Please select a question from below:
What is cardiac arrest?
What is an out-of-hospital cardiac arrest?
What is the incidence of out-of-hospital cardiac arrest?
What causes a cardiac arrest?
What is the treatment for out-of-hospital cardiac arrest?
What happens to the brain during a cardiac arrest?
What is induced hypothermia?
How is hypothermia induced?
What are the potential benefits of hypothermia?
Have there been any studies of hypothermia in cardiac arrest?
Have there been any studies using IV fluids to induce hypothermia in cardiac arrest?
What is the American Heart Association's recommendation regarding the use of hypothermia in cardiac arrest?
What is the HYPOTHERMIA study?
Who will be eligible to be in the HYPOTHERMIA study?
How will the study decide which treatment is provided?
Are there risks involved in the HYPOTHERMIA study?
In such an emergency situation, how is informed consent obtained?
How will a subject know if they were enrolled in the HYPOTHERMIA study?
Is it possible that a subject may be enrolled into more than one emergency study?
How will enrolled subjects’ medical information be kept confidential?
Is it possible to opt out of the study?
Who are the investigators for the HYPOTHERMIA study?
How can I get more information about the HYPOTHERMIA study? <
Cardiac arrest is a serious medical condition. During a cardiac arrest the heart stops beating effectively and is unable to pump oxygenated blood to the brain and the rest of the organs of the body. It usually occurs suddenly and unexpectedly. Death occurs within minutes.
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Cardiac arrest can happen any place. If the cardiac arrest occurs outside of the hospital it is referred to as an out-of-hospital cardiac arrest.
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Cardiac arrest is the number one killer of Americans each year. It kills more than 450,000 people annually.
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The most common underlying reason for patients to die suddenly from cardiac arrest is coronary heart disease. These people are at varying risks for cardiac arrest. In general, those with damaged hearts are at greater risk. Specific risk factors include a previous episode of cardiac arrest, a history of heart failure and a family history of sudden cardiac arrest. Other factors besides heart disease can cause cardiac arrest. They include respiratory arrest, electrocution, drowning, choking and drug overdoses. Cardiac arrest can also occur without any identifiable cause.
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The first step in the treatment of an out-of-hospital cardiac arrest is quick identification of the problem. This can be done by checking for signs of life (consciousness, movement, normal breathing). Once a cardiac arrest is confirmed, quick access to the 911 system is essential. The standard treatment for cardiac arrest is immediate CPR, which can be started by citizens before emergency medical providers are on the scene.
Once the emergency medical providers are on scene they continue CPR. Many times an electrical shock or shocks are given to the heart to try and restore a normal heartbeat. This is called defibrillation. Other procedures to treat patients in cardiac arrest are the placement of electrodes to monitor the heart’s electrical rhythm, the placement of an intravenous line (needle into the vein) to give fluids and medications and the placement of an endotracheal tube (tube into the lungs) to provide breathing.
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During a cardiac arrest, while the heart is not pumping effectively, the brain is left without oxygen. This can lead to cell damage. After a successful resuscitation, the brain also faces more damage from chemical reactions that occur when the blood starts to flow again.
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Induced hypothermia means cooling the body by reducing the body temperature to below normal. The normal body temperature is between 36° C -37° C (97° F -99° F). Mild to moderate hypothermia is 33° C -34° C (91.4° F –93.2° F).
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Induced hypothermia can be accomplished using several methods. Surface cooling methods such as cooling blankets placed under and on top of patients and ice packs placed in the groin and armpit areas are effective in decreasing temperature, but may take up to 6 hrs to do so. There are also invasive methods of induced hypothermia using catheters inserted into large blood vessels. As the blood circulates and comes in contact with these catheters cooling occurs.
This is a very quick and efficient way to lower body temperature; however the insertion of these catheters needs to be done in the hospital by a skilled physician. Another way to decrease the body’s temperature is to give cold fluid into the veins through an I.V. (small needle in the vein). This method has the advantage of lowering the body temperature quickly and can be done by non physician personnel such as paramedics and nurses.
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The exact mechanisms of the benefits of hypothermia on the brain are not fully understood. In simple terms, cooling has long been known to help protect the brain by slowing metabolism, thus reducing the brain’s need for oxygen and nutrients.
However it is believed that there are many other favorable chemical and physical mechanisms that occur in the brain as a result of hypothermia. One of the major reasons brain cells become damaged is thought to be due to calcium entry into the cells. Hypothermia decreases the entry of calcium into the cells. Hypothermia also decreases extra fluid build up in the brain that can occur with injury
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There have been two published studies showing that induction of mild to moderate hypothermia improves neurologic outcome after cardiac arrest. Both these studies used surface cooling methods such as cooling blankets and ice packs to induce hypothermia. Both studies were randomized trials. In a randomized trial subjects are put into one of two groups – a control group or a treatment group. At the time or enrollment each subject has a 50/50 chance of being in either group. The control group receives standard care and the treatment group receives the treatment, in this case hypothermia.
The Hypothermia after Cardiac Arrest Study Group, a multicenter European research group, randomized 275 adult subjects resuscitated from witnessed cardiac arrest. 137 subjects were assigned to induced hypothermia (32º-34ºC) and cooled with cooling blankets for 24 hours and 138 subjects were randomized to receive no cooling (normothermic group). These subjects received medications for sedation and to prevent shivering that might lead to warming. In the induced hypothermia group, 55% of the subjects had a favorable neurologic outcome at six months, as compared with 39% of the normothermic group. At six months, 41% of the hypothermic subjects had died; 55% of the normothermic subjects were dead. This study demonstrates not only neurologic improvement, but also an improvement in survival. They demonstrated no significant difference in complications between the induced hypothermia and usual care groups.
A second randomized trial was conducted in Australia by Dr. Steven Bernard. He induced hypothermia in subjects resuscitated from cardiac arrest. 77 subjects were included in the trial. 43 patients were assigned to induced hypothermia (33º C) and cooled with a cooling blanket, ice packs and wet sponges for 12 hours and 34 patients were randomized to receive no cooling. These subjects received medications for sedation and to prevent shivering that might lead to warming. There were no clinically significant adverse effects. In the induced hypothermia group, 49% of the hypothermic group were discharged alive, as compared with 26% of the normothermic group.
Both of these studies demonstrate an improvement in outcome in subjects who received hypothermia treatment after arrival to the hospital. The cooling methods were relatively slow, taking 4-6 hours to achieve a goal temperature of 32º-34ºC.
This has led to the idea of developing new ways to rapidly induce hypothermia with the hopes of improving patient outcomes even more. Initiating hypothermia in the out of hospital setting as soon as possible following cardiac arrest may be one way to accomplish this. This has not been examined as of yet. A reasonable hypothesis would be that rapid hypothermia would improve neurologic recovery to a greater extent than surface cooling initiated in the hospital.
There is animal data to support this hypothesis at this time. Investigators have demonstrated that delaying cooling of resuscitated dogs by only 15 minutes negated any improvement in neurologic recovery seen in the immediate hypothermia group. This study suggests that the neurologic improvements in human subjects obtained by surface cooling may be improved upon by a cooling method that rapidly induces hypothermia.
One of the simplest and most effective means to induced hypothermia is the infusion of cold IV solutions.
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There have been three small studies using cold IV to induce hypothermia in patients admitted to the hospital following cardiac arrest. Bernard in Australia has examined the infusion of 2-3 liters of cold fluid in a small pilot study. He cooled 22 cardiac arrest patients upon their arrival to the hospital using an infusion of cold IV fluids. The average temperature decrease was 1.9 ºC. No adverse effects were noted.
Investigators at Harborview Medical Center also tested the effectiveness and safety of giving cold IV fluids in a small pilot study of hospitalized cardiac arrest patients. 20 subjects were cooled using an infusion of 2 liters of a cold salt-water solution. This method effectively and rapidly cooled the patient. The temperature dropped 1- 2ºC over twenty minutes in all subjects. There were no adverse effects.
Investigators at Harborview Medical Center have also studied the infusion of cold IV given to patients before they arrive at the hospital. This study was called the “Pilot Study of Induced Hypothermia in Cardiac Arrest”. The purpose of the study was to test the hypothesis that hypothermia started in the field by Seattle paramedics could be done safely and effectively. In this study 100 subjects were randomized to receive either cooling with IV fluids or standard care before to being transport to the hospital. Temperature monitoring was done using an esophageal probe inserted into the subject’s esophagus (swallowing tube) by the paramedics. Subjects randomized to the hypothermia group were given medications for sedation to prevent shivering that might lead to warming. The study was completed in February 2006. Preliminary results showed an average temperature decrease between the temperature in the field and the hospital arrival temperature of 1.3 ºC. Preliminary results also show that there were no adverse effects.
The pilot study did show that Seattle paramedics were able to properly select appropriate patients for enrollment into the study. The pilot study may show a trend towards improvement in patient outcome. However a larger study is needed to show this more definitively. Because of the results of this pilot study investigators propose the larger trial mentioned below.
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The 2005 American Heart Association Guidelines for Cardiopulmonary Resuscitation recommends the following treatment for patients resuscitated from out of hospital cardiac arrest:
“Unconscious adult patients with ROSC (return of spontaneous circulation) after out of hospital cardiac arrest should be cooled to 32° to 34°C for 12 to 24 hours…”
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The full name of the HYPOTHERMIA study is the "Pilot Study of Induced Hypothermia in Cardiac Arrest." The purpose of the study is to eventually test the hypothesis that hypothermia started in the field by paramedics will increase the number of patients awakening after cardiac arrest.
Prior to the initiation of a larger randomized clinical trial, a smaller pilot study is proposed to determine if hypothermia can be safely and effectively started in the field by Seattle paramedics.
The "Pilot Study of Induced Hypothermia in Cardiac Arrest" is a randomized placebo controlled clinical trial to determine the safety and efficacy of inducing hypothermia in the field in cardiac arrest patients using a rapid infusion of 2 liters of a cold salt water solution.
Subjects will be given medications for sedation and to prevent shivering that might lead to warming. Temperature monitoring will be via an esophageal probe inserted into the subject’s esophagus (swallowing tube) by the paramedics. Fifty patients will be randomized to hypothermia and 50 patients will be randomized to no cooling. The primary outcome of this pilot study is to determine the difference in the subject’s first temperature and temperature at the time of arrival at the hospital.
If this small pilot study is successful in demonstrating a benefit a larger randomized trial of induction of hypothermia will be started. The long-term research goal is to complete a large randomized clinical trial to test the hypothesis that rapid induction of hypothermia in the field following cardiac arrest will improve the proportion of patients who survive.
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All subjects over the age of 18 years treated by the Seattle Fire Department for a cardiac arrest during the study period may be eligible for the study. The subject must be successfully resuscitated from the cardiac arrest – the emergency medical providers must have been able to reestablish a pulse.
The subject must also have a temperature > 33° C (93.5° F) and be unconscious. The cardiac arrest cannot be due to trauma such as a gunshot wound, stabbing, severe motor vehicle accident, etc. Induced hypothermia in this group of patients is not recommended.
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If a subject is eligible for the trial he or she will have a 50% chance of receiving the hypothermia treatment. This is decided at random or by chance, like flipping a coin. We believe that this type of study, called a randomized trial, will enable the truest determination of the best approach for the treatment of cardiac arrest.
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The potential risks involved in this trial include the following: discomfort or pain, too large of a temperature drop and fluid overload. There are safety measures built into the protocol to minimize any of these risks. In the studies cited above there have not been any of these complications reported.
All subjects enrolled in this trial are unconscious and therefore should not experience any pain. All subjects have an esophageal thermometer placed in order to accurately measure body temperature. These thermometers are routinely placed, with minimal discomfort, in hospitalized patients. A medicine, called pancuronium, is given to prevent shivering or moving. Paramedics breathe for subjects during this time. Pancuronium works by paralyzing all the muscles of the body, but does not cause sedation or relaxation.
A second medicine called diazepam is administered to keep subjects sedated so that, in the event that awakening occurs, subjects are not aware. There is a small risk of prolonged muscle weakness from these medicines. There is also a small risk of low blood pressure. Subjects are monitored closely and if this occurred, are treated according to standard Seattle Fire Department protocols. Subjects randomized to no cooling do not receive these medications as part of the study. However, they may receive them as part of their routine care.
The infusion of cold fluid should lower the temperature of the body. If the body’s temperature falls below 33° C (91.4° F) the paramedics will stop the cold fluid. Subjects may receive up to a total of 2 liters of cold I.V. fluid. This amount of fluid may cause strain on the heart and water to form in the lungs. Subjects’ vital signs are monitored closely. If this occurs, the paramedics will give medicines to correct this condition.
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Obtaining an “informed consent” from victims of cardiac arrest is impossible as the participant is unconscious and the family is either not immediately available or extremely distraught. To allow researchers to possibly improve the survival rate of individuals suffering from a life-threatening condition, the US Food and Drug Administration (FDA) has issued guidelines for the consent to be waived in emergency circumstances, as long as the research has the prospect of direct benefit to the patient. In order to be able to do a study using an “emergency waiver of consent” the following requirements established by the FDA must be met.
- A life-threatening situation with unproven or unsatisfactory treatment where research is necessary to improve outcome.
- Obtaining informed consent is not feasible because the patient is unresponsive and treatment must begin immediately.
- Participation in research has the prospect of direct benefit because the situation necessitates an intervention, science supports the potential of direct benefit and the risks of the research are reasonable compared to the medical condition.
- The research could not practicably be done without waiver of informed consent.
- The potential therapeutic window is short (in the case of cardiac arrest, treatment needs to be given within minutes).
- The researchers must develop informed consent procedures they will implement when it is possible to obtain consent.
- An Institutional Review Board (IRB) must approve the study.
This study meets these FDA requirements.
Participants or their legally authorized representative will be contacted as soon as possible after enrollment into the study. The purpose of this contact will be to provide information about the study and in some cases to ask permission for continued participation in the trial. Continuation in the trial means allowing access to medical records.
In an attempt to inform as many people as possible before the research begins, the researchers are required to disclose to the public the nature, risks and benefits of the study. The researchers want to provide the community with information about this study and an opportunity for people to ask questions about the potential risks and benefits involved. The researchers want to gather information from the community and inform as many people as possible about the study before, during, and after the research is conducted. This is being done through a variety of means:
- This website
- News stories
- Consultation with the administrative staff of the King County area paramedics
- Consultation with community leaders
- Community survey
A random sample of 200 King County area households were called and asked their opinion of waiver of consent and whether or not they would want the hypothermia treatment given to them without their consent.
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The subject or their legally authorized representative (LAR) will be notified soon after enrollment into the study. The subject or their LAR will be given written information about the trial and have an opportunity to answer questions.
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Yes, it is possible that a subject may also be enrolled into another emergency study for the treatment of cardiac arrest. If that were the case the subject or their LAR will be given written information about each trial and have an opportunity to ask questions.
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By law, researchers must protect the privacy of health information about subjects. We make every effort to keep the information confidential. All subjects enrolled in the trial will be assigned a code number. This code number is used on any data we collect. A key linking the subject to the code number is kept locked in a secure location and will be available only to the investigators. Once this study is completed this key will be destroyed.
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Yes, it is possible to opt out of this study. Patients who do not want to participate in this study can request an opt-out bracelet to wear. This bracelet needs to be worn during the time the study is being conducted in order to be identified as someone not wishing to be included in it. The bracelet will advise those seeing it about your wishes. However there is no guarantee that wearing this bracelet will prevent you from being treated in this trial. If you do get treated as part of this research trial please realize that the special treatment provided in this trial is in addition to all standard treatments and not in place of them. In the unlikely event that you are treated in this trial we will not use any of the information collected about you. Opt-out bracelets may be obtained by contacting the research coordinator.
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Principal Investigator:
Francis Kim, MD
Assistant Professor
Department of Medicine/Division of Cardiology
Harborview Medical Center
Co-investigators:
Michele Olsufka, RN
Research Nurse Coordinator
Department of Medicine/Division of Cardiology
Harborview Medical Center
Thomas Rea MD
Assistant Professor
Department of Medicine
Harborview Medical Center
David Carlbom, MD
Acting Instructor
Emergency Medical Services
Harborview Medical Center
Leonard Cobb, MD
Professor of Medicine
Department of Medicine/Division of Cardiology
Harborview Medical Center
Michael K. Copass, MD
Professor of Neurology
Director of Emergency Medical Services, Harborview Medical Center
Medical Director: Seattle Medic One & ALNW
Steve Deem, MD
Associate Professor
Department of Medicine/Division of Anesthesia
Harborview Medical Center
William Longsteth, MD
Professor of Medicine
Department of Medicine/Division of Neurology
Harborview Medical Center
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We anticipate that the HYPOTHERMIA study will contribute to a better understanding of how we can improve the treatment of patients that experience cardiac arrest. We hope that this study will improve outcomes from this very serious condition. We are very interested in your comments.
Please call Michele Olsufka, RN, Research Coordinator, with any questions or comments regarding the HYPOTHERMIA study.
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