Volatile anesthetics Flashcards
Modern inhaled anesthetics
Volatile anesthetics
- isoflurane
- desflurane
- sevoflurane
- –> all have ether moiety
- –> liquid at room temp
- –> desflurane has unique vapor pressure, uses own vaporizer
N2O is a gas at room temp
Why use inhalend anesthetics?
- Reliable effects
- Hallmark of general anesthesia –> cause unconsciousness, amnesia, immobility
- Level and effect of anesthesia can be safely monitored
- Inexpensive
- Ease of administration
Monitoring effects of anesthesia
Vital signs
- EKG rhythm, heart rate
- BP
- O2 sat
- with spontaneous respiration –> resp rate, tidal vol, pattern of respiration
Movement in response to surgery
Levels of exhaled gases –> O2, N2, CO2, N2O, volatile anesthetics
Goal of inhaled anesthetics
- To produce the anesthetic state by establishing a specific concentration of anesthetic molecules in the CNS
- Achieved by establishing the specific partial pressure of the agent in the lungs, which ultimately equilibrates with the brain
Mechanism of action
- poorly understood
- immobility –> acts on spinal cord
- amnestic effects –> acts on brain (hippocampus, amygdala, cerebral cortex)
- CNS depression
- –> enhance inhibitory neurotransmitters (GABA + glycine)
- –> block excitatory neurotransmitters (NMDA)
Definition
- partial pressure
- solubility
Partial pressure –> for any mixture of gases in a closed container, each gas exerts a pressure proportional to its fractional mass
Solubility –> used to describe tendency of a gas to equilibriate with a solution, hence determining its concentration in solution
- implications –> anesthetic gases administered via the lungs diffuse into blood until the partial pressures in alveoli and blood are equal
Minimum alveolar concentration (MAC)
Effects of inhaled anesthetics must be based on a dose –> this dose is the MAC
- MAC is the alveolar concentration of an anestetic at one atmosphere that prevents movement in response to a surgical stimulus in 50% of patients
- it is analogous to the ED50 expressed for IV drugs
- MAC>0.5 = amnesia
- MAC =1 = surgical anesthesia
- MACs are additive
- MAC declines 6% per decade of life –> highest at 6 months
Blood:gas partition coefficient or solubility
Blood brain partition coefficient
Blood:fat partition coefficient or solubility
oil-gas partition coefficient
Blood:gas partition coefficient or solubility –> solubility of a gas in blood
Blood brain partition coefficient –> mirrors blood-gas solubility
Blood:fat partition coefficient or solubility –> solubility of gas in tissue/fat
Oil-gas partition coefficient –> correlates lipid solubility with potency
- potency is roughly equivalent to MAC
- N2O <iso
MACs and solubilities
N20
- MAC = 104
- blood-gas partition coefficient = 0.46
- oil-gas partition coefficient = 1.4
- fat-blood solubility = 2.3
Isoflurane
- MAC = 1.17
- blood-gas partition coefficient = 1.46
- oil-gas partition coefficient = 91
- fat-blood solubility = 45
Sevoflurane
- MAC = 1.8
- blood-gas partition coefficient = 0.69
- oil-gas partition coefficient = 147
- fat-blood solubility = 48
Desflurane
- MAC = 6.6
- blood-gas partition coefficient = 0.42
- oil-gas partition coefficient = 19
- fat-blood solubility = 27
Factors that increase and decrease MAC
Factors that increase MAC
- increased central neurotransmitter levels –> MAO inhibitors, cocaine, levodopa, ephedrine, acute detroamphetamine administration
- chronic alcohol abuse
- hyperthermia
- hypernatremia
Factors that decrease MAC
- increased age
- metabolic acidosis
- hypoxia
- decreased CNS NT levels –> a-methyldopa, reserpine, chronic detroamphetamine administration, levodopa
- hypothermia
- hyponatremia
- pregnancy
- acute alcohol intoxication
- drugs –> lithium, lidocaine, opioids, barbiturates, alpha 2 agonists, ketamine
Pharmacokinetics of inhaled anesthetics
At equilibrium = PA = Pa = Pbr
Based on concentration gradient
- uptake from alveoli into systemic circulation
- uptake from circulation into brain
- redistribution of anesthetic throughout the body
Induction –> Pbr equilibrates with PA (and Pa) within 6-12 minutes
- highly perfused tissues equlibrate faster
The vascular system delivers blood to 3 physiologic tissue groups –> the vessel rich group, the muscle group and the fat group
- VRG = brain, heart, kidney, liver, digestive tract and glandular tissues
- anesthetic is delivered most rapidly to the VRG because of high blood flow –> here it diffuses according to partial pressure gradients
- CNS tissue takes in the anesthetic according to the tissue solubility, and at a high enough tissue concentration, unconsciousness and anesthesia are achieved
- increasing CNS tissue conc cause progressively deeper stages of anesthesia
PA mirrors the Pbr
- index of anesthetic depth
- reflection of rate of induction and recovery from anesthesia
- measure of potency
Thus, monitoring MAC of inhaled anesthetics provides an index of their effects in the brain –> anesthesia machine measures level of inspired and exhaled anesthetic gas
Factors determining PA
Inspired anesthetic partial pressure (PI)
- higher PI accelerates induction, offsets uptake into blood
- as uptake into the blood decreases, PI can be decreased to maintain a constant Pbr
Alveolar ventilation
- increased ventilation accelerates induction by more rapidly increasing PA
- offsets uptake into blood
Cardiac output
- influences uptake into the blood by controlling how much anesthetic is carried from the alveoli
- low CO speeds induction
Uptake and distribution
Uptake - follows ratio of fractional concentration of alveolar anesthetic to inspired anesthetic (FA/FI) over time
- the faster FA rises relative to FI, the faster the speed of induction since FA is proportional to PA
Solubility = main factor controlling rate of induction and emergence
- N2O<iso
Recovery from anesthesia
Inhaled anesthetic turned off
- PA = 0
- Patient breathes 100% oxygen
Partial pressure gradient reversed
- stored anesthetic in tissues diffuses down its concentration gradient into the blood and is exhaled
Similar to induction
- solubility of agent –> less soluble agents will allow faster emergence
- depends on alveolar ventilation –> more ventilation allows faster emergence
- depends on CO –> lower CO allows faster emergence
Different than induction
- tissue concentration –> tissues serve as a reservoir of inhaled anesthetics
- –> concentration depends on solubility and duration of anesthesia
- –> can have variable concentrations in different tissue
- metabolism –> minimal with modern anesthetics
Diffusion hypoxia
- occurs with N2O administration
- high initial outpouring of N2O from blood to alveoli can dilute and decrease PaO2
- hypoxia if patient breathes room air and not given enough high concentrations of O2
Desirable properties of an inhaled anesthetic
Anesthesia machine and breathing circuit
- lack of flammability
- ease of vaporization at room temp
- chemical stability
Lungs and breathing
- rapid induction and emergence
- lack of airway irritation
- bronchodilation
- lack of resp depression
Other requirements
- maintenance of MAP + HR
- low solubility in skeletal muscle and fat
- potency
Effects of inhaled anesthetics on circulatory system
MAP - decrease in MAP due to decrease in systemic vascular resistance
- N2O little change in MAP and SVR
HR –> small increase, iso>des
- no effect with N2O and sevo
Desflurane - transient circulatory stimulation with abrupt increase >1 MAC –> increase in HR + MAP
Little effect on CO
Few cardiac arrhythmias
Sevo may prolong QT interval
N2O - increases pulm vascular resistance
Cardioprotection –> ischemic preconditioning
- a preconditioning stimulus such as brief coronary occlusion and ischemia initiates a signaling cascade of intracellular events that reduces ischemia and reperfusion myocardial injury
- ischemic preconditioning seen with volatile anesthetics in patients with compromised regional perfusion
Effects of inhaled anesthetics on ventilation
- increase RR and decrease tidal vol –> minute ventilation preserved (RRxTV)
- decrease in FRC
- increase in dead space
- less efficient gas exchange with deeper anesthesia, PaCO2 increases
- less responsive to CO2 at higher MAC –> apnea
- inhalation induction –> best with seco and N20 (they are non-pungent)
- bronchodilation
- depression of pharyngeal and laryngeal reflexes
second gas effect of N2O
- ability of high volume uptake of one gas, N2O, to accelerate rate of increase of PA of concurrently administered “companion gas”
- “concentrating effect” - conc of second gas in smaller lung vol due to high vol uptake of the first gas
Effects of inhaled anesthetics on CNS
All cause cerebral vasodilation
- increased cerebral blood flow
- increased intracranial pressure
Uncoupling of CBF and CMRO2 –> decrease in CMRO2
Dose dependent EEG depression
N2) –> some mild analgesic properties
Other effects of inhaled anesthetics
Neuromuscular effects
- dose related skeletal muscle relaxation
- enhance activity of all paralytics
Decreased renal blood flow –> decreased GFR, decreased urine output
Decreased hepatic blood flow
Adverse effects - Compound A formation
Sevoflurane undergoes degradation in CO2 absorbents to form a vinyl ether called compound A
- production enhanced in low flow or closed circuit breathing systems, also warm or very dry CO2 absorbents
- well-defined species differences in the threshold for compound A induced nephrotoxicity
Adverse effects - CO and heat
Inhaled anesthetics degraded by CO2 absorbents to CO when normal water content of the absorbent (13-15%) is markedly decreased ( significant heat production, fires and patient injuries
Adverse effects - hepatic
Postop liver dysfunction associated with volatile anesthetics, commonly halothane
2 mechanisms
- more common form –> hepatocyte toxicity, relatively mild
- with repeat exposure, probably immune reaction to metabolites –> severe liver damage and fulminant hepatic failure
Unlike halothane, current volatile anesthetics have minimal adverse effects on the liver and might afford some protection for hepatocytes from ischemic and/or hypoxic injury
N2O toxicity
N2O decreases activity of vit B12 dependent enzymes = methionine synthetase and thymidylate synthetase
- Use > 24 hours –> megaloblastic anemia, pernicious anemia, neuropathy
Ability of N2O to expand air filled spaces –> most clinically relevant concern
- due to its greater solubility in blood compared to nitrogen
- N2O diffuses from blood into closed gas spaces (bowel, middle ear) easily
- 75% N2O can expand a pneumothorax to double or triple its size in 10 and 30 min, respectively
Malignant hyperthermia
Hypermetabolic reaction due to exposure to VA or succinylcholine
- 1/15,000 children, 1/50,000 adults
- 80% mortality without treatment, 5% with
- can occur during or a few hours after surgery
Mechanism
- autosomal dominant inheritance
- aberrant RYR1 receptor in skeletal muscle voltage gated Ca channel in T tubule
- uncontrolled CA release from SR
- sustained contractility and rigidity
- myocyte ischemia and cell death
- very increased CO2 production, anaerobic metabolism, severe acidosis
- hyperkalemia, myoglobinuria, renal failure
Signs of malignant hyperthermia
Exhaled CO2>55mmHg
Metabolic and respiratory acidosis
pH<7.25
Hyperthermia up to 43 °C
\+/- muscle rigidity
Hyper-/hypotension
Tachycardia, dysrhythmias
Renal failure
Disseminated intravascular coagulation (DIC)
Death:
Cardiac arrest, pulmonary/cerebral edemaTreatment of malignant hyperthermia
Discontinue triggering agents
Dantrolene 2.5 mg/kg, followed by infusion
Hyperventilate pt with 100% O2
Cool pt
Treat hyperK+, dysrhythmias, metabolic acidosis
Maintain good UO
Call for help
