Multiday ultraendurance athletic events stress the

Transcription

1 An Ultracyclist with Pulmonary Edema during the Bicycle Race Across America ANDREW M. LUKS, H. THOMAS ROBERTSON, and ERIK R. SWENSON Division of Pulmonary and Critical Care Medicine, University of Washington, Seattle, WA ABSTRACT LUKS, A. M., H. T. ROBERTSON, and E. R. SWENSON. An Ultracyclist with Pulmonary Edema during the Bicycle Race Across America. Med. Sci. Sports Exerc., Vol. 39, No. 1, pp. 8 12, Ultraendurance athletic events tax the limits of physiological homeostasis. Maintenance of sodium and water balance is a particularly difficult challenge in such events. We present the case of a 38-yr-old participant in the Bicycle Race Across America who developed severe pulmonary edema while cycling at an altitude of 2380 m on the fourth day of the race. With hospitalization and standard support for pulmonary edema, he made a quick, full recovery. A postrace work-up revealed no evidence of underlying cardiopulmonary disease or susceptibility to high-altitude pulmonary edema. His weight on the day of hospitalization was 2.7 kg greater than his prerace weight. We hypothesize that his excessive daily sodium intake (23 25 g, or meq) during the course of the race likely led to an expanded extracellular volume, increased hydrostatic pressure, and decreased oncotic pressure. These factors, in combination with ambient hypoxia, elevated cardiac output, and reduced renal perfusion expected with sustained, high-level exercise, may have led to the development of acute pulmonary edema. This case highlights the pitfalls of overly aggressive sodium intake in endurance races, particularly when such races are conducted at high altitude, where the hypoxia-induced rise in pulmonary artery pressures may amplify the effects of changes in hydrostatic and oncotic pressure that occur with extracellular volume expansion. Key Words: HIGH ALTITUDE, ULTRAENDURANCE, SODIUM LOADING Multiday ultraendurance athletic events stress the body`s ability to maintain sodium and water homeostasis. Despite the growth of this type of athletic competition, there are few data to guide adequate and safe repletion strategies. A recent, widely cited report (1) documented a 13% incidence of hyponatremia among nonelite marathon runners. Speedy et al. (26) reported an 18% incidence of hyponatremia among a cohort of participants in an ultradistance triathlon. Because 8 of the 11 athletes (73%) with severe hyponatremia (plasma sodium G 130 mmolil j1 ) either gained or maintained weight during the course of the race, they concluded that fluid overload was the predominant cause of the hyponatremia. An implication of these studies was that excessive water intake without sufficient sodium repletion can predispose to this condition. However, excessive sodium intake also poses problems. We present the case of a 38-yr-old participant in the Bicycle Race Across America who undertook an aggressive program of sodium repletion during the first 4 d of the race and subsequently developed pulmonary edema while riding at an elevation Address for correspondence: Andrew M. Luks, M.D., Fellow, Division of Pulmonary and Critical Care Medicine, Seattle Veterans Affairs Medical Center, 1660 S. Columbian Way S111-PULM, Seattle, WA 98108; aluks@u.washington.edu. Submitted for publication May Accepted for publication July /07/ /0 MEDICINE & SCIENCE IN SPORTS & EXERCISE Ò Copyright Ó 2007 by the American College of Sports Medicine DOI: /01.mss of 2380 m. This case demonstrates the pitfalls of overly aggressive sodium intake, particularly with heavy exertion at high altitude. CASE DESCRIPTION This extremely fit, well-trained 38-yr-old man participated in the Bicycle Race Across America, a 4920-km continuous race from San Diego, CA to Atlantic City, NJ. The race included more than 33,500 m of vertical climbing throughout the course of the event. Before the race, his only medical problem was mild hypertension, for which he was treated with irbesartan, an angiotensin receptor antagonist. Born and raised in Switzerland, the patient was a formerly competitive cross-country skier whose only history of problems at high altitude involved repeated episodes of mild acute mountain sickness at elevations above 3000 m. The patient planned to ride 21 out of every 24 h to finish the race in d. His dietary regimen included consumption of 23 g of sodium on day 1 of the race and 25 g on day 2. The dietary logs from subsequent days were lost, but the patient reported that he had maintained similar dietary sodium intake during the remainder of his race. The patient had no difficulties until the evening of the third day, when he developed increased dyspnea at his fixed race pace. As he climbed towards 2380 m the next morning, his dyspnea worsened, causing him to slow his pace and take frequent rest stops. He also developed blurry vision and a cough that produced white sputum. On two separate occasions, he stopped riding and used supplemental oxygen for 5 min. The supplemental oxygen, permitted under race rules as long as the participant is off the bicycle, did not improve his symptoms. 8

2 Given his worsening clinical condition, he and his support crew decided to seek medical attention. On arrival at a local medical facility in Pagosa Springs, CO (elevation 2290 m), he was noted to be severely dyspneic, cyanotic, and diaphoretic. He had a temperature of 39.2-C, blood pressure of 170/100 mm Hg, heart rate of 128 bpm, respiratory rate of 60 breaths per minute, and arterial oxygen saturation of 42 48% on room air. His body weight was 2.7 kg higher than his prerace weight. On exam, he had crackles throughout the right lung and at the left base. An electrocardiogram revealed sinus tachycardia without ischemic changes. Portable chest x-ray demonstrated opacities in the right middle, right lower, and left lower lobes. Laboratory studies (Table 1) revealed a total white blood cell count of mm 3 with a normal differential and a hematocrit of 38.2%. The chemistry panel included sodium of 139 mmolil j1 ;ureanitrogenof25mgidl j1 ; creatinine of 0.8 mgidl j1 ; albumin of 3.5 gidl j1 ; and total protein of 6.1 gidl j1. Of note, on laboratory studies conducted 3 months before the race, the patient had a hematocrit of 46%, albumin of 4.9 gidl j1, and total protein of 7.4 gidl j1 (Table 1). Blood cultures were negative. He was treated with 500 mg of intravenous methylprednisolone and two separate 20-mg doses of intravenous furosemide and oxygen before being transferred to a larger medical facility at a lower elevation in Albuquerque, NM (elevation of 1490 m). On transfer, the patient underwent a radionuclide ventilation perfusion scan that was interpreted as low probability for pulmonary embolism. A CT pulmonary angiogram showed no evidence of pulmonary embolism or pleural effusions, but it did reveal bilateral patchy ground glass opacities and a dense right middle-lobe infiltrate (Fig. 1). A lower-extremity venous duplex was negative for deep venous thrombosis. A transthoracic echocardiogram demonstrated a left ventricular ejection fraction of 65%, normal right and left ventricular size and function, no valvular abnormalities, and a pulmonary artery systolic pressure of mm Hg. He was continued on intravenous furosemide and started on inhaled salmeterol, moxifloxacin, and nifedipine. He was taken off the methylprednisolone that had been started at the original medical facility. Forty-eight hours after admission, the patient`s oxygen saturation had improved to 90% on room air, and he no longer had dyspnea at rest or with exertion. He was subsequently discharged from the hospital without further complications. Several weeks after the patient`s symptoms had resolved and he had returned home, he underwent further evaluation. A repeat chest x-ray was normal. On pulmonary TABLE 1. Comparison of selected laboratory values drawn 3 months before the Bicycle Race Across America and on initial presentation to the emergency room. Laboratory Test Prerace Value Emergency Room Value Sodium (mmolil j1 ) Albumin (gidl j1 ) Total protein (gidl j1 ) Hematocrit (%) FIGURE 1 Single slice from a CT pulmonary angiogram obtained on transfer to the second hospital, demonstrating a dense right middle-lobe infiltrate and patchy ground glass opacities in the left and right lung fields. function testing, the patient had a forced vital capacity (FVC) of 6.19 L (114% predicted), forced expiratory volume in 1 s (FEV 1 ) of 4.41 L (100% predicted), FEV 1 /FVC ratio of 71%, total lung capacity of 8.30 L (116% predicted), and a diffusion capacity for carbon monoxide of 33.6 mlimin j1 Imm Hg j1 (98% predicted). He then underwent a progressive cardiopulmonary exercise test, reaching a power output of 500 W (234% predicted) and a V O 2max of 63.9 mlikg j1 Imin j1 (156% predicted). The latter value was essentially unchanged from a prior cardiopulmonary exercise test performed 15 months before the bicycle race. At peak exercise, his heart rate reached 179 bpm (98% predicted), and his minute ventilation rose to 186 LImin j1, representing 100% of his maximum voluntary ventilation. He also demonstrated a clear anaerobic threshold, a small fall in his oxygen saturation from 100 to 96%, and a fall in his dead-space fraction from 0.29 at rest to 0.17 during exercise. Echocardiography revealed a pulmonary artery systolic pressure of mm Hg at rest, which did not change significantly after a 45-min exposure to an inspired oxygen concentration (FiO 2 ) of 0.12 at rest. An attempt to measure the pulmonary artery systolic pressure after exercising on a treadmill to 80% of his age-predicted maximum heart rate was unsuccessful because of difficulty identifying a clear tricuspid regurgitant jet at the end of exercise. DISCUSSION Acute pulmonary edema has been infrequently described in athletes engaged in ultraendurance events. McKechnie et al. (18) described two athletes who developed acute pulmonary edema during a 90-km running race; these outcomes were hypothesized to have been caused by changes in myocardial compliance with prolonged exercise. In addition to this case report, there is a large body of AN ULTRACYCLIST WITH PULMONARY EDEMA Medicine & Science in Sports & Exercise d 9

3 evidence that athletes develop interstitial edema during sustained heavy exercise. McKenzie et al. (19), for example, used magnetic resonance imaging to demonstrate a 9.4% increase in extravascular lung water in highly trained cyclists who had just completed 45 min of cycling at 76% V O 2max. Similarly, Anholm et al. (2) had welltrained cyclists ride between 5 and 131 km and used conventional radiography to demonstrate an increase in the lung edema score between the pre- and postride radiographs. It is possible that our patient`s case of acute pulmonary edema represents an extreme form of the processes described in these studies, exacerbated by the exceedingly long duration of cycling during this particular race. The fact that our patient`s problem developed at high elevation, albeit only a modestly high one, also raises the question of whether this represents a typical case of highaltitude pulmonary edema (HAPE). HAPE is a noncardiogenic form of pulmonary edema seen in unacclimatized lowlanders who ascend to high elevations. Symptoms develop anywhere from 2 to 5 d after ascent and include dyspnea on exertion, decreasing exercise performance, and a dry cough. As the illness worsens, patients develop dyspnea at rest, cyanosis, and a cough producing pink, frothy sputum; they can die if the disorder is not treated in time (6). The incidence of HAPE varies between 0.2 and 15%, depending on the altitude reached and the rate of ascent (5,23); the main risk factors are an overly fast ascent to too high an elevation, overexertion, and individual susceptibility. Although our patient decompensated at high altitude, his case is atypical for HAPE in several respects. First, he developed pulmonary edema at a relatively low elevation of 2300 m. HAPE is significantly more common at elevations above 3000 m (6), although cases have been described in Summit County, CO (24) (base elevation m), and a recent report described a series of patients with HAPE at elevations below 2400 m (11). Second, the patient does not fit the phenotype demonstrated by HAPE-susceptible individuals. Multiple studies have demonstrated that those with HAPE susceptibility have abnormal pulmonary vascular reactivity. In particular, while breathing air with a FiO 2 of 0.12 at rest, exercising in normoxia, or exercising while breathing an FiO 2 of 0.12, HAPE-susceptible individuals demonstrate significantly greater increases in their pulmonary artery pressure than non HAPE-susceptible individuals, with systolic pressures rising in many cases to more than 60 mm Hg (9,13). Our patient`s hypoxic pulmonary vascular response was found to be minimal; while breathing a FiO 2 of 0.12 for 45 min, there was little change in his systolic pulmonary artery systolic pressure (G 5 mm Hg). These observations fit well with the patient`s previous experience with exercise at altitude. Given this modest hypoxic vasoconstrictor response, we would argue that he does not have the characteristic phenotype of HAPE susceptibility and, as a result, would not have been expected to develop pulmonary edema at an elevation of 2300 m in the absence of another critical factor. In this case, we believe that the other factor was his aggressive sodium-loading regimen. Several studies suggest that high salt intake can lead to marked plasma volume expansion. Luetkemeier (16) performed a retrospective analysis of sodium intake and plasma volume expansion in cyclists engaged in a 5-d training regimen and found a mean increase in plasma volume of 4.5 mlikg j1 of body weight as well as a strong positive correlation (r = 0.81) between total estimated sodium intake and plasma volume expansion. Individuals who ingested between 750 and 850 meq of sodium during the course of 3 d experienced a 9- to 14-mLIkg j1 increase in plasma volume. Armstrong et al. (3) randomized subjects to either a high-sodium intake regimen (397 meqid j1 ) or a low-sodium intake regimen (97 meqid j1 ) during an 8-d training regimen (90 minid j1 in a warm environment) and found that on day 4, the high-sodium intake group had a statistically significant increase in plasma volume compared with the lowintake group. By the end of the training period, there was no longer a difference in plasma volume expansion between the high- and low-sodium intake groups, but both groups still had increases in plasma volume compared with their pretraining values. Even in the absence of extensive salt loading, there is evidence to suggest that ultraendurance athletic activity itself leads to plasma volume expansion. For example, Neumayr et al. (20) studied 16 ultraendurance cyclists during the 525-km Race Across the Alps and found that plasma volume expanded by 8% at the end of the race and by 22% after 1 d of recovery. The upper limit for maximal sodium excretion and defense of extracellular fluid volume in humans is not known. In resting conditions, the ability of the kidney to excrete sodium in the face of increased intake depends on the magnitude of the change in intake; in general, progressively more extracellular fluid expansion occurs with greater increases in sodium ingestion. In humans, an increase in dietary sodium from 10 to 150 meqid j1 is accompanied by 2-kg weight gain reflecting a 2-L expansion of the extracellular fluid (21). With heat and exercise, sodium losses occur in sweat as well, and thus the cumulative extracellular fluid gain with added sodium intake is less. In addition, renal blood flow decreases in proportion to the level of exertion (22), and with 21 hid j1 of exertion, our subject could be considered to have been in a mild form of functional renal failure. The data in exercising humans are limited but instructive. In a study employing a similar design as the one cited above, Armstrong et al. (4) demonstrated that despite increased urine and sweat sodium excretion, subjects randomized to the high-sodium intake regimen (397 meqid j1 ) had a net daily sodium gain of T 12.3 meq and an average gain of 916 T 98.9 meq during the 8-d training period. We have no measure of our patient`s urinary and sweat sodium losses, and thus we cannot calculate his net sodium retention. However, because the volume of distribution of sodium is limited to the extracellular space, the patient`s 2.7-kg weight gain suggests about a 3-L expansion of extracellular fluid. On the basis of our patient`s ideal 10 Official Journal of the American College of Sports Medicine

4 body weight (70 kg), this represents a 21% increase in the volume of the extracellular fluid. Given that plasma volume represents roughly 20% of extracellular fluid, we would predict that his plasma volume expanded by 600 ml. This represents about a 21% increase over his estimated prerace plasma volume of 2.8 L, which should, in turn, lead to a similar fall in his hematocrit and the concentration of plasma proteins. As reflected in Table 1, the actual changes in his hematocrit, total protein, and albumin varied slightly from these predicted values, but all followed the expected trend. An excessive gain in plasma volume is problematic with exercise at high altitude. All individuals who ascend to high altitude experience alveolar hypoxia, which leads to hypoxic pulmonary vasoconstriction and, in turn, elevated pulmonary artery pressure. Exercise leads to a further rise in these pressures. In non HAPE-susceptible individuals the rise in pulmonary arterial pressure usually does not cause a rise in capillary hydrostatic pressure sufficient to trigger frank pulmonary edema, although several studies suggest that some individuals develop asymptomatic mild interstitial fluid accumulation (8,17). Our patient used a very aggressive sodium-loading regimen (1000 meqid j1 ), which likely increased his plasma volume to a point where hydrostatic pressure was increased and oncotic pressures was decreased. In conjunction with the increased cardiac output and pulmonary blood flow associated with continuous submaximal exercise, these changes in the Starling forces caused fluid transit out of the vascular space to a degree that exceeded the normal active and passive reabsorptive processes in the lung. 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