JOURNAL HOME CME HOME THIS MONTH PAST ISSUES ETOC COLLECTIONS
AUTHORS REVIEWERS EDITORIAL BOARD FEEDBACK RSS HELP
A&A International Anesthesia Research Society
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a colleague
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via ISI Web of Science (9)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Schramm, B. M.
Right arrow Articles by Orser, B. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Schramm, B. M.
Right arrow Articles by Orser, B. A.
Anesth Analg 2002;94:1237-1240
© 2002 International Anesthesia Research Society

ANESTHETIC PHARMACOLOGY

Dystonic Reaction to Propofol Attenuated by Benztropine (Cogentin)

Belinda M. Schramm, MB BS, FANZCA, and Beverley A. Orser, MD PhD

Department of Anaesthesia, Sunnybrook & Women’s College Health Sciences Centre, University of Toronto, Canada

Address correspondence and reprint requests to Beverley Orser, MD, PhD, Department of Anaesthesia, Sunnybrook & Women’s College Health Sciences Centre, University of Toronto, 2075 Bayview Ave., Toronto, Ontario, M4N 3M5, Canada. Address e-mail to beverley.orser{at}utoronto.ca


   Abstract
Top
 Abstract
Introduction
 Case Report
 Discussion
 References
 

IMPLICATIONS: Neuroexcitatory movements associated with propofol anesthesia are well recognized. Here we report on the successful use of benztropine (2 mg) to abolish abnormal dystonic movements after propofol anesthesia. Forty-five case reports are reviewed, and a treatment strategy for abnormal movements during propofol anesthesia is provided.


   Introduction
Top
 Abstract
 Introduction
Case Report
 Discussion
 References
 
The administration of propofol has been associated with abnormal patient movements and seizurelike activity. Despite numerous case reports, there is no clear consensus regarding the neurogenic origin or therapeutic strategy for these adverse reactions. Here we describe a case of prolonged dystonic activity after propofol anesthesia that was terminated by benztropine. Previous cases are reviewed, and a treatment plan is provided.


   Case Report
Top
 Abstract
 Introduction
 Case Report
Discussion
 References
 
A 57-yr-old, 80-kg man required elective cardioversion. He had developed atrial fibrillation after an aortic valve replacement 4 mo earlier. Current drug treatment included ramipril, digoxin, furosemide, warfarin, atenolol, and occasionally lorazepam for anxiety. There was no history of drug allergy, neurological, hepatic, or renal disease. Physical examination was normal apart from a loud systolic ejection murmur.

After midazolam 1 mg, an initial bolus of propofol 80 mg (Diprivan, Zeneca Pharma, Mississauga, ON) was given. Within seconds the patient developed involuntary, arrhythmic, twitching movements of the upper limbs but responded to commands to open his eyes. Midazolam 1 mg was again administered followed by incremental bolus doses of propofol to a total of 350 mg. After this large dose, the patient lost consciousness but maintained spontaneous respirations and a patent airway. The involuntary upper limb movements progressed to spasmodic writhing of the upper limbs, whereas the lower limbs were in full extension. These movements occurred periodically every 15–30 s and lasted 3–4 s. The abdominal wall muscles contracted spasmodically with the appearance that the patient was struggling against an upper airway obstruction.

After loss of consciousness, the patient was successfully cardioverted. However, the writhing movements persisted, and he remained unconscious. After 30 min, benztropine 2 mg was given IV because the abnormal movements were consistent with a dystonic drug reaction. Within 1 min he regained consciousness, and the writhing movements stopped. He had no recall of events, despite having opened his eyes to command when the movements began, and described no discomfort. He was observed for 7 h with no recurrence of dystonic movements. The patient was advised to avoid propofol in the future. Interestingly, a review of the patient’s medical records indicated he had received a propofol infusion (50 µg · kg-1 · min-1) for 3 h during cardiac surgery. The propofol infusion was continued for 2 h in the intensive care unit then gradually weaned off without adverse effects.


   Discussion
Top
 Abstract
 Introduction
 Case Report
 Discussion
References
 
Neuroexcitatory reactions to propofol can take many forms, including opisthotonos (1), dystonia (2), masseter spasm (3), generalized tonic-clonic seizure (4), and athetosis (5). Abnormal movements associated with propofol have also been attributed to hysteria (6) and delirium (7). The pro- and anticonvulsant properties of propofol have been previously reviewed (8,9). However, despite numerous case reports, this is the first report of an apparently effective drug treatment in an adult patient.

A literature search performed using PubMed (www.ncbi.nlm.nih.gov/PubMed/) and the keywords propofol, dystonic reaction, opisthotonos, neuroexcitation, seizure, and acute dystonia in all combinations from 1966 to 2001 revealed 45 case reports (Tables 1 and 2) (10–35). Most cases occurred in young, female, day-surgery patients during emergence from anesthesia (1,3). Excitatory reactions to propofol seem to generally occur in two groups based on descriptions of the abnormal movements. These groups include either seizurelike (intermittent contractions with muscles alternatively contracting and relaxing) or dystonic (abnormal hypertonicity in the limbs) reactions. Patients that demonstrated evidence of both seizurelike and dystonic reactions were included in the seizurelike group.


View this table:
[in this window]
[in a new window]
  		Table 1. Seizure-like reactions
 

View this table:
[in this window]
[in a new window]
  		Table 2. Dystonic Reactions
 
Group 1: Seizurelike Reaction
Tonic-clonic or grand mal, generalized seizures after propofol (Table 1), occurred in patients with (36) and without (15) a history of epilepsy. The origin of these reactions is unknown because propofol has anticonvulsant properties (15). Makela et al. (15) proposed that propofol inhibits epileptic dampening, which is most likely to occur during rapid changes in propofol concentration at the induction of, or emergence from, anesthesia. Propofol may have a larger potency at subcortical centers thus producing an imbalance in excitatory-inhibitory centers (37). In vitroexperiments also revealed that propofol inhibits calcium channels that may reduce transmitter release from inhibitory neurons (38).

Group 2: Dystonic Reaction
Reactions have also been described as opisthotonos and dystonia, with no evidence of seizure activity (Table 2). These movements may be attributed to an imbalance of cholinergic-dopaminergic neurotransmitters in the basal ganglia because neuromuscular coordination involves a fine balance between dopamine receptors (inhibitory) and cholinergic receptors (excitatory) (39). Propofol is assumed to cause an imbalance of basal ganglia transmitters that produce an increase in excitatory cholinergic output.

The mechanisms underlying the effectiveness of benztropine are uncertain, particularly as cholinesterase inhibitors that increase nicotinic and muscarinic receptor activity are reported to antagonize the effects of propofol on consciousness (40). Benztropine is a tertiary amine with mixed anticholinergic, antihistaminic, and dopanergic properties (41). It may act by blocking intrastriatal cholinergic activity and thereby restoring central neurotransmitter balance. The recommended dose for treatment of drug-induced extrapyramidal side effects is 2 mg IV. This dose may be repeated every 30 minutes until symptoms resolve (41). Side effects are predictable because of drug actions (e.g., sedation, tachycardia, dry mouth).

Treatment Strategy
We propose that the management of excitatory reactions to propofol depends on the appearance of the abnormal movements. For a dystonic reaction, benztropine 2 mg IV is recommended because a previous study reported that benztropine provided a shorter time to recovery with fewer side effects than diphenhydramine (39). Diphenhydramine has also been reported to induce acute dystonia (42). In contrast to dystonic reactions, the management of seizurelike reactions should be the same as for any generalized seizure, with the exception of the administration of propofol.

In summary, propofol-induced neurological reactions can be divided into dystonic and seizurelike. Benztropine may be used to treat dystonic reactions and also as a rapid diagnostic tool to avoid unnecessary and costly investigations of abnormal neuroexcitatory movements (39).


   Acknowledgments
 
The authors thank Jenny Lam-McCulloch for her assistance with preparation of the manuscript.


   References
Top
 Abstract
 Introduction
 Case Report
 Discussion
 References
 

  1. Ries C, Scoates P, Puil E. Opisthotonos following propofol: a nonepileptic perspective and treatment strategy. Can J Anaesth 1994; 41: 414–19.[Abstract/Free Full Text]
  2. Ananthanarayan C. Dystonic reaction after anesthesia. Can J Anaesth 2001; 48: 101–3.[Free Full Text]
  3. Islander G, Vinge E. Severe neuroexcitatory symptoms after anaesthesia: with focus on propofol anaesthesia. Acta Anaesthesiol Scand 2000; 44: 144–9.[ISI][Medline]
  4. Finley G, MacManus B, Sampson S, et al. Delayed seizures following sedation with propofol. Can J Anaesth 1993; 40: 863–5.[Abstract/Free Full Text]
  5. DeFriez C, Wong H. Seizures and opisthotonos after propofol anesthesia. Anesth Analg 1992; 75: 630–2.[Free Full Text]
  6. Stoddart P, Gill R, Lim M. Hysteria: a cause for opisthotonus. Anaesthesia 1992; 47: 1014.
  7. Gadalla F, Spencer J. Prolonged delirium after propofol. Can J Anaesth 1996; 43: 877–80.[ISI][Medline]
  8. Jones G, Boykett M, Klock M. Propofol, opisthotonus and epilepsy. Anaesthesia 1988; 43: 905.
  9. Modica PA, Tempelhoff R, White PF. Pro- and anticonvulsant effects of anesthetics (Part I). Anesth Analg 1990; 70: 303–15.[Free Full Text]
  10. Cameron A. Opisthotonos again. Anaesthesia 1987; 42: 1124.[ISI][Medline]
  11. Wittenstein U, Lyle D. Fits after alfentanil and propofol. Anaesthesia 1989; 44: 532–3.
  12. Hendley B. Convulsions after cocaine and propofol. Anaesthesia 1990; 45: 788–9.
  13. Shearer E. Convulsions and propofol. Anaesthesia 1990; 45: 255–6.[ISI][Medline]
  14. Thomas J, Boheimer N. An isolated grand mal seizure 5 days after propofol anaesthesia. Anaesthesia 1991; 46: 508.
  15. Makela J, Iivanainen M, Pieninleroinen I, et al. Seizures associated with propofol anesthesia. Epilepsia 1993; 34: 832–5.[ISI][Medline]
  16. Sutherland M, Burt P. Propofol and seizures. Anaesth Intensive Care 1994; 22: 733–7.[ISI][Medline]
  17. Strachan A, Raithatha H. Propofol myoclonus. Can J Anaesth 1996; 43: 536–7.
  18. Cochran D, Price W, Gwinnutt C. Unilateral convulsions after induction of anaesthesia with propofol. Br J Anaesth 1996; 76: 570–2.[Abstract/Free Full Text]
  19. Harrigan P, Browne S, Quail A. Multiple seizures following re-exposure to propofol. Anaesth Intensive Care 1996; 24: 261–4.[ISI][Medline]
  20. Eimerl D, Steiner I. Case 2: 1995—seizures associated with propofol anesthesia. Isr J Med Sci 1996; 32: 334–6.[ISI][Medline]
  21. Bendiksen A, Larsen L. Convulsions, ataxia and hallucinations following propofol. Acta Anaesthesiol Scand 1998; 42: 739–41.[ISI][Medline]
  22. Herrema I. A 10-second convulsion during propofol injection? Anaesthesia 1989; 44: 700.
  23. McManus K. Convulsion after propofol/enflurane. Anaesth Intensive Care 1992; 20: 245.
  24. Dingwall A. Oculogyric crisis after day case anaesthesia. Anaesthesia 1987; 42: 565.[ISI][Medline]
  25. Saunders P, Harris M. Opisthotonus and other unusual neurological sequelae after outpatient anaesthesia. Anaesthesia 1990; 45: 552–7.[ISI][Medline]
  26. McHugh P. Acute choreoathetoid reaction to propofol. Anaesthesia 1991; 46: 425.
  27. Reynolds L, Koh J. Prolonged spontaneous movement following emergence from propofol/nitrous oxide anesthesia. Anesth Analg 1993; 76: 192–3.[Abstract/Free Full Text]
  28. Gildar J. Another case report of opisthotonos and propofol. Anesth Analg 1993; 76: 1171.
  29. Orser B, Oxorn D. Propofol, seizure and antidepressants. Can J Anaesth 1994; 41: 262–7.[Free Full Text]
  30. Hughes N, Lyons J. Prolonged myoclonus and meningism following propofol. Can J Anaesth 1995; 42: 744–6.[Abstract/Free Full Text]
  31. Zabani I, Vaghadia H. Refractory dystonia during propofol anaesthesia in a patient with torticollis-dystonia disorder. Can J Anaesth 1996; 43: 1062–4.[Abstract/Free Full Text]
  32. Bragonier R, Bartle D, Langton-Hewer S. Acute dystonia in a 14-yr old following propofol and fentanyl anaesthesia. Br J Anaesth 2000; 84: 828–9.
  33. Strowbridge N. Postoperative opisthotonus following the use of propofol. J R Army Med Corps 1989; 135: 79–80.[Medline]
  34. deLima J, Scarf M, Cooper M. Propofol "convulsions" again? Anaesth Intensive Care 1992; 20: 396–7.[ISI][Medline]
  35. Diltoer M, Rosseneu S, Ramet J, et al. Anticholinergic treatment for choreoathetosis in a child after induction with propofol. Anesth Analg 1996; 82: 669–75.
  36. Modica PA, Tempelhoff R, White PF. Pro- and anticonvulsant effects of anesthetics (Part II). Anesth Analg 1990; 70: 433–44.[Free Full Text]
  37. Borgeat A, Wilder-Smith O, Tassonyi E, Suter P. Propofol and epilepsy: time to clarify. Anesth Analg 1994; 78: 190–9.[Free Full Text]
  38. Orser B. Propofol-induced neuroexcitation and receptor desensitization. Can J Anaesth 1994; 41: 366–71.[Free Full Text]
  39. Lee A. Treatment of drug-induced dystonic reactions. JACEP 1979; 8: 453–7.[ISI][Medline]
  40. Meuret P, Backman S, Bonhomme V, et al. Physostigmine reverses propofol-induced unconsciousness and attenuation of the auditory steady state response and bispectral index in human volunteers. Anesthesiology 2000; 93: 708–17.[ISI][Medline]
  41. Schatzberg A, Nemeroff C. Textbook of psychopharmacology. 2nd ed. Washington DC: American Psychiatric Press, Inc, 1998.
  42. Etzel J. Diphenhydramine-induced acute dystonia. Pharmacotherapy 1994; 14: 492–6.[ISI][Medline]
Accepted for publication January 3, 2002.




This article has been cited by other articles:


Home page
 Br J AnaesthHome page
M. A. Allford
Prolonged myotonia and dystonia after general anaesthesia in a patient taking gabapentin
Br. J. Anaesth., August 1, 2007; 99(2): 218 - 220.
[Abstract] [Full Text] [PDF]

Home page
 Journal of Pharmacy PracticeHome page
S. R. White
Acute Dystonic Reaction and the Neuroleptic Malignant Syndrome
Journal of Pharmacy Practice, June 1, 2005; 18(3): 175 - 187.
[Abstract] [PDF]

Home page
 Anesth. Analg.Home page
J. Sprung, F. M. Choudhry, and B. A. Hall
Extrapyramidal Reactions to Ondansetron: Cross-Reactivity Between Ondansetron and Prochlorperazine?
Anesth. Analg., May 1, 2003; 96(5): 1374 - 1376.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a colleague
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via ISI Web of Science (9)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Schramm, B. M.
Right arrow Articles by Orser, B. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Schramm, B. M.
Right arrow Articles by Orser, B. A.

Lippincott, Williams & Wilkins Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999 HighWire Press