Brain Oriented Resuscitation In The First Hour – Strategies
Somashekhar M Nimbalkar
Satvik C Bansal
Global cerebral ischemia occurs commonly in patients who have a variety of clinical conditions including cardiac arrest (CA), shock, and asphyxia. Unfortunately, survival with neurologic sequelae is common for adult and pediatric victims of cardiac arrest. Neurologic sequelae from brain injury are varied and constitute a spectrum that includes coma, seizures, ischemic stroke, delirium, and neurocognitive impairment. Most of the damage in the first hour is due to reperfusion injury leading to release of inflammatory mediators and reactive oxygen radicals. In the first hour of resuscitation of the child who has had a cardiac arrest, the mainstay of therapy is supportive management which include maintaining near normal pH, permissive hypercapnia, reduction of cerebral edema, maintaining normothermia and euglycemia, maintaining blood pressure within normal limits, and maintaining nutrition. Therapeutic hypothermia, a novel intervention, shows promise but is not yet recommended widely outside of a research setting or a protocol based hospital environment.
Brain Oriented Resuscitation in the First Hour- Strategies
Cerebral Ischemia is defined as diminution of cerebral blood flow (CBF) to a critical threshold that propagates brain damage involving the entire brain or a selective region. Global cerebral ischemia occurs commonly in patients who have a variety of clinical conditions including cardiac arrest (CA), shock, and asphyxia. In addition to injury to other organs from systemic hypoperfusion, neurologic sequelae from brain injury are varied and constitute a spectrum that includes coma, seizures, ischemic stroke, delirium, and neurocognitive impairment.
Post-resuscitation neurologic management:
Meaningful neurologic survival represents the most clinically relevant outcome measure for cardiopulmonary resuscitation (CPR). Unfortunately, survival with neurologic sequelae is common for both adult and pediatric victims of cardiac arrest.
a. Supportive care
Following resuscitation from cardiac arrest, there is a period of increased sensitivity of the brain to secondary injury. The precipitants of secondary injury include hypotension, hypoxia, hyperglycemia, and hyperthermia.
Early post-resuscitative supportive care should focus on avoiding these causes of secondary injury.
- Avoid hypotension
- Maintain normoxia (avoid hypoxia and prolonged hyperoxia)
- Maintain euglycemia
- Avoid hyperventilation
- Avoid hyperthermia
Watch out for iatrogenic hyperventilation.
- Hyperventilation causes hypocapnia leading to vasoconstriction and decreased cerebral blood flow in children following traumatic brain injury[1,3] and in adults recovering from cardiac arrest. Decreased cerebral blood flow has been associated with poor outcomes in children with traumatic brain injury and severe hypocapnia (PaCo2<30) is associated with increased mortality.
- Hyperventilation can also decrease cerebral blood flow by increasing intra-thoracic pressure causing a decrease in cardiac output and cerebral venous return.
- In addition, respiratory alkalosis shifts the oxygen hemoglobin dissociation curve to the left reducing oxygen delivery to tissue.
b. Management of Cerebral edema:
Hypoxic-ischemic encephalopathy following resuscitation from cardiac arrest is characterized by cytotoxic cerebral edema. Progressive edema results in intracranial hypertension that can contribute to secondary ischemic injury by further reducing cerebral perfusion pressure.
- Standard treatment includes
- Promotion of venous drainage by elevation of the head at 30 degrees.
- Maintenance of midline head position
- Use of isotonic fluids
2. Hyperosmolar fluids (mannitol and hypertonic saline) can be used in cases of raised intracranial pressure. Supportive care management is aimed at maintaining normal blood pressure, pH, temperature and glucose.
c. Seizure management:
Early post-traumatic seizures (EPTS) are those that occur within the first week of head injury. In less severe traumatic brain injury, the occurrence of EPTS is < 5 %. Seizures markedly increase cerebral blood flow, glucose and oxygen consumption, and intracranial pressure, placing the brain at risk for secondary injury. Aggressive treatment of post-arrest seizures is indicated to prevent progression to status epilepticus.
Benzodiazepines are indicated for the initial acute treatment of post-resuscitation seizures. Longer-acting antiepileptic drugs are indicated if benzodiazepines are ineffective or if seizures rapidly recur.
- Barbiturates such as phenobarbital have the added advantage of decreasing cerebral metabolic rate while controlling seizures but may reduce cerebral perfusion pressure by causing systemic hypotension.
- Fosphenytoin is an alternative but it should be administered cautiously because of the risk of hypotension.
- Refractory Seizures may necessitate induction of a pharmacologic coma with a long-acting barbiturate such as pentobarbital. Pentobarbital is titrated in doses of 1 to 5 milligram per kilogram body weight (1-5 mg/kg) until cessation of clinical seizures occurs and is then followed by a continuous infusion. Hemodynamic consequences of pentobarbital include myocardial depression and vasodilation, and concomitant use of vasoactive infusions is typically necessary. Electroencephalographic (EEG) monitoring is indicated to ensure that electrical seizures are resolved.
d. Blood glucose control:
It has been seen that pediatric survivors of cardiac arrest demonstrated the occurrence of post- arrest hyperglycemia with mean blood glucose concentrations> 150 milligram per deciliter (mg/ dL) or >8.3 millimoles per liter (mmol/L). In an observational study of 101 children <14 years of age who underwent craniotomy for traumatic brain injury, perioperative hyperglycemia (serum glucose level >200 mg/dL) was found in 45% of children and is also significantly associated with a Glasgow coma scale <8.
Hypoglycemia as well as hyperglycemia have detrimental effects on the growing brain and hence strict control is to be maintained on the glucose levels for a better prognosis. This is achieved by close monitoring of glucose intake and insulin if necessary.
Is Therapeutic Hypothermia the future?
Measurement and control of temperature following cardiac arrest is an important part of patient management. After arrest, children commonly have an initial period of spontaneous hypothermia followed by a delayed (approximately 24 hours later) development of fever. These temperature changes are relevant because hypothermia is neuro-protective, whereas hyperthermia can exacerbate brain injury.
Hence, routine warming of patients during initial hypothermia is no longer recommended. Rewarming can negate the neuro-protective effects of hypothermia and may cause an ‘‘overshoot’’ of temperature that contributes to subsequent fever. Intentional induction or maintenance of hypothermia (therapeutic hypothermia) has recently been shown to be beneficial in adults recovering from cardiac arrest and is also recommended in newborns with birth asphyxia.
Thus, consideration should be given to actively cooling children who remain comatose following resuscitation from cardiac arrest. In addition, temperature should be monitored closely and fever should be treated aggressively.
American Heart Association currently recommends that ‘Therapeutic Hypothermia’ (32°C to34°C) may be beneficial for adolescents who remain comatose following resuscitation from a sudden, witnessed, out-of-hospital VF(ventricular fibrillation) cardiac arrest. It may also be considered for infants and children who remain comatose following resuscitation from cardiac arrest. The use of therapeutic hypothermia is increasing, however, currently only about 3.3 % of intensive-care specialists in the United States are using this protocol.
Pointers on Therapeutic Hypothermia
Induction of hypothermia after cardiac arrest is a time-sensitive intervention and most clinical trials allow a window of only six hours after resuscitation. Target temperatures are achieved most effectively with an endovascular cooling device, but external cooling methods have been used widely.
Although therapeutic hypothermia remains an unproven therapy in children after cardiac arrest, it is a well-accepted fact that hyperthermia exacerbates neurologic injury after a hypoxic- ischemic event.
Children who are successfully resuscitated frequently demonstrate temperature instability in the first 24 hours with a period of spontaneous hypothermia followed by rapid onset of hyperthermia. Clinicians should anticipate the possibility of fever and be prepared with interventions to restore normothermia as soon as possible.
- In the first hour of resuscitation of a child who has had a cardiac arrest, the mainstay of therapy is supportive management.
- Supportive management includes near normal pH maintenance, permissive hypercapnia, reduction of cerebral edema, maintaining blood pressure and acid base balance within normal limits, normothermia, normoglycemia, and maintaining nutrition.
- Therapeutic hypothermia is of promise but is not yet widely recommended outside of a research setting or a protocol based hospital environment with obtained consent from family or guardian.
- Most of the damage in the first hour is due to reperfusion injury leading to release of inflammatory mediators and reactive oxygen species.
Dr. Amee Amin for the editing of the manuscript.
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