Intravenous anaesthetics

From greek.doctor

Intravenous anaesthetics (IV anaesthetics) are drugs used to induce and maintain general anaesthesia which are administered intravenously (as opposed to inhaled anaesthetics).

While inhaled anaesthetics can be “fast-acting”, they’re still relatively slow and need a few minutes to kick in. Intravenous anaesthetics can cause anaesthesia in as little as 20 second. The anaesthetic effect stops when the drug redistributes from the CNS to other tissues. The duration of action is 5 – 10 minutes.

IV anaesthetics can be given in boluses or as continuous infusion via IV.

Compounds

The important IV anaesthetics are:

  • Propofol
  • Etomidate
  • Ketamine
  • Barbiturates
    • Thiopental
    • Methohexital

Although not technically anaesthetic agents, benzodiazepines and opioids can be combined with intravenous anaesthetics or used alone for conscious sedation:

Indications

All IV anaesthetics can be given in single IV doses for:

  • Induction of anaesthesia, which is later maintained by an inhalation anaesthetic
  • Induction of a short (5 – 10 minute) anaesthesia, for short surgeries or painful interventions

Some IV anaesthetics (especially propofol) can be given in continuous infusion for:

  • Production of long-lasting anaesthesia (total intravenous anaesthesia (TIVA))
  • Sedation of patients (in low doses)

Intravenous anaesthetics can either be used for induction of general anaesthesia alone (and using an inhaled anaesthetic for maintainance), or be used for both induction and maintainance. The latter is called total intravenous anaesthesia (TIVA). Propofol is the most commonly anaesthetic used for TIVA, usually combined with remifentanil.

  • Propofol is perhaps the most widely used IV anaesthetic as it has a rapid onset of action, within 20 seconds. It’s the standard drug for induction of anaesthesia, it can be used for TIVA, or for sedation of patients in the ICU.
  • Etomidate has the least depressive effect on the cardiovascular system, so it’s the preferred anaesthetic for induction of patients with haemodynamic instability or heart conditions. It cannot be used for maintainance as it inhibits the synthesis of cortisol.
  • Ketamine induces a state of dissociative anaesthesia, a form of anesthesia characterized by catalepsy, catatonia, analgesia, and amnesia. It has a stimulatory effect on the cardiovascular system. It’s especially used in emergency situations with polytrauma, shock, severe asthma. In low doses it can be used for pain management, in moderate doses it can cause conscious sedation, and in high doses it causes anaesthesia. Some believe it may be used to treat depression.
  • Benzodiazepines like midazolam, diazepam, lorazepam are used for conscious sedation during procedures like colonoscopies. They can be combined with opioids for general anaesthesia.
  • Opioids like remifentanil can be combined with propofol to provide TIVA.
  • Barbiturates are used for patients who have increased intracranial pressure.

The combination of fentanyl and a certain antipsychotic called droperidol was previously used to induce neuroleptanalgesia, a state where the patient is conscious but indifferent to pain. This is rarely used nowadays but has been asked on the exam.

Mechanism of action

All intravenous anaesthetics except ketamine activate the GABAA receptor. They may also inhibit receptors like neuronal acetylcholine receptor and NMDA glutamate receptor.

Ketamine blocks NMDA glutamate receptors in the CNS.

Pharmacokinetics

IV anaesthetics are lipophilic drugs that distribute rapidly to well-perfused organs like the brain immediately after IV injection. This rapid distribution is what causes anaesthesia to kick in so quickly.

Later the anaesthetic will redistribute to poorly perfused organs like muscles, skin and adipose tissue. When this happens the level of anaesthetic in the CNS will drop, causing the patient to recover from anaesthesia. In people with decreased perfusion or muscle and adipose tissue mass, this redistribution will take longer, and the anaesthesia will last longer as well.

The anaesthetic action of IV anaesthetics is terminated by redistribution and not by elimination. Because all IV anaesthetics follow the same pattern of redistribution, they all cause similar duration of action, 5 – 10 minutes.

All IV anaesthetics are eliminated by biotransformation. All IV anaesthetics have similar half-life of around 1 – 4 hours, except thiopental, which has a half-life of 12 hours. Because thiopental has such a long elimination half-life it would accumulate in the body if given as a continuous infusion. Thiopental is instead given in doses. All other IV anaesthetics have short half-lives and will not accumulate in the body, so they can be given as continuous infusion.

Adverse effects

  • Propofol has depressive and vasodilatory effects on the cardiovascular system. Administration of propofol can be painful at the infusion site
  • Etomidate inhibits cortisol synthesis.
  • Ketamine causes unpleasant experiences like weird dreams and hallucinations when recovering from the anaesthesia.

Propofol infusion syndrome

Propofol infusion syndrome (PRIS) is a rare but potentially lethal side effect of propofol. The drug can uncouple the oxidative phosphorylation in the mitochondria, which can cause lactic acidosis, rhabdomyolysis and acute renal failure.