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Barbiturate Coma Therapy

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Barbiturate Coma Therapy Barbiturate coma therapy Hee-Pyoung Park MD Department of anesthesiology and pain medicine SNUH Introduction • Brain damage resulting from head injury is the leading cause of death among individuals younger than 24 years of age. • The most hazardous is increased ICP. • High-dose barbiturates are used to control intracranial hypertension in selected patients. Indications • Potentially survivable head injury • No surgically treatable lesion accounting for intracranial hypertension • Other conventional therapies of controlling ICP have failed – Posture – Hyperventilation – osmotic and tubular diuretics – corticosteroids • ICP > 20 to 25 mmHg for more than 20 min or >40 mmHg at any time • Unilateral cerebral hemispheric edema with significant shift (> 0.7 mm) of midline structures shown on CT • A low Glasgow Coma score Benefits (I) • Decrease in CMRO2 – caused by decrease in synaptic transmission – presumably by affecting GABA transmission • Decrease in cerebral blood volume and ICP – due to increase in cerebrovascular resistance – due to vasoconstriction • Both CMRO2 and CBF are decreased in a dose dependent fashion – about 50% decrease at a dose sufficient to produce isoelectric EEG Benefits (II) • Promote or induce hypothermia • Increase in intracellular glucose, glucagon, and phosphocreatine energy store • Decrease in nitrogen excretion following acute head injury • Shunt blood from regions of normal perfusion to those of reduced CBF due to vasoconstriction Benefits (III) • Anticonvulsant prophylaxis • Stabilization of lysosomal membranes • Decrease in excitatory neurotransmitters and intracellular calcium • Free radical scavenging (thiopental only) Risks • Direct myocardial depressant • Increase in venous capacitance – due to central and peripheral sympatholytic action • Impaired gastrointestinal motility • Increased hepatic microsomal activity • Direct CNS depressant, resulting in unreliable neurological examination • Possible allergic reaction • Impaired lymphocyte immune response and function Goals • Maintenance ICP < 20 mmHg • Therapeutic EEG response – burst suppression – cortical electrical silence with preservation of SSEP and BAEF Dosing Regimens (I) • Pentobarbital – High dose Loading: 30-40 mg/kg over 4 hours (~2500mg/70kg) Maintenance: 1.8-3.3mg/kg/hr (~175mg/70kg) – Mid-level dose Loading: 10mg/kg over 30min, 20-25mg/kg over 4hr maintenance: 5mg/kg/hr for 3hrs,then 2-2.5mg/kg/hr with 5mg/kg bolus prn if serum level < 3mg/dl – Low dose Loading: 3-6mg/kg over 30min Maintenance: 0.3- 3mg/kg/hr – Therapeutic serum level: 2.5-4 mg/dl Dosing Regimens (II) • Thiopental: – Loading: 3mg/kg bolus 10-20mg/kg over 1 hr Maintenance: 3-5 mg/kg/hr Therapeutic serum level: 6-8.5 mg/dl Weaning: dosage is halved q 12 hr Monitoring Cardiovascular • A-line: arterial BP, blood gases • PA catheter: CO, CI, SV, SVR, PVR, right heart filling pres., PCWP • Bladder catheter: urine output Cerebrovascular and neurophysiological • ICP: maintain < 25 mmHg, preferably less • CPP: maintain > 70 mmHg • EEG: burst suppression, or cortical electrical silence optional • Brain temperature • Jugular bulb O2 monitor/ oxymeter catheter • Somatosensory or brainstem auditory evoked potentials (SSEP, BAEF) Other monitoring • Core body temperature: NP, TM, E – 32 to 35 degrees C is acceptable • Serum barbiturate levels • Nasogastric catheter: pH and output • Intake and output Duration • Therapy may be required for 7-14 days or longer, may be weaned after 3-6 days Therapeutic end points (I) • Success: – ICP < 20 mmHg for at least 48 hours – Resolution of intracranial mass effects or midline shift – ICP must remain controlled with conventional therapies Therapeutic end points • Failure: – Diagnosed brain death – Uncontrollable ICP despite adequate serum levels, EEG burst-suppression, or electrical silence – Intolerable side effects; • Hypotention not responsive to cardiac inotropes, peripheral vasopressors, or intravenous fluid therapy - cardiac isotopes: dopamine, dobutamine, epinephrine - peripheral vasopressors: ephedrine, phenylephrine - IV fluids: packed RBCs, albumine, hetastarch, LR • Progressive pulmonary dysfunction • Sepsis N = 432, trauma patients Study patients = 55, refractory intracranial hypertension Despite standardized medical management for severe TBI •opiates, benzodiazepines, elevation of the head of bed, avoidance of hypotension and hypercapnia and hyperosmolar therapy • 31 of 55 patients: EVD Pentobarbital infusion with continuous EEG monitoring to ensure adequate burst suppression 22 (40%) survived at discharge • 13 (68%) were normal or functionally independent Median minimum cerebral perfusion pressure after coma treatment was 42 mmHg in survivors and 34 mmHg in nonsurvivors (p = 0.013) Pentobarbital coma treatment of RIH may be even more important when other treatments of RIH, such as decompressive craniectomy, are not available. N = 39 High dose BCT group (21 patients): • 5 mg/kg/hour without BIS monitoing Low dose BCT group (18 patients): • 1.3 to 2.6 mg/kg/hour with BIS score of 40-60 Success definition: ICP was kept less than 20 mmHg for more than 48 hours Success rate: 72.2% (low) >> 38.1% (high) Summary • Barbiturate coma treatment in patients with refractory intracranial hypertension can be a useful tool when surgical treatments such as decompressive craniectomy are not available. .
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