UHM 2017, VOL. 44, NO. 3 – HYPERCAPNIA IN DIVING Hypercapnia in diving: a review of CO2 retention in submersed exercise at depth Sophia A. Dunworth BS 1,2, Michael J. Natoli MS 1,2, Mary Cooter MS 1, Anne D. Cherry MD 1,2, Dionne F. Peacher MD 1,2,3, Jennifer F. Potter MD 1,2,4, Tracy E. Wester MD 1,2,5, John J. Freiberger MD 1,2, Richard E. Moon MD 1,2,6 1 Department of Anesthesiology, Duke University Medical Center, Durham, N.C. 2 Center for Hyperbaric Medicine & Environmental Physiology, Duke University Medical Center, Durham, N.C. 3 Department of Anesthesia, University of Iowa, Iowa City, Iowa 4 Department of Anesthesiology, University of Virginia, Charlottesville, Virginia 5 Department of Anesthesia and Perioperative Medicine, Medical University of South Carolina, Charleston, S.C. 6 Department of Medicine, Duke University Medical Center, Durham, N.C. CORRESPONDING AUTHOR: Sophia Dunworth – [email protected] _____________________________________________________________________________________________________________________________________________________________________ ABSTRACT Carbon dioxide (CO2) retention, or hypercapnia, is a ventilation is reduced in diving due to changes in known risk of diving that can cause mental and physical respiratory load and associated changes in respiratory impairments leading to life-threatening accidents. control. Minute ventilation is further reduced by Often, such accidents occur due to elevated inspired hyperoxic attenuation of chemosensitivity. Physiologic carbon dioxide. For instance, in cases of CO2 elimination dead space is also increased due to elevated breathing system failures during rebreather dives, elevated in- gas density and to hyperoxia. The Haldane effect, a spired partial pressure of carbon dioxide (PCO2) reduction in CO2 solubility in blood due to hyperoxia, can rapidly lead to dangerous levels of hypercapnia. may contribute indirectly to hypercapnia through an Elevations in PaCO2 (arterial pressure of CO2) can increase in mixed venous PCO2. In some individuals, also occur in divers without a change in inspired PCO2. low ventilatory response to hypercapnia may also In such cases, hypercapnia occurs due to alveolar contribute to carbon dioxide retention. This review hypoventilation. Several factors of the dive environment outlines what is currently known about hypercapnia contribute to this effect through changes in minute in diving, including its measurement, cause, mental ventilation and dead space. Predominantly, minute and physical effects, and areas for future study. _____________________________________________________________________________________________________________________________________________________________________ Introduction hypercapnia as the cause of “shallow water blackouts.” Hypercapnia in diving was first described in the 1920s At that time, Royal Navy divers using oxygen rebreathers during an investigation of the dangers of deep diving. were found to become significantly impaired or to oc- A committee appointed by the British Admiralty found casionally lose consciousness in water too shallow to that divers often became unconscious or “greatly incite oxygen toxicity. These “blackouts” were attributed exhausted” with exertion at depth. Samples taken from to the narcotic effects of CO2 [2]. Subsequent work has the helmets of these divers showed carbon dioxide (CO2) confirmed the importance of carbon dioxide in com- levels equivalent to 9% CO2 at the surface (significantly pressed-air narcosis [3, 4]. With prolonged or high levels higher than even a normal end-tidal CO2 of 5-6%)[1]. of exposure to carbon dioxide, studies have demon- Later work during the Second World War explored strated both physical [5-8] and cognitive impairments _______________________________________________________________________________________________________________________ KEYWORDS: carbon dioxide; carbon dioxide retention; hypercapnia; PCO2; PaCO2; PETO2; diving; Haldane effect Copyright © 2017 Undersea & Hyperbaric Medical Society, Inc. 191 UHM 2017, VOL. 44, NO. 3 – HYPERCAPNIA IN DIVING [9-16]. Elevated carbon dioxide also increases the risk Subjects for oxygen toxicity [17, 18], likely due to vasodilation of Each study received institutional approval and informed the cerebral vasculature [19], which can lead to oxygen- consent. Data from a total of 49 subjects were included induced convulsions during dives considered to be with- in the present analysis, as there was some subject over- in the safe limit for oxygen exposure [20]. lap between the four studies. Subject exclusion criteria −1 −1 Carbon dioxide retention in diving is usually the included: VO2max < 30 mL·kg · min , ratio of FEV1 to result of alveolar hypoventilation. Both an increase in forced vital capacity < 0.75, or estimated body fat >3% dead space and a reduction in overall ventilation con- higher than the age- and sex-based upper limits (male < tribute to this effect. In some cases, a high inspired 35 years = 25%, ≥35 years = 28%; female < 35 years = 38%, partial pressure of carbon dioxide (PiCO2) contributes ≥ 35 years = 41%), contraindications to diving (ear or dramatically to elevations in arterial partial pressure of sinus infection and inability to autoinflate the middle CO2 (PaCO2). This can occur during rebreather dives ear), and pregnancy. due to exhaustion or malfunction of the CO2 absorbent. It is relevant to note that, at rest, partial rebreather Experimental procedures failure leading to elevated inspired PCO2 can be Experiments were conducted in a small water-filled pool compensated for by a small increase in ventilation [21]. inside a hyperbaric chamber. Submersed exercise took During exercise, however, elevations in inspired PCO2 place in the prone position, using an electronically braked are less tolerated and can lead to carbon dioxide reten- ergometer as previously described [27]. In two studies tion [22]. The resulting hypercapnia is often tolerated subjects were studied at rest and during submersed to an extent [23-25], but can lead to incapacitation or exercise at both the surface (1.0 atmosphere absolute to unconsciousness [3, 4, 7, 9, 11, 12, 15]. In divers, such (ATA)) and at a simulated depth of 37 meters of sea incapacitation is especially problematic and can be water (4.7 ATA) [27, 29]. One study examined subjects deadly [14]. during submersed exercise only at 1.0 ATA [28], and At this time, hypercapnia remains an unpredictable one study examined subjects during submersed exercise and sometimes lethal risk of diving. Yet, we are aware only at 4.7 ATA [30]. Studies during submersed exercise of only one recent comprehensive review of hyper- at 4.7 ATA were conducted over a range of inspired capnia in diving [26]. This review outlines what is oxygen partial pressures (PiO2 = 0.21, 0.7, 1.0, 1.3 and currently known about hypercapnia in diving — its 1.75 atmospheres/atm) with some variations in water measurement, cause and effects — and further explores temperature and work rate between the four experiments. two relevant topics: the relationship between end-tidal Nitrogen was used as the diluent in all experiments. Ex- and arterial PCO2 under submersed exercise conditions pired gas and arterial and venous blood samples were and the role of hyperoxia in the development of diving- collected at rest and six minutes into exercise, as well related hypercapnia, including a secondary analysis as at 16 minutes into exercise for two studies [29, 30]. of four previously published studies. Statistical analyses Methods The agreement between end-tidal and arterial PCO2 Data source was analyzed using Bland-Altman plots (matched pairs Data were obtained from four previously published analysis, JMP Pro 12, SAS Inc). The association of PiO2 studies: Cherry, et al. 2009 [27], Wester, et al. 2009 [28], with arterial to end-tidal PCO2 difference was analyzed Peacher, et al. 2010 [29] and Fraser, et al. 2011 [30]. using a repeated-measures mixed model (mixed model, Data points from Cherry, et al. with added external Statistical Analysis, Software, SAS Inc) that included breathing resistance or static lung load were excluded PiO2 as a fixed effect with a random effect for subject. from all analyses to reduce confounding factors. The association of PiO2 with minute ventilation (VE) and PaCO2 was analyzed using a repeated-measures mixed model (mixed model, Statistical Analysis Software, SAS Inc) that included PiO2 and external work rate as fixed effects with a random effect for subject. Post hoc 192 Dunworth SA, Natoli MJ, Cooter M, et al. UHM 2017, VOL. 44, NO. 3 – HYPERCAPNIA IN DIVING UHM 2017, VOL. 44, NO. 3 – HYPERCAPNIA IN DIVING Tukey tests were used for pairwise comparisons of all correction. Arterial blood gas measurements are made PiO2 conditions at 4.7 ATA of depth. The association at 37°C irrespective of a subject’s body temperature at of depth with VE and PaCO2 was analyzed using a the time of collection. As body temperature is increased mixed model including depth and external work rate during exercise, the reported values of PaCO2 will be as fixed effects with a random effect for subject (mixed lower than the actual PaCO2 in the subject, falsely model, Statistical Analysis Software, SAS Inc). Data are increasing the end-tidal to arterial difference. One displayed as means ± 95% confidence intervals. study found that correction of PaCO2 for body tem- The association of PiO2 with mixed venous PCO2 was perature accounted for 44% of the end-tidal arterial analyzed using a