Schramm, Belinda M. MB, BS, FANZCA; Orser, Beverley A. MD, PhD
Department of Anaesthesia, Sunnybrook & Women’s College Health Sciences Centre, University of Toronto, Canada
January 3, 2002.
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 email@example.com.
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.
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.
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 (http://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.
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 vitro experiments 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).
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).
The authors thank Jenny Lam-McCulloch for her assistance with preparation of the manuscript.
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