Successful resuscitation in a case of sudden cardiac arrest in an epileptic patient posted for spinal surgery.

A 17-year-old girl was posted for spinal surgery for traumatic spinal injury. The patient was a well-controlled epileptic with history of seizure since 8 years of her age. She was induced with thiopentone sodium and muscle relaxant atracurium was administered. Minutes after that, she had an episode of ventricular tachycardia, this converted to ventricular fibrillation despite of institution of cardiopulmonary resuscitation (CPR). CPR was continued for a prolonged period of 45 minutes and after 45 minutes, QRS complexes appeared and later sinus rhythm restored. Next 24 hours, she was kept on mechanical ventilation. Within 24 hours, Glasgow Coma Scale (GCS) improved and patient was conscious and extubated. We suggest that the neuromuscular blocking drug contributed to an anaphylactic reaction which might be the cause of cardiac arrest and highlight the importance of prolonged resuscitation and successful outcome in this scenario.

INTRODUCTION

We report a case of sudden cardiac arrest (SCA) following induction and muscle relaxant administration probably due to an anaphylactic reaction[1] from neuromuscular blocker, atracurium being the drug in this case.

Many well-described adverse drug effects, including anaphylactic and anaphylactoid reactions, have occurred after administration of neuromuscular blocking agents.[23] Several reports of anaphylactic reactions after administration of atracurium have appeared.[45]

Atracurium besylate, an intermediate acting non-depolarizing neuromuscular blocking agent, is one of the common agents causing anaphylaxis. It causes anaphylaxis due to – (1) chemically mediated histamine release from mast cell, (2) IGE-mediated anaphylaxis, and (3) cross sensitization.

CASE REPORT

An 18-year-old Muslim female patient was admitted with a history of traumatic paraparesis of lower limbs and pain in the lower back for last one month after falling from a height. She had a history of epilepsy since 8 years of age and for that she was taking phenytoin sodium and levetiracetam regularly. Investigations revealed that she had a wedge fracture at 3rd lumbar spine. Computerised Topographic (CT) scan of brain revealed general cortical dysthymia. She was posted in operation theater (OT) for lumbar pedicular screw fixation. There was no known history of hypersensitivity to any drug or food. She had normal metabolic activity with no other significant past medical or surgical history. She had no previous exposure to anesthesia. Preoperative investigations were within normal limit.

Preoperatively, patient was advised to continue antiepileptic drugs till day of operation. After informed consent was obtained, patient was taken up for anesthesia. The patient was fasted overnight (8 hours) and allowed free fluids till 2 to 3 hours preoperatively.

After receiving the patient in OT, monitors were attached and patient preparation was done in the trolley as prone position for surgery was required. The patient was in sinus rhythm with BP - 118/74 mm of Hg, Pulse - 68/min/regular, SpO2-98-99% in room atmosphere.

Patient was fasted overnight and received tab. Lorazepam 1 mg, ranitidine 300 mg the night before surgery. In the OT, patient was patient was preoxygenated with 100% oxygen for 5 minutes and received 1 mg midazolam, 100 mg tramadol hydrochloride, 0.02 mg glycopyrrolate as premedication. Then, the patient was induced with 200 mg thiopentone sodium and paralyzed with 20 mg atracurium besylate and intubated with a 7.5-mm endotracheal tube. With patient movement continuing, another 5 mg dose was administered. Within minutes after the 2nd dose, patient had sudden hypotension and pulse became impalpable. Electrocardiogram (E.C.G) showed episode of ventricular tachycardia. Heart sound were inaudible, BP and SpO2 were not recordable. At the moment of detection, cardiopulmonary resuscitation (CPR) was started according to ACLS 2010 protocol with HR100bpm, 5 cm depth of compression, RR10bpm of 1 second duration each, rotating compressors every 2 minutes, adrenaline repeated every 5 minutes, amiodarone bolus 300 mg. Intraoperative cardiac arrests are reported to have better prognosis as detection is earlier and prompt CPR. SpO2 was in the range of 80% and EtCO2 was in the range of 6-10 mm Hg. Considering the age of the patient and rapid detection and immediate institution of CPR, CPR was continued. It took a rigorous 45 minutes of continuous CPR, 6 DC shock all of 360 J monophasic shock and 9 mg of adrenaline in total and then QRS complexes were noted in the ECG at 30-45 bpm and gradually it came up to 60 bpm. The rhythm was sinus. ROSC was detected with etco2 > 10 mmhg, DBP > 20 mmhg. Carotid pulses were noted. After 5 minutes, BP was recorded to be 92/45 mmHg with EtCO2 rising to 37 mmHg, urine output started increasing, and SpO2 was 89-92%. Patient's pupils were dilated, not reacting and apnea continued. After another 30 minutes, patient started taking spontaneous respiration at a rate of 12-14/min. Pupils were still dilated, non reacting, GCS was 3 (patient intubated).

Patient was then transported to intensive therapeutic unit (ITU) with transport monitoring and epinephrine and dopamine infusions, ventilated with 100% oxygen by an Ambu bag.

In ITU, patient was kept in SIMV+PS MODE, TV – 6 ml/kg (350 ml), BR – 14/min, O2-0.8, PS – 14 cm H2O, PEEP - 5 cm H2O. Infusions were adrenaline (0.2 ug/kg/min) and dopamine (5 μg/kg/min). Phenytoin (5 mg/kg bolus) infusion over 6 hours followed by 100 mg TID was added. Low-dose steroid hydrocortisone 50 mg QID continued for 4 days.

In ITU, patient was stable hemodynamically with BP - 104/64 mmHg, pulse - 72/min/S.R, pupils - sluggishly reacting, and corneal reflex present.

After 4 to 5 hours, GCS started improving with patient responding to pain. Urine output was about 2 ml/kg/hr. SpO2-99-100% was maintained. Initially on examination of chest, few creps were present on the right side which gradually resolved with intratracheal suctioning only, without the need for diuretics. A broad-spectrum antibiotic was added.

Investigations sent on day 1 included complete blood counts, ECG, chest-x-ray (CXR), arterial blood gas, echocardiogram, coagulation profile, Blood sugar, urea creatinine, and LFT. All reports were within normal limits except ECG showed T wave inversions in lead V1-V3, CXR showed cardiomegaly, and creatinine was 1.7. An echo was advised to be done.

Patient was kept in PS of 8 cm H2O for 2 hours and clinically assessed. She was hemodynamically stable, conscious, oriented, urine output was normal; SpO2 was 99-100%. Thereafter, she was extubated after suctioning, 100% O2 administration and kept in a propped up position and nebulized with salbutamol and budesonide respules. She was observed after that and was stable.

After extubation, patient was complaining of lower limb pain which was probably caused by her previous trauma (spinal). She was also complaining of pain over lower sternum. Early alimentation was advised and fluids per mouth were ordered. Infusions were tapered off. The patient was kept in ITU for 48 hours post arrest and resuscitation and then transferred to orthopedic ward in a stable condition.

For confirmation of diagnosis of anaphylaxis, we performed intradermal prick test since serum tryptase assay was not available here. A small amount of erythema appeared at a concentration of 1:100 and a wheal and flare at 1:10. Full concentration of atracurium produced a significant wheal and flare. Skin testing by prick and intradermal injection to thiopentone, tramadol yielded negative results. Skin test results with the same concentration of atracurium in two healthy control subjects were negative.

Patient was advised to come for follow up after a month to the preanesthetic clinic and a brief minimental score examination was done. After the test, no cognitive dysfunction was noted.

DISCUSSION

Anaphylaxis is an acute, severe, and potentially life-threatening reaction that often is difficult to recognize during general anesthesia. The incidence of anaphylactic reactions during general anesthesia has been estimated to be 1 in 6 000, with neuromuscular blocking agents responsible for 80% of the cases.[6]

The diagnosis of anaphylactic reaction usually is based on clinical suspicion. Biochemical studies may be helpful in confirming the diagnosis.

Patients who have experienced anaphylactic reactions in the operating room require evaluation to identify the causal agent and to guide selection of medication for future anesthesia. Identification of the drug may be difficult because many medications are administered in a relatively short span of time. Skin testing is the method generally used to confirm specific drug hypersensitivity in patients after an anaphylactic reaction. Skin tests are standardized for IgE-mediated reactions and are highly specific.[7] After intradermal injection of the suspected allergen, an immediate reaction is characterized by the appearance of a wheal and flare, which is highly predictive of sensitization. Leynadier et al.[8] found a significant correlation between prick tests and intradermal injection in identifying the causative agent.

Cross-reactivity of neuromuscular blocking agents is frequent because of the quaternary ammonium radicals associated with this class of drugs. Cross-reactivity depends on the configuration of the antibody that is related to the structure of the molecule (distance between the quaternary ammonium ions, flexibility of the molecule). Muscle relaxants with a rigid backbone between the ammonium ions (pancuronium) are less reactive than those with flexible molecules (succinylcholine).[9] It is essential that any patient with a history of an allergic reaction to a neuromuscular blocking agent be tested for cross-reactivity.

In this case, airway establishment was uneventful and confirmed by EtCO2, SpO2, and auscultation. There was no aspiration. Even after the induction agent, there was no event noted and patient was stable. Preoperatively, check up did not reveal any cardiological problem with normal exercise tolerance, no history of palpitation, dizziness, syncope, dyspnea, and chest pain. The only problem from system-wise review was the history of epilepsy which was well controlled with drugs. All syringes were properly labeled and drugs diluted according to fixed values. There was no problem with administration or dosing of the drugs. These only confirmed that the arrest was probably precipitated by atracurium and especially it happened during emergence/reversal of patient as typically described in literatures.

Another point to be highlighted in this case is the prolonged CPR[10] that we continued for 45 minutes despite a refractory asystole despite of adequacy and early institution of CPR. The reason for prolonged arrest can be tried to be explained in the light of antiepileptic drugs which prolong the Na-K channels.

As in our patient, many patients with anaphylactic reactions have had no previous exposure to neuromuscular blocking drugs. An IgE-mediated reaction may occur on the first administration of these agents if the patient has been exposed to one of their components. The mechanism of anaphylactic reaction to muscle relaxants was suggested by the finding of cross-reactivity between muscle relaxants and substances with quaternary ammonium ions.[11] Sensitization to neuromuscular blocking agents is caused by the quaternary ammonium components of these drugs, which also are widely found in other drugs, foods, soaps, and cosmetics.[12] The high incidence of anaphylactic reaction to neuromuscular blocking agents in women may be explained by increased exposure to cosmetics and cleaning agents.[13]

CONCLUSION

In conclusion, this case highlights a SCA which was in all probability due to anaphylaxis due to a muscle relaxant, atracurium being the drug in this case. Although it is a rare complication, the drug in the report is a widely used one and therefore of considerable interest to us. Another important point noted is the prolonged resuscitation done in this case and due to early institution and adequacy of CPR, the neurologic outcome was good and no neurocognitive defect was noted.