Therapeutic Hypothermia in improving Neurological outcome after Cardiac Arrest

Background: Only a few patients survive cardiac arrest as it with widespread cerebral ischemia frequently leads to severe neurologic impairment. Aim: Our objective was to evaluate whether induced hypothermia improves neurologic recovery in survivors of primary cardiac arrest or not. Methods: We included randomized or quasi-randomized, recent controlled trials (from 2002 till now based on the electronic databases of PubMed/Medline, Scopus, and Cochrane were searched for relevant literature and studies of adults who were successfully resuscitated, where therapeutic hypothermia (TH) was applied within 6 hours after arrival at emergency department after sudden cardiac arrest especially when asphyxia is the cause of the arrest and where neurologic outcome was compared with no history of previous cardiac arrest. We excluded studies without a control group and historical researches. Result: In patients who have been successfully resuscitated after cardiac arrest due to ventricular fi brillation, therapeutic mild hypothermia increased the rate of a favorable neurologic outcome and reduced mortality. Conclusion: Mild resuscitative hypothermia in patients is feasible and safe. It improves short term neurologic recovery and survival in patients resuscitated from cardiac arrest of presumed cardiac origin. Its long-term effectiveness and feasibility at an organizational level need further research. Research Article Therapeutic Hypothermia in improving Neurological outcome after Cardiac Arrest Darine Ashraf Soudy* Clinical Hospital and Managed Care Dentistry, Dental Student at ERU Clinical Researcher HR Member at Spark ERU, Egypt Received: 07 May, 2018 Accepted: 07 July, 2018 Published: 09 July, 2018 *Corresponding author: Darine Ashraf Soudy, Clinical Hospital and Managed Care Dentistry, Dental Student at ERU Clinical Researcher HR Member at Spark ERU, Egypt, Tel: 0201098126332; Email:


Introduction
The heart has electrical system control rhythm of heart beat. And presence of problem or disease cause defect rhythm of heart beat. Arrhythmia has three shapes: -Increase in rhythm of heart beat -Decrease in rhythm of heart beat-stopping of heart beat, Sudden Cardiac Arrest (SCA). SCA is different from cardiac attack which is circulatory problem.
Although return of spontaneous circulation (ROSC) is crucial in the process of recovery from cardiac arrest, it is only the fi rst of many complex stages. Given the complexity of post cardiac arrest syndrome and its impact on the patient.
There is cellular changes associated with reperfusion injuries for example the mechanism of free radicals just like hydrogen peroxide or superoxide molecules in the blood causes a lot of damage, infl ammation may be part of this damage process as it is a visible sign of the body reaction. And other mechanism that has been proposed for causing reperfusion injury is within the cells themselves through the mitochondria (the power house of the cells) it turns out that they play a vital role in cell life and death.
When you deny the blood fl ow for the cells or organs so it is ischemia (lack of blood fl ow), which sets up a number of damaging pathways, these free radicals also called reactive oxygen species (ROS) are created that activate the infl ammation cascade to start occurring and enable mitochondria to be dysfunctional or the energy dysfunction.
When these tissues or cells are perfused (return of blood fl ow) all of the previous complications amplify within minutes after reperfusion and they get more intense and it is a remarkable thing, and if no serious control is done this cascade can become irreversible. Theses mechanisms cause blood vessel instability and blood pressure (BP) comes very unstable, cell death and brain swelling which is well known as cerebral edema that causes severe brain injury that can lasts [1].
Initial neurologic injury occurs when circulatory collapse impairs oxygen fl ow to the brain. Without oxygen, the brain DOI: http://dx.doi.org/10.17352/jnnsd.0000023 switches to anaerobic metabolism, which disrupts adenosine triphosphate-dependent cellular pumps, resulting in excessive calcium and glutamate excretion. This excess makes brain cells more excitable, leading to further hypoxemia, in turn causing mitochondrial and cellular death. Cellular death results in cerebral edema, producing further damage. The initial injury also disrupts the blood-brain barrier, which increases fl uid in the brain and worsens cerebral edema.
Once circulation is restored, reperfusion injury occurs and may persist for hours. During this time, cell death triggers an infl ammatory response in which the immune system releases neutrophils and macrophages to eliminate the dead cells. Unfortunately, this process produces free radicals that cause continued cell damage, worsening the infl ammatory response, which exacerbates cerebral edema. This vicious cycle continues to cause neurologic injury.

Discussion
When the Cardiac Arrest (CA) happens, the normal guidelines protocols as (CPR) are done, unfortunately not all the arrested patients survive, and only a few patients return back to their normal circulation. But even patients who return of systemic circulation not all of them are hospital discharged [2] (Figure 1).
Hypothermia counteracts neuro excitation in brain cells by stabilizing calcium and glutamate release, reducing the degree of cell death. Cerebral metabolism decreases 6% to 10% for every degree Celsius that body temperature drops. As cerebral metabolism declines, the brain needs less oxygen.
In essence, hypothermia counteracts many of the destructive mechanisms of cardiac arrest. Its effects resemble those of cardiac defi brillation, which makes the heart stop and then reset itself to a normal rhythm. Similarly, hypothermia halts destructive brain mechanisms and lets the brain reset itself to normal functioning.
Therapeutic hypothermia occurs in three phasesinduction, maintenance, and rewarming. Clinicians must control hypothermia and rewarming to prevent potential adverse effects.
Temperature should be monitored with a method that measures core temperature, such as use of an esophageal, bladder, or pulmonary artery catheter.
Duration of therapeutic hypothermia depends on facility protocol. No research is available on optimal duration. Some facilities start counting duration from the time cooling begins; others start when the patient reaches target temperature.
Nearly all adverse effects can be prevented or managed in an intensive care setting.
Pilot trial and recent studies show the importance of hypothermia for recovery after cardiac arrest .it shows that it was safe and feasible to mildly cool patients after CA.
Surface cooling was initiated within 62 minutes after CA .The target temperature (32-340C) was reached after 287 minutes and was maintained for an additional 24 hour.
The outcome was measured with the CPC score which subdivided into good outcome (CPC1 and CPC2), poor outcome (CPC 3 and CPC 4) or death [4].
Dr. Bernard at Dandenong hospital pointed to that cerebral perfusion injury occurs when cerebral blood fl ow is restored after cardiac arrest and resuscitation .increased intracellular levels of glutamate, an excitatory neurotransmitter released from pre-synaptic terminals., activate ion channel complex that cause calcium to shift from the extracellular to the intracellular fl uid leading to the accumulation of oxygen free radicals and the activation of degradative enzymes .In addition, cerebral hemodynamics may remain abnormal after resuscitation from cardiac arrest [5] . In 2007s, Acta Anathesiol Scand discussed that their experience indicates that patients who are haemo dynamically unstable after CA requiring support with IABP and adrenergic drugs can be safely treated with hypothermia. Their strategy was early revascularization with PCI and a liberal use of IABP to support failing circulation. It is not known whether hypothermia favors the heart as well as the brain with respect to the prevention of reperfusion injury. They conclude that TH will probably be a part of CPR in the future.
The rapid successful implementation of therapeutic hypothermia indicates that simple external cooling protocol was well accepted by everyone. Although not 100% successful in achieving the target temperature, the ease of application and absence of costs related to new equipment should make method an attractive way of starting up TH in any system .the present recommendation is to cool the patients as rapidly and as soon as possible [6].

Cooling protocol and feasibility
The rapid successful implementation indicates that our simple external cooling protocol was well accepted by everyone involved; paramedics, critical care nurses and physicians. Bernard et al. described his method as inconvenient for the nursing staff and a barrier to implementation TH in clinical practice [7], Although not 100% successful in achieving the target temperatures, the ease of application and absence of costs related to new equipment should make our method an attractive way of starting up TH in any system. All studies using external cooling methods have reported diffi culties with cooling all patients, and similar slow cooling rates have been a universal fi nding in the studies so far [3,5,7,8], Nonetheless, the present recommendation is to cool the patients as rapidly and as soon as possible [6,7,9,10] .
In 2016 ANZCOR puts guidelines provides advice on (TTM) during (PCA) period which is a therapy associated with improved out comes.
Guideline applies to adult arrested who require (ALS) after CA. it suggests TTM as opposed to no TTM for adults with in hospital cardiac arrest (IHCA) with any initial rhythm who remain unresponsive after ROSC) ,it suggest prevention and treatment of fever in persistently comatose adults after completion of TTM between 32 and 36 [11].
Hypothermia also show great effect in pulmonary complications after SCA, cardiogenic shock that was not responsive to usual therapy ,no risk for bleeding in hypothermic patients compared with normo thermic controls, does not signifi cantly increase metabolic acidosis or lactate levels for cardiac or neurologic surgery [12].
Hypothermia is contraindicated for pregnancy, Hypothermia before cooling efforts begin, bleeding problem ICV fi lter excluded from long cooling catheters (ICY) must use shorter cooling and existing DNR or DNI order. Patient's treated with hypothermia are exposed to the risk of hyperglycemia; and increased blood sugar levels are associated with increased morbidity and mortality. Tight control of blood sugar levels and insulin therapy has been associated with decreased morbidity and mortality. Increased blood sugar levels are associated with increase in the rate of infection, neuropathy and renal failure. Therefore, in hypothermic patients, tight control of blood sugar levels is essential [7].

Other complications
Hypothermia increases serum levels of amylase and liver enzymes. In addition, most patients undergoing hypothermia Fortunately, although hypothermia has adverse effects, but most of the complication of induction of hypothermia can be prevented or controlled in intensive care conditions. We fi nally conclude the great effect of hypothermia, but care should be taken during performing it to avoid its complications, continuous monitoring temperature should be done to obtain effective result and safe patient life [12] (Figure 3).

Use of therapeutic hypothermia in children
In 2003 there was insuffi cient evidence to make a recommendation on the use of TH in children resuscitated from cardiac arrest [14].
Until additional pediatric data become available, clinicians should tailor therapy for individual patients on the basis of their assessment of the risks and benefi ts of hypothermia.
Risk-benefi t assessment should take into account relevant data from laboratory models of asp hyxial arrest [6], results from trials of adult cardiac arrest [15], and reports on the use of hypothermia in treatment of neonatal asphyxia. The results of TH are generally favorable in laboratory models of hypoxic ischemic injury to immature brains of various species.
Preliminary data from clinical trials of perinatal asphyxia indicate that induced hypothermia is feasible and safe, but data on long-term neurological morbidity are not yet available [15].
It is diffi cult to extrapolate from these disparate sources of information, and thus there is no consensus yet for use of therapeutic hypothermia among clinicians who care for these critically ill children [14]. It is thought that therapeutic hypothermia can affect and simultaneously block multiple metabolic pathways, infl ammatory reactions and apoptosis processes that occur after an ischemic cascade, so they prefer hypothermia than normothermia [9]. Figure 3: An example of a hospital-based protocol for therapeutic hypothermia (TH) that summarizes key steps for initiation and implementation of hypothermia. IVB indicates intravenous bolus; NMBA, neuromuscular blocking agent; and T1DM, type 1 diabetes mellitus [12].  Many single-center studies and metaanalyses demonstrate that therapeutic hypothermia (TH), in which the body temperature is maintained at 32-35°C, exerts signifi cant neuro protection and attenuates secondary intracranial hypertension after traumatic brain injury (TBI). In 2015, two well-designed multi-center, randomized controlled trials were published that did not show favorable outcomes with the use of TH in adult patients with TBI compared to normothermia treatment (NT) [12].

Degree of Hypothermia
Neurologic outcome was evaluated after return of spontaneous circulation and was expressed in term of cerebral performance category (CPC Careful fl uid monitoring during rewarming is crucial because of the vasodilation that accompanies a body temperature rise.
Volume replacement may be needed to prevent fl uid defi cit and hypotension.
Duration of therapeutic hypothermia depends on facility protocol. No research is available on optimal duration. Some facilities start counting duration from the time cooling begins; others start when the patient reaches target temperature ( Figures 6,7).

Results
Throughout the studies we have discussed it shows that -92% Survival with good neurological outcome as it is feasible, safe used. Neither safety concerns nor costs should be a barrier for implantation of TH.
-4% of survivors after OHCA treated with TH the induced hemodynamic changes reversed after normothermia, while the need for vasopressor support persisted. Patients requiring addition of norepinephrine/epinephrine on top of dopamine had an increased 30-day all-cause mortality, as well as death from neurological injury.   No benefi t to prehospital initiation of therapeutic hypothermia in out-ofhospital cardiac arrest.
-6% shows worse outcome as • Hypothermia and rapid rewarming is associated with worse outcome following traumatic brain injury.
• Increased Thyroxin during Therapeutic Hypothermia predicts death in comatose patients after cardiac arrest.
• -Therapeutic hypothermia after cardiac arrest: another confounding factor in brain-death testing (A 10-monthold infant with reversible fi ndings of brain death).

Groups in knowledge (things for further researches)
-There is no evidence that hypothermia has the same effect on heart as brain.
-Many patients survive from cardiac arrest with high outcome but with different variations which still unclear.

Conclusion
Hypothermia is proving to be an extremely robust and important therapy for cardiac arrest survivors and so far the only therapy consistently shown to reduce mortality and improve neurological outcomes in cardiac arrest survivors.
Mild therapeutic hypothermia improves short term neurologic recovery and survival in patients resuscitated from cardiac arrest of presumed cardiac origin. Its long term effectiveness and feasibility at an organizational level need further.
Therapeutic hypothermia for the treatment of post cardiac arrest coma can be successfully implemented -k---intensive care practice with a major benefi t on patient outcome, which appeared to be related to the type and the duration of initial cardiac arrest and seemed maintained in patients with shock.
After studies, they conducted a prospective controlled trial comparing moderate induced hypothermia with normothermia in comatose survivors of (OOHCA). The study proved that hypothermia improves outcome more than normothermia.
The use of induced hypothermia after cardiac arrest requires an understanding of physiolological effect of (IH) in each organ system. -Mild resuscitative hypothermia in patients is feasible and safe. A clinical multicenter trial might prove that mild hypothermia is a useful method of cerebral resuscitation after global ischemic states .and not associated with an increase in length of stay in the ICU. And fi nally, hypothermia has different consedration for arrested children.
Most research contraindicate using hypothermia with them.
Mild hypothermia of 33 to 34°C seems to be a suffi cient compromise between benefi cial effects through mitigation of ischemic membrane damage and reperfusion. Injury and the risk of adverse effects through arrhythmic, infl ammatory, hemodynamic, and coagulation disorders. Hyperthermia is not tolerable any longer in the course of intensive care treatment after cardiac arrest; temperature control to normothermia with antipyretic drugs is the least that should be done.

Recommendation
Therapeutic hypothermia is recommended for the treatment of neurological injury after resuscitation from out-of-hospital cardiac arrest. Laboratory studies have suggested that earlier cooling may be associated with improved neurological outcomes.
Much of our recommendations around the therapy are based on limited literature and a lot of extrapolation.