PATIENT CARE MANUAL. Guideline For Managing Shivering In Neurocritical Care Patients Undergoing Therapeutic Temperature Modulation

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1 PATIENT CARE MANUAL MANUAL CODE: SUBJECT: Guideline For Managing Shivering In Neurocritical Care Patients Undergoing Therapeutic Temperature Modulation DATE ISSUED: DATE REVISED: SUPERSEDES: CROSS REFERENCES: Note: this is a guideline for medical management. Provider orders must accompany the use of this guideline. The hypothalamus sets a core temperature for the body. When the body temperature falls below this set point, the hypothalamus may activate our thermoregulatory defense mechanisms. Initially, cutaneous arterioles and veins constrict to reduce heat loss. If the differential between core temperature and the set point is sufficiently large, then shivering is triggered (increased heat production). The shivering threshold is the core temperature at which shivering is triggered. Shivering during therapeutic temperature modulation (TTM) undoes any benefit of TTM and may be harmful. From the perspective of TTM, a lower threshold is better. The following algorithm outlines how to reduce the risk of shivering, and treat shivering if necessary. The following tables will briefly describe the mechanism of action, dosing, monitoring, notable side effects and contraindications of each antishivering measure. Because of limited efficacy, multiple anti-shivering measures are typically required to control shivering Acetaminophen Reduces set point 1000g q8 hours LFTs q72 hours Hepatoxicitiy Significantly elevated LFTs Concomitant hepatotoxic meds Limited efficacy Page 1 of 7

2 Ibuprofen Reduces set point 400mg q6 hours Creatinine daily Nephrotoxicity May increase bleeding risk Elevated creatinine Concomitant nephrotoxic meds Coagulopathy/thromocytopenia Administer with PPI if long-term use planned Skin counter-warming (BAIR Hugger) Reduces shiver threshold and intensity Maximum temperature Highly effective; best risk:benfit ratio Magnesium sulfate Reduce shiver threshold; cutaneous vasodilation 25-50mg/kg IV over 20 minutes q6h prn serum Mg < 2.5 mg/dl HR, Blood pressure None at levels below 5 mg/dl Renal impairment Buspirone Reduce shiver threshold 30mg q8 hours Rare sedation Serotonin syndrome Multiple serotonergic medications Cut dose by 50% in anuric patients Page 2 of 7

3 Dexmedetomidine Reduce shiver threshold; may reduce set point; cutaneous vasodilation Start: 0.3 µg/kg/hour Range: µg/kg/hour Heart rate, blood pressure Bradycardia Hypotension Sedation Pre-infusion bradycardia or hypotension Abrupt cessation may result in withdrawal symptoms Elimination is prolonged in hepatic failure Only for patients who cannot be deeply sedated, e.g. patients who are not intubated, or who require very close following of their neurologic examination. Requires CCM attending approval Propofol Reduce shiver threshold; reduce set point Bolus: mg Infusion: µg/kg/min Heart rate, blood pressure If hypothermic, daily CPK and lactate Bradycardia, hypotension Propofol infusion syndrome (PrIS) rhabdomyolysis, lactic acidosis, renal failure, and/or refractory hypotension and bradycardia Pre-infusion hypotension or bradycardia Hypothermic patients have decreased propfol metabolism and are at increased risk of PrIS. Safe dose limits are as follows: 37 C 60 µg/kg/min 35 C 50 µg/kg/min 33 C 40 µg/kg/min Page 3 of 7

4 Meperidine Reduce shiver threshold; reduce set point mg IV q2 hours Maximum 600mg/24 hours Blood pressure Hypotension Increased ICP Seizures Serotonin syndrome Ileus MAO-I consumption Other serotonergic meds Impaired renal function Higher cumulative doses and/or impaired renal function lead to build-up of an epileptogenic metabolite Meperidine has a greater anti-shivering effect compared with standard opioids Fentanyl Reduce shiver threshold; reduce set point Bolus: 2 µg /kg Infusion: 1-8 µg/kg/hr Blood pressure Hypotension Increased ICP Ileus Hypothermic patients have decreased fentanyl metabolism. Recommended dose limits are as follows: 37 C 8 µg/kg/hr 35 C 6.5 µg/kg/hr 33 C 5 µg/kg/hr Page 4 of 7

5 Baseline Shivering Prophylaxis 1. Apply BAIR hugger surface warmer at maximum temperature 2. Buspirone 30mg enterally stat then q8h 3. If serum Mg < 2.5mg/dl, bolus magnesium sulfate 50mg/kg IV over 20 min, and maintain serum level > 2.5mg/dl 4. Ibuprofen 400mg enterally q6h + PPI or Tylenol 650mg enterally q6h standing 5. If temperature reduction is urgent, consider paralytic boluses (with adequate sedation) until goal temperature reached Yes Intubated? No If BSAS > 1 If BSAS > 1 Step 1 1. Continue Baseline interventions 2. Propofol - bolus 30-50mg, followed by drip at 25 µg /kg/hr Titrate up q10min until BSAS < 1 Max rates (µg/kg/min): 37C, 35C, 33C or Dexmedetomidine - only for select patients, see guideline text Start drip at 0.3 µg/kg/hr Titrate up q10min until BSAS < 1 Max rate: 1.5 µg/kg/hr Step 1 Dexmedetomidine - Start drip at 0.3 µg/kg/hr Titrate up q10min until BSAS < 1 Max rate: 1.5 µg/kg/hr If BSAS > 1 If BSAS > 1 Step 2 1. Continue Baseline and Step 1 interventions 2. Meperidine - 25mg IVP. Repeat q5min upto 4 doses until BSAS < 1 May repeat this dose q3h prn BSAS > 1 E.g. if 50mg total first time, use 50mg for future doses Max 600mg/day If BSAS > 1 Step 3 1. Consider stopping TTM weigh risks vs. benefits 2. Stop using meperidine, continue Baseline and Step 1 interventions 3. Fentanyl - bolus 2 µg/kg, followed by drip at 2 µg/kg/hr Repeat boluses and titrate up q10min until BSAS < 1 Max rates (µg/kg/hr): 37C, 35C, 33C or Paralytic drip - Must be deeply sedated. Discontinue all other shiver interventions. Bolus and titrate to achieve TOF 2/4 Step 2 Meperidine mg IVP q3h prn Hold for excess sedation BSAS 0 = No Shivering noted on palpation of the masseter, neck or thorax 1 = Visible or palpable shivering localized to the neck and/or thorax only 2 = Visible shivering of the arms, in addition to above 3 = Visible shivering of the arms and legs, in addition to above Page 5 of 7

6 References Sessler DI. Defeating normal thermoregulatory defenses: induction of therapeutic hypothermia. Stroke Nov;40(11):e Zweifler RM, Sessler DI. Thermoregulatory vasococonstriction and shivering impede therapeutic hypothermia in acute ischemic stroke patients. J Stroke Cerebrovasc Dis. 1996;6(2):100-3 Badjatia N, et al. Metabolic Impact of Shivering During Therapeutic Temperature Modulation: The Bedside Shivering Assessment Scale. Stroke. 39(12): , December Badjatia N, et al. Predictors and clinical implications of shivering during therapeutic normothermia. Neurocrit Care. 2007;6(3): Choi HA, et al. Prevention of Shivering During Therapeutic Temperature Modulation: The Columbia Anti-Shivering Protocol. Neurocrit Care Jan 6; /s Leslie K, et al. Mild hypothermia alters propofol pharmacokinetics and increases the duration of action of atracurium. Anesth Analg May;80(5): Caccia S, et al. Clinical pharmacokinetics of oral buspirone in patients with impaired renal function. Clin Pharmacokinet Mar;14(3):171-7 Doufas AG, et al. Dexmedetomidine and meperidine additively reduce the shivering threshold in humans. Stroke May;34(5): Talke P, et al. Dexmedetomidine does not alter the sweating threshold, but comparably and linearly decreases the vasoconstriction and shivering thresholds. Anesthesiology.1997 Oct;87(4): Lenhardt R, et al. Suppression of shivering during hypothermia using a novel drug combination in healthy volunteers. Anesthesiology Jul;111(1):110-5 Bicer C, et al. Dexmedetomidine and meperidine prevent postanaesthetic shivering. Eur J Anaesthesiol Feb;23(2):149-5 Bajwa SJ, et al. Reduction in the incidence ofshivering with perioperative dexmedetomidine: A randomized prospective study. J Anaesthesiol Clin Pharmacol Jan;28(1):86-91 Kim YS, et al. Optimal dose of prophylactic dexmedetomidine for preventing postoperative shivering. Int J Med Sci Aug 13;10(10): Usta B, et al. Dexmedetomidine for the prevention of shivering during spinal anesthesia. Clinics (Sao Paulo) Mittal G, et al. Randomised double-blind comparative study of dexmedetomidine and tramadol for post-spinal anaesthesia shivering. Indian J Anaesth May;58(3): Page 6 of 7

7 Reviewed by: Rishi Malhotra, MD Diahann Barthelemey, RN Maria Cullaro, RN Julie Chen, PharmD Adam Keene, MD Mark Sinnett, PharmD Pharmacy and Therapeutics Committee Page 7 of 7