Role of metabolic gases in bubble formation during hypobaric exposures.

Our hypothesis is that metabolic gases play a role in the initial explosive growth phase of bubble formation during hypobaric exposures. Models that account for optimal internal tensions of dissolved gases to predict the probability of occurrence of venous gas emboli were statistically fitted to 426 hypobaric exposures from National Aeronautics and Space Administration tests. The presence of venous gas emboli in the pulmonary artery was detected with an ultrasound Doppler detector. The model fit and parameter estimation were done by using the statistical method of maximum likelihood. The analysis results were as follows. 1) For the model without an input of noninert dissolved gas tissue tension, the log likelihood (in absolute value) was 255.01. 2) When an additional parameter was added to the model to account for the dissolved noninert gas tissue tension, the log likelihood was 251.70. The significance of the additional parameter was established based on the likelihood ratio test (P < 0.012). 3) The parameter estimate for the dissolved noninert gas tissue tension participating in bubble formation was 19. 1 kPa (143 mmHg). 4) The additional gas tissue tension, supposedly due to noninert gases, did not show an exponential decay as a function of time during denitrogenation, but it remained constant. 5) The positive sign for this parameter term in the model is characteristic of an outward radial pressure of gases in the bubble. This analysis suggests that dissolved gases other than N2 in tissues may facilitate the initial explosive bubble-growth phase.

Information about venous gas emboli improves prediction of hypobaric decompression sickness.

HYPOTHESIS: Information about venous gas emboli (VGE) detected in the pulmonary artery such as the occurrence of VGE, Grade of VGE, the time when VGE first appear, and the time course of the Grade or occurrence of VGE, could be used to better assess the probability of decompression sickness [P(DCS)] in any hypobaric decompression. We hypothesized that these data would improve the estimate of P(DCS) since objective measurements of the decompression stress are available for the individual. METHODS: A binary correlation and survival analysis approach were used on information from 1,322 hypobaric chamber exposures to establish the relationships between VGE and DCS. RESULTS: Based on the correlation analysis, the absence of VGE is highly correlated with the absence of a DCS symptom, as evident from a negative predictive value of 0.98. However, the presence of VGE in the pulmonary artery is not highly correlated with a subsequent DCS symptom, as evident from a positive predictive value of 0.39 for Grades III and IV VGE. The correlation results suggest the presence of VGE in the pulmonary artery is a necessary, but not sufficient, condition for DCS. Based on the survival analysis, the log logistic survival model, a one-variable model with two parameters gave a log likelihood (LL) of -757. This model was expanded to include seven additional variables, including four about VGE, and the nine-parameter model gave a better LL of -481. CONCLUSION: Information about VGE plus other variables known to influence DCS is useful to better assess the P(DCS) for hypobaric decompressions.

Utility of Doppler-detectable microbubbles in the diagnosis and treatment of decompression sickness.

BACKGROUND: Doppler-detectable microbubbles (DMB) are frequently used to evaluate altitude decompression stress. However, the role of DMB in the therapy of decompression sickness (DCS) has not been examined. HYPOTHESIS: The ability of Doppler to detect microbubbles during decompression (Doppler test) may be used in the diagnosis of DCS, and to aid clinical decisions about treatment options for DCS. METHODS: We examined the data on DMB and symptoms from NASA Database on DCS (n = 516). The accuracy of Doppler test was obtained from the Receiver Operating Characteristic (ROC) for DMB (grades I through IV), and efficacy was obtained by calculating predictive or post-test probabilities. Threshold analysis was used to obtain the probabilities for testing and/or treatment decisions. RESULTS: The Doppler test was useful for both screening and confirming DCS, when different criteria (grade I for screening; grade IV for confirming) were used for a positive test. Calculation of predictive values and threshold analysis showed that: 1) early recompression was the therapy of choice when post-test probability of disease was > 0.25 in individuals with non-specific pain at altitude, and early recompression with 100% oxygen for 2 h at site level was optimal therapy when this probability was > 0.33; 2) hyperbaric therapy was optimal when post-test probability was > 0.04 in individuals with uncertain symptoms post-flight. CONCLUSIONS: The Doppler test was of greater utility in excluding DCS than confirming its presence, and was useful in making therapeutic decisions on DCS when confronted with non-specific symptoms at altitude.

Relationship of the time course of venous gas bubbles to altitude decompression illness.

The correlation is low between the occurrence of gas bubbles in the pulmonary artery, called venous gas emboli (VGE), and subsequent decompression illness (DCI). The correlation improves when a "grade" of VGE is considered; a zero to four categorical classification based on the intensity and duration of the VGE signal from a Doppler bubble detector. Additional insight about DCI might come from an analysis of the time course of the occurrence of VGE. Using the NASA Hypobaric Decompression Sickness Databank, we compared the time course of the VGE outcome between 322 subjects who exercised and 133 Doppler technicians who did not exercise to evaluate the role of physical activity on the VGE outcome and incidence of DCI. We also compared 61 subjects with VGE and DCI with 110 subjects with VGE but without DCI to identify unique characteristics about the time course of the VGE outcome to try to discriminate between DCI and no-DCI cases. The VGE outcome as a function of time showed a characteristic short lag, rapid response, and gradual recovery phase that was related to physical activity at altitude and the presence or absence of DCI. The average time for DCI symptoms in a limb occurred just before the time of the highest fraction of VGE in the pulmonary artery. It is likely, but not certain, that an individual will report a DCI symptom if VGE are detected early in the altitude exposure, the intensity or grade of VGE rapidly increases from a limb region, and the intensity or grade of VGE remains high.

A probabilistic model of hypobaric decompression sickness based on 66 chamber tests.

One consequence of the NASA tissue ratio (TR) model is that calculated probability of decompression sickness [P(DCS)] is constant in tests at different ambient pressures so long as the ratio of P1N2 to P2 is the same in each test; P1N2 is N2 pressure in the 360 minute half-time compartment, and P2 is ambient pressure after decompression. We test the hypothesis that constant P(DCS) is better described by TRs that decrease as P2 decreases. Data were from 66 NASA and USAF hypobaric chamber tests resulting in 211 cases of DCS in 1075 exposures. The response variable was presence or absence of DCS while at P2. Explanatory variables were P1N2, P2, exercise at P2, (yes or no), time to DCS (failure time), and time to end of test in those without DCS (censored time). Probability models were fitted using techniques from survival analysis. The log likelihood for the two parameter log logistic survival model was -846 with only failure and censored times, -801 when TR [P1N2/P2] plus exercise were added, and -663 when modified TR [(((P1N2+cl)/P2)-1)c2] plus exercise were added, where c1 and c2 are fitted parameters in the five parameter model. Constant P(DCS) was better described by TRs that decrease as P2 decreases; a conclusion supported by additional empirical observations, and bubble growth models that are independent of DCS data. Exercise increased the P(DCS) at P2. As a description of decompression "dose", the modified TR was superior to TR over a wider range of experimental conditions.

Efficacy of Doppler ultrasound [correction of utrasound] for screening symptoms of decompression sickness during simulated extravehicular activities.

Doppler ultrasound is frequently used for monitoring circulating microbubbles during decompression to assess the symptoms of Decompression Sickness (DCS). This analysis was carried out to evaluate its effectiveness for screening symptoms of DCS during simulated extravehicular activities (EVA). The information from various hypobaric chamber studies carried out at the NASA Johnson Space Center, Houston, TX was used in this analysis (n=516). The circulating microbubbles were detected in the precordial area in 42% (218/516), and symptoms were reported in 16% (81/516) of these exposures. The accuracy of Doppler-detectable bubbles (Spencer grades) on all symptoms of DCS was examined by calculating measures of sensitivity and specificity. The efficacy of Doppler as a screening device was examined by calculating their positive predictive value (PPV) and negative predictive value (NPV). The results of these analyses indicated that the sensitivity of Doppler decreased, and the PPV increased with higher Spencer grades. However, the likelihood of detecting true negative cases (NPV) was consistently higher with all bubble grades. Due to the high false-positive rate and low prior probabilities of the risk of DCS, Doppler was found to be more useful to identify those who did not develop DCS, than to detect positive cases of DCS in the simulated EVA exposures.

Energy utilization rates during shuttle extravehicular activities.

The work rates or energy utilization rates during EVA are major factors in sizing of life support systems. These rates also provide a measure of ease of EVA and its cost in crew fatigue. From the first Shuttle EVA on the STS-6 mission in 1983, we have conducted 59 man-EVA and 341 man-hours of EVA. Energy utilization rates have been measured on each of these EVA. Metabolic rate was measured during each EVA using oxygen utilization corrected for suit leakage. From 1981-1987, these data were available for average data over the EVA or over large segments of the EVA. Since 1987, EVA oxygen utilization data were available at 2-minute intervals. The average metabolic rate on Shuttle EVA (194 kcal/hr.) has been significantly lower than metabolic rates during Apollo and Skylab missions. Peak rates have been below design levels, infrequent, and of short duration. The data suggest that the energy cost of tasks may be inversely related to the degree of training for the task. The data provide insight on the safety margins provided by life support designs and on the energy cost of Station construction EVA.

Early stopping of aerospace medical trials: application of sequential principles.

A two-period, crossover trial was conducted in the hypobaric chamber on human subjects to compare the influence of inflight exercise (experimental) and restricted activity (control) on altitude decompression sickness (DCS) during simulated extravehicular activities. Out of 39 pairs (total of 78 exposures), 4 cases of DCS occurred under control and 5 occurred under experimental conditions. Analysis of the crossover results showed that the P values for differences in DCS occurrence was 0.56. Under these circumstances, it was necessary to decide whether additional information would be obtained by accruing more subjects. This problem was examined by using a skew sequential design in which the "stopping rule" was based on an alpha of 0.05 (one-sided) and power of 80%. The result of this analysis was in favor of the null hypothesis, and the trial was terminated. The authors recommend the use of similar stopping rules in aerospace trials to optimize sample size without compromising statistical validity.

Epidemiology of decompression sickness under simulated space extravehicular activities.

Several ground-based trials were conducted by NASA at the Lyndon B. Johnson Space Center, Houston, TX, during 1982-90 to examine the risk of altitude decompression sickness (DCS) during space extravehicular activities. There were 22 different pressure profiles involving single and staged decompression procedures, each lasting from 180 to 360 min at the final altitude. A total of 164 healthy subjects participated in 426 exposures to altitude. Symptoms of DCS occurred in 17% (74/426) and circulating microbubbles by precordial Doppler ultrasound were detected in 42% (179/426) of all exposures. About 27% (20/74) of exposures with symptoms resulted in test abort, and one-third of all test aborts required treatment in the hyperbaric chamber. There was about 3.20 times (95% Confidence Interval [95% CI] = 1.56-6.66) higher risk of symptoms in the presence of Doppler-detectable microbubbles. Examination of individual risk factors showed that there was about 4.3 times (95% CI = 1.62-11.50) higher risk of symptoms with increasing number of exposures. These findings emphasize the importance of evaluating risk factors from ground-based trials for application in operational decision-making and treatment strategies.

Time to detection of circulating microbubbles as a risk factor for symptoms of altitude decompression sickness.

This study investigated the association between time at onset of circulating microbubbles (CMB) and symptoms of altitude decompression sickness (DCS), using Cox proportional hazard regression models. The study population consisted of 125 individuals who participated in direct ascent, simulated extravehicular activities profiles. Using individual CMB status as a time-dependent variable, we found that the hazard for symptoms increased significantly (at the end of 180 min at altitude) in the presence of CMB (Hazard Ratio = 29.59; 95% confidence interval [95% CI] = 7.66-114.27), compared to no CMB. Further examination was conducted on the subgroup of individuals who developed microbubbles during the test (n = 49), by using Cox regression. Individuals with late onset of CMB (> 60 min at altitude) showed a significantly reduced risk of symptoms (hazard ratio = 0.92; 95% CI = 0.89-0.95), compared to those with early onset (< or = 60 min), while controlling for other risk factors. We conclude that time to detection of circulating microbubbles is an independent determinant of symptoms of DCS.

The influence of prior exercise at anaerobic threshold on decompression sickness.

This study was conducted to examine the effects of exercise prior to decompression on the incidence of altitude decompression sickness (DCS). In a balanced, two-period, crossover trial, 39 healthy individuals (29 males, 10 females) of mean (S.D.) age 32.5 (7.7) years and body mass index 23.7 (3.4) were each exposed twice, without denitrogenation, to an altitude of 6,400 m (21,000 ft) in a hypobaric chamber. Under the experimental condition, subjects exercised at their predetermined anaerobic threshold levels for 30 min each day for 3 d prior to altitude exposure; the other condition was a non-exercise control. Under both conditions, subjects performed exercise simulating space extravehicular activities at altitude for a period of 3 h, while breathing 100% oxygen. There were nine preferences (untied responses) for DCS, four under control and five under experimental conditions; all were Type I, pain-only bends. No carryover effect between exposures was detected, and the test for treatment differences showed p = 0.56 (95% confidence interval = 0.34-0.58) for symptoms. No significant difference in DCS preferences was found after subjects exercised up to their anaerobic threshold levels during the days prior to decompression.

The physiology of spacecraft and space suit atmosphere selection.

The majority of the environmental factors which comprise the spacecraft and space suit environments can be controlled at "Earth normal" values, at optimum values, or at other values decided upon by spacecraft designers. Factors which are considered in arriving at control values and control ranges of these parameters include physiological, engineering, operational cost, and safety considerations. Several of the physiological considerations, including hypoxia and hyperoxia, hypercapnia, temperature regulation, and decompression sickness are identified and their impact on spacecraft and space suit atmosphere selection are considered. The past experience in controlling these parameters in U.S. and Soviet spacecraft and space suits and the associated physiological responses are reviewed. Current areas of physiological investigation relating to environmental factors in spacecraft are discussed, particularly decompression sickness which can occur as a result of change in pressure from Earth to spacecraft or spacecraft to space suit. Physiological considerations for long-term lunar or Martian missions will have different impacts on atmosphere selection and may result in the selection of atmospheres different than those currently in use.

Threshold altitude resulting in decompression sickness.

A review of case reports, hypobaric chamber training data, and experimental evidence indicated that the threshold for incidence of Altitude Decompression Sickness (DCS) was influenced by various factors such as prior denitrogenation, exercise or rest and period of exposure, in addition to individual susceptibility. Fitting these data with appropriate statistical models has the potential for estimating the frequency of occurrence of DCS at various altitudes under different experimental conditions and allows us to examine the influence of various factors on the threshold for DCS. This approach was illustrated by logistic regression analysis on the incidence of DCS below 9,144 m (30,000 ft). Estimations using these regressions showed that under a noprebreathe, 6-h exposure, simulated extravehicular activity profile, the threshold for symptoms occurred at approximately 3,353 m (11,000 ft); while under a no-prebreathe, 2-h exposure profile with knee-bends exercise, the threshold occurred at 7,925 m (26,000 ft). These examples showed that definition of threshold altitude should be qualified by the particular combination of experimental variables under which it was observed.

Blood biochemical and cellular changes during decompression and simulated extravehicular activity.

Blood biochemical and cellular parameters were measured in human subjects before and after exposure to a decompression schedule involving 6 h of oxygen prebreathing. The exposure was designed to simulate extravehicular activity for 6 h (subjects performed exercise while exposed to 29.6 kPa). There were no significant differences between blood samples from subjects who were susceptible (n = 11) versus those who were resistant (n = 27) to formation of venous gas emboli. Although several statistically significant (P less than 0.05) changes in blood parameters were observed following the exposure (increases in white blood cell count, prothrombin time, and total bilirubin, and decreases in triglycerides, very-low-density lipoprotein cholesterol, and blood urea nitrogen), the changes were small in magnitude and blood factor levels remained within normal clinical ranges. Thus, the decompression schedule used in this study is not likely to result in blood changes that would pose a threat to astronauts during extravehicular activity.

The effect of extended O2 prebreathing on altitude decompression sickness and venous gas bubbles.

The purpose of this study was to determine the effect of extended O2 prebreathing on symptom and bubble incidence during decompressions simulating extravehicular activity. The 38 subjects breathed O2 for a 6-h period prior to decompression to 4.3 psi. The subjects performed upper body exercise for 6 h. Subjects were monitored with a Doppler bubble detector and were encouraged to report all symptoms. Eight subjects were exposed to the same protocol after an 8-h prebreathe. Venous bubbles were detected in 18 of 38 subjects decompressed after the 6-h prebreathe. Four of these subjects reported symptoms of altitude decompression sickness. No symptoms or bubbles were detected in the eight subjects who had prebreathed 8 h. The incidence of symptoms and bubbles when combined with prior data on 3.5- and 4.0-hour prebreathes showed an inverse correlation to pre-breathing time. The incidence of symptoms was higher than has been reported for subjects exposed to decompression of shorter duration with less activity.

Hematological changes following repetitive decompressions during simulated extravehicular activity.

A study was performed to evaluate decompression procedures suggested for use prior to Space Shuttle extravehicular activity. Hematological parameters were measured in 12 male human subjects before and after exposure in an altitude chamber to a 3-day staged decompression schedule, with simulated extravehicular activity. Following the exposure, significant increases occurred in white blood cell count and activated partial thromboplastin time, and platelet aggregate ratio was significantly decreased. Pre-exposure samples from subjects who were susceptible to formation of venous gas emboli (VGE) exhibited a significantly lower degree of ADP-induced platelet aggregation and a significantly higher amount of lymphocyte blastogenic transformation in response to the mitogen phytohemagglutinin than samples from VGE-resistant subjects. The results indicate that, following this decompression profile, small but significant changes occur in several hematological parameters, and that levels of certain parameters may be related to susceptibility to VGE formation during decompression.

Blood biochemical factors in humans resistant and susceptible to formation of venous gas emboli during decompression.

Blood biochemical parameters were measured in 12 male human subjects before and after exposure to a staged decompression protocol, with simulated extravehicular activity, during 3 days. Following the exposure, significant changes occurred in several parameters, including increases in blood urea nitrogen, inorganic phosphate, potassium, and osmolality, and decreases in uric acid and creatinine. Pre-exposure blood samples from subjects who were susceptible to formation of venous gas emboli (VGE) during decompression exhibited significantly greater levels of total cholesterol, high density lipoprotein cholesterol, potassium, inorganic phosphate, calcium, and magnesium. The results indicate that, following this decompression profile, small but significant (P less than 0.05) changes occur in several blood biochemical parameters, and that levels of certain blood factors may be related to susceptibility to VGE formation during decompression.

Investigation of the combined effects of bedrest and mild hypoxia.

Subjects were exposed to an 8-h mild hypoxia exposure (8000 ft. equivalent, 2438 m) with and without a 28-h period of 6 degrees headdown bedrest. Anticipated responses to the bedrest and the hypoxia were observed. There was no indication that bedrest affected the arterial oxygenation or the oxygen gradient across the lungs of the subjects undergoing mild hypoxia. It is concluded that there is no evidence that would preclude an alveolar O2 pressure as low as 69 torr during contingency spacecraft operation.