Pisa 2002
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At present I have just these 7 papers.  I hope to upload the free papers soon.

Harper

Meakin

Franks

Leier

Rolly

Versichelen

White

Please note:

These abstracts were scanned from the set circulated to delegates.  I have not sought to reproduce all figures (though only a few are missing).   I have left the text largely unedited, hence variations in spelling and representation of decimals.  I have dared to correct a few obvious grammatical errors.      Please advise me of any crass mistakes.    The formatting will be sorted soon.

Do we still need non-rebreathing systems?

Dr G Meakin, Manchester

Breathing systems may be classified broadly into those which are fitted with a means of absorbing C02 (absorber systems - also called rebreathing systems) and those, which do not contain such units (non-absorber - non-rebreathing systems). (1) In the past, concerns about resistance to breathing and apparatus deadspace with the use of absorber systems led paediatric anaesthetists to use mainly non-absorber breathing systems. (2, 3) However, recent concerns for economy and environmental pollution have led to a renewed interest in the use of the circle absorber system in paediatric anaesthesia. (4) In this talk I am going to try to answer the question: - do we still need non-rebreathing systems in paediatric anaesthesia?

Characteristics of the ideal breathing system

The characteristics of the ideal breathing system would include:

• Simplicity

• Lightness

• Ease of use

• Low resistance

• Minimal deadspace

• Low compression volume

• Precise control of the delivered oxygen and anaesthetic concentrations

• Heat and moisture conservation

• Economical use of anaesthetic gases and the ability to scavenge waste gases

Clearly, no single system fulfils all of these requirements; therefore, the choice of breathing system for an individual patient will depend upon clinical circumstances and the patient's condition.

Clinical circumstances

During induction of anaesthesia, we may be more concerned about the ease of use of the breathing system, the ability to control anaesthetic concentrations and a low compression volume than with economy, since high flowrates are going to be required whatever system we choose. During maintenance of anaesthesia, when the inspired and expired anaesthetic concentrations have equilibrated, we may be more interested in using low flow rates to economize the use of anaesthetic agents. However, there may be little scope for low flow methods if the procedure is short. During recovery from anaesthesia economy is not a consideration and we may wish to have the convenience of a T-piece system.

Patients condition

The main patient condition relevant to our question is age. And here we have to be aware that the respiratory system of an infant is disadvantaged in various ways compared with that of an adult. (4) Accordingly, we will want to use a system with minimal resistance and deadspace. We will also want to use a system that is convenient to use in small children and has a low compression volume enabling us to control ventilation adequately in patients with a small tidal volume and low lung compliance. (5)

The circle system consists of a fresh gas inflow, inspiratory and expiratory breathing tubes with unidirectional valves, a spill valve, a reservoir bag, a carbon dioxide absorption unit and a fresh gas inflow. Putting the fresh gas inflow downstream and the spill valve upstream of the absorber improves the efficiency of the system by allowing expired gas from the patient to be vented preferentially.

The main advantages of the circle system are reduced loss of heat and moisture, economical use of anaesthetic gases and reduced operating theatre pollution. (6) From the point of view of their use in paediatric anaesthesia, there have been major concerns about increased resistance due to the inspiratory and expiratory valves and increased apparatus deadspace. (2, 3) Some authors hold the view that the system is relatively complex, bulky and prone to incorrect assembly. (7) It also has a relatively high compression volume and precise control of the delivered oxygen and anaesthetic concentrations can be difficult. (8)

Resistance to breathing during anaesthesia occurs in the breathing system and in the tracheal tube. Traditionally, it is measured in terms of the pressure drop across the equipment at a given flow rate. A study by Orkin and colleagues revealed that in a typical circle system the tubes and the absorber have about equal resistance and together account for about a third of the total resistance of the system (fig.l). (9) Three sets of valves tested had practically the same resistance and accounted for two-thirds of the total resistance. Their data indicate that for an average adult, whose peak flow under anaesthesia is about 35 litre min"', the pressure drop across the complete system should be less than 0.75 cm l-hO while that across the valves should be less than 0.5 cm HzO. Contrary to a widely held belief that the resistance imposed by older anaesthetic breathing systems was unduly high, these values appear to be quite acceptable. (10, 11) For an infant of 9 months, whose peak flow is about 10 litre min' ', the pressure drop across the systems tested by Orkin and colleagues should be less than 0.25 cm l-hO. By contrast, the pressure drop across a 3.5 mm tracheal tube in a 3 month old infant with a peak flow about 6 litre min'¹ should be approximately 2.5 cm H2O. (12) These figures suggest that the resistance of the tracheal tube in a young infant is at least 10 times that of the circle system.

Figl.

                        Litres per minute

Apparatus Deadspace.

Charlton and others have investigated the response of paediatric patients to an increase in apparatus deadspace. (14) These authors found that increasing the deadspace produced an immediate increase in end-tidal CO; in anaesthetised infants and children. However, tidal and minute volumes increased by 40-50% over the next 10 mm so that end-tidal CC>2 tensions returned to baseline values. They concluded that the short term ventilator/ response to an increased deadspace was adequate;

nevertheless, apparatus deadspace should be minimised in equipment designed for children and controlled ventilation should be used liberally in infants.

Compression volume

When we use a breathing system with controlled ventilation (manual or controlled) a certain amount of the tidal volume delivered to the system will be wasted due to compression of gas within the system. This volume, the compression volume, may be calculated from the volume of the breathing system and the ventilation pressure as shown below. (15)

If the volume of circle system is 5000 ml and we apply a ventilating pressure of 20 cm H20, this will increase the ambient pressure (approx 1000 cm HzO) by approximately 2%. Therefore, according to Boyle's Law, 2% x 5000 = 100 ml of gas will be compressed and this is wasted ventilation (compression volume = 100 ml;

compression factor = 100/20 = 5 ml/cm H;>0). If we wish to deliver a tidal volume of 500 ml to an adult patient at a pressure of 20 cm HzO, a ventilator volume of 600 ml will be necessary. In a child with a tidal volume 250 ml, a ventilator volume of 350 ml will be required and in a neonate with a tidal volume of 30 ml the ventilator volume should be 130 ml. Thus, the smaller the patient the greater the proportion of ventilation will be wasted by compression of gas in the system. Furthermore, the use of a standard "adult" circle system will result in a compression volume, which is many times greater than the tidal volume of an infant. The consequences of this are:

• Circle systems give a poor "feel" of the lung compliance in infants. (16)

• In the event of a decrease in lung compliance in an infant being ventilated with an circle system (e.g. spontaneous reversal of muscle relaxants) there may be a substantial reduction in tidal volume being proportional to the compression volume. (17)

• Increasing the inspiratory pressure may be of limited use in this situation since the compression volume will be further increased. (17)

• It may be impossible to ventilate the patient adequately with the circle system.

Jackson Rees system

The original Ayre's T-piece system consisted of a light metal T-tube with a main lumen of 1 cm diameter, and a smaller side tube at right angles to the main lumen through which the anaesthetic gas mixture was introduced: a length of rubber tubing attached to the open end of the T-piece acted as a reservoir for anaesthetic gases. (18) In 1950, Jackson Rees modified the system by attaching an open tailed bag to the reservoir tube, in order to facilitate controlled ventilation. (19) As there are no valves in the system, resistance to breathing is minimal. Apparatus deadspace is also minimal, but as there is no CC>2 absorber in the system fresh gas requirement is high (1.5-2 x minute volume during spontaneous ventilation).

When the T-piece is compared to our "ideal system", we see that it performs quite well in terms of simplicity, lightness, ease of use, low resistance, minimal deadspace, low compression volume and precise control of the delivered oxygen and anaesthetic concentrations. However, as might be expect, it performs badly on heat and moisture conservation, economical use of anaesthetic gases and the ability to scavenge waste gases.

Compression volume

The low volume of the T-piece system is reflected in a low compression volume. (8) Thus, a T-piece with a volume of 70 ml (tubing) plus 500 ml (bag) with a ventilation pressure of 20 cm HzO results in a compression volume of 2% x 570 = 11.4 ml (or less if the bag is only partly full). Therefore, in a neonate with a tidal volume of 30 ml, it will only be necessary to set the ventilator to deliver 41 ml to compensate for the compression volume and the compression volume of the T-piece (11 ml) is approximately 1/10^th that of the circle (100 ml). The consequences of this are:

• The delivered tidal volume relates quite closely to the actual tidal volume of the patient, so the anaesthetist should get a good "feel" for the lung compliance.

• If the compliance of the lung decreases (e.g. spontaneous reversal of muscle relaxants), the decrease in tidal volume will also be relatively small being proportional to the compression volume.

• This may be of vital importance when faced with an infant who has developed partial airway obstruction (bronchospasm or laryngospspasm) during induction or recovery from anaesthesia.

Conclusions

While standard circle systems have undoubted advantages for maintenance of anaesthesia they must be used with caution in infants owing to their large compression volumes. (8) This problem is only partly addressed by the use of small bore (15 mm) breathing hoses and a small (800-1000 ml) reservoir bag. In the case of a decrease in lung compliance in a patient with a low tidal volume, it may be difficult to maintain ventilation with a circle system and a T-piece should always be readily available. The T-piece system may still be the system of choice during induction and recovery of anaesthesia and as the sole breathing system for procedures of short duration. In these circumstances the T-piece may be safer and more convenient than the circle system whose main benefits will be less apparent owing to the need for high fresh gas flows. The inability to scavenge waste gases remains a major problem with the T-piece system.

References

1.     Conway CM. Anaesthetic breathing systems. BrJAnaesth 1985; 57: 649-657.

2.     Adriani J, Griggs T. Rebreathing in pediatric anesthesia: recommendations and descriptions of improvements in apparatus. AnesthesioJogy 1953; 14: 337-347.

3.     Stephen CR, Slater HM Agents and techniques employed in pediatnc anesthesia. Anesth Analg 1950; 29: 254-262.

4.     Meakin G. Low flow anaesthesia in infants and children. Br JAnaesth 1999;

83: 50-57.

5.     Nunn JF. Appliedrespiratory physiology. 3rd ed. London: Butterworths, 1987.

6.     Waters RM. Clinical scope and utility of carbon dioxide filtration in inhalation anesthesia. Anesth Analg 1924; 3: 20-22.

7.     Hughes DG. Paediatric anaesthetic equipment. In: Mather SJ, Hughes DG, eds. Handbook ofpaedialric anaesthesia. Oxford: Oxford University Press, 1991: 49.

8.     Cote CJ; Petkau AJ, Ryan JF, et al. Wasted ventilation measured in vitro with eight anesthetic circuits with and without inline humidification. Anesthesiology 1983;

59: 442-446.

9.     Orkin LR, Siegal M, Rovenstein EA. Resistance to breathing by apparatus used in anesthesia. II. Valves and machines. Anesth Analg 1957; 36(2): 19-26.

10.    Nunn JF, Exi-Ashi TI. The respiratory effects of resistance to breathing in anesthetized man. Anesthesiology 1961; 22: 174-185.

11.    Young TM. Carbon dioxide absorber. Anaesthesia 1971; 26: 78-79.

12.    Brown ES, Hustead RF. Resistance ofpediatric breathing systems. Anesth Analg 1969; 48: 842-849.

13.    Graft TD, Sewall K, Lim HS, el al. The ventilator/ response of infants of airway resistance. Anesthesiology 1966; 27: 168-175.

14.    Charlton AJ, Lindahl SGE, Hatch DJ. Ventilatory responses of children to changes in deadspace volume. BrJAnaesth 1985; 57: 562-568.

15.    Fisher DM. Anesthesia equipment for pediatrics. In: Gregory GA, ed. Pediatric Anesthesia, 4th edn. New York: Churchill Livingstone, 2002: 191-216.

16.    Carden E, Nelson D. A new and highly efficient circuit for paediatric anaesthesia. Can Anaesth Soc J 1972; 19: 572-582.

17.    Stayer SA, Bent ST, Campos CJ, et al. Comparison of the NAD 600 and Servo 900C ventilators in an infant lung model. Anesth Analg 2000; 90; 315-321.

18.    Ayre P. The T-piece technique. BrJAnaesth 1956; 28: 520-523.

19.   Jackson Rees G. Anaesthesia in the newbom. BMJ 1950; 2: 1419-1422.

Mechanisms of action of inhalational anaesthetics

N. P. Franks

Imperial College of Science, Technology and Medicine

The first anaesthetics to be used in surgery were inhalational agents (nitrous oxide, ether and chloroform), and the anaesthetic properties of the “inert” gas xenon has been known for over half a century.  Perhaps surprisingly, however, their mechanisms of action are still uncertain.  Indeed, until very recently, there had been no plausible molecular explanation offered for the anaesthetic action of nitrous oxide.  Because the potencies of most simple anaesthetics can be accurately predicted by fat solubility (the Meyer-Overton correlation), they have long been considered to be archetypal “non-specific” drugs. This apparent lack of specificity of general anaesthetics is unusual among drugs and simple biophysical correlations caused early workers to suppose that anaesthetics act directly on lipids (the Meyer-Overton Hypothesis).  This hypothesis was later extended by postulating that anaesthetic-induced changes in lipid structure and dynamics produce general anaesthesia by disrupting the activity of critical proteins such as membrane ion channels.  This traditional view, however, looks increasingly untenable. Quantitative studies over the past 20 years have shown that, at surgical levels, anaesthetic effects on lipid bilayers are extremely small.  Moreover, certain lipid-free proteins have been shown to be directly affected by a wide range of anaesthetics, with potencies essentially identical to those for general anaesthesia and crystallographic studies have revealed specific binding sites.  Finally, studies with optical isomers of general anaesthetics have revealed stereo-selective effects both on whole animals and on anaesthetic-sensitive neuronal ion channels.  Taken together, these findings indicate that general anaesthetics produce their effects at surgical levels by binding directly to proteins rather than to lipids.

Although general anaesthetics are non-specific in the sense that they come in diverse shapes and sizes with no common chemical groupings, their actions on neurons and their ion channels can be surprisingly selective.  For example, it has long been known that, in general, synaptic transmission is more susceptible to anaesthetic block than is conduction along axons.  Consistent with this observation, the voltage-gated Na+ and K+ channels involved in axonal conductance appear to be insensitive to general anaesthetics.  On the other hand, members of a genetically related superfamily of fast neurotransmitter-gated synaptic receptor channels (which include neuronal nicotinic ACh, GABA_A, 5‑HT3, and glycine receptors) can be very sensitive to anaesthetics.  In some cases, ion channels are affected by inhalational anaesthetics at concentrations well below their minimum alveolar concentrations. The mechanisms involved are beginning to be understood. There is growing evidence that even the simplest of anaesthetic gases, such as xenon, may act at specific targets in the central nervous system. While the GABA_A receptor has been identified as the most important single target for intravenous anaesthetics, the relevant targets for inhalational anaesthetics are much less certain and may include the GABA_A receptor, certain anaesthetic-activated potassium channels and the NMDA subtype of glutamate receptors.

Many questions remain regarding the molecular and cellular actions of inhalational general anaesthetics. What are the molecular forces that govern the interactions of these agents with their target sites?  Are a few critical targets involved, or are there many?  What happens at the molecular and cellular levels when inhalational anaesthetics interact with their targets?  In this lecture I will address these questions and review the experimental evidence from X-ray crystallography, enzymology and electrophysiology studies concerning the nature and identity of anaesthetic binding sites in the central nervous system. 

The Gas-Tight Airway

M Leier

Nuremburg

We are using highly developed anesthesia machines and monitors. The connection between anesthesia machine and patient is still variable with special advantages and disadvantages. The most adequate technique depends on type and length of surgery and, more important, on skill of the anesthetist. Endotracheal intubation is the golden standard, but mechanical ventilation can also be delivered by using a face mask. Between these techniques there is a large group of supraglottic airways. As an alternative for endotracheal intubation or face mask ventilation especially the laryngeal mask airway has reached importance.

An artificial airway should provide a good sealing between respirator and the patients trachea. On the one hand to ensure a gas tight seal, on the other hand to prevent leakage of fluid into the airway. Although endotracheal intubation is the way of choice to secure the airway and to avoid aspiration, there remains some doubt whether a endotracheal tube is always the best way to secure the airway. For example tonsillectomy in children with uncuffed tubes or patients in intensive care units with gastric reflux.

Asai could demonstrate in a benchtop model with a ventilated artificial trachea, that there is a rapid aspiration from above the cuff, even if the cuff is blocked correctly (1). After one hour of cuffed tracheal intubation the mucociliary clearence is a lot more impaired than after laryngeal mask intubation. The risk of retention of secretions by blocking the trachea with a cuff was significantly higher. The disturbance of tracheal mucous velocity caused by intubation reduces the physiologic tracheal cleaning function and can lead to atelectasis and pulmonal infection (2). Side effects and complications of endotracheal intubation may be serious or just unpleasant like coughing, sore throat, hoarseness or swallowing. Complaints are more often after endotracheal intubation than after use of laryngeal mask airway (3).

Supraglottic airways can be divided in three groups.

1. Without protection against aspiration

2. Antiaspiration strategy only by occlusion of the upper esophageal sphincter

3. Antiaspiration strategy by occlusion of the upper esophageal sphincter and drainage of the stomach

The oropharyngeal leak pressure correlates with the suitability of the supraglottic airway for controlled ventilation. There are several methods of testing, to determine the leak pressure. To avoid gastric insufflation and distension a qualitative assessment of gastroesophageal insufflation is advisable. Both, the leak at the neck and gastric insufflation, produce a dSifference between inspiratory and exspiratory volumes (leak fraction), which is easy to measure. A fresh gas flow close to the metabolic rate is the proof for a gas-tight airway. If a fresh gas flow of more than 300 ml/min is needed, you always have to reassure absence of gastric insufflation.

A gas-tight airway is essential for spontaneous breathing as well as for controlled ventilation, because sometimes a change in the planned surgical procedure requires conversion to mechanical ventilation and the use of relaxants.

Surgical procedures with peak airway pressures of 20 mbar or more (e.g. laparoscopy) require a seal pressure of at least 25 mbar to have a minimum safety gap between sealing and airway pressure. Otherwise the device has to be corrected or changed. Actually we investigate the possibility, safety and patients well-being of the LMA Pro-Seal vs. endotracheal intubation during laparoscopic cholecystectomy.

There is no extraordinary risk of pulmonal aspiration reported in literature using a supraglottic airway device. The incidence of postoperative complaints between the supraglottic devices differs, but is in general less than endotracheal intubation (4). Specially children profit by a low rate of coughing, swallowing and laryngospasm.

The gas-tight airway has a strong dependency with patients situation (5). Airway resistance and pulmonal compliance should be normal. The choice of anesthesia management, ventilation procedure, patients positioning and the use of muscle relaxant have a strong influence on the interaction of patient and anesthesia machine. It is obvious, that a supraglottic airway needs an open aperture of glottis. Anesthesia methods should provide a strong depression of airway reflexes. Using drugs like propofol, remifentanyl, alfentanyl and sevoflurane, a muscle relaxant is never required for insertion of the supraglottic airway and may be dispensable, even during smaller abdominal surgery and laparoscopy.

On the one hand, we establish a regime with minimal fresh gas flow to provide a save ventilation without gastric insufflation (6). On the other hand the supraglottic airways have a potential hazard of mucosal damage, because intracuff pressures are 60 mbar and more. Therefore the intracuff pressure should be reduced to Just seal pressure", which may lead to shortage of fresh gas in the anesthesia circle system, if airway conditions are changing.

A good insertion technique, an adapted anesthesia drug regimen and a adequate proficiency is advisable to use supraglottic airways in a optimum range (7). The optimal use is a fresh gas flow close to the metabolic rate and a cuff pressure as low as possible.

In our hospital supraglottic airways, especially LMA-ProSeal are standard for all patients with an empty stomach during short and long lasting surgical procedures, even during laparoscopy and abdominal surgery with and without muscle relaxants. A gas-tight supraglottic airway is a safe and probably a beneficial alternative to endotracheal intubation.

Literature;

1. Asai T, Shingu K, Leakage around high-volume, low-pressure cuffs apparatus A comparison of four tracheal tubes, Anaesthesia 2001 Jan; 56(1);38-42

2. Keller C, Brimacombe J, Bronchial mucus transport velocity in paralyzed anesthetized patients: a comparison of the laryngeal mask airway and cuffed trachea! tube, Anesth Analg. 1998 Jun;86(6): 1280-2

3. Honemann CW, Hahnenkamp K, MollhoffT, Baum JA, Minimal-flow

anaesthesia with controlled ventilation: comparison between laryngeal mask airway and endotracheal tube, EurJ Anaesthesiol. 2001 Jul;18(7):458-66.

4. Oczenski W, Krenn H, Dahaba AA, Binder M, EI-Schahawi-Kienzl I, Kohout S, Schwarz S, Fitzgerald RD. Complications following the use of the Combitube, tracheal tube and laryngeal mask airway. Anaesthesia. 1999 Dec;54(12):1161-5

5. Brimacombe JR, Keller C, Gunkel AR, Puhringer F, The influence of the

tonsillar gag on efficacy of seal, anatomic position, airway patency, and airway protection with the flexible laryngeal mask airway: a randomized, cross-over study of fresh adult cadavers, Anesth Analg 1999 Jul; 89(1): 181-6

6. Cameron AE, Sievert J, Asbury AJ, Jackson R, Gas leakage and the laryngeal mask airway. A comparison with the tracheal tube and the facemask during spontaneous ventilation using a circle breathing system, Anesthesia 1996 Dec;

51(12):1117-9

7. Lopez-Gil M, Brimacombe J, Cebrian J, Arranz J, Laryngeal mask airway in paediatric practice -A prospective study of skill acquisition by anesthesia residents, Anesthesiology 1996; 84:807-11

ADVANTAGES OF LOW FLOW ANAESTHESIA (LFA), FOREIGN GAS ACCUMULATION, CONTRAINDICATIONS.

G. ROLLY, M.D., Ph.D.

Gent, Belgium

The advantages of low flow/closed circuit techniques are several fold:

1) diminished consumption of anaesthetic gases and cost containment

2) environmental pollution reduction (for workplace and atmosphere)

For foreign gas accumulation, successively will be dealt: 1) The sources of unwanted gas; 2) The individual compounds concerned and their clinical relevance; 3) How can they eventually be removed out of the system?

The foreign gases found in the anaesthetic circuit can artificially be divided in 4 components: 1) The compounds formed in the body: acetone, CO, methane and hydrogen; 2) The compounds absorbed in the body: ethanol, CO and nitrogen; 3) The compounds produced in the breathing circuit: CO and degradation products of the inhalational agents, particularly compound A; 4) The compounds introduced in the breathing circuit, as contaminants of medical gases, by returned anaesthetic gas and by inversed leaks: nitrogen and argon. Some identical compounds can be found in the different situations.

Normally nitrogen (N₂) is present in the body. The normal content of the body, together with the lungs, amounts to about 2.7 l. During low flow/closed circuit anaesthesia sources of nitrogen can be: insufficient denitrogenation, use of side stream analysers, openig of a second soda lime canister still containing some nitrogen or a non airtight breathing system. If denitrogenation is performed with a high gasflow during 15-20 min, about 2 l of nitrogen is removed. The rest is slowly removed from less well perfused tissues and can give a nitrogen increase in the circuit during low flow conditions. The nitrogen can be 15 % and even higher during closed circuit. To eliminate nitrogen a high oxygen flow has to be given for at least 2-5 min. If no N₂O is used there is no danger of hypoxia, but if a high concentration of N₂O is used, lightening of anaesthesia has to be feared. Nitrogen can only be detected by mass spectrometry or a multigas analyser. In own research with rigid closed circuit anaesthesia mean concentrations of 10 % nitrogen were reached after 3 h, but individual values of 11 % were found.

Argon can accumulate in the circuit if in some exceptional circumstances oxygen concentrators are used. It is a noble and harmless gas. When long lasting low flow  is used, 5-6 % argon has been described, and in minimal flow techniques 8-15 %. The argon can be washed out by a high gasflow every 90 min.

Hydrogen is washed out of the lungs at a rate of 0.6 ml/min. In a closed circuit it can accumulate by 200 ppm/h, well below flammable concentrations (4.6-94 % in O₂; 5.8-86 % in N₂O).

Carbon monoxide (CO) gives more concern as it is intensily bound to haemoglobin. Physiological values of COHb are around 0.4-0.8 %, but higher in smokers (even 10 %). In  closed circuit Middleton reported that CO can increase with-in the range of 20-210 ppm; we found also a range of 7.5-164 ppm. Strauss found in closed system COHb values of 0.5-1.5 % in non-smokers and 3 % in smokers and Baum in minimal flow 1-1.5 % COHb. A toxicity index has been published by Henderson/Haggard: I_tox = CO(ppm) x t(h); 600 ppm/h beginning intoxication, vomiting and headache at 900 ppm/h, life-threatening conditions at 1500 ppm/h. The normal endogenous production is 0.42 ± 0.07 ml/h. The CO source in the circuit is: endogenous production, blood transfusion (smokers). Due to the high affinity to haemoglobin, intermittent short flushing is insufficient to eliminate CO, so closed circuit is not indicated in heavy smokers. The problem of CO intoxication during anaesthesia was particularly tackled by Moon, who described high values in 8 patients and others reported also accordingly.

The study of Fang and Eger could elegantly show that it was the dry absorbent, particularly Baralyme, but also soda lime which generated  the most CO. Amongst the anaesthetic agents, it is particularly desflurane, followed by enflurane. Sevoflurane seems to be exempt of this aspect. So the strong warning is put forward not to use dry soda lime (the so called Monday disease) or Baralyme. Originally it was said not to use too low flows, but on the countrary we can put forward that this can be a protection because of the moisture and water generation in the chemical reaction of CO₂ with soda lime. Baum could also show that the absorber’s utilization period had no influence on the COHb values. Another interesting study is also that no difference was found in the COHb values during closed circuit anaesthesia with desflurane and isoflurane. Baum could also show that COHb decreased after 60 min of minimal flow. In our own closed circuit studies we found also a decrease of CO ppm gas values.

Acetone is normally produced in the body by oxidative metabolism of free fatty acids . If the bloodconcentration exceeds 50 mg/l postoperative vomiting can occur, so maximally 20 mg/l should be present. Data mentioned in the literature were those of Morita , who reported 1.3 to 5.9 ppm in the circuit, whereas in our study  values of 30 to 40 ppm were recorded. The maximum allowed level in Germany is situated at 1000 ppm, whereas the US navy allows 2000 ppm . In long lasting anaesthesias Strauss could only find a difference between closed and semi-open systems after 6 h. The particular aspect of acetone is that it is highly soluble in water, fat and that it cannot be lowered by even short time flushing of the circuit. Therefore no minimal/closed circuit should be used in decompensated diabetes patients. For decreasing the metabolism of free fatty acids, infusion of low concentration glucose solutions is recommended.

Methane is normally produced in the intestine and is non toxic, but flammable. Values of methane during low flow and closed circuit anaesthesia have been reported by Barton and Nunn at 11 ppm and by our group at concentrations of 129 to 1976 ppm. Where is methane really coming from? Methane is present in the alimentary tract of animals and humans. It is produced primarily in the distal colon by fermentation of carbohydrates under strict anaerobic conditions by Methanobacterium ruminatium. Methane is liberated by reduction of carbon dioxide with hydrogen. Intestinal gas in humans contains up to 26 % methane. The main part is excreted in flatus, but a smaller part is taken up in blood. Because of the insolubility of methane in blood relative to air, 90 – 95 % of this gas is cleared in a single passage through the lungs. There are large individual differences: approximately 2/3 of subjects had methane concentrations of less than 1 ppm, and 1/3 concentrations ranging from 1 to 70 ppm. 80 % of patients with cancer of the large bowel had detectable levels of methane in their breath and 83 % of patients with aorto-iliac disease. Also patients with extensive ulcerative colitis and colonic polyposis produce high concentrations of methane. In rigid closed circuit conditions without intermittent flush we found higher values than reported before. In those closed circuit conditions during TIVA with the PhysioFlex apparatus, we found that in some patients “false” halothane concentrations were shown and in others not. There is some correlation between the methane concentrations and the “halothane” concentrations. This a very anoying fact, as if halothane is used, false high, so really lower concentrations are shown, eventually leading to a decrease of the set concentration and inducing a too light anaesthesia. Therefore an intense study was done in our department, showing that several gasanalysers are sensitive, others not . The analysers measuring the anaesthetic vapor at a wavelenght of 3.3 mm are very sensitive, whereas analysers measuring at 8.8 and at 10 mm are insensitive and have to be preferred for measurements during low flow and closed circuit anaesthesia. Although the influence is highest for halothane , it is  less for other gases such as enflurane and isoflurane and almost inexistent for sevoflurane.

As ethanol is concerned, this drug has a high gas/water solubility coefficient and can therefore accumulate in closed systems . The clinical consequences are that it can be dangerous to use a closed circuit in an alcoholised patient, so closed circuit or minimal flow techniques should not be employed when dealing with a patient having an alcohol intoxication.

Degradation products of volatile anaesthetics result from the reaction with CO₂ absorbents: CO formation with dry absorbents, as already mentioned; Comp A formation with sevoflurane. The volatile anaesthetic degradation is function of the anaesthetic agent itself, the type of CO₂ absorbent, the CO₂ production in the body and the temperature of the CO₂ absorbent, the fresh gasflow amount and the anaesthetic machine or respirator itself.

The reported values of Compound A during clinical anaesthesia are variously reported in the literaure. In an extensive study Kharash reported mean peak inspired concentrations of 30 ppm after 4 h and lesser expiratory concentrations, showing body uptake of compound A. However the individual concentrations varied considerably and extreme values of 65 ppm were noticed. The fundamental question is, are these potentially toxic? In rats toxicity has been shown. Comp A is supposed to form a gluthation conjugate which undergoes cleavage to cystein conjugate; renal uptake of cysteine and gluthation conjugates occurs , whereby intrarenal metabolism takes place by cysteine conjugate b lyase, whereby toxic reactive intermediates can be formed. However the levels of b lyase are different between humans and laboratory animals, wherein research was done. The controversy led the FDA to the low flow restriction of 2 l/min and later 1 l/min, whereas in the European countries no restriction was imposed.

In early studies with sevoflurane closed system PhysioFlex anaesthesia, we unexpectedly detected hardly 3-4 ppm compound A, what was later also found by the Funk group. Further in vitro research could show that this was due to the continuously internal flow of 70 l/min by the fan and also the lower canister temperature; by experimentally excluding the fan and replacing it by 2 classical unidirectional valves, the compound A production allmost tripled and the canister temperature increased by 12 °C. At the same time this modification gave us a suitable closed circuit model for additional research showing that newer developped KOH free absorbents like Sofnolime and KOH free Sodasorb produced even more compound A than the original Sodasorb. Recently additional data were published about minimal flow anaesthesia, showing mean values around 40 ppm, but also individual values around 60 ppm. Even without direct proof of toxicity, means of preventing generation of compound A are mandatory. Recent development of NaOH and KOH free absorbents are there. International reports and research of our own group published in Anesthesiology show that with Amsorb and the still experimental lithium hydroxide allmost no compound A is generated. During minimal flow clinical anaesthesia we could show that with a new Superia absorbent virtually no compound A is produced, compared to Sofnolime. The compound A conclusion can therefore be: 1) With the PhysioFlex closed circuit sevoflurane can safely be given; 2) KOH free absorbents are no improvement; 3) Only KOH and NaOH free absorbents are the future for safe closed and low flow sevoflurane anaesthesia.

Summarising  the topic of removal of foreign gases out of the circuit, we can say that sparingly soluble gases like N₂, methane and hydrogen are easily washed out by intermittent flush; 2) gases readily soluble in water or fat, like acetone and alcohol, can accumulate and therefore no closed circuit or minimal flow shall be used; 3) gases with a high affinity for blood, like CO, can be toxic and no closed circuit shall be used.

Relative contraindications for LFA are: shortlasting anaesthesia, insufficient control of breathing system air tightness, decompensated diabetes mellitus, alcoholics, heavy smokers, long lasting sevoflurane anaesthesia if classical soda limes are used. Absolute contraindications are: gas/smoke intoxication, septicaemia, apparatus not conforming to modern anaesthesia requirements.

Cardioprotective Effects of Volatile Anaesthetics

Wolfgang Schlack
University Clinic of Duesseldorf

The severity of myocardial ischaemia not only depends on the duration of ischaemia, but is also modified by the conditions of ischaemia (electrical activity, inotropic state, temperature etc). The last years have profoundly changed our understanding of myocardial injury during an ischaemic event: first, the severity of ischaemia and of myocardial damage can also be modified by interventions before the onset of ischaemia, i.e. by preconditioning. The current concept is that very short periods of ischaemia (like during angina) trigger the strongest known endogenous cardioprotective mechanism, ischaemic preconditioning. Second, although ischaemic myocardium can only be salvaged by reperfusion, reperfusion itself can lead to additional cellular injury that further augments the ischaemic state of injury. During the initial phase of reperfusion, injury is mainly caused by the consequences of ischaemic calcium overload together with the re-supply of energy that triggers several critical intracellular events, including activation of cellular enzymes and over-activation of contractile apparatus. Later during the time course of reperfusion, injury is further augmented by leukocytes that become activated and release a variety of mediators including oxygen derived free radicals. Reperfusion injury may cause cell death and infarction ("lethal reperfusion injury") or may only result in a delayed mechanical dysfunction of the myocardium ("stunning").

An increasing number of our patients who undergo surgery has significant coronary artery disease and the interaction of anaesthetic drugs with the mechanisms of ischaemia-reperfusion injury may become clinically important for the anaesthesiologist. Anaesthetics may interact with nearly all the above mentioned mechanisms:

Myocardial ischaemia: It was already described in 1969 that halothane - like all negative inotropic drugs - can reduce the severity of myocardial ischaemia 1. These findings of an (moderate) anti-ischaemic effect of inhalational anaesthetics were confirmed in a variety of experimental models and ischaemic conditions (isolated hearts, isolated papillary muscle, coronary occlusions with and without reperfusion, global myocardial ischaemia, cardioplegic arrest, hypoperfusion, cold storage of isolated hearts, demand ischaemia in patients etc).

Preconditioning was originally described as ischaemic preconditioning, i.e., very short periods of ischaemia that precede the main ischaemic period and offer substantial protection against ischemia-reperfusion injury.2 Several nonischemic stimuli can precondition the heart, including pharmacologic challenge by adenosine,3 opoids,4 and several halogenated inhalational anaesthetics 5 6-12 cardioprotection lasts for some hours after the application of the stimulus. After ischaemic preconditioning, a second window of protection appears after 24h lasting for about two days (late ischaemic preconditioning). The cardioprotection by late ischaemic preconditioning can be further augmented by anaesthetic preconditioning: five min of sevoflurane inhalation before a prolonged ischaemia reduced infarct size by 50% in already late preconditioned (short myocardial ischaemia 24 h before) rabbit hearts. In addition to animal studies, some work points to the existence of preconditioning in human myocardium:13 Preadministration of isoflurane 10 min before aortic cross-clamping and cardioplegic arrest during coronary artery bypass surgery has been shown to reduce myocardial damage in humans.
The protective effect of anaesthetic preconditioning is mediated by opening of the ATP regulated potassium channels of the mitochondrion,8 which also mediates the protective effect of ischaemic preconditioning. Ketamine can block this channel and prevent the cardioprotective effect of ischaemic preconditioning at clinically relevant concentrations.14; 15 The effect is stereospecific for the R(-)-isomer and does not occur with S(+)-ketamine. Cardioprotection by late preconditioning is also blocked by a single bolus dose of razemic ketamine, but not by S(+) ketamine.16 Barbiturates may also block the ATP regulated potassium channels, a blocking effect on preconditioning may only occur at supratherapeutical doses 17.

Lethal reperfusion injury: It was found recently that cardioprotection by halothane was much more pronounced if the substance was given to isolated hearts only during reperfusion compared to the situation when it was given before or during ischaemia.18 In isolated cells, it was possible to identify the underlying protective mechanism which consisted of a suppression of reperfusion induced calcium oscillations 19 that are responsible for immediate cell death at reperfusion. At the molecular level, we found that this mechanism is linked to an interaction of halothane with the sarcoplasmic reticulum ryanodine receptor of reperfused heart cells.20,21 In addition, halothane may also reduce secondary reperfusion injury caused by activated leukocytes.22 Even after cardioprotection by a cardioplegic solution, volatile anaesthetics confer additional protection during reperfusion.23 It was possible to confirm the protective effect of halothane against lethal reperfusion injury in vivo, where a marked reduction of infarct size was seen if 1 MAC halothane was given for the first 15 min of reperfusion after coronary occlusion 24. The cardioprotective effects were also shown to be independent of the haemodynamic side effects24. Cardioprotection against lethal reperfusion injury was also seen with desflurane, sevoflurane and enflurane in vitro25; 26 and in vivo preparations,27; 28 while surprisingly, no cardioprotective effect against lethal reperfusion injury was found for isoflurane, both in vitro26 and in vivo28. After protection against ischaemia by cardioplegic arrest, all inhalational anesthetics were found to have an additional protective effect against reperfusion injury,29; 30 but there were marked differences in the protective profile of the single substances and protection by some inhalational anaesthetics also depended on the composition of the cardioplegic solution.

Stunning: Some studies found a better functional recovery if isoflurane 31; 32 or halothane 31; 33; 34 were given. However, from these studies it is not entirely clear whether the better functional recovery results from a direct effect on the stunned myocardium or is a secondary effect of a reduction of the severity of myocardial ischaemia because the substances were given already before and during ischaemia.

Clinical perspective: To summarise, there is a large amount of experimental evidence that inhalational anaesthetics exert beneficial effects on different mechanisms of ischaemia-reperfusion injury. Given before ischaemia, they trigger the strongest known endogenous cardioprotective mechanism: preconditioning. Given after ischaemia, they have specific actions against reperfusion injury – even after cardioplegic arrest. Very promising are the first preliminary results which confirm the cardioprotective effects of inhalational anaesthetics in a clinical setting in patients. On the other side, other anaesthetics like ketamine can block cardioprotection and may be harmful in ischaemia reperfusion situations.


References

1. Spieckermann PG, Brückner JB, Kübler W, Lohr B, Bretschneider HJ: Preischemic stress and resuscitation time of the heart. Verh.Dtsch.Ges.Kreislaufforsch. 33:358-364, 1969
2. Murry CE, Jennings RB, Reimer KA: Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium. Circulation 74:1124-1136, 1986
3. Heidland UE, Heintzen PH, chwartzkopff B, trauer B-E: Preconditioning during percutaneous transluminal coronary angioplasty by endogenous and exogenouns adenosine. Am.Heart J. 140:813-820, 2000
4. McPherson BC, Yaho ZH: Morphine mimics ischemic preconditioning via free radical signals and mitochondrial K-ATP channels in myocytes. Circulation 103:290-295, 2001
5. Cope DK, Impastato WK, Cohen MV, Downey JM: Volatile anesthetics protect the ischemic rabbit myocardium from infarction. Anesthesiology 86:699-709, 1997
6. Kersten JR, Schmeling TJ, Hettrick DA, Pagel PS, Gross GJ, Warltier DC: Mechanism of myocardial protection by isoflurane - Role of adenosine triphosphate-regulated potassium (KATP) channels. Anesthesiology 85:794-807, 1996
7. Cason BA, Gamperl AK, Slocum RE, Hickey RF: Anesthetic-induced preconditioning. Previous administration of isoflurane decreases myocardial infarct size in rabbits. Anesthesiology 87:1182-1190, 1997
8. Kersten JR, Schmeling TJ, Pagel PS, Gross GJ, Warltier DC: Isoflurane mimics ischemic preconditioning via activation of K ATP channel- Reduction of myocardial infarct size with an acute memory phase. Anesthesiology 87:361-370, 1997
9. Ismaeil MS, Tkachenko I, Hickey RF, Cason BA: Colchizine inhibits isoflurane-induced preconditioning. Anesthesiology 91:1816-1822, 1999
10. Ismaeil MS, Tkachenko I, Gamperl AK, Hickey RF, Cason BA: Mechanisms of isoflurane-induced myocardial preconditioning in rabbits. Anesthesiology 90:812-821, 1999
11. Piriou V, Chiari P, Knezynski S, Bastion O, Loufoua J, Lehot JJ, Foex P, Annat G, Ovize M: Prevention of isoflurane-induced preconditioning by 5-hydroxydecanoate and gadolinium. Anesthesiology 93:756-764, 2000
12. Roscoe AK, Christensen JD, Lynch C: Isoflurane, but not halothane, induces protection of human myocardium via adenosine A1 receptors and adenosine triphosphate sensitive postassium channels. Anesthesiology 92:1692-1701, 2001
13. Belhomme D, Peynet J, Louzy M, Launay JM, Kitakaze M, Menasché P: Evidence for preconditioning by isoflurane in coronary artery bypass graft surgery. Circulation 100:340-344, 1999
14. Moloschavij A, Preckel B, Comfère T, Müllenheim J, Thämer V, Schlack W: Effect of ketamine and its isomers on ischemic preconditioning in the isolated rat heart. Anesthesiology 94:623-629, 2001
15. Müllenheim J, Fräßdorf J, Preckel B, Thämer V, Schlack W: Ketamine, but not S(+) blocks ischemia preconditioning in the rabbit heart in vivo. Anesthesiology 94:630-636, 2001
16. Müllenheim J, Rulands R, Wietschorke T, Fräßdorf J, Preckel B, Schlack W: Late preconditioning is blocked by racemic ketamine, but not by S(+) ketamine. Anesth.Analg. 93:265-270, 2001
17. Müllenheim J, Molojavyi A, Preckel B, Thämer V, Schlack W: Thiopentone does not block ischemic preconditioning in the isolated rat heart. Can.J.Anaesth. 2001(in press)
18. Schlack W, Hollmann M, Stunneck J, Thämer V: Effect of halothane on myocardial reoxygenation injury in the isolated rat heart. Br.J.Anaesth. 76:860-867, 1996
19. Schlack W, Siegmund B, Piper HM: Protection of isolated cardiomyocytes against reoxygenation-induced hypercontracture by halothane, Funktionsanalyse biologischer Systeme. Edited by Grothe J. Stuttgart, Gustav Fischer, 1999, pp in press
20. Schlack W, Siegmund B, Piper HM: Protective mechanism of halothane on myocardial reperfusion injury. Br.J.Anaesth. 76 Suppl. 2:411996(Abstract)
21. Siegmund B, Schlack W, Ladilov YV, Piper HM: Halothane protects cardiomyocytes against reoxygenation-induced hypercontracture. Circulation 96:4372-4379, 1997
22. Kowalski C, Zahler S, Becker BF, Flaucher A, Conzen PF, Gerlach E, Peter K: Halothane, isoflurane, and sevoflurane reduce postischemic adhesion of neutrophils in the coronary system. Anesthesiology 86:188-195, 1997
23. Preckel B, Stunneck D, Thämer V, Schlack W: Halothane reduces myocardial reperfusion injury after cardioplegic arrest. Br.J.Anaesth. 76 Suppl. 2:40-41, 1996(Abstract)
24. Schlack W, Preckel B, Barthel H, Obal D, Thämer V: Halothane reduces reperfusion injury after regional ischaemia in the rabbit heart in vivo. Br.J.Anaesth. 79:88-96, 1997
25. Schlack W, Preckel B, Stunneck D, Thämer V: Different inhalational anaesthetics have different protective effects against the reperfusion injury of the heart. Br.J.Anaesth. 78 Suppl. 1:45-46, 1997(Abstract)
26. Preckel B, Schlack W, Comfère T, Obal D, Barthel H, Thämer V: Effects of enflurane, isoflurane, sevoflurane, and desflurane on reperfusion injury after regional myocardial ischaemia in the rabbit heart in vivo. Br.J.Anaesth. 81:905-912, 1998
27. Preckel B, Schlack W, Obal D, Thämer V: Different effects of enflurane, isoflurane, sevoflurane, and desflurane on myocardial reperfusion injury in vivo. Br.J.Anaesth. 78 Suppl. 1:451997(Abstract)
28. Schlack W, Preckel B, Stunneck D, Thämer V: Effects of halothane, enflurane, isoflurane, sevoflurane and desflurane on reperfusion injury in the isolated rat heart. Br.J.Anaesth. 81:913-919, 1998
29. Preckel B, Schlack W, Thämer V: Enflurane and isoflurane, but not halothane, protect the heart against reperfusion injury after cardioplegic arrest with HTK solution. Anesth.Analg. 87:1221-1227, 1998
30. Preckel B, Thämer V, Schlack W: Beneficial effects of sevoflurane and desflurane against reperfusion injury after cardioplegic arrest. Can.J.Anaesth. 46:1076-1081, 1999
31. Warltier DC, Al-Wathiqui MH, Kampine JP, Schmeling WT: Recovery of contractile function of stunned myocardium in chronically instrumented dogs is enhanced by halothane or isoflurane. Anesthesiology 69:552-565, 1988
32. Kersten JR, Lowe D, Hettrick DA, Pagel PS, Gross GJ, Warltier DC: Glyburide, a KATP channel antagonist, attenuates the cardioprotective effects of isoflurane in stunned myocardium. Anesth.Analg. 83:27-33, 1996
33. Coetzee A, Moolman J: Halothane and the reperfusion injury in the intact animal model. Anesth.Analg. 76:734-744, 1993
34. White JL, Myers AK, Analouei A, Kim YD: Functional recovery of stunned myocardium is greater with halothane than fentanyl anaesthesia in dogs. Br.J.Anaesth. 73:214-219, 1994
 

NEW GENERATION CO₂ ABSORBENTS.

Prof. Dr. Linda VERSICHELEN

Ghent University, Gent, Belgium.

The technique of CO₂ absorption was  in 1915 introduced in the laboratory by Jackson , in 1923 applied in clinical practice by Waters and from 1923 on cyclopropane was succesfully used by rebreathing technique.

The first generally known warning about degradation products from a chemical reaction with CO₂ absorbents was with the drug trichlorethylene, whereby dichloracetylene could be formed, which is a potent nerve poison and can produce paralysis of the cranial nerves.

A second warning appeared when it was realised that also halothane could be degraded by soda lime, but with the move to high flows for using halothane,  the aspect was forgotten.

However with the newly developed sevoflurane again the aspect of degradation  products from the chemical reaction of the drug with absorbent came into the scope of interest. Indeed  Comp A could be formed and to a small extent also Comp B . The aspects of potential renal toxicity has induced the FDA to put a limit nowadays situated at 1 l/min for the fresh gas flow with sevoflurane. In Europe however, no regulations were imposed and it was let to the individual jugement of the anaesthesiologist. Another aspect became soon apparent, the eventual production of CO by the dried soda lime with desflurane.

All these aspects forced a renewed interest for the clinically used CO₂ absorbents. If we make abstraction of the Ba(OH)₂ containing Baralyme, which has hardly been used in Europe, all the classical “soda limes” contain a mixture of NaOH, KOH and Ca(OH)₂ in various amounts, together with water for hydration of the soda lime. During the chemical reaction CO₂ is bound to the above mentioned substances, finally forming CaCO₃ in an exothermic reaction. As during the recent years it became evident that NaOH and KOH are highly reactive products, research has been focused on developping new absorbents not containing these strong bases.

The new millennium requirements for CO₂ absorbents can be summarised as follows:

1)      They should effectively bind CO₂ ; the shape of the granules can be important.

2)      They should contain a colour indicator for the remaining effectiveness of the absorbent.

3)      There should be no propensity to generate: anaesthetic breakdown products, CO or any other untoward reaction.

4)      There sould be absence of any irritating effect.

The actually available CO₂ absorbents can be divided into 3 categories:

1)      NaOH and KOH containing absorbents: soda lime, Sodasorb, etc.

2)      KOH-free absorbents: Sofnolime, Medisorb, Drägersorb 800 plus, KOH-free Sodasorb, Spherasorb;

3)      NaOH and KOH-free absorbents: Amsorb, Superia, LoFloSorb, lithium hydroxide.

When assessing CO₂ absorbents several aspects are of utmost importance, such as the effective utilisation time, the eventual generation of toxic compounds under any circumstance, the adsorption or degradation of inhaled anaesthetics and finally the cost.

In this lecture particularly 2 new NaOH and KOH-free CO₂ absorbents will be discussed: AMSORB and SUPERIA, which both contain Ca(OH)₂. Own scientific research and available literature data on newer CO₂ absorbents will be discussed.

The consumption of CO₂ absorbents is dependent on several technical aspects: the well known importance of the fresh gas flow, the patient CO₂ production reflecting metabolism, the construction of the anaesthesia machine and particularly the size of the canister, equipment factors influencing fresh gas utilisation, the duration of anaesthesia, and finally the characteristics of the particular CO₂ absorbent. The useful life of CO₂ absorbents has recently been studied by Baum showing that the mean utilisation time was nearly identical for Dräger 800 plus, Sofnolime and Sperasorb, but was much less with the new Amsorb. This has also consequences as the cost of this new CO₂ absorbent is much higher than that of the older absorbents. The same group had also studied in the past the influence of the construction of the anaesthesia apparatus, showing that a Cicero machine is more performant than a AV 1 and a Sulla 800.

Elements that interfere in the eventual volatile anaesthetic degradation by CO₂ absorbents are: 1)  the volatile anaesthetic itself.

2)  the type of CO₂ absorbent (classical, KOH-free, NaOH and KOH-free)

3)      the temperature of the CO₂ absorbent

4)      the anaesthetic machine and size of canister.

Although it is now well known that Amsorb is not producing compound A when using sevoflurane, very few studies exist using it in minimal flow conditions. Recently we published a study comparing Amsorb and also the experimental  CO₂ absorbent lithium hydroxide  to some KOH-free CO₂ absorbents like Sofnolime and KOH-free Sodasorb and the classical Sodasorb. An in vitro closed circuit system connected to a living lungmodel was used, simulating as much as possible real clinical conditions. It was shown that with Amsorb and lithium hydroxide no compound A was generated during 2.1 % end-tidal sevoflurane, whereas with Sofnolime and KOH-free Sodasorb a significant amount of compound A was formed (~30-35 ppm), somewhat more than with Sodasorb (~20-25 ppm). Furthermore the canister temperatures during the 4 h duration administration were almost identical with the 5 CO₂ absorbents. The study clearly shows that only with CO₂ absorbents free of both NaOH and KOH no compound A is generated. Amsorb is now largely available, but because of the airway irritating effects lithium hydroxide is not yet ready for clinical use.

During an in vivo study in 14 patients we could show that in minimal flow conditions (500 ml/min) during 2 ½ h anaesthesia with 2.3 – 2.5 % sevoflurane end-tidal, no compound A was generated with Superia. With the comparator Sofnolime median (range) compound A inspiratory values of  25(16) ppm were found, somewhat less than those reported in a recent minimal flow study using Drägersorb (Goeters et al.). However we used a small volume canister included in the Datex-Ohmeda ADU system. No difference was noticed for the canister temperature between the 2 CO₂ absorbents.

The eventual generation of CO with the new CO₂ absorbents is much more difficult to test, apart from accidental reporting. However recently Kharash et al. performed an in vivo study in pigs on the formation of CO and compound A with hydrated and dehydrated Amsorb and classic and KOH-free Sodasorb. The CO formation and COHb formation occured with dehydrated with desflurane and isoflurane in the following order: Baralyme>>Sodasorb> Amsorb; with desflurane and Baralyme even peak CO concentrations of  9700 ppm were noticed and COHb increase with 37 %. However with Amsorb and Sodasorb they were undetectable. Compound A generation with sevoflurane 2.1 % and fresh or dehydrated Amsorb was absent, whereas with Baralyme and Sodasorb values of 20-40 ppm were found.

The effect of CO₂ absorbents on anesthetic degradation (delaying induction of anaesthesia) is sparcely studied. Karash et al. studied also this aspect by noticing the difference between the inspiratory and postabsorbent or end-tidal concentrations. With fresh CO₂ absorbents no significant difference is found, but with dehydrated CO₂ absorbents this was as follows: Amsorb< Sodasorb<Baralyme. This study shows that Amsorb has the least potential to delay induction. In our study with Superia and Sofnolime the amount of liquid sevoflurane to obtain almost identical end-tidal concentrations showed no statistical difference, suggesting that the 2 CO₂ absorbents behaved in the same way.

In summary the available experience with the new NaOH and KOH-free CO₂ absorbents clearly shows that these absorbents behave in the way predicted. After some technical changes in the design of canisters, they are the major improvement for safe use of minimal flow anaesthesia, although at a somewhat higher cost.

References:

1)      Baum J, Van Aken H. Calcium hydroxide lime –a new carbon dioxide absorbent: a rationale for judicious use of different absorbents. European J of Anaesthesiology 2000; 17: 597-600.

2)      Goeters C, Reinhardt C, Gronau E, et al. Minimal flow sevoflurane and isoflurane anaesthesia and impact on renal function. European Journal of Anaesthesiology 2001; 18: 43-50.

3)      Kharash ED, Powers KM, Artu AA. Comparison of Amsorb®, Sodalime and Baralyme® degradation of volatile anesthetics and formation of carbon monoxide and compound A in swine in vivo. Anesthesiology 2002; 96: 173-182.

4)      Versichelen LFM, Bouche MPLA, Rolly G, et al. Only carbon dioxide absorbents free of both NaOH and KOH prevent formation of compound A during in vitro closed-system sevoflurane: evaluation of five absorbents. Anesthesiology 2001; 95:750-5.

The future; more simple or more complex?

D White

England

The first low flow anaesthesia system to gain widespread use was the Waters to-and-fro. This was a system of great simplicity, although analysis shows that its function, like that of many simple things, is not so simple. The Waters system has the potential for liquid injection of agent but Us popularity arose from the introduction of cyclopropane shortly after Waters' original description. This gaseous agent required the use of a low flow system and it is relevant that the same requirement attaches to xenon at the present time. Adding agents in gaseous form to a low flow system is potentially more precise than use of a vaporiser because the flow of agent into the System can be accurately metered.

After the introduction of the Waters system the picture is one of increasing complexity. The circle system introduced valves, the attachment of ventilators was a further complication. In more recent years the introduction of various methods of measuring the composition of the gas mixtures in the system and the availability of devices giving electronic control of gas flow have hugely complicated the design and construction of anaesthetic machines in general and particularly those designed for low flow operation.

Is there any hope of simplifying these systems or at least reducing their complexity m any areas? The layout of piping in low flow systems has not changed m the last fifty years (at least) and the use of coaxial tubing to connect the patient to the machine is not is not a major complication. Putting circulators (small fans driving gas round the circle) is an advance, they eliminate valves in circle systems. By homogenising the gas mixture in the system they facilitate electronic control and they may also reduce or eliminate resistance to breathing. They do however require power to drive them and are in no way essential.

Modem anaesthetic gas analysers are complex devices and increase in complexity rather than the reverse. However a simple monitor has been described and manufactured. The Draeger Narkotest measured by deflection of a pointer the deformation of a polymer (rubber) on exposure to clinical I concentrations of halothane. If a polymer having the same solubility characteristics as the site of anaesthetic action in the brain were used in a meter of this sort then it would record the anaesthetic potency of any anaesthetic gas or mixture of gases, it would be a "MAC meter". It would not require a power supply and its slightly slow response would not bar its use in low flow systems in which the rate of change of gas composition is always sluggish.

After agent monitoring the other major source of complexity in modem anaesthetic machines is control of gas flow. In this area it can be said that the Rotameter has reigned supreme for at least seventy years. Provided the bobbin is rotating there is physical proof of the passage of the gas stream in measured quantity. It is not easy to see any better way of domg this. Electronic methods of measuring gas flow have been described and some of these have been applied to anaesthetic machines. Use of these devices has not been on a sufficient scale to record any serious failures. If signals from monitoring instruments are to be used to control the performance of the anaesthetic machine then the use of electronic control seems unavoidable.

There is one important exception to this statement. That is when the patient is breathing spontaneously. The depth and frequency of respiration is controlled by the central nervous system and the change in tills frequency and depth in response to surgical stimulus can be regarded as a. measure of depth of anaesthesia. It is appropriate therefore that these changes should be changed by opiates but not abolished (at least not in normal clinical practice).

If therefore the supply of anaesthetic to the system could be regulated by changes in the patient's respiratory pattern then he would be regulating the depth of his own anaesthetic. This is inherently superior to the anaesthetist imposing on the patient what he (the anaesthetist) considers to be the correct amount of anaesthetic. The use of a small and simple uncalibrated vaporiser mounted directly in a circle system has been shown to work m this manner. The fall in concentration of agent in the first twenty minutes of the anaesthetic (due to the lack of temperature compensation) is offset by the fall in requirement for anaesthetic in that time. The design of vaporisers for use in tin;? way can doubtless be improved as there has been a considerable element of chance in the successful design of existing models.

When the patient is paralysed by the use of muscle relaxants then the only signal available to control the anaesthetic is that from the EEG and a lot of work is currently in progress on this subject. The state of anaesthesia is one of absent or reduced response to external stimuli so it seems reasonable to assume that study of some form of evoked response has the best chance of success in finding a signal measuring depth of anaesthesia. Coupling lids to the anaesthetic machine would involve further electronic systems.

Are there any other possibilities which might be simpler than the EEG? Using a closed system it is simple to continuously measure me uptake of anaesthetic, by the body. In the paralysed patient. when ventilation is completely controlled, the cardiac output is the major factor controlling anaesthetic uptake. With increasing depth of anaesthesia the, cardiac output falls and vice versa. It can therefore be argued that when using a system in which a constant end-tidal concentration of anaesthetic is being maintained by electronically controlled injection of agent at a constant or near constant rate then a constant cardiac output is being maintained and therefore a constant depth of anaesthesia. This would apply after the first twenty minutes of anaesthesia and assumes correct fluid balance. Assumed is knowledge of the concentration of agent and opiate dosage which guarantees loss of awareness but that is another subject.

Conclusions. Modern anaesthetic machines are complex and likely to get more so. For routine clinical anaesthesia not all these electronic systems are necessary and some possible simplifications are discussed. The increasing cost of fully automated anaesthetic machines may impose limits on more complex technology if the clinical benefits are not apparent.