Nursing Pharmacology Chapter 14:  General Anesthesia

 

• Intravenous drugs: Rationale for use with inhalational anesthetics

  • Provide hypnosis

  • Enhance or provide analgesia

  • Provide muscle relaxation

  • Reduce visceral reflex responses

  • Enable lower doses of inhalational agent to be used

• I. V. Benzodiazepines

• I. V. Barbiturates

• I.V. Opioids

• Ketamine

• Propofol

• Combinations

• Intravenous Barbiturates: Anesthesia

  • Thiopental (Pentothal)

  • Methohexital sodium
    (Brevital Sodium)

  • Thiamylal Sodium (Surital)

• Thiopental

  • Overview:

    • Unconsciousness after 10 - 20 sec following i.v. injection (2.5% isotonic solution)

    • Rapid recovery (20-30 min) due to redistribution from brain to peripheral tissues

    • Thiopental (and other barbiturates) are poor analgesics and may actually increase (at inadequate dosage) sensitivity to pain.

    • This effect on pain may result in increased sympathetic activity: tachycardia, sweating, tachypnea, increased blood pressure and dilated pupils.

    • Initially, thiopental often causes coughing, laryngospasm and bronchospasm.

    • Dose-related respiratory depression, profound at higher doses.

    • Limited cardiovascular effects, except in the presence of hypovolemia, sepsis, or other circulatory instability. In that case a standard thiopental dose can result in a hypotensive response.

    • Skeletal muscle relaxation is transient.

    • Thiopental crosses the placental barrier and depresses the fetus.

  • Thiopental Advantages:

    • Rapid induction and fast recovery (faster recovery with methohexital)

    • Little postoperative excitement or vomiting

    • Useful in combination with other anesthetics

  • Thiopental Disadvantages

    • Cough, laryngospasm, bronchospasm

    • Histamine release

    • Overdosage difficult to reverse in the absence of specific barbiturate antagonists.

  • Thiopental Contraindications:

    • Variegate porphyria or acute intermittant porphyria: absolute contraindication.

    • In these cases, thiopental or other barbiturates can cause nerve demyelination and CNS lesions which may result in pain, weakness and life-threatening paralysis

  [Kennedy, S.K. and Longnecker, D.E., History and Principles of Anesthesiology 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, p 321 - 328.]

• Intravenous Benzodiazepines and Anesthesia

  •  Diazepam(Valium)
    prototype drug

  •  Midazolam (Versed)

  •  Lorazepam (Ativan)

• Diazepam

  • Drowsiness occurs several minutes after I.V. administration. Lorazepam slightly slower and Midazolam slightly faster onset compared to diazepam.

  • Benzodiazepines are effective in promoting sedation and reducing anxiety. They are amnestic in most patients.

  • Amensia is anterograde and lasts about 6 hours.

  • Used alone benzodiazepines have limited depressant effects on the cardiovascular/respiratory system.

  • CNS depression can be reversed by the specific anatagonist flumazenil (Romazicon).

  • When benzodiazepines are administered in combination with opioids, significant cardiovascular and respiratory depression may occur.

  • Benzodiazepines are not analgesic.

    • Benzodiazpines in Anesthesia

      • Benzodiazepines may be used alone for procedures not requiring analgesia, such as Endoscopy, DC cardioversion, Cardiac catherization, Certain radiological procedures

      • Benzodiazepines reduce the likelihood of seizures when local anesthetics are used for regional procedures

      • Benzodiazepines are often used in combination with other drugs for "balanced anesthesia"-which may include Opioids, Muscle relaxants, Thiopental for induction and an inhalational agent

      • Clinically: Lorazepam (Ativan) is a very effective anterograde amnestic; Midazolam (Versed) has a more rapid onset of action and a shorter duration

Kennedy, S.K. and Longnecker, D.E., History and Principles of Anesthesiology 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, p 324.

• Intravenous Opioids: Anesthesia:  Morphine, Meperidine (Demerol), Fentanyl (Sublimaze),Sufentanil (Sufenta), Alfentanil (Alfenta), Remifentanil

  • Opioids are used typically to suppliment inhalational or i.v. anesthetics.

  • Respiratory depression, hypotension, post-operative nausea or vomiting are associated with opioid use.

  • In certain procedures, large dose morphine can be used to obtain anesthesia;

  • Morphine-nitrous oxide combination has been used in cardiovascular surgery.

• Fentanyl (Sublimaze) and related agents

  • I.V. fentanyl causes analgesia and unconsciousness.

  • Compared to morphine, fentanyl is:

    •  more amnestic

    •  less likely to provoke hypotensive or hypertensive responses

    •  shortened duration of respiratory depression.

    •  These factors have led to fentanyl and related agents to become preferable to morphine.

  • Fentanyl is often combined with a muscle relaxant and nitrous oxide or low doses inhalational agent for anesthesia.

  • Alfentanil and sufentanil are more potent than fentanyl and produce analgesia and, at higher concentrations, anesthesia.

  • Remifentanil is a new potent agent which produces analgesia very rapidly.

    • It is readily metabolized resulting in a rapid recovery time.

  • Respiratory depression caused by opioids are reversible using specific narcotic antagonists, such as naloxone (Narcan).

    • The duration of action of naloxone is only 60 to 90 minutes so repeated dosing may be required to prevent recurrence of respiratory depression. (other narcotic antagonists: naltrexone (ReVia), nalmefene (Revex))

  Kennedy, S.K. and Longnecker, D.E., History and Principles of Anesthesiology 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, p 325 - 326.

   

• Intravenous Combinations: Neuroleptic-Opioids: Innovar

  • Neurolept analgesia is useful for minor surgical procedures, some radiological procedures, burn dressing, and endoscopy.

  • Neuroleptic agents such as droperidol (Inapsine) cause a reduction in anxiety and a state of indifference.

  • Droperidol is an antiemetic and has adrenergic blocking (alpha block) activity.

  • When combined with an opioid such as fentanyl (Sublimaze), a state of neurolept analgesia results.

  • Addition of nitrous oxide can transition neurolept analagesia to neurolept anesthesia.

  • Neurolept analgesia/anesthesia may be especially useful in the elderly, debililitated or seriously ill patient.

  • The combination of droperidol and fentanyl is Innovar.

  • Innovar produces slight circulatory effects, but can cause significant respiratory depression.

  • Droperidol can cause neuroleptic malignant syndrome (rarely).

  • The low incidence of extrapyramidal side effects associated with droperidol use may be effectively treated with the anti-cholinergic (anti-muscarinic) drug, benztropine (Cogentin).

  Kennedy, S.K. and Longnecker, D.E., History and Principles of Anesthesiology 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, p 326.

• Ketamine

  • Ketamine (Ketalar) produces a state that is characterized by sedation, amnesia, analgesia and immobility.

    • This type of anesthesia has been termed "dissociative anesthesia" because of patient's subjective impression of being dissociated from the environment.

  • Significant amnesia and analgesia rapidly follow injection.

  • Muscle tone tends to increase.

  • Arterial blood pressure, heart rate and cardiac output increase, probably due to increased sympathetic outflow.

  • Recovery is slower than with barbiturates, perhaps reflecting difference site of action (cortex/limbic for ketamine; brainstem for barbiturates).

  •  Awakening may be associated with bad dreams and hallucinations which may recur.

    •  These adverse experience are less common in children and can be diminished by concurrent administration of benzodiazepines.

  •  In conjunction with diazepam, ketamine may be useful in managing emergency surgery, trauma, dressing changes and certain pediatric radiological procedures.

  Kennedy, S.K. and Longnecker, D.E., History and Principles of Anesthesiology 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) The McGraw-Hill Companies, Inc.,1996, p 326- 327

• Propofol (Diprivan)

  • I.V.  propofol rapidly induces anesthesia, similar to thiopental.

  • Duration of propofol anesthesia can be increased by repeated administration or by combination with inhalational agents, nitrous oxide, or opioids.

  • Propofol causes peripheral vasodilation which leads to a decrease in blood pressure, but the agent is not arrhythmogenic.

  • Propofol does not adversely affect hepatic or renal function.

  • Emergence from propofol anesthesia is rapid with minimal postoperative confusion.

  • Postoperative GI upset occur at a similar frequency to that of thiopental.

  • Propofol is now commonly used in ambulatory surgery settings.

  Kennedy, S.K. and Longnecker, D.E., History and Principles of Anesthesiology 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) The McGraw-Hill Companies, Inc.,1996, p 326- 327

• Preanesthetic Medication: Rationale:  Preanesthetic Medication Properties:

  • Primary Goals

    • Anxiety relief without excessive sedation

    • Amnesia during perioperative period while retaining cooperation

    • Relief of preoperative pain

  • Secondary Goals

    • Reduction in the requirement for inhalational agents

    • Reduction in side effects associated with some inhalational agents.

      • Side effects include salivation, bradycardia, postanesthetic vomiting.

    • Reduction in acidity and volume of gastric contents.

    • Reduction of stress in perioperative period.

• Preanesthetic Medication: Sedative-Hypnotics

  • Benzodiazepines are frequently used as preanesthetics because of the following properties:

    • Anxiolytic

    • Sedation

    • Relatively little respiratory and cardiac depression

    • Raise threshold for CNS toxicity of local anesthetics

    • Amnesia

  • Barbiturates (pentobarbital and secobarbital) also produce sedation and reduce presurgical apprehension.

    •   However, barbiturates when administrated to patients in pain can result in disorientation.

  • Specific Agents

    • Diazepam (Valium): widely used, active orally, absorption unreliable by the parenteral route of administration; little effect on respiration and does not increase respiration depression caused by opioids.

    • Lorazepam (Ativan): oral or parenteral administration; good amnestic.

    • Midazolam (Versed): good amnestic, rapid onset, short duration; popular in same-day surgery setting due to rapid return of normal mental status; when administrated in combination with opioids, there is a decrease in catecholamine release in surgery;

    • Flumazenil (Mazicon), a benzodiazepine antagonist is effective in even more rapidly reversing sedative effects of midazolam (Versed)

• Preanesthetic Medication: Opioids

  • Opioids are frequently used as preanesthetics because of the following properties:

    • Presurgical pain relief

    • Anxiolytic (questionable)

    • Sedation

    • Reduction in the amount of general anesthesia required (about 10% - 20% reduction\

  • Adverse Effects: Opioids

    • Respiratory depression

    • Prolongation of awakening from general anesthesia

    • Biliary/uterine spasm due to effects on smooth muscle,

    • Wheezing in asthmatics,

    • Constipation/urinary retention

    • Nausea and vomiting,

    • Hypotension,

    • Respiratory depression resulting in increased ICP (due to CO₂ retention which produces cerebral vasodilation)

    • Pruritis

  • Morphine

    • Morphine: Clinical Uses

      • Relieves severe and chronic pain

      • Reduces pulmonary edema and pain of myocardial infarction

      • Reduces preoperative pain

      • Anxiolytic (controversial)

      • Relieves dyspnea in acute congestive heart failure

      • Reduces amount of inhalational agent required in General Anesthesia

    • Morphine: Contraindications (partial listing)

      • Hypersensitivity to opioids

      • Increased ICP (intracranial pressure)

      • Convulsive disorders

      • Acute alcoholism

      • Acute asthma

      • Severe respiratory depression

      • Prostatic hypertrophy

      • Severe hepatic or renal insufficiency

      • Acute ulcerative colitis

      • Addison's disease

      • Safe use in pregnancy not established (Category B; D in long-term use or high dose use)

    • Morphine:  Cautious Use (partial listing):

      • Toxic psychosis

      • Cardiac arrhythmias

      •  Emphysema

      •  Elderly

      •  Very young

      • Labor

    • Morphine: Side Effects (Partial listing)

      • CNS: respiratory depression, euphoria, dysphoria, CNS stimulation

      • CV: bradycardia, palpitations, syncope, orthostatic hypotension

      • GI: constipation, nausea, biliary colic

      • GU: Urinary retention/urgency

      • Allergic: pruritis

Shannon, M.T., Wilson, B.A., Stang, C. L. In, Govoni and Hayes 8th Edition: Drugs and Nursing Implications Appleton and Lange, 1995, pp 794-795; Kennedy, S.K. and Longnecker, D.E., History and Principles of Anesthesiology 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, p 304.]; Barash, P.G., Cullen, B.F, Stoelting, R.K. In, Handbook of Clinical Anesthesia (Third Edition), Lippincott-Raven, 1997, p.267, 639

• Meperidine [Demerol]

  • Meperidine [Demerol]: Clinical Uses

    • Relieves severe and chronic pain

    • Reduces preoperative pain

    • Anxiolytic (controversial)

    • Relieves dyspnea in acute congestive heart failure

    • Reduces amount of inhalational agent required in General Anesthesia

  • Meperidine [Demerol]:  Contraindications (partial listing)

    •  Hypersensitivity to meperidine

    •  Acute abdomen (prior to diagnosis)

    •  Convulsive disorders

    •  Severe respiratory depression

    •  Severe hepatic or renal insufficiency

    •  Acute ulcerative colitis

    •  Safe use in pregnancy (prior to labor) not established (Category B; D in long-term use or high dose use)

  • Meperidine [Demerol]:  Cautious Use (partial listing):

    • Increased ICP

    • Head injury

    • Supraventricular arrhythmia

    • Emphysema

    • Hepatic or renal impairment

    • Elderly

    • Addison's disease

    • Prostatic hypertrophy

    • Hypothyroidism

    • Glaucoma

  • Meperidine [Demerol]:Side Effects (Partial listing)

    • CNS: respiratory depression, dizziness, sedation, euphoria, dysphoria, CNS stimulation, convulsions

    • CV: bradycardia, tachycardia, palpitations, syncope, orthostatic hypotension, cardiovascular collapse/arrest (toxic doses)

    • GI: constipation, nausea, biliary colic, dry mouth

    • Allergic: pruritis

Shannon, M.T., Wilson, B.A., Stang, C. L. In, Govoni and Hayes 8th Edition: Drugs and Nursing Implications Appleton and Lange, 1995, pp 726-727

• Fentanyl [Duragesic, Sublimaze]

  • Fentanyl: Clinical Uses

    • Short acting analgesic used during perioperative periods.

    • Combined with droperidol or with diazepam producing neuroleptanalgesia

    • Suppliment in general/regional anesthesia

    • In high-risk cardiac surgery it may be used with a muscle relaxant and oxygen for anesthesia when the use of additional anesthetics cannot be tolerated

  • Fentanyl: Contraindications (partial listing)

    • Patients who have received MAO inhibitors within the previous 2 weeks

    • Myasthenia gravis

    • Severe respiratory depression

    • Safe use in children under 2 years not established

    • Safe use in pregnancy not established (Category C)

  • Fentanyl: Cautious Use (partial listing)

    •  Head injuries

    •  Increased ICP

    •  Renal/hepatic dysfunction

    •  Bradyarrhythmia

    •  Elderly

    •  Very young

    •  COPD/other respiratory conditions

  • Fentanyl:  Side Effects (Partial listing)

    • CNS: respiratory depression, sedation, convulsion (high dose)

    • CV: bradycardia, cardiac arrest, syncope, orthostatic hypotension

    • GI: constipation, nausea, vomiting

Shannon, M.T., Wilson, B.A., Stang, C. L. In, Govoni and Hayes 8th Edition: Drugs and Nursing Implications Appleton and Lange, 1995, pp 515-516

• Antiemetics

  • Hydroxyzine (Vistaril) and droperidol have useful antiemetic actions.

  • Postoperative nausea/vomiting may be reduced by substituting an NSAID (such as ketorolac) for opioids that would otherwise be used.

  • Ondansetron (Zofran)

    • 5-HT₃ receptor blocker

      • Minimal effects on dopamine, histamine, adrenergic or cholinergic receptor activity

    • Very effective for prevention of nausea and vomiting caused by chemotherapy or surgery. -- major role in management of severe nausea and vomiting due to anticancer drugs

    • Clinical Use:

      • Dosage: 4-8 mg IV (administered over 2-5 minutes just before anesthesia induction)

      • Highly effective in reducing postoperative nausea/vomiting incidence -- particularly in susceptible patient groups:

        • Ambulatory gynecologic surgery

        • Middle ear surgery

      • Oral or IV reduces incidence of postoperative vomiting in preadolescent children undergoing:

        • ambulatory surgery, e.g. tonsillectomy, strabismus surgery

      •  Ondansetron: effective both for prophylaxis and treatment of postoperative nausea/vomiting

        • decreases incidents and intensity of postoperative nausea and vomiting -- but does not totally eliminate this problem

        • Major advance: reduced side effects compared to previously used antiemetic drugs such as:

          • phenothiazines, antihistamines, butyrophenones

      • Propofol for induction and maintenance of anesthesia may be as effective as ondansetron in reducing/preventing postoperative nausea and vomiting

    • Side Effects:

      • Surgical patients:

        • 3% increased liver transaminase enzyme levels

        • 3% headache

      • No sedation, hypotension, dysphoria, extrapyramidal reactions which are side effects associated with other antiemetic drugs

  • Tropisetron (Navoban)

    • 5-HT₃ receptor blocker

    • Effective in managing symptoms induced by carcinoid syndrome-- also some gastrokinetic characteristics

    • Effective in preventing chemotherapy/radio therapy-induced emesis

    • Effective in preventing postoperative nausea/vomiting when administered before general anesthetic induction

  • Granisetron (Kytril)

    • More selective 5-HT₃ receptor blocker compared to ondansetron

    • Clinical Use:

      • Effective in the chemotherapy-induced emesis prevention

      • Effective in preventing postoperative nausea/vomiting

    • Elimination half-life: nine hours, compared to about three hours for ondansetron: suggesting less frequent dosing with granisetron.

    • Significantly higher cost-- could limit clinical use

  • Dolasetron (Anzemet)

    • Highly potent/selective 5-HT₃ receptor blocker

    • Clinical Use:

      • Effective in preventing chemotherapy-induced nausea/vomiting

      • Effective in reducing likelihood of postoperative nausea and vomiting

      • Antiemetic effect due to long-acting, active metabolite (hydrodolasetron; elimination half-life = approximately 8 hours)

  Kennedy, S.K. and Longnecker, D.E., History and Principles of Anesthesiology In, Goodmanand 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, p 304; Stoelting, R.K., "Renin, Plasma Kinins, and Serotonin", in Pharmacology and Physiology in Anesthetic Practice, Lippincott-Raven Publishers, 1999, pp 398-407

   

• Phenothiazines (e.g. promethazine, i.m.)

  • Properties that favor use as preanesthetics

    • Sedation

    • Antiarrhythmic

    • Antiemetic

    • Antihistaminic

  • These agents may be combined with an opioid or barbiturate.

  • Phenothiazines can prolong postanesthetic sleep, cause hypotension and respiratory depression.

• Butyrophenones (droperidol)

• Antihistamines

  • Sedation is a common side effect of antihistamines.

  • Hydroxyzine (Vistaril) is used (now less commonly) as a preanesthetic, although --benzodiazepines are used more frequently

    • Hydroxyzine  Vistaril

      • Produces CNS depression

      • Anticholinergic properties

      • Antiemetic properties

      • Antihistaminic properties

      • Bronchodilator properties

        • Clinical Uses

          • Reduces anxiety

          • Controls nausea and emesis

          • Reduces opioid requirement before/after surgery

          • Management of chronic urticaria, atopic/contact dermatoses

          • Treatment of alcohol withdrawal symptom

• Anticholinergics:  Anticholinergics are used as preanesthetics primarily to decrease vagal effects that occur during surgery.

  • Atropine

    • Dry mouth,

    • Blurred vision;

    • This dosage will not block parasympathetic effects induced by visceral traction, massage/manipulation of the carotid sinus or by succinylcholine.

    • I.V. atropine can reverse these effects.

  • Glycopyrrolate (Robinul) (quaternary amine):

    • Less sedation than scopolamine; 

    • Very effective against secretions;

    • Much less tachycardia than atropine; but more effective in blocking bradycardia.

    • Clinical Uses:

      • Parenteral use a preanesthetic medication;

      • Interoperative medication

      • Reversal of neuromuscular blockade

      • Management of peptic ulcer

      • GI conditions associated with hyperacidity, spasm, hyper motility

• Gastrokinetic Agents

  • Gastrokinetic agents: useful in reducing gastric fluid volume.

    • Rationale: Reduction of gastric fluid volume: important to decrease risk of aspiration pneumonitis

      • High-risk patients:

        • Acute pain; "full stomach" -- emergency surgery

        • Patient with hiatus hernia

        • Patient with esophageal reflux

    • Aspiration gastric contents may lead to chemical pneumonitis

    • Pulmonary aspiration of gastric content: rare in elective surgery

    • Drinking clear fluid -- up to three hours before surgery: no measurable gastric volume or pH effect in healthy children (age group: 2-12 years){note: healthy patients; clear liquids only}

    • in adults: possibly, relatively high-risk of pulmonary complications if aspiration volume:

      1. > 25 ml and

      2. pH < 2.5

  • Metoclopramide (Reglan)

    • Classification: dopamine antagonist

    • Gastrokinetic activity:

      • Stimulates upper gastrointestinal motility

      • Increases gastroesophageal sphincter tone

      • Relaxes the pylorus

      • Relaxes the duodenum

    • Increases of the rate of gastric emptying

      • Oral: 10 mg -- onset within 30-60 minutes

      • Parenteral: 5-20 milligrams -- 15-30 minutes before induction

        • IV administration over 3-5 minutes-- prevents abdominal cramping (occurs with more rapid infusion)

    •   No guarantee of gastric emptying with metoclopramide

      •  Significant gastric fluid could still remain

      •  Prior administration of other drugs (e.g. opioids) or concurrent atropine administration may offset metoclopramide's effect on the upper gastrointestinal tract.

      •  Gastric volume will not be reduced further (elective surgery) in the presence of already small gastric volumes

    •  May not be effective: following sodium citrate administration

    •  Particularly effective in reducing aspiration pneumonia risk when metoclopramide is combined with a H₂ receptor antagonist (e.g. Ranitidine) before elective surgery

    • Generally favorable risk: benefit ratio in the use of these drugs to reduce the risk of pulmonary complications from aspiration

  • Use of gastrokinetic drugs does not diminish the need for correct, diligent anesthetic techniques to protect the airway during anesthesia:

    • Induction

    • Maintenance

    • Emergence

Moyers, J.R., Preoperative Medication, Chapter 21, In: Clinical Anesthesia 3rd edition, (Barash, P.G., Cullen, B.F. and Stoelting, R.K., eds) Lippincott-Ravin, Philadelphia, New York, 1997, pp. 519-529.