a 56-year - old man ( height 162.3 cm , body weight 58.8 kg ) presented for emergency surgery of transurethral resection for bladder tumor due to bleeding associated with bladder cancer .
his medical history included hypertension , stage iv chronic kidney disease and benign prostatic hypertrophy .
there was no family history of mh , and he had not been anesthetized previously .
preoperatively , the patient had recurrent hematuria and a laboratory test revealed a hemoglobin ( hb ) concentration of 4.2 g / dl .
the patient received transfusion of 2 pints packed red blood cells , and the hb concentration increased to 6.8 g / dl .
glycopyrrolate 0.2 mg was injected intramuscularly as a premedication . in the operating room , an electrocardiogram , non
- invasive blood pressure measurement , and pulse oximetry were performed , and the bispectral index ( bis vista , aspect medical systems , inc . ,
the patient was preoxygenated for 2 minutes , and anesthesia was induced using 120 mg of 1% propofol and 12 mg cisatracurium .
after intubation , anesthesia was maintained using desflurane in a total fresh gas flow of 3 l / min of an air / oxygen mixture via an active humidified circuit with a heated wire in the inspiratory limb .
in addition , effect - site target - controlled infusion of remifentanil was adjusted between 2.5 and 4.0 ng / ml .
after consultation with the surgeon for considering the possibility of a radical cystectomy , catheters were placed in the right radial artery and right internal jugular vein as a precaution .
baseline measurements at onset of surgery were oxygen saturation ( spo2 ) 99% , arterial blood pressure ( abp ) 115/50 mmhg , heart rate ( hr ) 90 bpm , end - tidal co2 ( etco2 ) 37 mmhg , and esophageal temperature 36.5. approximately 120 minutes after anesthesia induction , abp was not checked . on inspection , right arm rigidity and lower extremity rigidity
repeated bolus injections of phenylephrine had a short duration , and hence a continuous infusion of norepinephrine was administered ( 0.05 g / kg / min ) .
the esophageal temperature was maintained at 36.2. we proceeded with manual hyperventilation to increase minute ventilation ( mv ) from 6.2 to 8.4 l / min ; however , etco2 remained above 60 mmhg .
bilateral breath sounds were clear without wheezing and the peak airway pressure remained unchanged . at this point ,
arterial blood gas analysis ( abga ) showed ph 7.032 , pao2 108.1 mmhg , paco2 73.1 mmhg and base excess ( be ) 10.8
the esophageal temperature increased gradually to 38.6. the clinical condition of the patient was suspected to be due to mh , and hence the operation was stopped and dantrolene sodium was prepared .
one hundred and fifty minutes after induction of anesthesia , hypotension still persisted and the hr gradually rose to 120 bpm .
next , a continuous vasopressin infusion was initiated and both the breathing circuit and soda lime canister were changed . in spite of increasing mv to 14.5 l / min , the retention of co2 intensified , and so the ventilator was replaced .
in addition , desflurane was discontinued and it was washed out with 100% o2 in 18 l / min fresh gas over a period of 10 minutes . at the same time , anesthesia was switched to 2% propofol ( fresofol 2% , fresenius kabi , granz , austria ) and the ventilator was replaced with continuous manual hyperventilation . to cool off the patient ,
ice packs were placed on the head and chest areas and cold saline irrigation was administered through the foley catheter and the levin tube .
the etco2 rose to more than 80 mmhg and the spo2 gradually decreased to 94% . at this point , the esophageal temperature was 41.7 and abga showed ph 7.039 , pao2 150.8 mmhg , paco2 90.9 mmhg and be 6.2 mmol / l .
also , serum potassium and lactic acid levels were 7.37 mmol / l and 11.7 mmol / l , respectively .
we administered 10 mg furosemide and a regular insulin infusion ( 10 iu / h ) . despite administration of norepinephrine and vasopressin ,
dantrolene sodium arrived in the operating room and it was reconstituted with sterile water as quickly as possible and administered through the central venous line .
the esophageal temperature at this point was 40.5 , but within the first 12 minutes following 60 mg dantrolene sodium , a rapid decrease in the esophageal temperature to 38.5 and a drop in etco2 to 32 mmhg were noted .
then , the infusion of dantrolene sodium was stopped and cpr was initiated immediately following chest compression and epinephrine injection .
after 15 seconds of cpr , ventricular fibrillation occurred and the patient 's cardiac rhythm converted back to sinus rhythm after a single defibrillation at 200 j. boluses of epinephrine 1 mg were injected 3 times . despite infusion of epinephrine and vasopressin , the patient 's abp did not improve .
we made a decision to initiate ecmo for providing hemodynamic support and activated an ecmo team .
peripheral venoarterial ecmo was applied by using a size of 15 french ( f ) arterial cannula ( biomedicus , medtronic , anaheim , ca , usa ) and a size of 21 f venous cannula ( biomedicus , medtronic , anaheim , ca , usa ) into the right femoral artery and vein , respectively . the initial blood flow rate was 3.5 l / min and the sweep gas - flow rate was 3.0 l / min .
the total down time for the first cardiac arrest was 80 minutes until ecmo was ready . after applying ecmo ,
the patient was then transferred to the surgical intensive care unit ( sicu ) running an ecmo .
no more dantrolene sodium was administered , because the rigidity of the right arm and the lower extremity had resolved , and etco2 , body temperature and abga had improved before the patient was transferred to the sicu .
iu / l ) and they continued to be elevated till the following morning ( ck 17,779
mh clinical grading scale score was 73 ( mh rank was 6 ,  almost certain ) .
a week later , he was inevitably scheduled for a radical cystectomy with an ileal - conduit due to the remnant bladder tumor , persistent hematuria in spite of arterial embolization and bladder necrosis . for general anesthesia
the patient 's vital signs were stable during the operation and the operation was completed uneventfully .
after one week , the patient displayed a hemodynamically stable state , was extubated , and then transferred to the general ward .
to our knowledge , early application of ecmo in severe cases of mh accompanied by cardiac arrest in spite of immediate treatment with dantrolene sodium has not yet been reported .
it is important that the prognosis of mh crisis depends on how soon mh is suspected and how rapidly an appropriate treatment is initiated ; because the mh crisis including rigidity , muscle breakdown , cardiac involvement and metabolic derangement , is aggravated as time passes .
however recently , the clinical manifestation of mh tended to have an insidious and delayed onset rather than a fulminant onset . therefore , the monitoring of raising etco2 , an early sign of mh in the perioperative period , is important for early administration of dantrolene sodium .
administration of triggering agents must be stopped immediately and anesthesia should be continued using intravenous opioids , sedatives , and , if necessary , non - depolarizing muscle relaxants .
the vaporizer used for administration of volatile anesthesia should be removed from the anesthesia machine and the patient should be hyperventilated with 100% oxygen at a maximum fresh gas flow , increasing the minute volume by approximately 23 fold , while aiming for an etco2 within the normal limits .
the gold standard for diagnosis of mh susceptibility is the caffeine - halothane contracture test . but dna analysis , requiring only a blood sample
however , as this test is not widely available , the diagnosis of mh can be made by clinical presentation in most cases .
therefore , we diagnosed mh based on clinical symptoms and the clinical symptom ceased on dantrolene administration . in our case ,
dantrolene sodium has been known to block the ryanodine receptors ( ryrs ) , and it acts directly on ryr1 and ryr3 isoforms , reduces the channel activation by calmodulin , and reduces the channel sensitivity to ca . notably dantrolene sodium does not have a negative inotropic effect on the heart because it does not block ryr2 , the cardiac ryrs .
however , several studies have suggested that dantrolene sodium might inhibit ca release via both ryr1 and ryr2 , and it can affect cardiac function under pathophysiologic conditions . due to the possibility of worsening cardiac function in a hemodynamically unstable condition
ecmo , as a device for cardiac resuscitation , was proposed in the early 1960s , and it has shown encouraging outcomes in patients with cardiac arrest .
in addition , ecmo is a therapeutic option increasingly used in the management of patients with refractory cardiorespiratory failure .
advances in technology have allowed such a treatment to be deployed more rapidly , and several descriptive series investigations have shown encouraging outcomes in patients with cardiac arrest .
this gradual increase in the use of ecmo has also been described in the the extracorporeal life support organization ( elso ) registry . according to these data , patients with myocarditis and cardiomyopathy benefit more from an ecmo treatment than patients with congenital defects or those who are in cardiogenic shock . in their 2005 cpr guidelines ,
the american heart association recommended the use of ecmo at institutions capable of deploying it rapidly in patients who had an in - hospital cardiac arrest , received good - quality cpr , and were thought to have a reversible cause of their cardiac arrest . despite the absence of controlled trials ,
there is principal support for the use of ecmo in the case of cpr in the aha / acc guidelines for advanced cardiac life support . in cases of malignant hyperthermia accompanied by cardiac arrest in spite of immediate treatment with dantrolene sodium , early application of ecmo for providing cardiopulmonary support
should be considered as a promising therapeutic option in order to improve the probability of patient survival when conventional cardiac arrest management has failed .
 malignant hyperthermia ( mh ) may lead to metabolic crisis of skeletal muscle in susceptible individuals following exposure to triggering agents such as volatile anesthetics or depolarizing muscle relaxants . 
 mh is a rare and a potentially lethal disease , which can lead to cardiac arrest . 
 we report a case of severe mh , in which the rapidly evolving signs of hypermetabolism eventually resulted in cardiac arrest . despite conventional treatments following cardiopulmonary resuscitation 
 , the patient 's vital signs did not improve . 
 therefore , we applied extracorporeal membrane oxygenation for providing hemodynamic support . 
Case Report
Discussion