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 [1][2][3]. The initial data supporting the efficacy of therapeutic hypothermia was collected in patients with coma following VF[4][5][6]. 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[7]. 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

Eligibility Criteria for Post-Cardiac Arrest Therapeutic Hypothermia

Relative Contraindications for Therapeutic Hypothermia:

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.

References

  1. Kuboyama K, Safar P, Radovsky A, Tisherman SA, Stezoski SW, Alexander H (1993). "Delay in cooling negates the beneficial effect of mild resuscitative cerebral hypothermia after cardiac arrest in dogs: a prospective, randomized study". Crit. Care Med. 21 (9): 1348–58. PMID 8370299. Unknown parameter |month= ignored (help); |access-date= requires |url= (help)
  2. Ginsberg MD, Sternau LL, Globus MY, Dietrich WD, Busto R (1992). "Therapeutic modulation of brain temperature: relevance to ischemic brain injury". Cerebrovasc Brain Metab Rev. 4 (3): 189–225. PMID 1389956. |access-date= requires |url= (help)
  3. Weinrauch V, Safar P, Tisherman S, Kuboyama K, Radovsky A (1992). "Beneficial effect of mild hypothermia and detrimental effect of deep hypothermia after cardiac arrest in dogs". Stroke. 23 (10): 1454–62. PMID 1412583. Retrieved 2011-03-02. Unknown parameter |month= ignored (help)
  4. Bernard SA, Gray TW, Buist MD, Jones BM, Silvester W, Gutteridge G, Smith K (2002). "Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia". N. Engl. J. Med. 346 (8): 557–63. doi:10.1056/NEJMoa003289. PMID 11856794. Unknown parameter |month= ignored (help); |access-date= requires |url= (help)
  5. "Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest". N. Engl. J. Med. 346 (8): 549–56. 2002. doi:10.1056/NEJMoa012689. PMID 11856793. Unknown parameter |month= ignored (help); |access-date= requires |url= (help)
  6. Holzer M, Bernard SA, Hachimi-Idrissi S, Roine RO, Sterz F, Müllner M (2005). "Hypothermia for neuroprotection after cardiac arrest: systematic review and individual patient data meta-analysis". Crit. Care Med. 33 (2): 414–8. PMID 15699847. Retrieved 2011-03-02. Unknown parameter |month= ignored (help)
  7. Dumas F, Grimaldi D, Zuber B, Fichet J, Charpentier J, Pène F, Vivien B, Varenne O, Carli P, Jouven X, Empana JP, Cariou A (2011). "Is Hypothermia After Cardiac Arrest Effective in Both Shockable and Nonshockable Patients?: Insights From a Large Registry". Circulation. doi:10.1161/CIRCULATIONAHA.110.987347. PMID 21321156. Unknown parameter |month= ignored (help); |access-date= requires |url= (help)
  8. Sunde K, Pytte M, Jacobsen D, Mangschau A, Jensen LP, Smedsrud C, et al. Implementation of a standardised treatment protocol for post resuscitation care after out-of-hospital cardiac arrest. Resuscitation 2007;73:29-39
  9. Kim F, Olsufka M, Longstreth WT Jr, Maynard C, Carlbom D, Deem S, et al. Pilot randomized clinical trial of prehospital induction of mild hypothermia in out-of-hospital cardiac arrest patients with a rapid infusion of 4 degrees C normal saline. Circulation 2007;115:3064-70


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