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| ADR REPORT |
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| Year : 2009 | Volume
: 55
| Issue : 1 | Page : 69-71 |
Convulsions with propofol: A rare adverse event
R Garg, M Dehran
Department of Anesthesiology and Intensive Care, All India Institute of Medical Sciences, Ansari Nagar, New Delhi -110 029, India
| Date of Submission | 06-Jun-2008 |
| Date of Decision | 22-Jul-2008 |
| Date of Acceptance | 25-Jul-2008 |
| Date of Web Publication | 24-Feb-2009 |
Correspondence Address:
R Garg
Department of Anesthesiology and Intensive Care, All India Institute of Medical Sciences, Ansari Nagar, New Delhi -110 029
India
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/0022-3859.48444
We present a rare but potentially harmful adverse reaction of propofol. A 50-year-old patient was posted for laparoscopic cholecystectomy, developed generalized convulsions after few seconds of propofol administration at anesthesia induction. Convulsions subsided with intravenous administrations of thiopentone and midazolam. Patient remained hemodynamically stable and surgery was uneventful. Blood sugar, serum electrolytes and arterial blood gas analysis were normal. Postoperatively, there was no evidence of postictal phase, serum electrolytes and postoperative computerized tomographic scanning of the head were normal. Patient had uneventful recovery. The administration of propofol has been associated with abnormal movements collectively termed as seizure-like phenomenon. Despite the claims that propofol may have proconvalsant activity, there is significant amount of evidence to the contrary also. The pathophysiological mechanisms behind the neuroexcitatory symptoms with propofol are unknown. Propofol alters the conscious state, the transition from the conscious state to anesthesia or vice versa may be a particularly vulnerable period and may be prolonged after the end of propofol administration.
Keywords: Anticonvulsant, convulsions, propofol, seizures
How to cite this article:
Garg R, Dehran M. Convulsions with propofol: A rare adverse event. J Postgrad Med 2009;55:69-71 |
Many anesthetic and analgesic drugs have been reported to produce seizures. Propofol has gained widespread popularity, especially in daycare surgery as an induction/sedation agent and for Total Intravenous Anesthesia. This case highlights a rare (incidence<1%) but potentially harmful complication of this intravenous anesthetic agent. [1]
| :: Case Report | |  |
A 50-year-old male patient was posted for laparoscopic cholecystectomy for chronic cholecystitis. On preanesthetic evaluation, patient was American Society of Anaesthesiologists physical status Class I, weighing 55 kg. History was not suggestive of any other comorbid illness including hypertension, diabetes, seizure disorder and tuberculosis. His pulse rate was 78 beats /min and regular. Blood pressure was 110/70 mm Hg in supine position. Investigations including hemogram, liver and renal function test, electrocardiogram and chest X-ray were normal. Patient was premedicated with tablet diazepam 10 mg and ranitidine 150 mg the night before and 1˝ h before anesthesia in the morning. In the operating room, monitoring included ECG, pulse oximetry, noninvasive blood pressure and capnography. After securing intravenous access, 100 µg of fentanyl was slowly administered intravenously. Anesthesia was induced with intravenous propofol administered slowly, a total of 100 mg (containing 20 mg of preservative-free lidocaine, xylocard) over 30 sec. After a few seconds patient had generalized tonic-clonic seizures which were more prominent over the trunk and upper extremity but lesser in the lower extremity. Seizures decreased with intravenous administrations of thiopentone sodium 125 mg. But the seizure activity recurred within 10 sec. Thiopentone 75 mg and midazolam 1 mg were administered. The seizures subsided completely. Thereafter, airway was secured with tracheal tube after achieving neuromuscular blockade with vecuronium bromide. Patient remained hemodynamically stable and surgery was uneventful. Intraoperatively, blood sugar, serum electrolytes and arterial blood gas analysis were normal. At the end, residual neuromuscular blockade was reversed and trachea was extubated when patient was fully conscious and had regular spontaneous breathing. He was shifted to postanesthesia care unit for further management. Postoperatively, there was no evidence of postictal phase, serum electrolytes and postoperative computerized tomographic (CT) scanning of the head were normal. Neurology consultation was taken which revealed no neurological abnormality. Patient had uneventful recovery.
| :: Discussion | | |
Propofol has gained worldwide acceptance as an induction agent since its launch in 1986. [2] The administration of propofol is associated with generalized tonic-clonic seizures, focal motor seizures, increased tone with twitching and rhythmic movements, opisthotonus and involuntary movements, collectively termed as seizure-like phenomenon (SLP). [3] Despite numerous case reports, there is no clear consensus regarding the prevention and management of such adverse events. SLP has been reported with propofol administration in healthy as well as in epileptic patients. [2],[4],[5],[6],[7] Many instances of mild dystonic reactions after administration of propofol may go unreported, some have even questioned about their occurrence as adverse. Such movements were observed in 75% of children receiving propofol as compared to 20% receiving thiopental. [6] These movements after propofol induction seem to be rare in adults. At present, the influence of dosage and speed of injection on their incidence is not clear.
Despite the claims that propofol has proconvulsant activity, there is significant evidence to the contrary. Propofol reduces the effective duration of convulsion during modified electroconvulsive therapy, thus favoring its anticonvulsant property. [8] Hewitt et al ., concluded from their study, using electrocorticography in patients with intractable epilepsy, that propofol has anticonvulsant activity without having any proconvulsant activity. [2] Propofol infusions have been shown to be effective in controlling status epilepticus (as assessed neurophysiologically). [4] The use of propofol, barbiturates or midazolam in the management of refractory status epilepticus has been reported. [9] Baraka et al., reported a patient with no history of epilepsy, undergoing spermatic veins ligation under epidural anesthesia with propofol sedation. At the end, after 5 min of propofol discontinuation, patient developed tonic-clonic convulsions. He concluded that these convulsions might be due to lidocaine- induced systemic toxicity, which was masked by the anticonvulsant action of propofol. [7]
The pathophysiological mechanisms of the neuroexcitatory symptoms with propofol are unknown. The typical electroencephalogram (EEG) pattern following propofol sedation in healthy volunteers is biphasic, consisting of an initial increase in frequency from alpha to beta waves, which is then followed by a slowing to delta waves. Meyer et al ., demonstrated in their study, distinct EEG patterns following propofol-induced sedation in children with epilepsy and children with learning difficulties with no occurrence of SLP of epileptic origin. [10] Drugs or a physiological state such as sleep which produces partial functional deafferentation of the cortex create conditions which promote synchronization of neuronal activity. The balance between inhibition and suppression of excitation, on the one hand, and production of synchrony on the other, determines if the overall effect is to activate or suppress epileptiform EEG discharges. [2] Spontaneous movements induced by propofol are not related to cortical activity and subcortical origin has been suggested. [6] In high doses propofol depresses both the cortex and subcortex thus acting as anticonvulsant and in low doses it may act as proconvulsant by inhibiting the inhibitory subcortex, resulting in the 'release' of normal hyperexcitability in the cortex. [4]
A criticism of these reports is that on many occasions combinations of drugs were administered, making the implication of propofol impossible, as many of the anesthetic agents may cause clinically evident seizures. There are reports of grand ma1 seizure-like motor behavior in patients after fentanyl. [11] The abnormal movements could be due to nonepileptic myoclonus produced by the interaction of these narcotics with opiate receptors leading to blockade of cortical inhibitory pathways. Patients treated with higher doses of fentanyl and its analogues may fail to exhibit seizure-like movements as high plasma opioid levels depress central neural centers. [11],[12]
Lidocaine is capable of producing seizures in toxic dose ranges by cortical hyperstimulation related to selective depression of inhibitory cortical synapses and neurons. [13] For attenuating the pain of propofol injection, 20 mg of preservative-free lidocaine was used in our patient, which is much less than its toxic dose.
Propofol preservatives could be the inciting factors which need to be investigated. Seizures subsequent to anaphylaxis with the drug or its adjuvants may be a possibility. But in the present case, this possibility is unlikely because no bronchospasm, erythema or hypotension was observed.
Seizures during anesthesia induction can result in dislodgement of intravenous cannula/lines, monitoring devices may injure the patient and dislodge laryngeal mask airway. [5] In our patient, the course of postoperative awakening was normal. Normal CT scan rules out any major anatomic visual causes. In this case, seizures developed after propofol administration, so we were in a dilemma whether to give more propofol for seizure suppression or to use some other drug. Controversy persists whether to use more propofol or some other anticonvulsant for seizure suppression as it is liable to precipitate seizures. Therefore, thiopentone and midazolam were used in our patient as they have been used effectively in the past. [12]
Since daycare surgery has gained great popularity and in the future probably will be even more common, we would like to stress the importance of seizure activity with propofol and a high vigilance is warranted perioperatively.
| :: References | | |
| 1. | Islander G, Vinge E. Severe neuroexcitatory symptoms after anaesthesia-with focus on propofol anaesthesia. Acta Anaesthesiol Scand 2000;44:144-9.  |
| 2. | Hewitt PB, Chu DL, Polkey CE, Binnie CD. Effect of propofol on the electrocorticogram in epileptic patients undergoing cortical resection. Br J Anaesth 1999;82:199-202. |
| 3. | Walder B, Tramer MR, Seeck M. Seizure like phenomenon and Propofol: A systematic review. Neurology 2002;58:1327-32. |
| 4. | Cochran D, Price W, Gwinnutt CL. Unilateral convulsion after induction of anaesthesia with propofol. Br J Anaesth 1996;76:570-2. |
| 5. | Rath GP, Bithal PK, Prabhakar H. Propofol induced myoclonus may dislodge laryngeal mask airway. Indian J Anaesth 2006;50:45-6. |
| 6. | Krauss JK, Akeyson EW, Giam P. Jankovic J. Propofol induced dyskinesias in parkinson's disease. Anesth Analg 1996;83:420-2. |
| 7. | Baraka A, Aouad M. Is propofol anticonvulsant or proconvulsant? Can J Anaesth 1997;44:1027-9. |
| 8. | Walder B, Seeck M, Tramer MR. Propofol versus methohexital for electroconvulsive therapy. J Neurosurg Anesthesiol 2001;13:93-8. |
| 9. | Rossetti AO, Reichharty MD, Schaller MD, Despland PA, Bogousslavsky J. Propofol treatment of refractory status epilepticus: A study of 31 episodes. Epilepsia 2004;45:757-63. |
| 10. | Meyer S, Shamdeen MG, Kegel B, Mencke T, Gottschling S, Gortner L, et al . Effect of propofol on seizure like phenomenon and electroencephalographic activity in children with epilepsy vs children with learning difficulties. Anaesthesia 2006;61:1040-7. |
| 11. | Fujimoto T, Nishiyama T, Hanaoka K. Seizure induced by a small dose of fentanyl. J Anesth 2003;17:55-6. |
| 12. | Parvianen I, Uusaro A, Kδlviδinen R, Kaukanen E, Mervaala E, Ruokonen E. High dose thiopental in the treatment of refractory status epilepticus in intensive care unit. Neurology 2002;59:1249-51. |
| 13. | Rezvani M, Finkelstein Y, Verjee Z, Ranilton C, Koren G. Generalized seizures following topical lidocaine administration during circumcision: Establishing causation. Paediatr Drugs 2007;9:125-7. |
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