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Xenon anaesthesia in a patient with susceptibility to malignant hyperthermia

A case report

Carlomagno, Mariella; Esposito, Clelia; Marra, Annachiara; Vargas, Maria; Corcione, Antonio

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European Journal of Anaesthesiology: February 2016 - Volume 33 - Issue 2 - p 147-150
doi: 10.1097/EJA.0000000000000302
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Editor,

Malignant hyperthermia is a rare pharmacogenetic disorder of skeletal muscle tissue that can be triggered by volatile anaesthetics, haloperidol, depolarising muscle relaxants and, in rare cases, by strenuous exercise and heat exposure.

Once malignant hyperthermia is triggered, an abnormally high release of calcium from the sarcoplasmic reticulum is initiated, resulting in a hypermetabolic state. This leads to tachycardia, muscle rigidity, hypercapnia, hyperthermia, hypoxia and lactate acidosis.1 The use of a well tolerated anaesthetic technique is vitally important for patients susceptible to malignant hyperthermia. Currently, the only alternative proposed in the literature to inhalational anaesthesia for a patient with a known sensitivity to malignant hyperthermia is the use of total intravenous anaesthesia (TIVA).1

Xenon, an inert noble gas with beneficial anaesthetic properties, could be helpful in this condition.2,3 Xenon has been investigated in susceptible swine as well as in-vitro human muscle strips without showing malignant hyperthermia type reactions. With the consent of our patient, we report on the use of xenon to induce and maintain anaesthesia in a patient with a positive test result for malignant hyperthermia.

In April 2014, a 31-year-old man (height 180 cm, weight 76 kg) was scheduled for a Hartmann's colonic resection for perforated diverticulitis and, in June 2014, for a reconstruction of intestinal continuity with colo-colonic anastomosis and cholecystectomy. He was transferred to our hospital for a suspected iatrogenic bile duct injury and underwent a laparotomy.

The patient reported a family history of malignant hyperthermia. The diagnosis of malignant hyperthermia was made in 2003 through muscle biopsy and an in-vitro contracture test for caffeine-halothane. The preoperative evaluation classified the patient as American Society of Anesthesiologists’ (ASA) physical status 2. Before the procedure, the operating room was prepared according to the Malignant Hyperthermia Association of the United States guidelines.4 The patient refused epidural anaesthesia for postoperative pain control. One hour before surgery, two intravenous cannulae (18-gauge) were inserted and we administered antibiotic prophylaxis and premedication with midazolam 0.04 mg kg−1, atropine 0.01 mg kg−1 and ondansetron 4 mg. In the operating room, general anaesthesia was induced with a target-controlled infusion (TCI) of propofol with a target blood concentration of 4 μg ml−1 and remifentanil 0.01 μg kg−1 min−1, titrated according to clinical and haemodynamic parameters (blood pressure and heart rate >20% of baseline) (Fig. 1a). In addition to remifentanil, sufentanil 10 μg was used as premedication, at induction and after 180 min of surgery. Rocuronium 0.6 mg kg−1 was used as a muscle relaxant after calibration and monitoring of train-of-four (TOF) at the start of the procedure. The introduction of xenon was preceded by a phase of ‘denitrogenation’ by administration of oxygen at a high flow rate for 10 min. This step is crucial in order to limit the amount of xenon when inducing anaesthesia. Xenon was administered using a closed circuit breathing system. The hypnotic concentration of xenon (40 to 45%) stabilised after about 2 min, reaching the desired concentration of approximately 60 to 70% in 8 min (Fig. 1b). The infusion of propofol was modified according to the bispectral index (BIS) and was stopped when the concentration of xenon reached 40%. Maintenance of anaesthesia was augmented by an infusion of remifentanil 0.01 to 0.04 μg kg−1 min−1, a mixture of oxygen 30% and xenon 60%, and rocuronium 0.07 mg kg−1 (according to TOF). During surgery, the patient was monitored using a five-lead ECG, noninvasive arterial pressure monitor, pulse oximeter, capnograph, BIS, analgesia nociception index (ANI), urine output and bladder temperature (Fig. 1c,d). For haemodynamic monitoring, we used a noninvasive cardiac output monitor (NICOM; Cheetah Medical, Boston, Massachusetts, USA) that recorded the following parameters: cardiac output (CO), cardiac index (CI), stroke volume variation (SVV) and stroke volume index (SVI) (Fig. 1e). Hydration was ensured by administration of intraoperative crystalloid 2 ml kg−1 h−1. No episode of intraoperative or postoperative haemodynamic instability occurred. Arterial blood gas samples were taken 140 min into surgery and showed no abnormality.

Fig. 1
Fig. 1:
Variables during anaesthesia. (a) Remifentanil infusion rate. (b) The averaged value of inspired and expired xenon concentration during anaesthesia. (c) Bispectral index (BIS) and analgesia nociception index (ANI). (d) End-tidal carbon dioxide tension (ETCO2) and temperature. (e) Haemodynamic monitoring. CI, cardiac index (l min−1 m−2); CO, cardiac output (l min−1); HR, heart rate (beats per min), SVI, stroke volume index (ml m−2); SVV, stroke volume variation (%).

At the end of the surgery, which lasted 210 min, sugammadex 2 mg kg−1 was administered on reappearance of T2. The trachea was extubated at a TOF ratio of 100%, and when upper airway reflexes were fully recovered and respiratory function was adequate.

The patient was observed in the operating room until full orientation and was then taken to the postanaesthetic care unit (PACU) for further surveillance for the first 24 h. Postoperative analgesia was provided using an elastomeric pump with ketorolac 180 mg, tramadol 500 mg, ranitidine 300 mg and ondansetron 8 mg. Postoperative pain was assessed regularly using a numerical rating scale (NRS). Rescue analgesia was provided (NRS ≥4) with ketorolac 30 mg because the patient reported an allergy to paracetamol. Two hours after anaesthesia, blood gas analysis showed no abnormality. Blood gas analysis remained normal throughout the postoperative period. In PACU, the patient was afebrile (peak body temperature 37.5°C), did not show haemodynamic instability and only presented moderate impairments of laboratory parameters, compatible with surgical stress. Postoperative evaluation did not show any adverse events or signs of intolerance and the patient was admitted to the ward during the first postoperative day.

Our purpose is to report on the use of xenon in a malignant hyperthermia susceptible patient undergoing laparotomy. In animal models, malignant hyperthermia sensitive swine initially anaesthetised with pentobarbital and then ventilated with 70% xenon in oxygen for 2 h did not develop malignant hyperthermia.4 Xenon exposure did not induce any changes in metabolic and haemodynamic parameters nor elevations of plasma catecholamine concentrations indicative of malignant hyperthermia. In contrast, in all animals, within 20 min after starting administration of halothane and succinylcholine, fulminant and fatal malignant hyperthermia episodes were reported.5 Furthermore, xenon 70% did not cause an increase in baseline tension of any malignant hyperthermia susceptible human muscle specimens, in contrast to halothane and caffeine.6

To our knowledge, this is the first case report describing the use of xenon in a patient with established susceptibility to malignant hyperthermia. We chose to use xenon because of its availability in our hospital (a referral centre for xenon anaesthesia), its safety profile in previous in-vitro and animal studies and its haemodynamic stability. Our patient had already undergone a reconstruction of intestinal continuity with a colo-colonic anastomosis, and an open Roux-en-y hepato-jejunal anastomosis, and had a high risk of bleeding and haemodynamic instability. Given the patient's condition and the risks associated with the planned surgery, we chose to use an anaesthetic strategy with the greatest hemodynamic stability. Xenon, compared with volatile anaesthetics and propofol, allows a remarkably ‘stable’ circulation with a higher arterial blood pressure.7 Indeed, xenon avoids vasodilatation and does not suppress cardiovascular feedback loops.7 However, the use of TIVA remains a well tolerated alternative for general anaesthesia in a haemodynamically stable patient with known sensitivity to malignant hyperthermia. The noble gas xenon offers many characteristics of an ideal anaesthetic including haemodynamic stability and rapid induction and emergence from anaesthesia regardless of its duration. In this case, under general anaesthesia with xenon, values of CO, SVI and heart rate were consistent. Furthermore, body temperature and end-tidal CO2 remained in the proper ranges.

In conclusion, the special characteristics of xenon may offer a new approach for well tolerated anaesthesia in a patient with susceptibility to malignant hyperthermia.

Acknowledgements relating to this article

Assistance with the article: none.

Financial support and sponsorship: none.

Conflicts of interest: none.

References

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4. http://www.mhaus.org/healthcare-professionals/be-prepared. [Accessed 15 June 2015].
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