Sedation & Paralytic Therapy
in the ICU
Leanna R. Miller, RN, MN, CCRN-CSC, PCCN-CMC, CEN, CNRN, NP
Education Specialist
LRM Consulting
Nashville, TN
Objectives
 Identify the purpose for pain, sedation, &
paralysis management in the ICU
patient
 Analyze and compare assessment
methods for determining appropriate
pain, sedation & paralysis management.
 Recognize and apply the different
pharmacotherapeutics used in the ICU
for pain, sedation, & paralysis.
Goals of Critical Care
Management
 Save the salvageable and relieve suffering
 Peaceful & dignified death without prolonging life
 Curative therapy should not supplant palliation of
pain
 Use of state-of-the-art interventions
 Aggressive & fast paced therapy according to need
 Quality pain management mandatory for all
patients
Consciousness/Sedation
The Balance of Analgesia, Sedation, and Paralytics to promote comfort
What is Sedation?
 Several Clinical Definitions:



process of establishing a state of calm
promoting a sense of well-being
reduction of anxiety and agitation through the
use of pharmacotherapy
 Sedation is NOT analgesia

80% of Doctors and 40% of ICU nurses
answered that benzodiazepines provided
analgesia (1990s)
Pathophysiology Response of
Stress and Anxiety
 Cardiovascular

Release of systemic epinephrine and
norepinephrine



Elevated HR and BP
Increased cardiac O2 demand
Decrease end-organ perfusion
 Endocrine

Release of Cortisol, Glucagon, Glucose

Hyperglycemia
Pathophysiology Response of
Stress and Anxiety
 Neurological

Increased response and activation of
peripheral pain fibers


Increased sensation to pain
Release of neurotransmitters in the brain



Pain
Agitation
Delirium
Pathophysiology Response of
Stress and Anxiety
 Immune

Increased levels of prostaglandins,
cortisol, glucose, cytokines,


Increase anti-inflammatory response
Decrease wound healing
SIGNIFICANT STRESS IN THE ICU PATIENT OVERALL CAUSES
ORGAN ISCHEMIA AND DECREASED HEALING
Analgesia
 Clinical Definition:

The absence of pain through the use of
pharmacotherapy
 Acute and chronic pain in the ICU activates
the stress response
 Patients with analgesia can still experience
anxiety
PAIN THERAPY - Myth
“One size fits all or
Set and forget therapy.
Its essentially a
maintenance therapy”
Truths
 Majority of ICU patents suffer moderate/severe pain
 40% are delirious & cannot communicate
 50% are either physically/emotionally distressed
 10-20% have no hopes of cure --- end-of-life in ICU
 Balance between pain relief & maintaining alertness
 Multidisciplinary team for multimodal therapies.
Pain in ICU
 Repeated episodes of acute pain localized
 Surgery/tissue inflammation immobility
 catheter/ apparatus discomfort/ nasogastric
& orogastric tubes
 endotracheal intubation/ suctioning/ chest
tubes
 phlebotomy/vascular access/physiotherapy
 routine turning & positioning the patient
Types of pain in ICU
 Somatic – most common –localized  opiates
 Visceral – cramping & colicky  anticholinergics
 Neuropathic – burning / shooting  antidepressants
 Mixed type  combination therapy
 Sustained or chronic pain of varying degrees
Inherent Problems
 difficult to differentiate due to lack of




communication
untreated pain affects all body systems
synergistic effect of pain on anxiety,
depression, sleep
all modalities are unpredictable & have
adverse effects
pain therapy to be tailored to individual
needs.
Assessment of pain in ICU
 Pain as the 5th vital sign- requires frequent
evaluation
 Cognitive impairment/delirium markers
• Behavioral (facial, FACS)
• Physiological (BP, HR, RR)
 Creative assessments (teaching hand movements,
blinking
 Subjective quantification (numeric/graphic scales –
W-B faces)
Assessment of pain in ICU
Treatment of Pain
 treatment of perceived & prevention of
anticipated pain
 Opiates – principal agents in ICU
- potent / lack ceiling effects
- mild anxiolytic & sedative
- relieves air hunger & suppresses cough in
respiratory failure
- improved patient – ventilator synchrony
- effective antagonist – naloxone
 lack amnesic effects /additional sedatives
required
Treatment of Pain
 adjuvant / non-pharmacological / multimodal
therapies
•
Simple Relaxation – must begin preoperatively




•
Jaw relaxation
Progressive muscle relaxation
Simple imagery
Music (either patient – preferred or “easy listening” are
effective in reducing mild to moderate pain
Complex Relaxation – must begin preoperatively


Biofeedback
imagery
Causes of Pain in the ICU?
The Messengers of Pain
• Direct tissue damage stimulates pain fibers
• Local Inflammatory mediators
•
Bradykinin, Prostaglandins, Cytokines
• Tissue Injury
•
•
•
Histamine
Serotonin
TNF
WHY IS THIS IMPORTANT?
Common Analgesic Drugs in the
CVICU
Drug
Dose
Onset
Peak
Duration
Morphine
Renal
1 - 4 mg
5 min
20 min
4 - 5 hrs
Fentanyl
Liver
25 – 100 mcg
1 - 2 min
3 - 5 min
30 - 60 min
Remifentanil
Plasma
.5 – 40
mcg/kg/h
<1 min
<1 min
3 - 10 min
Dilaudid
Liver
.25 – 2 mg
10 - 15 min
15 - 30 min
2 - 3 hrs
Toradol
Liver
15 – 30 mg
Immediate
1 - 3 min
6 - 8 hrs
A Focus on Morphine
 First narcotic to be used
 Narcotic standard
 Relies on good kidney function for excretion
 Stimulates mast cells to release histamine




Itching
Rash
Hypotension
Acute Asthma episode
 No longer used frequently due to newer drugs
A Focus on Fentanyl
 100x stronger then Morphine
 Fastest metabolizing narcotic used in the
CVICU
 Chest Wall Rigidity


can cause shortness of breath and difficulty
weaning
occurs most often with high IV bolus doses
 Decreases BP and HR
A Focus on Remifentanil
 Newest synthetic narcotic derived from Fentanyl
 Eliminated by plasma esterases
 Metabolism not dependent on liver or kidney function
 Elimination not dose dependent
 Advantages
 Organ independent metabolism
 Lack of accumulation
 Provides analgesia and sedation in ventilated patient
 Disadvantages
 Expensive
 Severe withdrawal
 Rebound hyperalgesia
A Focus on Toradol
 Is a potent IV/IM NSAID
 Decreases sternal incision pain and
inflammation
 Like many NSAIDs can be nephrotoxic

Know your patients BNP and Creatinine
 Can cause GI bleeding
 Usually not given if the patient is…
 Age >75
 Elevated creatinine
 Chest tube bleeding
 Low platelets
Sedation in ICU
 used in the agitated, ventilated & for
procedure discomfort
 to avoid self extubation & removal of
catheters
 NM blockade mandates analgesia &
sedation
 control of pain before sedation
 all have side effects – dose dependent
 analgesics are not sedatives/ Sedatives
are not analgesics
Common Sedatives in the ICU
Drug
Dose
Onset
Peak
Duration
Ativan
Liver
.5 - 2mg
5 min.
60-90 min
6 - 8 hrs
Versed
Liver
1 - 2mg
1.5 - 5 min
Rapid
2 - 6 hrs
Propofol
Liver*
Starts at 25
mcg/kg/min
<40 sec.
3-5 min
10 - 15 min
Precedex
Plasma
.2-.7
mcg/kg/hr
(3mcg/kg/hr)
15 - 30 min
30 min
60 - 120 min
Ketamine
2–7
mcg/kg/min
30 s
1 min
5 - 10 min
A Focus on Precedex
 Only sedative used that does not cause
respiratory depression
 Patients can be weaned and extubated while
on Precedex
 Usual titration range 0.2 – 0.7mcg/kg/hr

MD order >0.7mcg/kg/hr
 Titrate by 0.1-0.2mcg/kg/hr q30-45min
 Can cause SEVERE bradycardia and
hypotension
 Very expensive!
A Focus on Ketamine
 dissociative anesthetic  light sedation &
amnesia
 used as an adjunct for patients with
uncontrolled pain or inadequately sedated
 rarely used in the CVICU due to myocardial
depressant properties
 monitor for hallucinations and vivid dreams
Assessment of Pain and Sedation
Sedation scoring systems
 Assess levels to vary according to course





of ICU stay
Observational scales - 4 levels – min,
mod, deep, GA
Addenbrooke sedation scale 0-7 (vocal,
tracheal suction)
Ramsay sedation scale 1-6 (vocal,
glabellar tap)--aim for 3-4
Direct information- ideal to assess
analgesia & sedation
BIS – for deep sedated & paralyzed
RASS ASSESSMENT










+4
+3
+2
+1
0
-1
-2
-3
-4
-5
Combative, violent, danger to self/staff
Very agitated, pulls lines, tubes, aggressive
Agitated frequent non-purposeful movement, fights the vent
Restless / Anxious but not aggressive or vigorous
Alert and calm
Drowsy, not fully alert but can stay awake, eyes open to voice for >10sec
Light sedation, wake and makes eye contact for < 10 sec
Moderate sedation, moves/opens eyes to voice but no eye contact
Deep sedation, no response to voice but moves or opens eyes to physical stimulation
Unarousable, no response to stimuli
BIS monitor
BIS Monitoring
BIS Monitor
 BIS monitor utilizes EEG waveforms.
 reading is monitored from the patient’s
forehead.
 excessive muscle activity can interfere with
EEG detection
Bispectral Index
 BIS – an attempt to objectively monitor
patients sedation
 processed EEG measurement that
gives a score to help determine the
patient’s response to sedation
 useful to help titrate medication
 proper sensor placement is key to
accurate monitoring
Sensor Application
Apply sensor on forehead at angle
Circle #1: Centered, 2 inches above nose
Circle #4: Directly above eyebrow
Circle #3: On temple, between corner of eye
and hairline
Press around the edges of each circle to assure adhesion
Press each circle for 5 seconds
BIS Placement
 Make sure the forehead is clean and
dry!
 Label the sensor with date/time
 Replace sensor every 24 hours and
PRN
BIS Monitor
 implement BIS monitoring on all patients with
paralytic drips infusing
 purpose of BIS monitor is to provide a direct
measurement of the SEDATIVE effects on
the brain.
 goal for BIS Monitoring will be 40 – 60.

studies have indicated that this is a safe range
for no memory recall.
BIS Monitoring
Troubleshooting the BIS
 If the BIS increases suddenly or is higher
than expected:

Consider:





Is the sedative dose sufficient?
Is there an increase in stimulation?
When was the last analgesic given?
Is the patient adequately paralyzed? TOF?
Is the patient having a seizure
Troubleshooting the BIS
 If the BIS decreases suddenly or is lower than
expected:

Consider:



Has there been a decrease in stimulation or
increase in sedation/analgesia?
Is the patient significantly hypothermic?
Has there been a sudden significant drop in BP?
BIS Monitoring
 Always consider the overall picture of the
patient

Ex: if nothing significant has changed with
patient and BIS number suddenly reflects very
different readings then fall back to your overall
assessment of the patient
REMEMBER!
Look at the BIG PICTURE!
Do Not Forget
You are treating a patient not just the number
“Sedation Vacation”
 Assess for daily awakening
•
Exclusions
Increased ICP
 Neuromuscular blockade
 Significant ventilation support
 CABG, immediate post-op

“Sedation Vacation”
 Is patient awake and calm?
•
•
SAS 3 – 4
RASS 0 to -1
 If no, restart sedation @ ½ previous
dose
 If yes, proceed to spontaneous
breathing trial (SBT)
“Sedation Vacation”
 Assess for SBT
•
•
•
•
•
•
Calm & co-operative
Hemodynamically stable
PEEP < 8
FiO2 < 0.60
pH > 7.34
SpO2 > 90%
“Sedation Vacation”
 SBT Termination Criteria
•
•
•
•
•
•
•
RR > 35/min for > 5 minutes
SpO2 < 90% for > 2 minutes
New ectopy
HR change 20% from baseline
BP change 20% from baseline
Accessory muscle use
Increased anxiety/diaphoresis
“Sedation Vacation”
 Conduct SBT for 1 minute
•
•
•
•
Mode CPAP
PEEP = 0
PS @ least 5 – 10
FiO2 unchanged
Paralytics in the ICU
 Paralysis – the loss of voluntary muscular
function due to the administration of a
paralytic
 Neuromuscular Blockade Agent (NMB) –
Drugs that obstruct transmission of nerve
impulses to the muscle
 Neuromuscular Blockade agents DO NOT
BLOCK THE TRANSMISSION OF PAIN!!!!
Paralytics in the CVICU
 Sedation and Analgesics must always be
given FIRST
 Must use sedatives with an Amnesic affect


Benzodiazepines (VERSED)
High dose Propofol
 Paralytics are always given LAST
Why Do We Paralyze?
 Decreases O2 demand

ARDS
 Prevent Patient-Ventilator dysynchrony


VDR ventilators
BiVent
 Prevents Shivering in hypothermia patients


Shivering increases O2 demand
Raises patients temperature
 Open chest
Checklist for chemical paralysis
 Must be adequately sedated first before
paralytic administered
 Must have anxiolytic drip that has amnesic
properties
 Must have analgesic drip infusing
 Must have lubrication for eyes/eye bubbles
Common CVICU Paralytics
Drug
Dose
Onset
Peak
Duration
Vecuronium
.08 - .1 mg/kg
1 min
3-5 min
15-25 min
Pancuronium
.04 -.1 mg/kg
30-45 sec
3-4 min
35-65 min
Succinylcholine
.6 mg/kg
30-60 sec
1-2 min
4-10min
Nimbex
3 mcg/kg/min
1-2 min
2-5 min
25-44 min
A Focus on Vecuronium
 A non-depolarizing NMB
 Will NOT increase K+
 Full recovery from paralytic 25-40min
 Frequently used in the CVICU for intubation
or as a bolus drug before Nimbex
 Rarely used as a drip in the absence of
Nimbex

0.8-1.2mck/kg/min
A Focus on Succinylcholine
 A depolarizing NMB
 Can increase K+ ~ 0.5-1mEq/L


KNOW YOUR PATIENTS K+ before
administering
Does your patient have any renal disease?
 Metabolized by plasma cholinesterase


Very rapid metabolism ~5min
Does not rely on kidney or liver function
A Focus on Nimbex
 Is our primary titrating NMB used in the
CVICU
 Is also metabolized in the blood
 Standard dose is 3mcg/kg/min

Titrate range: 0.5-5mcg/kg/min
 Metabolism ~45min

Changes with hypothermia?
Successful Paralysis: How do we
know?
 Assessment



Movement
Spontaneous Breaths
Peripheral Nerve Stimulator
Peripheral Nerve Stimulators
 Peripheral Nerve
Stimulator – A device
that delivers a determine
electrical current to
create a muscular
contraction
 Used to determine the
amount of
neuromuscular blockade
a patient has
 An increase in NMB will
show a decrease
response to a peripheral
nerve stimulator at a set
current
Train of Four
 Train of Four – 4 consecutive impulses
generated from the peripheral nerve
stimulator resulting in 4 muscular twitches
 # of twitches seen = degree of NMB



No blockade – 4 twitches
Total blockade – 0 twitches
GOAL IS 1-2 TWITCHES
 Increase drip by 10% if >2 twitches
 Decrease drip by 10% if <1 twitch
Train of Four: Facial Nerve
 Place one electrode on
the face at the outer
canthus of the eye
(positive/red electrode)
 Place the second
electrode 2 cm below
and parallel with the
tragus of the ear
(negative/black
electrode)
 Watch and feel for facial
nerve contraction
Train of Four: Ulnar Nerve
Train of Four
 Must have 2x baseline TOFs before starting
NMBs
 Ulnar nerve is more preferred but facial nerve
is easier to see/assess
 Use alcohol pad to wipe clean and dry the
skin before applying electrode
 Electrodes must be changed 24 hrs
 Possibly inaccurate in hypothermia patients…
Helpful tips for TOF
 If checking the thumb – ensure the leads are
placed on the ulnar side of the arm(this is
where the nerve lies)
 Be careful with applying maximum MA’s when
leads are placed on the face – this can lead
to burns/scarring
 Check your battery
 Change your electrodes q24h
Putting it all Together
1. start BIS Monitoring
2. get a Baseline TOF on two locations
3. start Sedation and Analgesic Drips
4. titrate medication up until BIS 40-60
5. bolus paralytic
6. start paralytic drip
7. check TOF q30min until 1-2 twitches
8. monitor TOF and BIS and titrate drips to
endpoints
***** CRUCIAL POINT ******
 Prior to the administration of any paralytic
agent - sedation MUST be administered first.
If paralytic will be continued as an infusion,
sedation MUST also be continued.
 Sedation MUST be a drug that has amnesic
properties.
Drugs that have amnesic effects
 Benzodiazepine class
Examples:

Versed
 Propofol (in high doses) dose will be
individual to patient
Intravenous Medicines commonly
used in CVICU
 SEDATION
 Ativan *
 Versed *
 Propofol **
 Precedex ***
•
•
•
* Amnesic properties
** Amnesic in high
doses only
*** DOES NOT have
amnesic properties
 ANALGESIA
 Morphine
 Fentanyl
 Dilaudid
 Toradol
Case Study
 You are caring for a patient that has an open
chest, they are on a Nimbex, Fentanyl &
Versed gtts:

VS’s:



BP 160/90
HR 128
Vent Settings: SIMV 12, TV 450, PEEP 5, PS 10,
Spontaneous RR 12, 02 saturation 98%, TOF 2/4
Is anything wrong here?
Case Study
 Patient has open chest, Nimbex, Fentanyl &
Versed gtts:

VS’s




105/68
HR 80 Paced
Vent settings: SIMV 12, TV 600, PEEP 5, PS 10,
Spontaneous RR 16
TOF 2/4
Is anything wrong here?
Case Study
 Patient has open chest, has experienced
excessive blood loss through chest tubes,
Nimbex & Propofol gtts(5 mcg/kg/hr)
 VS’s
 BP labile 70’s to 100’s systolic
 HR 80’s paced
 Vent settings: SIMV 12, TV 400, PEEP 5,
PS 5, Spontaneous RR 14, 02 saturation 98%
 TOF 0/4
Is anything wrong here?
SCCM task force recommendations
 Benzodiazepines most popular for sedation
 Short term sedation
• Midazolam <3h (amnesic/ hypotension)
• propofol – infusion syndrome/ pancreatitis
 Long term – lorazepam <20h /diazepam>96h (not
for infusion)
 Delirium – haloperidol - neuroleptic syndrome/
torsade pointes
 Antagonist- flumazenil 0.2mg-1mg (withdrawal
seizures)
ReCap of Key Points
 Sedation:

Patient may still experience pain, goal is antianxiety/ – relaxation, goal is usually to give
amnesia
 Analgesia:

Used to treat pain, no anti-anxiety properties
 Paralytics:

Used to decrease skeletal muscle movement,
imperative that amnesic drugs be used in
combination with analgesic meds, MUST
sedate before paralyzing
ReCap of Key Points
 BIS Monitor:


Used to strictly assess patient’s sedation level
Goal is 40-60
 Peripheral Nerve Stimulator:


Used to strictly assess patients paralytic state
TOF goal is 1-2/4
Putting it all Together
1. start BIS Monitoring
2. get a Baseline TOF on two locations
3. start Sedation and Analgesic Drips
4. titrate medication up until BIS 40-60
5. bolus paralytic
6. start paralytic drip
7. check TOF q30min until 1-2 twitches
8. monitor TOF and BIS and titrate drips to
endpoints
Final Thoughts
give sedation/analgesia before paralytics
BIS assess for sedation
TOF assess for adequate NMB
If in doubt it never hurts to ask!
References
 Gelinas C. Management of pain in cardiac surgery ICU
patients: have we improved over time? Intensive Crit Care
Nurs. 2007;23(5):298-303.
 Girard TD, Shintani AK, Jackson JC, et al. Risk factors for
post-traumatic stress disorder symptoms following critical
illness requiring mechanical ventilation: a prospective cohort
study. Crit Care. 2007;11(1):R28.
 Jacobi J, Fraser GL, Coursin DB, et al. Clinical practice
guidelines for the sustained use of sedatives and analgesics
in the critically ill adult. Crit Care Med. 2002;30(1):119-141.
 Pandharipande PP, Pun BT, Herr DL, et al. Effect of
sedation with dexmedetomidine vs lorazepam on acute
brain dysfunction in mechanically ventilated patients: the
MENDS randomized controlled trial. JAMA.
2007;298(22):2644-2653.