Induction Agents

HPI PH, a 28-year-old GIRO woman presents to labor and delivery at 36 weeks gestation with elevated blood pressures and proteinuria, and receives a diagnosis of preeclampsia. She has a mild headache, but no right upper quadrant (RUQ) pain or visual symptoms. 

PE On physical examination she has 2+ pitting edema in her lower extremities and her hands are swollen. Lung and abdominal examination yields benign results, and she has brisk 3+ deep tendon reflexes (DTRs), but no clonus. Her fetus has a reassuring fetal heart tracing, and examination shov that her cervix is closed and noneffaced. 

Labs Laboratory tests include a CBC, type and screen, AST, ALT, and Cr. As part of her treatment, the plan is made to induce her labor. 

Cervical ripening is also accomplished in nonpharmacologic ways such as slow dilation of the cervix with an intracervical Foley catheter balloon or with laminaria tents. The laminaria are composed of seaweed and, as they absorb the fluid from the vagina and surrounding tissues, slowly expand over time. They are used more commonly in preparing the cervix for abortion than induction of labor. Acupuncture also has been cited in both cervical ripening and labor induction. 

Once the cervix has been ripened, or in patients who present with a favorable, soft cervix, labor induction can proceed with IV oxytocin (Pitocin ). This is a synthesized form of the same peptide composed of nine amino acids that is synthesized by the hypothalamus and secreted by the posterior pituitary. Although it will cause contractions beyond the late second trimester of pregnancy, these contractions do not always lead to labor. Labor also can be initiated or augmented by rupture of the amniotic and chorionic membranes, which is thought to up-regulate oxytocin receptors on the uterus and release prostaglandins. Nipple stimulation causes the increased release of oxytocin from the posterior pituitary and can be used to initiate corrtractions as well. 

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

The induction agents are highly immunosuppressive and, when given prior to some organ transplants (e.g., kidney transplant), allow for significant reductions in acute rejection... 

Thiopental remains the most popular IV induction agent. Its rapid and pleasant induction of anesthesia and its relatively low cost are among the reasons for its high acceptance rate by both the patient and the practitioner. Also, it does not induce obstructive secretions in the airway, produces little or no emesis, and does not sensitize the myocardium to endogenous catecholamines that may be released in response to the stress of surgery. It can, however, cause cardiovascular depression. 

Rapid recovery and its antiemetic properties make propofol anesthesia very popular as an induction agent for outpatient anesthesia. Propofol can also be used to supplement inhalational anesthesia in longer procedures. Both continuous infusion of propofol for conscious sedation and with opioids for the maintenance of anesthesia for cardiac surgery are acceptable techniques. 

A most important advantage of ketamine over other anesthetic agents is its potential for administration by the IM route. This is particularly useful in anesthetizing children, since anesthesia can be induced relatively quickly in a child who resists an inhalation induction or the insertion of an IV line. Ketamine has a limited but useful role as an IM induction agent and in pediatrics. 

There is good evidence that propofol exerts an anti-emetic effect. The mechanism of this is unclear, but animal studies have shown that it may involve depleting the area postrema of serotonin as well as direct GABA-mediated inhibition, or inhibition of dopamine release in the brain. This probably requires a plasma concentration of over 350 ng-mL-1, and therefore will be seen when propofol is used as an induction agent for very short cases, or when it is used as an infusion in longer cases. Nitrous oxide... 

Thiopental Rapid onset and rapid recovery (bolus dose) —slow recovery following infusion Standard induction agent causes cardiovascular depression avoid in porphyrias... 

Desflurane 0.42 1.3 6-7 < 0.05% Low volatility poor induction agent (pungent) rapid recovery... 

Barbiturates reduce hepatic blood flow and glomerular filtration rate, but these drugs produce no adverse effects on hepatic or renal function. Barbiturates can exacerbate acute intermittent porphyria by inducing the production of hepatic ct -aminolevulinic acid (ALA) synthase (see Chapter 22). On rare occasions, thiopental has precipitated porphyric crisis when used as an induction agent in susceptible patients. 

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). 

Jackson WL Jr. Should we use etomidate as an induction agent for endotracheal intubation in patients with septic shock A critical appraisal. Chest 2005 127 1031-8. 

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. 

Rifampicin is an enzyme inducer and can increase the incidence and severity of isoniazid-induced hepatitis. Carbamazepine is an enzyme induction agent and interacts with isoniazid, increasing its hepatotoxicity. Isoniazid toxicity is associated with fast acetylator genotype. Although his phenotype was unknown, the interaction with carbamazepine increases risk of this toxicity. 

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