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Anesth Analg 2003;96:165-167
© 2003 International Anesthesia Research Society

ANESTHETIC PHARMACOLOGY

Delayed Onset of Malignant Hyperthermia in Desflurane Anesthesia

Christian W. Hoenemann, MD*,{dagger}, Tobias B. Halene-Holtgraeve*, Michael Booke, MD, PhD*, Frank Hinder, MD, PhD*, Fritz Daudel, MD*, Alexander Reich, MD*, and Hugo Van Aken, MD, PhD*

*Department of Anesthesiology and Critical CareUniversitätsklinikum Münster, Münster; and {dagger}Department of Anesthesiology and Critical CareMarienhospital Vechta, Vechta, Germany

Address correspondence and reprint requests to C. W. Hoenemann, Klinik und Poliklinik für Anästhesiologie und Operative Intensivmedizin, Universitätsklinikum Münster, Albert Schweitzer Straße 33, 48129 Münster, Germany. Address e-mail to hoenemann@ anit.uni-muester.de.


   Abstract
Top
 Abstract
Introduction
 Case Report
 Discussion
 References
 

IMPLICATIONS: Animal-experimental studies demonstrate desflurane’s trigger effect for malignant hyperthermia (MH). In contrast to other anesthetics, the time interval from exposure to the occurrence of symptoms is much longer with desflurane. This case report focuses on MH induced by desflurane alone.


   Introduction
Top
 Abstract
 Introduction
Case Report
 Discussion
 References
 
Animal-experimental studies demonstrate that desflurane is a trigger for malignant hyperthermia (MH) (1). In contrast to halothane or succinylcholine, the interval from exposure to the occurrence of MH symptoms is much longer with desflurane (1–3). There are currently no results concerning the dose relation. Case reports focused on MH induced by desflurane are rare (4–7). In most cases, other trigger substances, such as succinylcholine, were also administered.

We report a case of MH that occurred after several hours of uneventful desflurane anesthesia. Application of dantrolene stopped the process. Because no other trigger substance was used, a causal link between desflurane and the observed symptoms seems very likely and was confirmed by postoperative testing.


   Case Report
Top
 Abstract
 Introduction
 Case Report
Discussion
 References
 
A 16-yr-old female patient, 44 kg, ASA physical status II, was scheduled for surgical correction of thoracic scoliosis. Apart from that, the girl was healthy and had already been anesthetized for minor surgery twice without any problem with use of isoflurane, thiopental, fentanyl, and rocuronium (45- to 60-min procedures). Anesthesia was induced with fentanyl (10 µg/kg), thiopental (4 mg/kg), and rocuronium (0.6 mg/kg) and was maintained with desflurane at 3 vol% after endotracheal intubation (Robert-Shaw double-lumen tube). In addition to standard monitoring, an arterial line (radial artery) and a central venous catheter (internal jugular vein) were inserted. A Foley catheter with a temperature tip was introduced to measure urine output and core body temperature. The patient was then turned into prone position to perform the dorsal release. A Bair Hugger® warming blanket (Augustine Medical, Eden Prairie, MN) was used to maintain normothermia. Blood loss was minimal (200 mL). Anesthesia was maintained as minimal-flow anesthesia (0.5 L/min, fraction of inspired oxygen 0.5 in air) with an end-expiratory desflurane concentration between 2.5 and 3 vol%. Repeated boluses of fentanyl were administered (1.1–2.2 µg/kg) up to a total of 20 µg/kg during the operation.

One-hundred-eighty minutes after the induction of anesthesia and shortly after the patient was turned into the left lateral position to perform the ventral stabilization of the spine, the heart rate increased from 80 to 110 bpm, and arterial blood pressure decreased from 120/65 mm Hg to systolic pressures of 90 mm Hg. At the same time, peak airway pressure increased from 25 to 33 cm H2O, and end-expiratory CO2 increased to 65 mm Hg. These hemodynamic and respiratory changes were initially interpreted as a result of one-lung ventilation and the surgical manipulation with chest retractors and lung hooks. The tidal volume was therefore reduced (from 480 to 400 mL), and the respirator frequency (10 to 14 breaths/min) and inspiratory/expiratory ratio (1:2 to 1:1) were increased. To correct hypotension, 1000 mL of crystalloid and colloid solutions were infused. Thirty minutes after the first symptoms, a severe respiratory acidosis was diagnosed, with arterial pH 7.11, PaCO2 74 mm Hg, PaO2 120 mm Hg, and base excess -6.7 mEq/L. Fresh gas flow was increased to 6 L/min, and the fraction of inspired oxygen was increased to 1.0. At this point, inspiratory peak pressures were as high as 40 cm H2O. Bladder temperature increased to 38°C, and the patient was cooled with the Bear Hugger® blanket. Another arterial blood gas analysis, during manual ventilation, 50 min after the first, confirmed the respiratory acidosis—arterial pH 7.01, PaCO2 98 mm Hg, PaO2 132 mm Hg, and base excess -8.9 mEq/L—without any imbalance of serum electrolytes. Because body temperature was still increasing, MH was diagnosed, and surgery was paused. Desflurane was turned off, and hypnosis was maintained by propofol. Fresh gas flow was adjusted to 10 L/min. Soda lime and tubes of the ventilation system were replaced. Hypercarbia could not be sufficiently corrected by hyperventilation. The patient became more and more hemodynamically unstable. Tachycardia up to 150 bpm, ST segment alterations, and systolic blood pressure decreased to 60 mm Hg (Table 1). At this time, body temperature was 40.8°C. Injection of 60 mg of dantrolene, 90 min after the first symptoms were observed, improved the patient’s situation within 10 min—heart rate 130 bpm, arterial blood pressure 100 mm Hg, peak airway pressure 26 cm H2O at constant tidal volume, body temperature 40.1°C, and end-expiratory CO2 and acid-base balance normal. Forced diuresis was induced with mannitol and furosemide to preserve renal function. Heart rate was further reduced by the administration of metoprolol. Four units of packed red blood cells, 2.5 L of lactated Ringer’s solution, 1.5 L of Haes solution, and 1 L of Gelafundine solution were given. The operation was finished, and another 10 mg of dantrolene was administered. The patient was then transferred to an intensive care unit. Repeated laboratory analyses showed a peak serum potassium of 6.8 mmol/L, creatine kinase 8670 U/L 12 h after surgery (from, initially, 39 U/L), and myoglobinuria of 37,100 ng/L. Temperatures decreased to values <38°C after 2 h and were approximately 37°C for the following 24 h. Two hours after the operation’s end, the patient was tracheally extubated. Within the next 24 h, nothing indicated a resumption of the MH episode. The patient was continuously observed by an anesthesiologist in the intermediate care unit (Table 2). The patient survived without any persistent damage, and she and her family were informed. An anesthesia problem card according to the guidelines of the German Society of Anesthesia and Intensive Care was given to all family members, and further testing in an MH center was arranged.


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  		Table 1. Intraoperative Laboratory Variables: Hemoglobin (Hb), Potassium (K), pH, End-Expiratory CO2 (ETco2), and Paco2 at Different Time Points
 

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  		Table 2. Postoperative Laboratory Variables: Creatin Kinase (CK), CK-MB (Isoform), Myoglobin in Urine, and Lactate dehydrogenase (LDH) at Different Time Points
 
Four months after surgery, four muscle biopsies were taken from our patient to perform in vitro contracture testing with halothane and caffeine. The muscle biopsies did not show any deposition for MH. Interestingly, the samples also did not contract during electric stimulation. This is unusual and was the first time in this center that a muscle sample could not be stimulated by an electric impulse. Additionally, the search for the most common mutations in the ryanodine receptor gene was negative. These findings made interpretation difficult. An electron microscopic analysis of the muscle biopsies showed increased glycogen granule accumulation in the subsarcolemmal position. Further testing under ischemic conditions showed that this accumulation was most likely the result of insufficient myoadenylate deaminase activity (and not of improper phosphorylase functioning in our patient). MH is passed on in an autosomal dominant manner. Testing of the family members indicated in a creatine kinase level in the mother of 105 U/L.


   Discussion
Top
 Abstract
 Introduction
 Case Report
 Discussion
References
 
The typical symptoms of MH in this patient were initially masked by the operative procedure. Later on, because of their persistence and extent, they clearly indicated MH. A missing coincidence makes it very unlikely that the volatile anesthetic induced a sympathetic activation. The first symptoms developed after 180 minutes of exposure time and showed a clear and exponential increase, together with later inadequate organ function. Besides hypercarbia, tachycardia, and increasing temperatures, the MH manifested itself in higher ventilation pressures and muscular rigidity. This delayed onset of MH has been reported before with the use of isoflurane, enflurane, or halothane. The delay of symptoms in these reports was between 8 and 26 hours (8,9).

There are four reports on MH episodes induced by desflurane (4–7). One is a case of a 13-year-old boy in whom the elimination of the trigger substances led to the end of the MH episode (6). In our case, this had no effect. Only the administration of dantrolene was able to break the vicious circle of MH and stabilize the situation. After this anesthesia with desflurane, our patient came back to the hospital for uneventful surgery in the ear-nose-throat (120 minutes) and orthopedic (240 minutes) departments. For both procedures, the anesthesiologist used propofol, remifentanil, and rocuronium.

In animal experiments, desflurane had a clear trigger effect in susceptible swine (1–3). This trigger effect of desflurane alone in swine is also present in humans. Desflurane most likely induced a MH-like episode in our case, because no other triggers were present. Despite its role as a "weak" trigger, MH fulminated the same severity as in cases in which "potent" triggers were administered. Previous uneventful anesthesia with isoflurane is no guarantee against MH.


   References
Top
 Abstract
 Introduction
 Case Report
 Discussion
 References
 

  1. Wedel DJ, Gammel SA, Milde JH, Iaizzo PA. Delayed onset of malignant hyperthermia induced by isoflurane and desflurane compared with halothane in susceptible swine. Anesthesiology 1993; 78: 1138–44.[ISI][Medline]
  2. Wedel DJ, Iaizzo PA, Milde JH. Desflurane is a trigger of malignant hyperthermia in susceptible swine. Anesthesiology 1991; 74: 508–12.[ISI][Medline]
  3. Bonome Gonzalez C, Alvarez Refojo F, Fernandez-Got C, et al. Malignant hyperthermia in a pig anesthesized with desflurane. Rev Esp Anestesiol Reanim 2001; 48: 81–4.[Medline]
  4. 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]
  5. Garrido S, Fraga M, Martin MJ, Belda J. Malignant hyperthermia during desflurane-succinylcholine anesthesia for orthopedic surgery. Anesthesiology 1999; 90: 1208–9.[ISI][Medline]
  6. Michalek-Sauberer A, Fricker R, Gradwohl I, Gilly H. A case of suspected malignant hyperthermia during desflurane administration. Anesth Analg 1997; 85: 461–2.[ISI][Medline]
  7. Fu ES, Scharf JE, Mangar D, Miller WD. Malignant hyperthermia involving the administration of desflurane. Can J Anaesth 1996; 43: 687–90.[Abstract/Free Full Text]
  8. Karan SM, Crowl F, Muldoon SM. Malignant hyperthermia masked by capnographic monitoring. Anesth Analg 1994; 78: 590–2.[Free Full Text]
  9. Murphy AL, Conlay L, Ryan JF, Roberts JT. Malignant hyperthermia during a prolonged anesthetic for reattachment of a limb. Anesthesiology 1984; 60: 149–50.[ISI][Medline]
Accepted for publication October 1, 2002.




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This Article
Right arrow Abstract Freely available
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Related Collections
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Right arrow Pharmacology

Lippincott, Williams & Wilkins Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999 HighWire Press