Intravenous Anesthetics: Barbiturates & Benzodiazepines

• Intravenous anesthetics induce rapid onset of stage III surgical anesthesia.
• They are easy to administer but can't be reversed by ventilation, requiring caution to avoid severe medullary depression.

Short-Acting Barbiturates

• Thiopental (Pentothal) and Methohexital (Brevital sodium) are examples.
• These enhance GABA effects on GABAA channels and directly open them at high doses, even without GABA.
• They depress respiratory and cardiac function, leading to decreased MAP and CO.
• These do not increase cerebral blood flow, which is an advantage for patients with head trauma or brain tumors.
• They are metabolized by the liver.
• These induce hepatic ALA synthase, which is the rate-limiting step in heme synthesis, potentially precipitating acute intermittent porphyria.
• They exhibit high lipid solubility for rapid induction and rapid redistribution from the CNS allows for quick recovery.

IV Benzodiazepines

• Diazepam (Valium) and Midazolam (Versed) are common examples, with Midazolam being water-soluble.
• These enhance GABA effects on GABAA channels, but unlike barbiturates, inhalation anesthetics, and ethanol, they do not open channels in the absence of GABA.
• These depress the CNS to a level below true anesthesia.
• They provide preoperative sedation and amnesia
• They depress respiratory function.

Flumazenil

• It is a benzodiazepine receptor antagonist.
• It accelerates recovery from benzodiazepine sedation.
• It makes respiratory depression less reversible.

Ketamine (Ketalar)

• It induces dissociative anesthesia with amnesia, catatonia, and analgesia.
• Patients may not lose consciousness, and their eyes may remain open.
• It has rapid, short duration.
• It is chemically related to PCP.
• It blocks NMDA receptors, which are excitatory receptors activated by glutamate.
• Ketamine is the only IV anesthetic that produces cardiovascular stimulation by centrally stimulating the sympathetic system, increasing HR, blood pressure, and cardiac output.
• It is useful for poor-risk geriatric patients and those in cardiogenic or septic shock.
• It increases cerebral blood flow and intracranial pressure.
• Emergence reactions from it include vivid dreams and hallucinations.
• Diazepam or midazolam given prior to ketamine reduces the incidence of such reactions.

Propofol (Diprivan)

• It is an extremely important IV anesthetic.
• It enhances GABAA-mediated inhibition.
• It has a very rapid onset and recovery, especially useful for outpatient surgery, since it is rapidly metabolized by the liver.
• It is also an antiemetic that reduces postoperative nausea and vomiting.
• It is used for both induction and maintenance.
• It can depress respiratory function and cause marked hypotension due to vasodilation.
• It is a negative inotrope.
• Prolonged infusion does not increase its half-life.

Etomidate (Amidate)

• It exhibits minimal cardiovascular and respiratory depression.
• It is safe to use in patients with limited cardiovascular reserves.
• It enhances GABAA-mediated inhibition.
• It lacks analgesic effects, requiring the co-administration of opioids.
• It offers rapid onset and recovery due to, and is extensively metabolized by the liver.
• Adverse effects include pain on injection, involuntary muscle movements in 50% of patients, postoperative nausea and vomiting, and adrenal suppression via inhibition of steroidogenesis, blocking 11-β-hydroxylation and decreasing cortisol after a single dose.

Dexmedetomidine (Precedex)

• It is a highly selective α2-adrenergic agonist.
• It induces hypnosis through stimulation of α2 receptors in the locus coeruleus, thus resembling a physiologic sleep state by activating endogenous sleep pathways.
• This also provides an analgesic effect in the spinal cord
• It decreases heart rate and systemic vascular resistance, leading to decreased blood pressure.
• It has mild respiratory effects.
• It is water soluble parenteral formulation.
• It provides sedative and analgesic effects without respiratory depression.
• It is used for short-term sedation of intubated/ventilated patients in the ICU.
• It serves as an adjunct to general anesthesia or provides sedation during awake fiberoptic tracheal intubation or regional anesthesia.
• It decreases the dose requirements for inhaled and injected anesthetics.

Opioid Analgesics

• Fentanyl (Sublimaze) is a potent mu opioid receptor agonist with a shorter duration of action than other opioids.
• High IV doses cause chest wall rigidity and prolong postoperative respiratory depression.
• Remifentanil (Ultiva) is an extremely short-acting opioid rapidly metabolized by esterases in blood and muscle.
• Opioid analgesics have minimal cardiovascular effects, making them advantageous for patients with minimal circulatory reserve.
• Their effects can be reversed by the antagonist naloxone.

Neuroleptanesthesia

• It is a combination of fentanyl, droperidol (a neuroleptic related to haloperidol and dopamine receptor blocker), and nitrous oxide.
• If droperidol is given to control nausea and vomiting, remember it has no analgesic effect.
• N₂O often induces nausea and vomiting.

Characteristics of Intravenous Anesthetic Agents

• Etomidate features: Rapid onset and moderately fast recovery, Cardiovascular stability; decreased steroidogenesis, and involuntary muscle movements
• Ketamine features: Moderately rapid onset and recovery, Cardiovascular stimulation; increased cerebral blood flow; emergence reactions impair recovery
• Midazolam features: Slow onset and recovery; flumazenil reversal available, Used in balanced anesthesia and conscious sedation; cardiovascular stability; marked amnesia
• Propofol features: Rapid onset and rapid recovery, Used in induction and for maintenance; hypoten- sion; useful antiemetic action
• Thiopental features: Rapid onset and rapid recovery (bolus dose)- slow recovery following infusion, Standard induction agent; cardiovascular depression; avoid in porphyrias
• Fentanyl features: Slow onset and recovery; naloxone reversal available, Used in balanced anesthesia and conscious sedation; marked analgesia