Neurotoxic effects of oxygen in hyperbaric environment : A case report

Introduction. Oxygen is an essential element of life in aerobic organisms. However, if not controlled, inhalation of oxygen under increased pressure in conditions of hyperbaric oxygen therapy can lead to serious damage and even death. Case report. We presented a 20-year-old male who had begun exhibiting symptoms of epilepsy during diving test in a hyperbaric chamber while inhaling 100% oxygen. He was immediately taken off oxygen mask and started breathing air and began rapid decompression. He lost consciousness, began foaming at the mouth, and had a series of tonic spasms. The patient was previously completely healthy and not on any medications. He was admitted for emergency treatment in our hospital, where he was treated for epilepsy. On admission, he complained of muscle and joint pain, and had erythematous changes on the forehead, neck and chest. All these changes occurred after leaving the hyperbaric chamber. Bloodwork revealed leukocytosis with neutrophil (Leukocytosis 16.0  109/L (reference values 4.00–11.00  109/L), Neutrophili 13  109/L (reference values 1.9–8.0  109/L), with elevated enzymes aspartate aminotransferase (AST) 56 U/L (reference values 0–37 U/L), alanin aminotransferase (ALT) 59 U /L, (reference values 25–65 U/L), creatine kinase (CK) 649 U/L, (reference values 32–300 U /L), lactate dehydrogenase (LDH) 398 U/L (reference values 85– 227 U/L). Because of pain and his condition we began treatment in a hyperbaric chamber at a pressure of 2.0 ATA for 70 minutes, resulting in a reduction of symptoms and objective recovery of the patient. Within 24 h, repeated laboratory tests showed a reduction of leukocytosis (13  109/L and neutrophils (7.81  109/L), and the gradual reduction of the enzymes AST (47 U/L), ALT (50 U/L, CK (409 U/L), LDH (325 U/L). Since head CT and EEG were normal, epilepsy diagnosis was ruled out. This fact, along with medical tests, facilitated the differential diagnosis and confirmed that this was a case of neurotoxic effects of oxygen while the patient was in a hyperbaric chamber, not epileptic seizures. Conclusion. This case report suggests that in patients with symptoms of epileptic seizures while undergoing treatment in a hyperbaric chamber, it is always important to think of neurotoxic effects of pure oxygen which occurs at higher pressures and with a longer inhalation of 100% oxygen. In these patients, reexposure to hyperbaric conditions leads to recovery. This effect is important in daily inhalation of 100% oxygen under hyperbaric conditions which is why the use of pure oxygen is controlled and diving is allowed in shallow depths and for a limited time.

227 U/L).Because of pain and his condition we began treatment in a hyperbaric chamber at a pressure of 2.0 ATA for 70 minutes, resulting in a reduction of symptoms and objective recovery of the patient.Within 24 h, repeated laboratory tests showed a reduction of leukocytosis (13  10 9 /L and neutrophils (7.81  10 9 /L), and the gradual reduction of the enzymes AST (47 U/L), ALT (50 U/L, CK (409 U/L), LDH (325 U/L).Since head CT and EEG were normal, epilepsy diagnosis was ruled out.This fact, along with medical tests, facilitated the differential diagnosis and confirmed that this was a case of neurotoxic effects of oxygen while the patient was in a hyperbaric chamber, not epileptic seizures.Conclusion.This case report suggests that in patients with symptoms of epileptic seizures while undergoing treatment in a hyperbaric chamber, it is always important to think of neurotoxic effects of pure oxygen which occurs at higher pressures and with a longer inhalation of 100% oxygen.In these patients, reexposure to hyperbaric conditions leads to recovery.This effect is important in daily inhalation of 100% oxygen under hyperbaric conditions which is why the use of pure oxygen is controlled and diving is allowed in shallow depths and for a limited time.

Introduction
People's attempts to stay under water while breathing air go back to the distant past.Throughout history there have been many attempts to create machines that would enable people to stay under water with more or less success.There also was always a desire to treat patients with many diseases under these conditions.
In 1662, British doctor Henshaw 1 constructed a ballshaped chamber into which he pumped air using two organ bellows, and tried to cure a number of diseases.The idea was that breathing compressed air has the therapeutic effect.
A Frenchman, Antoine Lavoisier (1743-1794), even though he was not a doctor, came to the conclusion that gas exchange takes place in the lungs.He was sure that the oxygen in the body converts into carbon dioxide, and that the nitrogen which he discovered is removed from the body unchanged.
Following the discovery of oxygen, Joseph Priestley (1733-1804) was the first to raise the question about the possibility of harmful effects of this gas on the body 2 .Oxygen was called "a vital gas" at that time, and Lavoiser described changes in the lungs caused by its inhalation.Only in 1899, after several experiments, Lorain -Smith found that breathing oxygen at a pressure greater than 0.6 bar after a prolonged exposure causes irreversible pathological changes in the lungs.In his honor, this phenomenon is called the Lorain -Smith effect.
In the excellent book "La pression barométrique", French physiologist Paul Bert in 1878, pointed out that breathing oxygen pressurized above 2 absolute bar causes convulsions similar to epilepsy.In deference to him, such cases are referred to as "Paul Bert effect" or neurotoxic effects of oxygen 2 .Others, starting with Berta, have proposed to replace air with oxygen during treatment process 4 .Behnke and Shaw 5 were the first to try this.Their work resulted in a recommendation of therapy based on the severity of the condition and first application of mixtures of oxygen and nitrogen different than normal air.Paul Bert effect is important in daily inhalation of oxygen, which is why its use is limited and diving is allowed in shallow depths and for a limited time.The most accepted mechanism is that oxygen inactivates ferments necessary for the performance of normal processes in nerve cells 6 .
Bert 4 also noted that rapid transition from higher to lower pressure leads to sickness and even fatality, so he suggested the prevention of decompression sickness by gradually decreasing pressure (gradual decompression).This is actually the first introduction of the prophylactic decompression procedure based on the principle of slow and continuous emergence.An important aspect of this early work was the recognition of safe limits of exposure to oxygen in relation to dose and time, and the highest possible oxygen pressure and the longest exposure time with the minimum possible risk of oxygen toxicity to the central nervous system 7,8 .Later, navies became interested in oxygen and expanded its use, speeding up the process of decompression and improving the efficiency and treatment of divers 9,10 .
Bert's other significant contribution to the practice of hyperbaric medicine was the recognition of oxygen toxicity to the central nervous system with application of oxygen under high partial pressures 6,7 .Oxygen toxicity on the central nervous system was not significant for many years as it was mainly related to diving until the use of sufficiently high partial pressures of oxygen in the clinical setting 11 .The mechanism of oxygen neurotoxicity explans that hyperbaric oxygen inactivates ferments responsible for bioregulation of vital processes in nerve cells, but there is also a view that dissolved oxygen disrupts a regular transport of oxygen and removal of carbon dioxide 6 .

Case Report
A 20-year-old male, a diver candidate became ill during testing in the hyperbaric chamber, and admitted to our hospital as an emergency case.The patient's history and medical records indicated that previously he was a healthy person who did not take any medication.While breathing 100% oxygen at the depth of 18 m for 60 minutes in the chamber, he developed problems that were manifested as the loss of consciousness, foaming at the mouth, and a series of convulsions of the entire body and limbs.
A companion in the chamber reacted by removing the mask and the patient began rapidly to ascent, and from that moment he stopped breathing 100% oxygen and breathed air during the ascent.After surfacing and exiting the hyperbaric chamber the patient was confused, he had nausea and queasiness, and within the next 50 minutes, he developed redness on the forehead, neck and chest, and conjunctival suffusion, with pain in the shoulders and muscles (Figure 1).

Discussion
Occurrence of neurotoxic effects of oxygen has been described in divers who do not comply with the depth of dive, and time for inhalation of 100% oxygen in a closed apparatus 12 .This effect can occur in a hyperbaric chamber in the event of inhalation of 100% oxygen over 2.0 ATA pressure in people who are particularly sensitive to elevated partial pressure of oxygen.
In this case report, we presented healthy person who had been tested in a hyperbaric chamber.While breathing 100% oxygen at the pressure of 2.8 ATA he exhibited a neurotoxic effect, with the appearance of clinical symptoms that resembled epileptic seizures .This effect is not unknown in the literature and is also called oxygen epilepsy or Paul Bert effect 2 .The clinical picture is consistent with epileptic seizure and may represent a major differential diagnostic problem to clinicians who are not familiar with diving diseases.Only later, as in the case of our patient, after neurological examination (EEG, CT and MRI of the head) neurotoxic effect of oxygen that the patient breathed at high pressure, and not epileptic seizure, was confirmed.
Also, with pressure reduction in the chamber and cessation of breathing 100% oxygen, symptoms disappear spontaneously and there is no need for further treatment in most cases.
However, immediately upon admission and after examination and the diagnosis, we placed our patient in a hyperbaric chamber where he was treated for pain in the muscles, joints, and erythema which appeared at the head, neck and chest and conjunctival suffusion.We did that at the pressure of 2.0 ATA for 70 minutes.Already in the course of treatment in the hyperbaric chamber, the patient's condition objectively and subjectively improved which was confirmed by laboratory findings.

Conclusion
We presented a case with neurotoxic effects of oxygen that occurred in the hyperbaric chamber.Such cases occur frequently when diving in a closed type apparatus.In particular, in such cases we emphasize the need to carefully and quickly perform a differential diagnosis to severe neurological diseases, but taking into account inhalation of 100% oxygen, which precedes the condition.The diagnosis is easy to establish following normal EEG, CT and MRI of the head findings, unlike a true epileptic attacks.

Fig. 1 -Fig. 2 -Fig. 3 -
Fig. 1 -Appearance of the patient before treatment with hyperbaric oxygen therapy: a) Changes on the skin of the face; b) Changes on the skin of the neck; c) Changes on the conjuctive (conjuctival suffusion)