154 Review Article Bruno Bissonnette MD FRCPC, Neuroleptanesthesia: Hilton Swan MBBS FANZCA, Patrick Ravussin MD,* current status Victor Un MD FRCPC Purpose: To review the current status and possible future of neuroleptanalgesia/anesthesia, techniques that may be nearly extinct. Souzce: Articles from 1966 to present were obtained from the Current Science and Medline databases. Search terms include neurolepananalgesia/anesthesia, conscious sedation, droperidol, benzodiazepines, propofol, keta- mine, and opioids. Information and abstracts obtained from meetings on this topic helped complete the collec- tion of information. Principal findings: Droperidol/fentanyl may still be clinically indicated in the management of surgical seizure therapy for electrocorticography. However, the high incidence of post-operative sedation and restlessness dis- courage its use for other surgical or diagnostic procedures. Many surgical interventions, once thought ideally suit- ed for neuroleptic agents, now meet better success with newer medications. The use of midazolam and/or propofol, in association with newer opioids, provides ideal anesthetic combinations. Conclusion: The advantages of newer anesthetic agents have redefined the clinical indications for neurolep- tanesthesia. In routine modem anesthesia, anxiolysis, sedation, and/or analgesia is better provided, with quicker recovery, by the new pharmacokinetic and pharmacodynamic characteristics of recent medications than by the neuroleptic component of neuroleptanesthesia. Objectif : Fake une revue de I'&at actuel et de I'Evolution possible de la neuroleptanalgEsie qui semble main- tenant presque abandonnEe. Souree..s : Des articles de 1966 A aujourd'hui ont ~t6 obtenus A partir d'une consultation de Current Science et de Medline. Les mots-clEs comprenaient : neuroleptanalg&ie, sedation du patient EveillE, dropEridol, benzodi- azEpines, propofol, k&amine et opiac&. Les informations et les rEsumEs provenant de sEminaires sur le sujet ont permis de completer la cueillette de donnEes. Constatadons principales : La combinaison de drop&idol et d'alfentanil peut &re indiquEe pour I'Electrocor- ticographie utilisEe dans le traitement chirurgical de I'Epilepsie. Cependant, I'importante incidence de sedation et d'agitation postop&atoires d&ourage son utilisation pour d'autres interventions chirurgicales ou diagnostiques. Nombre d'interventions chirurgicales o6 on a cru que les neuroleptiques &aient les agents idEaux sont maintenant mieux rEussies avec de nouveaux medicaments. I'emploi de midazolam et/ou de propofol, associ& aux nou- veaux opiac&, fournit les meilleures combinaisons. Conclusion : Les avantages des nouveaux anesthEsiques ont amenE A red~finir les indications cliniques de la neu- roleptanalg&ie. Dans la pratique de I'anesthEsie moderne, les medicaments r&ents assurent mieux la reduction de I'anxiEtE, la sedation et/ou I'analgEsie et permettent une r6cup&ation plus rapide que les composes utilis& en neuroleptanalg&ie, grace ~ leurs nouvelles caract&istiques pharmacocin&iques et pharmacodynamiques. From the Department of Anaesthesia, The Hospital for Sick Children, and University of Toronto, Toronto, Ontario, Canada and the Service d'Anesthesiologie,* H6pital Rrgional de Sion Herens Conthey, Switzerland. Address correspondence to: Dr. Bruno Bissonnette, Department of Anaesthesia, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario, M5G 1X8 Canada. Phone: 416-813-7445; Fax: 416-813-7543; E-mail: [email protected] Accepted for publication November 14, 1998 CAN J ANESTH 1999 / 46:2 / pp 154-168 Bissonnette et al.: NEUKOLEPTANESTHESIA 155 Conte~ts metabolic, and autonomic responses to nociceptive Introduction stimulation. They compared the anesthetic state to History that of certain selected animal species during hiberna- A The Neuroleptic Component tion. This new anesthetic technique, called ganglio- DROPERIDOL plegia or neuroplegia, used a lyric cocktail of three ALTERNATIVE DRUGS components: meperidine, promethazine, and chlor- Midazolam promazine. 2 It remains in use today in some pediatric Flumazenil centres, referred to as DPT (for their brand names, Ketamine: Dissociative Anesthesia Demerol, Phenergan, and Thorazine). Propofol The work of Campan and Lazothes I was expanded B The Opioid Component further by de Castro and Mundaleer 3 in Belgium. FENTANYL Using haloperidol (butyropherone) as a major neu- ALTERNATIVE DRUGS roleptic and phenoperidine (an opioid), they pro- Alfentanil duced a state of indifference and immobilization Sufentanil (often referred to by psychiatrists as mineralization) Remifentanil that they called neuroleptanalgesia. It was restricted to Conclusion patients who, under the combined influence of a neu- roleptic and an opioid, become analgesic, sedated, Abbreviations mineralized, and amnestic, maintaining autonomic, CBF: Cerebral blood flow neurological, and cardiovascular stability while able to CMRO2: Cerebral metabolic rate for oxygen comprehend and obey simple commands during CNS: Central nervous system surgery. 2 When the patient was rendered unconscious CPP: Cerebral perfusion pressure with the addition of N20 or a hypnotic drug, the term CSF: Cerebrospinal fluid neuroleptanesthesia was used. EEG: Electroencephalography When droperidol and fentanyl citrate, both intro- ICP: Intracranial pressure duced by Petr Janssen, 4,s became available, they replaced MAP: Mean arterial pressure haloperidol and phenoperidine as the most widely used PaCO2: Partial pressure of carbon dioxide compounds for inducing and maintaining neuroleptanal- PaO2: Partial pressure of oxygen gesia. Anesthesia was induced with Innovar, each millil- itre of which contained 2.5 mg of droperidol and 50 lag of fentanyl citrate, and supplemented with N20 and 02 T HE paucity of recent literature on neu- to attain neuroleptanesthesia. The drug combination was roleptanesthesia, once a topic of consider- titrated into a fast-running intravenous (iv) infusion until able interest in anesthesia, attests to its the patient was sedated and demonstrated some difficul- current uncertain clinical status. Has this ty in phonation from respiratory depression. Intubation technique, which defined a new anesthetic frontier 40 under direct laryngoscopy after topical anesthesia was yr ago, gone the way of ether and cyclopropane, to then possible, with or without muscle relaxants. become a subject only of historical interest? Re-evalu- However, this technique was not without problems, ation of its virtues and reassessment of its relevance to which included unconsciousness to the unrousable level, current practice is needed. This article, which discuss- venfilatory difficulties from muscular rigidity, and post- es the virtues and future of neuroleptanesthesia, is operative extrapyramidal excitation. intended to help clinicians understand and reassess These problems were caused by a lack of investiga- indications for a technique that may be nearly extinct. tion and understanding of the pharmacological effects of the individual components. 6 The tkxed-ratio mLxture History of Innovar, with the slow onset-slow offset droperidol The first reference to a neuroleptic anesthetic tech- and fast onset-fast offset fentanyl, was the obvious rea- nique was presented in 1954 by Campan and son for overdose and complications. The relatively slow Lazothes I in France. This new anesthetic technique onset time for droperidol (6-8 min) meant more fen- was designed to modify the effects of conventional tanyl was initially required for achieving sedation, general anesthesia in eliminating the perception of resulting in a relative overdose with development of nociceptive stimuli at the level of the cerebral cortex muscle rigidity and/or apnea. If not, as droperidol without affecting cognitive function. Its specific char- started to act, excessive sedation and respiratory depres- acteristics included modulation of certain endocrine, sion became evident; the relative overdose ofdroperidol 156 CANADIAN JOURNAL OF ANESTHESIA also caused extrapyramidal excitation. These complica- the cerebral vessels, the cerebral metabolic rate for tions could be prevented by separate, judicious admin- oxygen (CMRO2) remains unchanged. This may lead istration of each drug. 6,7 to a potential discrepancy between the metabolic sup- In the past 20 yr, numerous new anesthetic agents ply/demand ratio, which could become important in have become available, such as short-acting sedatives patients with impaired CBF from cerebrovascular ath- and hypnotics (midazolam and propofol) and the newer erosclerosis or surgical intervention, or with increased opioids (alfentanil, sufentanil, and remifentanil). To CMRO 2 from seizure activity. One of the advantages review the current status and list of indications and of droperidol is its lack of EEG effects,9 allowing reli- techniques for neuroleptanalgesia/anesthesia, we will able intra-operative EEG monitoring. It is not an anti- compare the pharmacology of droperidol and fentanyl convulsive agent; l~ in fact, droperidol can lower the with that of the newer alternative drugs. seizure threshold n and should be used with caution in Before proceeding, it seems appropriate to clarify patients with untreated epilepsy. This intrinsic effect some terms. Neuroleptanalgesia and neuroleptanes- might be an advantage during intra-operative record- thesia refer to the omission or addition, respectively, ing of seizure foci for intractable epilepsy; however, of N20 to the combination of a neuroleptic and