Inhalation Agents:
New Drugs, New Gas Flows

Alan Baxter, MB

Department of Anaesthesia, Ottawa Hospital - General Site and University of Ottawa

Lecture Objectives:

1. To review the theoretical and practical aspects of low and minimal flow anaesthesia
2. To place in perspective safety and other concerns about these techniques
3. To encourage the economical use of present generation and new agents

Introduction:

Despite the recent interest and advances in intravenous anaesthetics, opioids, and infusion techniques, the vast majority of general anaesthetics continue to involve primarily inhalational agents. Low or minimal flow anaesthesia allows the anaesthetist to supply to the patient only the actual amount of drugs and oxygen being taken up, avoiding waste. The technique has been in use since the early days of general anaesthesia, with popularity varying widely over the years. There has been a resurgence of interest in low flow anaesthesia over the last few years because of:

• economic concerns
• environmental concerns
• enhanced monitoring technology
• introduction of new (expensive) inhalational anaesthetics.

This presentation will focus on the practical application of the technique of low flow anaesthesia, and the new agents recently released or on the horizon in Canada.

Definitions:

Metabolic flow = 250 ml/min
Minimal flow = 250-500 ml/min
Low flow = 500-1000 ml/min
Medium flow = 1-2 l/min
High flow = 2-4 l/min
Very high flow = > 4 l/min

Vaporiser in circuit (VIC):

• doesn't meet CSA standards, therefore little used.

Vaporiser out of circuit (VOC):

• most familiar & commonly used.

Liquid injection techniques:

• Bolus injection - fluctuating concentrations in circuit.
• Infusion techniques - smoother.
• Lowe's nomogram.
• Too complicated, little/no advantage over VOC technique.

Early workers developed the circle system and Water's canister, with both VIC and VOC being popular. The popularity of low flow was enhanced by the use of explosive cyclopropane, but later diminished with the introduction of neuromuscular blockers and the introduction of accurate vaporisers such as the Copper Kettle and Fluotec series. Expansionist health care economics diminished economic concerns, and the publications of complexity of flows, uptake, and concentrations in circle also contributed to waning popularity. Enthusiasts later described injection techniques, nomograms, etc.

Advantages of low flows techniques:

• economics
• environmental
• uptake in action
• conservation of humidity and heat

Economics: The cost of volatile anaesthetics per case decreased from $19.20 to $15.16 (US) after promotion of low flow anaesthesia as cost containment measure at University of Michigan (NB incremental savings diminish as one approaches closed circuit flows).

Environmental: Chlorinated anaesthetics are broken down by UV radiation and may deplete ozone.

Uptake: Uptake is relatively large in the first few minutes of anaesthesia, and then diminishes as the gradient between the patient and the circuit shrinks. The time course of this depends on the solubility of the anaesthetic - insoluble drugs like nitrous oxide, desflurane, and sevoflurane have a rapid rise in concentration and reduction in uptake, while the uptake of more soluble isoflurane, enflurane, and halothane continues with larger amounts absorbed for a long time.

Initial high flows are needed to flush the circuit, replace the FRC and to provide gases for uptake into patient. Thereafter the basic principle of low flow is to maintain constant anaesthetic state by adding gases and vapours to the circuit at the same rate that the patient consumes them.

Why the reluctance to use lower flows?

• Habit
• Education
• Safety
  • hypoxic gas mixture
  • dependence on CO2 absorption
  • accuracy of vaporisers at low flows
• Anaesthetic concentration
• Complicated by use of formulae, nomograms, etc.

Equipment requirements

As for high flow or i/v anaesthesia, plus:

• rotameters calibrated to low flow (<1l)
  
• circle circuit and absorber
  
• volatile agent & N2O - in-circuit concentration monitor is desirable but not essential.

What else is happening in the circuit?

• humidification
• heat
• CO2
• other gases
• N2
• carbon monoxide
• methane
• acetone
• other inert gases
• degradation of agents
• some advocate periodic high flow flush of circuit.

New agents:

- Halogenation only with F-, cf isoflurane.
- Lower blood solubility allows more rapid adjustment of blood level, more rapid induction & recovery.

Sevoflurane: CFH2-O-CH-(CF3)2

• Decreased potency - MAC 2%.
• Insoluble & not pungent, minimal airway irritation - therefore effective for inhalational induction.
• Insoluble, therefore rapidly approaches steady state with reduced uptake under low flow conditions.
• Insoluble, therefore rapid elimination emergence, & psychomotor recovery.
• Most properties similar to isoflurane.
• Biodegradation 2%, to F- , ?risk of renal toxicity.
• Degraded to compound A (renal toxicity) by absorbents, therefore minimum flows of 2 l/min recommended.
• Halogenated only with F therefore ozone friendly.
• Best agent for paediatrics.

Desflurane: CHF2 -O-CFH-CF3

• Decreased potency - MAC 6%.
• No degradation by absorbents under normal (moist) condition, but will produce CO with dry absorbent.
• Pungency (>6%) limits usefulness for inhalational induction, especially in children, but this not a problem during maintenance.
• Insoluble, therefore rapidly approaches steady state with reduced uptake under low flow conditions.
• Insoluble, therefore rapid elimination emergence, & psychomotor recovery.
• Tachycardia with rapid deepening of anaesthesia.
• Little biodegradation 0.02%.
• Halogenated only with F therefore ozone friendly.
• Best agent for low flow anaesthesia.

Conclusions

There is little or no reason not to use low/minimal flow techniques with presently available agents, and economic & environ- mental advantages to doing so. With present understanding of anaesthetic uptake, and modern technology, there should be no increased safety concerns.

The new agents, sevoflurane and desflurane have several advantages over the present generation, agents but are not ideal and their cost-effectiveness has to be established.

Questions:

1. Which of the following circuit contaminants have caused clinical problems in man?

a) Methane
b) Acetone
c) Carbon Monoxide (carboxy-haemoglobin levels of up to 30% have been reported in patients)
d) Argon
e) Compound A

2. Low/minimal flow anaesthesia is inherently dangerous and requires enhanced patient monitoring because of :

a) Rapid and unpredictable fluctuations in inspired oxygen concentrations during anaesthesia
b) Difficulty with monitoring depth of anaesthesia c) Over-humidification of circuit contents
d) Exposion hazard
e) None of the above

3. Match the volatile drug with the relevant property (an agent may be the answer to more than one question):

1) Sevoflurane
2) Halothane
3) Isoflurane
4) Desflurane
5) Methoxyflurane

a) Lowest solubility
b) Best for inhalational induction
c) Has caused renal failure from fluride ion production
d) Least biodegradation
e) Least stable in vitro

Answers: a-4, b-1, c-5, d-4, e-1.

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