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.
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.
Effective delivery of TIVA requires the clinician to have a good knowledge and understanding of pharmacokinetics, pharmacodynamics, and pharmacokinetic–pharmacodynamic (PK-PD) modeling.
Important drug characteristics include induction dose, rate of administration, and ke0 (rate constant for the elimination of drug from the effect compartment; drugs with small ke0 values take longer to equilibrate between the blood and the effect compartment or biophase). Thus for a rapid sequence induction, drugs with a large ke0 are preferable (viz., propofol, thiopental, remifentanil, and alfentanil compared with midazolam, ketamine, and fentanyl).
Drug interactions are important in TIVA. Excepting 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. 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.
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.
If the patient shows signs of response during TIVA, additional IV supplementation can be achieved by bolus doses or by increasing the infusion rate, or the targeted concentration if using target-controlled infusion (TCI).
The elimination half-life and systemic clearance are not useful in TIVA for determining the offset of IV drugs. The context-sensitive half-time (CSHT) is more relevant, and modeled data and dynamic measurements correlate well.
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, coadministered therapies, and disease states.
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.
In 2011 we are still without any one drug that can provide all the requirements of anesthesia (ie, unconsciousness, analgesia, amnesia, and muscle relaxation). Consequently, administration of several different agents is needed to produce the desired end result. The use of intravenous agents to achieve these goals began with the introduction of the rapidly acting barbiturates in 1934. Despite the disastrous consequences after the use of thiopental at Pearl Harbor in 1941, intravenous anesthesia is now well established as an appropriate alternative to the traditional approach of volatile anesthetics alone; indeed, sometimes it is the preferred alternative. Further, intravenous anesthesia is a fundamental component ...