Malignant hyperthermia (MH) and thyroid storm are perioperative emergencies that may present with similar signs and symptoms. MH is an autosomal dominant pharmacogenetic disorder with an estimated incidence of episodes during anesthesia ranging from 1:10,000 to 1:250,000.1 The generally accepted prevalence is thought to be 1:50,000.2 The resulting hypermetabolic sequela requires immediate treatment to halt the reaction, or organ failure and death will ensue. Unfortunately, the presenting symptoms share many similarities with thyroid storm. Because the management of these crises is drastically different, proper rapid identification is essential. We encountered this dilemma in a patient with poorly controlled hyperthyroidism undergoing a total thyroidectomy. Hyperthermia, hypertension, metabolic acidosis, and tachycardia can be seen in both, but rapidly rising arterial carbon dioxide (PaCO2) and temperature and muscle rigidity suggest a diagnosis of MH over thyroid storm.
Written consent was obtained from the patient for this case report.
A 25-year-old, 82-kg man with a history of hyperthyroidism and Graves disease presented for a total thyroidectomy because of inadequate medical management despite propranolol 80 mg by mouth daily and methimazole 40 mg by mouth every 8 hours. His symptoms included palpitations, shaking, heat intolerance, and exophthalmos. The patient never had anesthesia, but both parents had experienced general anesthesia several times. There was no family history of anesthetic complications.
On the morning of surgery, he took his methimazole 40 mg and propranolol 80 mg. Preoperative vitals were heart rate (HR) 85 beats per minute, respiratory rate (RR) 18 breaths per minute, noninvasive blood pressure 138/98 mm Hg, peripheral capillary oxygen saturation 100%, and oral temperature (T) 36.9°C. Preoperative thyroid studies 4 months earlier showed free T3 of 1782 pg/dL and free T4 of 3.8 ng/dL. Two weeks before surgery, the thyroid-stimulating hormone was <0.01 μIU/mL and free T3 of 440 pg/dL.
Midazolam 2 mg was administered intravenously (IV) for extreme anxiety. Anesthesia was induced IV with fentanyl 100 μg, lidocaine 100 mg, propofol 200 mg, and succinylcholine 100 mg. A depolarizing muscle relaxant was used to avoid residual neuromuscular blockade and facilitate intraoperative recurrent laryngeal nerve monitoring. At no point was a nondepolarizing muscle relaxant used. During direct laryngoscopy, the provider noted that the patient’s jaw was “a little rigid” but was able to open the patient’s mouth and intubation was otherwise uneventful. After intubation, vital signs were HR 71, RR 12, noninvasive blood pressure 134/73 mm Hg, peripheral capillary oxygen saturation 95%, axillary T 36.3°C, and EtCO2 45 mm Hg. The ventilator settings on 100% (FIO2: 1.0) were tidal volume (TV) 550 mL, RR 12, and minute volume (MV) 6.6 L/min. Within 15 minutes of induction, the TV was increased to 675 mL (MV: 8.1 L/min) and FIO2 was decreased to 0.5. These settings were maintained for the next 45 minutes. General anesthesia was provided with desflurane in an air/oxygen mixture and a remifentanil infusion. No warming blanket or fluid warmer was used.
Approximately 1 hour into the case, T had risen to 37.4°C. The RR was increased to 14 (MV: 9.4 L/min) to keep the EtCO2 in the low-to-mid 40s mm Hg. Thirty minutes later, TV was increased to 700 and RR to 16 (MV: 11.2 L/min) to keep EtCO2 45 mm Hg. T at this time was 37.9°C. Blood pressure and HR remained unchanged. At this point, there was concern for a hypermetabolic reaction and help was called into the room. Over the next 20 minutes, both the temperature and EtCO2 rose more rapidly, and the patient was presumed to have MH. Volatile anesthetics were discontinued; a radial arterial line and two 16G peripheral IVs were inserted; 100% FIO2 was administered; and dantrolene 2.5 mg/kg IV was given (Revonto; US WorldMeds, LLC, Louisville, KY). A new ventilator with a clean circuit was brought into the room and connected to the patient. The axillary T peaked at 39.2°C and EtCO2 peaked at 95 mm Hg despite MV 18 L/min. The initial arterial blood gas (ABG) showed pH 7.13, PaCO2 92 mm Hg, PaO2 410 mm Hg, K+ 4.9 mEq/L, and bicarbonate 30 mEq/L. At this time, the patient developed tachycardia up to 110s and became hypotensive with a blood pressure nadir of 59/30. The patient received phenylephrine 600 μg IV in divided doses and tromethamine (THAM) solution 500 mL IV. There was rapid resolution of the hypotension and tachycardia. The patient’s groin and axilla were packed with ice, and a Foley catheter was placed. The color of the urine was not noted by the staff. Within 10 minutes, the ABG improved to a pH 7.32, PaCO2 50 mm Hg, PaO2 488 mm Hg, K+ 5.0 mEq/L, and bicarbonate 25 mEq/L. After 30 minutes, the patient’s blood gas values were normal. During the resuscitation, furosemide 40 mg, calcium chloride 2 g, and mannitol 12.5 g were also administered IV. The surgery was aborted after completion of a right hemithyroidectomy including the isthmus.
The patient was transferred to the intensive care unit intubated and sedated. He was continued on a dantrolene protocol for 24 hours. He was extubated the following morning, and the remainder of his postoperative course was uncomplicated. Serum myoglobin and creatine kinase peaked at >10,000 ng/mL and 17,995 U/L on postoperative day #0, respectively. On discharge, the patient displayed no ill effects; his creatine kinase was downtrending; he was neurologically intact; and he presented no evidence of renal failure, hyperkalemia, or rhabdomyolysis. Subsequent gene sequencing revealed a mutation (6757 C>T) causing an amino acid substitution (His2253Tyr) in the RYR1 receptor that has been confirmed in the literature to be present in 1 other patient with MH.3 Subsequent completion thyroidectomy was accomplished without incident under total IV anesthesia without triggering agents.
MH, a well-known but rare reaction to volatile anesthetics and succinylcholine, requires immediate diagnosis and treatment to prevent severe morbidity and mortality. Many of the clinical symptoms of MH are also manifestations of thyroid storm, another medical emergency requiring a different unique management. Early identification of MH is crucial to patient survival, because early removal of triggering agents and administration of dantrolene will interrupt the hypermetabolic reaction and cause resolution of symptoms. The classic symptoms of MH (hyperthermia, hypercapnia, tachycardia, and muscle rigidity) have significant similarities with that of thyroid storm (hypertension, hyperthermia, and tachycardia), which can lead to delayed diagnosis and treatment, or incorrect diagnosis altogether. Our patient had a preoperative history of Graves disease, including palpitations, heat intolerance, and hypertension, that was poorly controlled despite propranolol (80 mg by mouth daily) and very high doses of methimazole (40 mg by mouth 3 times daily). The patient’s calculated Burch and Wartofsky4 score was 40, which is suggestive of impending thyroid storm. Because of this overlap of symptoms and the severity of his Graves disease, additional laboratory information was originally sought, but the accelerating rise in EtCO2 and temperature caused us to initiate therapy for probable MH before the ABG results.
In retrospect, the masseter muscle rigidity present on induction, although with a low positive predictive value for MH, was the earliest suggestion of MH. The presence of masseter muscle rigidity does correlate with an incidence of MH of approximately 15%1 according to blood gas analysis and as high as 59% in children based on muscle biopsy,5 although only 5 of the 41 biopsy-confirmed MH-susceptible patients went on to develop MH symptoms after induction with volatile agents and/or succinylcholine. Despite the majority of studies surrounding masseter muscle rigidity being performed in children, masseter spasm in the setting of hyperthermia or hypercapnia, escalating minute ventilation, or any other symptom of MH should lead to immediate further investigation, if not treatment, for MH.
Our patient did not develop tachycardia until late in the presentation at which time he also developed severe hypotension. The absence of tachycardia, especially in the setting of perioperative β-blockade and/or remifentanil infusion, did not suggest either diagnosis. Higher HRs, according to the point system developed by Burch and Wartofsky,4 make thyroid storm more likely, especially in patients with a history of prior hyperthyroid symptoms. However, these symptoms can also be present in MH and therefore do not assist in discerning the 2 diagnoses.
The presentation of thyroid storm is not determined by thyroid function laboratory results; results in patients with thyroid storm may be similar to patients with compensated thyrotoxicosis.6 Likewise, massively elevated creatine kinase and myoglobin strongly suggest muscle injury like that seen in MH, but these laboratory results require more time to obtain than allowed in a crisis. The ABGs showed severe acidemia and severe hypercapnia, both of which strongly suggest MH over thyroid storm. The hypermetabolic state from thyroid storm, although capable of causing acidemia, is predominantly metabolic in origin as opposed to the simultaneous metabolic and respiratory acidosis that develop in MH.
The use of THAM for the correction of metabolic acidosis is debatable. However, the use of sodium bicarbonate rather than THAM could have worsened the hypercapnia and acidosis. THAM is also a diuretic that should improve the excretion of potassium and myoglobin. It is also able to buffer the excess carbon dioxide and theoretically improve the acidemia.7
Other symptoms which our patient did not develop that would suggest thyroid storm over MH include unexplained jaundice, heart failure, and severe central nervous system effects such as seizures and coma.5 The short episode of hypotension was attributed to severe acidemia rather than heart failure, as suggested by its rapid resolution with dantrolene, THAM, and phenylephrine. In addition, it is worth mentioning that a diagnosis of pheochromocytoma also shares many symptoms with both MH and thyroid storm. Our patient did not demonstrate the HR lability or hypertension after anxiolysis or induction of anesthesia that is typically seen in a patient with undiagnosed pheochromocytoma.
In conclusion, we examined the key points that help resolve diagnosing intraoperative MH from thyroid storm. The insidious rise of the temperature could have been from either syndrome, but the muscle rigidity on induction and the sudden acceleration of the hyperthermia as well as the severe respiratory acidosis suggested the presence of MH. In contrast, the patient displayed no signs of heart failure and his acidosis was more severe than that seen in thyroid storm. Rapid differentiation between MH and thyroid storm is critical because the management of each is unique.
Name: Sara M. Strowd, MD, MPH.
Contribution: This author helped write, edit, and format the manuscript.
Name: Michael B. Majewski, MD.
Contribution: This author helped write and edit the manuscript.
Name: Jennifer Asteris, MSN, CRNA.
Contribution: This author helped write and edit the manuscript.
This manuscript was handled by: Raymond C. Roy, MD.