Intravenous induction agents

Watkins J, Ward AM, Thornton JA Adverse reactions to intravenous induction agents. Br Med J 11 1978 2 1431. 

Etomidate inhibits adrenal function resulting in reduced steroidogenesis after administration of both single boluses and maintenance infusions (397). In a prospective cohort study of 62 critically ill patients who were mechanically ventilated for more than 24 hours, about half developed adrenal insufficiency on the day after intubation. Administration of a single intravenous dose of etomidate 0.2-0.4 mg/kg for intubation led to a 12-fold increased risk of adrenal insufficiency (398). Etomidate should therefore be avoided as an induction agent in critical illness, in particular in patients with septic shock, among whom the incidence of adrenal insufficiency is high (399,400,401). 

The rapid-acting barbiturates, such as methohexital (Brevital), are used as intravenous anesthetics/induction agents. Advantages are rapid anesthesia and short duration of action. A disadvantage is respiratory suppression with higher doses. 

Fryer J M 2001 Intravenous induction agents. Anaesthesia and Intensive Care Medicine 2 ... 

Ketamine relaxes smooth muscles in the airways and may therefore be a useful induction agent in children with asthma (6). If endotracheal intubation is required, lidocaine 1-2 mg/kg intravenously before intubation has been recommended, although the use of a laryngeal mask airway may be more appropriate. When used in combination with midazolam by infusion, ketamine provides analgesia and prevents and relieves bronchospasm (7). 

Propofol is a short-acting intravenous induction agent, which is dissolved in a mixture of long-chain triglycerides and soya bean emulsion. It is now in general use in daycare anesthesia and is being increasingly used in infusions in intensive care units. Recovery from anesthetic doses compares favorably with that after enflurane and isoflurane (1). 

Indications Intravenous induction agent of anesthesia Category Hypnotic Half-life 3-5 hours... 

Kanto J, Aaltonen L, Himberg J-J, Hovi-Viander M. Midazolam as an intravenous induction agent in the elderly a clinical and pharmacokinetic study. Anesth Analg (1986) 65,15-20. 

The onset of action is fast (within 60 seconds) for the intravenous anesthetic agents and somewhat slower for inhalation and local anesthetics. The induction time for inhalation agents is a function of the equiUbrium estabUshed between the alveolar concentration relative to the inspired concentration of the gas. Onset of anesthesia can be enhanced by increasing the inspired concentration to approximately twice the desired alveolar concentration, then reducing the concentration once induction is achieved (3). The onset of local anesthetic action is influenced by the site, route, dosage (volume and concentration), and pH at the injection site. 

Injectable anesthetics (p. 220) are frequently employed for induction. Intravenous injection and rapid onset of action are clearly more agreeable to the patient than is breathing a stupefying gas. The effect of most injectable anesthetics is limited to a few minutes. This allows brief procedures to be carried out or to prepare the patient for inhalational anesthesia (intubation). Administration of the volatile anesthetic must then be titrated in such a manner as to counterbalance the waning effect of the injectable agent. 

Usually various anesthetic agents are combined to increase efficacy and at the same time decrease toxicity and shorten the time to recovery. For example induction of anesthesia is obtained with an intravenous agent with a rapid onset of action like thiopentone and then anesthesia is maintained with a nitrous oxide/oxygen mixture in combination with halothane or a comparable volatile anesthetic. 

Propofol can be used for induction as well as maintenance of anesthesia. It is very lipophilic and induction of anesthesia takes place within 30 seconds. After a single dose the patient awakes in approximately 5 minutes and after anesthesia by continuous intravenous administration of longer duration recovery may take 10-15 minutes. It can be used in combination with the usual range of premedications, analgesics, muscle relaxants and inhalation anesthetic agents. 

Amide-type agents include articaine, lidocaine, bupivacaine, prilocaine, mepivacain and ropiva-caine. These are metabolized in the liver by microsomal enzymes with amidase activity. The amide group is preferred for parenteral and local use. If by accident rapidly administered intravascularly these agents, especially bupivacaine but also lidocaine, can produce serious and potentially lethal adverse effects including convulsions and cardiac arrest. They can more easily accumulate after multiple administrations. Intravenous lidocaine is sometimes used for regional anesthesia, for infiltration procedures, for the induction of nerve blockade and for epidural anesthesia. However, it is also used as an antiarrhythmic. Bupivacaine is a long-acting local anesthetic used for peripheral nerve blocks and epidural anesthesia. 

Intravenous anaesthetics are mainly used for rapid induction of anaesthesia, which is then maintained by an inhalational agent. They also serve to reduce the amount of maintenance anaesthetics. 

Of the intravenous agents, ketamine and thiopentone undergo complete placental transfer. Propofol is also rapidly transferred across the placenta, and propofol infusions should be used with caution during Caesarean section when a prolonged induction to delivery time is anticipated. However, neonates clear propofol rapidly and residual effects in healthy newborn are usually negligible. 

Ensuring an adequate depth of anesthesia depends on achieving a therapeutic concentration of the anesthetic in the CNS. The rate at which an effective brain concentration is achieved (ie, time to induction of general anesthesia) depends on multiple pharmacokinetic factors that influence the brain uptake and tissue distribution of the anesthetic agent. The pharmacokinetic properties of the intravenous anesthetics (Table 25-1) and the physicochemical properties of the inhaled agents (Table 25-2) directly influence the pharmacodynamic effects of these drugs. These factors also influence the rate of recovery when the administration of anesthetic is discontinued. 

Recovery is sufficiently rapid with most intravenous drugs to permit their use for short ambulatory (outpatient) surgical procedures. In the case of propofol, recovery times are similar to those seen with sevoflurane and desflurane. Although most intravenous anesthetics lack antinociceptive (analgesic) properties, their potency is adequate for short superficial surgical procedures when combined with nitrous oxide or local anesthetics, or both. Adjunctive use of potent opioids (eg, fentanyl, sufentanil or remifentanil see Chapter 31) contributes to improved cardiovascular stability, enhanced sedation, and perioperative analgesia. However, opioid compounds also enhance the ventilatory depressant effects of the intravenous agents and increase postoperative emesis. Benzodiazepines (eg, midazolam, diazepam) have a slower onset and slower recovery than the barbiturates or propofol and are rarely used for induction of anesthesia. However, preanesthetic administration of benzodiazepines (eg, midazolam) can be used to provide anxiolysis, sedation, and amnesia when used as part of an inhalational, intravenous, or balanced anesthetic technique. 

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