Intensive Care
Management from the Experts
Dr. David Seder Maine Medical Center
Dr William Parham ANW Intensivist Program
Dr Lisa Kirkland ANW Intensivist Program
Dr. Michael Mooney Program Director and Moderator
Objectives
Review the anticipated impact of therapeutic hypothermia on
cardiac output measurements
Describe the intravenous fluid infusion process for lowering body
temperature
Discuss use of short-acting sedation and paralytics for therapeutic
hypothermia
Summarize the induction, maintenance and rewarming phases of
therapeutic
h
i hypothermia
h
h
i
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Neurological Resuscitation
after Cardiac Arrest
Managing the patient during Induction, Maintenance,
and Rewarming…
David Seder MD
Maine Medical Center
Director of Neurocritical Care
Disclosures
• No financial conflicts
• ALL applications
li ti
described are offlabel!
• Grant support from
MMC NSI and MRC
http://www.neurocriticalcare.org
http://www.hypothermianetwork.com/INTCAR.htm
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Crit Care Med 2009;37 (Suppl):S211-S222.
Epidemiology of OHCA
• Cardiac arrest is common
– 295,000 OHCA per year in US
• 23% VF
• 31% Bystander CPR
– Median survival all rhythms 7.9%, VF 21%
– Best EMS systems: ie: Seattle 1998-2001 (resuscitated)
• 17.5% survival to hospital discharge
• 34% VT/VF subgroup
– IHCA adults: 19% (despite 95% witnessed or monitored)
• Mortality among patients surviving to be hospitalized
–
–
–
–
Ontario 72% (1994-2002)
Taipei 75% (2003-4)
Goteborg 68% (2003-5)
Rochester 65% (1998-2001)
Circulation 2010;Jan 26:e12-13
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Is the cup half empty?
• Nationally, the survival
rate of OHCA is < 8%
• Half of patients who
survive to be
hospitalized die in the
hospital
• Half of those who are
discharged from the
hospital have
neurological disability
• Why bother?
…or half full?
• 40% of MMC OHCA
survivors have GNO
• 55-60% with VT/VF &
without shock have
GNO
• A statewide program in
Az of bystander CPR,
CCR, and hypothermia
l d tto a ttripling
led
i li off
OHCA survival!
• These patients have
a chance
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Northern Hypothermia Network
Acta Anaesthesiol Scand. 2009 Aug;53(7):926-34
Acta Anaesthesiol Scand. 2009 Aug;53(7):926-34
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NHN CA outcomes
• 37 centers, 7 countries
• 986 patients received
TH after CA 20042008
• 26% CPC 1-2 among
asystole/PEA
Acta Anaesthesiol Scand. 2009 Aug;53(7):926-34
Factors associated with survival
Acta Anaesthesiol Scand. 2009 Aug;53(7):926-34
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From what do “survivors” die…?
Cause of death in IHCA
Cause of Death in
OHCA
9%
51%
23%
68%
HIE
Cardiac
MOSF
23%
HIE
Cardiac
26%
3rd
3
d
MOSF
Laver. Intensive Care Med 2004;30:2126
Mechanisms of brain injury in
circulatory arrest
• Primary Injury:
– “Energy failure” due to ATP depletion
• Secondary injury:
– Loss of transcellular electrolyte gradients
• Ca+, Na+, Cl- enter, K+ exits cell
• Water follows Na+ into cells causing cytotoxic edema
– Lipid peroxidases damage membranes
– Neurotransmitter release causes excitotoxicity
– Activation of apoptotic pathways
– Microvascular thrombosis
– Reperfusion injury
6-72h
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Other secondary injury…
• Uncontrolled seizure activity
• Hypotension,
Hypotension hypoperfusion
– Postresuscitation syndrome
– ICP crisis
– Autoregulatory failure
•
•
•
•
Fever
Re-arrest
Hypoxia
Derangements of glucose
metabolism
Neurology 2008;72:744
The hours after ROSC
• Mediators of cerebral blood flow after CA:
– Changes in blood viscosity
– Sludging of erythrocytes
– Development of platelet aggregates
• Heavy concentrations in post-ischemic tissue beds
– Imbalance of the coagulation system
– Endothelial flaps
p
– Compression by swollen glial cells
– Increased cerebral vascular tone and
resistance
Resuscitation 2003;58:337
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Cardiac arrest associated brain
injury “CAABI”
• “No flow” affects the
most metabolically
active areas of brain
– Cortex
– Basal ganglia
– Cerebellum
• “Low
Low flow”
flow affects the
watershed areas
between vascular
territories
75 yo man OHCA 4-2010
• Unwitnessed arrest
• VF on EMS arrival
• 35 minutes CPR
and resuscitation
• Therapeutic
hypothermia
• 108h after ROSC,
GCS 4
• CMO at family
request
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Shrunken eosinophilic neuron
(anoxic neuron) is the hallmark
of HIE
Pseudolaminar
necrosis
http://www.neuropathologyweb.org/chapter2/chapter2aHIE.html
Rationale for temperature modulation
after brain injury
“Death Spiral”
• Hypothermia drives
fatally injured cells
away from lysis and
toward apoptosis
• Hypothermia drives
marginally injured cells
away from apoptosis and
t
toward
d recovery
• Intracellular calcium
mediates injury and most
apoptotic pathways
Crit Conn 2008;7(4):16
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Anesthesia and Analgesia 1959;38 (6): 423
Anesthesia and Analgesia 1959;38 (6): 423
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Clinical evidence for TH after CA
• Largest RCT of TH in
OHCA survivors
– 275 patients
randomized to TH or
routine care
– Europe 1996-2001
• Absolute 16% increase
in chance of a good
neurological outcome
• Absolute 14% decrease in
6 month mortality
N Engl J Med 2002;346:549-56
Clinical evidence for TH after CA
N Engl J Med 2002;346:549-56
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Clinical evidence for TH after CA
New Engl J Med 2002; 346:557-63
• Australian
Randomized clinical
trial conducted 19961999
• Randomized on
alternating days to TH
or routine care
• TH: good outcome
49%, routine care
good outcome: 26%
(p=0.046)
Nonrandomized data
Polderman. Lancet 2008, 371:1955-1969.
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Lausanne
• 55 VT/VF OHCA
treated with TH 20022002
2004
• Compared to
historical controls
1999-02
• Similar DT,, severityy of
illness
• CPC 1-2: 56% vs.
26% pre-TH
Effect of the implementation of a therapeutic hypothermia protocol
on neurological outcome after out-of-hospital VF/VT arrest
-Crit Care Med 2006;34:1865
Japan
• 400 patients with
variable
i l
implementation
t ti off
TH
• Developed model
to isolate the
interaction
between use of
TH and outcomes
at different time
points.
• No benefit of TH
in DT < 15
minutes.
Crit Care. 2010 Aug 16;14(4):R155
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What are the risks of TH?
• More infections
– Lung
• Trends toward
more bleeding*
• Electrolyte shifts
• Clinically
insignificant
bradycardia
• Changes in drug
metabolism
HCASG. NEJM 2002;346:549-56
Skeptic’s arguments
• 3300 patients
• Many non–TH
screened
d iin HACA
patients
ti t were
to enroll 275 over 6
allowed to develop
years
fever
– Does not reflect “real
– Unfair comparitor?
world” experience
• Single multicenter
– Most commonly
RCT should not set
managed patients
standard of care
not included
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TTM Trial
• European trial of
TH (33C) vs TN
(36.5C) in CA
survivors
• Niklas Neilsen PI
• (INTCAR founder)
• Multinational trial
• Do we need to
“prove” the efficacy
of TH, again?
• What are the
consequences of a
poorly designed or
inconclusive trial
result?
2005 AHA ACLS Guidelines
• “Unconscious adult patients with ROSC after out-ofhospital cardiac arrest should be cooled to 32
32°C
C to
34°C (89.6°F to 93.2°F) for 12 to 24 hours when the
initial rhythm was VF (Class IIa).”
• “Similar therapy may be beneficial for patients with nonVF arrest out of hospital or for in-hospital arrest (Class
IIb).”
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Only 10% patients with OHCA
will meet RCT criteria for TH
•The decision to
initiate TH is usually
based on clinical
judgement of risk
and benefit, not on
proof!
Risks
Benefits
• Infections
• Bleeding
• Need for
sedation
N Engl J Med 2002;346:549-56
• Strongly neuroprotective
• Decreased mortality
• Better neurological
outcome
TH after Cardiac Arrest
•
Clinical criteria for therapeutic hypothermia
–
No more than 8 hours have elapsed since the
return of spontaneous circulation.
Encephalopathy is present, typically defined as the
patient being unable to follow verbal commands.
There is no life-threatening infection or bleeding.
Aggressive care is warranted and desired by the
patient or the patient’s surrogate decision-maker
–
–
–
•
•
Terminal underlying disease
Impending cardiopulmonary collapse
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The Devil’s in the details…
How to cool…
Baltimore, 1955
Portland, Maine, 2006
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Basics of Therapeutic Hypothermia
• There are 3 phases of treatment:
– Induction
• Rapidly bring the temperature to 32-34C
• Sedate with propofol or midazolam during TH
• Paralyze to suppress heat production
– Maintenance
• maintain the goal temperature at 33C
• Standard 12-24 hours (optimal duration is unknown)
• Suppress
pp
shivering
g
– De-cooling (rewarming)
• Most dangerous period: hypotension, cerebral edema, seizures
• Goal is to reach normal body temperature over 12-24h
• Stop all sedation when normal body temperature is achieved
Induction: how to cool
• Monitor core temperature
– Bladder
Bladder, esophagus,
esophagus or central venous/pulmonary
arterial
• Cold fluid
– 30cc/kg LR or 0.9%NS over 30 minutes
• 2-2.5C temperature reduction
– No adverse cardiovascular results
– Rare to cause pulmonary edema
• Ice packs and cooling mats
– Effective, but difficult to control rate of temperature
change
– Overcooling is dangerous
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Induction: how to cool
• Commercial cooling devices
– Servo
Ser o mechanism varies
aries temperature
temperat re of
circulating water or air (prevents overcooling)
– External (surface cooling) systems
• Hydrogel heat exchange pads
• Cold water circulating through plastic “suit”
• Cold water immersion – awaiting
g safety
y data
– Invasive (catheter based) systems
• Heat exchange catheter in SVC or IVC
• Plastic or metalic heat-exchange catheter
Cold IVF
• Polderman 2005
– 110 p
patients,, 2-3L over 50’
– 36.9°C to 34.6°C, MAP
increased by 15mmHg,
no pulmonary edema
Bernard 2003
- 22 patients 30cc/kg LR at 4°C
over 30 min:
i 3
35.5°C
°C to 33
33.8°C
8°C
Improvements in MAP, renal
function, no pulmonary edema
Polderman. Crit Care Med 2005;33:2744
Bernard. Resuscitation 2003;56:9
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Cold IVF
• 2-3L of Ringers
g
or Saline at 4C decreases
body temperature
– No effect on LVEF by echo
– Improved hemodynamic indices
Kim. Circulation 2005;112:715
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Induction – How I do it
• Examine and place BIS
monitor
o to
• Give 30-40cc/kg IVF at
4ºC over 30 minutes –
LR or NS
– Pressure bag, not IV
pump
• Sedate and p
paralyze
y
the patient
• Apply a commercial
cooling device
• Monitor and replace
potassium and
magnesium
• Antibiotics, usually
• Ventilate to a normal
pH, and PaO2>110
• Maintain
M i t i a MAP > 80
• CVC, Arterial
catheter, CO/CI/SVV
device
Comparison of cooling methods
• Traditional cooling
– inexpensive & available
– Effective
– Very high incidence
overcooling
INDUCTION
• Noninvasive cooling devices
– Safe – no insertion, lots of
clinical experience
– Effective, unless patients very
heavy
– Expensive
• Invasive cooling devices
MAINTENANCE
– Most effective at tight
temperature control
– Better for heavy patients
– Insertional dangers:
thrombosis, infection,
placement-related injury
– Expensive
Crit Care 2007;11:R91
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Outcomes with Surface vs
Endovascular Cooling
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Utility of the Medivance Arctic Sun
for TH after Cardiac Arrest
• Effective at Induction
–
–
–
–
80% within 4h
90% within 6h
100% within 9h
2 pts got adjuvant cooling:
• ice or fluids
• Effective at maintenance
– 96.7% of the maintenance
phase was spent in the
target temperature range
Jarrah. Neurocrit Care 2009;11:S23
• 90 patients with
OHCA – VF arrest
and TH randomized
• Moderate
hypoglycemia
– 18% vs 2%
– 72-108mg/dl
– 108-144mg/dl
108 144mg/dl
• No mortality
diff
difference
(33% vs
• Hypoglycemia defined
35%)
as <54mg/dl
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Measurement of Blood Glucose
• MMC prospectively enrolled
12 CA survivors and
measured concurrent AG,
VG, FBG
• Mean glucose values higher
during TH
• >20% discrepancy FBG vs
AG in 5% when T>36C,
T>36C and
17% when T<34%
• FBG values uniformly higher
than AG values
Maintenance: How I do it
• Surface cooling for most patients with bladder
or esophageal temperature
• Intravascular cooling if they need a CVC,
have skin problems, or if I have extra time
• cEEG
• CO/CI and preload monitoring
• MAP > 80
• Bispectral index when paralyzed to make
sure they’re “out”
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Five patients who were not out
• 5/204 awoke during TH
after CA
• All witnessed arrests
– 0-1 minute low flow
– 13-24 minutes No flow
• “BIS1” = BIS after first
dose of NMB
• BIS1: 43,52,54,52,63
• All were receiving
propofol and/or fentanyl
De-cooling
• Vasodilation causes hypotension
– May require several liters IVF
IVF, increased
vasopressors
• More shivering
• Inflammation increases at higher temperature
– “post-resuscitation” syndrome
• Increased ICP
• Watch for hyperkalemia
– Primarily in renal failure
• SEIZURES
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Patients do not
like to rewarm,
even if you call it
“decooling”.
Shivering
• Drives up systemic
metabolic rate
– Increased CO2 production
– Increased O2 consumption
– Major cardiac stressor
• Drives up cerebral oxygen
consumption
– Favors ischemia
• Uncomfortable
Stroke. 2008 Dec;39(12):3242-7.
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BIS monitor can be used to
quantify shivering
p=0.001
• EMG dB from
BIS monitor
correlated with
the validated
BSAS
• EMG p
power
correlates with
rate of cooling
CC -0.38
May. Crit Care Med 2009;37 (12 Supp); A467
Shiverplots
EMG
BSAS
40
*
*
4
*
*
30
3
2
20
1
10
0
0
-1
Time
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BSAS
50
5
22:55
0:13
1:31
2:49
4:07
5:25
6:43
8:01
9:19
10:37
11:55
13:13
14:31
16:30
17:48
19:06
20:24
21:42
23:00
EMG
G Power (dB)
60
Shiverplots
80
70
60
• Each additional
“shivering episode”
associated with
35% increase in
odds of GNO
50
40
30
20
10
0
80
70
60
50
40
30
20
10
0
Management of shivering
• Neuromuscular blockade
– Vecuronium bolus 0.1mg/kg
0 1mg/kg prn BSAS>2
– Cisatricurium in renal failure
• Propofol
• Alpha blockade
– Dexmedetomidine infusion or clonidine
•
•
•
•
Scheduled acetaminophen,
p
, buproprion
p p
Meperidine or fentanyl
Focal counterwarming
Magnesium infusion (serum level 3-4mg/dl)
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Sedation and analgesia during
therapeutic hypothermia
• Comfort
• Antiepileptic effects
• HCASG
– Midaz 0.125mg/kg/hr
– Fentanyl 2mcg/kg/hr
– Pancuronium 0.1 mg/kg
q2h
• 70kg man/32h
– 280mg midazolam
– 4480mcg fentanyl
– 224 mg pancuronium
– That’s a lot of drugs!
New Engl J Med 2002;346:549
Crit Care Med 2006;34:1865
Drug metabolism during
hypothermia: what do we know?
• Propofol concentrations 30% higher at 34ºC than 37ºC
(healthy volunteers)
Pharmacotherapy 2009;28:102
• Fentanyl concentrations ↑ 5%/↓ºC
Anesth Analg 1995;80:1007
Anesthesiology 1999;91:A444
• (healthy swine)
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Sedation
• Deep,
antiepileptic
sedation, or
• Light sedation
with cEEG, or
• BIS-guided
sedation
Seizures prior to therapeutic
hypothermia
• 19-34% incidence overall
• Myoclonic status epilepticus traditionally
associated with 100% mortality
• NCSE present, less common due to
absence of NMB
• Patients rarely received propofol or BDZ
-Ann Neurol 1994; 35:239–243
-Neurology 1988; 38:401–405
-Intensive Care Med 2006; 32:
836–842
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• 19 children cEEG
x72h during TH after
CA
• 9 (47%) seized
• 6/9 NCSE
• 7/9 generalized
• 8/9 during late TH or
rewarming periods
• 6 (32%) had SE
What do the seizures mean?
• Are they markers for
terrible and irreversible
brain injury?
• Are they causing active,
ongoing injury?
• Should we treat?
• If so, how?
h ?
MSE
NCSE
Neurology 2008;72:744
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ICU care following CA
• Many techniques
f performing
for
f
i TH
• Electrolytes
• Glucose
management
• Management of
shivering
• Perfusing BP
• Seizure detection
• Antibiotics for
aspiration or ALI
• Analgosedation
• Medication dosing
Hospital size and CA outcome
>109,000
>109
000 patients
in the NIS
Mortality was lower at urban, teaching, and large hospitals
Intensive Care Med 2009;35(3):505-11
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CA volume vs outcomes
• 4674 patients from 39
p
hospitals
• Overall mortality was
56.8%
– Not all patients comatose
• After adjusting for age
and severity of illness,
institutional mortality
ranged from 46% to 68%
• Annual case volume
strongly associated with
outcome
Resuscitation. 2009 Jan;80(1):30-4
Thank You!
Horstmann et al. Brain
atrophy
h in
i the
h aftermath
f
h off
cardiac arrest. NEUROLOGY
2010;74:306-312
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1. Central Venous Pressures
• Managing MAP > 60 and CVP >8
• CO /Index frequency
– Value during hypothermia ?
• Cardiac outputs on done upon arrival to ICU; what
should a protocol suggest to follow
• Cooling Cardiac output vs normal temp Cardiac
Output?
2. Sedation vs Paralytics
• Shorter acting Sedation and use of
Paralytics
• What about Versed, Precedex, Propofol ?
• Train of 4 monitoring,
D/C paralytic when temp back at 36. C vs 37.0 C
• Consider bolus dosing vs continuous drip
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3. EEG Monitoring
• Continuous EEG monitoring
• (Neuro Prognostication)
• Practicality/Benefits
• Seizures
4. LINES
• IV Fluids and Line Placement
• Order of events to utilize IV fluids to
cool faster
• Where is the best place to place lines
ICU, Cath Lab or ED?
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5. Non Phamaceutical
Interventions for shivering
• Shivering,
Shivering how do we control it?
• What are some Non pharmaceutical
interventions we can apply?
• Do
D heated
h t d ventt circuits
i it have
h
impact?
i
t?
6. Management of fever post
cooling
• How should we treat the “rebound
rebound
fever” after cooling is stopped?
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7. Magnesium Levels
• Magnesium levels, importance
• Goal of magnesium level during TH
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