**4. Malignant hyperthermia in liver transplantation**

### **4.1 Preoperative evaluation and investigation of susceptibility**

Preoperative evaluation is crucial for all liver transplant candidates and, although involvement of multiple specialties like surgery, gastroenterology, cardiology, nephrology and endocrinology may be beneficial, it does not dispense with a judicious assessment by an anesthesiologist. Before planning anesthesia in a patient with known or suspected susceptibility to malignant hyperthermia, complete information about previous anesthetic procedures including complications or adverse events and other medical reports is needed97. Such evaluation is best accomplished and documented with the use of systematic formularies, where all collected data are registered and the anesthetic technique is individualized according to the risk factors for MH. The survey should include questions regarding muscular disorders, complications, deaths, unexplained high fever or darkcolored urine after surgery. Symptoms like fever, cramps, muscular fatigue and weakness may suggest muscular disorders and susceptibility, but are overly common among candidates for liver transplantation and are of limited value.

All common premedications like opioids, benzodiazepines, barbiturates, anticholinergics, and antihistamines are safe, but phenothiazines should not be administered. There is no need for preoperative use of dantrolene, but it must be immediately available in the operating room.

It must be emphasized that uneventful previous anesthetics (even more than once) with MH-triggering agents do not preclude the occurrence of MH in future exposures56,98.

recently discovered in hepatocytes38. Whether dantrolene causes liver toxicity through these

Most of the patients with dantrolene hepatitis develop only mild and nonspecific symptoms (malaise, weakness, vomiting, fever, vomiting, jaundice)90, although fatal acute hepatic failure has been described93. Laboratory exams show different degrees of alterations in liver enzymes (alkaline phosphatase, AST, ALT) and bilirubin levels91. Histological findings of liver biopsies did not show a homogenous pattern, and multiple different descriptions were published (Table 1)20,88-90,92-95. If signs of hepatic injury develop during MH therapy, the treatment is mainly supportive and dantrolene should be stopped soon after control of the

In the two available reports of the use of dantrolene sodium during liver transplantation, there were alterations in postoperative laboratory exams, but the liver graft recovered uneventfully56,96. Actually, although dantrolene may pose an additive threat in the large set of perioperative injuries to the graft, abnormal symptoms and laboratory exams may be masked in the routine postoperative course of hepatic transplantation. Besides this, biopsies may not be of great help because histological patterns of dantrolene hepatitis do not greatly differ from those usually observed postoperatively in liver grafts. Consequently, prevention of dantrolene-induced hepatic injury is crucial. So, if malignant hyperthermia happens during liver transplantation, it seems prudent to, besides supportive treatment, use the

Less commonly reported effects are acne-like rash, pruritus, urticaria, fever, hypersensitivity

Preoperative evaluation is crucial for all liver transplant candidates and, although involvement of multiple specialties like surgery, gastroenterology, cardiology, nephrology and endocrinology may be beneficial, it does not dispense with a judicious assessment by an anesthesiologist. Before planning anesthesia in a patient with known or suspected susceptibility to malignant hyperthermia, complete information about previous anesthetic procedures including complications or adverse events and other medical reports is needed97. Such evaluation is best accomplished and documented with the use of systematic formularies, where all collected data are registered and the anesthetic technique is individualized according to the risk factors for MH. The survey should include questions regarding muscular disorders, complications, deaths, unexplained high fever or darkcolored urine after surgery. Symptoms like fever, cramps, muscular fatigue and weakness may suggest muscular disorders and susceptibility, but are overly common among

All common premedications like opioids, benzodiazepines, barbiturates, anticholinergics, and antihistamines are safe, but phenothiazines should not be administered. There is no need for preoperative use of dantrolene, but it must be immediately available in the

It must be emphasized that uneventful previous anesthetics (even more than once) with

MH-triggering agents do not preclude the occurrence of MH in future exposures56,98.

crisis, as dantrolene hepatitis is usually reversible after its withdrawal.

lowest effective dose of dantrolene for the shortest time possible.

**4.1 Preoperative evaluation and investigation of susceptibility** 

**4. Malignant hyperthermia in liver transplantation** 

candidates for liver transplantation and are of limited value.

pleural effusion with pericarditis.

operating room.

receptors or during its metabolism is unclear.

Some factors may have a role in attenuating MH crisis: pre-exposure hypothermia99, differential trigger potency for MH100 and variable genetic penetrance101. One of the described cases of MH during liver transplantation occurred in a patient who had previous uneventful general anesthetic31.

#### **4.2 Factors influencing the choice of anesthetic agents for liver transplantation and alternatives**

The choice of anesthetic agents for liver transplant surgery takes into account three key factors: maintenance of hemodynamic stability, lack of hepatic toxicity and pharmacokinetic profile102.

Circulation of cirrhotic patients is hyperdynamic, showing low systemic vascular resistance and high cardiac output103-104. The use of betablockers for the prevention of variceal bleeding may render these patients bradycardic and hypotensive on arrival at the operating room. Besides this, large volume paracentesis, manipulation of major vessels, presence of surgical retractors, high propensity to massive bleeding and the reperfusion syndrome may all, *per se*, result in profound intraoperative hemodynamic changes. To further aggravate the scenario, it is widely known that most drugs used in anesthesia have negative effects on the cardiovascular system. As a result, judicious choice of anesthetic agents may help alleviate the tendency toward hemodynamic instability – the following choices are considered reasonable105.


Local anesthetics, nondepolarizing muscle relaxants, barbiturates, benzodiazepines, droperidol, ketamine, nitrous oxide, opioids, propofol and vasoactive drugs are all safe drugs to administer to these patients115.
