malignant+hyperthermia


 * __ Malignant Hyperthermia: __** a hypermetabolic syndrome occurring in genetically susceptible patients after exposure to an anesthetic triggering agent.

MHS1 — Associated with the RYR1 gene on chromosome 19q13.1 MHS2 — Associated with the DHP receptor isolated to the 17q11.2-q24 locus MHS3 — Associated with the alpha-2/gamma subunit of the DHP receptor, linked to 7q21-q22 locus MHS4 — Linked to the 3q13.2 locus MHS5 — Encoding of the alpha-1 subunit of the DHP receptor and locus 1q32 MHS6 — Linked to chromosomal locus 5p
 * Epidemiology **
 * Genetic Basis**
 * Genes responsible for coding proteins of the **RYR1 and DHP receptors**
 * Approximately 50% of cases are inherited in an **autosomal dominant** fashion
 * Incidence is estimated to be about 1:30,000 administered anesthetics
 * Children <19 years account for between 45 – 52% of reported events
 * Males > females (2:1)
 * Classification:**

Depolarization via transverse tubule system à activates DHP receptors in T-tubule membrane à couples to RYR-1 receptors, which are calcium channels in wall of sarcoplasmic reticulum Calcium releases into the intracellular space à combines with troponin à allows actin and myosin to cross-link à MUSCLE CELL CONTRACTION Mutations encoding for abnormal RYR-1 or DHP receptors à trigger unregulated passage of Calcium à ACUTE MH CRISIS Accumulation of myoplasmic calcium à causes sustained muscle contraction à generates heat Accelerated levels of aerobic metabolism à produce carbon dioxide and cellular acidosis à depletes oxygen and ATP à muscle death à rhabdomyolysis à hyperkalemia and myoglobinuria
 * Pathophysiology **
 * Normal muscle physiology**:
 * Reuptake of calcium by the sarcoendoplasmic reticulum calcium ATPase** à **MUSCLE CELL RELAXATION**
 * Malignant hyperthermia:**

Inhalational Anesthetics halothane isoflurane enflurane sevoflurane desflurane Depolarizing muscle relaxant succinylcholine
 * Triggering agents **

>60 mm Hg with controlled ventilation, PETCO2 >60 mmHg or PaCO2 >65 mmHg with spontaneous ventilation. of succinylcholine, cola colored urine in the postoperative period. (101.8ºF).
 * Clinical manifestations **
 * Respiratory acidosis** —The presence of end-tidal CO2 >55 mmHg or PaCO2
 * Metabolic acidosis** — Base deficit >8 mEq, pH <7.25
 * Muscle rigidity** — Either severe masseter muscle rigidity or generalized rigidity.
 * Muscle breakdown** — Serum CK >20,000 IU/L or >10,000 IU/L without the use
 * Temperature** — Rapidly increasing temperature, or core temperature >38.8º C
 * Elevated resting serum CK**
 * Family history of MH** (autosomal dominant inheritance)

Definition: inability to open a patient's mouth after the administration of a triggering agent. Sign is **//not specific enough//** to make a definitive diagnosis in the absence of additional signs of hypermetabolism Normally masseter muscle tension increases after the administration of succinylcholine, but typically lasts only a few seconds. When MMR persists indicates initiation of acute MH in up to 30% of cases
 * Early Signs of Acute MH **
 * Hypercapnia**
 * most reliable initial clinical sign of acute MH
 * secondary to cellular hypermetabolism, which causes metabolic acidosis
 * Disproportionate increases in minute ventilation are required to normalize ETCO2 levels in the setting of MH.
 * The greatly increased exhaled CO2 heats the CO2 absorbent (ie, exothermic reaction) warming the ventilator absorbent canister.
 * Tachycardia**
 * may be associated with hypertension
 * HOWEVER, tachycardia is relatively nonspecific. Other causes of tachycardia and hypertension that need to be distinguished from MH include inadequate depth of anesthesia, sepsis, thyrotoxicosis, pheochromocytoma, cocaine toxicity, alcohol withdrawal, amphetamine toxicity, and sympathomimetic toxicity.
 * Calcium channel blockers are //absolutely contraindicated// in the acute management of MH since they can worsen hyperkalemia.
 * Masseter Muscle Rigidity**
 * Patients should undergo diagnostic testing for MH-susceptibility
 * Up to 50% will have a positive contracture test
 * Generalized muscle rigidity** — pathognomonic for MH

Plasma CK and urine myoglobin levels **peak around 14 hours** after an acute MH episode. Brownish or tea-colored urine indicates the presence of **myoglobinuria** Hyperthermia is **typically absent** when the diagnosis is initially suspected //Need to rule out// the many other causes of fever that are more common
 * Later Signs of Acute MH **
 * ECG Changes**
 * Due to elevated potassium levels from muscle breakdown
 * can occur rapidly in muscular patients
 * Presence of premature ventricular contractions may indicate life-threatening hyperkalemia à may degrade into ventricular tachycardia or ventricular fibrillation.
 * Rhabdomyolysis**
 * CK level > 20,000 units/ L is predictive of MH-susceptibility in over 80% of patients
 * CK level >100,000 units/L may be seen in muscular patients
 * Hyperthermia**
 * //Pathophysiology//**: Sustained muscle contraction from unregulated calcium release generates more heat than the body is able to dissipate.
 * Occurs **minutes to hours** following the initial onset of symptoms
 * Core body temperature may **rise 1ºC every 5 minutes**
 * Severe hyperthermia (up to 45ºC [113ºF]) à marked increase in carbon dioxide production and increased oxygen consumption à widespread **vital organ dysfunction**
 * Sepsis may be accompanied by fever, metabolic acidosis and elevations in CK, making it difficult to distinguish from MH.

Call for help: Initiate support:
 * Acute Management **
 * Call for MH crash cart
 * Notify the surgeon; complete surgical procedure as soon as feasible
 * Discontinue inhalational agents and succinylcholine
 * Hyperventilate with 100% oxygen
 * Increase ventilation rate and/or tidal volume to maximize ventilation and reduce the ETCO2
 * Use non-triggering agents for the remainder of the procedure, usually propofol
 * Give DANTROLENE:

//Mechanism of action:// Dantrolene binds to RYR1 à directly inhibits sarcoplasmic reticulum calcium release à reverses skeletal muscle hypermetabolism Has reduced mortality to 1-17% from 70%.  Dantrolene is supplied as a powder (20 mg) vial that also contains 3 g of mannitol and sodium hydroxide to maintain pH of 9 to 10. It should be mixed in 60ml of warmed sterile water to enhance its solubility.  Give a loading bolus of 2.5 mg/kg IV, with subsequent bolus doses of 1 mg/kg IV until the signs of acute MH have abated.  Watch for reversal of clinical signs (ETCO2 should normalize) ¡ Acute hypermetabolic process is usually reversed w/in minutes ¡ However, some patients, especially muscular males, may require initial dantrolene doses approaching 10 mg/kg IV.
 * Dantrolene **
 * only known antidote for MH**
 * Get blood gas/ labs**
 * Give bicarbonate for acidosis:**
 * Sodium bicarbonate 1 to 2mEq/kg IV push over 5 to 10 minutes
 * Cool the patient:**
 * Start when core temp >39C; stop when core temp <38C
 * Use cold saline for infusion; ice to body surface; lavage body cavities
 * Treat hyperkalemia:**
 * Hyperventilate
 * Calcium chloride: Slow IV infusion over 2 to 3 minutes for life-threatening hyperkalemia; repeat after 5 minutes if ECG changes persist; adult: 0.5 to 1gram (5 to 10ml of 10% solution); pediatric: 10 to 20mg/kg
 * Sodium bicarbonate: 1 to 2 mEq/kg IV push over 5 to 10 minutes
 * Insulin and dextrose: Monitor fingerstick glucose closely; adult: 10 units insulin IV push with 50ml 50% dextrose; pediatric: 0.1units insulin/kg IV push with 1ml/kg 50% dextrose
 * Treat dysrhythmias:**
 * Usually responds to treatment of acidosis and hyperkalemia
 * Use standard ACLS protocols
 * CCBs are //contraindicated// in the presence of dantrolene

CONTINUE DANTROLENE: __FOLLOW:__ Urine output: place Foley catheter; maintain at 1-2cc/kg/hr; diurese if needed Temperature: maintain <39C Blood gas: normalize pH; optimize pCO2 and pO2 Electrolytes: normalize Glucose: check hourly and correct Creatine kinase: check CK every 8 to 12 hours; alkalinize urine if CK >10,000IU/L Coagulation parameters: watch for disseminated intravascular coagulation (DIC) Contact MH hotline if necessary ([|www.mhaus.org], 800-MH HYPER)
 * Ongoing Care **
 * 1mg/kg every 4 to 6 hours or 0.25mg/kg/hour as continuous infusion
 * Maintain for at least 24 hours; further dosing may be indicated

Family history of anesthetic problems suggesting susceptibility (unexplained fevers or death) MH may triggered in susceptible patients who have had previous uneventful exposures to triggering agents Pre-treatment with dantrolene à generally not recommended for MH-susceptible patients, MH cart immediately available Consider Local or regional anesthesia, GA with non-triggering agents à barbiturates, opioids, propofol, benzodiazepines, nitrous oxide, non-depolarizing neuromuscular blockers may be used and safely reversed
 * Anesthesia for MH-Susceptible Patients **

Questions: Which of the following findings is NOT consistent with a diagnosis of MH? During emergency repair of a mandibular jaw fracture in an otherwise healthy 19 year old male, the patient’s temperature is noted to rise from 37 to 38 after 2 hours of surgery. Which of the following informational items would be LEAST useful in ruling out MH in this patient?
 * 1) PaCO2 150mmHg
 * 2) MVo2 50mmHg
 * 3) pH 6.9
 * 4) arterial oxygen saturation 85% on 100% Fio2
 * 5) onset of symptoms an hour after end of operation
 * 1) Normal heart and blood pressure
 * 2) History of negative caffeine-halothane contracture test carried out 6 months earlier
 * 3) History of uncomplicated GA at age 16 with halothane and succinylcholine
 * 4) Normal ABGs drawn when patients temperature reached 38
 * 5) No increase in respiration rate with spontaneous breathing