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  1. The availability of drugs with short blood-brain equilibration times (especially those with an ester linkage) enables the clinician to use intravenous anesthetics and analgesics where controllability is easy and recovery rapid.

  2. Total intravenous anesthesia (TIVA) offers some important advantages over inhalation anesthetics, including rapid recovery with minimal hangover and a low incidence of nausea and vomiting. TIVA may be the technique of choice for some operations.

  3. Effective delivery of TIVA requires the clinician to have good knowledge and understanding of pharmacokinetics, pharmacodynamics, and pharmacokinetic-pharmacodynamic (PK-PD) modeling.

  4. Important drug characteristics include induction dose, rate of administration, and ke0 (rate constant for the elimination of drug from the effect compartment; drugs with smaller ke0 values take longer to equilibrate between the blood and the effect compartment or biophase). Thus, for a rapid sequence induction, drugs with a greater ke0 are preferable (viz, propofol, thiopental, remifentanil, and alfentanil compared with midazolam, ketamine, and fentanyl).

  5. Drug interactions are important in TIVA. Except for ketamine, opiates and hypnotics potentiate each other and can result in synergistic cardiovascular and respiratory depression. This means the doses of each can be reduced when combined. There is a ceiling to the potentiating effect of the opiates, beyond which there is an increased incidence of adverse side effects and often delayed onset of spontaneous ventilation at the end of surgery.

  6. Ketamine is the only hypnotic drug with established analgesic properties; there are few data suggesting that the S (+) isomer has major advantages over the racemic mixture.

  7. If the patient shows signs of response during TIVA, additional intravenous supplementation can be achieved by bolus doses or by increasing the infusion rate or the targeted concentration if using target-controlled infusion (TCI).

  8. The elimination half-life and systemic clearance are not useful for determining the offset of intravenous drugs when using TIVA. The context-sensitive half-time (CSHT) is more relevant, and modeled data and dynamic measurements correlate well.

  9. Context-sensitive decrement times are useful indices of recovery from anesthesia. Recovery is influenced by other factors apart from the CSHT, including patient characteristics such as age, sex, body habitus, concurrent therapies, and disease states.

  10. Knowledge of the context-sensitive decrement times for opiates and hypnotics allows appropriate choice of drugs for the maintenance of anesthesia. CSHT also helps determine which infusions should be terminated at the end of anesthesia and which should be terminated some time beforehand.

  11. Two newer agents (remimazolam and remifentanil) are proving their importance in TIVA as their PK-PD profiles allow safer and better titration of dose to effect without risk of prolonged overdosage; their pharmacokinetic characteristics also aid patient recovery.

  12. Two other drugs presently in clinical evaluation (cyclopropyl-methoxycarbonyl metomidate [ABP-700] and alfaxalone in cyclodextrin [Phaxan-CD]) may prove useful additions to TIVA.


At this writing in 2016, a single drug that can provide all the requirements of anesthesia (ie, unconsciousness, analgesia, amnesia, and muscle relaxation) was still unavailable. Consequently, administration ...

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