BEFORE

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

Learning Objective

Describe the clinical indications and dosing recommendations of magnesium for patients undergoing therapeutic hypothermia

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

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

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

Complications of TH

Shivering Hemodynamic instability Glycemic control Electrolyte imbalances Coagulopathy Infection

“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

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

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.

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.

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.

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.

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

AFTER

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

Learning Objective

Describe the indications and dosing recommendations of magnesium for patients undergoing therapeutic hypothermia

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

Pain

SedationParalytics

Mechanism

Thermoregulation

Reduced shivering

Neuroprotection

Reduced shivering threshold

Increased comfort

No affect on gain of shivering

Vasodilation

Faster time to TTM

Higher comfort score

Heart rate

Benefits

NMBA-Sparing?

Role