Malignant Hyperthermia as A Side Effect of Blood Transfusion: A Rare Occurrence

Malignant hyperthermia (MH) is a rare autosomal dominant pharmacogenic disorder caused by volatile anaesthetics that results in a hypermetabolic state with potentially fatal consequences. Although the exact mechanism is unknown, MH is primarily associated with anesthesia exposure. Efforts to link MH and blood transfusion reactions have revealed an intriguing potential link, but current data is insufficient. Instances of blood incompatibility during transfusion, which raised the possibility of a transfusion reaction, prompted researchers to look into the possibility of MH. A case study, in particular, reports the development of MH following an autologous blood transfusion contaminated with Yersinia enterocolitica. The crucial question is whether blood incompatibility or a contaminated blood transfusion can cause malignant hyperthermia. This necessitates additional research to uncover the underlying pathological mechanism.

Malignant hyperthermia (MH) is a rare autosomal dominant inherited pharmacogenic skeletal muscle disorder that can develop after inhaling volatile anaesthetics and succinylcholine [1, 2]. Although the exact mechanism of MH is unknown, the pathological pathway is linked to an intracellular calcium defect [3], which results in abnormal contraction and a hypermetabolic state, resulting in ATP depletion, rhabdomyolysis, and heat production [4, 5]. We attempted to establish a link between malignant hyperthermia and blood transfusion reactions in our article. Although the current data was insufficient, few cases described situations where the possibility of blood incompatibility during blood transfusion was considered, leading to a suspicion of a transfusion reaction, and thus investigating the possibility of malignant hyperthermia as a result of blood incompatibility [2]. Another case study reported the case of a 13-year-old patient who developed malignant hyperthermia after receiving an autologous blood transfusion contaminated with Yersinia enterocolitica for an orthopedic surgery [6], raising the question: can blood incompatibility lead to malignant hyperthermia? Can a contaminated blood transfusion result in malignant hyperthermia? We will attempt to uncover this pathological mechanism in our review. referring to the condition known as malignant hyperthermia, which occurs when body temperature reaches 44 degrees Celsius [7]. Additional indications and manifestations include dyspnea, hypotension, tachycardia, oliguria, disseminated intravascular coagulation, septic shock, and, in the event that treatment is not received, death [8]. The majority of MH diagnoses are made clinically, and patients with the highest likelihood of MH are chosen using the MH clinical grading scale to assess clinical MH likelihood [9]. Understanding the cause of malignant hyperthermia is crucial to choosing the right course of treatment for the patient. Core temperature monitoring is a crucial component of safe anaesthetic management, and it should be followed by targeted symptomatic therapy [10].

Malignant hyperthermia (MH) is a rare but potentially fatal pharmacogenetic disorder caused by exposure to specific anesthesia agents, most notably succinylcholine [11]. Still, other possible causes include abnormalities related to the central nervous system, iatrogenic overheating, genetic conditions and blood transfusion reactions causing aberrant thermoregulatory control [10]. Fever or hyperthermia is regarded as a significant clinical indicator in a number of transfusion reactions, occurring either alone or in conjunction with other symptoms and signs related to blood transfusion [12]. These reactions include febrile non-hemolytic transfusion reactions, immediate or delayed hemolytic transfusion reactions, and bacterial contamination reactions, all of which are included in the category of transfusion pyrexia [13]. Despite the lack of data connecting blood transfusion and malignant hyperthermia, symptoms of MH, such as hemolysis, sepsis, shock, and hemorrhagic phenomena brought on by disseminated intravascular coagulation, can be mistakenly diagnosed as transfusion reactions (14), emphasizing the significance of a precise diagnosis [2]. While reading through and revising some cases and reviewing papers, we discovered that blood contaminated with bacterial infections like Staphylococcus and Yersinia [15, 6] may cause fulminant toxic symptoms, including MH. The pathophysiological pathway of blood transfusion as a triggering factor for MH is not well understood. Furthermore, there are other blood transfusion-related conditions such as blood mismatch and blood histocompatibility [2]. Elms et al. reported a case of a 22-year-old patient who developed malignant hyperthermia (MH) following a gunshot and suspected that the blood transfusion was the trigger [16]. This led us to believe that malignant hyperthermia following blood transfusion and other blood transfusion reactions may share the same pathological mechanism.

In a 1993 case study published by Sire JM et al., a 15-year-old patient undergoing autologous transfusion for prosthetic hip replacement surgery experienced Yersinia enterocolitica infection-related malignant fever, hypotension, tachycardia, and oliguria [17]. An additional case involving a 74-year-old patient that was documented by Richards, Kolins, and Trindade in 1992 emphasizes the possibility of Yersinia enterocolitica transmission through autologous transfusions, as the patient experienced fever, cyanosis, and respiratory distress [18]. A 64-year-old patient receiving a total right hip endoprosthesis implantation experienced fever, hypotension, anemia, and reduced renal function in another case report published by Haditsch M et al in 1994 due to Yersinia enterocolitica septicemia from autologous blood transfusion [19]. 

In this context, bacterial contamination of transfusion-ready blood may result in malignant hyperthermia, a sign or symptom that exacerbates the transfusion episode [20]. Because platelet concentrates are stored between 20 and 24 degrees Celsius, which is a temperature that allows for rapid bacterial proliferation, bacterial contamination is more common with platelet transfusions [21]. On the other hand, high temperature spikes, malignant hyperthermia, and disseminated intravascular coagulation are frequently associated with the transfusion of red blood cells contaminated with bacteria [22]. Some cases of pseudomonas cepacia and pseudomonas aeroginosa have been cultured from cryoprecipitate and plasma thawed in contaminated water baths, despite the fact that cell-free products like plasma and cryoprecipitate are stored frozen and are rarely linked to contamination [23]. These transfusions are linked to septicemia, MH, and high temperatures [22]. 

Malignant hyperthermia can additionally result from blood contaminated with malaria [24]. It was reported in 1911 [25] that the first case of malaria contracted through transfusion occurred. Transmission of the malaria-causing parasite Plasmodium falciparum through blood is significant because severe malaria symptoms, including high fever, headache, muscle aches, and spasms, can be brought on by a small amount of infected donor cells or by the infusion of small components like platelets cryoprecipitate and leucocytes [26, 27].

In contrast, there have been very few reports of cases of blood transfusion-induced malignant hyperthermia in which the patient experienced loss of consciousness, metabolic acidosis, and malignant hyperthermia; in these cases, the possibility of blood incompatibility was taken into account [2]. Malignant hyperpyrexia is often the result of blood transfusion reactions [28]. As a result, this is not the same as malignant hyperthermia, which anaesthetics frequently cause [29]. Even though both types of fever are fatal because they can raise body temperatures above 42 degrees Celsius [30], there is an increase in CD-154, a powerful cyclooxygenase 2 enzyme inducer, and PGE-2, an important fever inducer, in blood transfusion-induced hyperpyrexia [31]. To summarize, the pathophysiological pathway linking blood transfusion and malignant hyperthermia is unidentified, although a few case reports have reported malignant hyperthermia as a clinical manifestation of blood transfusion reactions caused by blood incompatibility or contamination.

Depending on the symptoms, signs, timing, intensity, and rate of development, MH can be classified as fulminant, abortive, or atypical; the fulminant form is thought to be the most severe [32]. A number of symptoms can indicate malignant hyperthermia (MH). One of the first is tachycardia [3]. Another early sign of MH is respiratory acidosis caused by hypercarbia, which is recognized by rising end-tidal CO2 [3, 33].  Additionally, due to myoglobinuria, which can cause severe renal failure, and hyperkalemia, which can cause a heart attack, rhabdomyolysis can also result in cola-colored urine [32, 34]. Hypoxia, disseminated intravascular coagulation, tachypnea, pulmonary edema, and coma are further consequences of MH [3, 35]. Moreover, a higher metabolic surge may reveal several organ failures [32].

The use of a clinical grading scale may aid in the determination of a diagnosis [9]. Importantly, individualized patient assessment is required to improve diagnosis accuracy. Malignant hyperthermia is classified clinically as having muscle stiffness, respiratory acidosis, hyperthermia, tachycardia, and respiratory acidosis [36]. Aside from clinical observations, genetic testing plays an important role in identifying people who are predisposed to MH, though it is not without limitations [37, 38].

Knowing that prompt action is necessary even in cases of dubious diagnosis is important when it comes to treating malignant hyperthermia (MH) [2]. The European Resuscitation Council (ERC) suggests adhering to the standard protocol of ABCDE (Airway, Breathing, Circulation, Disability, and Exposure) after the initial assessment of patients in any emergent condition [39]. Establishing IV lines is crucial for cooling the body; urinary catheters, arterial or central venous lines, or both, may be taken into consideration [39]. Dantrolene preparation shouldn't be postponed since it is the recommended therapy and plays a major role in treating malignant hyperthermia [40].

However, blood decontamination may also be taken into consideration following a blood transfusion reaction. An effective preventative measure that foresees the infiltration of newly emerging pathogens into the blood supply is pathogen inactivation [41]. When a patient receives a transfusion that contains contaminated blood, stopping the transfusion right away lowers the patient's bacterial load and for any specific concerns about blood decontamination or transfusion reactions, it is recommended to consult with a hematology specialist or other appropriate medical professional.

The direct correlation between blood transfusion and malignant hyperthermia (MH) is not well established. Though few studies have found a direct link between blood transfusion and malignant hyperthermia (MH), MH is most commonly associated with anaesthetic reactions rather than blood transfusions. Hyperthermia, however, can be the result of a number of conditions, including drug toxicity, and it can also be a symptom of transfusion reactions. Distinguishing between MH and other hyperthermia-causing factors, such as blood transfusion reactions, is critical. The overlap between MH symptoms and transfusion reactions makes accurate diagnosis and management of the condition crucial.

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Acknowledgment: The authors thank Dr. Hiba Hamdar, who supervised us reviewed our article, and gave us her valuable comments.

Authors' contributions: Each author has contributed in the same manner to this manuscript.