Anesth Analg 2004;98:548-549
© 2004 International Anesthesia Research Society
doi: 10.1213/01.ANE.0000097172.44227.0D
GENERAL ARTICLES
A Suspected Case of Delayed Onset Malignant Hyperthermia with Desflurane Anesthesia
Thomas J. Papadimos, MD MPH,
Mohamad Almasri, MD,
James C. Padgett, CRNA BS, and
Joanne E. Rush, CRNA MS
Department of Anesthesiology, Medical College of Ohio, St. Luke’s Hospital Heart Center, Maumee
Address correspondence and reprint requests to Thomas J. Papadimos, MD, 7162 Copperwood Lane, Sylvania, Ohio 43560. Address e-mail to TPapadimos{at}mac.com
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Abstract
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Desflurane has been identified as a weak triggering anesthetic of malignant hyperthermia that, in the absence of succinylcholine, may produce a delayed onset of symptoms. The prolonged interval after exposure may occur more than 6 h after the induction of anesthesia. The unintended underdosing of this patient with dantrolene and the prompt reversal of symptoms may be an attribute of the genetic expression of a weak triggering volatile anesthetic such as desflurane.
IMPLICATIONS: There are multiple genetic variations for malignant hyperthermia (MH) at the ryanodine receptor. Desflurane, as a sole trigger of MH, is weak, and on two occasions in the literature (including this case), less than optimal doses of dantrolene were given with a good result. There may be possible to engineer the risk of MH out of an anesthetic once the genetics of the ryanodine receptor are better understood.
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Introduction
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Malignant hyperthermia (MH), an anesthetic-related disorder of skeletal muscle calcium regulation, is triggered by succinylcholine and volatile anesthetics. It is characterized by hyperthermia, tachycardia, acidosis, and muscle rigidity (1). Several reports indicate that MH symptoms can become manifest after a prolonged exposure interval when desflurane is the only trigger (2–6). We report a case of suspected delayed onset MH during thoracotomy in which desflurane was the sole trigger.
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Case Report
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A 56-yr-old man presented for a right thoracotomy and tumor excision. His medical history included atrial fibrillation, chronic obstructive pulmonary disease, hypertension, tobacco, and excessive alcohol use. He had had a tonsillectomy as an adult without anesthetic complication and denied any allergies. His medications included ramipril, amiodarone, carvedilol, coumadin, and Percocet.
Preoperative physical examination revealed a well-nourished 80-kg man, 172 cm in height. Preoperative vital signs were: arterial blood pressure, 148/66 mm Hg; heart rate, 63 bpm; oxygen saturation, 95%, with a fraction of inspired oxygen (FIO2) = 0.2; and oral temperature, 37.0°C. Hemoglobin and hematocrit were 13 g/dL and 40%, respectively. Coumadin had been discontinued before surgery, and coagulation studies were acceptable. Cardiopulmonary examination revealed a regular rhythm without murmurs, and rhonchi were audible in the right upper lung fields. Chest radiograph and computerized tomography confirmed the mass.
The patient was premedicated with 2 mg of midazolam IV. A thoracic epidural and a left radial artery catheter were placed. After breathing 100% oxygen, anesthesia was induced with 250 µg of fentanyl IV, 200 mg of propofol IV, and 100 mg of lidocaine IV. After giving rocuronium 60 mg IV, a #37 left-sided double-lumen tube was inserted, and proper positioning was confirmed fiberoptically (both in the supine and left lateral decubitus position). Anesthesia was maintained with desflurane (range, 5–8 minimum alveolar anesthetic concentration) in oxygen with fentanyl boluses accompanied by additional rocuronium. The arterial blood gas (ABG) before one-lung ventilation was pH 7.36, PaCO2 43 mm Hg, PaO2 475 mm Hg, base excess -0.7 mmol/L, HCO3 24.5 mmol/L, and minute ventilation was 9 L/m. This minute ventilation was used for the first 300 min of anesthesia, which included the first 190 min of one-lung ventilation. The soda-lime canister was changed after the induction of anesthesia because color change indicated exhaustion. Between 300 and 335 min after the induction of anesthesia (190–225 min of one-lung anesthesia), the heart rate increased from 70 to 85 bpm, the end-tidal CO2 (ETCO2) increased from 44 to 53 mm Hg, and he remained afebrile. The ABG at this time was pH 7.20, PaCO2 67 mm Hg, PaO2 379 mm Hg, base excess -1.2 mmol/L, and HCO3 25 mmol/L. Venous CO2 was not measured. Minute ventilation was increased to 12 L/m, and gradually increased to 22 L/m (see below), and proper double-lumen tube placement was reconfirmed fiberoptically. The valves on the anesthesia machine were checked and were in working order. There were no significant changes in peak inspiratory pressures throughout the case.
At 395-min postinduction of anesthesia, during chest closure, while on two-lung ventilation (the double-lumen tube had been pulled back into the trachea and both lungs visibly expanded well), the heart rate increased to 120 bpm, ETCO2 increased to 80 mm Hg, and nasopharyngeal temperature increased to 38.9°C. The ABG was pH 7.16, PaCO2 92 mm Hg, PaO2 224 mm Hg, potassium 5.0 mmol/L, and minute ventilation was 22 L/m. MH was presumed, and desflurane administration was terminated. Dantrolene was given IV (retrospectively, it was discovered that half of the recommended dose of 2.5 mg/kg was given). The anesthesia machine was replaced with a Puritan-Benett 840 ventilator for the final 35 intraoperative min (430 total postinduction min). Propofol and fentanyl were used to ensure amnesia and analgesia. The patient was also packed with ice. The patient improved immediately with dantrolene; heart rate was 90 bpm, ETCO2 54 mm Hg (PaCO2 58 mm Hg; pH value of 7.35), and he became normothermic. The patient was moved to the intensive care unit, and dantrolene administration was inadvertently discontinued. Copious diuresis was ensured with furosemide and mannitol. Creatine phosphokinase was 2264 U/L after surgery and peaked at 4650 U/L 12 h later. Renal function was never compromised, and urine myoglobin levels were negligible. Thyroid function studies and cardiac enzymes were normal. The patient recovered uneventfully. He was counseled about MH and referred appropriately for diagnostic testing.
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Discussion
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Desflurane can trigger MH without the use of succinylcholine and may produce a delayed onset. This patient’s symptoms were delayed over six hours. The patient had a clinical grading scale of 43 (grade D5). Grades D5 (very likely) and D6 (almost certain MH) are defined by scores of 35–49 and 
50, respectively (7). The clinical grading scale uses six process indicators and a seventh "other" category indicator: rigidity, muscle breakdown, respiratory acidosis, temperature increase, cardiac involvement, family history, and "indicators not part of a single process" with 3–15 points awarded to subcategories of each indicator. Our patient was scored as follows: (a) arterial PaCO2 >60 mm Hg with appropriately controlled ventilation (15 points), (b) inappropriately increased temperature >38.8°C in the perioperative period (10 points), (c) inappropriate sinus tachycardia (3 points), (d) arterial pH value <7.25 (10 points), and (e) rapid reversal of MH signs of metabolic or respiratory acidosis with IV dantrolene (5 points). The increase in temperature was rapid (15 points), but the more conservative inappropriate increase in temperature category (10 points) was chosen; both left the patient as a D5.
Whereas Wedel et al. (2) demonstrated weaker triggering by desflurane than halothane in susceptible swine, it is interesting that there was no evidence for graded, slow onset triggering. The triggering, once started, was sudden. Further work by Allen and Brubaker (4) indicated that presentation of MH with desflurane use (without succinylcholine) may be delayed (53–380 minutes), and they also suggest that desflurane is a weak trigger. Several case reports are in agreement that, without succinylcholine exposure, desflurane causes delayed-onset MH (3,5,6).
Our patient had no other triggers but desflurane. The dramatic temporal response to dantrolene suggests this was indeed an MH event. Such a response to an unintended half dose of dantrolene may be representative of a weak triggering drug. In one report of desflurane-triggered MH, a suboptimal dose was given two hours after diagnosis with good result (the patient was in a remote location) (3). Whereas various anesthetics may trigger MH as different speeds, two important factors that may affect such triggering should not be overlooked. First, it must be noted that graded doses of dantrolene modify an MH porcine episode: 3 mg/kg, signs of MH still are detectable; 1 mg/kg, MH definite, but attenuated; and 0.1 mg/kg, no effect of dantrolene on MH (8). Second, depressants and nondepolarizing muscle relaxants delay the onset of MH in pigs (9). For example, a pig subjected to an inhaled induction with halothane triggers within three minutes. If the same pig is given a sleep dose of thiopental and then given halothane, the onset is 20 minutes. Therefore, should MH be diagnosed during desflurane anesthesia, it is of paramount importance that the recommended dose of 2.5 mg/kg of dantrolene be used. Nonetheless, this case raises the question of the relative lethality of desflurane as the sole trigger of MH, and it is a fascinating prospect to engineer or design an absence of MH risk into a drug. More investigation is required regarding delayed onset MH caused by weak triggering drugs and atypical presentations in light of the multiple MH genetic variations at the ryanodine receptor (10).
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References
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- Levitt RC. Prospects for the diagnosis of malignant hyperthermia susceptibility using molecular genetic approaches. Anesthesiology 1992; 76: 1039–48.[Web of Science][Medline]
- Wedel DJ, Gammel SA, Milde JH, et al. Delayed onset of malignant hyperthermia induced by isoflurane and desflurane compared with halothane in susceptible swine. Anesthesiology 1993; 78: 1138–44.[Web of Science][Medline]
- Michalek-Sauberer A, Fricker R, Gradwohl I, Gilly H. A case of suspected malignant hyperthermia during desflurane administration. Anesth Analg 1997; 85: 461–2.[Web of Science][Medline]
- Allen GC, Brubaker CL. Human malignant hyperthermia associated with desflurane anesthesia. Anesth Analg 1998; 86: 1328–31.[Web of Science][Medline]
- Lane JE, Brooks AG, Logan MS, et al. An unusual case of malignant hyperthermia during desflurane anesthesia in an African-American patient. Anesth Analg 2000; 91: 1032–4.[Abstract/Free Full Text]
- Hoenemann CW, Halene-Holtgraeve TB, Book M, et al. Delayed onset of malignant hyperthermia in desflurane anesthesia. Anesth Analg 2003; 96: 165–7.[Abstract/Free Full Text]
- Larach MG, Localio AR, Allen GC, et al. A clinical grading scale to predict malignant hyperthermia susceptibility. Anesthesiology 1994; 83: 771–9.
- Gronet GA, Milde JH, Theye RA. Dantrolene in porcine malignant hyperthermia. Anesthesiology 1976; 44: 488–95.[Medline]
- Gronert GA, Milde JH. Variations in onset of porcine malignant hyperthermia. Anesth Analg 1981; 60: 499–503.[Abstract/Free Full Text]
- Tong J, Oyamada H, Demaurex N, et al. Caffeine and halothane susceptibility of intracellular Ca2+ release is altered by 15 calcium release channel (ryanodine receptor) mutations associated with malignant hyperthermia and/or central core disease. J Biol Chem 1997; 272: 26332–9.[Abstract/Free Full Text]
Accepted for publication September 9, 2003.
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Abstract
Introduction
