Oxygen does harm ?

[bravofoxtrot]

Right, need to make my sentences more clear.

[Ace844]

Over the last year or so there have been a smattering of posts on the subject of which I am about to post. Since this is the nearest most appropriate topic to add this to after an extensive search, read on...This is a rarely discussed topic but could be important as it occasionally rears its ugly head in various areas and with pedi pts around the country.

(Ford: Clinical Toxicology @ 1st ed., Copyright © 2001 W. B. Saunders Company

Paraquat and Diquat

BRENT R. EKINS

RICHARD J. GELLER)

Essentials

• History or suspicion of paraquat or diquat ingestion, or history of unusual skin/mucous membrane exposure (Paraquat is a blue-green liquid; diquat is brown.)

• Paraquat and diquat: Rapid development of multisystem organ failure in cases of substantial ingestion (more than 40 mg/kg for paraquat)

• Paraquat: Gastrointestinal symptoms followed by renal failure and pulmonary fibrosis in moderate poisoning (ingestion of 20–40 mg/kg)[50]

• Laboratory confirmation by urine or blood level (quantitative) or sodium dithionite test (qualitative)

• Paraquat: Unexplained pulmonary fibrosis with or without other skin/mucous membrane effects

INTRODUCTION

Paraquat (1,1′-dimethyl-4,4′-bipyridylium dichloride) [CAS #1910-42-5] and diquat (1,1′-ethylene-2,2′-dipyridylium dibromide) [CAS #85-00-7] are the most commonly used herbicides in the bipyridylium quaternary ammonium compound group. Paraquat was first described in 1882. Subsequent to its development as an herbicide in the 1950s it was used as an indicator for chemical oxidation-reduction reactions and was known by the common name methyl viologen ( Fig. 106–1 ).

Bipyridylium herbicides (BHs) are used throughout the world as contact herbicides and as crop desiccants on products such as cotton. Product formulations differ by country. They are most commonly sold as liquids. Zeneca is the largest manufacturer/distributor in the United States. It produces paraquat most commonly as Gramoxone Extra (37.00 per cent w/v aqueous formulations paraquat ion), and diquat as Reward or Diquat Herbicide, both 36.4 per cent diquat cation. Granular and gel forms are also encountered.

Paraquat and diquat are highly potent systemic poisons. More is known about the human toxicology of paraquat than diquat, owing to the much higher frequency of reported exposures to paraquat causing sickness and death. An estimated lethal dose of 20 per cent paraquat is 10 to 20 mL for adults[12] and 4 to 5 mL for children.[18] Diquat is estimated to be slightly less toxic, with a lethal dose for adults of 6 to 12 g (30–60 mL of 20 per cent diquat).[51]

More than 1000 deaths per year from paraquat ingestion led Japanese authorities in 1986 to ban the use of 20 per cent paraquat. Almost any oral exposure to this concentration should be viewed as potentially fatal and should be managed accordingly. A mixture of 4.5 per cent w/v paraquat and 4.5 per cent w/v diquat is now used in Japan.[55]

In the United States, the American Association of Poison Control Centers reported 3 diquat and 29 paraquat fatalities between 1983 and 1998.[25] Overwhelmingly, American deaths are intentional and by ingestion, with rare cases of intentional injection.[1]

TOXICOLOGY/PATHOPHYSIOLOGY

Toxicology

Absorption

Gastrointestinal absorption rates for paraquat and diquat are similar.[2] Paraquat is known to be very rapidly but incompletely absorbed from the gastrointestinal tract. Absorption occurs primarily in the small intestine and is estimated to be 1 to 5 per cent in humans.[7] Extensive caustic injury to the gastrointestinal tract may increase the amount absorbed. Peak plasma levels occur within 2 hours of ingestion.[44]

Prolonged dermal contact time or contact with damaged skin is generally required for systemic absorption.[5] [8] [20] [44]

Figure 106-1 Diquat and paraquat structures. (From Sabapathy NN: Quaternary ammonium compounds. Toxicology 1994; 91:93.)

Inhalation of paraquat used in an agricultural/occupational setting does not allow sufficient absorption to cause systemic disease, because droplet size prohibits deep lung exposure and absorption.[23] Concern regarding the smoking of paraquat-sprayed marijuana in the early 1970s has proved unfounded, because paraquat is destroyed by pyrolysis.

A fatal case of paraquat absorbed per vagina has been reported.[36] Ocular exposure causes local caustic injury but is unlikely alone to produce systemic toxicity.

Distribution

Excluding bile, paraquat distributes most avidly to lung, kidney, liver, and muscle.[2] It has an apparent volume of distribution of 1.2 to 1.6 L/kg.[22] Also excluding bile, diquat distributes primarily to kidney, with less appreciable concentrations found in spleen, lung, liver, and muscle.[2]

Paraquat, but not diquat, is taken up against a concentration gradient by the type I and type II pneumocytes. This occurs through an ATP-dependent active transport mechanism.[45] A critical plasma threshold is needed for active pulmonary uptake to occur.[30] Experimentally, lung fibrosis can be induced by exposure of rat lung to diquat, but at doses much larger than required for paraquat.[28]

Metabolism

Paraquat elimination is virtually entirely renal and is accomplished by both glomerular filtration and active tubular secretion. Greater than 90 per cent is excreted unchanged within 12 to 24 hours of ingestion, if renal function remains normal.[22] Ingested diquat is excreted by the kidneys and gastrointestinal tract.[26]

Pathophysiology

Paraquat and diquat undergo cyclic reduction/oxidation in conjunction with NADPH and oxygen, resulting in the formation of the superoxide radical ( O2 − ). Dicationic bipyridyls are reduced by NADPH to monocationic free radicals and cyclically return to their original forms by giving up an electron to oxygen to form superoxide radical ( Fig. 106–2 ).

In the first phase of this cycle, dicationic paraquat (PQ2+ ) plus NADPH undergo a reaction producing the reduced paraquat ion (PQ1+ ) plus NADP+ . PQ1+ reacts almost immediately with O2 , regenerating PQ2+ plus the superoxide radical ( O2 − ). Assuming availability of NADPH and O2 , the redox cycle of paraquat continues on and on, with the continued depletion of NADPH, and generation of ( O2 − ).The superoxide free radical subsequently reacts with itself to form hydrogen peroxide (H2 O2 ), and with H2 O2 plus iron to form hydroxyl ( O2 − ) free radicals.[47]

The redox cycle involving paraquat, oxygen, and NADPH, as well as the subsequent generation of the hydroxyl free radical, spawns multiple mechanisms of cellular damage. Depletion of NADPH leads to cell death. Hydroxyl free radicals are highly toxic and react with lipids in cell walls, a destructive process known as lipid peroxidation.[54] DNA and proteins critical to cell survival are also destroyed by hydroxyl free radicals.

The cellular consequences of free radical formation (superoxide and others) by bipyridyls are the subject of a large body of medical literature.[10] [11] [18] [22] [37] [38] [47] [48] Experimental treatments aimed at modification of free radical pathophysiology have included deferoxamine, superoxide dismutase, alpha-tocopherol, and ascorbic acid in conjunction with forced diuresis. Unfortunately, none of these can be recommended at the present time.

Although the complete detail of paraquat-generated free radical toxicology is unknown, what is known is that the basis for poisoning is the interaction among paraquat, NADPH and oxygen. Oxygen at the cellular level, then, is a critical factor in the genesis of disease caused by paraquat. This is the basis for withholding supplemental oxygen in the early treatment of the paraquat-poisoned patient.

Bipyridyls are caustic and produce an injury similar to alkaline corrosives on contact with skin, eyes, and mucous membranes. The major target organs for systemic paraquat poisoning are the gastrointestinal tract, kidneys, and lungs. The gastrointestinal tract is severely injured by a direct corrosive effect when exposed to significant concentrations in a deliberate ingestion. The kidney is the organ of elimination for paraquat and diquat and has high concentrations of the bipyridyls compared with other organs.

Paraquat, but not diquat, is actively taken up by the lung through an energy-dependent process.[45] The lung undergoes a biphasic injury pattern after paraquat exposure. A destructive phase, characterized by destruction of alveolar epithelium, results from the consequences of the redox cycle.

Figure 106-2 Redox cycle of paraquat (PQ). (From Sabapathy NN: Quaternary ammonium compounds. Toxicology 1994; 91:93.)

Subsequently, a proliferative phase, regarded as a consequence of the destructive phase, produces additional destruction. In this second phase, normal epithelial cells are replaced by fibrous tissue, leading to massive pulmonary fibrosis, hypoxemia, and death.

CLINICAL PRESENTATION

A rapid but thorough history is imperative. Note the precise formulation of the substance involved, whether or not it was diluted or concentrated, the amount ingested, the time since ingestion, the presence or absence of food in the gut, and whether spontaneous emesis has occurred. A careful physical examination should include a search for oral, skin, or mucous membrane lesions. Vomitus should be examined for color and blood and saved for analysis.

Poisoning of children by both paraquat and diquat has been reported.[27] [42] The clinical approach for children who have been poisoned does not differ from that of poisoned adults.

Paraquat

Paraquat poisoning can be divided into three different presentations depending on the amount ingested or injected.[50]

Severe Toxicity

Ingestion of paraquat ion of greater than 40 mg/kg results in rapidly progressing multisystem organ failure (40 mg/kg is 14 mL of a 20 per cent solution for a 70-kg patient). Caustic mucous membrane damage, with vomiting, massive myonecrosis, and renal, hepatic, respiratory, cardiac, neurologic, adrenal, or pancreatic failure can cause death within hours to a few days, at most.

Moderate Toxicity

Ingestion of paraquat ion of 20 to 40 mg/kg produces a more indolent illness. Early symptoms include local damage to the gastrointestinal tract, including the oropharynx, severe vomiting, and gastrointestinal bleeding, as well as constitutional symptoms. Complications of this early phase have included pneumopericardium, pneumomediastinum, and pneumothorax.[9] Renal failure gradually occurs and may produce an unusually rapid rise in serum creatinine relative to the rise in blood urea nitrogen (low BUN/creatinine ratio). In one case seen by the authors, the observation of an unusually high creatinine value in a case of upper gastrointestinal bleeding (where one might expect to see an unusually large increase in BUN but not creatinine) led to the diagnosis of paraquat toxicity even though the patient denied ingestion. Eventually, in cases of moderate ingestions, pulmonary fibrosis intervenes after days or weeks. Death occurs in the majority of persons with 20- to 40-mg/kg ingestions of paraquat ion.

Mild Toxicity

Ingestion or injection of paraquat ion of less than 20 mg/kg produces no symptoms or only mild gastrointestinal tract symptoms. Full recovery is expected in all cases.[50] Bismuth[7] regards doses of less than 30 mg/kg as benign, 30 to 50 mg/kg as moderately severe, and greater than 55 mg/kg as lethal.

Although deliberate ingestion or injection is responsible for most cases of serious bipyridylium herbicide toxicity, morbidity and mortality can occur from other routes of exposure.

Skin exposure can cause death when prolonged or unusual contact with a concentrated BH occurs. Death has followed paraquat application to beard and scalp (to treat lice) and whole-body (except face) paraquat application to treat scabies.[13] Multiple case reports document death from prolonged exposure to clothes soaked in concentrated paraquat.[53] Cutaneous exposure to paraquat diluted according to directions or brief dermal exposure to concentrated paraquat is unlikely to cause systemic illness. Direct eye contact with concentrated solutions will produce caustic ocular injury dependent on contact time and concentration.

Community exposure to a paraquat drift in California caused a variety of local and some systemic symptoms, including cough, diarrhea, headache, nausea, fatigue, rhinorrhea, and excessive tearing. These symptoms were significantly increased when compared with a control population.[3] Careless occupational exposure can produce mucous membrane irritation: corneal and conjunctival inflammation, epistaxis, and sore throat.

Diquat

Diquat exposures produce signs and symptoms similar to those of paraquat except for one important system—the pulmonary system. Because diquat is not actively taken up by lung pneumocytes in a manner similar to paraquat, pulmonary fibrosis is typically missing from the clinical picture of diquat intoxication. Brainstem hemorrhagic infarction may be more common with diquat,[47] although there are insufficient numbers of case reports to draw this inference conclusively. The estimated lethal dose of diquat was 10 g in a 16-year-old and 4 g in a 60-year-old.[26] [42] [51] [52] A 10-year-old boy survived a 6-g ingestion.

Clinical syndromes that should suggest the possibility of BH poisoning are listed in Table 106–1 . Symptoms associated with BH poisoning are catalogued in Table 106–2 , along with differential diagnostic considerations.

DIFFERENTIAL DIAGNOSIS

A patient presenting with a history of BH ingestion and multisystem organ failure presents little diagnostic challenge.

TABLE 106-1 -- Clinical Syndromes Suggestive of Bipyridylium Herbicide Poisoning Unexplained acute renal failure

Idiopathic pulmonary fibrosis or symmetric perihilar infiltrates (paraquat only)

Unexplained multisystem organ failure

Severe gastroenteritis ± upper gastrointestinal bleeding ± oropharyngeal lesions

Brainstem hemorrhagic infarction

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TABLE 106-2 -- Clinical Manifestations Associated with Bipyridylium Herbicide Poisoning and the Differential Diagnosis of Toxins and Drugs That May Mimic It Acute Renal Failure Pulmonary Fibrosis (Paraquat Only) Multisystem Organ Failure Severe Vomiting/Diarrhea + Upper Gastrointestinal Bleeding

Acetaminophen Aluminum Abrin (rosary pea) Antineoplastic drugs

Aminoglycosides Amiodarone (chronic use) Colchicine Barium

Amphotericin B Antineoplastic drugs Fluorides Boric acid

Arsine Bleomycin Fluoroacetate (compound 1080) Carbamates

Beta-lactam antibiotics Cyclophosphamide Iodide Cardiac glycosides

Boric acid/borates Asbestos Iron Caustics

Cisplatin Beryllium Metals: Colchicine

Cyclosporine Chromium Arsenic Ethanol

Diethylene glycol Gold Barium Fluoride

Dinitrophenol Kaolin Chromium (hexavalent salts) Iodide

Ethylene glycol Nitrofurantoin (chronic use) Mercury (salts) Iron

Halogenated hydrocarbons Ozone Phosgene Metaldehyde

Metals: Phosgene Phosphine Metals:

Arsenic Silica (silicosis) Ricin (castor bean) Arsenic

Cadmium Talc Salicylates Chromium

Chromium Tocainide Zinc phosphide Mercury

Copper

Organic tin

Mercury (salts)

Thallium

Thallium

Mushroom and plant ingestions

Nonsteroidal anti-inflammatory drugs

Nicotine

Phosphine

Opioid withdrawal

Phosphorus

Organophosphates

Polymyxin

Paraldehyde

Radiographic contrast agents

Phenol

Sulfonamides

Phosphorus

Vancomycin

Podophyllin

Salicylates

Theophylline

Zinc chloride

Zinc phosphide

Less obvious are cases in which exposure has been accidental, of smaller magnitude, homicidal, or deliberately concealed by the patient. Table 106–2 lists some differential diagnostic considerations by clinical presentation and by specific toxin or disease exposure.

LABORATORY STUDIES

Quantitative BH testing is rarely obtainable in the clinical setting, being available at only a few reference laboratories. Testing can be used to confirm exposure and, in paraquat cases, to estimate prognosis. If the time of paraquat ingestion is known, probability of death can be estimated using a blood level and the Hart nomogram ( Fig. 106–3 ).[19]

The nomogram estimates the likelihood of survival (percentage) based on probability curves determined by blood paraquat levels drawn at specific times after ingestion.

BH levels do not indicate the need for specific medical interventions, such as is the case with the acetaminophen nomogram, and thus time is “not of the essence” in obtaining the results. They do assist in predicting severity of illness and probability of death.

Other indirect laboratory testing may help assess the patient and prevent the institution of invasive or ineffective measures in patients who cannot be expected to survive. Serial renal function tests, including serum creatinine and blood urea nitrogen, and blood electrolyte determinations measure the degree and progress of renal tubular injury. The presence of acute tubular necrosis is an ominous finding in the presence of BH intoxication. A baseline chest radiograph should be obtained for all paraquat cases.

Paraquat and diquat emergency testing can be arranged 24

Figure 106-3 Contour graph showing relation between plasma paraquat concentration (μg/mL), time after ingestion, and probability of survival. (From Hart TB: A new statistical approach to the prognostic significance of plasma paraquat concentrations. Lancet 1984; 2:1222.)

hours per day by calling ZENECA Ag Products Emergency Information Network: 1-800-FASTMED (1-800-327-8633). This contract service by Zeneca will provide advice and will make arrangements to ship samples from any location worldwide to a laboratory in California. Samples must be collected in a heparinized plastic syringe, then spun down and shipped in a plastic container on ice. Once the sample is received in the laboratory, turnaround time is 5 hours. Zeneca also provides an 800 number for information on specific products: 1-800-759-2500.

The presence of both paraquat and diquat may be determined quickly in qualitative fashion with the alkali/sodium dithionite urine test. This test is used primarily to exclude the diagnosis of a significant exposure. It reduces the BH to a free radical, creating a dramatic color change in urine. The test is performed by adding 10 mL of urine to 2 mL of 1 per cent sodium dithionite in 1 N sodium hydroxide.[4] [8] [44] A blue color change indicates paraquat, whereas diquat produces a yellow-green color. Sensitivity is such that a negative test is good evidence that significant BH ingestion has not occurred in the past 24 hours.

A respiratory index (RI) has been devised to measure pulmonary function trends in paraquat exposures.[49] This may be of more value in patients who present more than 36 hours after ingestion of BH. In a series of 51 patients, all 43 patients with an RI greater than or equal to 1.5 died; all 8 with an RI less than 1.5 survived (p<.0001). RI is calculated from arterial blood gas data and equals A − aDO2 /PO2 , where A − aDO2 is calculated:

The respiratory quotient ® was assumed to be 0.8.[7]

TREATMENT ( Table 106–3 )

Many empirical therapies for systemic BH exposures have been based on the postulated pathophysiology of these agents, but, unfortunately, most have not proven effective. At the time of a patient’s presentation to a health care provider, the outcome has usually already been determined by the degree of exposure. However, supportive care may be necessary for patients with a good prognosis and should be provided to those with a poor prognosis.

TABLE 106-3 -- Treatment of Bipyridylium Herbicide Poisoning Airway management and advanced life support, as needed

Decontamination

Gastrointestinal: multidose activated charcoal, 1 gm/kg PO

Dermal and ocular: copious irrigation

Intravenous crystalloids to maintain urine output at

1–2 mL/kg/hr

Oxygen: administer only for hypoxia

Analgesic and anxiolytic drugs, as needed

Extracorporeal removal

Hemoperfusion controversial, probably does not alter outcome

Hemodialysis only for renal failure

No role for forced diuresis or peritoneal dialysis

Decontamination

Although gastrointestinal decontamination has never been shown to change outcome in BH poisoning, early decontamination is probably the single most valuable therapy available for oral ingestions. Activated charcoal, 100 g for adults and 1 g/kg body weight for children, should be given unless there is a contraindication, such as protracted vomiting or severe burns of the oral mucous membranes. Multiple doses of activated charcoal have not been studied in BH ingestion; however, they should not cause harm provided emesis has been controlled. A total of three doses of activated charcoal at 2-hour intervals is sensible. Fuller’s earth and bentonite clay were at one time listed as the decontamination agents of choice, but activated charcoal is more easily available and probably as effective.[14] [30] [34]

Rapid absorption of BH and caustic injury to the gastrointestinal tract, as well as lack of proven efficacy, preclude significant roles for orogastric lavage, syrup of ipecac, or whole-bowel irrigation. Ipecac may be of value in a home setting if immediately available. The risk of worsening the gastrointestinal caustic injury must be balanced against the lethality of the amount ingested. Gastric lavage may be of value if performed within 1 hour of ingestion, but benefit must be balanced against risk of perforation.

The authors have seen deliberate ingestions of paraquat (4 patients) and diquat (1 patient) present to our community hospital. The sole survivor was a farmer who intended suicide by means of ingesting concentrated paraquat but who had the good fortune to eat a large “last meal” of pancakes. He then had spontaneous emesis and presented to the emergency department within 5 minutes of ingestion, where activated charcoal was immediately given, followed by orogastric lavage, followed by more activated charcoal.

Dermal and ocular exposures should be managed with copious irrigation. In the case of ocular exposure, pH should be monitored and irrigation continued until pH is normalized.

Extracorporeal Removal

Charcoal hemoperfusion (CHP) has been a controversial treatment of potentially lethal BH ingestions. Although Okenek and associates demonstrated increased clearance of paraquat using CHP in rodent studies[31] [32] [33] [35] and have strongly advocated this therapy in BH ingestions,[31] [32] [33] [35] the current consensus is that CHP does not change outcome.[5] [6] [15] [16] [17] [21] [29] [39] [40] [43] [50] Although charcoal hemoperfusion can increase elimination of BH, prognosis is not changed. This is because of at least three factors: (1) the patient has usually ingested many times the lethal dose; (2) there is no reliable way to rapidly separate lethal from nonlethal ingestions; and (3) the delay before the procedure begins is usually sufficient to allow absorption and distribution of fatal amounts of BH, even when the decision to hemoperfuse is made quickly. Furthermore, the renal clearance with normal kidneys is much greater than clearance by means of hemoperfusion.[41]

Hemodialysis (HD) may have to be performed because of acute renal failure, but neither HD nor peritoneal dialysis is effective in increasing BH clearance.

Supportive Therapies

Early crystalloid administration is important to correct dehydration, which is often severe, and to maintain a urine output of 1 to 2 mL/kg/hr. The primary mode of BH elimination is renal. An adequate urine output is critical to early elimination and may delay the onset of renal failure, which in turn slows elimination. There is no role for forced diuresis, however.

Supplemental oxygen should not be administered routinely. Oxygen may increase lung injury by providing additional substrate for superoxide radical formation. However, hypoxic breathing mixtures have not been shown to prevent this phenomenon,[5] and supplemental oxygen should be given to hypoxemic patients.

Good supportive care, including relief of pain and anxiety, is essential. Because medical therapy is so abysmally unsuccessful in reversing moderate to severe BH ingestions, the health care providers, their patients, and the patients’ families are often bewildered. The art of medicine is crucial here, as is a multidisciplinary approach to assisting with impending death. Honesty about prognosis, without taking away hope, and emphasizing what can be done (i.e., pain relief and pastoral and social service care) are keystone approaches to a grim situation.[50]

Lung transplantation has been unsuccessful.[46]

DISPOSITION

All patients suspected of BH ingestion should be admitted to the hospital. Either qualitative or preferably quantitative testing of BH levels should be performed. Aggressive supportive medical and psychiatric care should be initiated and continued as the clinical situation or laboratory-driven prognosis dictates.

SEQUELAE

Patients with significant BH exposures usually either die or recover fully. Long-term pulmonary fibrosis has been reported in survivors, but this is unusual.[24] Case reports documenting survival after diquat ingestion are rare, and little is known about long-term effects in survivors

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52. Williams PF, Jarvie DR, Whitehead AP: Diquat intoxication: Treatment by charcoal haemoperfusion and description of a new method of diquat measurement in plasma. Clin Toxicol 1986; 24:11–20.

53. Wohlfahrt DJ: Fatal paraquat poisonings after skin absorption. Med J Aust 1982; 1:512–513.

54. Yasaka T, Okudaira K, Fujito H, et al: Further studies of lipid peroxidation in human paraquat poisoning. Arch Intern Med 1986; 146:681–685.

55. Yoshioka T, Sugimoto T, Kinoshita N, et al: Effects of concentration reduction and partial replacement of paraquat by diquat on human toxicity: A clinical study. Hum Exp Toxicol 1992; 11:241–245.

Hope This Helps,

ACE844

[AZCEP]

Way to resuscitate a nearly dead thread Ace.

Good stuff there, per usual.

[Ace844]

"AZCEP,"

Thanks, I have been searching like mad for my old tox scenario (about this) which I thought I had posted here and have been unable to find. I thnk maybe it was posted at the 'original board' before this one and I fear maybe lost forever..

Then recently when you posted it in the 'educational thread' it got me to thinking. This is soemthing in which nearly everylevel of 'emergency' provider is pimped on and the next best thing was in a thread about 'how O2 does harm', also there was some great info here by "Ditch" as well.. So i know this was an thread, but felt that the '' might be able to make some use of it...

So Now the question is whatelse can we add here??? Come on guys, any more great examples and info on how this 'begnign' medicine is not so?

Out Here,

ACE844

[AZCEP]

Here's my small contribution

http://www.mindspring.com/~divegeek/oxyconcern.htm

An Oxygen Provider's Concern About Oxygen Toxicity

by

Larry "Harris" Taylor, Ph.D.

In DAN Oxygen Provider classes, there is often a question about oxygen toxicity and whether or not this is an issue at the first responder level. This article addresses that concern and provides a reason for believing the oxygen toxicity risk to a diver receiving treatment from a diving oxygen provider is minimal.

This material is copyrighted and all rights retained by the author. This article is made available as a service to the diving community by the author and may be distributed for any non-commercial or Not-For-Profit use.

All rights reserved.

Go To Site Page: Home About "Harris" Articles War Stories Biblios Editorials Links Site Map Fini

Oxygen is a primary component in the biochemical reactions that sustain life. We cannot survive without it. There is, however, a downside to oxygen. Oxygen is a chemically extraordinarily promiscuous element. It is always seeking other chemical components with which to react. One view of atmospheric science maintains that if it were not for the much more chemically inert and abundant nitrogen present in our atmosphere, that our planet long ago would have burned to cinders in an oxygen-driven torch. This concern was first expressed by Lavosier (who gave oxygen its name in the late 1770's). He observed the increase in flammability of a candle exposed to an oxygen-rich atmosphere and stated, 'the animal powers be too soon exhausted in this kind of pure air." Consider the biochemical reaction:

Oxygen + Anything It can find è “Bad Stuff”

Oxygen, in biological systems, continually forms “bad stuff,” (extremely reactive materials like free radicals, super-oxides, radical anions, etc. Think of this "bad stuff" as "body rust.") that interferes with normal physiological processes. Because these undesirable constituents are always formed in an oxygen atmosphere, our body has evolved over geological time a set of natural biochemical defenses (like super-oxide dismutase, reducing enzymes systems like glutiathione, etc) to cope with these undesirable "bad stuff" species as they are formed.

Problems, like CNS oxygen toxicity, occur when the amount of this “bad stuff” formed exceeds the body’s capacity to deactivate this "bad stuff." Le Chatelier’s principle (an increase in one of the components on the left side of a chemical reaction will force the reaction process to the right). suggests that an increase in oxygen concentration will generate more "bad stuff." The higher the oxygen concentration, the more "bad stuff:" formed. So, increases in oxygen partial pressure will lead to enhanced formation of so-called highly reactive oxygen species. It is the presence of too much and/or too many of these "bad stuff" moieties that leads to physiological problems.

A Threshold Disease

Chemical reactions (like Oxygen + Anything It can find è “Bad Stuff” ) require that the reacting molecules collide with each other in order to react. So, in general, the more concentrated the reactants (chemists call this "mass action"), the faster the reaction proceeds. So, an increase in the partial pressure of a gaseous reactant will increase the reaction rate.

One way of understanding oxygen toxicity is to assume that body removal of "bad stuff: proceeds at a fixed rate. A homeostasis rate developed over time to adequately dispose of "bad stuff" while allowing the necessary oxygen reactions that drive our energy metabolism to proceed. (If all oxygen reactions were stopped, we would cease to function.) As oxygen molecules per unit volume of tissue increase (either by increase in concentration of oxygen in the breathing mix or by increases in pressure), more "bad stuff" forms. Since waste disposal of "bad stuff" works at a fixed rate, the "bad stuff" begins to accumulate. This increase in "bad stuff" eventually overwhelms the body defenses and accumulated highly reactive oxygen species do their damage.

There are two types of oxygen toxicity: Central Nervous System (CNS) toxicity can lead to a highly excitatory state (like an epileptic seizure). The rapid depth-related onset strongly suggests a direct chemical reaction with oxygen involving the formation of a central nervous system excitant (like NO. ). Since empirical evidence (diver seizure and death) has indicated the approximate threshold (varies with individual diver's body chemistry on day of dive) is 1.4 to 1.6 ata, divers limit their risk to this malady by keeping the partial pressure of oxygen in their breathing mix below 1.4 ata. Breathing pure oxygen in a first aid scenario at sea level (1.0 ata oxygen) is well below the established threshold. NOAA has developed a table for approximating the depth/time dependent exposure. Use of this table is typically discussed in oxygen-enriched dive training classes. CNS toxicity is not considered a significant risk factor in air diving at recreational depths. It is a major risk factor in non-air diving to depths beyond typical recreational levels.

The second type of oxygen toxicity is termed pulmonary or whole-body oxygen toxicity. This situation arises from changes in the respiratory and circulatory system's cellular structure when exposed to high concentrations of oxygen. Typically, this takes many hours and is characterized by gradually increasing difficulty in breathing. The respiratory people have developed a system of measuring oxygen exposures to monitor amount of oxygen dose received (and therefore, relative risk). They have defined an Oxygen Toxicity Unit (OTU) as 1 OTU = 1 minute of breathing 100% oxygen at sea level. Since it has been observed that most people can tolerate 24 hours of breathing pure oxygen without trouble, the accepted allowable dose is 1440 OTU's (1 OTU per min x 60 min/hr x 24 hr/ day) per day

.

The "Numbers"

I believe the relative concerns are about oxygen toxicity can be best expressed by looking at some computer-generated numbers, with the understanding that different computer programs may give slightly different absolute values for the numbers quoted. The exact numerical value is NOT as important as the relative magnitude of the number and its comparison to the accepted tolerance limits. Besides, in the clinical situation, even though numbers are important tracking devices and guidelines, therapeutic protocols (time/depth/breathing gas) are evaluated and determined by the medical staff based on individual patient behavior and needs. Lastly, while 1440 OTU's is the allowed daily dose of oxygen, under physician's care in a hyperbaric procedure, doses in excess of 1700 OTU's may be acceptable.

A diver breathing 100% Oxygen at sea level (1 ata pressure) accumulates 1 OTU per minute. An injured diver breathing from a demand inhalator mask typically consumes a DAN jumbo D cylinder in approximately 50 minutes. So, each DAN cylinder consumed represents about 50 OTU 's delivered to the patient. Thus, a diver would need to consume (1440 0TU allowed per day / 50 OTU per cylinder) 28.8 DAN jumbo D cylinders in a continuous 24-hour session to reach the allowed whole body daily dose. Most divers do NOT carry this quantity of oxygen with them AND, more importantly, transfer of the patient to the emergency medical chain of response occurs long before oxygen toxicity becomes a critical factor.

Now, let's address accumulation of OTU's during recreational diving on typical recreational diving breathing gases.

Table One examines the % CNS toxicity (as a measure of CNS toxicity risk) and accumulated OTU's (as a measure of whole body or pulmonary toxicity risk) for dives on air to the no decompression limits of the US Navy tables. These numbers are well below the daily-allowed dose of 1440 OTU.

Table 1: Oxygen Toxicity Values While Breathing Air

Depth (fsw)

Time (min)

% CNS

OTU's

40

200

0

0.00

50

100

12

9.10

60

60

8

14.67

70

50

8

19.04

80

40

7

20.40

90

30

7

19.11

100

25

6

19.07

110

20

6

17.85

120

15

5

15.51

130

10

4

12.10

140

10

5

13.50

There has been some discussion in the recreational diving literature, especially in the early 1990's, about withholding oxygen to divers who have made dives using a breathing mix of oxygen-enriched air. So, let's look at "the numbers" for oxygen-enriched air. Table Two is a compilation of oxygen toxicity values for dives to the no decompression limits while breathing NOAA Mix 1 (32 % oxygen). Again, these values are far below thresholds of concern.

Table 2: Oxygen Toxicity Values While Breathing NOAA Mix 1 (32 % Oxygen)

Depth (fsw)

Time (min)

% CNS

OTU's

40

310

55

149.19

50

200

45

133.17

60

100

29

84.16

70

60

20

60.80

80

50

22

59.42

90

40

20

54.38

100

30

18

46.32

110

25

18

43.55

120

25

22

47.71

130

20

36

42.15

In addition, Table Three is a compilation of oxygen toxicity values for dives to the no decompression limits while breathing NOAA Mix 2 (36 % oxygen). As with Mix 1, these values are below thresholds of concern.

Table 3: Oxygen Toxicity Values While Breathing NOAA Mix 2 (36 % Oxygen)

Depth (fsw)

Time (min)

% CNS

OTU's

40

310

68

200.48

50

200

56

166.46

60

100

35

103.36

70

60

26

73.35

80

60

31

85.01

90

50

31

80.43

100

40

31

72.39

110

30

42

60.36

To help put this is a bit more of a proper perspective, consider (only for the purposes of examining the "numbers" for oxygen toxicity: this is certainly not a suggested mission profile. The "numbers" here are taken to absurdity only for purposes of illustration) making three consecutive dives, with no surface interval, to 60 fsw for 60 minutes. The accumulated % CNS and OTU's for this series of decompression dives is shown below in Table Four.

Table 4: Oxygen Toxicity Values For Three Consecutive Dives of 60 fsw for 60 minutes

Mix

% CNS

OTU's

Air

25

43.90

Mix1 (32 % O2)

54

152.40

Mix 2 (36 % O2)

64

188.49

It should be obvious that even after three consecutive 60 fsw dives for 60 minutes, a diver would be well below the allowed OTU accumulation of 1440. I also suggest that, especially in Michigan waters, thermal considerations have more control of the dive durations than whole body oxygen toxicity while diving conventional mixes to traditional recreational diving depths.

Hyperbaric treatment of DCI will involve added exposure to high concentrations of oxygen and significantly add to the OTU accumulation. Table Five lists approximate OTU values for the standard US Navy Treatment Tables.

Table 5: Oxygen Toxicity Values For Standard US Navy Treatment Tables

Treatment Table

Approximate OTU's

5

297

6

607

6A

820

So, even with a DCI treatment for an air embolism (Table 6A) for a diver injury at the conclusion of three consecutive dives to 60 fsw on NOAA Mix 2, the total whole body oxygen exposure (820 + 188 = 1008 OTU's) is less than the acceptable standard daily dose of 1440 OTU's.

Conclusion

As a first responder on the scene of a diving accident, the administration of the highest concentration oxygen available (see Why100 %) is the definitive treatment for a diagnosed diving malady. There is no justification to the belief that concerns over oxygen toxicity should mandate with holding this critical "denitrogenation" agent from a recreational diver suffering from DCI who has been diving on air or oxygen enriched air It is, however, important that first responders note the time and type of administration device (an estimate of O2 concentration delivered) utilized in treatment so that medical professionals can track OTU's should treatment in a chamber be required. It is also important to monitor patient ease of breathing, especially in exposures of more than a couple of hours. If the patient begins to show signs of discomfort or reports respiratory distress, then a few minutes of air breathing should remove the discomfort. Following this air break of a couple of minutes, the patient would be returned to the highest concentration oxygen available until either the gas is exhausted or the patient is transferred to a higher medical authority.

Bottom Line: Under most recreational diving conditions, first responders treating a diving incident with oxygen will transfer medical care of an injured diver to the emergency medical community long before oxygen toxicity becomes an issue.

Acknowledgements

The oxygen toxicity values were calculated using the GUE Deco Planner

I put the link in there because there are some pretty cool graphics that go with this, but I can't get them to show up in the quote. The tables look better in the original also.

[cldutcher]

I didn't notice if this was mentioned yet but some research shows that giving oxygen to acute stroke pt's may do more harm then good. The idea behind it is that with the added oxygen the brain basically thinks everything is okay and can even cause vasoconstriction which in turn can worsen the stroke. So by not giving oxygen and allowing the brain to compensate there was a dramatic increase in pt outcomes. Obviously if the pt is hypoxic then they need oxygen but it shouldn't be used in every case. I searched for the article but was unable to find it. It was a study done in sweden and was accepted by the american heart association if i remember correctly. Maybe someone else would have better luck finding it. :dontknow:

[cldutcher]

Here is the link

http://www.strokecenter.org/trials/TrialDetail.aspx?tid=396

[mountainman999]

The same has also been suggested over hear for cardiac patients because of the vaso constrtive effects of oxygen some services are now using 60% rather than 100% o2