For the next 30 min, ETco2 continued to increase reaching a maximal value of 46 mm Hg. His temperature increased to 39.4°C; at the same time BP decreased to 60/28 and HR increased to 140 bpm (Figs. 1 and 2). Hemodynamic instability was treated with IV crystalloids as well as 5% albumin and boluses of phenylephrine (1 μg/kg). One unit of packed red blood cells was transfused. At that time, estimated blood loss was recorded as 350 mL and a total of 4 L of crystalloids and 250 mL of albumin had been given. Four and a half hours after anesthetic induction, urine output started to increase. An internal jugular catheter for central venous pressure monitoring was placed to guide fluid management. Four hours and 50 min after induction, ABG showed severe acidosis, hyperkalemia, and moderate anemia: pHa 7.19, Paco2 39 mm Hg, Pao2 386 mm Hg, HCO3 15 mEq/L, base excess −12 mmol/L, K 7.2 mEq/L, Hb 5.3 g/dL, Hct 13.8%. Hyperkalemia was treated with 50% dextrose (100 mL) with insulin (60 U), sodium bicarbonate (100 mEq), and calcium chloride (1 g). A second unit of packed red blood cells was transfused with 10 mg of furosemide to force diuresis. By this time, the total dose of dantrolene (350 mg including 52 g of mannitol) had been given and a gradual improvement in variables was noted. His vital signs stabilized and the patient was transported to the postanesthesia care unit with the endotracheal tube in situ. The next ABG sample showed improvement of acid–base balance (Table 1). The patient was transported to the intensive care unit for further care.
Treatment with dantrolene was continued (1 mg/kg) every 6 h for the next 72 h, as well as IV hydration (200 mL/h) with forced diuresis (furosemide 40 mg, 21 g of mannitol in dantrolene formulation). Sedation was provided with fentanyl and propofol infusion. Temperature and ETco2 were closely monitored. The endotracheal tube was removed in the intensive care unit 12 h after admission. Vital signs remained stable for the next 24 h. The creatine phosphokinase peak was 21,803 U/L 26 h after induction of anesthesia (Table 2).
Seventy hours after the episode of MH, the patient was brought back to the operating room for urgent median nerve internal neurolysis and repair with sural nerve grafting. Vital signs were stable, creatine phosphokinase was 12,624 U/L (Table 2), and urine myoglobin was negative. The patient had received a scheduled dose of dantrolene before surgery (2 mg · kg−1 · d−1). Anesthesia was provided with interscalene brachial plexus block (40 mL of 0.625% l-bupivacaine with 1:200,000 epinephrine) placed using a nerve stimulator and minimum alveolar anesthetic concentration (midazolam/fentanyl/propofol). Standard noninvasive monitors were used, including rectal temperature. The intraoperative course was uneventful. Dantrolene was discontinued on the next day. The patient was discharged home 3 days later.
The present case is noteworthy in several aspects. First, there are only rare published case reports of MH in individuals of black African descent. The incidence may be as infrequent as 1:250,000, whereas another study reported 1 case of MH in 170,000 anesthetics (1–4). However, 12.5% percent of the reports of adverse metabolic/muscular reactions to anesthesia in the North American Malignant Hyperthermia Registry in which the race of the patient was noted, report African ancestry (communication from the Registry office). These data suggest a similar incidence of MH in individuals of African and Caucasian descent. The implication is that MH cases in minority groups are under-reported in the literature.
Second, only a few cases have documented MH in humans exposed to desflurane. In one case report, a patient received desflurane for 90 minutes before severe hypercarbia developed (5). In another, the patient received succinylcholine as well as desflurane. Tachycardia was the first sign and was initially attributed to a desflurane-induced sympathetic hyperactivity (6). The onset of hypercarbia was noticed as early as 30 minutes after induction with desflurane when succinylcholine was given (7). The enhancing effect of succinylcholine in the development of MH is presumably caused by its stimulating effect on skeletal muscle metabolism (8).
Third, the relatively slow onset of MH in this case may be attributed to the effect of nondepolarizing relaxants (rocuronium) (9) and the small dose of desflurane, a less potent triggering drug than halothane (10). Of 6 MH-susceptible swine, 4 did not develop MH when they were exposed to desflurane until they also received succinylcholine (11,12). This was supported by Allen and Brubaker (13) who reported that although desflurane may be a weaker MH trigger, the onset of MH is shortened by the administration of succinylcholine (14). Kunst et al. (15) investigated the effect of desflurane on calcium release from the sarcoplasmic reticulum in skinned skeletal muscle fibers and found that it induces only a small calcium release which supports the clinical observation that desflurane is a weak MH trigger. An increase in ETco2 is the earliest sign of MH. As reported by others (16), the gradual and repeated adjustment of MV to maintain normocarbia (Fig. 1) helped to mask an increasing CO2 production and the diagnosis of MH for several hours. The patient’s excellent physical condition enabled his cardiovascular system to respond to the increasing metabolic demand with the help of intermittent increases in MV. This illustrates the fact that ETco2 must always be evaluated in conjunction with MV. When MV requirement exceeds the predicted value, further investigation is necessary (16). If all other sources of increased MV requirement are excluded, an increased central venous or femoral venous CO2 to Paco2 gradient may help to confirm the diagnosis of MH (17,18).
Fourth, this patient had preexisting muscular injury before exposure to triggering drugs, as well as vascular injury, which required vascular clamping. One might question whether the intraoperative problems were secondary to injury of normal muscle rather than a response of abnormal muscle to drugs. If so, the preexisting injury did not produce increased metabolism in the first 3 hours of the anesthetic. There have been only 3 reported cases of compartment syndrome complicating MH and 1 of these patients had underlying myopathy (19–21). In none of these cases was compartment syndrome present before the diagnosis of MH. In this patient, CO2 production increased before reperfusion of the injured upper extremity. After removing vascular loops, hemodynamic instability and a further increase in ETco2 occurred. Perhaps reperfusion of the extremity was responsible for the severe hypotension in this patient (22), but it cannot explain the preexisting increase in CO2 production and core temperature.
Fifth, there are few case reports of a second anesthetic administration within 3 days after an acute MH episode.
The abnormal vital signs and laboratory values present in this case produced 61 points on the MH clinical grading scale. This is equivalent to an almost certain likelihood of MH being present (23). Without follow-up contracture testing, it cannot be said with certainty that this was a case of acute MH. Nevertheless, administration of dantrolene was followed by resolution of the abnormal vital signs and acidosis. Until a more readily available test of MH susceptibility can be performed at bedside it is reasonable to assume that an episode of increasing metabolism and muscle injury occurring during anesthesia is an episode of MH.
There are several lessons learned from this case. The incidence of MH in minority groups is probably under-reported. Being alert to the possibility of MH, appropriate monitoring, and careful evaluation of capnographic data in conjunction with MV adjustments throughout the case are extremely important. A nontriggering anesthesia can be given safely even 3 days after an episode of increased metabolism and significant rhabdomyolysis.
1. Peltz B, Carstens J. An unusual case of malignant hyperpyrexia. Anaesthesia 1975;30:346–50.
2. Rizk SF. Malignant hyperpyrexia in a Negro. Br J Anaesth 1973;45:233.
3. Lombard TP, Couper JL. Malignant hyperthermia in a black adolescent. S Afr Med J 1988;73:726–9.
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.
5. Michalek-Sauberer A, Fricker R, Gradwohl I, et al. A case of suspected malignant hyperthermia during desflurane administration. Anesth Analg 1997;85:461–2.
6. Fu ES, Scharf JE, Miller WD. Malignant hyperthermia involving administration of desflurane. Can J Anaesth 1996;43:687–90.
7. Garrido S, Fraga M, Martin M, et al. Malignant hyperthermia during desflurane-succinylcholine anesthesia for orthopedic surgery. Anesthesiology 1999;90:1208–9.
8. Gronert GA, Theye RA. Suxamethonium-induced porcine malignant hyperthermia. Br J Anaesth 1976;48:513–7.
9. Gronert GA, Milde JH. Variations in onset of porcine malignant hyperthermia. Anesth Analg 1981;60:499–503.
10. Hoenemann CW, Halene-Holtgraeve TB, Brooke M, et al. Delayed onset of malignant hyperthermia in desflurane anesthesia. Anesth Analg 2003;96:165–7.
11. Wedel DJ, Gummel 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.
12. Wedel DJ, Iaizzo PA, Milde JH. Desflurane is a trigger of malignant hyperthermia in susceptible swine. Anesthesiology 1991;74:508–12.
13. Allen GC, Brubaker CL. Human malignant hyperthermia associated with desflurane anesthesia. Anesth Analg 1998;86:1328–31.
14. Armstrong S, Russell WJ. The onset of MH. Anesth Analg 2000;91:1560.
15. Kunst G, Stucke AG, Graf BM, et al. Desflurane induces only minor Ca++ release from sarcoplasmic reticulum of mammalian skeletal muscle. Anesthesiology 2000;93:832–6.
16. Karan SM, Crowl F, Muldoon S. Malignant hyperthermia masked by capnographic monitoring. Anesth Analg 1994;78:590–2.
17. Gronert GA, Theye RA. Halothane-induced porcine malignant hyperthermia: metabolic and hemodynamic changes. Anesthesiology 1976;44:36–43.
18. Gronert GA, Ahern CP, Milde JH. Treatment of porcine malignant hyperthermia: lactate gradient from muscle to blood. Can Anaesth Soc J 1986;33:729–36.
19. O’Donnel CJ, Beck DH, Taylor BL, et al. Upper limb compartment syndromes: a complication of malignant hyperthermia in a patient with ill-defined myopathy. Br J Anaesth 1995;74:343–4.
20. Ball DR. Malignant hyperthermia and compartment syndrome. Br J Anaesth 1995;75:369.
21. Johnson IAT, Andrzejowski JC, Currie JS, et al. Lower limb compartment syndrome resulting from malignant hyperthermia. Anaesth Intensive Care 1999;27:292–4.
22. Warren JD, Blumberg PC, Thompson PD. Rhabdomyolysis: a review. Muscle Nerve 2002;25:332–47.
© 2005 International Anesthesia Research Society
23. Larach MG, Localio AR, Allen GC, et al. A clinical grading scale to predict malignant hyperthermia susceptibility. Anesthesiology 1994;80:771–9.