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Overview

• ³Patient Assessment-Estimating the extent and basis of patient anxiety

  •  The extent of anxiety appears to be associated with the particular procedure being performed:

    • 85.7% of patients were about to undergo cancer surgery and 79% of patients about to undergo major genitourologic procedures report anxiety

    • 57.2% of patients undergoing other procedures report anxiety

  •  Patient presurgical concerns (ranked in order):

    1. Blindness

    2. Cancer diagnosis

    3. Loss of an organ

    4. Absence of a diagnosis

    5. Postoperative pain (the anesthesia provider, using a variety of techniques and medications, can minimize the unphysiologic condition of pain; The presence of postoperative pain may be a contributing factor for postoperative cardiovascular morbidity)

• Psychological factors to consider

  • Appropriate levels of fear-the anesthesia provider may help set the patient's expectations:

    • Postsurgical dissatisfaction may be related to unrealistic presurgical expectations, possibly due to inadequate or incomplete preoperative discussion with the patient concerning the procedure and possible outcomes

  •  Presurgical explanations should take into account the anxiety-state of the patient, i.e. a very anxious patient may have even further anxiety as a result of such discussions 

  • Anesthesia providers may aid the patient in coping with preoperative anxiety by suggesting that patients focus their attention to other more pleasing or at least distracting activities

  •  Examples of effect of coping mechanisms which can be promoted by the anesthesia provider

    1.  Helping the patient view themselves as part of rather than separate from the health-care providing team. This type of "empowerment" reduces the likelihood of the patient regarding himself as an "victim" and can help the patient recognize their role in the decision-making process that led to surgery

    2. The anesthesia provider may help the patient assume a level of control concerning their environment and situation-for example use of breathing control in promoting relaxation.  Providing opportunities for control may be especially important for children and young adolescence -- for example allowing a child to choose on which finger the pulse oximeter is to be placed would be such an example

    3.  Relaxation methods: The anesthesia provider may suggest contraction/relaxation cycles of muscles in a small region, such  toes or ankles

    4. Mental distraction-such  music, selective attention, etc.  approaches which promote relaxation may be useful.

• Time of administration: 1-2 hours before anesthesia induction

• Outpatient setting: IV premedication just before surgery

  • Typically drugs are given closer to the time of surgery, i.e. the patient may arrive at the surgical setting without being premedicated (possibly anxious) with the idea of receiving medication just before the procedure

• Primary goals for premedication (premedication agents may include antihistamines, antiemetics, alpha₂ adrenergic receptor agonists, antacids, histamine receptor (H₂) antagonists, opioids, benzodiazepines, gastrointestinal stimulants)

  • Anxiolytic effects -- reduction in patient anxiety with expected  reduction in circulating catecholamines

  • Sedation

  • Reduction in preoperative pain (analgesic effect)

  • Amnesia-the use of an amnestic agent is common with midazolam (Versed) often employed.  Midazolam (Versed) belongs to the benzodiazepine category of drugs

  • Reduction in secretion -- antisialagogue effect

  • Increase in gastric fluid pH with a decrease in gastric fluid volume-these effects are designed to reduce risk which may be associated with aspiration

  • Reduction of autonomic nervous system reflex responses-To accomplish this effect sometimes antimuscarinic agents are used in as a consequence surgical stimulation of muscarinic receptors are less likely to provoke adverse cardiac effects (e.g. bradycardia, arrhythmias)

  • Reduction in required anesthetic amounts -- Premedication with sedative-hypnotic agents and/or opioids to reduce the amount of anesthetic required to achieve a given level of anesthesia.  The advantages may include more rapid emergence upon completion of the case

  • Prophylaxis with respect to allergic reaction (e.g. antihistamines may be helpful)

• Additional premedication issues:

  •  Reduced cardiac activity (e.g., an anticholinergic drug such as atropine may prevent bradycardia associated for example with surgical-induced stimulation of muscarinic receptors). 

    • To manage cardiac vagal activity, antimuscarinic agent should be administered DURING surgery, just prior to the expected need or in response to vagal stimulation

  • Reduction/avoidance of postoperative nausea and vomiting-facilitated with I. V. antiemetic drug administration JUST PRIOR to awakening (this approach is probably better than waiting for symptom developments and then treating the nausea)

  • Postoperative analgesia may be best approached by use of IV opioids or neuraxial opioids JUST PRIOR to symptom development-here administration may be best provided just before awakening or just before a painful surgical action

• Circumstances in which sedative-hypnotic (depressant) and other pharmacological premedication would be warranted:

  1. Cardiac surgery

  2. Cancer surgery

  3. In the presence of pre-existing pain

     • Pain management is extremely important in all perioperative phases.  

       • This point of view is consistent with the consideration that pain is "unphysiologic". 

       • Preoperative pain may cause hypertension and other effects which may cause cardiovascular problems.  

       • Similarly, inadequate post-operative pain management may contribute to postoperative cardiac morbidity/mortality

  4. Regional anesthesia

•  Some circumstances in which sedative-hypnotic (depressant) pharmacological premedication would NOT be warranted:

  1. In the hypovolemic patient

  2. In the presence of significant, severe pulmonary disease (additional respiratory depression associated with sedative-hypnotics would be ill-advised)

  3. Intracranial pathology

  4. Reduced level of consciousness

  5. Probably not in elderly patients

  6. Newborns (< 1 years of age)

• Factors that influence the choice those drugs for premedications and associated dosages

  • Whether the surgery is classified as "inpatient" or "outpatient"

  • Whether the surgery is being performed as an elective or emergency procedure

  • Concerns about the ability of the patient to tolerate the drug

  • Patient age and weight and physical status

  • Anxiety level of the patient-Recall that an anxious patient is likely to have elevation of circulating catecholamines which may cause a suboptimal cardiovascular preoperative state

  • Whether the patient has had an adverse response to the particular medication during a previous procedure-This consideration emphasizes how important an adequate history or chart review is in deciding medication choice.

• ³Routes of Administration:

  • Most common = intramuscular

    • Complications associated with intramuscular administration:

      • Sciatic nerve injury

      • Suboptimal drug absorption

      • Frequently "intramuscular" injection is actually deposited in adipose tissue, not muscle [frequency = 95% for women; 85% for men]

  • Administration for children (children may find needles and rectal administration objectionable)

    • Intranasal administration for children may be best; intranasal route of administration results in more rapid onset (compared to oral) with for example midazolam (Versed) and is also  beneficial because the approach does not require patient cooperation

  • Incremental intravenous sedation -- problem

    • Enough time must be allowed for the drug to take effect before additional dosage delivery

  • Oral premedication -- problem

    • Peak effect may not be realized before induction and significant and prolonged drug presence may complicate emergence following short surgical procedures [residual premedication, taken orally, maybe removed by stomach suctioning after induction]

Benzodiazepines

• Overview:

  • Most commonly used sedative/anxiolytic

  • Anxiolytic effectiveness is observed at dosages which do not result in cardiopulmonary depression or excessive sedation

  • Certain benzodiazepines also exhibit significant anterograde amnesia (amnesia subsequent to drug administration).  

    •  Examples of these benzodiazepines include midazolam (Versed) and lorazepam (Ativan).

    •  These agents may also cause, on predictably, some degree of retrograde amnesia as well.

  • Benzodiazepines may also be used the night before schedule surgery in management of pre-surgical insomnia-- examples include lorazepam (Ativan), temazepam (Restoril), and triazolam (Halcion)

  • Sometimes benzodiazepines used pre-surgically can result in prolonged and excessive sedation.  Patients receiving lorazepam (Ativan) at high dosages (total dose > 4 mg orally at 5 ug/kg) may be most susceptible to this excessive sedation.  

    • A benzodiazepine antagonist, flumazenil (Romazicon) may be used to reverse benzodiazepine effects.

  • Intramuscular injection of diazepam (Valium) may be painful because diazepam (Valium) is dissolved in the irritating solvent propylene glycol; intramuscular injections of midazolam (Versed) does not cause local irritation since the chemical characteristics of midazolam (Versed) do not require the use of propylene glycol as a solvent (an aqueous solvent is used)

*Medication may be administered by the intravenous route as well

•  Adverse Effects: benzodiazepines

  •  Major adverse effects

    • Respiratory depression

    • Reduction in cognitive and motor function

  •  Inpatient considerations:

    • If cognitive function need not be immediately returned to normal following procedure, lorazepam (Ativan) (oral) may be appropriate the morning of surgery

  •  Outpatient considerations:

    • Diazepam (Valium) (oral)

    • Midazolam (Versed) (IV), particularly appropriate

  • Factors/conditions which increase likelihood of preoperative excessive sedation associated with the use of benzodiazepines and other sedative hypnotics:

    • Infancy, advanced age (elderly patients), chronic debilitating disease or malnutrition, pregnancy, renal dysfunction, hepatic dysfunction, pulmonary dysfunction, adrenal insufficiency, myasthenia gravis, myotonia, sickle cell disease, acute drug/ethanol intoxication⁵.

• ³Midazolam (Versed) and diazepam (Valium) comparisons:

  • Pharmacokinetic issues:

    • Midazolam (Versed): short half-life (1-4 hours); diazepam (Valium), including active metabolites: long half-life 20-100 hours

    • In elderly patients, diazepam (Valium) half-life may be extended to several days (midazolam (Versed) half-life may be extended by eight hours)

  •  Diazepam (Valium) metabolites: oxazepam which is Serax and desmethyldiazepam are active

  •  Weak midazolam (Versed) metabolites suggest that in the outpatient setting, midazolam (Versed) would be preferred.  Quicker recovery and  greater amnesia have been found with midazolam (Versed).

  • Midazolam (Versed) in combination with opioids: cautious use in view of possible respiratory depression leading to inadequate oxygenation.  Nalbuphine (0.2 mg/kg) and midazolam (Versed) (0.09 mg/kg) may be the most appropriate combination in order to minimize respiratory complications at least in patients undergoing minor oral surgery

•   Pediatric uses of  Midazolam (Versed)³:

  • Oral midazolam (Versed) (0.5 mg/kg) is useful in preventing "facemask phobia"

  • Following oral administration (midazolam (Versed), 0.5 mg/kg) the child is typically easily separated from parents and willing to accept monitoring and facemask

  • At a midazolam (Versed) dosage of 0.75 mg/kg, most pediatric patients (90%) undergo induction without crying or combative behavior

  • At these dosages, midazolam (Versed) effects last <  1 hour and do not appear to prolong recovery

  • Midazolam (Versed) administration (occasionally in combination with atropine, e.g.) can be facilitated by mixing with cherry syrup or with a melted popsicle.

  •  Special circumstances:

    •  In pediatric patients with congenital heart disease, midazolam (Versed) may improve oxyhemoglobin saturation in most cases; however in some children with cyanotic heart disease (3 of 17 tested) desaturation may occur with a reduction of greater than 10%.  

      • Accordingly,  pulse oximetry monitoring is essential.

  • Children with a compromised airway: midazolam (Versed) premedication would not be advised because apnea following midazolam (Versed) administration may be associated with an inability to mask ventilate

    • Crying itself (which may be made less likely by midazolam (Versed) administration) can worsen airway obstruction in the presence of, for example, epiglottitis or laryngeal papillomatosis, a condition of multiple papilloma grows on the larynx caused by a viral infection-this condition occurs with approximately equal frequency and children and adults.  

     

• Intranasal midazolam (Versed) administration (0.2 mg/kg)

  • Less patient cooperation required (appropriate for combative children)

  • Quicker onset compared to oral Route of Administration

  • Occasionally (rare), midazolam (Versed) made evoked a hyperexcitability reaction-some anesthesia providers may wish to employ midazolam (Versed) only with relatively uncooperative patients

• ³Lorazepam (Ativan)

  • Overview

    • No active metabolites; short half-life (approximately 15 hours)

    • Half-life not influenced by patient age

  • Pharmacokinetic/metabolism characteristics

    • Reduced, compared to diazepam (Valium), rate of CNS access secondary to relatively less lipophilicity

    • Onset of action for both diazepam (Valium) and lorazepam (Ativan) is similar, about 30-60 minutes

    • CNS effects e.g. psychomotor impairment, may be observed for 12 hours following the single lorazepam (Ativan) dose

    • Metabolism:

      • Glucuronidation (conjugation) followed by renal excretion

      • Glucuronidation reactions tend to be less susceptible to effects of aging or hepatic disease, i.e. typically no significant change in half-life as a function of age or liver dysfunction

  • Comparing lorazepam (Ativan) and diazepam (Valium):

    • Dosage -- 2 mg orally of lorazepam (Ativan) is about equal to 10 mg oral diazepam (Valium)

    • Sedation following a single 2 mg dose less about five hours

    • At higher dosages, such as 5 mg, anterograde amnestic effects may last up to about eight hours

    • Disorientation following the 5 mg dose may last as long as 17 hours; this finding suggests that the upper dosage limit for lorazepam (Ativan) perhaps should be 4 mg

    • Diazepam (Valium) --

      • At the 10 mg level: typically no amnesia

      • At the 20 mg level, about 30% of patients exhibit amnesia (4 mg of lorazepam (Ativan) (oral) results in an amnesia frequency of > 70%)

  • Lorazepam (Ativan) uses:

    • Appropriate for patients undergoing major surgical procedures which will be followed by intensive care unit monitoring

    • Advantage for seriously ill (critically ill) patients include:

      • Absence of myocardial depression or vascular smooth muscle relaxation even at doses above 9 mg 

    • Concerning typical premedication in patients with heart disease, sedative and anxiolytic action of flurazepam (Dalmane) (orally administered; 0.06 mg/kg, administered 90 minutes prior surgery) was comparably effective to a more traditional premedication regimen consisting of intramuscular morphine (0.1 mg/kg) combined with scopolamine

• 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, 2001

• ⁵Kathleen R. Rosen and David A. Rosen, "Preoperative Medication" pp. 61-70 in  Principles and Procedures in Anesthesiology (Philip L. Liu, ed) J. B. Lipincott Company, Philadelphia, 1992