Carbon Dioxide Toxicity: Chronic Hypercapnia

The need for defining tolerance limits to CO2 for long exposures is becoming increasingly important with the development of saturation diving, the use of submersibles and extended submarine patrols (see Chapter 67).

Marked adaptation to inspired CO2 levels between 0.5 per cent and 4 per cent has been demonstrated. This adaptation is characterized by an increased tidal volume, a lower respiratory rate and a reduction in the ventilatory response to hypercapnia produced by exercise.

Biochemically, there is a reversal of the initial increase in hydrogen ion concentration, a rise in the plasma bicarbonate and a fall in the plasma chloride, i.e. mild compensated respiratory acidosis. There is a slight rise in PaCO2. These latter changes are almost complete in 3 to 5 days’ exposure, although there is a significant reduction in the ventilatory response in the first 24 hours. There is also a rise in serum calcium and other mineral changes.

While at rest, the average diver can tolerate a surface equivalent of up to 4 per cent inspired CO2 (a PICO2 of 30 mm Hg), without incapacitating physiological changes. During exercise, alveolar ventilation does not increase sufficiently to prevent a significant degree of CO2 retention as shown by an elevation of PaCO2. This loss of the ventilatory response to CO2 (of the order of 20 per cent in submariners) may also be of great significance in the saturation diver, particularly during exercise.

Carbon Dioxide Toxicity: Acute Hypercapnia

Causes

Excluding asphyxia and drowning, there are five main mechanisms of CO2 toxicity in diving:

  1. Failure of an absorbent system, e.g. in closed-circuit or semi-closed-circuit rebreathing apparatus, submarines, saturation complexes.
  2. Inadequate ventilation of an enclosed environment, e.g. in standard dress or other helmet diving and compression chamber diving where flushing is required to remove CO2.
  3. Inadequate pulmonary ventilation, e.g. in deep diving where the work of breathing dense gases is greater, or with increased resistance from the equipment.
  4. Physiological adaptations to diving (‘CO2 retainers’).
  5. Contamination of breathing gases by CO2.

Whatever the cause, CO2 toxicity is much more rapid when the diver is exercising and producing large amounts of CO2.

Serious carbon dioxide toxicity is most com-monly encountered in divers using closed-circuit or semi-closed-circuit rebreathing equipment. It is also seen where there is inadequate ventilation of an enclosed space such as a helmet, recompression chamber or submarine.

In diving operations that rely on recycling of respiratory gases, the most common method of CO2 removal uses the reaction between alkali metal (sodium, lithium) hydroxide reagents (e.g. Protosorb, Sodasorb, Baralyme, Dragersorb) and carbonic acid:

Other techniques, some still being developed, include cryogenic freeze-out of CO2 with liquid air or oxygen, molecular sieves, electrolytic decomposition into carbon and water and the use of peroxides and superoxides that generate oxygen while removing CO2.

FAILURE OF THE ABSORBENT SYSTEM

This failure in rebreathing sets may have the following causes:

Inefficiency of absorbent material

This may be caused by large granule size, poor packing (resulting in poor contact between absorbent and gas because of ‘channeling’ of gases), low environmental temperature, low alkali content, low water content or sea water contamination.

Equipment design faults

The canister should be of adequate size and adequate length compared with its cross-sectional area. It should be insulated against extreme temperature changes. In circuit rebreathing equipment, the gas space between the absorbent granules ideally should exceed the maximum tidal volume, so that there is time for absorption during the next part of the respiratory cycle. In pendulum rebreathing equipment, excessive functional dead space between the diver’s mouth and the canister causes inhalation of expired CO2.

Operator error

CO2 build-up may result if the diver fails to pack the canister properly with active absorbent, undertakes excessive exertion or exceeds the safe working life of the set (Case Report 18.1).


CASE REPORT 18.1

AB, an experienced open-circuit diver and recent aficionado of deep, closed-circuit rebreather diving using mixed gases, was diving to 85 metres on a wreck. Shortly after reaching the bottom, he became agitated and was acting irrationally. His diving companion tried to assist but was unable to calm him down. The diving companion indicated that AB should begin his ascent but was not able to make his intention understood. After approximately 1 minute of struggling, AB became unconscious with his mouthpiece still in situ. His companion held him and began an ascent to his first decompression stop.

At approximately the 70-metre depth, they encountered the next pair of divers descending, and AB was transferred to their care and assisted to 35 metres, where the second pair of divers was obliged to stop for decompression. They inflated AB’s buoyancy vest and he ascended unconscious and unaccompanied rapidly to the surface.

AB surfaced near the boat and was rapidly retrieved from the water and oxygen administered – initially by bag and mask ventilation, although he rapidly resumed breathing. He was transferred to a hyperbaric facility and recompressed after formally being intubated and ventilated because of his depressed state of consciousness. He had omitted significant decompression obligations and had experienced a rapid ascent, so he was presumed to be highly likely to have significant decompression illness on top of the primary cause of this event. His condition improved rapidly and he was extubated the following morning, with normal neurological function. He had no recall of beginning to feel breathless toward the end of the descent.

An examination of his equipment revealed a misassembled absorbent system whereby circuit gas was able to by-pass the absorbent canister and flow freely from the expiratory limb of the circuit to the inspiratory limb. On arrival at the recompression facility, an arterial blood gas had returned a PaCO2 value of 78 mm Hg.

On reflection, AB admitted to making the same error on a previous occasion, but he had been able to exit the water before any serious consequences had ensued.

Diagnosis: CO2 intoxication secondary to absorbent system failure resulting from misassembly. Closed-circuit rebreather diving is complex and requires meticulous attention to detail. Perhaps it is best suited to obsessive-compulsive personality types (see Chapter 62).


INADEQUATE VENTILATION OF THE ENVIRONMENT

In helmet and recompression chamber dives, there must be a sufficient volume of gas supplied to flush the enclosed system of CO2. In the same way that PaCO2 is dependent on alveolar ventilation, the level of CO2 in the enclosed space is inversely proportional to the ventilation of that space. When corrected to surface volumes, this means progressively greater amounts of gas must be supplied as the diver or chamber goes deeper.

INADEQUATE PULMONARY VENTILATION

At depth, this situation is primarily the result of the increased density of the respired gases. This causes an increased resistance to gas flow, both in the breathing apparatus and in the diver’s own airways. Using the less dense helium as the diluent gas instead of nitrogen avoids this problem. Tight wetsuits, harnesses and buoyancy compensators further restrict thoracic movement and place an increased workload on the diver’s respiratory muscles. The extent to which this load is overcome varies greatly among divers, but there is often some elevation of the alveolar PCO2.

PHYSIOLOGICAL ADAPTATIONS TO DIVING (‘CO2 RETAINERS’)

In the diving literature, CO2 is often incriminated as a major factor producing loss of consciousness, with rebreathing equipment and while employing high oxygen pressures in gas mixtures. There have been many adequately investigated cases to verify this.

There are also divers who tolerate high PCO2 levels – ‘CO2 retainers’ (see later). These divers are more likely to experience neurological oxygen toxicity at lower oxygen pressures or durations. The explanation given is that the higher PaCO2 causes cerebral vasodilation and thus a larger oxygen load to the brain. These problems are more likely with oxygen or gas mixture diving equipment and with rebreathing sets (see Chapters 4 and 63).

High oxygen levels in the inspiratory gas have been thought since the 1950s (e.g. several reports from Lanphier from 1950 to 1958) to reduce the respiratory response to CO2. Most later reports suggest that at an aerobic work rate, ventilation is not altered whether the subject breathes 100 per cent oxygen or air.

Kerem and his co-workers1 demonstrated that while breathing high oxygen pressures, established divers had significantly lower sensitivity to high CO2 levels. These Investigators concluded that the divers had an impaired CO2 response that was either inherent or acquired. Kerem and colleagues also demonstrated that the mean end-tidal PCO2 was significantly higher than that in non-divers and diving trainees, when breathing nitrox with 40 per cent O2 at both 1 and 4 ATA.

In relation to open-circuit equipment using air (scuba), the relevance of CO2 as a contributor to significant diving problems is more dubious. Many divers do, however, reduce their ventilation voluntarily to conserve air and allow mild elevations of their PaCO2. This practice of long inspiratory and expiratory pauses that reduce minute ventilation is called ‘skip breathing’ and often results in headache at the end of a dive that clears rapidly after surfacing. This practice is not generally advised, but it is common among relatively inexperienced divers trying to extend their dive time. A link with serious diving injury has not been established.

The general physiology literature assumes that PaCO2 is held remarkably constant during both rest and exercise, within a very narrow range of a few millimitres of mercury. Dempsey and Pack2, in a text on the regulation of breathing, stated that ‘significant, sustained CO2 retention is extremely rare in health, even under the most extreme conditions of exercise intensity and flow limitation’.

Yet, significant exercise (O2 uptake >60 per cent of maximal) under water and using scuba, produces an elevation of PaCO2 and is sometimes marked (PaCO2 >60 mm Hg). With increasing depth, a progressively greater amount of energy is required to breathe and rid the body of CO2. At extreme depth, the work of breathing may produce enough CO2 to exceed the ability to expire CO2, and this has been postulated as a mode of death in some deep divers.

Different regulators produce varying degrees of resistance to ventilation, with the potential for CO2 retention. Resistance also rises with inadequate maintenance of the regulator or the deposition of foreign bodies and salt particles. Maintaining regulator performance to an acceptable level can be difficult. The CO2 retention is usually minor and does not lead to CO2 toxicity. It does, however, increase with exposure to depth and with low scuba cylinder pressure driving the gas through the regulator.

Perhaps more important than the consistent but mild CO2 build-up with normal scuba diving is the occasional atypical subject who responds inadequately, either at depth or on the surface, to raised CO2 levels. It may be that these divers progressively elevate their CO2, as an alternative to increasing their ventilation, when the resistance to breathing increases. Under these conditions, it is theoretically possible that toxic levels may eventuate.

In diving parlance these divers are referred to as ‘CO2 retainers’, a concept based heavily on the work of Lanphier. This concept has received widespread acceptance in the diving medical fraternity, but is not widely accepted among more conventional physiologists.

If, indeed, there are such divers who are CO2 retainers, then the explanation for this is conjectural. Some investigators have suggested that the ability to tolerate higher than normal CO2 levels will permit the subject to achieve greater diving success. These divers may succeed with deep breath-hold diving, tolerate the high CO2 levels in helmet diving or tolerate increased breathing resistance from equipment or increased gas density with depth. In this situation the CO2 retainer would be self-selecting – being more successful during diver training and therefore over-represented in the established diver population – where they have been observed by physiologists such as Lanphier.

A more plausible explanation for high PaCO2 levels in divers, for the various reasons referred to previously, is that divers develop an adaptation allowing them to tolerate the higher levels of CO2 encountered while diving. Similarly, as ‘skip breathers’ continue to dive, this breathing pattern becomes habitual, and a tolerance to CO2 would develop.

‘Skip’ or ‘controlled’ breathing may not only put divers at risk of problems from CO2 toxicity, oxygen toxicity, nitrogen narcosis and pulmonary barotrauma, but it also induces bewilderment among diving respiratory investigators.

There have been cases reported of divers who had otherwise unexplained episodes of unconsciousness and who were later shown to have a markedly reduced ventilatory response to elevated PaCO2. It is suggested that a combination of CO2 toxicity and nitrogen narcosis may have induced unconsciousness in some of these divers, but in others the depth is too shallow to incriminate significant nitrogen narcosis.

Some of the divers who have lost consciousness with scuba at depths around 30 metres have not only been very experienced divers, but also have had asthma. The traditional CO2 retention in these subjects may be a contributing factor.

Equating the respiratory response to CO2 among divers with that of patients with chronic obstructive pulmonary disease or those with sleep apnoea has little clinical or research merit.

In 1992, Donald4 reviewed many of the studies frequently referenced both here and by others and not only cast considerable doubt on their methodology and conclusions, but also argued against any continuing support for the concept of CO2 retainers as a separate group of divers.

CONTAMINATION

Some buoyancy vests are fitted with a CO2 cartridge to inflate the vest in an emergency. A diver who, in a panic situation, inflated the vest and then breathed this gas would rapidly develop CO2 toxicity.

In limestone cave diving, gas pockets may form under the roof. A diver may be tempted to remove the regulator and breathe in this gas, which, not being replenished, will gradually accumulate CO2. Such a diver may then develop CO2 toxicity.

In practice, ‘contamination’ is much more likely the result of the failure of absorbent systems, as described earlier.

Clinical features

These features depend on the rate of development and degree of CO2 retention. They vary from mild compensated respiratory acidosis, detected only by blood gas and electrolyte estimations, to rapid unconsciousness with exposure to high PICO2 (Case Report 18.2). Although CO2 is a respiratory stimulant, most of its effects result from the acidosis it produces and are neurologically depressant.


CASE REPORT 18.2

WS, a very fit dive instructor, experienced two episodes of unconsciousness under similar conditions, about 1 year apart. They both were associated with diving between 30 to 50 metres depth, non-stressful and requiring little exertion. They both occurred 10 or more minutes after reaching the sea bed, and there were no problems during descent, and specifically no difficulty with middle ear autoinflation.

Other divers on the same dives used similar scuba equipment and gases from the same compressor (his own dive shop) and experienced no difficulty.

The first episode resulted in a sensation of imminent loss of consciousness, to a severe degree, and caused him to ditch his weight belt and ascend, with help. With the ascent he regained his normal state of awareness. On his second episode he totally lost consciousness and was brought to the surface by one of the companion divers. He was fully conscious and alert within a few minutes of surfacing. Following this dive he was aware of a dull headache.

The only contributory factors that could be ascertained were as follows:

He was renowned for consuming extremely small quantities of air, and he did admit to employing ‘skip breathing’ in the earlier part of his diving career – although such a voluntary decision was not made in recent years. He had asthma of moderate degree. He had not taken any anti-asthmatic medication before the dives. He then sold his diving practice and refrained from diving activities.

Provisional diagnosis: combined carbon dioxide/nitrogen narcosis effect with possible asthma contribution.

Whatever the explanation, remember the maxim that any diving accident not explained and not prevented will recur under similar conditions.


At 1 ATA, a typical subject breathing air to which 3 per cent CO2 has been added doubles the respiratory minute volume. There is no disturbance of central nervous system function. A 5 to 6 per cent CO2 supplement may cause distress and dyspnoea accompanied by an increase, mainly in tidal volume but also in respiratory rate. There is a concomitant rise in blood pressure and pulse rate. Mental confusion and lack of coordination may become apparent. A 10 per cent inspired CO2 eventually causes a drop in pulse rate and blood pressure and severe mental impairment. A 12 to 14 per cent level will cause loss of consciousness and eventually death by central respiratory and cardiac depression if continued for a sufficient time (PaCO2 greater than 150 mm Hg); 20 to 40 per cent inspired CO2 rapidly causes midbrain convulsions – extensor spasms – and death.

These effects occur at progressively lower inspired concentrations with increasing depth because toxicity depends on partial pressure, not inspired concentration.

If the inspired CO2 is allowed to increase gradually (as may occur with a rebreathing set with failing absorbent), the following sequence is observed on land. The subject notices dizziness, unsteadiness, disorientation and restlessness. There is sweating of the forehead and hands, and the face feels flushed, bloated and warm. Respiration increases in both depth and rate (Case Report 18.3). Muscular fasciculation, incoordination and ataxia are demonstrable. Jerking movements may occur in the limbs. The subject becomes confused, ignores instructions and pursues tasks doggedly. Gross tremor and clonic convulsions may appear. Depression of the central nervous system may lead to respiratory paralysis and eventually death if the high PICO2 is not discontinued.


CASE REPORT 18.3

JF was doing a compass swim using a closed-circuit 100 per cent oxygen rebreathing set at a maximum depth of 5 metres. He had difficulty keeping up with his companion and noticed that his breathing was deep and the gas seemed hot. He ventilated his counterlung with fresh oxygen but still had breathing difficulty. Just before being called up after 33 minutes in the water, his companion noted that JF ‘got a new burst of speed, but kept adding more gas to his counterlung’.

On reaching the tailboard of the boat, JF complained that he was nearly out of gas. His eyes were wide, his face flushed and his respirations panting and spasmodic. He then collapsed and stopped breathing. His face mask was removed, and he was given mouth-to-mouth respiration, then 100 per cent oxygen as breathing returned. He was unconscious for 5 minutes, and headache and amnesia extended for several hours after the dive.

Oxygen percentage in the counterlung was 80 per cent and the activity time of the unused absorbent was reduced to 32 minutes (specification 61 minutes). The canister (plus absorbent) from JF’s set was placed in another set, and a fresh diver exercised in a swimming pool using this. He was unable to continue for more than 5 minutes because of a classic CO2 build-up.

Diagnosis: CO2 toxicity.


Underwater, the diver may not notice sweating and hot feelings, given the cool environment. Incoordination and ataxia are much less obvious because movements are slowed through the dense medium and the effect of gravity is almost eliminated. Hyperpnoea may not be noted by the diver performing hard work or engrossed in a task. With the rapid development of hypercapnia, there may be no warning symptoms preceding unconsciousness. During the recovery period, the diver may remember an episode of lightheadedness or transitory amblyopia, but these occupy only a few seconds and there is therefore insufficient time to take appropriate action.

A throbbing frontal or bitemporal headache may develop during a slow CO2 build-up (while still conscious) or after a rapid build-up (during recuperation).

An exercising diver in the water may have little warning of carbon dioxide toxicity prior to becoming unconscious.

If the diver is removed from the toxic environment before the onset of apnoea, recovery from an episode of acute CO2 toxicity is rapid, and the diver appears normal within a few minutes. He or she may complain of nausea, malaise or severe headache for several hours. The headache does not respond to the usual analgesics or ergotamine preparations.

Early workers in this field observed the ‘CO2 off effect’, i.e. a brief deterioration in the clinical state when a significant CO2 exposure is abruptly suspended and the diver breaths normal air. This observation has been less often reported more recently.

CO2 retention enhances nitrogen narcosis (see Chapter 15), and it renders the diver more susceptible to oxygen toxicity (see Chapter 17). Conversely, there is evidence that nitrogen narcosis does not exacerbate CO2 retention by depressing ventilatory response. The hyperoxia of depth may slightly reduce ventilatory drive. It is also believed that CO2 increases the possibility of decompression sickness by increasing tissue perfusion and by increasing red blood cell agglutination (see Chapter 11).

Prevention and treatment

Although it is often the practice to familiarize divers who use rebreathing sets with the syndrome of CO2 toxicity under safe control conditions, so that appropriate action can be taken at the first indication, this may not assist divers while underwater. In the water there may be few warning symptoms before the problem results in incapacitation. Familiarization will at least alert divers to the problem. Divers should be encouraged to report any unusual symptoms to their companions.

The ideal prevention is by CO2 monitoring and using an alarm system to warn of rising levels. CO2 has been referred to as ‘the dark matter of diving’ because a workable system of real-time monitoring while immersed has proven elusive. At present, and despite concerted efforts from a number of manufacturers, this monitoring is practical for recompression chambers, habitats and submarines, for example, but not yet for self-contained rebreathing apparatus.

If CO2 levels are not monitored, then attention must be paid to adequate ventilation of chambers, avoidance of hard physical work, keeping within the safe limits of the CO2 absorbent system and other factors. Even with these precautions, accidents will still happen.

It critical to appreciate that the percentage of CO2 in the inspired gas becomes increasingly important as the pressure increases. Although 3 per cent CO2 in the inspired air at the surface produces little effect, at 30 metres (4 ATA) it is equivalent to breathing 12 per cent on the surface and would be incapacitating. At very great depth, minimal percentages of CO2 are dangerous.

The diver using underwater rebreathing apparatus should be well trained in what to do when CO2 toxicity is suspected. The diver should stop and rest, thus reducing muscular activity and CO2 production. At the same time he or she should signal the diving partner because assistance may be required and unconsciousness may be imminent. Either the diver or the companion should flush the counterlung with fresh gas, ditch the affected diver’s weights and reach the surface by using positive buoyancy. In deep diving, it may be necessary to return slowly to a submersible chamber. On arrival at the surface or submersible chamber, the diver should immediately breathe from the atmosphere.

Attempts to identify and therefore isolate the CO2 retainers have been unsuccessful. Personnel selection is therefore not feasible at this stage. Prevention includes advising against any skip breathing or other gas conservation techniques, but it is difficult to enforce. Equipment should not impose a significant breathing resistance, even at maximal workloads. The replacement of helium for nitrogen in mixed gas diving is often effective.

First aid treatment simply requires removal from the toxic environment. Maintenance of respiration and circulation may be necessary for a short period. PCO2 and pH return to normal when adequate alveolar ventilation and circulation are established.

Carbon Dioxide Toxicity: Respiratory Physiology

Carbon dioxide (CO2) is normally present in the atmosphere in a concentration of 0.03 to 0.04 per cent by volume of dry air. This represents a partial pressure (PCO2) of 0.23 to 0.30 mm Hg. It is one of the products of metabolism of protein, carbohydrates and fats produced in the mitochondria in roughly the same volume as oxygen is consumed. For example:

Glucose (a carbohydrate) + oxygen = carbon dioxide + water + energy

The resultant CO2 has to be transported from the tissues by the circulation and eliminated by exhalation from the lungs.

The normal PCO2 in arterial blood (PaCO2) is about 40 mm Hg and for mixed venous blood is about 46 mm Hg. Some factors that determine arterial PCO2 are summarised in Figure 18.1. PCO2 in the alveolar gas (PaCO2) is in equilibrium with that of the pulmonary veins and is therefore also about 40 mm Hg. Being a product of metabolism, the amount of CO2 produced is unchanged, so the PaCO2 is constant irrespective of depth (unlike oxygen and nitrogen, which reflect the pressures in the inspired gas).

Some factors that influence the partial pressure of carbon dioxide (PCO2). V/Q, ventilation-perfusion. (Adapted from Nunn JF. Applied Respiratory Physiology. 3rd ed. London: Butterworth; 1987.)
Figure 18.1 Some factors that influence the partial pressure of carbon dioxide (PCO2). V/Q, ventilation-perfusion. (Adapted from Nunn JF. Applied Respiratory Physiology. 3rd ed. London: Butterworth; 1987.)

CO2 is the most potent stimulus to respiration. The central medullary chemoreceptors in the brain are stimulated by increases in arterial CO2 and acidosis. In normal conditions, adjustments in ventilation keep the arterial and alveolar CO2 partial pressure remarkably constant. The peripheral chemoreceptors (carotid and aortic bodies) are primarily responsive to hypoxaemia (increasing respiration) but also respond to increases in acidosis and CO2 concentration.

The solubility of CO2 is about 20 times that of oxygen so there is considerably more CO2 than oxygen in simple solution (most of the oxygen is transported bound to haemoglobin). CO2 is transported in the blood in both plasma and red cells. In each 100 ml of arterial blood, 3 ml are dissolved, 3 ml are in carbamino compounds (with haemoglobin and plasma proteins) and 44 ml are carried as bicarbonate (HCO3−).

At rest, approximately 5 ml of CO2 per 100 ml blood are given up from the tissues and liberated in the lungs. About 200 ml of CO2 are produced and excreted per minute. If this CO2 is retained in the body (e.g. from rebreathing), the PaCO2 will climb at the rate of 3 to 6 mm Hg per minute.

With exercise, much larger amounts of CO2 are produced. The working diver can produce more than 3 litres of CO2 per minute for short periods, and 2 litres per minute for more than half an hour, usually without serious alteration in PaCO2 – as a result of a concomitant increase in respiration.

Because ventilation matches any increased CO2 production, while diving, the arterial and hence alveolar CO2 tensions should be maintained at approximately 40 mm Hg despite increasing environmental pressure. Therefore, the alveolar CO2 percentage decreases with increased depths. In contrast, because the source is from the inspired gas, the alveolar partial pressure of oxygen (PO2) and the partial pressure of nitrogen (PN2) increase with depth, but the percentages show little change.

PaCO2 is the primary drive to respiration, as discussed earlier, and it is intimately related to alveolar ventilation. As every breath-hold diver knows, deliberate hyperventilation can drive the PaCO2 down and extend breath-hold time (see Chapters 16 and 61). The exact relationship between PaCO2 and alveolar ventilation is shown in the following equation:

Where k is a conversion factor to convert conditions at STPD (standard temperature and pressure, dry) to BTPS (body temperature and pressure, saturated); VCO2 is the CO2 production in litres per millimetre STPD; Va is the alveolar ventilation in litres per minute BTPS; and PICO2 is the inspired carbon dioxide partial pressure.

Alterations in PaCO2 have widespread effects on the body, especially on the respiratory, circulatory and nervous systems. Apart from the hypocapnia produced by hyperventilation, the more frequent derangement in diving is hypercapnia, an elevation of CO2 in blood and tissues. This may be an acute effect or chronic. Where hypercapnia produces pathophysiological changes dangerous to the diver, the term ‘CO2 toxicity’ (or CO2 poisoning) is used.