Sedation, Analgesia, and Neuromuscular Sedation, Analgesia, and Neuromuscular Blockade in the Adult ICU Blockade in the Adult ICU Giuditta Angelini, MD Giuditta Angelini, MD University of Wisconsin Madison, WI Gil Fraser, PharmD, FCCM Gil Fraser, PharmD, FCCM Maine Medical Center Portland, ME Doug Coursin, MD, FCCM Doug Coursin, MD, FCCM University of Wisconsin Madison, WI
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Sedation, Analgesia, and Neuromuscular Blockade in the Adult ICU
Sedation, Analgesia, and Neuromuscular Blockade in the Adult ICU. Giuditta Angelini , MD University of Wisconsin Madison, WI Gil Fraser, PharmD , FCCM Maine Medical Center Portland, ME Doug Coursin , MD, FCCM University of Wisconsin Madison, WI. - PowerPoint PPT Presentation
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Sedation, Analgesia, and Neuromuscular Blockade in the Sedation, Analgesia, and Neuromuscular Blockade in the Adult ICU Adult ICU
Giuditta Angelini, MDGiuditta Angelini, MDUniversity of Wisconsin
Madison, WI
Gil Fraser, PharmD, FCCMGil Fraser, PharmD, FCCMMaine Medical Center
Portland, ME
Doug Coursin, MD, FCCMDoug Coursin, MD, FCCMUniversity of Wisconsin
Madison, WI
What We Know About ICU Agitation/DiscomfortWhat We Know About ICU Agitation/Discomfort
Prevalence• 50% incidence in those with length of stay > 24 hours
Primary causes: unrelieved pain, delirium, anxiety, sleep deprivation, etc.
• Lack of respiratory depression• Analgesia, especially for surgical patients• Rapid onset, titratable, with a short elimination
half-time• Sedation with ease of orientation and
arousability• Anxiolytic• Hemodynamic stability
Characteristics of an ideal sedation agents for the ICU
The Challenges of ICU Sedation
• Assessment of sedation• Altered pharmacology• Tolerance• Delayed emergence• Withdrawal• Drug interaction
Sedation
SedativesCauses for Agitation
Undersedation
Sedatives
Causes for AgitationAgitation & anxietyPain and discomfortCatheter displacementInadequate ventilationHypertensionTachycardiaArrhythmiasMyocardial ischemiaWound disruptionPatient injury
Oversedation
Sedatives
Causes for Agitation
Prolonged sedationDelayed emergenceRespiratory depressionHypotensionBradycardiaIncreased protein breakdownMuscle atrophyVenous stasisPressure injuryLoss of patient-staff interactionIncreased cost
• Full bladder• Uncomfortable bed position• Inadequate ventilator flow rates• Mental illness• Uremia• Drug side effects• Disorientation• Sleep deprivation• Noise• Inability to communicate
Correctable Causes of Agitation
Causes of Agitation Not to be Overlooked
• Hypoxia• Hypercarbia• Hypoglycemia• Endotracheal tube malposition• Pneumothorax• Myocardial ischemia• Abdominal pain• Drug and alcohol withdrawal
Sedation needs to be protocolized and titrated to goal:• Lighten sedation to appropriate wakefulness daily.
Effect of this strategy on outcomes:• One- to seven-day reduction in length of sedation and mechanical
ventilation needs
• 50% reduction in tracheostomies
• Three-fold reduction in the need for diagnostic evaluation of CNS
Daily Goal is Arousable, Comfortable SedationDaily Goal is Arousable, Comfortable Sedation
SCCM practice guidelines can be used as a template for institution-specific protocols.
Titration of sedatives and analgesics guided by assessment tools:• Validated sedation assessment tools (Ramsay Sedation Scale [RSS],
Use Non-pharmacologic Treament,Optimize the Environment
ALGORITHM FOR SEDATION AND ANALGESIA OF MECHANICALLY VENTILATED PATIENTS
Use Pain Scale * toAssess for Pain
Use Sedation Scale **
to Assess forAgitation/Anxiety
Use Delirium Scale *** toAssess for Delirium
Is the Patient Comfortable & at Goal?
Lorazepam viainfusion?
Use a low rate and IVPloading doses
1
2
3
4
Jacobi J, Fraser GL, Coursin D, et al. Crit Care Med. 2002;30:119-141.
Pain
Assess Pain Separately
Visual Pain Scales
0 1 2 3 4 5 6 7 8 9 10
No pain Worst possible pain
Signs of Pain
• Hypertension
• Tachycardia
• Lacrimation
• Sweating
• Pupillary dilation
Principles of Pain Management
• Anticipate pain• Recognize pain
– Ask the patient– Look for signs– Find the source
• Quantify pain • Treat:
– Quantify the patient’s perception of pain– Correct the cause where possible– Give appropriate analgesics regularly as required
• Remember, most sedative agents do not provide analgesia• Reassess
Nonpharmacologic Interventions
• Proper position of the patient
• Stabilization of fractures
• Elimination of irritating stimulation
• Proper positioning of the ventilator tubing to avoid traction on endotracheal tube
Address PainAddress Pain
Set G oalfor
Analgesia
Hem odynam ically UnstableFentanyl 25 - 100 m cg IVP Q 5-15 m in, orHydromorphone 0.25 - 0.75 m g IVP Q 5 - 15 m in
Hem odynam ically stableMorphine 2 - 5 m g IVP Q 5 - 15 m in
Repeat until pain controlled, then scheduled doses + prn
Use Pain Scale * toAssess for Pain
Reassess goal daily,T itrate and taper therapy to m aintain goal,Consider daily wake-up,Taper if > 1 week high-dose therapy & m onitorfor withdrawal
Is the Patient Com fortable & at Goal?
OpiatesOpiates
Benefits• Relieve pain or the sensibility to noxious stimuli
• Sedation trending toward a change in sensorium, especially with more lipid soluble forms including morphine and hydromorphone.
Risks• Respiratory depression
• NO amnesia
• Pruritus
• Ileus
• Urinary retention
• Histamine release causing venodilation predominantly from morphine
• Morphine metabolites which accumulate in renal failure can be analgesic and anti-analgesic.
• Meperidine should be avoided due to neurotoxic metabolites which accumulate, especially in renal failure, but also produces more sensorium changes and less analgesia than other opioids.
Agent Dose (iv)
Half-life Metabolic pathway
Active metabolites
Fentanyl 200 g 1.5-6 hr Oxidation None
Hydromorphone 1.5 mg 2-3 hr Glucuronidation None
Morphine 10 mg 3-7 hr Glucuronidation Yes (Sedation in RF)
BMJ 1974;2:656-659Crit Care Med 1999;27:1325-1329J Clin Psychopharmacol 1990;10:244-251Crit Care Med 1999;27:1271-1275
Scale Description
1 Anxious and agitated or restless, or both
2 Cooperative, oriented, and tranquil
3 Response to commands only
4 Brisk response to light glabellar tap or loud auditory stimulus
5 Sluggish response to light glabellar tap or loud auditory stimulus
6 No response to light glabellar tap or loud auditory stimulus
The Ramsay Scale
Score Description Definition
7 Dangerous agitation
Pulling at endotracheal tube, trying to strike at staff, thrashing side to side
6 Very agitated Does not calm despite frequent verbal commands, biting ETT
5 Agitated Anxious or mildly agitated, attempting to sit
4 Calm and cooperative
Calm, awakens easily, follows commands
3 Sedated Difficult to arouse, awakens to verbal stimuli, follows simple commands
2 Very sedated Arouse to physical stimuli, but does not communicate spontaneously
1 Unarousable Minimal or no response to noxious stimuli
The Riker Sedation-Agitation Scale
The Motor Activity Assessment Scale
Score Description Definition
6 Dangerous agitation
Pulling at endotracheal tube, trying to strike at staff, thrashing side to side
5 Agitated Does not calm despite frequent verbal commands, biting ETT
4 Restless and cooperative
Anxious or mildly agitated, attempting to sit
3 Calm and cooperative
Calm, awakens easily, follows commands
2 Responsive to touch or name
Opens eyes or raises eyebrows or turns head when touched or name is loudly spoken
1 Responsive only to noxious stimuli
Opens eyes or raises eyebrows or turns head with noxious stimuli
0 Unresponsive Does not move with noxious stimuli
What Sedation Scales Do
• Provide a semiquantitative “score”• Standardize treatment endpoints• Allow review of efficacy of sedation• Facilitate sedation studies• Help to avoid oversedation
What Sedation Scales Don’t Do
• Assess anxiety
• Assess pain
• Assess sedation in paralyzed patients
• Predict outcome
• Agree with each other
BIS Monitoring
BIS Monitoring
BIS Range Guidelines
Awake
Responds to loud commands or mild prodding/shaking
Low probability to explicit recallsUnresponsive to verbal stimuli
Burst suppression
Flat line EEG
Responds to normal voice Axiolysis
Moderatesedation
Deep Sedation
100
80
60
40
20
0
BIS
Set G oalfor
Sedation
Acute Agitation #
Midazolam 2 - 5 m g IVP Q 5 - 15 m in untilacute event controlled
Ongoing Sedation #
Lorazepam 1 - 4 m g IVP Q 10-20 m in untilat goal then Q 2 - 6 hr scheduled + prn, orPropofol start 5 m cg/kg/m in, titrate Q 5 m inuntil at goal
IVP Dosesm ore often than Q
2hr?
Consider continuousinfusion opiate or
sedative
> 3 Days Propofol?(except neuro pt.)
Convert toLorazepam
Benzodiazepine or Opioid:Taper Infusion Rate by
10-25% Per Day
Use Sedation Scale **
to Assess forAgitation/Anxiety
Lorazepam viainfusion?
Use a low rate and IVPloading doses
Yes
Reassess goal daily,T itrate and taper therapy to m aintain goal,Consider daily wake-up,Taper if > 1 week high-dose therapy & m onitorfor withdrawal
Enhanced effects on both positive (agitation) and negative (quiet) symptoms
Efficacy = haloperidol?• One prospective randomized study showing equal efficacy of olanzapine
to haldol with less EPS
Issues• Lack of available IV formulation
• Troublesome reports of CVAs, hyperglycemia, NMS
• Titratability hampered- QTc prolongation with ziprasidone IM
- Hypotension with olanzapine IM
Neuromuscular Blockade (NMB) (Paralytics) in the Adult ICUNeuromuscular Blockade (NMB) (Paralytics) in the Adult ICU
Used most often acutely (single dose) to facilitate intubation or selected procedures
Issues• NO ANALGESIC or SEDATIVE properties
• Concurrent sedation with amnestic effect is paramount analgesic as needed
• Never use without the ability to establish and/or maintain a definitive airway with ventilation
• If administering for prolonged period (> 6 - 12 hours), use an objective monitor to assess degree of paralysis.
Neuromuscular Blockade in the ICUNeuromuscular Blockade in the ICU
Current use in ICU limited because of risk of prolonged weakness and other complications• Maximize sedative/analgesic infusions as much as possible prior to
adding neuromuscular blockade
Indications• Facilitate mechanical ventilation, especially with abdominal
compartment syndrome, high airway pressures, and dyssynchrony
• Assist in control of elevated intracranial pressures
• Reduce oxygen consumption
• Prevent muscle spasm in neuroleptic malignant syndrome, tetanus, etc.
• Protect surgical wounds or medical device placement
- Prolonged binding to acetylcholine receptor to produce depolarization (fasciculations) and subsequent desensitization so that the motor endplate cannot respond to further stimulation right away
• Nondepolarizers- Blocks acetylcholine from postsynaptic receptor competitively
Quick Onset Muscle Relaxants for IntubationQuick Onset Muscle Relaxants for Intubation
Patients with aspiration risk need rapid onset paralysis for intubation.
Not usually used for continuous maintenance infusions
Rocuronium• Nondepolarizer with about an hour duration and 10% renal elimination
• Dose is 1.2 mg/kg to have intubating conditions in 45 seconds
Succinylcholine• Depolarizer with a usual duration of 10 minutes
• All or none train of four after administration due to desensitization (can be prolonged in patients with abnormal plasma cholinesterase)
• Dose is 1 - 2 mg/kg to have intubating conditions in 30 seconds
Potential Contraindications of SuccinylcholinePotential Contraindications of Succinylcholine
Increases serum potassium by 0.5 to 1 meq/liter in all patients
Can cause bradycardia, anaphylaxis, and muscle pain
Potentially increases intragastric, intraocular, and intracranial pressure
Severely elevates potassium due to proliferation of extrajunctional receptors in patients with denervation injury, stroke, trauma, or burns of more than 24 hours
Other distinguishing features• Pancuronium causes tachycardia
• Vecuronium has neutral effects on hemodynamics but has several renally excreted active metabolites
• Elimination of cisatracurium is not affected by organ dysfunction, but it is expensive
Monitoring NMBAsMonitoring NMBAs
Goal - To prevent prolonged weakness associated with excessive NMBA administration
Methods:• Perform NMBA dose reduction or cessation once daily if possible
• Clinical evaluation: Assess skeletal muscle movement and respiratory effort
• Peripheral nerve stimulation - Train of four response consists of four stimulae of 2 Hz, 0.2 msec in
duration, and 500 msec apart.
- Comparison of T4 (4th twitch) and T1 with a fade in strength means that 75% of receptors are blocked.
- Only T1 or T1 and 2 is used for goal in ICU and indicates up to 90% of receptors are blocked.
Monitoring Sedation During ParalysisMonitoring Sedation During Paralysis
Bispectral index is based on cumulative observation of a large number of clinical cases correlating clinical signs with EEG signals.
While used to titrate appropriate sedation (and amnesia) in anesthetized patients to the least amount required, not proven to achieve this goal.
Increased potential for baseline neurologic deficit and EEG interference in ICU patients
No randomized controlled studies to support reliable use in ICU.
Other neuromonitoring (awareness) modalities are likely to be developed.
Cessation of NMB as soon as safe in conjunction with other patient parameters should be a daily consideration.
Complications of Neuromuscular Blocking AgentsComplications of Neuromuscular Blocking Agents
Associated with inactivity:• Muscle wasting, deconditioning, decubitus ulcers, corneal drying
Associated with inability to assess patient:• Recall, unrelieved pain, acute neurologic event, anxiety
Associated with loss of respiratory function:• Asphyxiation from ventilator malfunction or accidental extubation,
atelectasis, pneumonia
Other:• Prolonged paralysis or acute NMBA related myopathy
- Related to decreased membrane excitability or even muscle necrosis
- Risk can be compounded by concurrent use of steroids.
Sample NMBA ProtocolSample NMBA Protocol
ReferencesReferences
Jacobi J, et al. Crit Care Med. 2002;30:119-141.
Jones, et al. Crit Care Med. 2001;29:573-580.
Cammarano, et al. Crit Care Med. 1998;26:676.
Ely, et al. JAMA. 2004;292:168.
Case Scenario #1Case Scenario #1
22-year-old male with isolated closed head injury who was intubated for GCS of 7
He received 5 mg of morphine, 40 mg of etomidate, and 100 mg of succinylcholine for his intubation.
He is covered in blood spurting from an arterial catheter that was just removed, and he appears to be reaching for his endotracheal tube.
What sedative would you use and why?
What are the particular advantages in this situation?
How could you avoid the disadvantages of this drug?
Case Scenario #1 - AnswerCase Scenario #1 - Answer
Propofol will rapidly calm a patient who is displaying dangerous behavior without need for paralysis.
Titratable and can be weaned quickly to allow for neurologic exam
Can treat seizures and elevated ICP which may be present in a head trauma with GCS of eight or less
Minimizing dose and duration will avoid side effects.
Case Scenario #2Case Scenario #2
54-year-old alcoholic who has been admitted for Staph sepsis
Intubated in the ICU for seven days and is currently on midazolam at 10 mg/hour
His nurse was told in report that he was a “madman” on the evening shift.
Currently, he opens his eyes occasionally to voice but does not follow commands nor does he move his extremities to deep painful stimulation.
Is this appropriate sedation?
What would you like to do?
How would you institute your plan of action?
Case Scenario #2 - AnswerCase Scenario #2 - Answer
This patient is oversedated. Not only can a neurologic exam not be performed, but it would be unlikely to be able to perform a wakeup test within one 24-hour period.
Given the need to examine the patient, midazolam should be stopped immediately.
Rescue sedatives including midazolam should be available if agitation develops.
Flumazenil should be avoided.
Case Scenario #3Case Scenario #3
62-year-old, 65-kg woman with ARDS from aspiration pneumonia
Her ventilator settings are PRVC 400, RR 18, PEEP 8, and FIO2 100%. She is dyssynchronous with the ventilator and her plateau pressure is 37 mm Hg.
She is on propofol at 50 mcg/kg/min, which has been ongoing since admit four days ago.
She is also on norepinephrine 0.1 mcg/kg/min and she was just started on steroids.
What do you want to do next?
Do you want to continue the propofol?
Why or why not?
What two iatrogenic problems is she likely at risk for?
Case Scenario #3 - AnswerCase Scenario #3 - Answer
This patient needs optimization of her sedatives, and potentially chemical paralysis to avoid complications of ventilator dyssynchrony and high airway pressures.
If you continue to use propofol, higher doses are required and the patient is already on norepinephrine. In addition, if paralysis is used, you do not have reliable amnesia.
She is at risk for propofol infusion syndrome and critical illness polyneuropathy.
Withdrawal
• Withdrawal from preoperative drugs
• Sudden cessation of sedation– Return of underlying agitation