Anoxic brain injury medical therapy

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

Medical therapy for anoxic brain injury, includes the use of therapeutic hypothermia. This has been associated with a reduction in ischemic brain injury, particularly in animal models. There are specific guidelines associated with the use of therapeutic hypothermia, as there can be significant complications and side effects from using this method of treatment.

Medical Therapy

Therapeutic Hypothermia (TMH)

Hypothermia has been associated with a reduction in ischemic brain injury in animal models . The initial data supporting the efficacy of therapeutic hypothermia was collected in patients with coma following VF. In the Bernard study, the number of people discharged to home or a rehabilitation facility was 49% of patients (21/43) treated with hypothermia versus 26% (9/34) treated with normothermia (univariate p=0.046, multivariate p=0.011). While patients with a shockable rhythm such as VT/VF derive significant benefits from therapeutic hypothermia, patients with non-shockable rhythms such as PEA and asystole may not derive the same benefits. While 39% (274/708) of patients with VT/VF treated with TMH achieved an acceptable level of neurologic outcome (cerebral performance categories level 1 or 2) at discharge, only 16% (68/437) of patients with PEA/asystole treated with TMH achieved an acceptable outcome. In multivariate analyses, TMH was associated with increased odds of an acceptable neurological outcome (multivariate odds ratio = 1.90) in patients with VT/VF, while in contrast TMH was not associated with acceptable neurological outcome (multivariate odds ratio = 0.71) in patients with PEA/asystole.

Complications and Side Effects Associated with Hypothermia

• Hypothermia activates the sympathetic nervous system causing vasoconstriction and shivering. Shivering increases O₂ consumption by 40-100%. Sedatives, opiates, and neuromuscular blockers can counteract these responses and enhance the effectiveness of active cooling. However, initiating paralysis in a patient that is already hypothermic should be avoided because it can result in a precipitous drop in core body temperature. Elderly patients will cool more quickly than younger or obese patients.
• Hypothermia shifts the oxyhemoglobin curve to the left may result in decreased O₂ delivery. However, the metabolic rate is also lowered, decreasing O₂ consumption / CO₂ production, cardiac output and cerebral blood flow. Ventilator settings may need to be adjusted due to decreased CO₂ production, using temperature corrected blood gases.
• Hypothermia initially causes sinus tachycardia, then bradycardia. With temp <30º C there is an increased risk for arrhythmias. With temp <28º C there is an increased risk for ventricular fibrillation. The severely hypothermic myocardium (<30°C) is less responsive to defibrillation and medications. Therefore it is extremely important to keep temp >30ºC.
• Hypothermia can induce coagulopathy which is treatable with platelets and FFP.
• Hypothermia-induced diuresis is to be expected and should be treated aggressively with fluid and electrolyte repletion. Magnesium, phosphorus and potassium should be monitored closely and maintained in the normal (because it will rebound to very high) range.
• Decreased insulin secretion and sensitivity leads to hyperglycemia, which should be treated aggressively.
• Re-warming too rapidly can cause vasodilation, hypotension, and rapid electrolyte shifts.

Eligibility Criteria for Post-Cardiac Arrest Therapeutic Hypothermia

• Meets eligibility criteria for Post-cardiac Arrest Care Pathway
• Comatose at enrollment with a Glasgow Coma Motor Score <6 pre-sedation (i.e., patient doesn’t follow commands)
• No other obvious reasons for coma
• No uncontrolled bleeding
• Hemodynamically stable with no evidence of:

• Uncontrollable dysrhythmias
• Cardiogenic shock
• Refractory hypotension (MAP <60 mm Hg) despite preload optimization and use of vasoactive medications

• No existing, multi-organ dysfunction syndrome, severe sepsis, or comorbidities with minimal chance of meaningful survival independent of neurological status

Relative Contraindications for Therapeutic Hypothermia:

• Prolonged arrest time (> 60 minutes)
• Thrombocytopenia or other coagulopathies
• Pregnancy (Therapeutic hypothermia can potentially be performed on pregnant female in consultation with OB/GYN)

Guidelines for Therapeutic Hypothermia

Preparation

If criteria are met, the patient is cooled using the induced hypothermia protocol for 24 hours to a goal temperature of 32-34° C (89-93° F). The patient should be cooled to the target temperature as quickly as possible. The 24-hour time period is from the time of initiation of cooling

1. Place arterial line for blood pressure monitoring.
2. A continuous temperature monitor with bladder probe or esophageal catheter will aid in cooling process and prevents overcooling.
3. Use of secondary temperature device (Exergen) is also recommended to monitor temperature as bladder probe is accurate only if there is adequate urine output. This alternative temperature probe can be any core temperature monitor that is compatible with the Arctic Sun console.

Methods

External Cooling with Cooling Blankets and Ice

1. Eligibility should be confirmed and materials should be gathered.
2. Obtain two cooling blankets and cables (one machine) to sandwich the patient between them. Each blanket should be covered with a sheet to protect the patient’s skin.
3. Cisatracurium (Nimbex) should be administered via microinfusion for paralysis. Bolus of 150mcg/kg and a maintenance dose of 2mcg/kg/min is used. Use of BIS or train of four are not recommended.
4. Propofol (Diprivan) or Midazolam (Versed) to be administered for sedation. Propofol- Bolus (optional) 0.3-0.5mg/kg followed by infusion of 1mg/kg/hour while patient is paralyzed. Midazolam- Bolus (optional) 0.05mg/kg followed by infusion of 0.125mg/kg/hour.
5. Pack the patient in ice (groin, axilla, side of neck and chest) and additional measures can also be used as needed to achieve the target temperature. Packing ice on top of chest should be avoided as ventilation may be impaired.
6. Cold saline infusion via a peripheral line or femoral venous catheter (NOT via jugular or subclavian line) can be performed to assist in achieving target temperature. 30cc/kg of 4°C normal saline over 30minutes.
7. Monitor vitals with attention towards arrhythmia detection.
8. Ice bags should be removed once target temperature is reached and the temperature should be maintained using cooling blankets.

External Cooling with Arctic Sun Vest Device

1. Eligibility should be confirmed and materials should be gathered.
2. Patient’s temperature should be noted and cooling pads should be placed on patient as per manufacturer’s guidelines.
3. Set target temperature after applying pads.
4. Sedate and paralyze the patient with agents mentioned above to control shivering.
5. External pacing pads can also be used with these pads. Place external pacing pads on the chest and cover with Arctic Sun pads.
6. Rewarming strategies as mentioned below.

Supportive Therapy

1. A mean arterial pressure (MAP) of more than 90mm of Hg is preferred for cerebral perfusion. In addition to hypothermia, hypertension improves neuroprotection. Target MAP should be determined by the treating physician taking into account the cardiac safety and advantage of higher cerebral perfusion pressures.
2. Monitor the patient for arrhythmias. Active cooling should be discontinued and actively re-warmed when significant dysrhythmias, hemodynamic instability or bleeding develops.
3. Electrolyte panel, glucose and complete blood count should be measured at 12hours and 24hours.
4. Arterial blood gases should be measured at the patient's actual body temperature. CO₂ should be maintained in the normal range (35-45).
5. Blood cultures should be drawn at 12 hours after the initiation of cooling as infections will be masked during the cooling phase.
6. Skin should be checked every 2 hours for burns caused by cold blankets. If the Arctic Sun device is utilized, skin should be checked every 6 hours.
7. Using a secondary temperature monitoring device when using the Arctic Sun is recommended. The patient temperature on the Arctic Sun, the secondary temperature source and the water temperature of the Arctic Sun are recorded. The water temperature will help to determine the work of the machine in trying to maintain target temperature.

Re-warming

This is the most critical phase, as the previously constricted peripheral beds start to dilate with resultant hypotension as mentioned above.

Re-warming of the patient is begun 24hours after the initiation of cooling. It is recommended that the body be re-warmed at the rate of 0.5-1ºC every hour, thereby approximately 8-12hrs to passively re-warm up to a target temperature of 36ºC (96.8ºF).

Re-warming phase is a total of 72 hours, with passive re-warming for 24hours and controlled re-warming for 48hours.

Passive Re-warming

At 24 hours (after the initiation of cooling) -

1. Remove cooling blankets (and ice if still in use).
2. Paralysis and sedation must be maintained until target temperature of 36ºC is reached: paralysis is discontinued first followed by midazolam once train of 4 is achieved.
3. Monitor patient for hypotension related to re-warming.
4. Monitor patient for hyperkalemia during re-warming.

Controlled Re-warming

If the Arctic Sun cooling vest is used, program the machine for controlled rewarming over 6-8 hours. Dial the desired warming on the machine to maintain a target temperature for the next 48 hours.

The patient should be on constant follow-up with the stroke service to reassess the neurological status after the discontinuation of hypothermia.