Pharmacological Behavior Guidance Flashcards
Olfactory (I) sensory
Nose
Optic (II) sensory
Eye
Oculomotor (III) motor
All eye muscles except those supplied by IV and VI
Trochlear (IV) motor
Superior oblique muscle
Trigeminal (V) sensory and motor
Sensory: face, sinuses, teeth, etc.
Motor: muscles of mastication
Abducent (VI) motor
External rectus muscle
Facial (VII) motor
Muscles of the face
Vestibulocochlear (VIII) sensory
Inner ear
Glossopharyngeal (IX) motor and sensory
Motor: pharyngeal musculature
Sensory: posterior part of tongue, tonsil, pharynx
Vagus (X) motor and sensory
Motor: heart, lungs, bronchi, gastrointestinal tract
Sensory: heart, lungs, bronchi, trachea, larynx, pharynx, gastrointestinal tract, external ear
Accessory (XI) motor
Sternocleidomastoid and trapezius muscles
Hypoglossal (XII) motor
Muscles of the tongue
Branches of the trigeminal nerve
- V1: Ophthalmic branch
- V2: Maxillary branch
- Superior alveolar nerve - V3: Mandibular branch
- Inferior alveolar nerve
- Lingual nerve
How does local anesthetic work?
- Blocks sodium channels reversibly
- Inhibit depolarization and conduction of action potentials (at least 3 nodes of Ranvier must be blocked)
- LA must enter the nerve, therefore must be fat soluble
- Only possible with non-ionized molecule
Local anesthetic composition
- Lipophilic (substituted benzene ring) —> penetration of anatomic barriers
- Intermediate chain (amide or ester)
- Hydrophilic (amino terminus) —> ensures drug will not precipitate in interstitial fluid
Composition of articaine
Contains a thiopene ring with an ester group
Are local anesthetic bases or acids?
- All common LAs are weak bases (pKa 7.5 to 9.5), prepared in salt form by addition of HCl
- Only basic form can diffuse into the nerve
What happens when pKa = pH?
50% of the LA is uncharged
Meaning of low pKa?
Low pKa —> more non-ionized molecules = more effective
Result of low pH in areas of infection on LA
Low pH in areas of infection will decrease non-ionized %
Mental (anesthesia)
“Soft tissue” block
Posterior superior alveolar nerve block
- May not always anesthetize the mesiobuccal root of the 1st maxillary molar
- In conjunction with palatal anesthesia?
Conventional IA injection technique
- Palpate deepest portion of coronoid notch
- Insert needle between pterygomandibular raphe and deep tendon of temporalis
Long buccal nerve
- Will sometimes innervate primary and permanent molars —> anesthetize buccal to the last tooth to be treated
Mandibular foramen in a child
- Slightly below the plane of occlusion
- More anterior than in adults
- Growth is downward and forward at condyles and along the posterior surface of the ramus
- The distance from lingula to anterior border is fairly stable with growth, while other dimensions change
Injection pain causes
- Mechanical trauma from needle penetration
- Distention of tissue from cartridge contents
- Anesthetic properties (temperature, pH, etc.)
Needle gauge
- Larger is less likely to break
- Larger is easier to aspirate through
- Larger is less likely to deflect
What determines anesthesia?
- LA proximity to nerve
- Degree of ionization
- Concentration of solution
- Volume injected
- Time
Name the ester local anesthetics
- Novocaine
- Tetracaine
- Benzocaine
- Cocaine
- Procaine
Where are ester local anesthetics metabolized?
Hydrolized in plasma by pseudocholinesterase.
Major metabolite of ester anesthetics
PABA is a major metabolite, responsible for most allergic reactions
Name the amide local anesthetics
- Lidocaine
- Mepivacaine
- Bupivicaine
- Prilocaine
- Ropivacaine
Where are amide local anesthetics metabolized?
- Metabolized by liver in cytochrome P450.
Most common topical anesthetic
- 20% benzocaine
Precaution with benzocaine
- Large dose may cause methemoglobinemia in young children, however has been reported after a single dose
- Consult healthcare professional for use under age 2
pKa of Lidocaine
7.8
Lidocaine
- Gold standard
- 1:100,000 epi standard, 1:50,000 for some surgical procedures
- 2% (20mg/mL)
- Duration pulpal anesthesia (45 min), soft tissues (2-3 hours)
Prilocaine
- 4% plain
- 3% with 1:200,000 epinephrine
- pKa 7.8
- Methemoglobinemia
- Shouldn’t use in pregnant women (risk of methemoglobinemia in unborn child)
Methemoglobinemia
- Induced by metabolite, ortho-toluidine
- Methemoglobin contains the ferric (Fe 3+) form of iron.
- The affinity for oxygen is impaired.
Precaution with G6PD patients (LA)
Prilocaine
Treatment for methemoglobinemia
Methylene blue
Mepivacaine
- 3% plain
- 2% with 1:20,000 levonordefrin
- pKa = 7.7
Articaine
- 4% with 1:100,000 epinephrine
- pKa = 7.8
- High tissue diffusion (liposolubility) due to thiophene substitution for benzene ring
- Only amide LA to contain an ester group
- Metabolism 90% plasma, 10% liver = more rapid removal from circulation that other LAs
Can articaine substitute for block anesthesia?
- 30 patients (4-8 years) were randomly assigned to receive nerve block with Lidocaine or infiltration with articaine
- Procedures were pulpotomies or pulpectomies
- Researchers recorded Pain and Sound/Eye/Motor (SEM) scores
- Pain scores were higher for block injections during administration and during pulp extirpation
Vasoconstrictors
- Longer duration, requiring less volume
- Anesthetic stays local
- Less bleeding during procedures
Vasoconstrictors counteracts ____ of amide
Vasodilation
Vasoconstrictors _____ due to slower release of drug into bloodstream
Decreases systemic toxicity
Maximum dosage of vasoconstrictor
- Epinephrine (1:100,000 = 10 microgram/mL)
- Max dose 200 microgram (approximately 11 cartridges 2% lido with 1:100,000 epinephrine)
Epinephrine effects on the cardiovascular system
Increased:
- Systolic and diastolic pressure
- Cardiac output
- Stroke volume
- Heart rate
- Contraction strength
- Myocardial oxygen consumption
Use of epinephrine in cardiac patients
- Generally not associated with any significant cardiovascular effects in healthy patients or those with mild to moderate heart disease
- Reduced dosages or local anesthetics without vasoconstrictors are indicated for patients with more significant disease
- Epinephrine-impregnated retraction cord should be used cautiously or avoided in certain situations
Recommended max dose for articaine with epi (AAPD)
7 mg/kg
Recommended max dose for lidocaine with epi (AAPD)
4.4 mg/kg
Recommended max dose for mepivicaine (plain or with epi) [AAPD]
4.4 mg/kg
Recommended max dose for prilocaine (plain or with epi) [AAPD]
6 mg/kg
Local anesthetic overdose
- Local anesthetics are not selective, and may interfere with impulse transmission in any excitable tissue (e.g. central nervous system)
- Inhibitory cortical neurons or synapses are highly susceptible to transmission block
- Disruption of these pathways may result in disinhibition of excitatory neurons
Symptoms of a local anesthetic overdose
- Generalized tonic-clinic seizures
- CNS depression
- Hypotension
- Bradycardia
- Respiratory depression
Management of a local anesthetic overdose
- Place in supine position
- Administer oxygen
- CPR as necessary if cardiac function disrupted
Pharmaceutical management of local anesthetic overdose
- Seizure management with benzodiazepines (e.g. IV midazolam 0.1-0.2 mg/kg)
- 20% lipid emulsion (1.5 mL/Kg over 1 min, traps unbound amide LA)
- Fluid bonus of 10-20 mL/kg balanced salt solution and phenylephrine (0.1 mcg/kg/, min)
OraVerse (Phentolamine Mesylate)
- Reduces anesthesia time by approximately 50%
- 0.4mg/1.7mL
- Maximum recommended dose
- 2 cartridges for adults and adolescents 12 years of age and older
- 1 cartridge for patients 6-11 years of age and over 66 lbs
- 1/2 cartridge for children 3-11 years of age and weighing 33-66 lbs
OraVerse is not recommended for this age group
- Children <3 years of age or under 33 lbs (15 kg)
- A dose of more than 1 cartridge has not been studied in children <4 years
FDA pregnancy risk category A
Adequate and well-controlled studies have failed to demonstrate a risk to fetus
FDA pregnancy risk category B
Either:
1) Adequate and well-controlled studies have failed to demonstrate a risk, but animal studies have shown adverse effect
OR
2) Human studies are lacking, but animal studies have failed to demonstrate risk
FDA pregnancy risk category C
No adequate and well-controlled studies have been performed in pregnant women, but animal studies are lacking or have shown risk to fetus. Potential benefit may warrant use despite potential risk.
Local anesthetics that are category A
Sodium fluoride ** not anesthetic
Local anesthetics that are category B
- Lidocaine
- Prilocaine
Local anesthetic that are category C
- Articaine
- Mepivacaine
- Bupivacaine
Blood/gas coefficient of nitrous oxide
0.47 —> poorly soluble in blood
Is nitrous oxide flammable?
Nonflammable, but supports combustion in presence of O2.
Minimum alveolar concentration of nitrous oxide
104
Minimum alveolar concentration of sevoflurane
3.3
Minimum alveolar concentration of isoflurane
1.2
Minimum alveolar concentration of halothane
0.87
Nitrous oxide
- No noxious smell
- Mild myocardial depressant, mild sympathomimetic effects cancel each other
Sevoflurane
- Somewhat pungent
- Allows very rapid induction
- HIgher rate of emergence excitement
- Decreases respiratory rate and tidal volume
- Increases heart rate, no change in BP
Isoflurane
- Pungent noxious smell
- Inexpensive
- Greater incidence of laryngospasm, coughing
- Used for maintenance
Halothane
- No noxious smell
- Allows rapid induction
- Inexpensive
- Used for maintenance
- Decreases tidal volume, increases respiration
- Decreases BP, no change in HR
Anesthetic properties of nitrous oxide
- Low blood solubility results in rapid induction and awakening
- MAC approximately 104% (incapable of full anesthesia by itself)
- Used in anesthesia to achieve more rapid induction/recovery because MAC is additive with other, slower-acting anesthetics
- Minor depression in cardiac output + slight increase in peripheral resistance = little change in BP
Stage I of Guedel’s stages of anesthesia
- Patient relaxed, able to follow instructions
- Some pain reduction
- Four planes (from analgesia to hallucinations and loss of consciousness)
Stage II of Guedel’s stages of anesthesia
- Deepended CNS depression
- Excitement/delirium/jerky movements
- Laryngospasm may occur
Stage III of Guedel’s stages of anesthesia
- Patient unconscious, laryngeal and pharyngeal reflexes inactive
- Used for major surgical procedures
- Four planes
Stage IV of Guedel’s stages of anesthesia
- Medullary paralysis, death
Concentration effect
- The higher the concentration of nitrous oxide, the more rapidly the alveolar concentration approaches the inspired concentration.
- Higher concentrations effectively increase alveolar ventilation.
Second gas effect
- Other anesthetic gases administered with high concentrations of N2O rush inward to replace nitrous oxide that is absorbed by the pulmonary blood.
- Oxygen delivery is also enhanced.
Composition of the air that we breathe
- 78% is nitrogen
- 21% is oxygen
Elimination of nitrous oxide
- Essentially all is exhaled unchanged
- 0.004% metabolized to nitrogen in the GI tract
Effects of nitrous oxide
- Body warmth
- Tingling hands and feet
- Circumoral numbness
- Auditory effects
- Euphoria
- May aid with local anesthesia (patient is more still, and doesn’t interpret pressure, vibration, as pain)
Mechanism of action of nitrous oxide
- Inhibition of the N-methyl-D-aspartate (NMDA) of the excitatory glutamate receptor
- Stimulation of the aminobutyric acid (GABA) and alpha-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptors
- May promote release of endogenous opioid neurotransmitters (endorphins/day orphans)
Adverse effects of nitrous oxide
- Increases volume of any closed air pocket in the body
- Nausea and vomiting (0.5 to 1.2% of patients)
- Longer duration
- Fluctuation in concentration
- Lack of titration
- Increased concentrations
Indications for nitrous oxide
- Anxious patients
- Long procedures
- Painful procedures
- Patients with simple restorative needs, unlikely to tolerate LA
- Gag reflex
- Difficulty obtaining local anesthesia
Contraindications for nitrous oxide
- Moderate to severe asthma
- Current respiratory infection
- Acute otitis media (blocked Eustachian tube) or recent middle ear surgery
- Chronic obstructive pulmonary disease
- Severe emotional disturbances
- First trimester of pregnancy
- Methylenetetrahydrofolate reductase deficiency
- Severe psychiatric imbalance
- Precooperative
- Mouth breathers
- Treatment with bleomycin sulfate
- Cobalamin (vitamin B-12) deficiency
Med consult indicated prior to use of nitrous oxide in these circumstances
- Severe COPD (chronic hypercarbia)
- Congestive heart failure
- Sickle cell disease (maintain oxygen saturation)
- Acute otitis media
- Recent tympanic membrane graft
- Acute severe head injury (intracranial pressure)
Genetics of methylenetetrahydrofolate reductase deficiency
- Autosomal recessive
- Gene mutation at C677T and A1298C locations
What is methylenetetrahydrofolate reductase (MTHFR) responsible for?
- For folate metabolism and homocysteine regulation
- Unconverted homocysteine can cause neurological death
Why is nitrous oxide contraindicated in MTHFR deficiency?
- Nitrous oxide inhibits the transformation of homocysteine to methionine and subsequently leads to an accumulation of unconverted homocysteine in affected children
- Unconverted homocysteine can cause neurological death
What also affects homocysteine levels?
Homocysteine levels can also stem from deficiencies in vitamin B12, folic acid, and vitamin B6.
Diffusion hypoxia
- Theoretically when N2O administration is stopped, large quantities of N2O may diffuse from blood into alveoli and dilute oxygen.
- Can be eliminated by administration of 100% O2 following N2O administration
- Importance is really in scavenging expired N2O, and reducing N2O pollution
- Also important to raise chair and allow patient to recalibrate
Emergency oxygen requirements
Positive pressure O2 delivery system:
- 15 L/min flow recommended when using bag valve mask to delivery positive pressure O2
- Capable of administering >90% O2 at 10L/min for at least 60 min (650L, “E” cylinder)
Define minimal sedation “anxiolysis”
- Responds normally to verbal stimulation
- Cognitive function and coordination may be impaired
- Ventilatory and cardiovascular functions unaffected
- Typical of patients sedated with N2O/O2
Define moderate sedation “conscious sedation”
- Responds purposefully to verbal commands, alone, or accompanied by light tactile stimulus
- No interventions are required to maintain a patent airway; spontaneous ventilation is adequate
- Cardiovascular function is usually maintained
- Intended level for most dental oral sedation
Define deep sedation/analgesia
- Patient cannot easily be aroused, but responds purposefully following repeated or painful stimulation
- Ability to independently maintain ventilatory function may be impaired; may require assistance in maintaining a patent airway – spontaneous ventilation may be inadequate
- Cardiovascular function is usually maintained
- Typical of patients who are “oversedated” in the dental office
Define general anesthesia
- Drug-induced loss of consciousness during which patients are not arousable, even by painful stimulation
- Ability to independently maintain ventilatory function is often impaired; often require assistance in maintaining a patent airway
- Cardiovascular function may be impaired
ASA I
Healthy, normal child
ASA II
- Child with mild systemic disease
- Controlled asthma, controlled diabetes
ASA III
- Child with severe systemic disease
- Active wheezing, diabetes mellitus w/ complications, heart disease that limits activity
ASA IV
- Child with severe systemic disease that is a constant threat to life
- Status asthmatics, severe BPD, sepsis
ASA V
- Child who is moribund and not expected to survive without the procedure
- Cerebral trauma, pulmonary embolus, septic shock
ASA classifications appropriate for in-office sedation
ASA I and II
Importance of birth history
- Premature birth (<37 weeks gestation)
- Delayed airway development
- Early life intubation
- Possible pulmonary barotrauma
- Increased incidence of laryngeal stenosis
Obesity and drug administration for sedation
Before drug administration, special attention must be paid to the calculation of dosage; for obese patients, most drug doses should likely be adjusted lower to ideal body weight rather than actual weight.
Ear, nose, throat (airway) evaluation
- Obstructive sleep apnea/sleep disordered breathing
- Snoring
- Known airway problems
- Difficulty swallowing
- History of difficult intubation
Cardiac evaluation
- Any cardiac surgery
- Heart defect/murmur
- Congestive heart failure
- Irregular heartbeat/palpitations
- High BP
- Cardiac patients are generally not appropriate candidates for outpatient procedural sedation/GA **
Respiratory evaluation
- Asthma (recent of frequent hospitalization, poor control)
- Recent pneumonia or other URI
- Chronic lung disease (cystic fibrosis, COPD)
- Home O2 requirement
Upper respiratory infections
- Patients with a current URI with THICK SECRETIONS demonstrated the highest rate of adverse event:
- 9% required suctioning
- 8.7% developed cough
- 8.1% had desaturation
- 22.2% overall developed some type of adverse airway event
- Patients with clear secretions do not seem to pose the same risk
How long to wait for sedation with recent URI?
4-6 weeks from last URI
Gastrointestinal evaluation
- Symptomatic GERD (aspiration)
- Liver disease
- Parenteral nutrition (g-tube, j-tube)
Renal evaluation
- Acute or chronic renal failure
Neurologic evaluation
- Epilepsy/seizures (especially with poor control)
Musculoskeletal evaluation
- Scoliosis affecting mobility and/or lung function
- Muscular dystrophy
Muscular dystrophy treatment
Dantrolene
Hematologic disorders evaluation
- Anemia
- Sickle cell disease
- Bleeding disorder (hemophilia, Von Willebrand disease)
- History of cancer (even patients in remission may pose increased risk)
Endocrine/metabolic evaluation
- Diabetes
- Hypo/hyperthyroidism
- Adrenal disorders
- Inborn errors of metabolism
Genetic disorder evaluation
- Any syndrome should be investigated thoroughly
Behavioral problems evaluation
- Autism (unpredictability of sedation, behavioral meds may cause sedation)
- ADHD (stimulant medications)
- ODD
Evaluation of miscellaneous/other items
- Abnormal labs or studies
- Multiple allergies (especially recent allergic reaction: increased histamine in system)
Greatest risk factors for adverse sedation events
- Under age 5
- Premature birth
- ASA III+
- Chronic reactive airway disease
- Current URI with opaque (green/yellow) secretions
- Obesity (OR 1.7-2.2)
- Obstructive sleep apnea (OSA)
- Developmental delay/intellectual disability
Difference between child and adult airway
- Increased airway resistance
- Relatively larger head, tongue, and epiglottis
- Narrow nasal passages (obligate nasal breathers)
- Significant lymphoid tissue possible
- Larger head to body size ratio
- Less developed mandible
- Children with OSA may have altered mu receptors and require less opioid med
Anatomic differences: pediatric versus adult airway
- Airway narrowest at the cricoid cartilage until 8 (versus epiglottis)
- Larynx located more cephalic (C2-6 in a child versus C4-5 in an adult)
- Head and tongue proportionately larger in infants
- Floppy, long epiglottis
- Vocal cords angled upward, more anteriorly
- Short trachea, flexed neck
- Airway more reactive; infants prone to developing laryngospasm
Normal vital signs for 3-6 months
HR (beats/min): 110-160
BP (mmHg) upper end: 90/65
Respiratory rate (breaths/min): 30-45
Normal vital signs for 6-12 months
HR (beats/min): 90-160
BP (mmHg) upper end: 100/65
Respiratory rate (breaths/min): 22-38
Normal vital signs for 1-3 years
HR (beats/min): 80-150
BP (mmHg) upper end: 105/70
Respiratory rate (breaths/min): 22-30
Normal vital signs for 3-6 years
HR (beats/min): 70-120
BP (mmHg) upper end: 110/75
Respiratory rate (breaths/min): 20-24
Normal vital signs for 6-12 years
HR (beats/min): 60-110
BP (mmHg) upper end: 120/75
Respiratory rate (breaths/min): 16-22
Normal vital signs for >12 years
HR (beats/min): 60-100
BP (mmHg) upper end: 135/85
Respiratory rate (breaths/min): 12-20
Cardiac output
Stroke volume x heart rate
- Heart rate is the main determinant in children
- Increased respiratory rate, cardiac index, and greater proportional distribution of cardiac output to organs allows for more rapid uptake of potent inhaled anesthetics
Mallampati scale
Provides a measure of available air space and relative soft tissue obstruction
Brodsky scale
- Commonly used by ENT physicians to assess tonsils prior to removal
- Considered as a risk factor for obstructive sleep apnea
Brodsky 0
Surgically removed tonsils
Brodsky 1
Tonsils hidden within tonsil pillars
Brodsky 2
Tonsils extending to the pillars
Brodsky 3
Tonsils are beyond the pillars
Brodsky 4
Tonsils extend to midline
NPO guidelines
- Ensures that the patient arrives with an empty stomach
- Minimizes chances for emesis and subsequent aspiration
- Maximizes absorption of the drug
NPO guideline regarding clear liquids
2 hours prior
NPO guideline regarding breast milk
4 hours prior
NPO guideline regarding infant formula, nonhuman milk, light meal
6 hours prior
Medications and NPO guidelines
It is permissible for patient to take routine medications with a sip of clear liquid or water on the day of the procedure
Monitoring equipment for when bidirectional verbal communication between the provider and patient is appropriate and possible
1) capnography – preferred
2) amplified, audible pretracheal stethoscope or precordial stethoscope – strongly recommended
Monitoring equipment for when bidirectional verbal communication is not appropriate or not possible
1) Monitoring of ventilation by capnography – preferred
2) amplified, audible pretracheal stethoscope, or precordial stethoscope – REQUIRED
Blood pressure cuff (sphygmomanometer)
Blood pressure should be assessed before sedation and prior to discharge (minimum)
Heart rate/pulse oximeter monitor
Heart rate and blood oxygen saturation must be monitored every 5 minutes throughout the procedure
Type of light absorbed by oxygenated hemoglobin
infrared light
Type of light absorbed by deoxygenated hemoglobin
red light
Hemoglobin
- Protein in red blood cells that caries oxygen
- Four protein molecules (adults):
- 2 alpha-globulin chains
- 2 beta-globulin chains
- Range:
- Children 11-13 gm/dl
- Adults 12-18 gm/dl
Precordial stethoscope
A stethoscope (with microphone) affixed to the patient’s suprasternal notch helps detect respiratory alteration or distress
Pharmacokinetics of sedation drugs
- Oral absorption: 30-60 minutes
- Affected by presence of food
- Lipophobic drugs are less absorbed than lipophilic drugs
Pharmacodynamics of sedation drugs
- Interaction of drug and receptors in site of action
Pharmacotherapeutics of sedation drugs
- Principles guiding choices of drugs
- Efficacy, toxicity, onset, duration of drug action
Common oral agents (benzodiazepines)
- Diazepam (Valium)
- Midazolam (Versed)
Common oral agents (antiemetic/antihistaminic)
- Hydroxyzine (Vistaril, Atarax)
- Promethazine (Phenergan)
- Diphenhydramine (Benadryl)
Common oral agents (barbiturate/hypnotic)
Chloral hydrate
Common oral agents (narcotic)
- Meperidine (Demerol)
- Morphine
Chloral hydrate
- Sedative/hypnotic
- Non-analgesic
- Mucosal irritant
- Has been reported to induce laryngospasms
- Non-reversible
Where is chloral hydrate metabolized and excreted?
- Metabolized by the liver to chlortriethanol (an alcohol)
- Increase in liver’s metabolic enzymes may interact with other therapeutic agents
- Excreted via the kidney
Adverse reactions with chloral hydrate
- Warfarin: competition for plasma protein binding increases anticoagulant effect
- Furosemide: diaphoresis, tachycardia, hypertension
Meperidine
- Synthetic opioid analgesic, sedative, antispasmodic
- Very bitter taste
- Reversible
- Produces histamine release from mast cells
- Injection can cause local reactions and itching
- Direct stimulation of chemotrigger zone in medulla may cause emesis
- May be spasmogenic to the smooth muscle of the GI tract
- Caution with local anesthetics, as threshold level for seizures may be lowered when used in combination
Contraindications for meperidine
- MAO inhibitors, SSRIs, tricyclic antidepressants
- With seizure disorders (proconvulsant active metabolite)
- Severe asthma (histamine release)
Where is meperidine metabolized and excreted?
Metabolize day the liver, excreted by the kidney
Midazolam
- Anterograde amnesia (cannot recall events AFTER administration)
- Paradoxical reaction possible
- Hiccups
- Non-analgesic
- Reversible binding to CNS GABA receptors
- Alpha-hydroxymidazolam metabolite may contribute to sedative effect
- Treatment of skeletal muscle spasm (seizure)
Midazolam and calcium channel blockers
Calcium channel blockers (verapamil and dilitiazem) inhibit CYP3A enzymes required for midazolam metabolism, increasing bioavailability
Where is midazolam metabolized?
Metabolized by the liver, excreted by the kidney
Diazepam
- Anterograde amnesia (less than midazolam)
- Paradoxical reaction possible
- Reversible binding to the CNS GABA receptors
- Treatment of skeletal muscle spasm (seizure)
- Long half-life
- Active metabolites (desmethyldiazepam) lead to long half-life
- Lipophilic, accumulating in fat and further increasing half-life
Hydroxyzine
- H1 Antihistamine: anticholinergic, antihistaminic, antiemetic
- Drowsiness
- Decreases nausea, vomiting
- Decreases secretions, may cause bronchodilation
- Possible extra-pyramidal activity yielding jerky limb movements
- Non-reversible
Where is hydroxyzine metabolized and excreted?
Metabolized by the liver, excreted by the kidney
Interactions/warnings for herbal medications and sedation medication
- Herbal medications may alter sedation drug pharmacokinetics through inhibition of the cytochrome P450 system
• St. John’s wort, ginkgo, ginger, ginseng, garlic = increased or decreased medication (midazolam, cyclosporine, tacrolimus)
Kava and sedation medication interaction
Kava may increase sedation through gamma aminobutyric acid
Valerian and sedation medication interaction
Valerian may produce sedation through gamma aminobutyric acid
Sedation medication warning for promethazine (Phenergan)
Black box warning on promethazine (Phenergan) for fatal respiratory depression in children < 2 years
Warning regarding codeine
2013 FDA warning regarding codeine for post-operative pain management (children with duplicated cytochromes have greater prodrug conversion and potential overdose)
Metabolism of sedation drugs — First Pass Phenomenon
Drugs absorbed in enteric routes go to liver via portal circulation
How sedation works in the brain
Midazolam potentiates GABA receptor
*channel opens and chloride ions enter cell —>
neuronal firing inhibited —>
sedation and respiratory depression
Discharge criteria
Score of 0 or 1 on University if Michigan Sedation Scale
0 - Awake and alert
1 - Minimally sedated: tired/sleepy, appropriate response to verbal conversation and/or sound
2 - Moderately sedated: somnolent/sleeping, easily aroused with light tactile stimulation or a simple verbal command
3 - Deeply sedated: deep sleep, arousable only with significant physical stimulation
4 - Unarousable
The modified maintenance of wakefulness test
The child remains awake in a darkened calm environment for 20 minutes
Hypoxia in infants and children
- Higher basal metabolic rate = higher O2 consumption and CO2 production
- Higher ventilation requirement
- Only way to increase O2 and ventilation is to increase respiratory rate due to low capacity
Benzodiazepine reversal
Flumazenil (Romazicon)
- Very short half life-likely to have to push repeat doses
- Half life of benzodiazepines is greater than flumazenil
- Initial onset 1-2 minutes
- Maximum effect 6-10 minutes
- Dose = 0.01 mg/kg
Meperidine HCl Antagonist (Opioid)
Naloxone (Narcan) • Competitive antagonist • Onset 1-2 minutes • Monitor for rebound sedation • Dose 0.1 mg/kg given IV/IM/SC (can repeat)
Loud hypoxia
- Foreign body
- Snoring
- Wheezing
- Choking
- Laryngospasm
Cascade of events
- Hypoxia
- Bradycardia
- Cardiac arrest
- Death
CPR order
Compressions —> Airway —> Breaths
When to start CPR?
Start compressions within 10 seconds of recognition of cardiac arrest.
Rate of compressions per minute (CPR)
100-120 compressions/min
Ratio of compressions to breaths when alone (CPR)
30:2 for healthcare provider whenever you are alone
Ratio of compressions to breaths with second rescuer
15:2 for children with 2nd rescuer
Rescue breathing
- Adults 10-12/min (q 5-6 sec)
- Children 12-20/min (q 3-5 sec)
- Advanced airway 10/min (q 6 sec)
Deep compressions (depth for CPR)
- At least 2 inches, Adult
- 2 inches, 1/3 chest, Child
- 1.5 inches, infants
Management if laryngospasm
1) Positive pressure ventilation
2) Deepen sedation (for titrated IV sedation)
3) Give muscle relaxant
4) Tracheal intubation
5) Surgical airway
Laryngospasm Notch Maneuver “Larson Maneuver”
Firmly push the soft tissue just behind the earlobes of the patient’s ears (the “laryngospasm notch”). Push at a point as superior as you can go in this notch. Push both sides firmly inward towards the skull base. Simultaneously, push anteriorly similar to a jaw-thrust maneuver. This should break the laryngospasm within 1-2 breaths.
Management if airway obstruction
1) Reposition airway
2) Perform jaw thrust
3) Insert oral airway
4) Insert nasal trumpet
5) Insert supraglottic airway (LMA or other)
6) Tracheal intubation
7) Surgical airway
Management of Apnea
1) Bag-mask ventilation
2) Reposition airway
3) Perform jaw thrust
4) Insert oral airway
5) Insert nasal trumpet
6) Insert supraglottic airway (LMA or other)
7) Tracheal intubation
8) Surgical airway
Sizing endo Tracheal tubes
Uncuffed tube size = (age/4)+4 or (age+16)/4
Cuffed tube size = (age/4)+3.5
Example: 5 yr old = 5.25 -> 5 mm uncuffed tube
**when age unknown, the width of the fifth finger (pinky) can be used to estimate tube size
Maintenance fluid therapy
- <10kg = 4 mL/kg/hr
- 11kg - 20kg = 40mL/hr + 2mL/kg/hr for each kg over 10
- > 20kg = 60mL + 1mL/kg for each kg over 20
Example: 18 kg pt -> 40mL/hr + 18mL/hr = 58mL/hr
Adverse sedation events causes
- Drug dosage more influential than drug choice
- Lack if appropriate monitoring
- Very you’ve (< 3 y/o) at greatest risk
- 41% involved local anesthesia overdose
- Most deaths occurred among 2-5 year olds in an office setting, with a general/pediatric dentist as the anesthesia provider
- The majority of the pediatric deaths involving a general/pediatric dentist were associated with moderate sedation
