The treatment of rhabdomyolysis by all causes and (therefore) CPT deficiency consists of:
The general management and treatment of rhabdomyolsis is, of course, in the first place dependent on the underlying cause. In the situation of the CPT 2 deficient patient, the major cause of the rhabdomyolysis, namely CPT 2 deficiency itself, cannot be remedied.
What should be done in case of a CPT 2 deficient patient is to further avoid, or treat, all other known attack triggering situations. For a list of these triggers, please look under the heading "Attack triggers".
If an infectious disease is the trigger, that should be treated, including the accompanying fever. However, the patient should not use such common drugs as paracetamol or ibuprofen (Advil) as this could worsen the situation (see further under the heading "Attack triggers").
Fasting should be avoided as well, and corrected with carbohydrate rich food or glucose infusion if necessary (and not just saline solution).
General management of drug overdose or a triggering drug (see further under the heading "Attack triggers") includes termination of further exposure, reduction of absorption, enhancement of metabolism and excretion of the offending drug as appropriate.
Features of drug overdose, particularly in comatose patients, namely, hypothermia, hyperthermia, hypoxia, hypovolemia and hypotension, should be identified and treated.
Measures should also be taken to stop further muscle damage. These include control of excessive muscle activity, such as in severe agitation and convulsions and abnormal posturing in unconscious patients. Sedatives, or in some cases anticonvulsants, may be required to control convulsions. Overdose with phenothiazines may require the administration of anticholinergic agents to control dystonic reactions.
Once reversible causes and triggers are identified and treated, then the next objective is to prevent any complications from developing, the main one being acute renal failure (ARF)
Early correction of hypovolemia reduces the often present hypovolemia, caused by massive fluid loss in the damaged muscles, and the incidence of renal failure. Sometimes several liters per hour are required during the initial management, and 300-500 ml/hour once hemodynamic stability has been achieved. Indices of volume status such as urine output, urine sodium concentration and BUN-creatinine ratio may be misleading and invasive hemodynamic monitoring may be necessary.
Various types of fluid composition and infusion regimes have been suggested in rhabdomyolysis in general but in the case of CPT 2 deficiency a 5% glucose solution (or higher) is recommended.
Although it may be difficult, it is essential to maintain a urine output of 300 cc/hour or more.
Alkalinization of urine prevents the dissociation of myoglobulin into globin and ferrihemate, which are toxic to the renal tubules. The possibility of aggravation of hypocalcemia by large doses of bicarbonate through metabolic alkalose should be born in mind, as should the worsening of calcium deposits in muscle and other tissues (although this seems to be rather uncommon, especially if hypovolemia is corrected). Absorption of calcium deposits can lead to hypercalcemia in the diuretic phase of recovery of ARF. It should be born in mind that high urine flows may increase urinary pH without bicarbonate administration.
Calcium administration should therefore be done with caution and perhaps only as therapy in the case of severe hyperkalemia or if ventricular dysfunction causes hypoperfusion.
The administration of mannitol, and furosemide to augment diuresis should be considered. They also reduce intracompartment pressure and its attendant complications.
It should be born in mind that mannitol may reduce renal tubular oxygen consumption by reducing sodium absorption. Also osmotic diuresis without adequate volume replacement might cause hypovolemia.
Treatment to prevent the development of ARF in the case of rhabdomyolysis is controversial.
A rational approach follows :
These measures are continued until myoglobinuria has resolved. (cave: this is done unless volume overload limits intravenous fluid intake or serum osmolality limits mannitol administration)
If there is no response in urine output to these measures, then furosemide is administered at a dose of 40 mg intravenously and increased to 200 mg or until a diuresis occurs.
Hyperkalemia should be corrected if potassium levels exceed 6 mEq /L. However, conventional therapy for this condition with glucose infusions (50 mL of 50% dextrose) and insulin (10 units regular), beta agonists and sodium bicarbonate (usually 50-100 mmol), may be ineffective because of loss of sarcolemmal integrity. The use of exchange resins such as sodium polystyrene sulphonate (25-50 g resin mixed with 100 mL of 20% sorbitol given orally, or 50 g of resin and 50 mL of 70% sorbitol, mixed in 150 mL of tap water, given as a retention enema), or early dialysis may be necessary.
If hyperuricemia is severe (uric acid > 20mg/L) allopurinol can be used. Hyperphosphatemia should be treated with phosphate binders.
The indications for hemodialysis are standard and include failure
of conservative measures in the management of acute tubular necrosis, severe
acidosis, rapid increase in serum potassium and CK levels, and hypocalcemia.
In the case of severe rhabdomyolysis, CVVH (Continuous Venous Venous Hemodialyis
and hemofiltration) is preferred, as this type of dialysis is the modality of
choice in very sick patients, and also has a higher filtering capacity over
a 24-hour period. The CVVH apparatus should be set at the highest clearing volume
(which amounts to approx. 3 liters per hour).
Local therapy is extremely important in rhabdomyolysis of either traumatic or nontraumatic origin. Close attention should be paid to the decline of serum CK levels. If these do not fall by 50 % over 48 hours, a careful search should be made for evidence of increased tissue pressures in the involved muscle groups. If it is found, close attention should be focused on neurovascular function in affected limbs. If circulatory compromise is evident, fasciotomy should be performed. In the absence of compartment syndrome, debridement of necrotic muscle with intact overlying skin is contraindicated given the risk of infection of the open wound. This contrasts with situations where the skin has been broken, such as a compound crush injury where wide debridement of the necrotic muscle is indicated.
|Version||Revision date||Revised by||Comment|
|1.0||14 august 2000||MHN|