Sedation and Analgesia�(with a little bit on NMB)

Alexandra Wilson MD

Indications for sedation/analgesia

• Reduce anxiety and pain
• Motion control
• Decrease metabolic demands
• Decrease PVR
• Decrease ICP
• Improve synchrony with ventilator
• Decrease stress response

Mode of administration

IV BOLUS ADMINISTRATION

• Used for short term or low dose analgesia /sedation
• More nursing intensive
• Greater potential for breakthrough pain/anxiety

CONTINUOUS INFUSION

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• Utilized when prolonged analgesia and sedation needed
• Less labor intensive
• Better analgesia, initial bolus important
• Need for dedicated IV site if also have programmed boluses on pump

�Goals for procedural sedation/continuum of consciousness

Awake,

baseline

General

anesthesia

Minimal

sedation

Moderate

sedation

Deep

sedation

Level of sedation�Risk 🡺 🡺 🡺 🡺 🡺 🡺

Sedatives

Sedation goals in the ICU

• To produce a calm but responsive state
• Benefits- anxiolysis, amnesia, facilitation of care, safety, decreased metabolic demands
• Disadvantages- abstinence syndrome, prolonged ventilator course
• Unique situations: Pulm HTN, CHI, failing myocardium
• Need multidisciplinary discussion
• Goals need to be evaluated daily

COMMONLY USED DRUGS

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• α agonists
• Benzodiazepines
• Ketamine
• Propofol

Dexmedetomidate “Precedex”

• Highly selective alpha -2 agonist
• Sedative, anxiolytic, analgesic
• Dose load 0.5-1 mcg/kg
• +/-Initial bolus 0.5 – 1 mcg/kg over 15 min
• Infusion 0.2- 1 .5mcg/kg/hour
• Adverse rxn bradycardia ,hypotension, hypertension

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Benzodiazepines

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• Bind CNS GABA receptors
• Amnesia but no analgesia
• Antegrade and retrograde
• Anxiolysis
• Respiratory Depression
• Cardiac depression
• Paradoxical reactions approx 3.4%

Midazolam (Versed)

• advantages:
• Rapid onset/offset
• No pain with injection
• PO, IV, IM, IN dosing routes
• onset 1-5 min after IV administration, 45-60 min duration
• available reversal agent
• Flumazenil dose 10mcg/kg IV (max 0.2mg)

But… more affect on wakefulness than resp depression, seizure risk

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What sedation should you request

• Which procedures are correctly matched with appropriate level of sedation?

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1. Burn debridement for a 18 mo with 20% TBSA burns and deep sedation

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B. LP in septic 1yo (not intubated) and deep sedation

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C. Head MRI for a 11-mo and minimal sedation

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Midazolam

• Disadvantages
• Short half-life: continuous infusion
• Active metabolites watch in liver dysfunction
• Dosing
• 0.05-0.1 mg/kg IV/IM (max start 2mg then titrate)
• 0.5mg/kg po (max 10-15mg)
• 0.2mg/kg IN (max 10-15 mg)
• Gtt .05-0.1mg/kg/hr IV

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Lorazepam (ativan)

• advantages:
• Longer acting
• Onset 15-30 min IV
• Duration 8 hours
• No active metabolites-metabolized by glucoronyl transferase better in liver dysfunction

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Lorazepam (ativan)

• Disadvantages
• Slower onset /longer half-life
• Propylene glycol
• Dosing
• 0.05-0.1 mg/kg IV (max 2 mg may repeat)

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Ketamine

• Dissociative anesthetic
• Non competitive NMDA receptor antagonist: blocks glutamate
• results in amnesia,analgesia
• also adenergic and anticholinergic effects

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Ketamine

• Advantages
• provides both analgesia and amnesia
• preserves upper airway tone and reflexes
• causes bronchodilation
• Less cardiac depression

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Ketamine

• Disadvantages
• Previously thought to 🡹 ICP ¹

^{(class C evidence that does not)}

• Increase IOP
• Laryngospasm (low risk)
• Hypersecretory response
• Emergence phenomenon/agitation
• Dosing:
• 0.2-1mg/kg IV onset 30 sec can titrate
• Gtt 5-20mcg/kg/min

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^1.Ann Emerg Med. 2015 Jan;65(1):43-51.e2

PROPOFOL

• Sedative/hypnotic
• Rapid onset (20-50 seconds) easy to titrate
• Quick recovery
• Lack of active metabolites
• Metabolized in liver
• Excreted in urine

PROPOFOL

• Disadvantages
• Decreased sympathetic tone→ contraindicated in hemodynamically unstable
• Moderate respiratory depression
• Pain with injection/infusion site-lidocaine
• Reports of anaphylaxis contraindicated in pts with soybean oil, egg lecithin allergies?
• Metabolic acidosis reported with use > 24 hrs → Contraindicated for long term use

Etomidate

• Non Barbituate anesthetic agent
• Advantages
• Limited cardiovascular effects
• decreases ICP
• Disadvantages
• Pain
• Myoclonus
• Nausea /vomiting
• Adrenal suppression
• Dose 0.3mg/kg IV

Case 1

• 3 week old infant with respiratory failure
• What medications and what dosages would you choose to provide sedation/analgesia?

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A. propofol infusion 3mg/kg/hr

B. versed gtt @ 0.5mg/kg/hr and fentanyl at 1 mcg/kg/hr

C. Versed gtt @ .05 mg/kg/hr and fentanyl @ 1 mcg/kg/hr

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Case 2

• 9yo with 18% TBSA burns admitted yesterday
• VS HR 140 BP 110/50 RR 25
• You are asked to provide procedural sedation for burn debridment and dressing changes

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• What complication from sedation would you be concerned about in this patient?

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Case 2 continued

• You choose to sedate her with ketamine. When she awakens she is crying, disoriented and agitated What treatment might you consider?
• A. Zyprexa
• B. More ketamine
• C. Versed
• D. Morphine

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Analgesia �

What is Analgesia?

“Relief of the perception of pain without intentional production of a sedated state. Altered mental status may be a secondary effect of medications administered for this purpose.”

Local analgesia for procedures

• EMLA /LMX Cream
• Apply to intact skin with occlusive dressing 30-60 min prior to procedure
• Buffered Lidocaine
• (1 ml bicarb/9 ml 1% lidocaine)
• Maximum dose lidocaine (1%=10mg/ml)
• 4 mg/kg without epinephrine
• 7 mg/kg with epinephrine

i.e. 10kg child 4 x 10 /10 = 4cc lidocaine

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Analgesia: Opioids

• Provide analgesia and sedation, NOT amnesia
• Act similarly as a class
• Produce delayed gastric emptying, decreased intestinal peristalsis, and urinary retention
• Narcotic to be used:
• Morphine
• Fentanyl
• Hydromorphone (dilaudid)

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OPIOIDS

• ROUTE OF ADMINISTRATION
• IV
• Oral
• Transdermal
• MODE OF ADMINISTRATION
• Intermittent/on demand (as necessary)
• Fixed interval
• Continuous infusion
• PCA

Fentanyl

• Advantages
• 100x more potent than morphine
• shorter duration than morphine
• onset in 2-3 min, lasts 30-60 min
• less histamine release than morphine
• available reversal agent
• naloxone

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Fentanyl

• Disadvantages:

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• “Steel chest” or “rigid chest” phenomenon
• more likely with large bolus dose
• Treat with reversal of fentanyl or paralyzation

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Morphine

• Opioid
• Advantages
• longer acting analgesia
• Less expensive than fentanyl
• Disadvantages
• Histamine release - wheezing, hypotension
• Longer onset than other opioids

Hydromorphone “Dilaudid”

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• 5-7 x as potent as morphine
• Less histamine release

Tolerance

• The same dose of medication no longer has the same effect as when first started
• More commonly occurs in patients on long term continuous infusions of sedatives or analgesics rather than intermittent dosing

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Dependence not Addiction

• Removing medication results in withdrawal symptoms
• To avoid withdrawal, may need to wean sedative or analgesic
• Distinct from addiction

Withdrawal symptoms

Opioid

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Gastrointestinal (diarrhea, vomiting, feeding intolerance)

CNS: tremors, seizures, agitation, insomnia, yawning, sneezing), and sympathetic hyperactivity

Autonomic dysfunction: tachycardia, diaphoresis, hypertension, tachypnea, nasal stuffiness, hyperpyrexia

�Benzodiazepine

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CNS: agitation, restlessness, irritability, delirium, hallucinations, seizures

Sympathetic hyperactivity: tachycardia, hypertension, tachypnea, hyperpyrexia

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Withdrawal symptoms

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• Alpha-agonist: rebound hypertension, tachycardia, agitation, insomnia 

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Treatment Withdrawal

Opioid Methadone

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Precedex Ativan

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Versed Clonidine

narcotic and benzodiazepine weaning guidelines

• < 3 days: No taper necessary

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• 3-4 days: Discontinue infusion +/-wean gtt over 24-36 hours.

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• 5-13 days: Start a “short course” methadone/lorazepam wean. Start methadone and lorazepam 1-2 days prior to discontinuing infusions. Wean gtts 25% q 6hrs after 2 doses Wean methadone and lorazepam 20% q day

• ≥14 days: Start a “long course” methadone/lorazepam wean. Same as “ short course” but wean QOD.

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Alpha agonist withdrawal

http://intranet.seton.org/clinicalres/

pediatric_evidence-based_practice_guidelines/

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Neuromuscular Blockade

Achieves profound weakness of striated muscle without affecting the function of the cerebral cortex, smooth muscle or the myocardium.

Neuromuscular Blockade

• NEVER muscle relax a patient without assuring adequate sedation/analgesia beforehand.
• ALWAYS confirm the patient is easily hand-bag-ventilated prior to paralyzing

Muscle Relaxants

Depolarizing muscle relaxants

• Stimulate motor nerve endings
• Non-depolarizing muscle relaxants
• Compete at receptor site

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Monitoring�Muscle Relaxants

• Progression of weakness:
• small rapidly moving muscles of the fingers and eyes
• muscles of the neck, limbs and trunk
• muscles of respiration
• Recovery occurs in reverse order; the diaphragm recovers first

Monitoring�Muscle Relaxants

Nerve stimulators:

• Stimulate nerve causing contraction of the corresponding muscle.
• Train-of-four :

1 out of 4 twitches = 90% receptor blockade

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Muscle Relaxants�Depolarizing Agents

• Succinylcholine
• Imitates the affects of acetylcholine
• Initial fasciculations followed by paralysis
• Rapidly metabolized by pseudocholinesterase
• Quick onset/short duration

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Succinylcholine – adverse effects

• Bradycardia
• Hyperkalemia
• Increased intracranial and ocular pressure
• Muscle pains
• Malignant hyperthermia
• Rhabdomyolysis

Succinylcholine

• Contraindications
• Patients with hyperkalemia
• Patients with massive tissue destruction or CNS injury (muscle wasting, burns, trauma, myopathies, UMN disease)
• patients with a family history of malignant hyperthermia.

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Muscle Relaxants�Non-depolarizing Agents

• Competitively inhibit the binding of acetylcholine
• Most are steroid based

Non depolarizing NMB (steroid based)

Atracurium and Cisatracurium

• Non-depolarizing
• Short duration
• Best to use as continuous infusion
• Hofmann elimination
• Ideal agent in hepatorenal failure

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Case 3

• 9 mo with unknown neuromuscular disease presents with impending resp failure what meds do you want for intubation?

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• A. Fentanyl,versed and vecuronium
• B. Morphine,versed and vecuronium
• C. Fentanyl, versed and succinylcholine
• D. Fentanyl, ativan and vecuronium

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Case 4

• 5yo with myocarditis and a pericardial effusion what medication(s) would you choose for deep sedation for pericardialcentesis and why?
• A. Propofol
• B. Ketamine
• C. Dexmedetomidine
• D. Versed

Summary

• Determine sedation/analgesia goals
• Consider side effects
• Be aware of tolerance and withdrawal