that metoclopramide is a dopamine antagonist: Metoclopramide (Reglan) not be given to patients who are taking dopamine antagonists, tricyclic antidepressants, sympathomimetic agents, or monoamine oxidase inhibitors (metoclopramide (Reglan) may cause hypertensive crises in patients with pheochromocytoma). Complications/side effect associated with metoclopramide (Reglan)-- Extrapyramidal Neurological side effects --: Frequency = 1%, more common in children and at those higher doses used to manage chemotherapy-induced vomiting.  Diphenhydramine (Benadryl) may be effective in limiting these side effects. Tremor, torticollis {limited neck motion due to shortening of the sternocleidomastoid muscle; idiopathic spasmodic torticollis is classified as a focal dystonia and may be seen more commonly with neuroleptics and L-DOPA},opisthotonus {abnormal postures and defined as rigidity with severe back arching what they had thrown backwards -- the extent of the syndrome can be visualized in that if a personal were layed on his/her back only the back of the head and heels would touch the  surface}, oculogyric crisis {an acute dystonia:"A spasmodic movement of the eyeballs into a fixed position, usually upward, that persist for several minutes or hours"} Opisthotonus Opisthotonus: image from Mount Allison University., used with permission Torticollis "Picture 1. 69-year-old woman presenting with torticollis and fever" "Picture 2. Soft-tissue neck radiograph demonstrates retropharyngeal abscess appearing as torticollis." 5From: " Torticollis" Authored by Michael Ross, MD, Staff Physician and Associate Director of EMS, Department of Emergency Medicine, Metrowest Medical Center Coauthored by Susan Dufel, MD, FACEP, Program Director, Associate Professor, Department of Traumatology and Emergency Medicine, Division of Emergency Medicine, University of Connecticut School of Medicine, emedicine site: http://www.emedicine.com/emerg/topic597.htm return to main menu 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, pp 551-565, 2001 5Michael Ross and Susan Dufel "Torticollis" emedicine, http://www.emedicine.com/emerg/topic597.htm