Newly diagnosed with Pearson Syndrome

Some individuals with metabolic and mitochondrial diseases are more sensitive to physiologic stressors such as minor illness, dehydration, fever, temperature extremes, surgery, anesthesia, and prolonged fasting/starvation. During such stress, rapid systemic decompensation may occur. Preventative measures are aimed at avoiding, or at very least not exacerbating such decompensation.

Mainstays of treatment during or prior to acute metabolic decompensation in mitochondrial and metabolic disease includes keeping patients well-hydrated, providing sufficient anabolic substrate (typically through IV dextrose), correcting secondary metabolic derangements, avoiding pharmacological mitochondrial toxins, and providing cofactor and/or salvage therapies

General guidelines on this topic as well as other aspects of care for these patients is available online at bit.ly/mitocare.

Laboratory Parameters

• Basic chemistries, glucose, CBC, liver function (synthetic and cellular), ammonia, glucose, ketosis and lactic acidosis should be monitored and any derangements corrected
• If acutely acidotic with a pH < 7.22 or bicarbonate level < 14 mM, metabolic acidosis can be controlled by administering sodium bicarbonate as a bolus (1 mEq/kg) followed by a continuous infusion
• Hyperammonemia can occur due to secondary inhibition of the urea cycle. As treatment for the metabolic decompensation proceeds, the ammonia level should diminish. A level > 200 uM may require salvage therapy or dialysis
• Any underlying infection and fever should be aggressively treated
• Hypothyoridism and/or cortisol deficiency can develop during critical illness. These should be assessed for and treated when needed.

IV fluids and Nutrition

• Dextrose/electrolyte therapy should be considered if a patient is unable to maintain oral fluid intake in the face of a catabolic stressor, including fever, illness or vomiting
• A hospital admission should be considered, not exclusively for dehydration, but to prevent catabolism by providing an anabolic food in the form of dextrose
• Clinical and laboratory assessment of the patient's cardiac and renal status should be performed prior to aggressive fluid therapy
• Hydration and substrate therapy involves providing 5 or 10% dextrose containing IV fluids given at 1.25-1.5X times the maintenance rate. A high dextrose delivery with D10 or D20 might be needed, especially if acidosis or metabolic derangements are not correcting with 5% dextrose containing fluids. When a higher dextrose delivery is given, insulin may also be needed. Insulin not only controls hyperglycemia but also serves as a potent anabolic hormone, promoting protein and lipid synthesis. Insulin is typically given in the intensive-care-unit setting with the initial dose in the 0.05-0.1 U/kg/hour range, and titrated accordingly
• IV fluids should not contain Lactated Ringers solution
• Fluids should be weaned based on laboratory parameters, oral intake and resolution of the underlying metabolic stressor
• Once the initial crisis passes, enteral or parenteral feeding should be provided as soon as medically feasible (typically within 24-48 hours). Protein can be added if hyperammonemia has resolved and there is no concomitant disorder of protein catabolism. If there is no primary or secondary fatty acid oxidation dysfunction, lipids may also be added
• Once the patient's laboratories begin to normalize, restarting the patient on their home-based diet is advised

Medication contraindications

• Medications that should generally be avoided during times of illness in individuals with mitochondrial disease include valproic acid, statins, metformin, high-dose acetaminophen, aminoglycoside antibiotics, linezolid and erythromycin
• There are no absolute contraindications and these medications can be given if an alternative medication is not available or appropriate as long as a prior adverse reaction to the medication has not occurred
• Should a medication such as valproate be used for the first time during an acute illness, liver enzymes, ammonia and synthetic liver function should be closely monitored
• In addition to the medications noted above, long-term use of select anti-HIV therapy, traditional neuroleptics, and select chemotherapeutic agents may worsen mitochondrial function in some individuals

Antioxidant therapy

• Levo-carnitine therapy during an acute illness may be beneficial. It should be given intravenously at a dose of at least 100 mg/kg/day. If the patient is on a higher oral dose, that dose should be used intravenously for treatment
• Any other home-based supplements and antioxidants being given should be continued by mouth if possible

Anesthesia

• Questions on anesthetic sensitivity in mitochondrial patients remain though patients are at an increased risk of anesthesia-related complications
• Some individuals with mitochondrial metabolic diseases might be more sensitive to volatile anesthetics and need a much lower dose to achieve a bispectral (BIS) index of <60. This effect has been seen more in patients with reduced complex 1 capacity. Sevoflurane might be better tolerated than isoflurane and halothane
• One should consider slow titration and adjustment of volatile and parenteral anesthetics to minimize hemodynamic changes
• Caution must be used with muscle relaxants in those mitochondrial patients with underlying myopathy, neuropathy or decreased respiratory drive
• Debate remains as to the potential risk of propofol administration in mitochondrial disease patients. However, propofol has been routinely used in mitochondrial patients for brief periods of sedation (less than 30-60 minutes) without apparent clinical problems. Limiting propofol use to short procedures and brief periods of sedation is advisable for now
• Local anesthetics are generally well-tolerated in patients with mitochondrial defect
• There is no clear established link between malignant hyperthermia and mitochondrial disease

Fasting and surgery

• During pre- and post-operative fasting, catabolism should be prevented by using dextrose-containing IV fluids. IV fluids are continued until the time of discharge, since they are intended to deter catabolism and not simply treat dehydration
• A pre-operative admission to begin IV dextrose during a period of fasting is recommended
• IV fluids should not contain Lactated Ringers solution. Normal saline alone should not be used unless the patient cannot tolerate dextrose containing IV fluids
• Routine chemistries, a complete blood count, liver function (synthetic and cellular), ammonia, glucose, ketosis and lactic acidosis should be monitored and any derangements corrected

Stroke Management

• Stroke-like episodes in primary mitochondrial disease typically have correlating visible magnetic resonance imaging abnormalities.
• IV arginine hydrochloride a dose of 0.5 grams/kg should be administered urgently in the acute setting of a stroke-like episode associated with the MELAS m.3243 A>G mutation in the MTTL1 gene and considered in a stroke-like episode associated with other primary mitochondrial cytopathies as other etiologies are being excluded.
• Patients should be reassessed after 3 days of continuous IV therapy.
• The use of daily oral arginine supplementation to prevent strokes should be considered in MELAS syndrome