1. Sedation & Paralytic Therapy in the ICU
Leanna R. Miller, RN, MN, CCRN-CSC, PCCN-CMC, CEN, CNRN, NP
Education Specialist
LRM Consulting
Nashville, TN

2. 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.

3. 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

4. Consciousness/Sedation
The Balance of Analgesia, Sedation, and Paralytics to promote comfort

5. 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)

6. 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

7. 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

8. 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

9. 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

10. Its essentially a maintenance therapy”
PAIN THERAPY - Myth
“One size fits all or
Set and forget therapy.
Its essentially a maintenance therapy”

11. 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.

12. 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

13. 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

14. 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.

15. 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)

16. Assessment of pain in ICU

18. 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

19. 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

20. Causes of Pain in the ICU?
Routine care: Suctioning, turning,
Surgical Incisions
Lines/Chest tubes

21. The Messengers of Pain Bradykinin, Prostaglandins, Cytokines Histamine
Direct tissue damage stimulates pain fibers
Local Inflammatory mediators
Bradykinin, Prostaglandins, Cytokines
Tissue Injury
Histamine
Serotonin
TNF

22. WHY IS THIS IMPORTANT?

23. Common Analgesic Drugs in the CVICU
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
min
Remifentanil
Plasma
.5 – 40 mcg/kg/h
<1 min
min
Dilaudid
.25 – 2 mg
min
min
2 - 3 hrs
Toradol
15 – 30 mg
Immediate
1 - 3 min
6 - 8 hrs

24. 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

25. 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

26. 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

27. 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

28. 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

29. Common Sedatives in the ICU
Drug
Dose
Onset
Peak
Duration
Ativan
Liver
.5 - 2mg
5 min.
60-90 min
6 - 8 hrs
Versed
1 - 2mg
min
Rapid
2 - 6 hrs
Propofol
Liver*
Starts at 25 mcg/kg/min
<40 sec.
3-5 min
min
Precedex
Plasma
.2-.7 mcg/kg/hr (3mcg/kg/hr)
min
30 min
min
Ketamine
2 – 7 mcg/kg/min
30 s
1 min
min

30. 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 mcg/kg/hr q30-45min
Can cause SEVERE bradycardia and hypotension
Very expensive!

31. 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

32. Assessment of Pain and Sedation

33. 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

34. RASS ASSESSMENT +4 Combative, violent, danger to self/staff
+3 Very agitated, pulls lines, tubes, aggressive
+2 Agitated frequent non-purposeful movement, fights the vent
+1 Restless / Anxious but not aggressive or vigorous
0 Alert and calm
-1 Drowsy, not fully alert but can stay awake, eyes open to voice for >10sec
-2 Light sedation, wake and makes eye contact for < 10 sec
-3 Moderate sedation, moves/opens eyes to voice but no eye contact
-4 Deep sedation, no response to voice but moves or opens eyes to physical stimulation
-5 Unarousable, no response to stimuli

35. BIS monitor

36. BIS Monitoring

37. BIS Monitor BIS monitor utilizes EEG waveforms.
reading is monitored from the patient’s forehead.
excessive muscle activity can interfere with EEG detection

38. 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

39. 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

40. BIS Placement Make sure the forehead is clean and dry!
Label the sensor with date/time
Replace sensor every 24 hours and PRN

41. 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.

42. BIS Monitoring

43. 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

44. 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?

45. 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

46. REMEMBER!
Look at the BIG PICTURE! Do Not Forget You are treating a patient not just the number

48. “Sedation Vacation” Assess for daily awakening Exclusions
Increased ICP
Neuromuscular blockade
Significant ventilation support
CABG, immediate post-op

49. “Sedation Vacation” Is patient awake and calm?
SAS 3 – 4
RASS 0 to -1
If no, restart ½ previous dose
If yes, proceed to spontaneous breathing trial (SBT)

50. “Sedation Vacation” Assess for SBT Calm & co-operative
Hemodynamically stable
PEEP < 8
FiO2 < 0.60
pH > 7.34
SpO2 > 90%

51. “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

52. “Sedation Vacation” Conduct SBT for 1 minute Mode CPAP PEEP = 0
least 5 – 10
FiO2 unchanged

53. 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!!!!

54. 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

55. 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

56. 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

57. Common CVICU Paralytics
Drug
Dose
Onset
Peak
Duration
Vecuronium
mg/kg
1 min
3-5 min
15-25 min
Pancuronium
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
2-5 min
25-44 min

58. 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
mck/kg/min

59. 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

60. 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?

61. Successful Paralysis: How do we know?
Assessment
Movement
Spontaneous Breaths
Peripheral Nerve Stimulator

62. 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

63. 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

64. 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

65. Train of Four: Ulnar Nerve

66. 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…

67. 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

68. Putting it all Together
start BIS Monitoring
get a Baseline TOF on two locations
start Sedation and Analgesic Drips
titrate medication up until BIS 40-60
bolus paralytic
start paralytic drip
check TOF q30min until 1-2 twitches
monitor TOF and BIS and titrate drips to endpoints

69. ***** 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.

70. Drugs that have amnesic effects
Benzodiazepine class
Examples:
Versed
Propofol (in high doses) dose will be individual to patient

71. 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

72. 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?

73. 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?

74. 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?

75. 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)

76. ReCap of Key Points Sedation: Analgesia: Paralytics:
Patient may still experience pain, goal is anti-anxiety/ – 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

77. ReCap of Key Points BIS Monitor: Peripheral Nerve Stimulator:
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

78. Putting it all Together
start BIS Monitoring
get a Baseline TOF on two locations
start Sedation and Analgesic Drips
titrate medication up until BIS 40-60
bolus paralytic
start paralytic drip
check TOF q30min until 1-2 twitches
monitor TOF and BIS and titrate drips to endpoints

79. Final Thoughts give sedation/analgesia before paralytics
BIS assess for sedation
TOF assess for adequate NMB
If in doubt it never hurts to ask!

80. References
Gelinas C. Management of pain in cardiac surgery ICU patients: have we improved over time? Intensive Crit Care Nurs. 2007;23(5):
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):
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):