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• Anticholinergic Agents

  • Overview:

    • Evaluated on a case-by-case basis, anticholinergics may be included in some preanesthetic medication protocols

    • Factors which influence the likelihood that in anticholinergic would be included are

      • (1) the need for antisialagogue effects;

      • (2) the facilitation of sedative/amnestic effects 

      • (3) the the need to reduce/eliminate reflex bradycardia (Reflex bradycardia in children may occur subsequent to laryngeal stimulation, laryngospasm, or hypoxia.  Prophylactic use  of atropine or glycopyrrolate (Robinul) [oral or intravenous] may prevent this reflex action)

    • Compared to other drugs, anticholinergics should not be considered effective in decreasing gastric fluid volume or increasing gastric fluid pH (patients had increased risk for aspiration pneumonitis can be managed using other drugs, e.g. prokinetic agents (metoclopramide (Reglan)), antacids, H₂ receptor antagonists.

  • Antisialagogue effects:

    • Most currently used inhaled/intravenous anesthetics do not cause significant salivation.  Therefore, routine use of anticholinergic (antimuscarinic) drugs which cause "dry mouth",  i.e. antisialagogue effects, would not be needed.

    • Ketamine (Ketalar) is an exception in that its use may provoke excessive salivation.

    • However, under some circumstances, antimuscarinic agents are appropriate for antisialagogue purposes. 

      •  For instance, preoperative anticholinergics may be helpful when tracheal tube is in place to decrease oral secretions during general anesthesia

      • Antisialagogue effects are helpful in procedures involving bronchoscopies or intra-oral surgeries.

      • When local anesthetics are used, antisialagogue effects limit the dilution of the anesthetic by excessive secretion

  • Vagolytic effects of anticholinergics:

    • Acetylcholine exhibits normally a negative chronotropic effect on the heart (reduces heart rate in part by increasing K⁺ channel conductance at the SA node; increased K⁺ conductance will tend to hyperpolarize the membrane, i.e. more negative, requiring increased time to threshold and therefore reduced rate)

    • Generally, heart rate is controlled by the autonomic nervous system with the parasympathetic (cholinergic) component dominant.  Therefore, there is a "tonic" level of autonomic inhibition of heart rate.  Usually, the vagolytic activity of anticholinergic drugs account for an increase in heart rate or a block of effects that would otherwise decrease heart rate causing bradycardia.

    • Intraoperative factors that can promote bradycardia: 

      • Traction on extraocular muscles or abdominal viscera

      • Carotid sinus stimulation

      • Following multiple doses of succinylcholine (Anectine)

        • atropine or glycopyrrolate (Robinul), by IV administration appear equally effective in blunting bradycardic responses to multiple succinylcholine (Anectine) doses.

    • Route of Administration:

      • Intramuscular: relatively unreliable

      • Probably better choice: by IV administration just prior to surgery and/or anticipated stimulus which would cause the bradycardic response

  • Specific anticholinergic (antimuscarinic) drugs:

    • Three common  anticholinergic drugs: scopolamine, atropine, and glycopyrrolate (Robinul).

    • Comparisons between these agents:

      • Scopolamine is a more potent (about threefold) an antisialagogue compared to atropine and scopolamine is noted to exhibit significantly enhanced CNS actions such as sedation.

        • Scopolamine is less likely to increase heart rate, compared atropine, along with providing relatively greater sedation and amnesia.

          • Amnestic effects:

            1. Scopolamine is more effective than atropine but probably less effective than commonly used benzodiazepines, e.g. midazolam (Versed), lorazepam (Ativan), or diazepam (Valium)

            2. Scopolamine's amnestic effect is additive to that obtained with benzodiazepines

            3. From the patients point of view, the combination scopolamine + morphine was "better"  as compared to morphine + atropine.

      • Scopolamine may be the drug choice when both antisialagogue effects and sedation are desired

      • By contrast, glycopyrrolate (Robinul) is about twice as effective as an antisialagogue compared to atropine, does not exhibit CNS actions, and has an extended duration of action compared atropine.  When sedation is not required but antisialagogue effects are, glycopyrrolate (Robinul) may be a good choice

      • Dosages (intramuscular): atropine: 0.3-0.6 mg (adult); scopolamine: 0.3-0.6 mg (adult); glycopyrrolate (Robinul): 0.2-0.3 mg (adult)

  • Side effects of anticholinergic agents:

    • "Central anticholinergic syndrome": more likely observe following scopolamine or "high-dose" atropine

      • Symptoms:

        • Confusion, obtundation, restlessness, and delirium

      • Older patients more susceptible

      • Anticholinergic CNS toxicity may be potentiated by inhalational agents

      • Treatment: try 1-2 mg physostigmine (Antilirium), by IV administration [rationale: physostigmine (Antilirium), a tertiary-amine anticholinesterase would be expected to gain ready access to the CNS where inhibition of acetylcholinesterase should increase free acetylcholine that could overcome competitive muscarinic receptor blockade caused by the anticholinergic medications.

    • Anticholinergic drugs relax the lower esophageal sphincter, in theory promoting reflux and increasing aspiration risk.  However, this effect has not been clinically demonstrated.  Nevertheless, in patients with known reduced lower esophageal sphincter tone, such as patients with hiatal hernia, already present an aspiration risk that may be further  increased by the use of anticholinergics.

    • Ocular effects.

      • In  theory, mydriasis and cycloplegia which would be induced by anticholinergic agents would appear undesirable in glaucoma patients.  However, the low anticholinergic doses used preoperatively would be unlikely to produce adverse  ocular effects.

      • Atropine and glycopyrrolate (Robinul) would probably be less likely to increase intraocular pressure compared to scopolamine

      • Usually, patients being treated for glaucoma, take their medication (eyedrops) as usual before surgery with low-dose (anesthesia-dose) anticholinergics used intraoperatively as needed

    • Pulmonary effects, secondary to  reduced vagal activity:

      • Increase in respiratory dead space.  Following anticholinergic agents, and dependent on pre-existing cholinergic tone, dead space may increase by 25%-33%.

      • Bronchial smooth muscle relaxation occurs with anticholinergic drugs.  

        • This effect is used to advantage in asthma management by administration of ipratropium (Atrovent).  

        • Normally, but variably, there is some bronchial smooth muscle tone maintained by the parasympathetic component of the sympathetic nervous system.  Reduction of bronchial smooth muscle tone following anticholinergics is thus expected.

      • Effect of anticholinergic agents on bronchial secretions:

        • Secretions would tend to thicken with drying.

        • As a result of  secretion thickening, airway resistance may increase, a concern of particular consequence of patients with cystic fibrosis for example

    • Anticholinergic drug effects on control of body temperature:

      • Anticholinergic's cause an increase in body temperature due to reduced sweating.  Sweat glands are normally innervated by sympathetic cholinergic fibers (an unusual innervation, given the most sympathetic fibers release norepinephrine not acetylcholine).  Therefore, blockade of muscarinic receptors,  by inhibiting sweating, increases body temperature, which may be of clinical concern if the patient is a child with a fever.

• α-2  receptors agonists:

  • Preoperatively, clonidine (Catapres) an α-2 adrenergic receptor agonist, causes sedation and reduces autonomic nervous system reflects responses.  

    • These responses may include those secondary to catecholamine release in general and hypertension and tachycardia in particular. 

  • Centrally-acting agents, such as clonidine (Catapres), reduce sympathetic autonomic outflow by acting mainly at α-2 presynaptic receptor sites. (note that α-2 receptors have been found and extra-synaptic and postsynaptic sites as well)  Presynaptic stimulation decreases transmitter release.

Physiology of the α 2-adrenoceptor agonists receptor. Adapted from
dexmedetomidine.com 

• Clonidine (Catapres)-dosage for preoperative medication = 5 μg/kg, orally. 

  • At this dosage clonidine (Catapres) will produce sedation and reduced autonomic nervous system reflects responses.

  • Preoperatively, 2-5 μg/kg orally may reduce preoperative myocardial ischemia in patients who likely have coronary vascular disease

  • Clonidine (Catapres) also may be used for patients not only with uncontrolled hypertension but also have the need for urgent surgery.  

    • However, significant impairment of autonomic function, in particular attenuation of sympathetic responses, may mask hidden volume loss and delay compensation for the unrecognized hypovolemic state

• ⁵Dexmedetomidine (Precedex) is a newer and potentially more specific/potent α-2 receptor agonist compared clonidine (Catapres).   

  • Dexmedetomidine (Precedex) exhibits both central and peripheral actions. Anxiolytic, analgesic, sedative, and sympatholytic characteristics have been attributed to dexmedetomidine (Precedex).  These characteristics are considered beneficial in the perioperative  stressful setting. 

  • Dexmedetomidine (Precedex) was initially approved by the FDA for use in short-term sedation of intensive care patients (May 2000, Abbott Laboratories);

  • Dexmedetomidine (Precedex), like clonidine (Catapres), enhances the anesthetic effect of intravenous and volatile agents as well as those used for regional block.  

    • Dexmedetomidine (Precedex) apparently reduces by about 20%-30% the amount of thiopental (Pentothal) required for induction.

  • At least one report has suggested increased patient tiredness following dexmedetomidine (Precedex)

• Side Effects for α-2 receptor agonists include bradycardia and dry mouth

⁴Steroids

• Overview: patients who may need need steroid administration  immediately before surgery

  1. Patients being treated for hypoadrenocorticism

  2. Patients who have pituitary-adrenal axis suppression due to ongoing or previous steroid treatment -- generally more suppression would be anticipated if the treatment had been for longer duration and at higher dosages

  3. General rule: consider preoperative treatment give the patient has been on steroids for one month in the last six months preceding surgery

• The major clinical perioperative consequences of  pituitary-adrenal axis suppression is the inability of the patient to respond properly to surgical stress.  Accordingly, supplemental steroid protocols could include:

  • Method #1:  25 mg of cortisol preoperatively followed by IV infusion of 100 mg cortisol during the next 12-24 hours (adult patients)

  • Method #2: administration of 100 mg of hydrocortisone (Cortef, Solu-Cortef) intravenously before, during and then after the procedure.  This approach is an effort to estimate a maximal amount of steroids that would be released in response to surgical stress.  Generally, the risk-benefit ratio for steroid administration and dosage is small.

Antibiotics:

• Context for use: 

  • Antibiotics are considered for administration immediately before surgery for "contaminated, potentially contaminated, or dirty surgical wounds."

  • Prophylactic antibiotics may be used for certain patients groups including:

    • Elderly patients

    • Immunosuppressed patients

    • Patients taking steroids

    • Patients who are at risk for development of endocarditis, including patients with valvular heart disease, patients who have mitral valve prolapse, and patients who have prosthetic valves.

• The reason that the anesthesia provider is involved in antibiotic administration is that the antibiotics will be administered immediately preceding the surgical procedure-just before potential contamination could occur.

• Approximately 60%-70% of patients receive antibiotics intraoperatively or just prior to the beginning of the procedure.

• The antibiotics class most commonly used is the cephalosporins.

• Side effects and complications may occur with antibiotic administration.  The side effects may include:

  1. Allergic reactions

  2. Hypotension

  3. Bronchospasm-examples here might be penicillin or vancomycin (Vancocin)

• Side effect frequency: Approximately 5% of patients have some "allergic" reaction to cephalosporin.  Furthermore, the cross-reactivity between cephalosporins and penicillins is estimated to be about 5%-20%

• Some antibiotics are noted for their tendency because nephrotoxicity (renal toxicity).  

  • These antibiotics include the aminoglycosides, vancomycin (Vancocin) and polymixins.

• Ototoxicity is associated both with vancomycin (Vancocin) and aminoglycoside administration.

• A specific side reaction of clindamycin (Cleocin) use is pseudomembranous colitis.  

• Aminoglycosides enhanced neuromuscular-blocking properties of muscle relaxants.

Insulin:

• Overview: Because of interruption of normal eating schedules and the stress associated with surgery, specific plans are required to manage the insulin-dependent patient.  

  • Collaboration between the anesthesia provider surgeon and endocrinologist is the basis for determining how insulin will be provided.

• Several approaches (methods) are available.

  1. One approach is the administration of 1/4 to one-half of the usual daily intermediate-acting insulin dose preoperatively in the morning of surgery followed by a glucose-containing fluid infusion.

  2. A second approach is the administration of no insulin or no glucose preoperatively accompanied by intraoperative  blood glucose monitoring, allowing regular insulin or glucose administration intraoperatively and postoperatively as required

  3. A third approach is based on initiation of insulin and glucose infusion immediately preoperatively along with frequent serum glucose level determinations

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, pp. 364-367 (Hardman, J.G, Limbird, L.E, Molinoff, P.B., Ruddon, R.W, and Gilman, A.G.,eds) TheMcGraw-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

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