Sara Pitoni, Helen L. Sinclair and Peter J.D. Andrews. Presented by : R4 蔡為民 Supervised by : Dr. 楊煦星

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1 Sara Pitoni, Helen L. Sinclair and Peter J.D. Andrews Presented by : R4 蔡為民 Supervised by : Dr. 楊煦星

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3 The incidence of out-of-hospital sudden cardiac arrest in industrial countries is reported to be between 35.7 and cases per 100,000, with a mean of 62 cases per 100,000 each year. Less than half of victims who develop return of spontaneous circulation (ROSC) survive to leave the hospital alive, and the cause of death is anoxic brain injury in most patients with ROSC who die within one month of the cardiac arrest. Medscape, Therapeutic Hypothermia Updated: Jun 29, 2010

4 Many researchers have investigated the potential for therapeutic hypothermia to improve outcome after acute brain injury. Prospective, randomized trials have shown, in a variety of patient populations, that even mild hypothermia causes numerous adverse effects. Shivering is one of the most common hypothermia-induced complications.

5 Physiology of Thermoregulation

6 NORMAL BODY TEMPERATURES Core Temperature and Skin Temperature The temperature of the deep tissues of the body the core of the body remains very constant, within ± 0.6 C sweating-to-shivering range The skin temperature, in contrast to the core temperature, rises and falls with the temperature of the surroundings. The skin temperature is the important temperature when we refer to the skin s ability to lose heat to the surroundings. Guyton - Textbook Of Medical Physiology 11th ed

7 Circadian Variation + Range of 1 C over 24 hours + Highest 6-8 pm + Lowest 4-6 am Endocrine status can alter circadian variation: e.g. Estrogen and progesterone release on day 14 of the menstrual cycle cause internal temperature to be C higher at baseline. Infants Variation with Age limited thermoregulatory response partly due to the immaturity of the CNS but also due to a relatively large surface area to body mass ratio. elderly vulnerable to variations in environmental temperature.in the cold enviroment inadequate catecholamine release contributes to a poor vasoconstrictor reflex Thermoregulation Human Physiology Dr. James Betts Univeristy of BATH

8 Infants rely on nonshivering thermogenesis and brown adipose tissue rather than shivering. Brown adipose tissue in adults was considered vestigial but a cervical-supraclavicular depot has been recently demonstrated; its presence possibly correlates with body metabolic activities but its role in cold-induced thermogenesis has yet to be proved

9 Thermal Sensations Guyton - Textbook Of Medical Physiology 11th ed

10 Thermal Sensations Guyton - Textbook Of Medical Physiology 11th ed

11 Cutaneous thermoreception Transient Receptor Potential Transmembrane proteins serving as molecular/cellular sensors for a variety of physiological/pathological functions. Mammalian TRP channels are organized into six families: classical (TRPC) vanilloid (TRPV) melastatin (TRPM) muclopins (TRPML) polycystin (TRPP) ANKTM1(TRPA)

12 Body core thermoreceptors Afferent signals ascend via thermosensory neurons through pathways such as the spinothalamocortical tract and lateral parabrachial neurons.

13 The cold signals activate the lateral parabrachial nucleus neurons, which promote excitatory inputs to drive GABAergic interneurons to inhibit other inhibitory output neurons in the medial preoptic subregions of the preoptic area. This results in a disinhibition of thermogenesis-promoting neurons in dorsomedial hypothalamus and the rostral ventromedial medulla. These fibres activate spinal sympathetic and somatic motor circuits to increase thermogenesis

14 Efferent responses: Vasoconstriction and Shivering

15 EFFERENT RESPONSES Vasoconstriction and Shivering Thermoregulation in intensive care patients is largely autonomic and manifests as arterio-venous shunt vasoconstriction and shivering at low CBT.

16 Shivering Shivering is less efficient than vasoconstriction as defense from cold because much of the heat generated by the peripheral muscles is released to the environment rather than being retained in the core Sustained shivering can double the basal metabolic rate in young, fit people but is considerably less effective in the elderly

17 Shivering During hypothermia treatment, shivering can generate significant heat and can make the induction of hypothermia very difficult. The Bedside Shivering Assessment Scale (BSAS)

18 Eurotherm3235Trial Shivering Detection Guideline

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20 Physical methods MST contributes around 20% to the control of vasoconstriction and shivering, and 50% to thermal comfort. Each 1 C of cutaneous warming compensates for approximately 0.28 C core hypothermia. Generalized skin warming appears to be more effective in reducing shivering and minimizing hypothermia sideeffects

21 Volatile and Intravenous Anaesthetics Volatile anaesthetics profoundly blunt normal control of body temperature. They widen the interthreshold range to 4.0 C Enflurane, isoflurane, sevoflurane and desflurane reduce the thermoregulatory cold defence threshold with a nonlinear dose response manner, so that impairment increases at higher doses.

22 Volatile and intravenous anaesthetics Propofol Neuro-protection, antiseizure Widen the interthreshold range Linearly reduce the shivering threshold in a dose-dependent manner Propofol infusion at sedative doses, producing a plasma concentration of 2µg/ml, lowers the shivering threshold to approximately 35 C. A plasma concentration of 4µg/ml, compatible with general anaesthesia, further lowers the threshold to approximately 34 C.

23 OPIOIDS Pure µ-receptor agonists and combined µ and k-agonists are commonly used to treat cooled patients. alfentanil, fentanyl and morphine have been demonstrated to be less effective than meperidine and higher incidence of re-shivering was found

24 Meperidine (Demerol ) Multireceptor activity α- 2b adrenoreceptor activity seems to play a much more important role than k-agonism in decreasing the shivering threshold twice as much as the vasoconstriction threshold

25 α-2 Central agonists Clonidine (Catapres) and dexmedetomidine Generate an increase in the interthreshold range indicative of central thermoregulatory inhibition. Intraoperative administration of a-2 central agonists can be as beneficial against shivering as meperidine a-2 central agonists, significantly affecting heart rate and blood pressure, can be safely combined with other antishivering drugs such as meperidine, buspirone and nefopam to effectively treat shivering.

26 Muscle relaxants Very effective at stopping shivering. They do not suppress the central neurological triggers. Mask insufficient sedation and seizure activity in patients with traumatic or postanoxic brain injury May increase the risk of developing critical illness polyneuromyopathy

27 Other agents Nefopam Nonsedative benzoxazocine analgesic drug inhibiting the re-uptake of monoamines. Slightly reduce the shivering threshold without impairing other thermoregulation responses such as vasoconstriction or sweating. Conjunction with alfentanil, it seems to reduce the shivering threshold more than with clonidine

28 OTHER AGENTS Ketanserin and ondansetron Slightly reduce postoperative, short-term, shivering Magnesium adjunctive antishivering therapy, has been shown to reduce the shivering intensity, resulting in muscle relaxation without further sedation Increase the cooling rate and comfort in volunteers treated with meperidine

29 Drug combinations There is no single ideal drug available to suppress shivering, particularly when due to induced hypothermia. Meperidine can be safely combined with a2-agonists, buspirone and nefopam to reduce shivering. Meperidine and buspirone co-administration has shown a synergistic interaction leading to a greater than expected reduction of shivering threshold

30 Conclusion

31 Conclusion The optimal thermoregulatory approach to minimize shivering during hypothermia combines surface warming during core cooling, together with drugs acting synergistically or additively. Sedation with propofol and µ-agonists can be of benefit in reducing shivering in an intensive care environment. Meperidine and clonidine can also be administrated in a nonintensive care environment. Key importance is that electrolytes are maintained within normal range, with particular attention being paid to magnesium levels.

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