Mild Therapeutic Hypothermia - Essay Example

The Use Running Head: THE USE The Use of Mild Therapeutic Hypothermia Using Cooled Intravenous Fluids After Cardiac Arrest to Improve the Neurologic Outcome: A Quantitative Study In APA Style The Use 2 Abstract Recent studies have shown that mild hypothermia (core temperature of 32 C - 34 C) induced by surface cooling devices improves the neurological outcome after out-of-hospital cardiac arrest resuscitation (Kim, Olsufka, Carlbom, 2005). Results from those studies however, showed that the approach of using surface cooling is "slow and logistically difficult in busy emergency departments" (Bernard, 2004) and that the effectiveness of mild hypothermia can be improved if initiated as soon as possible after return of spontaneous circulation (Kim, et al 2005). This study will enroll patients of ventricular fibrillation and asystole as the initial rhythyms to assess whether the induction of cooled intravenous fluid is a safe, fast and effective technique that will improve the neurological outcome after cardiac arrest. Random selection of patients with ventricular fibrillation or pulseless ventricular tachycardia and asystole or pulseless electrical activity will either undergo therapeutic hypothermia using surface cooling devices as the standard form of treatment or will receive the cooled intravenous fluid infusion of normal saline. The Use of Mild Therapeutic Hypothermia Using Cooled Intravenous Fluids After Cardiac Arrest to Improve the Neurologic Outcome Cardiac arrest with widespread schemia frequently leads to severe neurologic impairment (Holzer, 2002). Recovery without residual neurologic damage after cardiac arrest with global The Use 3 cerebral ischemia is rare (Holzer, 2002). Cardiorespiratory arrest, cardiac arrest or cardiopulmonary arrest is the sudden cessation of the normal circulation of the blood due to failure of the heart to effectively contract during systole. Out-of -hospital cardiac arrest is a leading cause of unexpected death in the developed world, occurring in about 1 in 1,500 adult each year (Bernard, 2004). Prognosis after cardiac arrest with an overall survival rate of less than 6%, is unfavorable. Cardiac arrest outcomes depend on the rhythym: 33% of patients with ventricular fibrillation or pulseless ventricular tachycardia survive, comparing with less than 2% of patients with asystolic or pulseless electrical activity. Other rhythyms and cardiac arrest complications/conditions which comprise less than 2% include subarachnoid hemorrhage or trauma, pregnant women, pediatrics, coma after near-drowning, hanging and other causes of asphyxia. About 60% of cardiac arrest survivors regain consciousness; of these, one-third experience irreversible cognitive disabilities. Emergency life support focus on early aggressive resuscitation; but unluckily, most patients who survive do sustain anoxic brain injury (Green, 2007). Anoxic brain injury is that condition wherein the brain is severely deprived of oxygen. The blood is unable to flow to the brain due to bleeding or injury. After cardiac arrest, chemical cascades resulting in brain injury are created by the free radicals and other mediators in the brain. Three phases of brain injury after hypoxic insult are identified: early, intermediate and late (Howes, 2005). The early stage is described as the utilization of glucose, oxygen and energy due to the direct The Use 4 cessation of blood flow in the brain. The intermediate phase is described as the release of neurotoxic mediators and excitatory amino acids in the brain, occurring hours post arrest. The late phase occurs when cerebral edema and blood-drain barrier are increased. Seizures and neuronal death then happen, occurring up to 24 hours post arrest. Induced mild therapeutic hypothermia (core temperature of 32 - 34 C) diminishes cell injury, and cerebral neuronal healing is increased by the reduction of intracranial pressure and cerebral oxygen demand, thus suppressing the release and production of free radicals (Green, 2005). On the other hand, despite the potential advantages, adverse effects such as arrythmias, infection and coagulopathy may occur ("Circulation", 2003). Research on the use of mild hypothermia has been conducted extensively as a neuroprotectant in acute brain injury with studies having been first initiated as far back as the 1950's (Heard, 2007), but was later abandoned without being formally tested in clinical trials. Interest in hypothermia was revived in the early 1980's with the induction of hypothermia in animals. It provided evidence that "the main mechanism by which hypothermia can help resuscitate the brain after normothermic cardiac arrest is a synergistic effect of the deleterious chemical cascades, enegy loss depolarization, calcium influx, excitotoxicity, free radical reactions, membrane failure, DNA fragmentation and damage to mitochondria" (Heard, 2007). Recently in the 1990's, therapeutic The Use 5 hypothermia has been re-introduced in the clinical practice. Studies have shown that cardiac arrest due to ventricular fibrillation (VF) has improved neurological outcome with the use of induced mild therapeutic hypothermia using surface cooling devices i.e., the use of ice packs to groin, axilla and neck and the use of cooling mattress with cover as adjunct, to maintain core temperature at 32 - 34 C (Holzer, 2002). Very recent studies have also shown that cardiac arrest due to asystole has improved neurological outcome with the use of mild therapeutic hypothermia using the same cooling devices (Foedisch et al., 2008). Based upon the body of published evidence to date, the Advanced Life Support of the International Liaison Committee on Resuscitation has endorsed the use of therapeutic hypothermia for patients with anoxic brain injury after out-of-hospital cardiac arrest (Heard, 2007). The Canadian Association of Emergency Physicians had also endorsed the same as well (Howes, 2005). The endorsement from the two associations were based on the two prospective, randomized, controlled trials conducted in 2002 (the HACA trial and the Bernard trial) which used the surface cooling method. Ice packs were placed to the groin, axillae and neck and a cooling mattress with cover was used as an adjunct to attain a target core temperature of 32 - 34 C. Sedation and neuromuscular blockers were used before the induction of hypothermia in order to prevent shivering. The treatment is now regarded as the standard of care for this condition (Bernard, The Use 6 2004). "Results from animal models suggest that the effectiveness of mild hypothermia could be improved if initiated as soon as possible after return of spontaneous circulation" (Kim, et al., 2005). It was hypothesized in the Bernard study that "early initiation of rapid cooling, preferably in the field soon after return of spontaneous circulation, will have the maximum benefit in both neurological outcome and survival. Several other methods have been proposed to induce rapid hypothermia, including placement of intravascular heat exchange catheters and cooling helmets" (Kim, et al., 2005). But these methods are still in the very stages of study. Methods Sample. The population of interest for this study is all adults 18-75 years old, male or female with a witnessed cardiac arrest, have ventricular fibrillation or pulseless ventricular tachycardia, or asystole or pulseless electrical activity as the initial rhythym, an estimated interval of 5-15 from the patient's collapse to the first attempt at resuscitation, an interval of not more than 30 minutes from collapse to return of spontaneous circulation (ROSC), and unconscious upon admission (Holzer, 2002). Other inclusion criteria are the informed consent to be provided by the authorized representative/next of kin/family member. The exclusion criteria include: 1. Comatose or vegetative state prior to cardiac arrest. 2. Positive to pregnancy test. The Use 7 3. Cardiogenic shock patients 4. Coagulopathy complications. 5. Temperature of < 35 C. 6. Patients in coma or vegetative state prior to cardiac arrest. 7. Evidence of hypotension prior to initiation of hypothermia or for more than 30 minutes after return of spontaneous circulation. 8. Terminally ill patients preceding the arrest with life expectancy of less than 1 year. 9. Evidence of hypoxia before initiation of mild therapeutic hypothermia and for more than 15 minutes after the return of spontaneous circulation. 10. Patients who are taking high doses of vasopressors. 11. Patients with continued refractory ventricular arrhythmias upon enrollment. The sampling frame (i.e, the listing of accessible population) will be obtained from the records in the emergency department in the hospital setting upon admission, to ensure representativeness. The number of subjects to be enrolled in the trial will be determined by inclusion/exclusion criteria. The study will be a randomized, controlled trial wherein patients with ventricular The Use 8 fibrillation and asystole as the initial rhythyms will be randomly selected to either undergo mild therapeutic hypothermia using the rapid infusion of 2 L of 4 C cold, normal saline or receive a standard treatment with mild hypothermia using surface cooling devices. The clinical trial will be up to two years. Design. The study is a quantitative experimental type of research design whereby the subjects (referring to the patients enrolled in the clinical trial) are measured before and after treatment. The study will be designed as a randomized, controlled trial. Random sampling is designed so that each member of the accessible population will have an equal chance of being chosen for treatment and also to avoid bias in the selection process. Biases usually result from differential selection of respondents from the comparison groups. Random assignment also lessens the chance that either group is not typical of the population. The quantitative study design is constructed to ensure construct validity, internal validity external validity and reliability in order that confidence in the findings will be established. The unit of analysis are the individuals (patients). Approved protocol and consent procedure by the institutional review board (IRB) will be made and obtained. The patient's family/legal next of kin will be fully informed about the procedures and risks involved in research and written consent for participation will be obtained from them. The Use 9 If there will be objections at any time during the clinical trial, the patient/s will be withdrawn from the trial. The patient participation is voluntary and he/she is entitled to be free from undue embarrassment, harassment, anxiety and/or discomfort.To ensure confidentiality and anonymity for the participants, the principal investigator/sponsor has/have the obligation to protect patient information ("Institutional Review Board for the Protection of Human Subjects", 2007). The treatment assignments will be randomly generated by a computer random number generator (Hopkins, 2000) and sealed envelopes containing the treatment assignments are prepared and opened immediately upon patient enrollment (Holzer, 2002). The patient is then assigned to a specified group. Procedure. All patients will be sedated and will receive standard care. Sedation will be induced by intravenous administration of medazolam and fentanyl (Holzer, 2002). Shivering during cooling leads to warming and will increase overall energy consumption, thus making cooling more difficult. To counter it, neuromuscular blocker pancuronium will be induced by intravenous administration (Holzer, 2002). For the experimental group, the patients will undergo rapid infusion of 2 L of 4 C cold, normal saline. "One-liter bags of normal saline will be stored in a 4 C refrigerator before use. Each liter will be rapidly infused into an 18-gauge peripheral intravenous line placed in the arm. Two liters of 4 C normal saline will be infused during a The Use 10 period of 20-30 minutes with an intravenous pressure bag inflated to 300 mm Hg" (Kim, et al., 2005). Baseline vital signs will be taken before the infusion. Temperature (to be measured using esophageal probes and bladder probes), blood pressure and heart rate will be measured every 15 minutes for the first hour and then hourly for a total of 12 hours and as clinically indicated. Baseline laboratory tests will include potassium, chloride, sodium, creatinine, hematocrit, blood urea nitrogen, glucose, platelet count, white blood cell count and international normalized ratio. These laboratory tests will be repeated 1 hour after infusion of 4 C normal saline (Kim, et al., 2005) and as clinically indicated also. Cardiac hemodynamic data will be obtained using the transthoracic echocardiography, to be accomplished before fluid administration and 1 hour after completion of the 4 C normal saline infusion. Mitral E and A wave velocities and tissue Doppler E velocity will be measured from a standard apical, 4-chamber view. Pulmonary artery pressures will be calculated from the central venous pressure estimates and the velocity of tricuspid regurgitation, and the central venous pressures will be calculated from the evaluation of inferior vena cava size. After the infusion of 4 C normal saline, active cooling with the use of cooling blankets will be used to maintain mild hypothermia for 24 hours, after which the patients will be allowed to rewarm passively. For the control group, a target core temperature of 32 - 34 C will be attained and maintained for 24 The Use 11 hours using the standard care of surface cooling. Passive rewarming will then be applied for 8 hours and active rewarming to normothermia will follow. Measurements, Data Collection and Analysis. Protocols on baseline characteristics, details on cardiac arrest, out-of-hospital procedures and events, cooling and rewarming procedures, neurological and functional outcome scores at discharge, information on possible adverse events and death will all be documented. Analysis is performed as data are collected in order to guide decisions for further data collection. The Utstein style which is a standardized guideline/format for publication of academic articles in emergency medicine, outlining which type of data should be reported, will be used to record data on cardiac arrest for individual patients. A collection of the recommended variables will enable interhospital and intrahospital comparisons and support national and international research. The Glasgow Outcome Scale, an assessment measurement of outcome after severe brain damage, will monitor the neurological status, whereas the Pittsburgh Cerebral Score will measure the neurologic outcome. The scales were developed primarily to facilitate the assessment and recording of initial severity of brain dysfunction. The stata 10, which is a complete statistical software package for managing, graphing and analyzing data will be used in this clinical trial. The Use 12 References Arrich J. (2005). Clinical application of mild therapeutic hypothermia after cardiac arrest. Critical Care, 9: 297. Bernard, S. (2004). Therapeutic hypothermia after cardiac arrest. The Medical Journal of Australia, 181: 468-469. Circulation (2003). The American Heart Association, 108: 118-121. Foedisch, M., Viehofer A., Richling, N., Holzer, M., Herold, I. et al. (2008). Good neurological recovery at ICU discharge of asystole patients treated with induced mild hypothermia. Critical Care, 12 (2): 373. Green, R. & Howes W. (2007). Stock your emergency department with ice packs: a practical guide to therapeutic hypothermia for survivors of cardiac arrest. Canadian Medical Association Journal, 176: 759-762. Heard, K. (2007). Induction of mild hypothermia in resuscitated cardiac arrest patients. ClinicalTrials.gov, NCT00282373. Holzer, M. (2002). Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest. New England Journal of Medicine, 346: 549-556. Hopkins, W. (2000). Quantitative research design. Sportscience. The Use 13 Howes, D. (2005). Position statement and guidelines for the use of hypothermia after cardiac arrest. Canadian Association of Emergency Physicians, C4. Indiana University of Pennsylvania. (2007). Institutional Review Board for the Protection of Human Subjects. . Kim, F., Olsufka, M., Carlbom, D., Deem, S., Longstreth, W., et al. (2005). Pilot study of rapid infusion of 2 L of 4 C normal saline for induction of mild hypothermia in hospitalized, comatose survivors of out-of-hospital cardiac arrest. Circulation, 112: 715-719. Read More