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 many clinicians 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 to induce 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 blood brain 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.

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.

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 to anesthesia 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!

CASE DISCUSSION: PREMEDICATION OF THE SURGICAL PATIENT

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

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 Medications Commonly 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 of (90 min), but intravenous midazolam has an are even better in pharmacokinetic profile. Dysphoria, prolonged sedation, and clinical usefulness droperidol. Other preoperative -adrenergic blockade limit the discussed

medications

subsequent chapters: anticholinergics in Chapter 11 and antihistamines, antiemetics, and antacids in Chapter 15.

Which Factors Must Be Considered in Selecting the Anesthetic Premedication 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 also affect 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.