sedation neuromuscular blockade
Download
Skip this Video
Download Presentation
SEDATION & NEUROMUSCULAR BLOCKADE

Loading in 2 Seconds...

play fullscreen
1 / 58

SEDATION & NEUROMUSCULAR BLOCKADE - PowerPoint PPT Presentation


  • 132 Views
  • Uploaded on

SEDATION & NEUROMUSCULAR BLOCKADE. Pediatric Critical Care Medicine Emory University Children’s Healthcare of Atlanta. Objectives. Definition Signs & Symptoms Categories Shock physiology Treatments. Myths. Children don’t feel pain/anxiety; underestimation of pain

loader
I am the owner, or an agent authorized to act on behalf of the owner, of the copyrighted work described.
capcha
Download Presentation

PowerPoint Slideshow about ' SEDATION & NEUROMUSCULAR BLOCKADE ' - urian


An Image/Link below is provided (as is) to download presentation

Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.


- - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - -
Presentation Transcript
sedation neuromuscular blockade

SEDATION & NEUROMUSCULAR BLOCKADE

Pediatric Critical Care Medicine

Emory University

Children’s Healthcare of Atlanta

objectives
Objectives
  • Definition
  • Signs & Symptoms
  • Categories
  • Shock physiology
  • Treatments
myths
Myths
  • Children don’t feel pain/anxiety; underestimation of pain
  • Masking symptoms of progressing injury
  • Side effects: respiratory depression & cardiovascular compromise
  • Addiction
truths pain
Truths - Pain
  • Pathophysiology of pain

Tissue damage  release local mediators (bradykinin, substance P, prostoglandins, K+)  heighten nociception  facilitate the communication of painful sensations to the spinal cord & brain

Tissue injury  release of histamine & serotonin  increase pain sensitivity in areas surrounding the site of initial injury

truths pain1
Truths - Pain
  • All nerve pathways for the conduction of painful stimuli & awareness of pain are functional by 24 wk EGA
  • Failure to manage painful stimuli increases perception of pain for future painful events
  • Lack of pain control increases the stress responses
      • Simons SH, van Dijk M. van Lingen RA et al: Randomized controlled trial evaluation effects of morphine on plasma adrenaline/noradrenaline concentration in newborns. Arch. Dis Child Fetal Neonatal Ed. 2005; 90: F36-F40
truths side effects
Truths – Side Effects
  • Respiratory & hemodynamic compromises
    • Potentiates with combination with other sedatives & analgesics
    • Understanding the pharmacokinetics and effects of these agents
truths addiction
Truths - Addiction
  • Definitions:
    • Addiction
    • Tolerance
    • Dependence
  • Dependence:
    • 1/3 pts who received tx>4wks
    • Continuous infusion: tolerance develops within days
      • Riss, J.; Cloyd, J.; Gates, J.; Collins, S. (Aug 2008). "Benzodiazepines in epilepsy: pharmacology and pharmacokinetics.". Acta Neurol Scand118 (2): 69–86. doi:10.1111/j.1600-0404.2008.01004
  • Risk factors:
    • Dependent personality
    • Short acting benzo
    • Long-term use of benzo
sedation a continuum
Sedation – A Continuum
  • Analgesia
  • Minimal sedation
  • Moderate sedation
  • Deep sedation
  • General anesthesia
sedation a continuum1
Sedation – A Continuum
  • Awake/ Drowsy/ Gen. Anest.
  • Baseline Anxiolysis
  • Moderate Deep
  • sedation sedation
sedation measurement tools
Sedation Measurement Tools
  • Modified Ramsey Score
    • 0 – unresponsive
    • 1 – responsive to noxious stimuli
    • 2 – responsive to touch or name
    • 3 – calm & cooperative
    • 4 – restless & cooperative
    • 5 – agitated
    • 6 – dangerously agitated & uncooperative
sedation measurement tools1
Sedation Measurement Tools
  • Bispectral Index (Bis)
    • Measure level of consciousness by algorithmic analysis of EEG
    • Scale 0 (silent EEG) to 100 (fully awake)
    • Good tools to use for deep sedation/anesthesia, doesn’t differentiate level of consciousness for moderate to deep sedation
          • Mason KP et all: Value of bispectral index monitor in defferentiating between moderate and deep Ramsay Sedation Scores in children. Paediatr Anaesth. 2006 Dec; 16 (12):1226-31
sedative hypnotic
Sedative - Hypnotic
  • Sedation, motion control, and anxiolysis
  • NO analgesia
  • Classes
    • Benzodiazepines
    • Barbiturates
    • Chloral hydrate
    • Diprivan
    • α –adrenergic agonists
sedation neurotransmitters
Sedation Neurotransmitters
  • GABA: inhibitory neurotransmitter in the brain
  • Glycin: inhibitory neurotransmitter in the spinal cord & brain stem
  • Glutamate: excitatory receptors
sedation benzodiazepines
Sedation - Benzodiazepines
  • Augment GABA & glycin transmission  binding to receptors  influx Cl-  hyper-polarization  resistance to neuronal excitation
  • BZD bind to receptor complex  enhance GABA binding to its receptors  increase in GABA efficiency
  • BZD increase the frequency of Cl- channel opening  increase GABA potency
sedation benzodiazepines1
Sedation - Benzodiazepines
  • Effects: anxiolytic, amnestic, anti-convulsant, hypnotic, sedative, skeletal muscle relaxant
  • Decrease CMRO2 & CBF
  • Impair anterograde amnesia,
  • Affect ventilatory response to both hypoxia & hypercapnea
  • Potentiate effect with alcohol & narcotics
  • Decrease both pre & after-load  decrease MAP with min effect on CO
sedation benzodiazepines2
Sedation - Benzodiazepines
  • Tolerance involves GABAA receptor
    • Down regulation
    • Alterations to the subunit configuration
    • Uncoupling & internalizing of the BZD binding site
    • Change in gene expression
  • Others
    • Paradoxical reaction – disinbition usually in children or older adults with h/o alcohol abuse or ones with underlying aggressive behavior
    • Rebound insomnia & anxiety after only 7 days
    • Long lasting memory deficit with long term use
    • Worsening of depression
sedation benzodiazepines3
Sedation - Benzodiazepines
  • Withdrawal syndrome
    • Anxiety, insomnia, nightmares, seizures, psychosis, hyper-reflexia
    • Post midazolam infusion phenomenon
    • Slow tapering to decrease withdrawal
bzd midazolam
BZD - Midazolam
  • Most commonly used sedative
  • Water soluble (less thrombophlebitis)  less pain with injection
  • IV, IM, PO, IN, PR, Buccal
  • Metabolized by P450 (CYP) enzymes & by glucuronide conjugation
  • Side effects:
    • Post midazolam infusion phenomenon
    • A “midazolam infusion syndrome”: delayed arousal hrs to days after discontinuation, associated with high dose infusion
    • “Hang over”: psychomotor & cognitive function impairment to the next day
bzd lorazepam
BZD - Lorazepam
  • Highly protein bound, extensively metabolized into inactive forms
  • Lipophobic  confine in the vascular space
  • IV, IM, PO, SL
  • Solvent: polyethylene & propylene glycol hyperosmolar metabolic acidosis with prolonged infusion
  • Injectable solution contains benzyl alcohol
  • Uses:
    • Status epilepticus
    • Alcohol withdrawal syndrome, catatonia
    • Anti-emetic
bzd diazepam
BZD - Diazepam
  • IV, IM, PO (100% bio-availability), PR (90%)
  • Highly protein bound, cross BBB & placenta, excrete in stools
  • Lipophilic  evenly distributed  accumulative effect with repeat doses
  • High risk of thrombophlebitis, pain with injection
  • P450 + glucuronidation in liver long t ½ metabolite
  • Uses: anxiety, insomia, seizure, muscle spasm, restless leg syndrome, alcohol and BZD withdrawal
sedation barbiburates
Sedation - Barbiburates
  • GABAA receptor (different from BZD)  increases duration of Cl- channel opening  increases GAGA efficacy
  • Block AMPA receptor (glutamate subtype)
  • Decrease CMRO2 & CBF
  • Side effects: myocardial depression, hypotension
  • Effects: CNS depressants (mild sedation  anesthesia); anxiolytic, hypnotic, anti-convulsants (except Methohexital)
  • Uses:
    • Surgical anesthesia
    • Delirium tremens
    • Seizures
    • Insomnia
sedation chloral hydrate
Sedation - Chloral Hydrate
  • Sedative & hypnotic: short term use for insomnia
  • Enhance GABA receptor complex
  • Tolerance with long term use
  • Overdose: N/V, convulsion, confusion, irregular breathing, arrhythmias, coma
    • SV, junctional or ventricular arrhythmias including torsades de pointes
  • Side effects: rash, gastric discomfort, myocardial depression, hepatic failure
    • Hyperbilirubinemia: displace bilirubin from albumin sites
slide25

Sedation - Chloral Hydrate

Alcohol

dehydrogenase

Chloral Hydrate

Trichloroethanol (TCE)

T ½ 8-12hr

45% protein bound

30-60 min peak

Glucuronidation

Trichloroacetate (TCA)

T ½ 67 hrs

Inc. 3-4X in neonates

Displace bili from albumin

CNS depression

sedation diprivan
Sedation - Diprivan
  • 10% soybean oil, 2.25% glycerol, 1.2% egg phosphatide
  • Protein bound; metabolized by conjugation in liver + extra hepatic elimination
  • Potentiate GABAA receptor activity  slow the closing of the Cl-channels
  • Rapid distribution to peripheral tissue  ultra short effects
  • T ½ 2-24 hrs
sedation diprivan1
Sedation - Diprivan
  • Adverse effects:
    • Pain with injection, pro-bacterial growth, produce green urine
    • Negative inotrope, potent vasodilitation, bradycardia
    • Potent respiratory depressant
    • Deplete trace element (Zinc) in prolonged infusion
    • “Propofol infusion syndrome”
    • “Gasping syndrome”
sedation adrenergic agonists
Sedation - α-adrenergic Agonists
  • α-1 agonist: stimulates phospholipase C activity
    • Vasoconstriction, mydriasis
    • Use a vasopressrs, nasal decongestants, eye exam
  • α-2 agonist: inhibits adenylyl cyclase activity
    • Reduce brainstem vasomotor center-mediated CNS activation
    • Use: anti-hypertensive, sedative, opiate & alcohol withdraw
    • α-2a: sedation, sleep, analgesia, sympatholysis
    • α-2b: vasoconstriction, anti-shivering, endogenous analgesia
sedation adrenergic agonists1
Sedation - α-adrenergic Agonists
  • Clonidine: α-2: α-1 = 200:1
    • Large volume of distribution, long T½ 12-24 hrs
    • Acts on receptors in the locus coeruleus (stress & panic)
    • Prevent pre-synaptic release of NE in the sympathetic nervous system  anti-hypertensive
    • Acts on peripheral α-2  vasoconstriction
  • Dexmetomidine: α-2: α-1 = 1600:1
    • T½ 1.5-3 hrs, ½ excrete unchanged in urine
    • Min respiratory depression, sedated yet easily aroused
    • Highly lipophilic, cross BBB
    • Effective in CV symptoms for cocaine intoxication
    • Reduce sympathetic activity  decrease HR & BP
    • Rapid infusion  hypertension due to activation of α-1
sedation ketamine
Sedation - Ketamine
  • Dissociate anesthesia (similar in structure of PCP)  hallucigenic, analgesic, amnestic
  • NMDA (glutamate) antagonist  analgesic;
  • Binds to opioid receptors (μ & sigma) in high dose
  • Increases catecholamines release & cholinergic receptor stimulation  bronchodilator, mucous production, increase SVR, HR, CO
  • Increasse CBF & CRMO2
  • Metabolized to Norketamine to excrete in urine
analgesia
Analgesia
  • Oucher Scale by Judy Beyer, modified by Wong: self report with faces & numerical pain scale
  • Pain physiological responses – observational pain scale (OPS)
    • HR & BP
    • Measuring level of adrenal stress hormone
  • COMFORT score:
    • Behaviors: alertness, facial tension, muscle tone, agitation, movement
    • Physiologic responses: HR, respiration, BP
analgesia1
Analgesia
  • Anti-pyretic & non-opioid
  • Opiod
  • Methadone
analgesia antipyretic or non opioid
Analgesia – Antipyretic or Non-opioid
  • Cyclo-oxygenase (COX) 1,2,3: inhibit prostaglandins production (peripheral & central)
    • Cox 1:protective prostaglandins  preserve gastric lining integrity; maintain normal renal function
    • Cox 2: inducible by pro-inflammatory cytokines & growth factors; in both brain & spinal cord: nerve transmission for pain & fever
  • Useful for inflammatory processes (bony or rheumatic)
analgesia antipyretic or non opioid1
Analgesia – Antipyretic or Non-opioid
  • Aspirin:
    • Alter platelet function; can cause gastric irritant
  • Ketorolac
    • Platelet dysfuncion  serious risk of GI bleeding
  • Trilisate (choline magnesium trisalicylate; ASA like compound)
    • No SE on platelet
    • Use in post-op pain or cancer patients
  • Paracetamone
    • Central Cox 3, no anti-inflammatory activity
  • Naproxen
    • Cox 1 inhibitor
analgesia opioids
Analgesia - Opioids
  • Terms:
    • Agonist
    • Antagonist
    • Partial agonist
  • Receptors: µΚδσ
    • Inhibit synaptic transmission in CNS and myenteric plexus
    • Found in pre-synaptic, decrease release of excitatory neurotransmitter for nociceptive stimuli
    • Coupling with G-protein, regulate trans-membrane signaling by regulate cAMP
analgesia morphine
Analgesia – Morphine
  • µ2 agonist: analgesia, sedation, euphoria, resp. depression
  • K and δ agonist: spinal analgesia, miosis, psychomimetic effects
  • Glucuronide metabolism  M3G (exrete) & M6G (active metabolites)
  • Poor lipid solubility, protein binding
  • SQ, IV, IT, epidural
analgesia morphine1
Analgesia – Morphine
  • Increase in sensory threshold for pain
  • Respiratory depression: decrease RR, MV & response to CO2
  • Miosis: pupillary constriction via oculomotor nucleus
  • Decrease stress hormones: ACTH, ADH, prolactin, GH & epi
  • Uncertain response to N/V: act on chemo-trigger zone + depress vomiting center
  • Smooth muscle relaxation: directly or via vagus nerve
  • Increase biliary tract tone  biliary colic
  • Urinary retention via increase tone in bladder detrusor muscle or vesical sphincter
  • Histamine release  bronchospasm or CV collapse
analgesia fentanyl
Analgesia - Fentanyl
  • 100X >morphine
  • Strong agonist at the µ and K
  • Lipophilic: cross BBB  rapid onset with short duration 2/2 rapid redistribution
  • Block systemic & pulmonary hemodynamic effect of pain
  • Prevent biochemical & endocrine stress (catabolic)
  • Adverse effects: N/V, constipation, dry mouth, somnolence, confusion, anesthesia (weakness), sweating

Severe AE: glottic & chest wall rigidity with rapid infusion (>5mcg/kg)

analgesia other fentanyls
Analgesia – Other Fentanyls
  • Sufentanil
    • 5-10x > Fentanyl, most potent opioid in clinical practice
    • Smaller volume of distribution, faster recovery after prolonged infusion
  • Alfentanil
    • 5x < Fentanyl, short duration 5-10 min
    • Useful for RSI with ICP
  • Remifentanil
    • Metabolized by plasma esterase with short t ½
    • Potent µ with mild K & δ effects, potent respiratory depression, no histamine release
    • Similar kinetics in neonates & adults
    • Very expensive
analgesia other opioids
Analgesia – Other Opioids
  • Meperidine
    • K receptor agonist; strong opioidergic, anticholinergic and antispasmodic; Local anesthetic properties – surgical spinal analgesia
    • Superior to Morphine for billiary spasm or renal colic
    • Metabolized to normeperidine - twice as toxic
    • “Serotonin syndrome” with CNS excitatory effects: tremors, ms spasm, myoclonus, psychiatric changes & seizure
    • Interact with MAOIs  agitation, delirium, headache, convulsions, hyperthermia (Libby Zion Law)
    • Contraindicated in liver, kidney disease, seizure disorder, enlarged prostate or urinary retention, hypothyroidism, asthma, Addison’s disease.
analgesia other opioids1
Analgesia – Other Opioids
  • Codein
    • Methylmorphine: analgesic, anti-tussive, anti-diarrheal
    • Alkaloid found in opium poppy (papaveraceae)
    • Convert to morphine in the liver by P450 and to active metabolites
    • Prolonged use  physical dependence & psychologically addictive; mild withdrawal symptoms
    • Preserve pupillary signs
analgesia other opioids2
Analgesia – Other Opioids
  • Tramadol (Ultram, Tramal)
    • Weak µ agonist, release serotonin, inhibits reuptake of norepinephrine
    • Therapy for most neuralgia and chronic pain
    • Hard to wean due to effects on opioid, serotonin/NE activity
    • Decrease seizure threshold
  • Hydromorphone (Dilaudid)
    • Centrally acting opioid class on µ receptor, 8x > morphine
    • Water soluble with quick onset
    • Lack of toxic metabolite, lower dependency, less nausea
    • Brief but intense withdrawal
analgesia opioid antagonist
Analgesia – Opioid Antagonist
  • Naloxone
    • Competitive antagonist with high affinity for µ receptor in CNS  rapid onset of withdrawal
    • IV with fast onset of action; T½ 30-81 min
analgesia other
Analgesia – Other
  • Methadone
    • Acts on opioid receptors without the euphoric effects  prevent narcotic withdrawal syndrome
    • Binds on NMDA (N-methyl-D-aspartate) antagonist against glutamate  decrease craving for opioids & tolerance
analgesia withdrawal
Analgesia – Withdrawal
  • Neurologic excitability: Sleep disturbances, agitation, tremors, seizures, choreoartheroid movements
  • GI disturbances: V/D
  • Autonomic dysfunction: hypertension, tachycardia, tachypnea, fever, frequent yawning, sweating or goose flesh,
neuromuscular blockade
Neuromuscular Blockade
  • Large highly charged water - soluble molecules at physiologic pH can’t cross BBB, placenta, GI
  • Onset is more rapid & less intense at the laryngeal muscle (vocal cord) & peripheral muscle
  • Diaphragm is the most resistant to paralysis
neuromuscular blockade1
Neuromuscular Blockade
  • Types
    • Depolarizing: mimic action of acetylcholine
    • Non-depolarizing: competitively block ACH receptors
  • Classifications
    • Short: succinylcholine, mivacurium
    • Intermediate: atracurium, vecuronium, rocuronium, cisatracurium
    • Long: pancuronium, doxacurium, pipecuronium
nmb depolarizing
NMB: Depolarizing
  • Succinylcholine
    • Stimulates all cholinergic receptors
    • Binds directly to the postsynaptic ACH receptors
    • Metabolized by pseudocholinesterase
    • Also binds to muscarinic receptors of SA node  negative inotrope and chronotrope
    • Short duration due to high volume of distribution
    • Prolonged & repeat exposure membrane can repolarize but remain refractory to subsequent depolarization  “Phase II block”, clinical resemblance to non-depolarizing agents.
    • Prolonged effects in hepatic dysfunction, hyper-magnesia & pregnancy
nmb depolarizing1
NMB: Depolarizing

Succinylcholine

Contraindications

  • History of malignant hyperthermia (personal or family)
  • Neuromuscular disease involving denervation
  • Muscular dystrophy
  • Stroke over 72 hours old
  • Rhabdomyolysis
  • Burn over 72 hours old
  • Significant hyperkalemia
nmb depolarizing2
NMB: Depolarizing

Succinylcholine

Malignant hyperthermia:

  • Myopathic metabolic disorder
  • Autosomal dominant
  • Sympathetic hyperactivity, mucular rigidity acidosis and hyperthermia
  • Uncontrolled increase in skeletal muscle oxidative metabolism  hypoxia, hypercapnea and hyperthermia
  • Treatment: dantrolene, cooling and sedation
nmb depolarizing3
NMB: Depolarizing

Succinylcholine

Side effects

  • Trismus: masseter muscle spasm (can associate with MH)
  • Fasciculations: via nicotinic activation
  • Bradycardia: via muscarinic activation at SA node especially children; can occur in adults in repeated dose or infusion
  • Rhabdomyolysis and muscle pain
  • Transient ocular hypertension: safe in open globe injury if use in conjunction with sedation
  • Mild increase in intra cranial pressure
nmb non depolarizing
NMB: Non-Depolarizing
  • Competitively inhibits the postsynaptic Ach receptors of the neuromuscular motor endplate
  • Prevents depolarization & inhibits all muscle function
  • Categories
    • Benzylisoqyinolinium: atracurium, mivacurium
      • Histamine release
      • Can cause autonomic ganglionic blockade
    • Aminosteroids: rocuronium, vecuronium, pancuronium
nmb non depolarizing1
NMB: Non-Depolarizing
  • Low plasma protein binding capacity
  • 4 routes of elimination: renal excretion, hepatic excretion, biotransformation, tissue binding
  • Types
    • Short: Mivacurium
    • Intermediate: atracurium, Vecuronium, Rocuronium, cisatrocurium
    • Long: d-tubocurarine, pancuronium, pipecuronium, doxacurium
nmb non depolarizing reversal
NMB: Non-Depolarizing reversal
  • Abx, hypotension, hypothermia, acidosis & hypocalcemia prolong or potentiate NMB
  • Duration of reversals are the same in all 3 classes
  • Neostigmine
    • 25-70 mcg/kg
  • Edrophonium
    • Faster acting
    • 125-250 mcg/kg
ad