Section 2: Scientific Principles
Part B: Intravenous Anesthetics
Chapter 10: Intravenous Opioid Anesthetics

Neuroleptanalgesia-Anesthesia

In 1949, Laborit and Huygenard 864  introduced the concept of an anesthetic technique that blocked not only cerebrocortical responses but also some cellular, endocrine, and autonomic mechanisms usually activated by surgical stimulation. This state was called “ganglioplegia” or “neuroplegia” (artificial hibernation) and was achieved by the use of a lytic cocktail consisting of chlorpromazine, promethazine, and meperidine. From this idea, De Castro and Mundeleer 865  derived the concept of neuroleptanalgesia, which involved the combination of a major tranquilizer (usually the butyrophenone droperidol) and a potent opioid analgesic (fentanyl) to produce a detached, pain-free state of immobilization and insensitivity to pain. Neuroleptanalgesia is characterized by analgesia, absence of clinically apparent motor activity, suppression of autonomic reflexes, maintenance of cardiovascular stability, and amnesia in most, but not all, patients. The addition of an inhalation agent, usually N2O, improves amnesia and has been called neuroleptanesthesia.

“Neuroleptic” drugs traditionally include the phenothiazines (e.g., chlorpromazine) and the butyrophenones (e.g., haloperidol and droperidol). The phenothiazines are rarely used as an anesthetic adjuvant in the United States because of associated hypotension. Droperidol can also cause hypotension, but it is usually less severe and transient. Sedation after droperidol, especially after at least 0.1 mg•kg– 1, may last much longer than the analgesic used (e.g., fentanyl) and may result in a patient who is apparently calm yet suffering from pain and mental anguish. 866  The commercial preparation of droperidol-fentanyl (Innovar) is frequently the principal component of neuroleptanalgesia for monitored anesthesia care when analgesia and a tranquil patient are desirable. Innovar is also commonly used in a balanced anesthetic technique that usually employs N2O.

Butyrophenones cause sedation, tranquility, immobility, and antiemesis. One of their side effects includes an extrapyramidal syndrome with face and neck dyskinesia, oculogyric crises, torticollis, agitation, and hallucinations. Droperidol, like other butyrophenones, affects GABA receptors and alters the balance of dopamine and acetylcholine in certain brain sites. Droperidol‘s effects on dopamine receptors (antidopaminergic) not only account for much of the drug‘s behavioral effects but also cause its side effects. Administering droperidol alone, without analgesics or other sedatives, often produces feelings of discomfort or dysphoria in patients. The cardiovascular effects of droperidol are most often limited to mild hypotension that is thought to be mediated through a-adrenergic blockade. Droperidol has an antiarrhythmic action that is effective during halothane anesthesia or following epinephrineinduced arrhythmias. 867  Droperidol may be of some benefit in patients with Wolff-Parkinson-White syndrome. 868  There is little respiratory depression induced by droperidol, although significant variability exists, and occasional respiratory depression may be noted. Droperidol and other butyrophenones may enhance hypoxic-induced increases in ventilation in humans because of their antidopaminergic effects at the carotid body. 869 

Droperidol can be used as a premedicant (0.025–0.075 mg•kg– 1 IM), an antiemetic (0.01–0.02 mg•kg– 1 IV), an adjunct for awake intubations (0.025–0.1 mg•kg– 1 IV) and as treatment for agitated, belligerent, or psychotic patients (0.05–0.2 mg•kg– 1 IV or IM). Neuroleptanalgesia with droperidol and an opioid such as fentanyl may still be useful for “monitored anesthesia care” in a variety of clinical circumstances including ophthalmic operations, endoscopic and bronchoscopic examinations, neurodiagnostic procedures, and excision of epileptogenic foci. Combining alfentanil (5 mg•kg– 1 as a bolus and/or an infusion, 1.5 mg•kg– 1 •min– 1 ) with droperidol and N2O has been reported to be useful in providing patient comfort for awake craniotomies. More recently, remifentanil, in combination with propofol, has been used successfully as an anesthetic technique for awake craniotomy. 870 

In the past, neuroleptanesthesia with droperidol and fentanyl proved useful in patients undergoing neurologic, cardiac, and general surgical procedures. Neuroleptanesthesia has also been proposed for removal of pheochromocytomas. 871, 872 

Neuroleptanalgesia or neuroleptanesthesia is contraindicated in patients receiving monoamine oxidase inhibitors (MAOI), in those who abuse drugs or alcohol, or those with Parkinson disease. The introduction of newer drugs with superior pharmacologic properties, combined with “fast track” approaches in most surgical patients, has reduced the utility of neuroleptic techniques.