This case represents the first instance of severe malignant hyperthermia after ECT. It highlights the delayed onset of malignant hyperthermia following an ECT session, emphasizing the need for psychiatrists to be vigilant in identifying its emergence in psychiatric wards. The symptom relief provided by dantrolene underscores its pivotal role in the therapeutic approach to malignant hyperthermia.
Mechanisms of Malignant Hyperthermia
The underlying mechanisms of malignant hyperthermia involve the excessive release of calcium from the sarcoplasmic reticulum, a crucial calcium store within skeletal muscle cells, into the cytoplasm. This dysregulation is provoked by depolarizing neuromuscular blocking agents, predominantly suxamethonium, and volatile inhalation anesthetics (Rosenberg et al., 2015). This disruption results in a marked increase in skeletal muscle metabolic processes, leading to enhanced muscle fiber contraction, increased oxygen consumption, elevated carbon dioxide production, and accelerated depletion of adenosine triphosphate, alongside associated heat production (Rosenberg et al., 2015). These physiological changes give rise to the clinical presentations observed, including hyperthermia and muscle rigidity.
Suxamethonium is routinely employed as a muscle relaxant during ECT due to its rapid onset of action and ultra-short duration, making it suitable for the brief anesthesia required in ECT procedures that typically last only a few minutes (Dao et al., 2023). However, it is important to note that depolarizing muscle relaxants like suxamethonium, along with volatile inhalational anesthetics, are known to trigger malignant hyperthermia (Rosenberg et al., 2015).
Difference in Symptoms between Malignant Hyperthermia, Neuroleptic Malignant Syndrome and Serotonin Syndrome
In the present case, the patient exhibited fever, altered consciousness, and limb muscle rigidity that were also observed in neuroleptic malignant syndrome (Tse et al., 2015) and serotonin syndrome (Wang et al., 2016). However, either of them was unlikely in this case, considering lemborexant was the only medication administered post-admission. The significant effectiveness of dantrolene treatment in this case may also indicate the improbability of neuroleptic malignant syndrome and serotonin syndrome. White et al. (2000) noted the limited therapeutic efficacy of dantrolene in neuroleptic malignant syndrome, while Jones et al. (2005) highlighted the unverified effectiveness of dantrolene in serotonin syndrome. It is crucial to bear in mind the potential occurrence of malignant hyperthermia during ECT, especially considering that psychiatrists more commonly encounter conditions like neuroleptic malignant syndrome and serotonin syndrome, which often take precedence in differential diagnoses. A misdiagnosis could result in a delay in appropriate treatment.
Characteristics of malignant hyperthermia in this potentially lethal case
It is well-recognized in malignant hyperthermia that tissue hypoxia and muscle breakdown can lead to increased serum creatine kinase levels. However, in this case, the serum creatine kinase level rose modestly to 171 U/L on the third hospital day, which may be considered to be an atypical presentation. This observation might be ascribed to generally lower creatine kinase values in females than males (Neal et al., 2009) and the association between muscle mass and creatine kinase levels (Garcia et al., 1974). Notably, this patient exhibited a slender build with a Body Mass Index of 18.6 kg/m². According to the study by Sheila et al. in 2014, approximately 35% of 129 patients diagnosed with malignant hyperthermia exhibited peak creatine kinase values below 1000.
According to Larach et al 2006, only 9.4% of 181 malignant hyperthermia patients showed disturbance of consciousness. However, this patient experienced a prolonged alteration in consciousness. The extent of consciousness impairment due to malignant hyperthermia considerably varies, with reported cases ranging from a rapid recovery within 90 minutes (Lee et al., 2010) to prolonged cognitive disruption exceeding 40 days, ultimately resulting in the sequelae of severe cognitive dysfunction (Minami et al., 2023). This case was complicated by dehydration and its associated hyponatremia, which may also have affected the disturbance of consciousness.
Calcium channel blockers we used to treat severe hypertension (over 200 mmHg) might have intensified malignant hyperthermia symptoms by increasing calcium concentrations in skeletal myocytes, along with associated muscle rigidity (Rosenberg et al., 2015). A more suitable approach could have employed an antihypertensive agent without calcium channel inhibitory effects.
Compared with the previous report of malignant hyperthermia after ECT (Lazarus et al., 1991), our case is deemed more severe as the fever persisted for several days and was accompanied by impaired consciousness, which required the administration of dantrolene.
Warning to psychiatrists
Detection and diagnosis of malignant hyperthermia significantly depend on the judgment of psychiatrists. In the case we observed, malignant hyperthermia manifested two hours after ECT, aligning with prior research findings. Visoiu et al. (2014) noted a median time of 76.5 minutes from the induction of anesthesia to the onset of malignant hyperthermia in cases reported since 1998. Furthermore, they reported that the upper third quartile duration from the initiation of anesthesia to the onset of malignant hyperthermia was 148.3 minutes. However, as Litman et al. (2008) reported, postoperative malignant hyperthermia is rare, occurring in just 10 out of 528 suspected cases. Given the considerably shorter duration of ECT compared to general surgery, the probability of postoperative malignant hyperthermia after ECT might be higher.
Therefore, malignant hyperthermia after ECT is primarily considered to occur in a psychiatric ward and be detected by psychiatrists, rather than in the operating room by anesthesiologists. It is therefore critically important to closely monitor for indicators of malignant hyperthermia, including abnormal vital signs, such as elevated temperature, tachycardia, high blood pressure, and tachypnea, as well as characteristic physical presentations, such as muscle rigidity, masseter spasm, and cola-colored urine (Larach et al., 1994), for a few hours after ECT in a psychiatric ward.