Anaesthesia Inhalation Agents and reactions with absorbents

Inhalation agents

The inhalation agents that are commonly used in Africa and other places where resources are limited are ether and halothane. When it is available, trichloroethylene is also used.
In the West halothane has been displaced by newer agents: isoflurane and sevoflurane. (Halothane is still widely used in paediatric anaesthesia.) These are far more costly than halothane and will not be considered in detail, though if you get the chance to use isoflurane you will be impressed how good the recovery is compared to halothane. Ether, of course, is never used in the western world and trichloroethylene has a diminishing number of users world-wide and is hard to get. (Laboratory grade is still available).

Ether (diethyl ether)

This is a very cheap agent as it is non-halogenated, made from sugar cane via ethanol using recycled sulphuric acid. With suitable fire precautions, it could easily be made locally in any country with the will to be self-sufficient. Dr William T.G.Morton, a dentist from Boston, Massachusetts is considered as the person responsible for discovering/inventing the practical use of anaesthesia for surgery. He demonstrated its effects on a famous occasion in Boston, USA, in 1846 and this event has become recognised world-wide as the "first anaesthetic".

Physical properties: Low boiling point: 35°C. High SVP (Saturatated Vapour Pressure) at 20°C : 425 mm Hg. Blood/Gas partition coefficient: 12 (high), MAC (Mean Alveolar Concentration): 1.92% (low potency).

Ether is highly volatile and inflammable. In oxygen, it is explosive. It has a very strong and characteristic smell.

Advantages:

Stimulates respiration and cardiac output, maintaining blood pressure and causes bronchodilatation, all due to its sympathomimetic effect mediated by adrenaline release.
A good sole anaesthetic agent because of its analgesic effect.
Does not relax the uterus like halothane but gives good abdominal relaxation.
A safe agent.

Disadvantages:

Flammable
Slow onset
Slow recovery
Secretions needing atropine
Bronchial irritation, so inhalation induction of anaesthesia by mask is very difficult because of coughing.
P.O.N.V. (postoperative nausea and vomiting) is sometimes seen in Africa but is a major disadvantage in the West, where patients vomit much more.

Indications: Any general anaesthetic, but especially good for Caesarean section (because the baby tolerates it and the uterus contracts well), and major cases with intubation. It is life saving for poor risk cases using a low dose. Also indicated when no supplementary oxygen is available.

Contra-indications: There are no absolute contra-indications for ether.

Scavenging should be carried out (where possible) to avoid contact between heavy inflammable ether vapour and diathermy apparatus or other electrical devices that may spark and also to prevent exhaled vapour blowing at the surgeon.

Practice points: The best method is to give a high concentration to a paralysed, intubated patient. Thus after atropine, thiopentone, suxamethonium and intubation, generous IPPV (Intermittent positive pressure ventilation) is commenced with ether 15-20% and then according to the patient's needs, the ether is reduced after about 5 minutes to 6-8%. Remember vaporiser performance is variable. Poor risk, septic or shocked patients may need only 2%.

It seems to be purely fortuitous, but the patients that benefit most from ether anaesthesia, such as Caesarean section and emergency laparotomy (which comprise over 90% of all major surgery in Africa) do not need diathermy. Where diathermy is essential, eg. in paediatric surgery, halothane is a better drug, so the conflict between ether and diathermy rarely arises. At our hospital, we do not allow ether to be used with diathermy.

Halothane ("Fluothane")

Physical properties: Boils at 50°C, SVP at 20°C: 243mmHg. Blood /Gas partition coefficient:2.3, MAC 0.75%.

Advantages:

Well tolerated, non-irritant, potent (low MAC) agent, which is relatively insoluble in blood, giving rapid induction
low dose maintenance and rapid recovery
There is predictable, dose-related depression of the respiratory and cardiovascular systems.
The ideal inhalation induction agent.

Disadvantages:

Perhaps too potent, and overdose is easy.
Poor analgesic properties necessitating deep planes of anaesthesia before surgery and especially intubation can be tolerated.
No post-operative analgesia.
Uterine relaxation and haemorrhage at concentrations above 2%
Hypotension, dysrhythmias and especially dangerous with adrenaline where cardiac arrest in VF (Ventricular Fibrillation) readily occurs.
Post-operative shivering.
"Halothane hepatitis" may very rarely occur. It is extensively metabolised in the body and is best avoided within three months of a previous halothane anaesthetic unless the indications to use halothane are considered to override the risk of this rare condition.

Indications: almost all general anaesthesia, especially paediatrics. Inhalation induction especially in upper airway obstruction.

Contra-indications: simultaneous administration with adrenaline, especially during spontaneous breathing. High dose for Caesarean section or uterine evacuation. History of unexplained hepatitis following a previous anaesthetic.

Dosage: Induction with 3%, reducing to 1.5% for maintenance. Children need 2% for maintenance. Over 4% for more than a few minutes will produce an overdose.

Practice Points: Halothane alone is not ideal because it has no analgesic properties. You need high concentrations to abolish reflex activity, eg. straining on the endotracheal tube. This becomes expensive and may also be unsafe. The common clinical situation of an intubated patient breathing spontaneously high concentrations of halothane in oxygen and air is potentially hazardous in the presence of heart disease.

Nitrous oxide is commonly used for analgesia; opioids or regional blocks are alternatives.

Supplementary oxygen is mandatory when using halothane to avoid hypoxia.

Trichloroethylene ("Trilene")

Physical properties: Boils at 87°C (high), SVP at 20°C: 60 mmHg. Blood/Gas partition coefficient: 9 (high), MAC 0.17%

Advantages:

Non-irritant
Safe
Good analgesia during and after surgery
Cardiovascular stability
Very cheap, because one uses so little

Disadvantages:

Low volatility, slow onset of effect because of high blood solubility and low boiling point making it impossible to get concentrations that are high enough
It is a potent agent because you need little to produce an effect, BUT it is a weak anaesthetic because, despite this, vaporisers cannot produce high enough concentrations because the volatility is so low.
Dysrhythmias may occur with adrenaline
Prolonged recovery, because of high blood solubility.

Indications: analgesic supplement to halothane or used on its own for minor procedures such as fracture manipulation, debridement etc.

Contraindications: overdosage in the elderly. Closed circuit with soda-lime. Best avoided in very small babies.

Dosage: 0.5 - 1% initially, reducing to 0.2 - 0.5%.

Practice Points: Switch off 20-30 minutes before the end of a long operation to avoid prolonged sedative effects. Its ideal function is to give background analgesia for long cases using halothane as the main anaesthetic but it is also very good given with halothane for a fast turn-over of short cases using inhalation induction.

The newer agents:

Enflurane: was a replacement for halothane, now used infrequently.

Isoflurane: Boils at 48°C. SVP at 20°C: 250mmHg, Blood/Gas partition coefficient: 1.4, MAC: 1.15. In general use, good recovery because of relatively low blood solubility, but induction difficult because of irritating bad smell, minimal metabolism, no arrhythmias but causes hypotension, six times the cost of halothane. Big cost reductions when used in a low flow system.

Desflurane: Boils at 23.5°C, SVP at 20°C: 673 mmHg, Blood/Gas partition coefficient 0.4 (low), MAC: 5-10%. Replacement for enflurane, requires a specially designed vaporiser, has come and gone without me ever seeing it!

Sevoflurane: Boils at 58.5°C, SVP at 20°C: 160 mmHg, Blood/Gas partition coefficient 0.6 (low), MAC: 1.7-2%. Expensive, but costs can be reduced if used in a low flow system. There may be problems with sevoflurane and carbon dioxide absorbers, baralyme in particular, but these are currently being investigated. Ultra low solubility resulting in ultra rapid induction and recovery especially as it is non-irritant and sweet smelling. High volatility and high percentage required.

How should volatile agents be used? One way is to use them for inhalation induction of anaesthesia followed by maintenance with the same or another agent as your sole anaesthetic. The patient puts him or herself to sleep by breathing via a close-fitting mask and provided the smell is accepted and the stage II excitement effects are not excessive, this is a very satisfactory method of inducing general anaesthesia for minor cases without gastric aspiration risk. Lung disease, smoking or drinking habit, obesity and high uptake situations (see above) will make this method slower and prolong stage II effects. Loss of airway in an obese patient may be dangerous. Ideal for a fast turn-over of lots of short procedures on thin patients.

The other way is to give an intravenous induction followed by the volatile agent for maintenance of anaesthesia. Very often the intravenous induction will include intubation of the trachea as well. All general anaesthesia for major cases will be done this way.

Carbon Monoxide production in anaesthesia

Reports concerning CO (Carbon Monoxide) toxicity from the interaction of halogenated ether anaesthetics and C02 (Carbon Dioxide) absorbents have received a great deal of attention. The experimental conditions in which this phenomenon can be induced on a lab bench involve absorbents deliberately dried to a very abnormally low (or absent) water content a highly unusual situation. Questions have been raised as to what all this means.

Clinical decisions are most difficult when there is incomplete scientific knowledge. This is currently the situation the clinician faces in deciding how to react, if at all, to recent reports of the potential threat of anaesthesia-induced carbon monoxide toxicity.

Carbon monoxide 'CO' is toxic in very low concentrations. The severity of toxicity depends both on the duration of exposure and on the concentration inhaled. Other influencing factors include the level of exercise and coexisting medical conditions. From a practical standpoint, exposure to greater than 50 ppm (parts per million) for eight hours should be avoided. Even brief exposure to greater that 200 ppm is considered hazardous. Carbon monoxide reacts with haemoglobin (Oxygen transporting protein in red blood cells) to form deoxyhemoglobin (haemoglobin without oxygen). Textbooks of environmental medicine provide standard tables that predict carboxyhemoglobin (Haemoglobin that has 'CO' bound to it instead of Oxygen) level as a function of carbon monoxide concentration in inspired air and of duration of exposure. For example, exposure to 1,000 ppm for one hour would be expected to produce 30% carboxyhemoglobin.

The toxicity of carbon monoxide is by no means limited to direct replacement of oxygen on haemoglobin. Even a small concentration of carboxyhemoglobin causes the oxygen-haemoglobin dissociation curve to shift sharply to the left, thereby preventing the normal unloading of oxygen in the capillary bed. Thus, the patient can suffer tissue hypoxia (lack of oxygen) while the blood partial pressure of oxygen is high. Moreover, carbon monoxide also poisons the cytochrome enzyme system, further depressing the utilization of oxygen.

It is difficult to know exactly at what carboxyhemoglobin levels mortality occurs because most victims receive therapeutic oxygen between the time of exposure and arrival at a health care facility where the carboxyhemoglobin level is determined. However, the peak level can be estimated. It is generally thought that death may result from carboxyhemoglobin levels of 50 percent in young healthy victims. Patients with underlying cardiovascular disease may be at risk from significantly lower levels.

In recent years, anaesthesiologists have not concerned themselves very much with iatrogenic (Iatros means physician in Greek, and -genic, meaning induced by) carbon monoxide poisoning. This is in part because closed circle anaesthesia fell out of favour after cyclopropane disappeared from clinical use. With closed circle anaesthesia, there had been occasional reports of carbon monoxide build up in the anaesthetic circuit, especially in patients who had required significant blood transfusions. Smoking by the blood donor and haemoglobin destruction were thought to be factors.

A case of unanticipated carbon monoxide toxicity (the patient was receiving desflurane). The case occurred Monday morning and it was postulated that something happened to the anaesthesia system during prolonged disuse which ultimately led to the release of carbon monoxide.

It has been reported, however, that clinically insignificant amounts of carbon monoxide were found after experimentally exposing anaesthetic agents to soda lime. It was postulated that carbon monoxide might be absorbed by soda lime and then released after a period of disuse. Flushing the system with a high fresh gas flow seemed reasonable.

Recent clinical reports of increased carbon monoxide (CO) haemoglobin concentrations in children anaesthetized with sevoflurane that had passed through dry soda lime seem to contradict the laboratory experience with this anaesthetic. To examine discrepancies between laboratory investigations and clinical experiences, Experiments have been carried out to measure CO formation from five different volatile anaesthetics passed through an absorber system that permitted temperature changes. (Wissing BMC Anesthesiology 2005, 5:6 doi:10.1186/1471-2253-5-6 )

Experiments were conducted in triplicate. Either 2.5% or 5% of five inhalational anaesthetics (desflurane, enflurane, isoflurane, halothane, and sevoflurane) were passed for 2 hours through an absorber canister filled with dried soda lime. Baseline CO production was first determined using dry soda lime and a flow of 2 l/min O2 with no volatile anaesthetic and using fresh wet soda lime and a flow of 2 l/min with 5% anaesthetic. CO concentrations were continuously measured at the absorber outlet. Additional experiments were conducted to confirm the sevoflurane results because the magnitude of CO production was unexpected and because of the potential of various breakdown products. CO was detected with all anaesthetics passed through dry soda lime, but the time course and rate of CO production and the time course of temperature changes differed between the agents. Measurable amounts of CO were found immediately after desflurane, enflurane, or isoflurane came in contact with the soda lime; with sevoflurane, there was a time delay between contact and CO production. CO production peaked initially and was highest with desflurane, followed by enflurane, isoflurane, sevoflurane, and halothane. The temperature of the absorbent increased with all anaesthetics, but was highest for sevoflurane. As a result of these experiments, the researchers caution that although CO production is clearly higher than with other agents, some CO-in possibly relevant amounts-is produced by sevoflurane. Adequate precautions should be taken to ensure that soda lime in absorbers does not become desiccated.

Previous studies, in which volatile anaesthetics were exposed to small amounts of dry soda lime, generally controlled at or close to ambient temperatures, have demonstrated a large carbon monoxide (CO) production from desflurane and enflurane, less from isoflurane, and none from halothane and sevoflurane.

However, there is a report (Anesthesiology: Volume 95(5) November 2001 pp 5A-6A Henkel, Gretchen) of increased CO haemoglobin in children who had been induced with sevoflurane that had passed through dry soda lime. Because this clinical report appears to be inconsistent with existing laboratory work, the authors investigated CO production from volatile anaesthetics more realistically simulating conditions in clinical absorbers.

Methods :
Each agent, 2.5 or 5% in 2 l/min oxygen, were passed for 2 h through a Drager absorber canister (bottom to top) filled with dried soda lime (Dragersorb 800). CO concentrations were continuously measured at the absorber outlet. CO production was calculated. Experiments were performed in ambient air (19-20[degrees]C). The absorbent temperature was not controlled.

Results :
Carbon monoxide production peaked initially and was highest with desflurane (507 +/- 70, 656 +/- 59 ml CO), followed by enflurane (460 +/- 41, 475 +/- 99 ml CO), isoflurane (176 +/- 2.8, 227 +/- 21 ml CO), sevoflurane (34 +/- 1, 104 +/- 4 ml CO), and halothane (22 +/- 3, 20 +/- 1 ml CO) (mean +/- SD at 2.5 and 5%, respectively).

Conclusions :
The absorbent temperature increased with all anaesthetics but was highest for sevoflurane. The reported magnitude of CO formation from desflurane, enflurane, and isoflurane was confirmed. In contrast, a smaller but significant CO formation from sevoflurane was found, which may account for the CO haemoglobin concentrations reported in infants. With all agents, CO formation appears to be self-limited.

Volatile Anaesthetic Degradation

Consequences of volatile anaesthetic degradation by carbon dioxide absorbents that contain strong base include formation of compound A from sevoflurane, formation of carbon monoxide (CO) and CO toxicity from desflurane, enflurane and isoflurane, delayed inhalation induction, and increased anaesthetic costs. Amsorb (Armstrong Ltd., Coleraine, Northern Ireland) is a new absorbent that does not contain strong base and does not form CO or compound A in vitro. An investigation compared Amsorb, Baralyme (Chemetron Medical Division, Allied Healthcare Products, St. Louis, MO), and sodalime effects on CO (from desflurane and isoflurane) and compound A formation, carboxyhemoglobin (COHb) concentrations, and anaesthetic degradation in a clinically relevant porcine in vivo model.

Methods:
Pigs were anesthetized with desflurane, isoflurane, or sevoflurane, using fresh or partially dehydrated Amsorb, Baralyme, and new and old formulations of sodalime. Anaesthetic concentrations in the fresh (preabsorber), inspired (postabsorber), and end-tidal gas were measured, as were inspired CO and compound A concentrations and blood oxyhemoglobin and COHb concentrations. RESULTS: For desflurane and isoflurane, the order of inspired CO and COHb formation was dehydrated Baralyme >> soda-lime > Amsorb. For desflurane and Baralyme, peak CO was 9,700 +/- 5,100 parts per million (ppm), and the increase in COHb was 37 +/- 14%. CO and COHb increases were undetectable with Amsorb. Oxyhemoglobin desaturation occurred with desflurane and Baralyme but not Amsorb or sodalime. The gap between inspired and end-tidal desflurane and isoflurane did not differ between the various dehydrated absorbents. Neither fresh nor dehydrated Amsorb caused compound A (Compound formed from chemical reactions between the agent and CO2 absorbent) formation from sevoflurane. In contrast, Baralyme and sodalime caused 20-40 ppm compound A. The gap between inspired and end-tidal sevoflurane did not differ between fresh absorbents, but was Amsorb < sodalime < Baralyme with dehydrated absorbents.

Conclusion
Amsorb caused minimal if any CO formation, minimal compound A formation regardless of absorbent hydration, and the least amount of sevoflurane degradation. An absorbent like Amsorb, which does not contain strong base or cause anaesthetic degradation and formation of toxic products, may have benefit with respect to patient safety, inhalation induction, and anaesthetic consumption (cost).

Submitted by John Sandham

Sources: