Intravenous Induction Drugs

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Intravenous Induction Drugs

• The University of Kansas
• Nurse Anesthesia
• Shelley Barenklau CRNA, MS

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HISTORY

• First intravenous drugs for general anesthesia
  were opioids
• Barbiturates 1930s
• Thiopental (Pentothal) 1935

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DRUG CLASSES

• Thiobarbiturates (Thiopental)
• N-Methylated Oxybarbiturate (Methohexital)
• Benzodiazepines (Diazepam, Midazolam)
• Imidazoles (Etomidate)
• Alkylphenol (Propofol)
• Arylcyclohexylamines (Ketamine)

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BARBITURATES

• Mechanism of action GABA-mediated inhibition
• High lipid solubility leads to rapid onset of
  anesthesia
• Reversibly bound to plasma proteins (plasma
  albumin)

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Barbiturates

• Dose-related respiratory depression
• Increase venous dilation (? C.O.)
• Potent cerebral vasoconstrictor (? ICP)
• Extravascular injection painful, tissue damage
• Dose-dependent histamine release
• Absolute contraindication - Porphyria

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Thiopental (Pentothal)

• Prepared as a 2.5 solution, dissolve in 0.9 NS
• Loss of consciousness within 15-30 seconds
• Dose 3-4 mg/kg IV adult
  Child 5-6 IV mg/kg
• Metabolized in liver
• Pain on IV injection
• Reduce dose in the elderly

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Methohexital (Brevital)

• 1 solution (vials 100 or 500 mg)
• Dose 1-2 mg/kg IV
• Ultra-short acting barbiturate
• Primarily used for ECT, dental procedures,
  cardioversion
• Myoclonia (excitatory movements)
• Hiccups
• Pain on injection
• Seizures

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Etomidate (Amidate)

• Dose 0.2 - 0.4 mg/kg IV adult
• Preparation 2 mg/ml
• Cardiovascular stability
• Reduces intracranial pressure
• Involuntary movements (myoclonia), tremor
• Short duration of action

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Etomidate

• Increases postoperative nausea/vomiting
• Directly depresses cortisol output / supress
  immune system
• Anticonvulsant properties
• ? ICP

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Propofol (Diprovan)

• 2,3-diisopropyl phenol
• Milky-white emulsion
• Milk of amnesia
• 10 soybean oil
• 2.5 glycerol
• 1.2 purified egg lecithin

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Propofol

• Decreases blood pressure
• Direct myocardial depression and peripheral
  vasodilation (dose-dependant)
• Decrease cardiac output and SVR
• Decrease minute ventilation
• Decrease ICP

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Propofol

• High clearance rate (rapid emergence from
  continuous infusion)
• Antiemetic properties
• Anticonvulsant properties
• Pain on injection

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Propofol

• Preparations
• 1 solution in oil emulsion
• 2 solution in oil emulsion
• 20 ml and 50 ml preparations

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Propofol

• Induction Dose
• Adult 1.0 - 2.5 mg/kg IV
• Child 2.5 3.5 mg/kg IV
• Adult gt 55 years consider decreasing dose
• Sedation 100 200 mcg/kg/min
• Hypnosis 25 75 mcg/kg/min
• (Barash, 4th ed., p.333)

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Propofol

• Highly versatile drug
• Used in the operating room and ICU
• Administered IV for induction of anesthesia and
  maintenance (bolus continuous)
• Used for sedation
• Can supplement regional anesthesia

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Propofol Considerations

• Generic formulation contains sodium bisulfite
  (caution with asthma)
• Judicial use with elderly, debilitated, and
  cardiac compromised patients
• Fatal syndrome associated with long-term,
  high-dose administration
• Egg allergy

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Benzodiazepines

• Multiple clinical uses
• Anxiolysis
• Amnesia
• Sedation
• Muscle relaxation
• Hypnosis
• Anticonvulsant
• Treat insomnia

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Benzodiazepines

• Commonly used in anesthesia practice
• Midazolam (Versed)
• Lorazepam (Ativan)
• Diazepam (Valium)
• Additional benzodiazepines
• (p. 120 Nagelhout)
• Flumazenil (Romazicon) - Antagonist

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Benzodiazepines

• Depress CNS by binding to the benzodiazepine
  receptor on the GABA receptor complex.
• Modulates GABA (the major inhibitory
  neurotransmitter in the CNS)
• Classifications based on half-lives
• Versed-- short acting
• Ativan -- intermediate duration
• Valium -- long duration

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Diazepam (Valium)

• Lipid soluble
• Large volume of distribution
• Totally dependent on hepatic metabolism
• Produces anterograde amnesia
• Reduce dose in the elderly
• Treatment of status epilepticus
• Pain on injection, thrombophlebitis

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Midazolam (Versed)

• Similar potency to diazepam
• Short acting (rapidly metabolized by hepatic
  oxidizing enzymes)
• Rapid onset (high lipid solubility rapidly
  crosses the blood-brain barrier)
• Dose-dependent decrease in ventilation
• ? cerebral metabolic oxygen requirements
  cerebral blood flow

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Versed dosing

• Induction dose 0.1 0.2 mg/kg IV adult
  (over 30-60 seconds)
• Preoperative dose
• IV / IM 0.05 mg/kg 0.1 mg/kg (children)
  Adult 0.5 mg 3 mg IV
• Oral 0.05 mg/kg 1 mg/kg (30 min prior)
• Rectal / Intranasal 0.2 0.3 mg/kg

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Flumazenil (Romazicon)

• Benzodiazepine antagonist
• Titrate to desired level of sedation
• Initial dose 0.2 mg IV repeat doses at 0.1
  mg IV (max total 1 mg IV)
• Duration of action 30-60 minutes
• Continuous infusion 0.1 0.4 mg/hr IV

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Ketamine (Ketalar)

• Phencyclodine derivative (dissociative
  anesthesia)
• Analgesic and amnesia
• Metabolized by hepatic microsomal enzyme
• active metabolite Norketamine
• Can cause psychic disturbances, hallucinations,
  delirium

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Ketamine

• Cardiac stimulant
• Increase heart rate
• Increase mean arterial blood pressure
• Increase cardiac output
• Increase myocardial contractility
• Increases central venous pressure

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Ketamine

• Potent bronchodilator
• Increases cerebral blood flow / ICP
• Causes nystagmus (? IOP)
• Generally maintains resp/airway reflexes
• Increases postop nausea / vomiting
• Increases salivation respiratory secretions
• Treat with Glycopyrolate (Robinul)
• Elimination ½ half-life is 2-3 hours

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Clinical uses of Ketamine

• Shock or cardiovascular instability
• Severe dehydration
• Bronchospasm
• Severe anemia
• Burn dressing changes
• OB acute hemorrhage
• Poor risk patients (trauma /elderly)

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Ketamine doses

• Induction dose 1 - 2 mg/kg IV
• IM 4 8 mg/kg
• Analgesic doses - 0.44 mg/kg IV
• See also p. 115 (Nagelhout)

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Clinical considerations

• Read drug labels carefully to avoid medication
  errors
• Synergistic drug interactions
• Small doses of 2 or drugs can produce large
  effects
• Draw up induction drugs with sterile technique
• Label anesthesia drugs properly
• Discard syringes after each case
• Remove air bubbles from drug syringes and IV
  tubing

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REVIEW

• Clinical drug calculation related to anesthesia

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Metric Equivalents

• WEIGHT
• 1 mg 1000 mcg
• 1 g 1000 mg
• 1 kg 2.2 lb 1000 g
• VOLUME
• 1000 ml or cc 1 L

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Temperature Conversion

• To convert Fahrenheit to Celsius
• 1. subtract 32
• 2. divide by 1.8

• To convert Celsius to Fahrenheit
• 1. multiply by 1.8
• 2. add 32

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Percentages

• The term percent () means per hundred.
• In the fraction, the numerator is the percentage
  and the denominator is always 100
• Example 5 written as a fraction is 5/100
• So, 5 5/100 0.05
• Example 0.5 0.5/100 5/1000 0.005

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Percentages

• Change percentage to a decimal
• Move the decimal 2 places to the left and drop
  the percent sign 2 0.02
• Convert a decimal to a percentage
• Move the decimal point 2 places to the right and
  add the percent sign 0.02 2

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Percentages

• given is the number in grams per 100 ml
• Bupivacaine 0.75 .75 gm in 100 ml
  0.0075 g/ml 7.5 mg/ml
• Short-cut method multiply by the by 10

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Concentration

• 11000 solution
• 1 gm in 1000 ml 1000 mg in 1000 ml
• 1 mg/ml

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Concentration

• 1 200,000 solution
• 1 gm in 200,000 ml
• 1000 mg in 200,000 ml
• 0.005 mg in 1 ml, (0.005 x 1000 )
• 5 mcg/ml

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Local Anesthestics

• Avoid toxicity / maximum doses
• Calculate lidocaine 2 20 mg/ml
• Max dose 4.5mg/kg (no epinephrine)
• Patient weighs 70 kg
• How much can the surgeon inject safely?
• 4.5 X 70 315 mg
• 315 mg 20 mg/ml 15.75 ml available to inject

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Insulin

• Typically administered in 1 ml or 0.5ml insulin
  syringe, calibrated to U-100 insulin
• Remember insulin is 100 units per ml
• Use insulin syringe, not TB syringe to avoid
  large overdose

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Ratio Proportions

• Example Ancef (Cefazolin sodium)
• Powered form 1 g in vial
• Patient 10 kg
• Surgeon wants a dose of 25 mg/kg IV given.
• Dilute with 10 ml NS, 1g 10 ml (100mg/ml)
• Dose 25 x 10 250 mg needed
• 100mg/1ml X 250mg/x ml 100x 250mg
• Divide each side by 100. x 2.5 ml of Ancef

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Phenylephrine

• Vial contains 10 mg/ml (1000 mcg/ml)
• MUST Dilute
• Mix with 9 ml of diluent (saline, LR, etc.)
• Concentration 1 mg/ml (1000 mcg/ml)
• Take 1 ml of the above concentration
  (1mg/ml) and mix with additional 9 ml of diluent
  to obtain a concentration of 100 mcg/ml
• Desired concentration 100 mcg/ml (LABEL DRUG)

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Phenylephrine

• Additional dilution method
• Vial contains 10 mg/ml
• Obtain 0.1 ml of drug and dilute with 9.9ml of
  diluent (saline, LR)
• 0.1 ml of drug 1 mg
• Concentration 0.1 mg/ml 100 mcg/ml

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Ephedrine

• Vial contains 50 mg of drug
• Mix with 4 ml diluent (LR, saline, etc.)
• Concentration 50 mg/ 5 ml
• 10 mg/ ml
• MUST Dilute

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final thoughts

• Pay attention to small detail regarding
  medications and drug calculation