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BEFORE
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Don’t Give Mag the Cold Shoulder: The Role of Magnesium in
Therapeutic HypothermiaNadia Awad, Pharm.D.
Clinical Assistant Professor, Emergency MedicineErnest Mario School of Pharmacy
Rutgers, The State University of New Jersey
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Learning Objective
Describe the clinical indications and dosing recommendations of magnesium for patients undergoing therapeutic hypothermia
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Clinical Vignette
TM is a 54-year-old male who is brought in to your emergency department after experiencing a cardiac arrest at home
Both the paramedics and the emergency medicine physicians confirm ventricular fibrillation on the cardiac monitor
With multiple rounds of resuscitation, return of spontaneous circulation (ROSC) is achieved
The decision is made to initiate therapeutic hypothermia
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The Basics
Therapeutic hypothermia (TH): • Induction of hypothermia in patients following
cardiac arrest or traumatic brain injury to reserve neurological function
• Benefits:• Delays the progression of inflammatory cascade• Reversal and/or prevention of cerebral ischemia by
improving oxygen supply-demand mismatch
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The Phases of TH
0 4 8 12 16 20 24 28 32 36 40 44 48
3837363534333231
Deg
rees
(Cel
sius
)
Hours from Initiation of TH
Initiation of Cooling
Maintenance
Rewarming
NormothermiaCritical role of the
EM Pharmacist
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Complications of TH
Shivering Hemodynamic instability Glycemic control Electrolyte imbalances Coagulopathy Infection
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“Shiver Me Timbers!”
Shivering in TH: • Autonomic response to counter the effects of
hypothermia• Occurs more commonly at temperatures between
35 and 37°C • With resultant heat generation and potential
hyperthermia:• Delays in achievement of core body temperature• Increased metabolic rate• Increased oxygen demand
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Typical Treatment Strategies for Shivering
Sedation and analgesia:• Mitigation of shivering• Results in vasodilation to expedite surface cooling
Preferential for use of agents with short half-lives If persistent, use of neuromuscular blockade agents
(NMBAs)• Intermittent bolus administration of non-depolarizing
NMBAs
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Magnesium for Shivering: Say What??
Mechanism:• N-methyl D-aspartate (NMDA) receptor antagonist
Manifestation of effects:• Facilitates thermoregulation to nonadrenergic and
serotonergic neurons to counter the effects of hyperthermia
• Reduces post-anesthetic shivering• May offer neuroprotection through cerebral vasodilation
due to effects on smooth muscle toneAltura et al. Magnesium 1984; 3:195-211.
Kizilirmak et al. Ann N Y Acad Sci 1997; 813:799-806.Schmid-Elsaesser et al. Stroke 1999; 30:1891-1899.
Lysakowsky et al. Anesth Analg 2007; 104:1532-1539.
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The Proof is in the Evidence
Experimental study (N = 9)• Healthy volunteers• Invasive cooling via infusion of lactated Ringer’s solution
Intervention:• Control: normal saline• Magnesium: 80 mg/kg IV bolus followed by infusion of 2 g/hr
Results:• Reduction in shivering threshold (p = 0.04)• Increase in shivering comfort (p = 0.019)• No difference in gain of shivering response (p = 0.344)
Wadhwa et al. Br J Anaesth 2005; 94:756-762.
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The Proof is in the Evidence…Again
Experimental study (N = 22)• Healthy volunteers
Active cooling via surface cooling technique for a maximum of 5 hours
Randomized to receive one of four interventions:1) Meperidine 50 to 100 mg IV (n = 5)2) Meperidine plus buspirone, 30 to 60 mg PO (n = 4)3) Meperidine and ondansetron, 8 to 16 mg IV (n = 5)4) Meperidine, ondansetron, and magnesium sulfate, 4 to 6 g IV
bolus followed by 1 to 3 g per hour infusion (n =8)
Zweifler et al. Stroke 2004; 35:2331-2334.
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The Proof is in the Evidence…Again
Results:• Achievement of vasodilation greater in those who
received magnesium than other interventions• 88% (7 of 8) versus 29% (4 of 14) (p = 0.024)
• Shorter time in achievement of target tympanic temperature of 35°C (p = 0.039)
• Higher comfort scores in magnesium group (p < 0.01)• No significant differences in SBP, DBP, MAP, or oxygen
saturation• Some significant decreases in HR
Zweifler et al. Stroke 2004; 35:2331-2334.
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Take Home Message
Magnesium can provide some benefit in patients undergoing TH• Reduces shivering threshold• Improved patient comfort
A bolus dose of 4 g of intravenous magnesium sulfate can be reasonably and safely administered for such patients
Can be considered as an adjunctive treatment for refractory shivering in TH that does not improve with standard therapies
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AFTER
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Don’t Give Mag the Cold Shoulder: The Role of Magnesium in Therapeutic Hypothermia
Nadia Awad, Pharm.D., BCPSClinical Assistant Professor, Emergency Medicine
Ernest Mario School of PharmacyRutgers, The State University of New Jersey
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Learning Objective
Describe the indications and dosing recommendations of magnesium for patients undergoing therapeutic hypothermia
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Phases of TH
0 4 8 12 16 20 24 28 32 36 40 44 48
3837363534333231
Deg
rees
(Cel
sius
)
Hours from Initiation
Critical Role of the EM Pharmacist
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Pain
SedationParalytics
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Mechanism
Thermoregulation
Reduced shivering
Neuroprotection
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Reduced shivering threshold
Increased comfort
No affect on gain of shivering
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Vasodilation
Faster time to TTM
Higher comfort score
Heart rate
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Benefits
NMBA-Sparing?
Role