inhalational agents: individual agents Flashcards
when was halothane introduced?
1956
what are the properties of halothane?
- blood:gas- 2.4
- MAC- 0.76%
- MAC awake- 55% of MAC
- MW 197.4
- vapor pressure- 244 torr at 20 C
what is the chemical name of halothane?
2-bromo-2-chloro-1, 1, 1,-trifluoroethane
describe halothane
- sweet, non-pungent odor
- nonflammable
- stable in soda lime, but decomposes rubber products and most metals
- requires storage in dark bottles and preservative, thymol, to prevent spontaneous oxidative decomposition
- breaks down to hydrochloric acid, hydrobromic acid, chloride, bromide, and phosgene
- thymol remaining in vaporizer after vaporization can cause vaporizer turnstiles or temp compensating devices to malfunction (high flows to flush out)
what are cardiac effects of halothane?
- dose dependent myocardial contractility depression
- decreased CO and BP
- 2 MAC causes 50% drop in BP and CO
- slow conduction through AV node to cause junctional rhythms, wandering pacemaker, bradycardia
- inhibits baroreceptor reflex (no reflex tachycardia w/ drop in BP)
how does halothane cause myocardial depression?
interferes w/ Na-Ca exchange and intracellular Ca utilization
*depression accentuated by beta blocking agent, propranolol, and calcium channel blockers
if halothane is combined with aminophylline, what results?
serious ventricular arrhythmias
how does halothane effect myocardium’s response to catecholamines?
- sensitizes the myocardium to catecholamines
* *hypercarbia enhances the sensitization
what is the maximum dose of epinephrine safe to use w/ halothane?
- adults: 1.5 mcg/kg subq
- add lidocaine 0.5% doubles max dose to 3 mcg/kg subq
- children: 7.8-10 mcg/kg (w/ and w/o lidocaine)
what are respiratory effects of halothane?
- excellent bronchodilator; reverses asthma-induced bronchospasm (best according to M&M; probably no difference from sevo)
- works by inhibiting intracellular calcium mobilization
what are CNS effects of halothane?
- direct cerebral vasodilation
- cerebral autoregulation is attenuated
- *must hyperventilate prior to initiation of halothane
- *at 1.1 MAC and MAP of 80, halothane increases CBF by 190% (more than iso)
describe halothane hepatitis
- no clear mechanism
- possibly: antibody that binds to hepatocytes previously exposed to halothane
- hepatotoxic metabolites are produced in hypoxic situation (enzyme induction), immune response, allergic reaction, familial factors
- this antibody response may involve liver microsomal proteins that have been modified by trifluoroacetic acid as the triggering agents
- incidence 1 in 35,000 fatal, hepatic necrosis (1 in 10,000 jaundice)
- hepatitis d/t other inhaled agents only 1 in 1 million
- incidence is higher if halothane exposure repeats within 28 days
what are risk factors of halothane hepatitis?
- liver hypoxia (causes reductive metabolism v. oxidative)
- sepsis
- obesity
- age over 40 y/o
- female
- enhanced metabolism/induced enzymes (smokers, alcoholics, poly-pharmacy pts.)
- rarely reported in prepubescent children, even w/ preexisting liver disease
what are the effects of halothane on hematology?
-like sevo, may cause a decrease in platelet aggregation and increases in bleeding time
when was isoflurane introduced?
1981
what are the properties of isoflurane?
- blood:gas- 1.4
- MAC- 1.17%
- MAC awake- 38% of MAC
- MW- 184
- vapor pressure 240 torr at 20 C
describe isoflurane
- pungent, ether-type smell
- isomer of enflurane
- stable, nonflammable
- no preservative necessary
what are cardiac effects of isoflurane?
- minimal myocardial depression (less than halothane); decreased O2 demand more in heart than other organs
- CO preserved by increased HR r/t baroreflexes (also partially preserved) (CO not affected by 1-1.8 MAC iso)
- SV decreases, but CO remains nearly constant d/t compensation
- rapid increase in concentration causes increases in HR, BP, and norepinephrine (more in young, healthy pt.)
- heart remains efficient even up to 1.9 MAC
- mild beta stimulation causes vasodilation, decreased SVR and BP
what are the effects of isoflurane on coronary artery perfusion?
- decreases coronary vascular resistance w/ coronary blood flow increased or unchanged
- unlike NTG which dilates larger vessels taking blood flow away from smaller areas needing it, isoflurane dilates small endocardial coronary arteries within the heart muscle
- coronary artery steal: w/ studies that suggest the steal, MAP fell significantly (less than 60) and other suggest it doesn’t occur
how does isoflurane effect blood pressure?
- BP is decreased based on dose; this is mainly d/t SVR reduction
- hypovolemic pts. may not tolerate this reduction (trauma)
- carotid sinus baroreceptor reflex is maintained at 1 MAC, but depressed at 2 MAC
describe respiratory effects of isoflurane
- causes greater respiratory depression than halothane
- tachypnea is less pronounced resulting in enhanced reduction in Vm (will usu. have decreased Vt compensated by increased RR)
- pungent and irritating to some airway; however, overall good bronchodilator (not as good as halothane)
what are CNS effects of isoflurane?
- greater than 1 MAC, increases CBF and ICP
- hyperventilation that accompanies the introduction of isoflurane can minimize effect on ICP
- when isoflurane is used for deliberate hypotension, it decreases cerebral O2 demand
- At 2 MAC, isoelectric EEG; provides brain protection during episodes of cerebral ischemia
describe hepatic effects of isoflurane
- hepatic oxygenation better maintained b/c hepatic artery perfusion and hepatic venous oxygen saturation are preserved
- isoflurane metabolized to fluoride ions, trifluoroacetic acid (halothane hepatitis), and formic acid
- no real concerns for inorganic fluoride levels
when was desflurane introduced?
1992
what are properties of desflurane
- blood:gas- 0.42
- MAC- 6.6%
- MAC awake- 34%
- MW- 168
- boiling point: 22.8 degrees C (73 degrees F)
- vapor pressure: 669 torr at 20 degrees C
- boiling point significantly different from other agents (48-58 C)
what is the chemical name for isoflurane?
1-chloro-2,2,2-trifluoroethyl-difluoromethyl-ether
what is the chemical name for desflurane?
1-fluoro-2,2,2-trifluoroethyl-difluoromethyl-ether
describe desflurane
- differs from isoflurane only in the substitution of a fluorine atom for a chlorine atom on the alpha ethyl carbon
- low boiling point, high vapor pressure requires temp controlled vaporizer and special bottle to prevent vaporization during pouring; vaporizer heats liquid to form gas which is blended w/ diluent gas flow
- stable in MOIST absorbent (dry absorbent causes CO)
- requires no preservatives
- pungent
what is the result of increased fluorination from isoflurane to desflurane?
- increased vapor pressure
- enhanced molecular stability
- decreased potency
what are the effects of dry CO2 absorbent on desflurane?
degradation of desflurane into carbon monoxide
what are the effects of desflurane’s pungents odor on airway?
- increased airway irritation
- increased salivation
- breath holding
- coughing
- laryngospasm
- w/ concentration greater than 6% on induction
- avoid in smokers w/ reactive airways
how does the decreased potency of desflurane affect its MAC?
- MAC changes w/ age, but d/t its decreased potency, desflurane MAC changes are much larger
- 0.6-0.7 yrs.: 9.96%
- 25 yrs.: 7.25%
- 36-49 yrs: 6.0%
- 65 yrs.: 5.17%
what is the fat:gas solubility of desflurane and what is the significance?
- 13 compared to 70 for isoflurane
* does not like to be stored in fat, so good use w/ obese (esp. w/ sleep apnea) if cases are longer
what is the significance of desflurane’s low blood:gas solubility?
- blood:gas solubility of 0.42, very similar to N2O of 0.46
- more rapid increase and decrease in alveolar concentration w/ lower soluble agents
- faster recovery
- wake up times approx. 50% faster than w/ isoflurane
describe desflurane effect on heart rate
- rapid increase in concentration above 6% can cause sympathetic stimulation w/ increased HR and BP
- can double HR and BP w/ change from 4% to 8% in less than one minute
- most commonly seen in young, healthy pts. w/ little opioid (max increases inverse w/ age; elderly, decreased change in HR but see increased change in BP)
- occurs both w/ N2O and w/o
- returns to normal with 5 minutes (if go back don’t and increase % fast again, wont see effect again)
- beta blockers may block this effect
- caution w/ CAD pts.
what can help limit the change in HR and BP w/ desflurane?
- fentanyl 1.5 mcg/kg prior to increasing concentration
- don’t exceed 6%
- increase (even above 6%) slowly minimizes changes
- alfentanil, sufentanil, clonidine, beta blockers
- esmolol affects the increase in HR, but doesn’t change increase in BP
- lidocaine 1.5 mg/kg minimizes HR response, but not BP response
- propofol and N2O have no effect
how does desflurane effect SVR?
-decreases, but to lesser extent than w/ isoflurane (has a bigger increase in NE)
how does desflurane effect coronary vascular resistance?
- decreased resistance to coronary blood flow
- redistribution (coronary steal) not seen w/ CAD present
what are respiratory effects of desflurane?
- respiratory depression similar to isoflurane up to 1.66 MAC of desflurane
- HPV preserved as it is w/ sevoflurane and isoflurane
what are neuromuscular effects of desflurane?
- causes fade w/ tetanus at 3% to 12%
- potentiated pancuronium, vecuronium, rocuronium, and SCh in a dose dependent manner (steroid class non-depolarizers)
- dose dependent: increased concentration, increased potentiation
what are CNS effects of desflurane?
- EEG changes similar w/ isoflurane
- burst suppression at 1.24 MAC
- no seizure activity
- cerebral blood flow similar to isoflurane during 1 and 1.5 MAC
- increases CBF and ICP in normocarbic, normotensive pt.
- consider use during deliberate hypotension d/t rapid titratibility and reduction of CMRO2 and CPP
describe metabolism of desflurane
- least metabolized at 0.02%
- minute amount of trifluoroacetic acid produced
- no increase in serum inorganic fluoride
when was sevoflurane introduced?
- 1990 (Japan)
- 1995 (US)
what are the properties of sevoflurane?
- blood:gas- 0.69
- MAC- 1.8%
- MAC awake- 34%
- MW- 200
- vapor pressure- 170 torr at 20 C (lowest)
- MAC at 0.6 yr.-25yrs: 2.5-2.6%
what is the chemical name of sevoflurane?
Fluoromethyl-2,2,2 trifluoro-1-(trifluoromethyl) ethyl ether
describe sevoflurane
- nonpungent, sweet smelling
- low solubility (more than des) blood:gas- 0.69, fat:gas 37
- unstable
describe how sevoflurane is unstable
- can spontaneously degrade, must have water added as a preservative
- reactive w/ CO2 absorbent to produce compound A
- potential for fire w/ dry absorbent
- can degrade to hydrogen fluoride w/ reaction w/ glass bottle packaging, anesthesia equipment and manufacturing impurities (water added and bottles changed to plastic)
- hydrogen fluoride can cause acid burns to lungs and mucosa
what is done to prevent effects of compound A
- minimum of 1 L/min flow up to 2 MAC hrs
- greater than 2 MAC hrs. use no less than 2 l/min
- increased flow decreases CO2 being rebreathed and exposed to absorbent and keeps temp down
describe effects of sevoflurane’s solubility
- shorter cases, quicker emergence (similar to des)
- longer cases seems to act more like iso
how does sevoflurane effect myocardium and HR?
- myocardial depression comparable to isoflurane at equal MAC concentration (protectant effect; decreases work and O2 consumption)
- rarely may see bradycardia; treat by decreasing concentration
- prolonged QT interval; use w/ caution w/ pts. w/ previously prolonged QT (leads to torsades)
what are the effects of sevoflurane on SVR?
- reduces SVR in slightly less magnitude than isoflurane
- different mechanism than iso: reduces resistance through the aortic arch (arterioles at higher concentrations and abruptly)
- isoflurane reduces arteriolar resistance gradually and dose dependently
what is the effect of sevoflurane on baroreflex?
-preserved to greater extent than w/ other agents
what are effects of sevoflurane on respiratory?
- bronchodilator
- Stoelting states it causes least degree of airway irritation among available agents
- good for smokers, irritable airways, COPD, etc.
how does sevoflurane compare to halothane for inhalation inductions?
- slightly faster (least soluble)
- less pt. movement
- quicker onset of immobility
- fewer airway problems
- some studies contradict
- at high concentrations, sevo causes less myocardial depression than halothane
describe sevoflurane effects during an inhalation induction on a healthy, unpremedicated adult
- given capacity breaths of up to 7% sevo
- loss of lash reflex in 1 min
- acceptance of LMA in 1.7 min
- laryngoscopy, intubation in 4.7 min
- capacity breaths: asked to take big, deep breaths and blow all out (decreasing FRC by decreasing ERV) then take big vital capacity breaths to fill alveoli w/ sevo
how does sevo effect HPV?
preserved as with des and iso
what are neuromuscular effects of sevoflurane?
- similar to other agents, enhanced intensity and duration of NMB
- may prolong duration of rocuronium longer than isoflurane (but less than des)
what are CNS effects of sevoflurane?
- autoregulation preserved up to 1.5 MAC
- cerebral vasodilation similar to that w/ isoflurane
- EEG may have evidence of seizure activity (7% concentration)
what are the effects of sevoflurane on platelet aggregation?
- inhibited more strongly than w/ halothane, d/t the suppression of arachadonic acid, probably d/t inhibition of cyclooxygenase
- not clinically evident
describe metabolism of sevoflurane
- 5-8% metabolized by C-P450 to produce inorganic fluoride
- levels of serum fluoride greater than 50 mcm/L in 7% of pts., but no evidence of clinically significant renal dysfunction (no increase in BUN or creatinine)
- metabolized by liver and some kidney; if just kidney would probably see damage
- different from other agents since no trifluoroacetic acid produced
when was nitrous oxide introduced
discovered by Priestly in 1772; used for analgesia/anesthesia in 1840s
what are the properties of N2O?
- blood:gas- 0.46
- MAC- 104%
- MAC awake- 64% of MAC
- MW- 44
- critical temp- 35.5 C
- vapor pressure- gas form at 20 degree C
what is the chemical structure of N2O?
N=N=O
*only inorganic agent (no carbon)
describe N2O
- inorganic
- low molecular weight
- odorless (sweet smelling)
- low solubility; equilibrates rapidly (inspired 70% achieves 90% equilibration in 15 min)
- low potency (cant get to MAC unless in hyperbaric chamber)
- nonflammable; but supports combustion
- N2O stored in a liquid-gas equilibrium in blue cylinder
- 745 psi liquid in equilibrium w/ gas
- stable in soda lime
- impurities in N2O: N2, NO, NO2, water vapor
- does not combine w/ hgb, carried in solution in blood
- induces hepatic enzymes
describe metabolism of N2O
- less than 0.004% metabolized by intestinal flora (pseudomonas)
- not metabolized by human body (liver/kidneys)
what are cardiac effects of N2O?
- myocardial depression directly
- young healthy: sympathetic stimulation and increased SVR d/t increased endogenous catecholamines
- increased PVR, esp. if PVR already slightly elevated (pulm. HTN, congenital heart w/ shunts) *avoid N2O
- preexisting CV disease (LV dysfunction), myocardial depression enhanced (less than MAC equivalent of potent agents) *avoid
- *although myocardial depressant effects directly, often see increased BP, CO, and HR d/t stimulation of catecholamines
what are respiratory effects of N2O?
- at concentrations less than 50%, no increase in PaCO2
- increases RR more than other agents (maintains Vm better than other agents)
- response to hypoxia is reduced w/ even small amount of N2O (like potent agents, not dose dependent)
what are neuromuscular effects of N2O?
- does not potentiate NMB
- at high concentrations, causes skeletal muscle rigidity
what are CNS effects of N2O?
- produces analgesia and amnesia
- analgesia d/t increase in enkephalins produced
- nystagmus occurs w/ 50% nitrous
- cerebral vasodilation less than potent agents (helps to decrease increase in CBF w/ other agents)
- increases CMRO2
describe GI effects of N2O
- gas in the bowel will increase in size w/ the use of N2O
- increased incidence of PONV
what are uterine/reproductive effects of N2O?
- does not effect uterine tone
- weak teratogen when used in high concentrations for prolonged time frame (just don’t use w/ pregnant women)
describe N2O effect on vitamin B12 dependent enzymes
- N2O inhibits methionine synthetase, which is necessary for myelin formation, and thymidylate synthetase, which is necessary for DNA synthesis
- prolonged exposure can result in bone marrow depression- megaloblastic anemia, and even neurological deficiencies- peripheral neuropathies and pernicious anemia
how long after exposure to N2O are critically ill pts. ability to synthesize DNA decreased?
up to 6 days after exposure
w/ one study, what did the results show d/t no use of N2O?
- decreased PONV
- decreased wound infection
- decreased fever
- decreased pneumonia
- decreased atelectasis
describe the diffusion of N2O
- 34x more soluble than nitrogen in the blood
- absorbed into air-filled spaces faster than nitrogen moves back into the blood causing expansion of the “bubble”
- no N2O use w/ GI, pneumothorax, tympanoplasty, CVL placements, ect.
what are the immunologic effects of N2O?
- affects chemotaxis and motility of polymorphonuclear leukocytes for phagocytosis, which is necessary for the inflammatory response to infection
- decreased wound healing and increased infection
describe diffusion hypoxia associated w/ N2O
- Nitrous is so insoluble that it returns to alveoli so rapidly in such volumes that it dilutes other gases including O2
- the hypoxia that can occur can be avoided if supplemental O2 is administered for the first 5-10 min after N2O is discontinued
describe the 2nd gas effect associated w/ N2O
- administering high concentrations of N2O will cause an increase of the alveolar concentration of a second gas
- Fick’s Law
- theoretic
what caution should be taken with N2O in regards to O2?
- when N2O is utilized, the O2 concentration must be decreased
- care must be taken to avoid hypoxia, esp. in special populations
- C-section: common practice to deliver no more than 50% N2O prior to the delivery of the infant
what are occupational risks of N2O?
- with no scavenging, reduced fertility
* w/ scavenging, no difference in fertility and birth defects w/ general population
