2003/11/26 Chih-Min Liu 1 Postanesthetic Shivering Epidemiology, Pathophysiology, Prevention and Management

2003/11/26 2Chih-Min Liu Reference Perioperative Shivering Perioperative Shivering Physiology and Pharmacology Physiology and Pharmacology Anesthesiology 2002; 96: Anesthesiology 2002; 96: Postanesthetic Shivering Postanesthetic Shivering Epidemiology, Pathphysiology, and Approaches to Prevention and Management Epidemiology, Pathphysiology, and Approaches to Prevention and Management Drugs 2001; 61 (15): Drugs 2001; 61 (15): Clinical Anesthesiology, third edition Clinical Anesthesiology, third edition Chapter 6: Patient monitors; Chapter 6: Patient monitors;

2003/11/26 3Chih-Min Liu Clinical Considerations Hypothermia: < 36 o C Hypothermia: < 36 o C O 2 consumption x 5; decrease saturation; myocardial ischemia and angina O 2 consumption x 5; decrease saturation; myocardial ischemia and angina Increased mortality rate Increased mortality rate Monitoring site: Monitoring site: Tympanic membrane: brain temperature Tympanic membrane: brain temperature Nasopharyngeal mucosa: core temperature Nasopharyngeal mucosa: core temperature Rectum: slow response in change to core temp Rectum: slow response in change to core temp Esophagus Esophagus

2003/11/26 4Chih-Min Liu Epidemiology 40-60% after volatile anesthetics 40-60% after volatile anesthetics Young male adult, rare in elder (age impairs thermoregulatory control) Young male adult, rare in elder (age impairs thermoregulatory control) Length of anesthesia or surgery Length of anesthesia or surgery Peri-op rewarming procedure: if not Peri-op rewarming procedure: if not Mild hypothermia Mild hypothermia The more serious hypothermia, the higher the probability The more serious hypothermia, the higher the probability Anesthetic used Anesthetic used Less common with propofol; more with halogenated agent, pentothal Less common with propofol; more with halogenated agent, pentothal

2003/11/26 5Chih-Min Liu Pathophysiology Consequence of postanesthetic shivering Consequence of postanesthetic shivering Discomfort Discomfort Increased pain Increased pain IICP, IOP IICP, IOP O 2 consumption (VO 2 ): more 40 – 120% O 2 consumption (VO 2 ): more 40 – 120% Increased minute ventilation Increased minute ventilation Cardiac morbidity Cardiac morbidity

2003/11/26 6Chih-Min Liu Pathophysiology Two types of postanesthetic shivering Two types of postanesthetic shivering Thermoregulated shivering Thermoregulated shivering With cutaneous vasoconstriction, the response of hypothermia With cutaneous vasoconstriction, the response of hypothermia Perioperative hypothermia Perioperative hypothermia Non-thermoregulated shivering Non-thermoregulated shivering Mechanism unknown Mechanism unknown Postoperative pain related? Postoperative pain related?

2003/11/26 7Chih-Min Liu Pathophysiology Origins of Postanesthetic Shivering Origins of Postanesthetic Shivering Perioperative hypothermia Perioperative hypothermia Postoperative pain Postoperative pain Perioperative heat loss Perioperative heat loss Direct effect of certain anesthetics Direct effect of certain anesthetics Hypercapnia or respiratory alkalosis Hypercapnia or respiratory alkalosis The existence of pyogens The existence of pyogens Hypoxia Hypoxia Early recovery of spinal reflex activity Early recovery of spinal reflex activity Sympathetic overactivity Sympathetic overactivity

2003/11/26 8Chih-Min Liu Perioperative hypothermia Phase I: 1st hour Internal redistribution: from center to peripheral Phase II: 2-4 hours Heat loss: skin, viscera Phase III: Steady-state

2003/11/26 9Chih-Min Liu Pathophysiology Early recovery of spinal reflex activity Early recovery of spinal reflex activity Residual effect of anesthetics on the inhibiting control exercised by supraspinal structure Residual effect of anesthetics on the inhibiting control exercised by supraspinal structure Propofol in low concentration may have less effect on certain central structure such as the reticular formation, thus faster recovery of descending inhibiter control Propofol in low concentration may have less effect on certain central structure such as the reticular formation, thus faster recovery of descending inhibiter control

2003/11/26 10Chih-Min Liu Temperature-regulating system Thermosensors Skin to hypothalamus Afferent pathway, integration area Spinal cord Modulate: NRM( serotonin), LS(NE) Integration inputs: PO-AH Efferent pathway Central descending shivering pathway: PH Multiple inputs>common efferent signal Spinal α motor neurons, axons

2003/11/26 11Chih-Min Liu Pathophysiology Human defenses to hypothermia: Human defenses to hypothermia: Skin vasomotor activity Skin vasomotor activity Nonshivering thermogenesis Nonshivering thermogenesis Cell metabolic without mechanical work, Neonate Cell metabolic without mechanical work, Neonate Shivering Shivering Sweating Sweating Shivering is the last-resort defense Shivering is the last-resort defense

2003/11/26 12Chih-Min Liu Pathophysiology Shivering Shivering Several types Several types 4-8 Hz., waxing-and-waning pattern 4-8 Hz., waxing-and-waning pattern Postanesthetic tremor Postanesthetic tremor Thermoregulatory inhibition abruptly dissipates, thus increasing the shivering threshold toward normal Thermoregulatory inhibition abruptly dissipates, thus increasing the shivering threshold toward normal New, near-normal threshold activate shivering New, near-normal threshold activate shivering Shivering like activity Shivering like activity Pain in post-op and labor female Pain in post-op and labor female

2003/11/26 13Chih-Min Liu Prevention & Management Perioperative Hypothermia Prevention Perioperative Hypothermia Prevention Limiting the effects of internal redistribution Limiting the effects of internal redistribution Skin surface rewarming with forced-air warmer for 30 minutes Skin surface rewarming with forced-air warmer for 30 minutes Reduce heat loss Reduce heat loss Radiation from skin surface Radiation from skin surface Room temperature > 23 o C if the op field is large Room temperature > 23 o C if the op field is large Cover the patient as much as possible Cover the patient as much as possible Intravenous fluid rewarming Intravenous fluid rewarming

2003/11/26 14Chih-Min Liu Prevention & Management Passive prevention is not enough Passive prevention is not enough Active heat transfer Active heat transfer Cutaneous patch is the most efficient Cutaneous patch is the most efficient Forced warm air better then … Forced warm air better then … Water circulation blankets Water circulation blankets 1/3 cover of the cutaneous surface is enough 1/3 cover of the cutaneous surface is enough Under GA > vasodilatation > heat loss Under GA > vasodilatation > heat loss

2003/11/26 15Chih-Min Liu Prevention & Management Physical treatment Physical treatment Shivering threshold: Shivering threshold: skin 20%, core 80% skin 20%, core 80% Raise temp to inhibit postoperative shivering: Raise temp to inhibit postoperative shivering: skin 4 o C = core 1 o C skin 4 o C = core 1 o C Radiation heat system Radiation heat system Forced air warmer: Forced air warmer: reduce frequency and duration of shivering reduce frequency and duration of shivering

2003/11/26 16Chih-Min Liu Prevention & Management Medical treatment Medical treatment Opiates Opiates Tramadol, Ketanserin, Nefopam and Ondensetron Tramadol, Ketanserin, Nefopam and Ondensetron α2-Adrenergic Agonists α2-Adrenergic Agonists Other drugs Other drugs

2003/11/26 17Chih-Min Liu Opiates Meperidine Meperidine Demoral Demoral Κ-opioid receptor Κ-opioid receptor Shivering threshold Shivering threshold Vasoconstriction Vasoconstriction Sweating Sweating Others: Others: Pure μ-receptor agonists Pure μ-receptor agonists Morphine, alfentanyl, fentanyl Morphine, alfentanyl, fentanyl Sites of action Sites of action PO-AH, dorsal raphe nucleus neurons, RMN, LS, and the spinal cord PO-AH, dorsal raphe nucleus neurons, RMN, LS, and the spinal cord

2003/11/26 18Chih-Min Liu Meperidine( Demoral) Sweating Vasoconstriction Shivering threshold

2003/11/26 19Chih-Min Liu Tramadol, Ketanserin, Nefopam and Ondensetron The balance of Norepinephrine and serotonin(5-HT) in the PO-AH controls the body temperature set point The balance of Norepinephrine and serotonin(5-HT) in the PO-AH controls the body temperature set point 5-HT induce hyperthermia; α2-Adrenergic Agonists (clonidine) reduce core temperature 5-HT induce hyperthermia; α2-Adrenergic Agonists (clonidine) reduce core temperature Opposite modulatory inputs from NE and serotonergic neurons shifting the shivering threshold Opposite modulatory inputs from NE and serotonergic neurons shifting the shivering threshold All 4 drugs acts on the serotonin neuromediator All 4 drugs acts on the serotonin neuromediator Encourage the inhibiting effect of serotonin on OP-AH Encourage the inhibiting effect of serotonin on OP-AH

2003/11/26 20Chih-Min Liu Tramadol, Ketanserin, Nefopam and Ondensetron Tramadol Tramadol Inhibits reuptake of 5-HT, NE, dopamine and facilitate 5-HT release Inhibits reuptake of 5-HT, NE, dopamine and facilitate 5-HT release Site of action: Pons Site of action: Pons Analgesic effect, non-opioid analgesic Analgesic effect, non-opioid analgesic 1 mg/kg for shivering, reduce threshold by 0.8 o C 1 mg/kg for shivering, reduce threshold by 0.8 o C Nefopam Nefopam Inhibits reuptake of 5-HT, NE, dopamine and lower normal body temperature Inhibits reuptake of 5-HT, NE, dopamine and lower normal body temperature Analgesic effect, 0.15mg/kg or 20mg Analgesic effect, 0.15mg/kg or 20mg Ketanserin Ketanserin Low efficacy Low efficacy Antihypertensive effect, 5 HT 2 antagonist, 10mg Antihypertensive effect, 5 HT 2 antagonist, 10mg Ondensetron Ondensetron Antiemetic, 5 HT 3 antagonist, 8mg Antiemetic, 5 HT 3 antagonist, 8mg

2003/11/26 21Chih-Min Liu α2-Adrenergic Agonists Clonidine 75μg Clonidine 75μg lower the threshold of cutaneous vasoconstriction and shivering by 0.5 o C lower the threshold of cutaneous vasoconstriction and shivering by 0.5 o C Bolus & perfusion: Bolus & perfusion: At the end of op: 1.5 or 3μg/kg At the end of op: 1.5 or 3μg/kg Cardiac surgery: 200 to 300μg Cardiac surgery: 200 to 300μg Mechanism: Mechanism: Central Central Shivering centre is under inhibiting control of the preoptic anterior hypothalamic region Shivering centre is under inhibiting control of the preoptic anterior hypothalamic region α2-Adrenergic Agonists probably strengthened it α2-Adrenergic Agonists probably strengthened it Dexmedetomidine Dexmedetomidine

2003/11/26 22Chih-Min Liu Other drugs Other drugs Other drugs NMDA receptor antagonist: NMDA receptor antagonist: Ketamine Ketamine Magnesium sulfate 30mg/kg Magnesium sulfate 30mg/kg Methylphenidate 20mg Methylphenidate 20mg Analeptic agent, block reuptake of 5-HT Analeptic agent, block reuptake of 5-HT Physostigmine 0.04mg/kg Physostigmine 0.04mg/kg Central acting cholinesterase inhibitor Central acting cholinesterase inhibitor Doxapram 100mg or 1.5mg/kg Doxapram 100mg or 1.5mg/kg Respiratory stimulant, central action on pons Respiratory stimulant, central action on pons Recovery of the descending inhibitor control of the supraspinal effecting centers Recovery of the descending inhibitor control of the supraspinal effecting centers

2003/11/26 23Chih-Min Liu Conclusion Hypothermia is associated with shivering and many complications, patient should be kept normothermia Hypothermia is associated with shivering and many complications, patient should be kept normothermia Prevention of hypothermia consists of limiting heat loss and active rewarming system Prevention of hypothermia consists of limiting heat loss and active rewarming system Effective treatment of shivering will reduce metabolic heat production and must be accompanied by an effective active heating system. Effective treatment of shivering will reduce metabolic heat production and must be accompanied by an effective active heating system. Skin surface rewarming is less efficient then medical treatment with meperidine, tramadol, or, in certain situations, clonidine Skin surface rewarming is less efficient then medical treatment with meperidine, tramadol, or, in certain situations, clonidine All antishivering drugs except ketanserin have some analgesic properties in humans, suggested that pain and thermoregulation are tightly connected All antishivering drugs except ketanserin have some analgesic properties in humans, suggested that pain and thermoregulation are tightly connected No single structure or pathway is responsible for the shivering response No single structure or pathway is responsible for the shivering response

2003/11/26 Chih-Min Liu 24 Thanks for your attention