Update in Therapeutic Hypothermia Post Cardiac Arrest
Allison Forni, PharmD, BCPSClinical Pharmacy Specialist
UMass Memorial Medical Center, Worcester MA
Learning Objectives
• Learning Objective 1: Describe controversies on who, how, and when to initiate therapeutic hypothermia post cardiac arrest.
• Learning Objectives 2: Breakdown and evaluate the pharmacotherapy considerations for patients requiring therapeutic hypothermia.
Patient Case
• AS is a 92 yo male suffering a cardiac arrest at SNF due to respiratory failure. The patient was down for unknown period of time. Bystander CPR was initiated, EMS arrived 4 minutes after call, presenting rhythm was asystole. Patient received 1 round of epinephrine and atropine and had ROSC 5 minutes after EMS arrival. Patient transferred to BWH ED, initial GCS 3 (no sedatives given), in sinus tachycardia.
What elements of this patient case make the application of TH
controversial?
Cardiac Arrest
Loss of cerebral perfusion
Anaerobic glycolysis
Depolarization
ATP depletion, intracellular acidosis
Normalization of blood flow
Free oxygen radical
generation
Inflammatory response
Ischemic Insult Reperfusion
Targeted Temperature Management (TTM) as a treatment modality for cardiac arrest
• History
• Clinical practice of TTM should specify:• A description of the
intended temperature profile
• The thermoregulatory interventions used to achieve the target
• The actual performance of the TTM strategy
• The primary and secondary outcomes that the TTM intended to achieve
Temperature Effect
36°C Increased activity attempting to warm up, skin pale, numb, and waxy, muscles tense, fatigue, and signs of weakness.
34°C–35°C Uncontrolled intense shivering, still alert but movements uncoordinated, and pain and discomfort due to coldness.
31°C–33°C Shivering slows or stops, muscles stiffen, mental confusion, apathy, speech slowed and slurred, breathing slower and shallow, and drowsiness.
31°C Skin cold, pupils dilated, extreme weakness, slurred speech, exhausted, denies problems, resists help, gradual loss of consciousness,and progressive respiratory arrest and arrhythmias.
Nunnally ME. CCM 2011; 29(5): 1113‐1125
2014 Midyear Clinical Meeting Update in Therapeutic Hypothermia Post Cardiac Arrest
© 2014 American Society of Health-System Pharmacists 1
Rationale for TTM
• Post‐ischemic effects are temperature dependent
• Increased temperature enhances harmful effects of free radicals and activates NMDA receptors
Peberdy MA et al. Circulation 2010, 122:S768‐S786Nunnally ME et al. CCM 2011; 29(5): 1113‐1125Castren M, et al. Acta Anaesthesiol Scand 2009; 53: 280‐288.
Critical Care Consensus Recommendations:“The jury STRONGLY RECOMMENDS targeted
temperature management to a target of 32°C–34°C as the preferred treatment (vs. unstructured temperature management) of out‐of‐hospital adult cardiac arrest
victims with a first registered electrocardiography rhythm of ventricular fibrillation or pulseless ventricular
tachycardia and still unconscious after restoration of spontaneous circulation (strong recommendation,
moderate quality of evidence).”
AHA recommendation:“We recommend that comatose (ie, lack of
meaningful response to verbal commands) adult patients with ROSC after out‐of‐hospital VF cardiac arrest should be cooled to 32°C to 34°C (89.6°F to 93.2°F) for 12 to 24 hours (Class I, LOE B). Induced hypothermia also may be considered for comatose adult patients with ROSC after in‐hospital cardiac arrest of any initial rhythm or after out‐of‐hospital cardiac arrest with an initial rhythm of pulseless electric activity or asystole (Class IIb, LOE B).”
Physiologic effects of TTM
Protective• Reduce cerebral metabolism
• Reduce cerebral blood flow
• Reduce ion pump dysfunction and neuroexcitation
• Reduce mitochondrial injury
• Decrease intracellular acidosis and intracranial hypertension
• Decrease free radical production
• Decrease apoptosis
Deleterious• Cardiovascular effects
• Glucose and electrolyte abnormalities
• Reduction in GI motility
• Coagulopathy
• Immunosuppression
Bernard SA, et al. NEJM 346: 557‐563. 2002;
Side Effects of TTM
Biochemical and Hematologic Values
Urine output
Electrolyte loss
Insulin secretion
Insulin sensitivity
Creatinine Clearance
Platelet count
Platelet aggregation
Infection
Cardiac Effects
VT/VF
Cardiac Output
Bradycardia
HACA Investigators. NEJM 2002; 346(8): 549‐556.
Patients 275 enrolledDifferences= DM, CV disease, bystander CPRExclusion Criteria
77 randomizedNo differences in baseline characteristicsExclusion Criteria
Intervention 32-34ºC by bladder temp with surface cooling over 24hrs (cooled over 4hrs, warmed over 8hrs)
33ºC within 2 hrs of ROSC and maintained for 12hrs with active rewarming over 6 hrs
Endpoints Primary= favorable neurologic outcome at 6 months
Primary= neurologic outcome at discharge
Bernard SA, et al. NEJM 346: 557‐563. 2002.
Randomized Controlled Trials
Patient Case
• AS is a 92 yo male suffering a cardiac arrest at SNF due to respiratory failure. The patient was down for unknown period of time. Bystander CPR was initiated, EMS arrived 4 minutes after call, presenting rhythm was asystole. Patient received 1 round of epinephrine and atropine and had ROSC 5 minutes after EMS arrival. Patient transferred to BWH ED, initial GCS 3 (no sedatives given), in sinus tachycardia.
What else do you want to know about
this patient?
Is this patient a candidate for TH?
2014 Midyear Clinical Meeting Update in Therapeutic Hypothermia Post Cardiac Arrest
© 2014 American Society of Health-System Pharmacists 2
Who
What
When
How
Why
Patient Selection
• Variability in:
• Initial rhythm
• Witnessed vs unwitnessed
• In hospital vs out of hospital
• Time to BLS
• Total ischemic time
Comatose lack of meaningful response to verbal commands
Return of spontaneous circulation
McNicol DR et al. Circulation 2012; 26(21) Supplement
• Time since ROSC
• Baseline body temperature
• Etiology of arrest
• Hemodynamic parameters
• Exclusion criteria
HACA Investigators. NEJM 2002; 346(8): 549‐556.
Complications during THWho
What
When
How
Why
Time Course of TH
• Time to initiation
• Time to achievement of target temperature
Nielsen N et al. Acta Anaesthesiol Scand 2009; 53: 926‐943Wolff B et al. International Journal of Cardiology 2009; 133: 223–228
Goal: To reduce the patient’s body temperature to goal as quickly as possible• Rapid induction reduces risk for side
effects• Patient management problems
Goal: To tightly control the patients core body temperature with a maximum fluctuation of 0.2‐0.5º Celcius• Increased stability of the patient
but longer‐term side effects
Induction Maintenance Reversion
Polderman KH, et.al Critical Care Med 2009.37(3);1101‐1120.
Maintain controlled
normothermia
Goal: To rewarm the patient in a slow and controlled fashion at 0.2 to 0.5 º Celsius per hour Risks associated with speed of
rewarming
? hrs0 hrs ? hrs
Duration of TH
2014 Midyear Clinical Meeting Update in Therapeutic Hypothermia Post Cardiac Arrest
© 2014 American Society of Health-System Pharmacists 3
Who
What
When
How
Why
Timing of TH
In hospital vs out of hospital
Out‐of hospital patients are generally well or at least
physiologically well compensated before cardiac arrest
whereas hospitalized patients are heterogeneously ill
Nielsen N et al. Acta Anaesthesiol Scand 2009; 53: 926‐943Nunnally ME et al. CCM 2011; 29(5): 1113‐1125Wolff B et al. International Journal of Cardiology 2009; 133: 223–228
Time since ROSC
The relationship between the onset of hypothermia and the
resulting neuroprotection is unclear
Effect of Presenting Rhythm
TH and favorable outcome:Nonshockable rhythm
• Retrospective cohort study of patients with a witnessed out of hospital cardiac arrest with an initial rhythm of PEA or asystole
TH and unfavorable outcome:Shockable vs Nonshockable rhythm
Testori C et al. Resuscitation 2011; 82: 1162‐1167.Terman SW et al. CCM 2014; 42: 2225‐2234.
• Retrospective cohort study of patients with a witnessed out of hospital cardiac arrest treated with TH
Who
What
When
How
Why
Which of the following should be considered when selecting a
technique for cooling:
Speed of induction
Maintenance of a narrow temperature range
Ability to provide controlled rewarming
All of the above
Ideal Technique for Cooling
• Ideal technique:
• Rapid temperature reduction
• Cooling of target organs• Maintain temperature in a narrow range
• Controlled rewarming
• Easy transport and use during CPR• Easy to use during routine care
2014 Midyear Clinical Meeting Update in Therapeutic Hypothermia Post Cardiac Arrest
© 2014 American Society of Health-System Pharmacists 4
Temperature Management• Cold fluids (4ºC)
• 30‐40 mL/kg
• Limitations: poor for maintenance, overcooling, volume
• Ice packs and cooling blankets
• Advantages: low cost
• Limitations: low cooling rate, skin damage, temperature maintenance, nursing care
• Hydrogel‐coated cooling pads
• Advantages: temperature maintenance, use with routine care
• Limitations: high cost, skin complications (rare)
• Intravascular devicesSeder DB, et al. CCM 2009; 37(7): S211‐S222.
Temperature Induction & Maintenance
Hoedemaekers CW et al. Critical Care 2007; 11(4): 1‐9.
Overcooling
Temperature # ptsTotal n=32
< 32 C 20
< 31 C 9
< 30 C 4
• Survival to hospital discharge:
• 30 % temp < 32 C
• 58% temp > 32 C
• NS
Retrospective chart review at 3 large teaching hospitals
Target temperature 32‐34 CUtilized surface cooling techniques
Merchant RM et al. CCM 2006; 34 (12): S490
The target temperature for TH is well defined:
Yes
No
Retrospective chart review of 828 adult patients following a witnessed out of hospital cardiac arrest with a GCS < 8 at
admission. Evaluated the effects of spontaneuousnormothermia (< 37.5 C) comparded with mild TH.
Horburger D et al CCM 2012; 40: 2315‐2319.
Normothermia vs Hypothermia
International trial in 36 ICUs that randomly assigned 950 unconscious adult patients to a target temperature
of 33 C or 36 C following cardiac arrest
Outcome 33C group
36 C group
P value
≥ 1 serious ADE 93% 90% 0.09
Hypokalemia 19% 13% 0.02
Nielson N et al. NEJM 2013
2014 Midyear Clinical Meeting Update in Therapeutic Hypothermia Post Cardiac Arrest
© 2014 American Society of Health-System Pharmacists 5
Who
What
When
How
Why
Outcomes following cardiac arrest have improved over time:
True
False
Cardiac Arrest Outcomes
• Survival to hospital discharge has improved over time• For all rhythms
• 2000 13.7%• 2009 22.3%
• Rates of clinically significant neurologic disability (CPC score at discharge, >1) among survivors has decreased over time• For all rhythms
• 2000 32.9%• 2009 28.1%
• Early recognition, resuscitation, postresuscitation care
Girota S et al. N Engl J Med 2012;367:1912‐20.
Patient Case
• AS is a 92 yo male suffering a cardiac arrest at SNF due to respiratory failure. The patient was down for unknown period of time. Bystander CPR was initiated, EMS arrived 4 minutes after call, presenting rhythm was asystole. Patient received 1 round of epinephrine and atropine and had ROSC 5 minutes after EMS arrival. Patient transferred to BWH ED, initial GCS 3 (no sedatives given), in sinus tachycardia.
What elements of this patient case make the application of TH
controversial?
Key Takeaways
• Key Takeaway #1
• Clinical Controversy regarding the application of TTM exists in multiple areas including who, what, when, how, and why
• Key Takeaway #2
• The strongest grade of recommendation is given for out‐of‐hospital adult cardiac arrest patients with a first registered rhythm of ventricular fibrillation or pulseless ventricular tachycardia who are unconscious after ROSC
2014 Midyear Clinical Meeting Update in Therapeutic Hypothermia Post Cardiac Arrest
© 2014 American Society of Health-System Pharmacists 6
Pharmacotherapy Considerations in Management of Therapeutic
Hypothermia: focus on shivering and glucose
Paul M. Szumita, PharmD, BCPSClinical Pharmacy Practice Manager
Director Critical Care Pharmacy Residency ProgramBrigham & Women’s Hospital, Boston, MA
Objective
• Breakdown and evaluate the pharmacotherapy considerations for patients requiring therapeutic hypothermia wit a focus on shivering management and glucose management
Complications of TH• Infection/pneumonia• bleeding• Acid/base• Shivering/not meeting target temperature• Electrolytes (Potassium, magnesium, phosphate)• Glucose management• Hemodynamics (Bradycardia and hypotension)• Mechanical ventilation• Pharmacokinetic alterations• Seizure and myoclonus
Empey PE, et al. Crit Care Med. 2013 Oct;41(10):2379‐87. Perbet, S, et al. Am J Respir Crit Care Med. Vol 184.2011: 1048–1054, 2011Geurts M, et al. Crit Care Med. 2014 Feb;42(2):231‐42. Mikkelsen M, et al. Crit Care Med. 2013 Jun;41(6):1385‐95.Noyes AM, Lundbye JB. J Intensive Care Med. 2013 Dec 25. [Epub ahead of print]
Yes
No
Not formalized
Not sure
Does your institution have a protocol for prevention, assessment and management of shivering?
Shivering• Involuntary oscillatory
skeletal muscle activity• Shivering “threshold” is ~1°C
below the vasoconstriction threshold
• Activates autonomic and hemodynamic responses
• Increases the resting energy expenditure and caloric consumption
• Typically happens in the induction phase
• Once in maintenance of TH shivering less frequently a complication
Seder DB, Van der Kloot TE. Crit Care Med . 2009; 37: S211‐22Badjatia N, Strongilis E, et al. Stroke 2008; 39: 3242‐4Logan A, et al. Crit Care Nurse. 2011 Dec;31(6):e18‐30.
Park SM, et al. Crit Care Med. 2012 Nov;40(11):3070‐82.
• Frequent assessment is key • Pharmacologic and non‐
pharmacologic strategies can be used to prevent and treat shivering
• Non‐pharm• Head and hand warming• Warming blankets
• Pharm: Neuromuscular blockers, opioids and sedative use and higher magnesium levels have been associated with significant reductions in shivering
Thermoregulatory Defenses
Sessler DI. CCM 2009; 37(7): S203‐S210
Threshold (Celsius)
38
37
36
35
Sweating Constriction Shivering
Men
Women
2014 Midyear Clinical Meeting Update in Therapeutic Hypothermia Post Cardiac Arrest
© 2014 American Society of Health-System Pharmacists 7
Induction
Phase
Maintenance
Phase
Rewarming
Phase
Maintenance of Normothermia
24 hrs
0 hrs 72 hrs
Shivering
Goal: To rewarm the patient in a slow and controlled fashion at 0.2 to 0.5 º Celsius per hour Risks associated with
speed of rewarming Maintain normothermia
with cooling pads for 48 hours after rewarming
TimelineShivering assessment
• Bedside Shivering Assessment Scale• 0 = none
• No shivering noted on palpitation of masseter, neck or chest wall
• 1 = Mild• Shivering localized to the neck and/or thorax only
• 2 = Moderate• Shivering involves gross movement of the upper extremities
• 3 = Severe • Shivering involves gross movement of the trunk and upper and lower extremities
Badjatia N, Strongilis E, et al. Stroke 2008; 39: 3242‐47
Propofol
Midazolam
Dexmedetomidine
Neuromuscular blocker with a sedative
Which primary agent is the primary sedative agent used to management of shivering at your institution?
Medication used to Manage Shivering
• Magnesium• Opioids
• Remifentanil• Meperidine• Fentanyl• Morphine
• Dexmedetomidine • Clonidine• Propofol• Neuromuscular blockers• Ketamine• Midazolam• buspirone
Bjelland T, et al. Intensive Care Med (2012) 38:959–967
Controversies and Questions
• What agent or combination of agents to has the best outcomes?
• Should all patients get NMB?
• How deep should we sedate the patients?
Light vs. Deep Sedation on clinical outcomes and mental health after critical illness
p = 0.03
p =0.47
p = 0.02
Significant patient characteristics/metrics/outcomes
Light Deep P value
PTSD score ICU discharge*
52 57 0.39
PTSD score 4wks post ICU*
46 56 0.07
*Data presented in mean †Data presented as n (%) of Event Scale-Revised PTSD
Single center, prospective, open label trial of 137 ICU patients requiring mechanical ventilation randomized to light (Ramsey 1‐2) or deep (Ramsey 3‐4) sedation at Geneva Hospital Switzerland. Extensive exclusion criteria, removing high risk patients and those with baseline cognitive dysfunction.
Treggiari MM, et al. Crit Care Med. 2009 Sep;37(9):2527‐34.
2014 Midyear Clinical Meeting Update in Therapeutic Hypothermia Post Cardiac Arrest
© 2014 American Society of Health-System Pharmacists 8
Moderate Level of Sedation/Analgesia May be Appropriate… however
• Moderate level of sedation/analgesia is possible with minimal need for NMB
• In healthy volunteers; cooling has been achieved in conscious patients
• However:
• Lower requirements for sedatives have been associated with worse outcomes in some studies
• May be a marker of poor neurologic outcomes (patients are worse off to begin with)
• NMB MAY be associated with better outcomes….May TL, et al. Neurocrit Care. 2014 Jun 25. [Epub ahead of print]
Testori C, et al. Crit Care. 2011;15(5):R248.Burjek, NE, et al. Crit Care Med. 2014 May;42(5):1204‐12
Salciccioli JD, et al. Resuscitation. 2013 Dec;84(12):1728‐33.
Neuromuscular blockers: to add or not?• Shivering is associated with better outcomes observationally• Shivering patients are more likely to receive NMB; therefore selection bias may explain
• Continuous or bolus?• Bolus was associated with:
• Quicker to target temp• Less total exposure to NMB• Equal time in TOF
• Many believe NMB should be used for breakthrough shivering only due to side effects of NMB
• Perhaps a X1 dose at induction (future study)Noyes AM, Lundbye JB. J Intensive Care Med. 2013 Dec 25. [Epub ahead of print}Jurado LV, et al. Pharmacotherapy. 2011 Dec;31(12):1250‐6. Noyes AM, Lundbye JB. J Intensive Care Med. 2013 Dec 25. [Epub ahead of print
Magnesium Therapy
• Reduces shivering thresholds
• Produces peripheral vasodilation and increases cooling rates
• Has antiarrhythmic properties
• Some animal data indicate added neuroprotection
Zweifler RM, Voorhees ME, et al. Stroke 2004; 35: 2331‐34
Patient Case
• AS 92 yo male suffering cardiac arrest at SNF due to respiratory failure. Patient was down for unknown period of time. Bystander CPR initiated, EMS arrived 4 minutes after call, presenting rhythm was asystole. Patient received 1 round of epinephrine and atropine and had ROSC 5 minutes after EMS arrival. Patient transferred to BWH ED, initial GCS 3 (no sedatives given), in sinus tachycardia.
• Pt on propofol and fentanyl infusion• 2 hours into cooing pt temp is 35 degrees with shivering score of 2
Increase Propofol and fentanyl infusions
bolus NMB
Start dexmedetomidine
Continuous NMB
For AS what would you do to treat the current shivering?
Example Prevention and Management of Shivering Strategy
• Prevention• Non‐pharmacologic
• Warm hand, head and heating blanket• Magnesium bolus 4‐6 grams X1 (run over 4 hours)• Low dose opioid and propofol infusions
• Frequent assessment with bedside shivering scale• Treatment of breakthrough
1. Simultaneous Bolus opioid and propofol drip titration Q 10 min X3
2. NMB bolus Q10 min X33. NMB infusion (refractory only)
• Turn off infusions during rewarming
2014 Midyear Clinical Meeting Update in Therapeutic Hypothermia Post Cardiac Arrest
© 2014 American Society of Health-System Pharmacists 9
Glucose During TH
• Hyperglycemia is associated with (observational) increase in poor outcomes
• Neurologic
• Mortality
• Hyperglycemia and hypoglycemia are common
• Hyperglycemia typically during cooling
• Hypoglycemia during rewarming
Daviaud F, et al. Intensive Care Med. 2014 Jun;40(6):855‐62. Kim SH, et al. Am J Emerg Med. 2014 Aug;32(8):900‐4 . Forni AA et al. Crit Care Med. Dec 20124(12):1‐328.
Same IV insulin protocol as other ICU patients
Same IV insulin protocols as other ICU patients with a few provisions
Different IV insulin protocol
Not sure
How does your institution manage hyperglycemia during Therapeutic Hypothermia?
Guidelines from Professional Organizations on ICU Blood Glucose (BG) Goal
Year Organization Patient Population
BG Treatment Threshold
(mg/dL)
BG Target
(mg/dL)
BG Hypoglycemia
Definition(mg/dL)
Updated since NICE-
SUGAR, 2009
2009 AACE and ADA ICU patients 180 140–180 <70 Yes
2013 Surviving Sepsis Campaign
ICU patients 180 <180 Not stated Yes
2009 Institute for Healthcare Improvement
ICU patients 180 <180 <40 Yes
2012American College of Critical Care Medicine (ACCM)
ICU 150
<150 (Trauma)
<180(Stroke+)
<70 Yes
2013 American College of Physicians ICU patient Not stated 140–200 Not stated Yes
2008 American Heart Association
ICU patients with ACS
180 90–140 Not stated No
Kavanagh BP et al. N Engl J Med. 2010; 363:2540-6.Qaseem A et al. Ann Intern Med. 2011; 154:260-7.
Jacobi J. Crit Care Med. 2012; 40:3251-76.Finfer S et al. N Engl J Med. 2009; 360:1283-97.
IV Insulin in the ICU Setting
Jacobi J. Crit Care Med. 2012; 40:3251‐76.Moghissi ES et al. Diabetes Care. 2009; 32:1119‐31.
Antihyperglycemic Therapy
InsulinRecommended
Oral Antidiabetic DrugsNot generally recommended
IV Insulin
Critically ill patients in the ICU
SC Insulin
Non‐critically ill patients
Ins, n 2 3 4 6 7 7 7 8 9 9 9 8 9 9 10 10 9 9 8 9 9 9 8 8 8 6 5 5 5 5 5 5 5 5 5 5 3
BG, n 2 5 7 7 6 7 9 7 10 10 9 9 9 9 11 10 10 8 11 10 10 11 9 11 9 9 10 11 8 7 7 7 7 7 5 5 4
Forni AA et al. Crit Care Med. 40(12):1‐328, December 2012
Managing Hyperglycemia during TH
• No consensus on “how to manage” hyperglycemia specifically related to TH
• Is the typical 180 mg/dL or below appropriate for these patients?
• Typically require high doses of insulin during cooling
• Insulin requirements lower during rewarming
2014 Midyear Clinical Meeting Update in Therapeutic Hypothermia Post Cardiac Arrest
© 2014 American Society of Health-System Pharmacists 10
Example Strategy for Managing Glucose during TH
• Initiate IV insulin when glucose is greater than 200mg/dl
• Do not exceed 50 units insulin / hour • Stop continuous intravenous insulin when glucose levels drop to less than 200 mg/dl, unless type 1 diabetes mellitus
• If patient has type 1 diabetes, continue IV insulin at a rate of 0.5 units/hour
• Check glucose every 30 minutes if glucose < 80 mg/dl until rewarming complete and glucose stabilized > 100 mg/dl
Potassium
• TH increases urine output (wasting of K) and pushes K into the cell during cooling
• Potassium replacement:
• Consider replete potassium to maintain levels >4.0 mEq/L
• Typically discontinue K+ repletion 4 hours prior to rewarming, unless K+ is less than 3.5
• Potassium levels may continue to be elevated hours past re‐warming and require continued frequent electrolyte monitoring
Alterations in Medication Pharmacokinetics
• Metabolism • Altered temperature= altered enzyme activity
• Conformational shape changes at receptor site
• Less activation or inactivation of drug and metabolite
• Prolongation of prodrug conversion to active drug
• Higher serum concentrations of active compounds which result in toxic effects
• Accumulation of metabolites
• Elimination• Biliary clearance
• Impaired hepatic blood flow
• Renal clearance
• Renal blood flow decreased
• Impaired CrCL during maintenance and effect reversed upon rewarming
• Increased UOP thought to be due
to impaired tubular secretion Tortorici MA, et al. CCM 2007; 35: 2196‐2204.
• Absorption • Slow rate of availability
• Onset delay
– Prolongation of time to Cmax
• Reduction in gastric motility causes variability with oral dosage formulations
• Distribution• Vd dependent upon:
– Blood flow redistribution
– Blood pH increases and pCO2 decreases
• Drugs with pKa of 7‐8 are most affected during IH
– Alterations in protein binding
– Lipid solubility
– Tissue binding capacityArpino PA and Greer DM. Pharmacotherapy 2008; 28(1): 102‐111.
Empey PE, et al. Crit Care Med. 2013 Oct;41(10):2379‐87.
Example ‐ Patient Monitoring Guideline
• Seizure v myoclonus• EEG (goal less than 18
hours from admission)
• BIS in the rare case of NMB• Not reliable for sedative
drip titration
• TOF in the rare case of NMB• Baseline• Continue sedation until a
4/4 TOF is achieved
• RASS• Goal RASS ‐4 to ‐5 prior to
cooling
• Temperature• 2 methods of
measurement
• Shivering assessment scales
• Electrolytes, glucose, coagmonitoring
• Hemodynamic• Heart rate (bradycardia
common)• If clinical bradycardia, can warm to 93‐95 to see clinical effect
• MAP (goal > 90)• CVP (goal greater than 8
typically)
Badjatia N,et al. Stroke 2008;39:3242‐3247.
Quality Metrics ‐ Example
Times Minutes Goal
Downtime <15 min
ROSC to TH initiation <60 min
ROSC to ICU
ROSC to target temperature <300 min
ED to ICU time
TH initiation to target temperature <240 min
ICU to target temperature <180 min
Arctic Sun to target temperature <180 min
ICU to EEG <18 hours
Hypoglycemia occur? None
Breakthrough shivering meds given? List meds
Therapeutic hypothermia after cardiac arrest guideline Core
Management
• Patient selection• Cooling and rewarming process• Shivering• Electrolyte repletion• Hemodynamics and ventilation• Glucose management• Seizure and myoclonus• Prognosis
2014 Midyear Clinical Meeting Update in Therapeutic Hypothermia Post Cardiac Arrest
© 2014 American Society of Health-System Pharmacists 11
Key Takeaways• Key Takeaway #1
• Shivering is common complication leading to delays to target temperature. Prevention, regular assessment and management strategies are imperative.
• Key Takeaway #2
• Hyper and hypoglycemia are common during and cooling, maintenance and rewarding and are associated with poor outcomes.
QUESTIONS?
2014 Midyear Clinical Meeting Update in Therapeutic Hypothermia Post Cardiac Arrest
© 2014 American Society of Health-System Pharmacists 12
Top Related