Abstract
Purpose
To review the current status and possible future of neuroleptanalgesia/anesthesia, techniques that may be nearly extinct.
Source
Articles from 1966 to present were obtained from the Current Science and Medline databases. Search terms include neurolepananalgesia/anesthesia, conscious sedation, droperidol, benzodiazepines, propofol, ketamine, and opioids. Information and abstracts obtained from meetings on this topic helped complete the collection 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 discourage its use for other surgical or diagnostic procedures. Many surgical interventions, once thought ideally suited 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 neuroleptanesthesia. In routine modern 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.
Résumé
Objectif
Faire une revue de l’état actuel et de l’évolution possible de la neuroleptanalgésie qui semble maintenant presque abandonnée.
Sources
Des articles de 1966 à aujourd’hui ont été obtenus à partir d’une consultation de Current Science et de Medline. Les mots-clés comprenaient: neuroleptanalgésie, sédation du patient éveillé, dropéridol, benzodi-azépines, propofol, kétamine et opiacés. Les informations et les résumés provenant de séminaires sur le sujet ont permis de compléter la cueillette de données.
Constatations principales
La combinaison de dropéridol et d’alfentanil peut être indiquée pour l’électrocorticographie utilisée dans le traitement chirurgical de l’épilepsie. Cependant, l’importante incidence de sédation et d’agitation postopératoires décourage son utilisation pour d’autres interventions chirurgicales ou diagnostiques. Nombre d’interventions chirurgicales où on a cru que les neuroleptiques étaient les agents idéaux sont maintenant mieux réussies avec de nouveaux médicaments. L’emploi de midazolam et/ou de propofol, associés aux nouveaux opiacés, fournit les meilleures combinaisons.
Conclusion
Les avantages des nouveaux anesthésiques ont amené à redéfinir les indications cliniques de la neuroleptanalgésie. Dans la pratique de l’anesthésie moderne, les médicaments récents assurent mieux la réduction de l’anxiété, la sédation et/ou l’analgésie et permettent une récupération plus rapide que les composés utilisés en neuroleptanalgésie, grâce à leurs nouvelles caractéristiques pharmacocinétiques et pharmacodynamiques.
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References
Campan L, Lazothes G. L’hibernothérapie en chirurgie cérébrale, sa justification clinique et pathologénique. In: Laborit H, Huguenard P (Eds.). Practique de l’Hibernothérapie en Chirurgie et en Médicine. Paris: Masson et Cie, 1954: 137–80.
Bailey PL, Stanley TH. Intravenous Opioid anesthetics.In: Miller RD (Ed.). Anesthesia, 4th ed. New York: Churchill Livingstone Inc., 1994: 291–389.
de Castro G, Mundeleer P. Anesthésie sans sommeil: “neuroleptanalgésie”. Acta Chir Belg 1959; 58: 689–93.
Janssen PAJ, Niemegeers CJE, Schellekens KHL, Verbruggen FJ, Van Neuten JM. The pharmacology of dehydrobenzperidol, a new potent and short-acting neuroleptic agent chemically related to haloperidol. Arzniemittelforschung 1963; 13: 205–8.
Janssen PAJ. A review of the chemical features associated with strong morphine-like activity. Br J Anaesth 1962; 34: 260–8.
Foldes FF. Neuroleptanesthesia for general surgery. Int Anesthesiol Clin 1973; 11: 1–35.
Foldes FF, Kepes ER, Kronfeld PP, Shiffman HP. A rational approach to neuroleptanesthesia. Anesth Analg 1966; 45: 642–54.
Richter JJ. Current theories about the mechanisms of benzodiazepines and neuroleptic drugs. Anesthesiology 1981; 54: 66–72.
Marshall BM, Gordon RA. Electroencephalographic monitoring in anaesthesia with droperidol and fentanyl. Can Anaesth Soc J 1968; 15: 357–61.
Hashem A, Frey HH. The effect of neuroleptics and neuroleptic/analgesic combinations on the sensitivity to seizures in mice. Anaesthetist 1988; 37: 631–5.
Herrick IA, Craen RA, Gelb AW, et al. Propofol sedation during awake craniotomy for seizures: patient-controlled administration versus neurolept analgesia. Anesth Analg 1997; 84: 1285–91.
Soroker D, Barzilay E, Konichezky S, Bruderman I. Respiratory function following premedication with droperidol or diazepam. Anesth Analg 1978; 57: 695–9.
Cottrell JE, Wolfson B, Siker ES. Changes in airway resistance following droperidol, hydroxyzine, and diazepam in normal volunteers. Anesth Analg 1976; 55: 18–21.
Prokocimer P, Delavault E, Rey F, Lefevre P, Mazze RI, Desmonts JM. Effects of droperidol on respiratory drive in humans. Anesthesiology 1983; 59: 113–6.
Ward DS. Stimulation of hypoxic ventilatory drive by droperidol. Anesth Analg 1984; 63: 106–10.
Whitwam JG, Russell WJ. The acute cardiovascular changes and adrenergic blockade by droperidol in man. Br J Anaesth 1971; 43: 581–91.
Sumikawa K, Amakata T. The pressor effect of droperidol on a patient with pheochromocytoma. Anesthesiology 1977; 46: 359–61.
Sumikawa K, Hirano H, Amakata T, Kashimoto T, Wada A, Izumi F. Mechanism of the effect of droperidol to induce catecholamine efflux from the adrenal medulla. Anesthesiology 1985; 62: 17–22.
Long G, Dripps RD, Price HL. Measurement of antiarrhythmic potency of drugs in man: effects of dehydrobenzperidol. Anesthesiology 1967; 28: 318–23.
Bertoló L, Novakovi L, Penna M. Antiarrhythmic effects of droperidol. Anesthesiology 1972; 37: 529–35.
Santos A, Datta S. Prophylactic use of droperidol for control of nausea and vomiting during spinal anesthesia for cesarean section. Anesth Analg 1984; 63: 85–7.
Lerman J, Eustis S, Smith DR. Effect of droperidol pretreatment on postanesthetic vomiting in children undergoing strabismus surgery. Anesthesiology 1986; 65: 322–5.
Yentis SM, Bissonnette B. Ineffectiveness of acupuncture and droperidol in preventing vomiting following strabismus repair in children. Can J Anaesth 1992; 39: 151–4.
Thomson D, Geller E, Lauven P, Whitwam J. Midazolam and flumazenil: the agonist-antagonist concept for sedation and anaesthesia. Acta Anaesthesiol Scand 1990; 92(Suppl): 108–9.
Goodchild CS. GABA receptors and benzodiazepines. Br J Anaesth 1993; 71: 127–33.
Lauven PM, Kulka PJ. Anaesthesia techniques for midazolam and flumazenil — an overview. Acta Anaesthesiol Scand 1990; 92(Suppl): 84–9.
Murphy PJ, Erskine R, Langton JA. The effect of intravenously administered diazepam, midazolam and flumazenil on the sensitivity of upper airway reflexes. Anaesthesia 1994; 49: 105–10.
Brown CR, Sarnquist FH, Canup CA, Pedley TA. Clinical, electroencephalographic, and pharmacokinetic studies of a water-soluble benzodiazepine, midazolam maleate. Anesthesiology 1979; 50: 467–70.
Artru AA. Dose-related changes in the rate of cerebrospinal fluid formation and resistance to reabsorption of cerebrospinal fluid following administration of thiopental, midazolam, and etomidate in dogs. Anesthesiology 1988; 69: 541–6.
Giffin JP, Cornell JE, Shwiry B, Hartung J, Epstein J, Lim K. Intracranial pressure, mean arterial pressure, and heart rate following midazolam or thiopental in humans with brain tumors. Anesthesiology 1984; 60: 491–4.
Dundee JW, Wilson DB. Amnesic action of midazolam. Anaesthesia 1980; 35: 459–61.
Splinter WM, MacNeill HB, Menard EA, Rhine EJ, Roberts DJ, Gould MH. Midazolam reduces vomiting after tonsillectomy in children. Can J Anaesth 1995; 42: 201–3.
Forster A, Juge O, Louis M, Nahory A. Effects of a specific benzodiazepine antagonist (RO 15-1788) on cerebral blood flow. Anesth Analg 1987; 66: 309–13.
Schulteam Esch J, Kochs E. Midazolam and flumazenil in neuroanaesthesia. Acta Anaesthesiol Scand 1990; 92(Suppl): 96–102.
Fleischer JE, Milde JH, Moyer TP, Michenfelder JD. Cerebral effects of high-dose midazolam and subsequent reversal with RO 15-1788 in dogs. Anesthesiology 1988; 68: 234–42.
Chiolero RL, Ravussin PA, Freeman J. Using flumazenil (Ro 15-1788) after prolonged midazolam infusion for anaesthesia for intracranial surgery. Ann Fr Anesth Reanim 1988; 7: 17–21.
Chiolero R-L, Ravussin P, Anderes J-P, Ledermann P, de Tribolet N. The effects of midazolam reversal by RO 15-1788 on cerebral perfusion pressure in patients with severe head injury. Intensive Care Med 1988; 14: 196–200.
Idvall J, Ahlgren I, Aronsen KR, Stenberg P. Ketamine infusions: pharmacokinetics and clinical effects. Br J Anaesth 1979; 51: 1167–73.
Rudkin GE, Osborne GA, Finn BP, Jarvis DA, Vickers D. Intra-operative patient-controlled sedation. Comparison of patient-controlled propofol with patient-controlled midazolam. Anaesthesia 1992; 47: 376–81.
Doze VA, Shafer A, White PF. Propofol-nitrous oxide versus thiopental-isoflurane-nitrous oxide for general anesthesia. Anesthesiology 1988; 69: 63–71.
Valanne J, Korttila K. Effect of a small dose of droperidol on nausea, vomiting and recovery after outpatient enflurane anaesthesia. Acta Anaesthesiol Scand 1985; 29: 359–62.
Doze VA, Westphal LM, White PF. Comparison of propofol with methohexital for outpatient anesthesia. Anesth Analg 1986; 65: 1189–95.
Misfeldt BB, Jörgensen PB, Spotoft H, Rønde F. The effects of droperidol and fentanyl on intracranial pressure and cerebral perfusion pressure in neurosurgical patients. Br J Anaesth 1976; 48: 963–8.
Artru AA. Effects of halothane and fentanyl anesthesia on resistance to reabsorption of CSF. J Neurosurg 1984; 60: 252–6.
Moss E, Powell D, Gibson RM, McDowall DG. Effects of fentanyl on intracranial pressure and cerebral perfusion pressure during hypocapnia. Br J Anaesth 1978; 50: 779–84.
Jessop E, Grounds RM, Morgan M, Lumley J. Comparison of infusions of propofol and methohexi-tone to provide light general anaesthesia during surgery with regional blockade. Br J Anaesth 1985; 57: 1173–7.
Dubois A, Balatoni E, Peeters JP, Baudoux M. Use of propofol for sedation during gastrointestinal endoscopies. Anaesthesia 1988; 43(Suppl): 75–80.
Dertwinkel R, Nolte H. Continuous sedation for regional anesthesia with propofol (Disoprivan®) and midazolam (Dormicum®). A comparative study. Reg Anaesth 1988; 11: 84–91.
Fanard L, Van Steenberge A, Demeire X, van der Puyl F. Comparison between propofol and midazolam as sedative agents for surgery under regional anaesthesia. Anaesthesia 1988; 43(Suppl): 87–9.
Herrick IA, Craen RA, Gelb AW, et al. Propofol sedation during awake craniotomy for seizures: electrocorticographic and epileptogenic effects. Anesth Analg 1997; 84: 1280–4.
White PF, Negus JB. Sedative infusions during local and regional anesthesia: a comparison of midazolam and propofol. J Clin Anesth 1991; 3: 32–9.
Taylor E, Ghouri AF, White PF. Midazolam in combination with propofol for sedation during local anesthesia. J Clin Anesth 1992; 4: 213–6.
Valtonen M, Salonen M, Forssell H, Scheinin M, Viinamäki O. Propofol infusion for sedation in outpatient oral surgery. A comparison with diazepam. Anaesthesia 1989; 44: 730–4.
Beller JP, Pottecher T, Lugnier A, Mangin P, Otteni JC. Prolonged sedation with propofol in ICU patients: recovery and blood concentration changes during periodic interruptions in infusion. Br J Anaesth 1988; 61: 583–8.
Parke TJ, Stevens JE, Rice AS, et al. Metabolic acidosis and fatal myocardial failure after propofol infusion in children: five case reports. BMJ 1992; 305: 613–6.
Morrison JD, Loan WB, Dundee JW. Controlled comparison of the efficacy of fourteen preparations in the relief of postoperative pain. BMJ 1971; 3: 287–90.
Koehntop DE, Rodman JH, Brundage DM, Hegland MG, Buckley JJ. Pharmacokinetics of fentanyl in neonates. Anesth Analg 1986; 65: 227–32.
Scott JC, Ponganis KV, Stanski DR. EEG quantitation of narcotic effect: the comparative pharmacodynamics of fentanyl and alfentanil. Anesthesiology 1985; 62: 234–41.
Tempelhoff R, Modica PA, Spitznagel EL Jr. Anticonvulsant therapy increases fentanyl requirements during anaesthesia for craniotomy. Can J Anaesth 1990; 37: 327–32.
Schell RM, Kern FH, Greeley WJ, et al. Cerebral blood flow and metabolism during cardiopulmonary bypass. Anesth Analg 1993; 76: 849–65.
Michenfelder JD, Theye RA. Effects of fentanyl, droperidol, and Innovar on canine cerebral metabolism and blood flow. Br J Anaesth 1971; 43: 630–6.
Murkin JM, Farrar JK, Tweed WA, McKenzie FN, Guiraudon G. Cerebral autoregulation and flow/metabolism coupling during cardiopulmonary bypass: the influence of PaCO2. Anesth Analg 1987; 66: 825–32.
Jamali S, Ravussin P, Archer D, Goutallier D, Parker F, Ecoffey C. The effects of bolus administration of opioids on cerebrospinal fluid pressure in patients with supratentorial lesions. Anesth Analg 1996; 82: 600–6.
Todd MM, Warner DS, Sokoll MD, et al. A prospective, comparative trial of three anesthetics for elective supratentorial craniotomy. Propofol/fentanyl, isoflurane/nitrous oxide, and fentanyl/nitrous oxide. Anesthesiology 1993; 78: 1005–20.
Fitch W, Barker J, McDowall DG, Jennett WB. The effect of methoxyflurane on cerebrospinal fluid pressure in patients with and without intracranial space-occupying lesions. Br J Anaesth 1969; 41: 564–73.
Fitch W, Barker J, Jennett WB, McDowall DG. The influence of neuroleptanalgesic drugs on cerebrospinal fluid pressure. Br J Anaesth 1969; 41: 800–6.
Sari A, Okuda Y, Takeshita H. The effects of thalamonal on cerebral circulation and oxygen consumption in man. Br J Anaesth 1972; 44: 330–4.
Cold GE, Christensen KJS, Nordentoft J, Engberg M, Pedersen MB. Cerebral blood flow, cerebral metabolic rate of oxygen and relative CO2 reactivity during neurolept anaesthesia in patients subjected to craniotomy for supratentorial cerebral tumours. Acta Anaesthesiol Scand 1988; 32: 310–5.
Miller R, Tausk HC, Stark DCC. Effect of Innovar, fentanyl and droperidol on the cerebrospinal fluid pressure in neurosurgical patients. Can Anaesth Soc J 1975; 22: 502–8.
Manninen P, Contreras J. Anesthetic considerations for craniotomy in awake patients. Int Anesthesiol Clin 1986; 24: 157–74.
Archer DP, McKenna JMA, Morin L, Ravussin P. Conscious-sedation analgesia during craniotomy for intractable epilepsy: a review of 354 consecutive cases. Can J Anaesth 1988; 35: 338–44.
Gignac E, Manninen PH, Gelb AW. Comparison of fentanyl, sufentanil and alfentanil during awake craniotomy for epilepsy. Can J Anaesth 1993; 40: 421–4.
Bowdle TA, Rooke GA. Postoperative myoclonus and rigidity after anesthesia with opioids. Anesth Analg 1994; 78: 783–6.
Bovil JG. Opioids.In: Dundee JW, Clarke RSJ, McCaughey W (Eds.). Clinical Anaesthetic Pharmacology. Philadelphia: Churchill Livingstone Inc., 1991: 203–30.
Vejlsted H, Hansen M, Jacobsen E. Postoperative ventilatory response to carbon dioxide following neurolept anaesthesia. Acta Anaesthesiol Scand 1977; 21: 529–33.
Greene MJ. Some aspects of the pharmacology of droperidol. Br J Anaesth 1972; 44: 1272–6.
Smedstad KG, Rigg JRA. Control of breathing after fentanyl and Innovar anaesthesia. Br J Anaesth 1982; 54: 599–604.
Harper MH, Hickey RF, Cromwell TH, Linwood S. The magnitude and duration of respiratory depression produced by fentanyl and fentanyl plus droperidol in man. J Pharmacol Exp Ther 1976; 199: 464–8.
Becker LD, Paulson BA, Miller RD, Severinghaus JW, Eger EI II. Biphasic respiratory depression after fentanyl-droperidol or fentanyl alone used to supplement nitrous oxide anesthesia. Anesthesiology 1976; 44: 291–6.
Stoeckel H, Hengstmann JH, Schüttler J. Pharmacokinetics of fentanyl as a possible explanation for recurrence of respiratory depression. Br J Anaesth 1979; 51: 741–5.
Ostheimer GW, Shanahan EA, Guyton RA, Daggett WM, Lowenstein E. EfFects of fentanyl and droperidol on canine left-ventricular performance. Anesthesiology 1975; 42: 288–91.
Graves CL, Downs NH, Browne AB. Cardiovascular effects of minimal analgesic quantities of Innovar®, fentanyl, and droperidol in man. Anesth Analg 1975; 54: 15–23.
Trudnowski RJ, Mostert JW, Hobika GH, Rico R. Neuroleptanalgesia for patients with kidney malfunction. Anesth Analg 1971; 50: 679–84.
Lindahl-Nilsson Ch, Lundh R, Groth C-G. Neurolept anaesthesia for the renal transplant operation. Acta Anaesthesiol Scand 1980; 24: 451–7.
Graham TP Jr, Atwood GF, Werner B. Use of droperidol-fentanyl sedation for cardiac catheterization in children. Am Heart J 1974; 87: 287–93.
Kay B. Neuroleptanesthesia for neonates and infants. Anesth Analg 1973; 52: 970–3.
Stanski DR, Hug CJ. Alfentanil—a kinetically predictable narcotic analgesic (Editorial). Anesthesiology 1982; 57: 435–8.
Roure P, Jean N, Leclerc A-C, Cabanel N, Levron J-C, Duvaldestin P. Pharmacokinetics of alfentanil in children undergoing surgery. Br J Anaesth 1987; 59: 1437–40.
Goresky GV, Koren G, Sabourin MA, Sale JP, Strunin L. The pharmacokinetics of alfentanil in children. Anesthesiology 1987; 67: 654–9.
Fragen RJ, Booij LHDJ, Braak GJJ, Vree TB, Heykants J, Crul JF. Pharmacokinetics of the infusion of alfentanil in man. Br J Anaesth 1983; 55: 1077–81.
Shafer A, Sung M-L, White PF. Pharmacokinetics and pharmacodynamics of alfentanil infusions during general anesthesia. Anesth Analg 1986; 65: 1021–8.
Welling EC, Donegan J. Neuroleptanalgesia using alfentanil for awake craniotomy. Anesth Analg 1989; 68: 57–60.
Markovitz BP, Duhaime A-C, Sutton L, Schreiner MS, Cohen DE. Effects of alfentanil on intracranial pressure in children undergoing ventriculoperitoneal shunt revision. Anesthesiology 1992; 76: 71–6.
Pokela M-L, Ryhänen PT, Koivisto ME, Olkkola KT, Saukkonen A-L. Alfentanil-induced rigidity in newborn infants. Anesth Analg 1992; 75: 252–7.
Bovill JG, Sebel PS, Blackburn CL, Oei-Lim V, Heykants JJ. The pharmacokinetics of sufentanil in surgical patients. Anesthesiology 1984; 61: 502–6.
Sanford TJ Jr. A review of sufentanil. Semin Anesth 1988; VII: 127–36.
Murkin JM, Farrar JK, McNeill B, Gelb AW, Lok P. Cerebral oxygen consumption during sufentanil anesthesia: measurement by N2O uptakevs133xenon clearance. Can J Anaesth 1990; 37: S32.
Mayer N, Weinstabl C, Podreka I, Spiss CK. Sufentanil does not increase cerebral blood flow in healthy human volunteers. Anesthesiology 1990; 73: 240–3.
Jung R, Shah N, Reinsel R, et al. Cerebrospinal fluid pressure in patients with brain tumors: impact of fentanyl versus alfentanil during nitrous oxide-oxygen anesthesia. Anesth Analg 1990; 71: 419–22.
From RP, Warner DS, Todd MM, Sokoll MD. Anesthesia for craniotomy: a double-blind comparison of alfentanil, fentanyl, and sufentanil. Anesthesiology 1990; 73: 896–904.
Shupak RC, Harp JR. Comparison between high-dose sufentanil-oxygen and high-dose fentanyl-oxygen for neuroanacsthesia. Br J Anaesth 1985; 57: 375–81.
Meretoja OA, Rautiainen P. Alfentanil and fentanyl sedation in infants and small children during cardiac catheterization. Can J Anaesth 1990; 37: 624–8.
Glass PS, Hardman D, Kamiyama Y, et al. Preliminary pharmacokinetics and pharmacodynamics of an ultra-short-acting opioid: remifentanil (GI87084B). Anesth Analg 1993; 77: 1031–40.
Davis PJ, Lerman J, Suresh S, et al. A randomized multicenter study of remifentanil compared with alfentanil, isoflurane, or propofol in anesthetized pediatric patients undergoing elective strabismus surgery. Anesth Analg 1997; 84: 982–9.
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Bissonnette, B., Swan, H., Ravussin, P. et al. Neuroleptanesthesia: current status. Can J Anesth 46, 154–168 (1999). https://doi.org/10.1007/BF03012550
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DOI: https://doi.org/10.1007/BF03012550