**3. Etiology**

them constitutes 79% of the air we breathe [3]. The increase of the nitrogen pressure negatively affects the central nervous system (CNS). It is usually seen at depths of more than 30 m [4]. Nitrogen narcosis is characterized by decreased intellectual function and decreased neuromuscular transmission performance, a tendency to laugh, decreased attention and decisionmaking, emotional state, and impaired behavior. Nitrogen narcosis does not cause permanent damage to the body, but mental and motor deterioration can lead to serious problems in the underwater [2]. These effects increase as the partial pressure of nitrogen increases, but it is not related to the time remaining at the same depth [5]. These changes have been seen for centuries as they are known when diving with compressed air due to nitrogen pressure. Other inert gases with similar effects have been described (neon, argon, krypton, xenon, and

110 Hyperbaric Oxygen Treatment in Research and Clinical Practice - Mechanisms of Action in Focus

In diving with compressed air, nitrogen narcosis is the most important factor limiting depth. When it is necessary to work deeper than 40–50 m, it is necessary to get help from gas with less narcotic effect such as helium. Nitrogen narcosis is responsible for most of the dive acci-

The cause of acute toxicity of hyperbaric oxygen therapy is related to oxygen partial pressure [6]. Although oxygen is a necessary gas to survive, oxygen can show toxic effects at high partial pressures and long-term exposures. Oxygen poisoning can be seen in long-term oxygen therapy in intensive care, in closed or semi-closed circuit diving, in saturation dives, on decompressions on the surface, in recompression and hyperbaric oxygen therapy [7].

Oxygen intoxication is caused by reactions between free oxygen radicals and cell components [8]. Gamma amino butyric acid (GABA) has frequently been studied in studies conducted in this regard [9]. Excess oxygen causes the generation of uncontrolled stimuli in the central nervous system by reducing GABA outflows [8]. It is thought that seizures developing in 3

The poisoning caused by air inhalation in a high-pressure environment was first described by Junod in 1835 [2]. In 1861, Green made a dive with divers with 48 m of compressed air, observing that the divers developed to sleep, their decision-making powers were impaired, and they saw hallucinations. Paul Bert stated that divers were poisoned at high depths in 1878. In 1903, Hill and McLeod described the intellectual functions of tunnel workers as inadequate at 5.5 ATA pressure. In 1930, Damant reported that memory problems had developed in 10 ATA. In 1932, Hill and Phillips thought these effects could be claustrophobic or psychological. According to a report by the British Navy in 1933, the section entitled "Loss of semiconsciousness" states that divers who have dived at 60–106 m have received hand signals sent

In 1935, Behnke and his colleagues described the currently accepted theory of nitrogen narcosis. Narcosis is caused by an increase in partial pressure of nitrogen, which is an inert gas. The

ATA and above hyperbaric oxygen therapy are related to this [10].

to them, but no one remembers it when it comes to the surface [1].

hydrogen) [1].

**2. History**

dents and dive-related deaths.

It is thought that the mechanism of nitrogen narcosis is the same as general anesthesia with volatile gases. All inert gases that produce anesthetic effects behave in the same way. These gases are composed of simple molecules with no structural properties and do not show chemical changes in the body [3].

Many researchers have attempted to understand the physical behavior of these gases and have found a close relationship with the oil dissolution feature. According to the Meyer-Overton hypothesis, there is a parallel between the dissolution of anesthetics in oil and potency of the narcotic effect. It stated that when the gases pass through cell oils at a certain molar concentration, they will show an effect of narcosis. In this case, the inert gas molecule affects the cell membrane function in the brain. However, there are some discrepancies in terms of the physical properties of the inert gases and their narcotics abilities (**Table 1**). For example, argon is two times more narcotic than nitrogen. However, their fat/water solubility ratios are similar. However, despite all these incompatibilities, narcotic behavior is parallel to physical characteristics in general [5].

According to Henry's Law, as soon as the partial pressure of nitrogen increases, it begins to dissolve more in the body and in the plasma. Nitrogen cannot be used by the body like oxygen. When we breathe compressed air during diving, many molecules enter our bodies and quickly dissolve in our bodies due to the height of the environmental pressure. When we dive 15 m sea water, the nitrogen partial pressure will double up. With the increase in depth, the narcosis signs will begin to appear. As is known, anesthetic symptoms occur when diving is 15 m or more, and we briefly explain it with the Martini Act (**Figure 1**) [4].

The dissolution hypothesis in oil has been tried to be understood by the concept of critical volume. Here, in order to develop the effect of narcosis, the inert gas must affect on the fat part of cell membrane to swell. In human studies, it has been confirmed that gas has a positive correlation with oil solubility by developing slightly to moderate narcosis.


Many studies have focused on the cause of stimulation in the central nervous system. Stimulant-inhibitory synapses, molecules, and receptors are the basis of this effect. Among them, gamma-amyno butiric acid (GABA) is the most important inhibitory molecule. GABA is an important inhibitory neurotransmitter which made from glutamine after a series of reactions in the central nervous system (**Figure 2**). GABA receptors have been shown to be

The most important of the stimulating molecules is dopamine. Nitrogen accumulation increases the levels of dopamine, causing cortex and thalamus stimulation, which are brain regions (**Figure 3**). Nitrogen accumulation causes a reversal of uptake and an increase in dopaminergic levels. This situation leads to stimulation in the thalamus and striatum, which is the inhibitor center. This explains some neuromuscular disorders belonging to nitrogen

In order to explain the acute toxic effects of hyperbaric oxygen therapy, it is necessary to

those containing sulfurized sulfhydryl groups. This effect of free oxygen radicals is widely

For example, the antioxidant defense system in the body can resist life to the oxygen pressure normally found in atmospheric air, or even slightly more. This value is 0.4–0.5 atmospheres (1 ATA at sea level, oxygen is approximately one-fifth in the air). Now, let's take a 30-m dive with air. In this case, total pressure will be 4 ATA, and if the oxygen forming partial pressure of air is pO2 = 0.8 ATA, this value exceeds the antioxidant defense system of the body. The

body is damaged acutely by oxygen at a depth of 30 m for a long time.

values disrupt the function of enzymes, especially

Toxic Effects of Hyperbaric Conditions http://dx.doi.org/10.5772/intechopen.78392 113

responsible for the formation of nitrogen narcosis [8].

focus on enzyme metabolism. High pO2

**Figure 2.** GABA and dopamine metabolism.

narcosis [9].

accepted [7].

**Table 1.** Narcotic effects and physical properties of some gases.

**Figure 1.** Martini Yasası.

In general, although these physical theories refer to the fatty part of the cell membrane, it has been shown that this narcotic effect is due to specific receptors and influences synaptic transmission. Some studies have shown that cell membranes are resistant to narcotics and cell membrane proteins and lipoproteins are responsible for this.

Many studies have focused on the cause of stimulation in the central nervous system. Stimulant-inhibitory synapses, molecules, and receptors are the basis of this effect. Among them, gamma-amyno butiric acid (GABA) is the most important inhibitory molecule. GABA is an important inhibitory neurotransmitter which made from glutamine after a series of reactions in the central nervous system (**Figure 2**). GABA receptors have been shown to be responsible for the formation of nitrogen narcosis [8].

The most important of the stimulating molecules is dopamine. Nitrogen accumulation increases the levels of dopamine, causing cortex and thalamus stimulation, which are brain regions (**Figure 3**). Nitrogen accumulation causes a reversal of uptake and an increase in dopaminergic levels. This situation leads to stimulation in the thalamus and striatum, which is the inhibitor center. This explains some neuromuscular disorders belonging to nitrogen narcosis [9].

In order to explain the acute toxic effects of hyperbaric oxygen therapy, it is necessary to focus on enzyme metabolism. High pO2 values disrupt the function of enzymes, especially those containing sulfurized sulfhydryl groups. This effect of free oxygen radicals is widely accepted [7].

For example, the antioxidant defense system in the body can resist life to the oxygen pressure normally found in atmospheric air, or even slightly more. This value is 0.4–0.5 atmospheres (1 ATA at sea level, oxygen is approximately one-fifth in the air). Now, let's take a 30-m dive with air. In this case, total pressure will be 4 ATA, and if the oxygen forming partial pressure of air is pO2 = 0.8 ATA, this value exceeds the antioxidant defense system of the body. The body is damaged acutely by oxygen at a depth of 30 m for a long time.

**Figure 2.** GABA and dopamine metabolism.

In general, although these physical theories refer to the fatty part of the cell membrane, it has been shown that this narcotic effect is due to specific receptors and influences synaptic transmission. Some studies have shown that cell membranes are resistant to narcotics and cell

membrane proteins and lipoproteins are responsible for this.

**Figure 1.** Martini Yasası.

**Gases Molecular** 

**weight**

**Table 1.** Narcotic effects and physical properties of some gases.

**Volume Solubility in oil at 37°C**

112 Hyperbaric Oxygen Treatment in Research and Clinical Practice - Mechanisms of Action in Focus

Helium 4 2.370 0.015 1.70 0.23 Neon 20 1.709 0.019 2.07 0.28 Hydrogen 2 2.661 0.040 3.10 0.55 Nitrogen 28 3.913 0.067 5.25 1.00 Argon 40 3.218 0.140 5.32 2.33 Krypton 83.7 3.978 0.430 9.60 7.14 Xenon 131.3 3.105 1.700 20.00 25.64

**Separation coefficient** 

**narcotic effect**

**(oil:water)**

There is no direct pathological change to acutely CNS oxygen poisoning in humans. In animal experiments, tissue death was demonstrated in the nervous system. Serious exposures can cause damage to the brain and spinal cord in the spinal cord. Even a 30-min dive with 4 ATA pure oxygen (30 m) can cause structural changes in the gray matter in the spine of front horn [7].

The mechanism of CNS oxygen poisoning is not fully known. Oxygen is believed to have

Signs and findings are described in a wide range of fans. Nausea, vomiting, dizziness, ringing in the ears, incoordination, tunnel vision, irritability, pallor, sweating, heart rate slowing (bradycardia), lips, and hands twitching, eyes widening of the baby, hiccups, to remember the recent past, hallucination, confusion (confusion) are chief of the signs and findings. However, the most dramatic of these is the seizure, namely the convulsion. It is typical that conscious-

The most common finding is a face twenty in the oxygen pressure on 2 ATA. The sign of paleness in the face is due to hyperoxia-induced vasoconstriction. Similarly, the loss of sensation

Even though the depth is the same, being in the water reduces the resistance to oxygen poisoning considerably compared to being in dry air in the pressure chamber. Water and diving stress increase the susceptibility to oxygen poisoning. Also underwater, the signs mentioned above cannot be noticed, but the divers are noticed that they are poisoned when they have convulsions. Convulsions underwater are dangerous because they can lead to suffocation or barotrauma. Therefore, many authorities have determined the maximum depth of pure oxygen diving underwater to be 10 m. Other causes that reduce the threshold value of CNS

Facial twitch usually results in convulsions. During convulsion, all body stimuli develop and the tonic phase called full contraction begins. During this time, breathing is interrupted. The tonic phase usually lasts 30 s and is accompanied by loss of consciousness. This period approximately takes 1 min, followed by the head, neck, trunk, and legs in large contraction followed by clonic phase. After the clonic phase, the contractures decrease and the respiration starts with hyperventilation, and after a while consciousness comes back. The diver does not remember any part of the event. The concentration of carbon dioxide has increased because of being held breath during the convulsion. However, contrary to normal epilepsy patients,

poisoning are exercise, hypothermia, increased calm carbon dioxide levels [10].

and the free oxygen derivatives affecting the CNS metabolism.

1.7 ATA for 7 h, 1.8 ATA for 3 h, 2 ATA for 50 min and 3 ATA for

pressure on 2 ATA and above [6].

pressure increases. According to Clark

Toxic Effects of Hyperbaric Conditions http://dx.doi.org/10.5772/intechopen.78392 115

**6. Clinical signs and symptoms**

As a rule, poisoning is seen when exposed to pO2

30 min showed signs of MSS poisoning [7].

ness is closed during convulsion [7].

in the fingers is the result of vasoconstriction [9].

Oxygen poisoning occurs more rapidly as the pO2

evolved by the increase of pO2

and Lambertsen's work; pO<sup>2</sup>

**Figure 3.** Dopamine-induced thalamus and cortex.
