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Thread: Case Report: Hypothermia for a pediatric patient with an isolated cervical SCI

  1. #1

    Case Report: Hypothermia for a pediatric patient with an isolated cervical SCI

    J Spinal Cord Med. 2018 Sep 19:1-4.

    Therapeutic systemic hypothermia for a pediatric patient with an isolated cervical spinal cord injury.

    Pelletier JH1, Mann CH2,3, German BT2,3, Williams JG3,4, Piehl M2,3.

    While uncommon, spinal cord injuries most frequently occur in adolescent and young adult males. Established treatment options are limited and focused on supportive care. Therapeutic systemic hypothermia is an emerging experimental treatment currently undergoing clinical trials in adults.

    Here we report a case of a 13-year-old male with an American Spinal Injury Association Impairment Scale grade C traumatic cervical spinal cord injury treated with 48 hours of therapeutic systemic hypothermia who made a complete neurological recovery. To our knowledge, this is the youngest such case report.

    This case suggests that consideration should be given to including pediatric patients in future clinical trials of therapeutic hypothermia for spinal cord injury.
    “As the cast of villains in SCI is vast and collaborative, so too must be the chorus of hero's that rise to meet them” Ramer et al 2005

  2. #2

    Mechanisms and Treatments of Hypothermia in Spinal Cord Injury

    Quote Originally Posted by Wise Young View Post
    Wise Young, Ph.D., M.D.
    W. M. Keck Center for Collaborative Neuroscience
    Rutgers University, Piscataway, New Jersey 08854

    Many people have posted questions about hypothermia (low body temperature) and poor body temperature regulation (poikilothermia) after spinal cord injury. This is a review of the mechanisms of body temperature regulation after spinal cord injury and some common sense solutions.

    Hypothermia Mechanisms

    Hypothermia indicates body temperature that is lower than the normal body temperature of 37±0.3 degrees C. Hypothermia may result from many causes but the term is most commonly used to refer to lower body temperature due to heat loss. Because body temperature is usually higher than ambient (surrounding) temperature, the body loses heat to the environment. The body maintains its temperature by producing heat (due to metabolism or expenditure of energy, usually through muscle activity such as shivering), peripheral vasoconstriction (narrowing of blood vessels) in skin to reduce heat dissipation and arteriovenous shunting (direct passage of blood from artery to vein) of blood from the skin, and reduction of sweating to cool the body.

    The body controls temperature through the sympathic and parasympathetic nervous system, as well as local tissue regulation of blood flow through nitric oxide.
    ? The sympathetic nervous system controls vasoconstriction and arteriovenous shunting by releasing norepinephrine (noradrenalin) acting on alpha-adrenergic receptors on blood vessels. Sympathetic neurons are located in various parts of the brain and spinal cord, sending signals to neurons situated in peripheral sympathetic ganglia, as well as the adrenal glands.
    ? The parasympathetic system is mediated by the vagal nerve which is the 10th cranial nerve. The parasympathetic system uses acetycholine to act on muscarinic receptors. Activation of these receptors cause vasodilation, but mostly in the salivary glands, the heart, stomach, genital structures (such as the prostate), and other internal organs, such as the bladder (Young, et al., 1988).
    ? Nitric oxide is a potent vasodilatory factor that is released by cells and tissues that are ischemic. For example, during exercise, muscles release a vasodilator substance called nitric oxide (NO) which blocks sympathetic vasoconstriction and causes vasodilation or increased blood flow to the muscles (Clifford, et al. 2002).

    The hypothalamus is the brain's central temperature processor for controlling core temperature. The hypothalamus causes vasoconstriction and arteriovenous shunting of blood flow from skin when core temperature falls below 37 degrees C and sweating when it senses temperature above 37 degrees C. Temperature sensors are located all over the body and in the central nervous system, sending signals to the hypothalamus, which integrates the signals and then sends commands via the parasympathetic and sympathic nervous system (autonomic nervous system) to different parts of the body to control temperature regulation.

    Measuring Core Temperature
    Core temperature can be accurately measured from the tympanic membrane (the "ear-drum") using infra-red sensing technology (Source). The device (see figure) is inserted into the ear and a shutter is opened for 0.1-0.3 seconds to collec infra-red light from the eardrum with a sensitive pyroelectric crystal detector. The eardrum is located close to the hypothalamus. If placed properly into the ear, this device is the most accurate reflection of core body temperature, better than traditional rectal temperature or mouth temperatures.
    Professional devices, such as the FirstTemp Genius Tympanic Ear Thermometer, can be purchased at significant discounts from eBay (Source).

    Doctors often assess central thermoregulatory control of the body by measuring the core temperature at which the body starts to sweat, called sweating threshold, normally 37±0.3 degrees C. The core temperature at which skin begins to cool (vasoconstriction and arteriovenous shunting) is called the vasoconstrictive threshold, normally 36.4±0.3 degrees C. The range in which no sweating or vasoconstriction occurs is called the interthreshold range (Kurz, et al. (1998)). In addition, there is also the temperature at which shivering starts, called the shivering threshold, normaly 35.6±0.3 degrees C.

    Poikilothermia (poikilo=variegated, thermia = temperature) is a Greek word which is sometimes applied to organisms that are "cold-blooded" or whose temperature varies with the environment (Source). It is sometimes used to refer to people who have lost their temperature regulation, e.g. the poikilothermic syndrome. Poikilothermic people have an abnormally wide interthreshold range. A person with poikilothermia may have sweating, vasoconstrictive, and shivering threshold of 38.3, 34.4, and 31.8 degrees C respectively.

    Causes of Hypothermia

    In people without injuries, the term hypothermia (low body temperatures) is usually applied to describe people when thermoregulation fails in a normal or cool environment. The body's temperature sensing system can be fooled or impaired under certain circumstances. In normal subjects, the most common medical cause of hypothermia is drugs. These include anesthetics, sedatives, alcohol, and opioids (Jorenby, et al., (1988)) and other drugs that impair thermal sensation or regulation.

    Hyperthermia results when thermoregulation fails in a warm environment. For example, in hot environments, vasodilation and sweating may not adequately cool the body during intense exercise. In normal subjects, the most common cause of hyperthermia is fever, resulting from release of pyrogens (fever-causing factors) due to infection or inflammation. Pyrogens increase prostaglandins, which are produced by cyclooxygenase (COX) in the central nervous system. COX inhibitors such as aspirin and acetaminophen (Tylenol) inhibit the production of prostaglandins and hence fever.

    People with multiple sclerosis and brain injury may have damage to the hypothalamus and develop the poikilothermic syndrome, where they lose ability to thermoregulate. Damage to the hypothalamus often cannot be seen on magnetic resonance images but is inferred when people develop the poikilothermic syndrome, a condition in which there is loss of thermoregulation. Poikolothermia, however, is a sufficiently rare phenomena after brain injury that, when it occurs, it is reason to suspect spinal cord injury. For example, the presence of early poikilothermia in children with brain injury may be a clue to the presence of occult spinal cord injury (Sneed & Stover).

    Hypothermia and Spinal Cord Injury

    Spinal cord injury and other lesions of the central nervous system affect temperature regulation of the body by interrupting both temperature sensing and spinal sympathetic nervous system that controls vasoconstriction and sweating. Damage to spinal sympathetic pathways will reduce the ability of the brain to regulate blood flow and sweating in the body. Spinal cord injury may also reduce or provide abnormal temperature sensations to the brain. Thus, a person with spinal cord injury particularly at cervical levels will often feel cold even though core temperature may be normal because increased or abnormal activity of thermal information.

    Many conditions may contribute to hypothermia in people with spinal cord injury. Stroke, diabetes, malnutrition, bacterial infection, and thyroid disease may contribute to hypothermia. People with poor blood flow (due to arteriosclerosis) are more susceptible to hypothermia. These need to be ruled out as well. A common cause of hypothermia is taking of multiple drugs that affect the sympathetic and parasympathetic system, as well as anti-depressants and drugs that affect serotonin and dopamine levels in the brain. The elderly and very young are particularly susceptible to perioperative hypothermia.

    Many drugs can aggravate hypothermia in people with spinal cord injury. Virtually all anesthetics that have been tested impair thermoregulation. These include opioids, inhalational anesthetics, propofol, spinal, and epidural anesthetics, either through central effects on the brain and hypothalamus, impairment of vasoconstriction or shivering responses (Frank, 2004. This is true of both regional and general anesthesia. Many drugs when taken in overdose will impair thermal regulation and cause hypothermia.

    Drugs that Aggravate Hypothermia
    Several drugs commonly taken by people with spinal cord injury may affect their body temperature.
    ? Baclofen (Lioresal). Because it is a GABA-B receptor agonist, baclofen depresses the nervous system. Baclofen and nitrogen oxide synthase inhibitors interact to cause synergistic hypothermia in rats (Rawis, et al., 2005). Baclofen overdose in dogs will cause hypothermia (Wismer, 2004). Approximately 1% of people who take baclofen develop hypothermia (Source).
    ? Tizanidine (Zanaflex). The sympathetic nervous system uses norepinephrine to act on alpha-adrenergic receptors to cause skin vasoconstriction and arteriovenous shunting. Tizanidine is an alpha-adrenergic receptor agonist and therefore will cause vasoconstriction at high doses, contributing to hypothermia. Both tizanidine and another alpha-adrenergic receptor agonist clonidine reduces core temperature in mice (Kameyama, et al., 1986).
    ? Diazepam (Valium). This GABA receptor agonist reduces core body temperatures of rats (Zarrindast & Dibayan, 1989). In some clinical series, diazepam was reported to cause hypothermia in as many as 15% of patients (Source). Many related drugs such as Zolpidem and Triazolam also contribute to hypothermia in rats (Rowlett, et al., 2001).
    ? Amitriptyline (Elavil). High doses of this tricyclic antidepressant may contribute to hypothermia, particularly in combination with anticholinergic drugs such as oxybutynin (Source). The mechanism is unclear although rat studies suggest that amitriptyline interacts with several neurotransmitters to produce hypothermia, including drugs that reduce brain serotonin levels. High-dose theophylline (50 mg/kg), dibutyryl cAMP, and parachloroamphetamine (PCAO) strongly antagonized the effects of amitriptyline-induced hypothermia (Lee, et al., 1977).
    ? Topiramate (Topamax). This is an anti-epileptic drug that blocks voltage-sensitive sodium channels, enhances activity of GABA, and blocks the action of excitatory glutamate receptors. It is very popularly used for migraine headaches and is sometimes used to treat neuropathic pain in people with spinal cord injury. In 2003, the FDA asked Johnson & Johnson to add warnings concerning hypothermia to the label for Topamax (Source although little published data exists on the subject.
    ? Fluoxetine (Prozac). This serotonin uptake blocker and related drugs have been reported to cause hypothermia when combined with other drugs, probably related to alterations in brain serotonin levels (Source).
    ? Acetaminophen (Tylenol). This drug is of course the most popularly used drug in the world for reduction of fever. In high doses (300 mg/kg), the drug may cause hypothermia (Ayoub, et al. 2004).
    ? Other drugs. Many tranquilizers (e.g. phenothiazines), sedatives and hypnoics (barbiturates, benzodiazepines), anti-depressants (tricyclis), vasoactive drugs (vasodilators), alcohol (causes vasodilation and interfere with carbohydrate metabolism), methyldopa, and narcotics such as morphine and oxycontin may contribute to hypothermia.

    Drugs the Reduce Hypothermia

    Several drugs may reduce hypothermia.
    ? Oxybutinin (Ditropan). This drug is popularly used to treat bladder spasticity in people with spinal cord injury. It is often also used to suppress hyperhydrosis or excessive sweating (Stolman, 2003). It is an anti-cholinergic drug that inhibits the parasympathetic systems that mediate sweating and vasodilation. Since sweating and vasodilation both contribute to hypothermia, this drug may be useful for reducing sporadic hypothermia (Source).
    ? Gabapentin (Neurontin). This drug is often used to treat chronic neuropathic pain in people with spinal cord injury. Several studies suggest that gabapenin reduces the frequency of ?hot flashes? and hypothermic episodes in post-menopausal women (Guttoso, 2000).
    ? Duloxetine. This is an anti-depressant to suppresses both norephineprhine and serotonin uptake in the brain (Source). This drug significantly attenuates reserpine (a norepinephrine blocker) induced hypothermia in mice (Katoh, et al. 1995, Bymaster, et al. 2001)).
    ? Lithium. This drug has been used to treat hypothermia in a patient who became hypothermic after accidental electric shock (Lieb, et al., 1980). Note that overdose of lithium may cause hypothermia. For example, an isolated case of severe hypothermia was reported from use of combination lithium and diazepam (Source). This may be due to inhibition of sympathetic responses in the case of lithium overdose.

    Treatment of Hypothermia

    Although the main cause of hypothermia in the United States is due to cold weather, it is interesting the New Mexico, generally regarded to be a relatively temperate state, had the second highest rate of hypothermic deaths in the country in 2002 (Source) because of unrecognized effects of sudden dips in ambient temperature. For people with spinal cord injury, hypothermia due to sudden changes in environmental temperature is deadly. It is important to use core temperature to monitor temperature and not rectal or mouth. Hypothermia is a common cause of incoherence and loss of brain function in people with spinal cord injury. People should be alert for early symptoms of hypothermia and undertake preventative measures, e.g. drinking warm fluids and preventing heat loss.

    Severe hypothermia can kill. It reduces brain function, compromises respiration, and can cause fatal cardiac arrythmias (Source). The last is usually what kills people. Since hypothermia depresses cardiac pacemaker cells, causing a slow heart rate or bradycardia, it can be refractory to standard therapies such as atropine. Atrial and ventricular arrythmias as common. Cardiac arrest and ventricular fibrillation occurs at about 25 degrees C. Lidocaine and defibrillation are often ineffective for reversing cardiac arrythmia that develop in hypothermic patients. A drug called bretyllium (5 mg/kg) has been recommended for treating cardiac arrythmias associated with hypothermia but this drug has not been available in emergency rooms since 1999 (Source). Emergency personnel therefore should try to warm patients before they carry out cardiopulmonary rescuscitation since the procedure is unlikely to be successful and may precipitate a fatal arrythmia. The approach is warm the patient up before resuscitation. Complications of hypothermia should be detected and treated. For example, a common side-effect of hypothermia is increased serum potassium levels (hyperkalaemia).

    Long-term treatments of hypothermia are common sense. The first and most important approach is to keep warm. The second is to avoid or minimize drugs that compromise thermoregulation. For example, alcohol causes vasodilation and heat loss and should be avoided when cold conditions are anticipated. Many of the drugs that are given to people with spinal cord injury aggravate hypothermia. If one cannot avoid these drugs, their dose should be minimized since their effects on thermoregulation are usually dose-dependent. Finally, don?t ignore hypothermia. The brain and body does not operate well under hypothermic conditions. It stresses all the systems of the body and should be corrected.
    "We must overcome difficulties rather than being overcome by difficulties."

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