Targeted temperature management
Targeted temperature management, previously known as therapeutic hypothermia or protective hypothermia, is an active treatment that tries to achieve and maintain a specific body temperature in a person for a specific duration of time in an effort to improve health outcomes during recovery after a period of stopped blood flow to the brain. This is done in an attempt to reduce the risk of tissue injury following lack of blood flow. Periods of poor blood flow may be due to cardiac arrest or the blockage of an artery by a clot as in the case of a stroke.
Targeted temperature management improves survival and brain function following resuscitation from cardiac arrest. Evidence supports its use following certain types of cardiac arrest in which an individual does not regain consciousness. The target temperature is often between 32 and 34 °C. Targeted temperature management following traumatic brain injury is of unclear benefit. While associated with some complications, these are generally mild.
Targeted temperature management is thought to prevent brain injury by several methods, including decreasing the brain's oxygen demand, reducing the production of neurotransmitters like glutamate, as well as reducing free radicals that might damage the brain. Body temperature may be lowered by many means, including cooling blankets, cooling helmets, cooling catheters, ice packs and ice water lavage.
Medical uses
Targeted temperature management may be used in the following conditions:Cardiac arrest
The 2013 ILCOR and 2010 American Heart Association guidelines support the use of cooling following resuscitation from cardiac arrest. These recommendations were largely based on two trials from 2002 which showed improved survival and brain function when cooled to after cardiac arrest.However, more recent research suggests that there is no benefit to cooling to when compared with less aggressive cooling only to a near-normal temperature of ; it appears cooling is effective because it prevents fever, a common complication seen after cardiac arrest. There is no difference in long term quality of life following mild compared to more severe cooling.
In children, following cardiac arrest, cooling does not appear useful as of 2018.
A recent Cochrane Review summarized available evidence on the topic and found that targeted temperature management around 33 °C may increase the chance to prevent brain damage after cardiac arrest by 40%.
Neonatal encephalopathy
has been proven to improve outcomes for newborn infants affected by perinatal hypoxia-ischemia, hypoxic ischemic encephalopathy or birth asphyxia. A 2013 Cochrane review found that it is useful in full term babies with encephalopathy. Whole body or selective head cooling to, begun within six hours of birth and continued for 72 hours, reduces mortality and reduces cerebral palsy and neurological deficits in survivors.Open heart surgery
Targeted temperature management is used during open-heart surgery because it decreases the metabolic needs of the brain, heart, and other organs, reducing the risk of damage to them. The patient is given medication to prevent shivering. The body is then cooled to. The heart is stopped and an external heart-lung pump maintains circulation to the patient's body. The heart is cooled further and is maintained at a temperature below for the duration of the surgery. This very cold temperature helps the heart muscle to tolerate its lack of blood supply during the surgery.Adverse effects
Possible complications may include: infection, bleeding, dysrhythmias and high blood sugar. One review found an increased risk of pneumonia and sepsis but not the overall risk of infection. Another review found a trend towards increased bleeding but no increase in severe bleeding. Hypothermia induces a "cold diuresis" which can lead to electrolyte abnormalities – specifically hypokalemia, hypomagnesaemia, and hypophosphatemia, as well as hypovolemia.Mechanism
The earliest rationale for the effects of hypothermia as a neuroprotectant focused on the slowing of cellular metabolism resulting from a drop in body temperature. For every one degree Celsius drop in body temperature, cellular metabolism slows by 5–7%. Accordingly, most early hypotheses suggested that hypothermia reduces the harmful effects of ischemia by decreasing the body's need for oxygen. The initial emphasis on cellular metabolism explains why the early studies almost exclusively focused on the application of deep hypothermia, as these researchers believed that the therapeutic effects of hypothermia correlated directly with the extent of temperature decline.In the special case of infants with perinatal asphyxia, it appears that apoptosis is a prominent cause of cell death and that hypothermia therapy for neonatal encephalopathy interrupts the apoptotic pathway. In general, cell death is not directly caused by oxygen deprivation, but occurs indirectly as a result of the cascade of subsequent events. Cells need oxygen to create ATP, a molecule used by cells to store energy, and cells need ATP to regulate intracellular ion levels. ATP is used to fuel both the importation of ions necessary for cellular function and the removal of ions that are harmful to cellular function. Without oxygen, cells cannot manufacture the necessary ATP to regulate ion levels and thus cannot prevent the intracellular environment from approaching the ion concentration of the outside environment. It is not oxygen deprivation itself that precipitates cell death, but rather without oxygen the cell can not make the ATP it needs to regulate ion concentrations and maintain homeostasis.
Notably, even a small drop in temperature encourages cell membrane stability during periods of oxygen deprivation. For this reason, a drop in body temperature helps prevent an influx of unwanted ions during an ischemic insult. By making the cell membrane more impermeable, hypothermia helps prevent the cascade of reactions set off by oxygen deprivation. Even moderate dips in temperature strengthen the cellular membrane, helping to minimize any disruption to the cellular environment. It is by moderating the disruption of homeostasis caused by a blockage of blood flow that many now postulate, results in hypothermia's ability to minimize the trauma resultant from ischemic injuries.
Targeted temperature management may also help to reduce reperfusion injury, damage caused by oxidative stress when the blood supply is restored to a tissue after a period of ischemia. Various inflammatory immune responses occur during reperfusion. These inflammatory responses cause increased intracranial pressure, which leads to cell injury and in some situations, cell death. Hypothermia has been shown to help moderate intracranial pressure and therefore to minimize the harmful effects of a patient's inflammatory immune responses during reperfusion. The oxidation that occurs during reperfusion also increases free radical production. Since hypothermia reduces both intracranial pressure and free radical production, this might be yet another mechanism of action for hypothermia's therapeutic effect. Overt activation of N-methyl-D-aspartate receptors following brain injuries can lead to calcium entry which triggers neuronal death via the mechanisms of excitotoxicity.
Methods
There are a number of methods through which hypothermia is induced. These include: cooling catheters, cooling blankets, and application of ice applied around the body among others. As of 2013 it is unclear if one method is any better than the others. While cool intravenous fluid may be given to start the process, further methods are required to keep the person cold.Core body temperature must be measured to guide cooling. A temperature below should be avoided, as adverse events increase significantly. The person should be kept at the goal temperature plus or minus half a degree Celsius for 24 hours. Rewarming should be done slowly with suggested speeds of per hour.
Targeted temperature management should be started as soon as possible. The goal temperature should be reached before 8 hours. Targeted temperature management remains partially effective even when initiated as long as 6 hours after collapse.
Prior to the induction of targeted temperature management, pharmacological agents to control shivering must be administered. When body temperature drops below a certain threshold—typically around —people may begin to shiver. It appears that regardless of the technique used to induce hypothermia, people begin to shiver when temperature drops below this threshold. Drugs commonly used to prevent and treat shivering in targeted temperature management include acetaminophen, buspirone, opioids including pethidine, dexmedetomidine, fentanyl, and/or propofol. If shivering is unable to be controlled with these drugs, patients are often placed under general anesthesia and/or are given paralytic medication like vecuronium. People should be rewarmed slowly and steadily in order to avoid harmful spikes in intracranial pressure.
Cooling catheters
Cooling catheters are inserted into a femoral vein. Cooled saline solution is circulated through either a metal coated tube or a balloon in the catheter. The saline cools the person's whole body by lowering the temperature of a person's blood. Catheters reduce temperature at rates ranging from per hour. Through the use of the control unit, catheters can bring body temperature to within of the target level. Furthermore, catheters can raise temperature at a steady rate, which helps to avoid harmful rises in intracranial pressure. A number of studies have demonstrated that targeted temperature management via catheter is safe and effective.Adverse events associated with this invasive technique include bleeding, infection, vascular puncture, and deep vein thrombosis. Infection caused by cooling catheters is particularly harmful, as resuscitated people are highly vulnerable to the complications associated with infections. Bleeding represents a significant danger, due to a decreased clotting threshold caused by hypothermia. The risk of deep vein thrombosis may be the most pressing medical complication.
Deep vein thrombosis can be characterized as a medical event whereby a blood clot forms in a deep vein, usually the femoral vein. This condition may become potentially fatal if the clot travels to the lungs and causes a pulmonary embolism. Another potential problem with cooling catheters is the potential to block access to the femoral vein, which is a site normally used for a variety of other medical procedures, including angiography of the venous system and the right side of the heart. However, most cooling catheters are triple lumen catheters, and the majority of people post-arrest will require central venous access. Unlike non-invasive methods which can be administered by nurses, the insertion of cooling catheters must be performed by a physician fully trained and familiar with the procedure. The time delay between identifying a person who might benefit from the procedure and the arrival of an interventional radiologist or other physician to perform the insertion may minimize some of the benefit of invasive methods' more rapid cooling.