Targeted temperature management

Targeted temperature management (TTM) previously known as therapeutic hypothermia or protective hypothermia is an active treatment that tries to achieve and maintain a specific

Targeted temperature management improves survival and brain function following resuscitation from cardiac arrest.^[4] Evidence supports its use following certain types of cardiac arrest in which an individual does not regain consciousness.^[1] The target temperature is often between 32–34 °C.^[4] Targeted temperature management following traumatic brain injury is of unclear benefit.^[5] While associated with some complications, these are generally mild.^[6]

Targeted temperature management is thought to prevent brain injury by several methods, including decreasing the brain's oxygen demand, reducing the production of

Medical uses

Targeted temperature management may be used in the following conditions:

Cardiac arrest

The 2013

However, more recent research suggests that there is no benefit to cooling to 33 °C (91 °F) when compared with less aggressive cooling only to a near-normal temperature of 36 °C (97 °F); it appears cooling is effective because it prevents fever, a common complication seen after cardiac arrest.[9] There is no difference in long term quality of life following mild compared to more severe cooling.^[10]

In children, following cardiac arrest, cooling does not appear useful as of 2018.^[11]

Neonatal encephalopathy

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 25–32 °C (79–89 °F). 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 15 °C (60 °F) for the duration of the surgery. This very cold temperature helps the heart muscle to tolerate its lack of blood supply during the surgery.[13]^[14]

Adverse effects

Possible complications may include: infection, bleeding,

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%.^[19] Accordingly, most early hypotheses suggested that hypothermia reduces the harmful effects of ischemia by decreasing the body's need for oxygen.^[20] 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.^[21]

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.^[20]

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.^[20]

Targeted temperature management may also help to reduce

There are a number of methods through which hypothermia is induced.[15] These include: cooling catheters, cooling blankets, and application of ice applied around the body among others.^[15][23] As of 2013 it is unclear if one method is any better than the others.^[23] While cool intravenous fluid may be given to start the process, further methods are required to keep the person cold.^[15]

Core body temperature must be measured (either via the esophagus, rectum, bladder in those who are producing urine, or within the pulmonary artery) to guide cooling.^[15] A temperature below 30 °C (86 °F) should be avoided, as adverse events increase significantly.^[23] The person should be kept at the goal temperature plus or minus half a degree Celsius for 24 hours.^[23] Rewarming should be done slowly with suggested speeds of 0.1 to 0.5 °C (0.18 to 0.90 °F) per hour.^[23]

Targeted temperature management should be started as soon as possible.^[24] The goal temperature should be reached before 8 hours.^[23] Targeted temperature management remains partially effective even when initiated as long as 6 hours after collapse.^[25]

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 36 °C (97 °F)—people may begin to shiver.^[26] It appears that regardless of the technique used to induce hypothermia, people begin to shiver when temperature drops below this threshold.^[26] Drugs commonly used to prevent and treat shivering in targeted temperature management include acetaminophen, buspirone, opioids including pethidine (meperidine), dexmedetomidine, fentanyl, and/or propofol.^[27] 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.^[25]

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 1.5 to 2 °C (2.7 to 3.6 °F) per hour. Through the use of the control unit, catheters can bring body temperature to within 0.1 °C (0.18 °F) 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.^{[28][29][30][31][32]}

Adverse events associated with this invasive technique include bleeding, infection, vascular puncture, and deep vein thrombosis (DVT).^[33] Infection caused by cooling catheters is particularly harmful, as resuscitated people are highly vulnerable to the complications associated with infections.^[34] 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.^{[citation needed]}

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

Transnasal evaporative cooling is a method of inducing the hypothermia process and provides a means of continuous cooling of a person throughout the early stages of targeted temperature management and during movement throughout the hospital environment. This technique uses two cannulae, inserted into a person's nasal cavity, to deliver a spray of coolant mist that evaporates directly underneath the brain and base of the skull. As blood passes through the cooling area, it reduces the temperature throughout the rest of the body.^[citation needed]

The method is compact enough to be used at the point of cardiac arrest, during ambulance transport, or within the hospital proper. It is intended to reduce rapidly the person's temperature to below 34 °C (93 °F) while targeting the brain as the first area of cooling. Research into the device has shown cooling rates of 2.6 °C (4.7 °F) per hour in the brain (measured through infrared tympanic measurement) and 1.6 °C (2.9 °F) per hour for core body temperature reduction.^[35][36]

Water blankets

With these technologies, cold water circulates through a blanket, or torso wraparound vest and leg wraps. To lower temperature with optimal speed, 70% of a person's surface area should be covered with water blankets. The treatment represents the most well studied means of controlling body temperature. Water blankets lower a person's temperature exclusively by cooling a person's skin and accordingly require no invasive procedures.^{[citation needed]}

Water blankets possess several undesirable qualities. They are susceptible to leaking, which may represent an electrical hazard since they are operated in close proximity to electrically powered medical equipment.^[37] The Food and Drug Administration also has reported several cases of external cooling blankets causing significant burns to the skin of person. Other problems with external cooling include overshoot of temperature (20% of people will have overshoot), slower induction time versus internal cooling, increased compensatory response, decreased patient access, and discontinuation of cooling for invasive procedures such as the cardiac catheterization.^[38]

If therapy with water blankets is given along with two litres of cold intravenous saline, people can be cooled to 33 °C (91 °F) in 65 minutes.^{[citation needed]} Most machines now come with core temperature probes. When inserted into the rectum, the core body temperature is monitored and feedback to the machine allows changes in the water blanket to achieve the desired set temperature. In the past some of the models of cooling machines have produced an overshoot in the target temperature and cooled people to levels below 32 °C (90 °F), resulting in increased adverse events. They have also rewarmed patients at too fast a rate, leading to spikes in intracranial pressure. Some of the new models have more software that attempt to prevent this overshoot by utilizing warmer water when the target temperature is close and preventing any overshoot. Some of the new machines now also have 3 rates of cooling and warming; a rewarming rate with one of these machines allows a patient to be rewarmed at a very slow rate of just 0.17 °C (0.31 °F) an hour in the "automatic mode", allowing rewarming from 33 °C (91 °F) to 37 °C (99 °F) over 24 hours.

Cool caps

There are a number of non-invasive head cooling caps and helmets designed to target cooling at the brain.

Hypothermia has been applied therapeutically since antiquity. The Greek physician Hippocrates, the namesake of the Hippocratic Oath, advocated the packing of wounded soldiers in snow and ice.^[20] Napoleonic surgeon Baron Dominique Jean Larrey recorded that officers who were kept closer to the fire survived less often than the minimally pampered infantrymen.^[20] In modern times, the first medical article concerning hypothermia was published in 1945.^[20] This study focused on the effects of hypothermia on patients with severe head injury. In the 1950s, hypothermia received its first medical application, being used in intracerebral aneurysm surgery to create a bloodless field.^[20] Most of the early research focused on the applications of deep hypothermia, defined as a body temperature of 20–25 °C (68–77 °F). Such an extreme drop in body temperature brings with it a whole host of side effects, which made the use of deep hypothermia impractical in most clinical situations.

This period also saw sporadic investigation of more mild forms of hypothermia, with mild hypothermia being defined as a body temperature of 32–34 °C (90–93 °F). In the 1950s, Doctor Rosomoff demonstrated in dogs the positive effects of mild hypothermia after brain ischemia and traumatic brain injury.

TTM has been studied in several use scenarios where it has not usually been found to be helpful, or is still under investigation, despite theoretical grounds for its usefulness.[45]

Stroke

There is currently no evidence supporting targeted temperature management use in humans and clinical trials have not been completed.

Animal studies have shown the benefit of targeted temperature management in traumatic central nervous system (CNS) injuries. Clinical trials have shown mixed results with regards to the optimal temperature and delay of cooling. Achieving therapeutic temperatures of 33 °C (91 °F) is thought to prevent secondary neurological injuries after severe CNS trauma.[49] A systematic review of randomised controlled trials in traumatic brain injury (TBI) suggests there is no evidence that hypothermia is beneficial.^[50]

Cardiac arrest

A clinical trial in

As of 2015 hypothermia had shown no improvements in neurological outcomes or in mortality in neurosurgery.[53]

Naegleriasis

TTM has been used in some cases of naegleriasis.^[54]

See also

• Deep hypothermic circulatory arrest

References