**4.6 Management and treatment of MH during anesthesia for liver transplantation**

#### **4.6.1 Intraoperatively**

Protocols for MH treatment prioritize four mainstays: immediate discontinuation of trigger agents, administration of antidote (sodium dantrolene), life support measures and prevention of complications124-125.

In the acute phase of MH the following steps are recommended:


General dosing regimens recommend an initial bolus of 2.5 mg.kg-1, which can be repeated every 5 minutes until normalization of the hypermetabolic state and the disappearance of all MH symptoms. After this initial control, a continuous intravenous dantrolene infusion at 10 mg.kg-1.day-1 should be given for at least 24 h after initial successful therapy76.

Although this is the classical regimen, it may be excessive and deleterious in liver transplantation patients. In this scenario, although the diseased liver is removed and a new liver graft is transplanted, the transplanted liver unavoidably sustains warm, cold, and reperfusion injuries during graft procurement and transplantation129. Dantrolene sodium is considered hepatotoxic and the hepatic effects of dantrolene on such liver allografts are unknown. As a result, it seems prudent to use the lowest effective dose for the shortest time possible.

There are two published case reports of MH in liver transplantation, with identical clinical presentation and successful treatment with lower than usual dantrolene doses56,96. One of the reports used a 1 mg.kg-1 dose intraoperatively, followed by 1 mg.kg-1 every eight hours for 36 hours; the authors observed signs of hepatic

Protocols for MH treatment prioritize four mainstays: immediate discontinuation of trigger agents, administration of antidote (sodium dantrolene), life support measures and

1. **Immediate discontinuation of triggering agents:** some MH crisis may be attenuated or aborted with discontinuation of triggering agents. When MH or MMR is identified soon after induction, postponement of the surgery is commonly recommended119. In liver transplant surgery, however, the decision to postpone the procedure is very tough. The anesthesiologist is faced with a patient who has a delicate clinical status that may be worsened either by a MH crisis or by returning to the waiting list. All the medical team

2. **Call for help:** initiation of measures to treat MH, including the laborious process of dantrolene dilution, may be troublesome for one only anesthesiologist. Consequently the presence of another health professional (preferably an anesthesiologist) may be of

3. **Adjust ventilation:** increase minute ventilation to lower EtCO2 and use 100% oxygen.

4. **Administer the antidote:** Dantrolene is the drug of choice in treatment of malignant hyperthermia127. The contents of each bottle should be diluted in 60 mL of sterile water rather than solutions such as 5 percent dextrose in water or bicarbonate because the extra molecules in solution lead to a salting-out effect with greater difficulty in dissolving dantrolene. If it does not dissolve immediately, producing a clear yellow to yellow-orange color, it should be heated under tap water or autoclaved for a few minutes128. In a dire emergency, it should be administered through a blood filter without concern for crystals. Dantrolene should be preferentially administered through a large bore peripheral or central venous access to avoid local inflammatory phlebitis at

General dosing regimens recommend an initial bolus of 2.5 mg.kg-1, which can be repeated every 5 minutes until normalization of the hypermetabolic state and the disappearance of all MH symptoms. After this initial control, a continuous intravenous dantrolene infusion at 10 mg.kg-1.day-1 should be given for at least 24 h after initial

Although this is the classical regimen, it may be excessive and deleterious in liver transplantation patients. In this scenario, although the diseased liver is removed and a new liver graft is transplanted, the transplanted liver unavoidably sustains warm, cold, and reperfusion injuries during graft procurement and transplantation129. Dantrolene sodium is considered hepatotoxic and the hepatic effects of dantrolene on such liver allografts are unknown. As a result, it seems prudent to use the lowest effective dose for

There are two published case reports of MH in liver transplantation, with identical clinical presentation and successful treatment with lower than usual dantrolene doses56,96. One of the reports used a 1 mg.kg-1 dose intraoperatively, followed by 1 mg.kg-1 every eight hours for 36 hours; the authors observed signs of hepatic

There is no need to change the breathing circuit or the soda lime canister126.

**4.6 Management and treatment of MH during anesthesia for liver transplantation** 

In the acute phase of MH the following steps are recommended:

**4.6.1 Intraoperatively** 

valuable help.

the infusion site.

successful therapy76.

the shortest time possible.

prevention of complications124-125.

should be involved in this sentence.

dysfunction 9 days after the transplant, which was attributed to dantrolene and had spontaneous resolution56. In the other report, the same intraoperative dose was used (1 mg.kg-1) and no maintenance dose was used; in this case, no signs of liver graft dysfunction were observed96.

Therefore, to minimize the risks of graft toxicity by dantrolene, it seems prudent to adopt intraoperative doses of 1 mg.kg-1, which may be repeated every 30 minutes until control of symptoms. Next, the patient should be closely observed for MH recrudescences; if these occur, a regimen of 1 mg.kg-1 every eight hours for 36 hours should be instituted.

