Skip to main content
Log in

Rigidity, hyperpyrexia and coma following fluphenazine enanthate

  • Published:
Psychopharmacologia Aims and scope Submit manuscript

Abstract

Beginning one day after receiving fluphenazine enanthate (Prolixin Enanthate®), 25 mg, subcutaneously, an acute schizophrenic girl with mixed schizoaffective and excited catatonic symptomatology became mute and withdrawn, then developed severe muscular rigidity and hyperpyrexia, and finally became comatose. The patient developed large increases in serum creatine phosphokinase (CPK) activity by the third day of this syndrome. The previously described symptoms, which have been labeled the neuroloptic “malignant” syndrome (Delay and Deniker, 1968), diminished with supportive treatment and intravenous benztropine mesylate (Cogentin®). Because of renewed psychotic behavior, phenothiazine treatment was eventually restarted, including treatment with fluphenazine enanthate, without recurrence of the extrapyramidal or hypothalamic symptoms. The difficulty in distinguishing between the neuroleptic “malignant” syndrome and Stauder's “acute lethal catatonia” is emphasized. The relationship between these syndromes and malignant hyperpyrexia is discussed. Possible causes of the increased serum CPK activity are discussed.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Acheson, J., James, D. C., Hutchinson, E. D., Westhead, R.: Serum-creatinekinase levels in cerebral vascular disease. Lancet 1965 I, 1306–1307.

    Google Scholar 

  • Allan, R., White, H. D.: Side effects of parenteral long-acting phenothiazines. Brit. med. J. 1972 I, 221–222.

    Google Scholar 

  • Aronson, S. M., Volk, B. W.: Studies on serum aldolase activity in neuromuscular disorders. I. Clinical applications. Amer. J. Med. 22, 414–421 (1957).

    Google Scholar 

  • Bodi, T., Share, I., Levy, H., Moyer, J. H.: Clinical trial of phencyclidine (Sernyl) in patients with psychoneurosis. Antibiot. med. 6. 79–84 (1959).

    Google Scholar 

  • Britt, B. A.: Recent advances in malignant hyperpyrexia. Anesth. Analg. Curr. Res. 51, 841–849 (1972).

    Google Scholar 

  • Britt, B. A., Locher, W. G., Kalow, W.: Hereditary aspects of malignant hyperpyrexia. Canad. Anaesth. Soc. J. 16, 89–98 (1969).

    Google Scholar 

  • Bruns, F. H., Bergmeyer, H. Y.: Fructose-1, 6-diphosphate aldolase. In: Methods of enzymatic analysis, H. U. Bergmeyer, ed., pp. 724–731. New York-London: Academic Press 1965.

    Google Scholar 

  • Delay, J., Deniker, P.: Drug-induced extrapyramidal syndroms. In: Handbook of Clinical neurology, diseases of the basal ganglia, Vol. 6, P. J. Vinken and G. W. Bruyn, eds. pp. 248–266. Amsterdam: North-Holland Publ. Co 1968.

    Google Scholar 

  • Denborough, M. A., Forster, J. F. A., Lovell, R. R. H., Maplestone, P. A., Villiers, J. D.: Anesthetic deaths in a family. Brit. J. Anaesth. 34, 395–396 (1962).

    Google Scholar 

  • Denborough, M. A., Hudson, M. C., Forster, J. F. A., Carter, N. G., Zapf, P.: Biochemical changes in malignant hyperpyrexia. Lancet 1970 I, 1137–1138.

    Google Scholar 

  • Dillon, J. B.: Parenteral long-acting phenothiazines. Brit. med. J. 1972 I, 807.

    Google Scholar 

  • Dubo, H., Park, D. C., Pennington, R. J. T., Kalbag, R. M. Walton, J. N.: Serum creatine kinase in cases of stroke, head injury and meningitis. Lancet 1967 II, 743–748.

    Google Scholar 

  • Furniss, P.: The etiology of malignant hyperpyrexia. Proc. roy. Soc. Med. 64, 218–220 (1971).

    Google Scholar 

  • Gordon, E., Januszko, D. M., Kaufman, L.: A critical survey of Stiff-Man syndrome. Amer. J. med. 42, 582–599 (1967).

    Google Scholar 

  • Hawks, D., Mitcheson, M., Ogborne, A., Edwards, G.: Abuse of methylamphetamine. Brit. med. J. 1969 II, 715–721.

    Google Scholar 

  • Henry, P., Barat, M., Bourgeois, M., Tignol, P.: Syndrome malin mortel succédent à une injection d'emblée d'oenanthate de fluphénanzine. Presse méd. 79, 1350 (1971).

    Google Scholar 

  • Herschkowitz, N., Cumings, J. N.: Creatine kinase in cerebrospinal fluid J. Neurol. Neurosurg. Psychiat. 27, 247–250 (1964).

    Google Scholar 

  • Issacs, H., Barlow, M. B.: Malignant hyperpyrexia during anaesthesia: Possible association with subclinical myopathy. Brit. med. J. 1970 I, 275–277.

    Google Scholar 

  • Issacs, H.: The genetic backround to malignant hyperpyrexia revealed by serum creatine phosphokinase estimations in asymptomatic relatives Brit. J. Anaesth. 42, 1077–1084 (1970b).

    Google Scholar 

  • Kalow, W., Britt, B. A., Terreau, M. E., Haist, C.: Metabolic error of muscle metabolism after recovery from malignant hyperthermia. Lancet 1970 II, 895–898.

    Google Scholar 

  • LaCour, D., Juul-Jensen, P., Reske-Nielsen, E.: Malignant hyperthermia during anesthesia. Acta anesth. scand. 15, 299–317 (1971).

    Google Scholar 

  • Lisak, R. P., Graig, F. A.: Lack of diagnostic value of creatine phosphokinase assay in spinal fluid. J. Amer. med. Ass. 199, 750–751 (1987).

    Google Scholar 

  • Luby, E. D., Cohen, B. D., Rosenbaum, G., Gottlieb, J. S., Kelley, R.: Study of a new schizophrenomimetic drug-Sernyl. Arch. Neurol. Psychiat. (Chic.) 81, 363–369 (1959).

    Google Scholar 

  • Lui, W. Y.: Creatine phosphokinase in cerebospinal fluid. Develop. med. Child Neurol. 14, 467–475 (1972).

    Google Scholar 

  • McQuillen, M., Tucker, L., Pellegrino, E.: Syndrome of subacute generalized muscular stiffness and spasm. Arch. Neurol. (Chic.) 16, 165–174 (1967).

    Google Scholar 

  • Meltzer, H. Y.: Muscle enzyme release in the acute psychoses. Arch. gen. Psychiat. 21, 102–112 (1969).

    Google Scholar 

  • Meltzer, H. Y.: Increased creatine phosphokinase and aldolase activity in acutely psychotic patients: Case reports. J. Psychiat. Res. 7, 249–262 (1970).

    Google Scholar 

  • Meltzer, H. Y.: Creatine phosphokinase activity in cerebrospinal fluid. Amer. J. Dis. Child. 122, 85 (1971a).

    Google Scholar 

  • Meltzer, H. Y.: Factors influencing serum creatine phosphokinase levels in the general population: The role of race, activity and age. Clin. chim. Acta 33, 165–172 (1971b).

    Google Scholar 

  • Meltzer, H. Y.: Muscle toxicity produced by phencyclidine and restraint stress. Res. Comm. chem. Path. Pharmacol. 3, 369–382 (1972a).

    Google Scholar 

  • Meltzer, H. Y.: Central core fibers in an acutely psychotic patient: Evidence for a neurogenic basis for the muscle abnormalities in the acute psychoses. Arch. gen. Psychiat. 27, 125–132 (1972b).

    Google Scholar 

  • Meltzer, H. Y.: Effects of phencyclidine and restraint at 2‡ C on rat plasma creatine phosphokinase activity. Res. Comm. chem. Path. Pharmacol. 5, 117–127 (1973).

    Google Scholar 

  • Meltzer, H. Y.: Grinspoon, L., Shader, R.: Serum creatine phosphokinase and aldolase activities in acute schizophrenic patients and their relatives. Comp. Psychiat. 11, 552–558 (1970).

    Google Scholar 

  • Meltzer, H. Y., Holzman, P. S., Hassan, S. Z., Guschwan, A.: Effects of phencyclidine and stress on CPK and aldolase activities. Psychopharmacologia (Berl.) 26, 44–53 (1972).

    Google Scholar 

  • Meltzer, H. Y., Moline, R.: Plasma enzymatic activity after exercise: Study of psychiatric patients and their relatives. Arch. gen. Psychiat. 22, 390–397 (1970a).

    Google Scholar 

  • Meltzer, H. Y.: Muscle abnormalities in acute psychoses. Arch. gen. Psychiat. 23, 481–491 (1970b).

    Google Scholar 

  • Meltzer, H. Y., Mrozak, S., Boyer, M.: Effect of intramuscular injections on serum creatine phosphokinase activity. Amer. J. med. Sci. 259, 42–49 (1970).

    Google Scholar 

  • Nathan, M. J.: Creatine phosphokinase in the cerebospinal fluid. J. Neurol. Neurosurg. Psychiat. 30, 52–55 (1967).

    Google Scholar 

  • Penn, A. S., Rowland, L. P., Fraser, D. W.: Drugs, coma and myoglobinuria. Arch. Neurol. (Chic.) 26, 336–343 (1972).

    Google Scholar 

  • Purkis, I. E., Horrelt, O., DeYoung, C. G., Fleming, R. A. P., Langley, G. R.: Hyperpyrexia during anesthesia in a second member of a family with associated coagulation defect due to increased intravascular coagulation. Canad. Anaesth. Soc. J. 14, 183–192 (1967).

    Google Scholar 

  • Reske-Nielsen, E., Kratholm, S.: Malignant hyperthermia: A fatal case provoked by anesthesia in asymptomatic encephalitis. Acta anesthesth. scand. 15, 319–324 (1971).

    Google Scholar 

  • Rosalki, S. B.: An improved procedure for serum creatine phosphokinase determination. J. Lab. clin. med. 69, 696–705 (1967).

    Google Scholar 

  • Rosenbaum, G. R., Cohen, B. D., Luby, E. D., Gottlieb, J. S., Yelen, D.: Comparison of Sernyl with other drugs. Arch. gen. Psychiat. 1, 651–656 (1959).

    Google Scholar 

  • Seeman, P.: The membrane action of anesthetics and tranquilizers. Pharmacol. Rev. 24, 583–656 (1972).

    Google Scholar 

  • Sherwin, A. L., Norris, J. W., Bulcke, J. A.: Spinal fluid creatine kinase in neurologic disease. Neurology (Minneap.) 19, 993–999 (1969).

    Google Scholar 

  • Stauder, H. K.: Die tödliche Katatonie. Arch. Psychiat. Nervenkr. 121, 271 (1934).

    Google Scholar 

  • Steers, A. J. W., Tallack, J. A., Thompson, D. E. A.: Fulminating hyperpyrexia during anesthesia in a member of a myopathic family. Brit. med. J. 1970 II, 341–343.

    Google Scholar 

  • Van Der Veen, K. J., Willebrands, A. F.: Isoenzymes of creatine phosphokinase in tissue extracts and in normal and pathological sera. Clin. chim. Acta 13, 312–316 (1966).

    Google Scholar 

  • Wolintz, A. H., Jacobs, L. D., Christoff, N., Solomon, M., Chernik, N.: Serum and cerebrospinal fluid enzymes in cerebrovascular disease. Arch. Neurol. (Chic.) 20, 54–61 (1969).

    Google Scholar 

  • Zsigmond, E. K., Starkweather, W. H., Duboff, G. S., Flynn, K. A.: Abnormal creatine-phosphokinase isoenzyme pattern in families with malignant hyperpyrexia. Anesth. Analg. Curr. Res. 51, 827–837 (1972a).

    Google Scholar 

  • Zsigmond, E. K.: Elevated serum-creatine phosphokinase activity in a family with malignant hyperpyrexia. Anesth. Analg. Curr. Res. 51, 220–225 (1972b).

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Meltzer, H.Y. Rigidity, hyperpyrexia and coma following fluphenazine enanthate. Psychopharmacologia 29, 337–346 (1973). https://doi.org/10.1007/BF00429281

Download citation

  • Received:

  • Revised:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00429281

Key Words

Navigation