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Rational Administration of Intravenous Anesthesia

General anesthesia requires that adequate levels of anesthetic drugs be rapidly

attained in the brain and that they be maintained during the time required for surgery. This

is a concept that applies equally well to anesthesia achieved by inhalation anesthetics,

intravenous drugs, or both. However, the routine clinical practice of anesthesia by manyclinicians seems to approach the goal of maintaining therapeutic levels of anesthesia

differently depending on whether inhalation or intravenous anesthetics are used. This

mystifies me. Why do clinicians continuously administer inhalation drugs with the aid of a

vaporizer, but intermittently administer intravenous drugs by bolus injections?

With inhalation drugs the minimum alveolar concentration (MAC) is known and is

achieved relatively quickly (usually by giving more than the desired brain concentration

"overpressurized") and then equilibration of inspired to expired gaseous anesthetic occurs.

Maintenance of inhalation anesthesia is achieved by continuously administering the drug

with this equilibrium. With intravenous drugs a bolus (usually a large "overdose") is given toinduce anesthesia rapidly. However, maintenance of intravenous anesthesia is

conventionally done by an inconstant infusion (intermittent bolus) or by a constant

fixed/dose infusion that seldom achieves equilibrium between blood and brain. There usually

is an ever changing blood and consequent brain level in contrast to the equilibrium achieved

with an inhalation anesthetic.

It has never seemed rational to administer intravenous drugs intermittently and not

by continuous infusion. Ideally the infusion rate would be determined by the known

pharmacokinetics of the drug to achieve constant bloodbrain levels. Figure 1 shows the

contrast between continuous infusion and intermittent bolus administration. Problems with a

bolus technique are obvious: there are great variations in the blood levels, which cause

anesthesia to be too deep right after the bolus and then too light before the next bolus.

Repeated bolus administrations also tend to promote drug accumulation in patients, making

it more difficult to arouse patients at the conclusion of surgery.


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It has not previously been routine to administer intravenous drugs continuously for two

principal reasons: (1) most anesthetic drugs were not suited for continuous infusions, and

(2) infusion pumps were not simple and easy to operate. These reasons are no longer valid.

Drugs such as midazolam, propofol, alfentanil, and remifentanil are ideally suited to

continuous infusion. Likewise, infusion technology has advanced to the point that

sophisticated pumps with preset programs make it easy to set a precise, individualized

infusion rate for continuous infusion.

Another important advance in infusion anesthesia has been the use of a computer to

administer anesthetics continuously using pharmacokinetic principles.1,2 This technology is

called "target-controlled infusion" (TCI). The pharmacokinetics of the anesthetic drug to be

used are in a "chip" within the computer-controlled syringe pump. The clinician sets a

desired therapeutic blood or brain (effect site) level of anesthetic and the computer infuses

the drug, first by rapid infusion to attain a therapeutic level, and then by continuous

infusion at an exponentially declining rate to maintain a constant drug level in the patient.

This technology has been described for propofol,3,4 and has been used worldwide with the

Diprifusor in over 13 million patients.5

What is the advantage of TCI over other continuous infusion methods? The

differences between TCI and continuous manual infusion are not great, but TCI is superior

to an intermittent bolus.6 The major advantage of TCI is that it produces a stable

intravenous anesthetic that permits the clinician to titrate to the required level with less

chance of overdosing or underdosing the patient. This is the same advantage that the

vaporizer provides the clinician using an inhalation anesthetic: relatively constant blood

(brain) levels are easily titrated to the desired effect.


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At some point in the future, intravenous anesthetic drugs will be delivered by

intelligent infusion pumps that are able to individualize the administration based on the

pharmacokinetics of the drug in that patient, and maintain a desired brain concentration

based on a feedback signal. Sophisticated systems of the future will include a "closed-loop"

intravenous and inhalation anesthesia system (Figure 2). The clinician would activate the

system by choosing a desired drug level utilizing the processed electroencephalographic

(EEG) reading. Processed EEG signaling similar to the existing bispectral (BIS) system now

available will undoubtedly be used to close the loop.7 Such an automated system will be able

to administer anesthetic drugs to rapidly attain and maintain the patient at the desired level

of anesthesia. The depth of anesthesia or sedation (in nongeneral anesthesia settings) will

be maintained automatically, akin to cruise control of an automobile. This technology will

also have applications in intensive care units, in emergency departments, and in a host of

other nonoperating room settings.

Anesthesiologists will teach others the science behind the seemingly simple patient care

applications of these new drug delivery technologies. This "robotic-like" approach toanesthesia and sedation cannot be viewed as a threat to the practice of anesthesia, but

must be embraced as another step in the progress of the field of anesthesiology.7 It will

allow anesthesiologists to improve patient care in multiple settings even when not

personally present!


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CASE DISCUSSION: PREMEDICATION OF THE SURGICALPATIENT

An extremely anxious 17-year-old woman presents for uterine dilatation and

curettage. She demands to be asleep before going to the operating room and does not want

to remember anything.

What Are the Goals of Administering Preoperative Medication?

Anxiety is a normal emotional response to impending surgery. Minimizing anxiety is

usually the major goal of preoperative medication. For many patients, the preoperative

interview with the anesthesiologist allays fears more effectively than sedative drugs. Other

psychological objectives of preoperative medication include relief of preoperative pain and

perioperative amnesia.

There may also be specific medical indications for preoperative medication:

prophylaxis against postoperative nausea and vomiting (5-HT3s) and against aspiration

pneumonia (eg, antacids), prevention of allergic reactions (eg, antihistamines), or

decreasing upper airway secretions (eg, anticholinergics). The goals of preoperative

medication depend on many factors, including the health and emotional status of the

patient, the proposed surgical procedure, and the anesthetic plan. For this reason, the

choice of anesthetic premedication is not routine and must follow a thorough preoperative

evaluation.

What Is the Difference between Sedation and Anxiety Relief?

This distinction is well illustrated by the paradoxic effects of droperidol. Patients may

appear to an observer to be adequately sedated but on questioning may be quite anxious.

Anxiety relief can be measured only by the patient.

Do All Patients Require Preoperative Medication?

Nocustomary levels of preoperative anxiety do not harm most patients. Some

patients dread intramuscular injections, and others find altered states of consciousness

more unpleasant than nervousness. If the surgical procedure is brief, the effects of some

sedatives may extend into the postoperative period and prolong recovery time. This is

particularly troublesome for patients undergoing ambulatory surgery. Specific

contraindications for sedative premedication include severe lung disease, hypovolemia,

impending airway obstruction, increased intracranial pressure, and depressed baseline


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mental status. Premedication with sedative drugs should never be given before informed

consent has been obtained.

Which Patients Are Most Likely to Benefit from Preoperative

Medication?

Some patients are quite anxious despite the preoperative interview. Separation of

young children from their parents is often a traumatic ordeal, particularly if they have

endured multiple prior surgeries. Chronic drug abusers may benefit from premedication to

decrease the risk of withdrawal reactions. Medical conditions such as coronary artery

disease or hypertension may be aggravated by psychological stress.

How Does Preoperative Medication Influence the Induction of

General Anesthesia?Some preoperative medications (eg, opioids) decrease anesthetic requirements and

can smooth induction. Intravenous administration of these medications just prior to

induction is a more reliable method of achieving the same benefits, however.

What Governs the Choice between the Preoperative MedicationsCommonly Administered?

After the goals of premedication have been determined, the clinical effects of the

agents dictate choice. For instance, in a patient experiencing preoperative pain from a

femoral fracture, the analgesic effects of an opioid (eg, fentanyl, morphine, meperidine) will

decrease the discomfort associated with transportation to the operating room and

positioning on the operating room table. Respiratory depression (drops in oxygen

saturation), orthostatic hypotension, and nausea and vomiting make opioid premedication

less desirable.

Barbiturates are effective sedatives but lack analgesic properties and can produce

respiratory depression. Benzodiazepines relieve anxiety, often provide amnesia, and are

relatively free of side effects. Like barbiturates, however, they are not analgesics. Diazepam

and lorazepam are available orally. Intramuscular midazolam has a rapid onset (30 min)

and short duration (90 min), but intravenous midazolam has an even better

pharmacokinetic profile. Dysphoria, prolonged sedation, and -adrenergic blockade limit the

clinical usefulness of droperidol. Other preoperative medications are discussed in

subsequent chapters: anticholinergics in Chapter 11 and antihistamines, antiemetics, and

antacids in Chapter 15.


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Which Factors Must Be Considered in Selecting the AnestheticPremedication for This Patient?

First, it must be made clear to the patient that for safety reasons, anesthesia is not

induced outside the operating room. Long-acting agents such as morphine or droperidol

would not be a good choice for an outpatient procedure. Lorazepam and diazepam can alsoaffect mental function for several hours. One alternative is to establish an intravenous line

in the preoperative holding area and titrate small doses of midazolam, with or without

fentanyl, using slurred speech as an end point. At that time, the patient can be taken to the

operating room. Vital signsparticularly respiratory ratemust be continuously monitored.

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