Calculated risk of pulmonary and central nervous system oxygen toxicity: a toxicity index derived from the power equation.

BACKGROUND: The risk of oxygen toxicity has become a prominent issue due to the increasingly widespread administration of hyperbaric oxygen (HBO) therapy, as well as the expansion of diving techniques to include oxygen-enriched gas mixtures and technical diving. However, current methods used to calculate the cumulative risk of oxygen toxicity during an HBO exposure i.e., the unit pulmonary toxic dose concept, and the safe boundaries for central nervous system oxygen toxicity (CNS-OT), are based on a simple linear relationship with an inspired partial pressure of oxygen (PO2) and are not supported by recent data. METHODS: The power equation: Toxicity Index = t2 × PO2c, where t represents time and c represents the power term, was derived from the chemical reactions producing reactive oxygen species or reactive nitrogen species. RESULTS: The toxicity index was shown to have a good predictive capability using PO2 with a power c of 6.8 for CNS-OT and 4.57 for pulmonary oxygen toxicity. The pulmonary oxygen toxicity index (PO2 in atmospheres absolute, time in h) should not exceed 250. The CNS-OT index (PO2 in atmospheres absolute, time in min) should not exceed 26,108 for a 1% risk. CONCLUSION: The limited use of this toxicity index in the diving community, after more than a decade since its publication in the literature, establishes the need for a handy, user-friendly implementation of the power equation.

Bubble size on detachment from the luminal aspect of ovine large blood vessels after decompression: The effect of mechanical disturbance.

Bubbles nucleate and develop after decompression at active spots on the luminal aspect of ovine large blood vessels. Series of bubbles were shown to detach from the active spot with a mean diameter of 0.7-1.0mm in calm conditions. The effect of mechanical disturbance (striking the bowl containing the vessel or tangential flow) was studied on ovine blood vessels stretched on microscope slides and photographed after hyperbaric exposure. Diameter on detachment after a heavy blow to the bowl was 0.87 ± 0.43 mm (mean ± SD), no different from bubbles which detached without striking the bowl (0.86 ± 0.28 mm). Bubble diameter on detachment during pulsatile tangential flow at 234 cm/min, 0.99 ± 0.36 mm, was not smaller than that seen in the same blood vessels in calm conditions (0.81 ± 0.34 mm). The active spots were stained for lipids, proving their hydrophobicity. The most abundant active spots, which produced only a few bubbles, did not stain for lipids thereafter. The possibility that phospholipids were removed along with detached bubbles may correlate with acclimation to diving. The finding of bubble production at the active spots matches observed phenomena in divers: variable sensitivity to decompression, acclimation to diving, the effect of elevated gas load on increased bubble formation, a higher bubble score in the second dive on the same day, and unexplained neurological symptoms after decompression. Large bubbles released from the arterial circulation give serious cause for concern.

Flow resistance, work of breathing of humidifiers, and endotracheal tubes in the hyperbaric chamber.

Humidification of inspired gas is critical in ventilated patients, usually achieved by heat and moisture exchange devices (HMEs). HME and the endotracheal tube (ETT) add airflow resistance. Ventilated patients are sometimes treated in hyperbaric chambers. Increased gas density may increase total airway resistance, peak pressures (PPs), and mechanical work of breathing (WOB). We tested the added WOB imposed by HMEs and various sizes of ETT under hyperbaric conditions. We mechanically ventilated 4 types of HMEs and 3 ETTs at 6 minute ventilation volumes (7-19.5 L/min) in a hyperbaric chamber at pressures of 1 to 6 atmospheres absolute (ATA). Peak pressure increased with increasing chamber pressure with an HME alone, from 2 cm H2O at 1 ATA to 6 cm H(2)O at 6 ATA. Work of breathing was low at 1 ATA (0.2 J/L) and increased to 1.2 J/L at 6 ATA at minute ventilation = 19.5 L/min. Connecting the HME to an ETT increased PP as a function of peak flow and chamber pressure. Reduction of the ETT diameter (9 > 8 > 7.5 mm) and increase in chamber pressure increased the PP up to 27.7 cm H2O, resistance to 33.2 cmH2O*s/L, and WOB to 3.76 J/L at 6 ATA with a 7.5-mm EET. These are much greater than the usually accepted critical peak pressures of 25 cm H2O and WOB of 1.5 to 2.0 J/L. Endotracheal tubes less than 8 mm produce significant added WOB and airway pressure swings under hyperbaric conditions. The hyperbaric critical care clinician is advised to use the largest possible ETT. The tested HMEs add negligible resistance and WOB in the chamber.

Oxygen pretreatment as protection against decompression sickness in rats: pressure and time necessary for hypothesized denucleation and renucleation.

Pretreatment with HBO at 300-500 kPa for 20 min reduced the incidence of decompression sickness (DCS) in a rat model. We investigated whether this procedure would be effective with lower oxygen pressures and shorter exposure, and tried to determine how long the pretreatment would remain effective. Rats were pretreated with oxygen at 101 or 203 kPa for 20 min and 304 kPa for 5 or 10 min. After pretreatment, the animals were exposed to air at 1,013 kPa for 33 min followed by fast decompression. Pretreatment at 101 or 203 kPa for 20 min and 304 kPa for 10 min significantly reduced the number of rats with DCS to 45%, compared with 65% in the control group. However, after pretreatment at 304 kPa for 5 min, 65% of rats suffered DCS. When pretreatment at 304 kPa for 20 min was followed by 2 h in normobaric air before compression and decompression, the outcome was worse, with 70-90% of the animals suffering DCS. This is probably due to the activation of "dormant" micronuclei. The risk of DCS remained lower (43%) when pretreatment with 100% O(2) at normobaric pressure for 20 min was followed by a 2 h interval in normobaric air (but not 6 or 24 h) before the hyperbaric exposure. The loss of effectiveness after a 6 or 24 h interval in normobaric air is related to micronuclei rejuvenation. Although pretreatment with hyperbaric O(2) may have an advantage over normobaric hyperoxia, decompression should not intervene between pretreatment and the dive.

Energetic efficiency in trained and sedentary rats after exposure to normobaric and hyperbaric oxygen.

INTRODUCTION: Contradictory results have been obtained regarding the beneficial effect of hyperbaric oxygen (HBO) on exercise performance. The purpose of this study was to investigate the effect of different combinations of pressure and time in hyperoxia on the energetic efficiency of trained and sedentary rats. METHODS: At the end of the training period, rats were exposed to one of three protocols: 1) 100% normobaric oxygen for 24 h; 2) HBO at 2 ATA for 4 h; 3) HBO at 2.5 ATA for 6 h. After the hyperoxic exposures, V(O2max) was evaluated and compared with preexposure values. RESULTS: The slope of the linear section of the oxygen consumption-velocity curve in the trained rats was significantly steeper after exposure to either 100% normobaric oxygen for 24 h or HBO at 2 ATA for 4 h than before the exposure. The opposite was found for the sedentary rats. After exposure to HBO at 2.5 ATA for 6 h, the slope of the oxygen consumption-velocity curve in the trained rats did not differ from the pre-exposure slope. However, the highest velocity these rats reached was lower than their maximum velocity before this exposure. In the sedentary rats, the slope of the oxygen consumption-velocity curve was found to be steeper after the 2.5 ATA exposure compared with the preexposure slope. CONCLUSIONS: Our results suggest that exposure to 100% normobaric oxygen for 24 h and HBO at 2 ATA for 4 h induces a reduction in the energetic efficiency of trained rats, but improves energetic efficiency in sedentary rats.

Recovery from central nervous system oxygen toxicity in the rat at oxygen pressures between 100 and 300 kPa.

No symptoms related to central nervous system (CNS) oxygen toxicity have been reported when diving with oxygen rebreathers at depths shallower than 3 msw. We hypothesised that recovery from CNS oxygen toxicity will take place when the PO(2) is less than 130 kPa. We exposed rats to a high PO(2) (mainly 608 kPa) to produce CNS oxygen toxicity. The latency to the first electrical discharge (FED) preceding convulsions was determined as the animal's control latency. Thereafter, the rat was exposed to the same PO(2) for 60% of its latency, then to a lower PO(2) for 15 min (sufficient time for full recovery in normoxia), and finally to the high PO(2) again until appearance of the FED. If recovery from CNS oxygen toxicity takes place during the interim period, the latency for the final exposure to the high oxygen pressure should not be shorter than the control. The latencies to CNS oxygen toxicity for exposure to the high oxygen pressure after a 15-min interim period at 21, 101, 132, 203, 304, 405, and 456 kPa were 110, 110, 125, 94, 85, 54 and 38% of the control value, respectively. Only after the last two interim pressures were the latencies significantly shorter than control values. The remaining latencies were not significantly different from 100%. Recovery from CNS oxygen toxicity in the rat takes place at a PO(2) anywhere between 21 and 304 kPa. The present findings support our previous suggestion that recovery from CNS oxygen toxicity in humans will take place at a PO(2) below 130 kPa. If our findings are corroborated by further human studies, this will justify including recovery in the algorithm for CNS oxygen toxicity in closed-circuit oxygen divers.

Hyperbaric oxygen pretreatment reduces the incidence of decompression sickness in rats.

We have previously hypothesised that the number of bubbles evolving during decompression from a dive, and therefore the incidence of decompression sickness (DCS), might be reduced by pretreatment with hyperbaric oxygen (HBO). The inert gas in the gas micronuclei would be replaced by oxygen, which would subsequently be consumed by the mitochondria. This has been demonstrated in the transparent prawn. To investigate whether our hypothesis holds for mammals, we pretreated rats with HBO at 304, 405, or 507 kPa for 20 min, after which they were exposed to air at 1,013 kPa for 33 min and decompressed at 202 kPa/min. Twenty control rats were exposed to air at 1,013 kPa for 32 min, without HBO pretreatment. On reaching the surface, the rat was immediately placed in a rotating cage for 30 min. The animal's behaviour enabled us to make an early diagnosis of DCS according to accepted symptoms. Rats were examined again after 2 and 24 h. After 2 h, 65% of the control rats had suffered DCS (45% were dead), whereas 35% had no DCS. HBO pretreatment at 304, 405 and 507 kPa significantly reduced the incidence of DCS at 2 h to 40, 40 and 35%, respectively. Compared with the 45% mortality rate in the control group after 24 h, in all of the pretreated groups this was 15%. HBO pretreatment is equally effective at 304, 405 or 507 kPa, bringing about a significant reduction in the incidence of DCS in rats decompressed from 1,013 kPa.

Hyperbaric oxygen therapy for reduction of secondary brain damage in head injury: an animal model of brain contusion.

Cerebral contusions are one the most frequent traumatic lesions and the most common indication for secondary surgical decompression. The purpose of this study was to investigate the physiology of perilesional secondary brain damage and evaluate the value of hyperbaric oxygen therapy (HBOT) in the treatment of these lesions. Five groups of five Sprague-Dawley rats each were submitted to dynamic cortical deformation (DCD) induced by negative pressure applied to the cortex. Cerebral lesions produced by DCD at the vacuum site proved to be reproducible. The study protocol entailed the following: (1) DCD alone, (2) DCD and HBOT, (3) DCD and post-operative hypoxia and HBOT, (4) DCD, post-operative hypoxia and HBOT, and (5) DCD and normobaric hyperoxia. Animals were sacrificed after 4 days. Histological sections showed localized gross tissue loss in the cortex at injury site, along with hemorrhage. In all cases, the severity of secondary brain damage was assessed by counting the number of terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) and caspase 3-positive cells in successive perilesional layers, each 0.5 mm thick. Perilesional TUNEL positive cells suggested the involvement of apoptosis in group 1 (12.24% of positive cells in layer 1). These findings were significantly enhanced by post-operative hypoxia (31.75%, p < 0.001). HBOT significantly reduced the severity and extent of secondary brain damage expressed by the number of TUNEL positive cells in each layer and the volume of the lesion (4.7% and 9% of TUNEL positive cells in layer 1 in groups 2 and 4 respectively, p < 0.0001 and p < 0.003). Normobaric hyperoxia also proved to be beneficial although in a lesser extent. This study demonstrates that the vacuum model of brain injury is a reproducible model of cerebral contusion. The current findings also suggest that HBOT may limit the growth of cerebral contusions and justify further experimental studies.

Hyperoxia may reduce energetic efficiency in the trained rat.

BACKGROUND: Several studies have been conducted in recent years in the attempt to improve running performance by the use of hyperbaric oxygen, but there is disagreement as to whether this has any beneficial effect. The purpose of this study was to measure the effect of 24 h breathing 100% O2 in normobaric conditions on energetic efficiency in the trained rat. METHODS: Experiments were carried out on trained rats whose oxygen consumption was evaluated during the training period and on its completion. At the end of the training period, the rats were divided into two groups: 1) rats exposed to air (21% O2) in normobaric conditions; and 2) rats exposed to 100% O2 in normobaric conditions. In addition, two groups of sedentary rats were used: 3) sedentary rats exposed to air (21% O2) in normobaric conditions; and 4) sedentary rats exposed to 100% O2 in normobaric conditions. Energetic efficiency was estimated by measuring O2 consumption at submaximal exercise (45 m.min-1, 10 degrees incline). RESULTS: Training alone reduced O2 consumption by 18% during submaximal exercise. Exposure to 100% oxygen for 24 h in normobaric conditions reversed the effect of complete training by elevating the O2 consumption by 17%, which was close to the oxygen consumption of the rats during the incomplete training period. CONCLUSIONS: Our results suggest that prolonged exposure to hyperoxia induces a reduction in the energetic efficiency of the trained rat. The relevance of these findings to sports and diving is discussed.

Model of CNS O2 toxicity in complex dives with varied metabolic rates and inspired CO2 levels.

INTRODUCTION: Clinical hyperbaric oxygen (HBO) therapy and the use of pure oxygen or gases having a high partial pressure of oxygen in diving carry a risk of central nervous system (CNS) oxygen toxicity. Previously, we solved the power equation K = t2(PO2/101.3)C for humans, where t is the exposure time, PO2 is the oxygen pressure, and K is the cumulative oxygen toxicity index. The value of c was 6.76, and a symptom may appear when K reaches a threshold value Kc = 2.31 X 10(8) (Arieli et al. J Appl Physiol 2002; 92:248-56). METHODS AND RESULTS: The calculation of K for a complex exposure profile made it possible to estimate risk from the normal distribution for a metabolic rate of 1.28 L x min(-1), Z = [ln(K0.5)-9.63]/2.02 and for 0.9 L x min(-1), Z = [ln(K0.5)-11.19]/1.35. The predicted risk was in agreement with the reported risk in composite exposures. The parameters c and ln(Kc) in the power equation are linearly related to metabolic rate (M) and inspired CO2 in rats. Due to the assumed similar relationship between the data from rats and humans, the mean time to CNS oxygen toxicity (tc(M)) as a function of metabolic rate may be calculated for humans as follows: tc(M) = [(e(-2.85 M + 31.8))/(PO2/101.3)(-7.45 M + 39.6)]0.5, where M is metabolic rate in units of resting metabolic rate. A parallel equation for the mean time to toxicity as a function of PCO2 was derived for the rat. This equation can be transformed to express the latency in humans, once the parameters for humans are known. CONCLUSIONS: The power equation that predicts oxygen toxicity in humans was extended to include a complex diving profile as well as the effects of metabolic rate and CO2.

Hyperbaric oxygen may reduce gas bubbles in decompressed prawns by eliminating gas nuclei.

It is accepted that gas bubbles grow from preexisting gas nuclei in tissue. The possibility of eliminating gas nuclei may be of benefit in preventing decompression sickness. In the present study, we examined the hypothesis that hyperbaric oxygen may replace the resident gas in the nuclei with oxygen and, because of its metabolic role, eliminate the nuclei themselves. After pretreatment with oxygen, prawns were 98% saturated with nitrogen before explosive decompression at 30 m/min. Ten transparent prawns were exposed to four experimental profiles in a crossover design: 1) 10-min compression to 203 kPa with air; 2) 10-min compression with oxygen; 3) 10-min compression with oxygen to 203 kPa followed by 12 min air at 203 kPa; and 4) 10 min in normobaric oxygen followed by compression to 203 kPa with air. Bubbles were measured after explosive decompression. We found that pretreatment with hyperbaric oxygen (profile C) significantly reduces the number of bubbles and bubble volume. We suggest that hyperbaric oxygen eliminates bubble nuclei in the prawn.