A rare but potentially harmful adverse reaction to propofol is reported. A 33-year-old patient who was scheduled for septorhinoplasty, with American Society of Anesthesiologists (ASA) status I, developed abnormal muscular movements including opisthotonus posture after a few seconds of propofol administration at anaesthesia induction. 

Presentation

His condition persisted for less than three minutes in spite of 500mg of propofol. Convulsions subsided within two minutes of rocuronium. The patient remained haemodynamically stable after 20 minutes with the introduction of remifentanil, and surgery was uneventful. 

Blood sugar, serum electrolytes and arterial blood gas (ABG) analysis were normal except for slight hyponatraemia and hypocalcaemia. Post-operatively, there was no evidence of abnormal muscular phase. Serum electrolytes and blood sugar, electrocardiography and chest x-ray (CXR) were normal. The man was admitted to the intensive care unit (ICU) for close monitoring for 24 hours. The patient had an uneventful recovery. 

The administration of propofol has been associated with abnormal movements collectively termed ‘seizure-like phenomena’. Despite claims that propofol may have proconvulsant activity, there is a significant amount of evidence to the contrary. The pathophysiological mechanisms behind the neuroexcitatory symptoms with propofol are unknown. Propofol alters the conscious state and the transition from the conscious state to anaesthesia or vice versa may be a particularly vulnerable period.

Case report

A 33-year-old male patient was listed for septorhinoplasty. On pre-anaesthetic evaluation, the patient was ASA class I, weighing 84kg. History was not suggestive of any other comorbid illness, eg. hypertension, diabetes or seizure disorder. However, the patient was an alcoholic. 

He had no history of previous anaesthetics and was not on any regular medication. He was allergic to penicillin. On arrival he seemed to be very anxious and slightly sweaty. His pulse was 90-100 beats/min and regular. Blood pressure was 140/85mmHg. Investigations including full blood count (FBC) were normal.

The patient was not premedicated before being anaesthetised. In the operating room, monitoring included: electrocardiogram (ECG), pulse oximetry, non-invasive BP, temperature monitoring and capnography. After securing intravenous access, 100µg of fentanyl was slowly administered intravenously. 

Anaesthesia was induced with intravenous propofol administered slowly, a total of 350mg over 30 seconds. After a few seconds the patient started jerky movements which were more prominent over the trunk and upper extremity and lesser in the lower extremity, and also had opisthotonic posture, making it difficult to maintain his airway. He was given more propofol, with up to 500mg propofol given to him altogether, but the jerky movements remained during induction. Guedel’s airway was inserted to maintain his airway, and once EtCO2 was traced with a bag ventilation, rocuronium 80mg was given and the patient’s abnormal movements subsided, with bag ventilation becoming easier.

Episodes of abnormal movements remained there for < 3 minutes. Endotracheal intubation was also difficult, grade 3 on laryngoscopy, and endotracheal tube (ETT) was inserted with a bougie after three attempts in total. ETT was deemed secured after listening bilaterally to his chest. Seizure-like movements stopped after two minutes of muscle relaxants. The seizures then subsided completely. 

During intubation the patient desaturated low 90s and after being put on ventilator his SpO2 remained < 95% for the next 20 minutes with FiO2 0.65-1.0. Peak airway pressure was high, around 26-28mmHg, so the patient was ventilated with pressure-controlled ventilation (PCV) to achieve good tidal volume. There was no sign of bronchospasm. 

Haemodynamically the patient was slightly unstable with a fluctuating heart rate of 65-95 beats per minute and, although BP, after initial surge, remained stable with the introduction of remifentanil, the ECG showed tall T-like changes. Surgery was otherwise uneventful. 

Morphine 6mg, paracetamol 1,000mg and ondansetron was administered. Intraoperatively, blood sugar and ABG analysis were done to find out about electrolytes, specifically potassium. On ABG analysis abnormally detected findings were:

• Sodium 131mmol/L
• Calcium 0.88mmol/L
• HCO3 14
• BE –9.

However, these findings were normal:

• Potassium 4.7mmol/L
• PH 7.38
• PCO2 3.8kpa
• PO2 10.9kpa
• Blood sugar 6.6mmol/L.

The patient was settled as surgery progressed. ECG leads were adjusted and his heart rhythm became normal.

At the end of surgery, residual neuromuscular blockade was reversed with sugammadex and trachea was extubated when the patient was fully conscious and had regular spontaneous breathing. 

He was kept in the post-anaesthesia care unit (PACU) for further management. He was fully awake with 98% SpO2 on 0.35 FiO2. ECG rate was in the 80s and rhythm was normal and regular. The patient was fully conscious with no episode of any abnormal movements in PACU. Post-operatively he was transferred to the intensive care unit (ICU) for closed monitoring and there was no evidence of abnormal muscular movements phase during his 24-hour stay in ICU. 

Other investigations, eg. serum electrolytes, 12-lead ECG, CXR, urea and erythrocytes (U+Es), were all normal. Toxicology screening and alcohol levels were normal. ABG analysis was normal after 12 hours in ICU. 

Medical consultation was taken, which revealed no neurological abnormality. The patient had an uneventful recovery. 

Discussion

Propofol has been commonly used as an induction agent since 1986.1,2 The administration of propofol is associated with generalised tonic-clonic seizures, focal motor seizures, increased tone with twitching and rhythmic movements, and opisthotonus and involuntary movements – collectively termed as seizure-like phenomena (SLP).1,3 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.2,4-9 Many instances of mild dystonic reactions after administration of propofol may go unreported, some have even questioned whether or not their occurrence is adverse. Such movements were observed in 75% of children receiving propofol compared to 20% receiving thiopental.6 

These movements after propofol induction seem to be rare in adults, but there have been some case reports regarding SLP, both at induction and in the post-operative period, which have been previously reported on.1,5-7

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 (ECT), thus favouring its anticonvulsant properties.10,11 

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.4 However, the use of propofol in the management of refractory status epilepticus has been reported along with thiopentone.12

The 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 that distinct EEG patterns followed propofol-induced sedation in children with epilepsy, and children with learning difficulties with no occurrence of SLP of epileptic origin.13 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 an anticonvulsant, and in low doses it acts as a proconvulsant by inhibiting the inhibitory subcortex. This results in the ‘release’ of normal hyperexcitability in the cortex.4

On many occasions combinations of drugs have been administered, as many of the anaesthetic agents (including propofol) can cause clinically evident seizures. There are reports of grand mal seizure-like motor behaviour in patients after taking fentanyl.11 The abnormal movements could be due to non-epileptic myoclonus produced by the interaction of these narcotics with opiate receptors, leading to the blocking 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 centres.14 In this case, however, the 1mcg/kg fentanyl given three minutes before induction was not the source of these abnormal movements.

Seizures subsequent to anaphylaxis with the drug or its adjuvants may be a rare possibility. But in the present case, this possibility is unlikely because no erythema or hypotension was observed. However, peak airway pressure was increased, but there were no signs of bronchospasm on auscultation.

Serum electrolytes via ABGs showed sodium was slightly low at 131mmol/L and calcium at 0.88mmol/L was also low, however, hyponatraemia and hypocalcaemia may cause seizure-like activity, but these values were not critically low in this patient. Toxicology screen was normal so other drugs, possibly causing SLP, were ruled out.

In this patient, the course of post-operative awakening was normal and there was no evidence of post-operative abnormal muscular movements. There are case reports showing abnormal opisthotonus posture from propofol with seizures possibly developing. Controversy persists about whether or not to use more propofol or some other anticonvulsant for seizure suppression as it is liable to precipitate seizures after administration of propofol.