reported that the pulmonary ventilation of a man could be predicted from his alveolar pco2 and deep body temperature, and anticipated that CO2 would

Transcription

1 THE RESPIRATORY AND CARDIOVASCULAR RESPONSE TO IMMERSION IN COLD AND WARM WATER. By W. R. KEATINGE and M. EVANS. From the Department of Experimental Medicine, University of Cambridge. (Received for publication 20th July 1960) During their first few minutes of immersion in stirred water at 5 and 150 C. the pulmonary ventilation of twelve unclothed men was high, and their end-tidal PCO2 fell. The pco2 then returned to or a little above its original level but did not greatly exceed it even in working experiments lasting 20 min. in water at 50 C. or 40 min. in water at 150 C. Although work reduced or reversed the initial fall in pco2, these results therefore do not bear out predictions that the pco2 would rise to dangerous levels during hard work in cold water, at least in immersions of moderate duration. In water at C. the men's heart rates rose steadily, in water at 250 C. they fell and remained low, and in water at 5 and 150 C. they rose and then fell. Repeated immersion at 150 C. reduced or abolished the early respiratory and heart rate responses to immersion and the metabolic response, but did not significantly increase the falls in rectal temperature. Clothing also reduced the reflex responses to immersion. A number of ventricular extrasystoles were observed during the first 2 min. of immersion in water at 150 C., and it is suggested that ventricular fibrillation due to increased venous and arterial pressures, adrenaline, and hyperventilation, may be responsible for some cases of sudden death in cold water. THIS paper describes observations on the end-tidal pco2, pulmonary ventilation, heart rate, and electrocardiographs of twelve men during immersion in water at temperatures between 5 and C. Cotes [1954 and 1955] has reported that the pulmonary ventilation of a man could be predicted from his alveolar pco2 and deep body temperature, and anticipated that CO2 would accumulate in the body to reach dangerous concentrations during hard work in cold water. Sudden death in cold water without drowning is generally [Simpson, 1958] attributed to vagal arrest of the heart following inhalation of cold water into the naso-pharynx and glottis. However, it has seemed possible that ventricular fibrillation might be responsible for some of these cases; an increase in venous pressure may follow sudden exposure to cold [Bondurant, Hickam and Isley, 1957; Keatinge and McCance, 1957] and a rise in filling pressure may precipitate ventricular fibrillation in isolated hearts [Keatinge, 1959], while adrenaline is known sometimes to cause ventricular fibrillation after chloroform [Levy, 1914] and to facilitate it without chloroform in isolated hearts [Goodford, 1958]. The effect of adaptation by repeated immersion in cold water has also been assessed, since the heart rate and blood pressure responses to the immersion of a hand in ice water [Glaser and Whittow, 1957] are reduced by repetition. The design of the experiments and the subjects have been described in the preceding paper.* * A full account of individual results is available for reference at the National Institute for Medical Research, Mill Hill, London, N.W.7. 83

2 84 Keatinge and Evans METHODS Alveolar Air Determinations.-An apparatus, which would sample the last few ml. of each expiration and operate on a man whose head was moving vigorously, yet not hamper him, has been described already [Keatinge, 1958]; a simple and light double valve was fitted in the path of the subject's expired air and connected by fine plastic tubing to a collecting bag that provided its own suction. The gas collected was analyzed in a Haldane apparatus. As with other types of end-tidal sampling devices [Keatinge, 1958] samples gave an accurate indication of the composition of air in the alveoli of the lungs during hyperventilation, although slightly diluted when the subject was breathing quietly. The valve jammed on only one occasion out of some 600 collections in the present experiments. Normally one sample was collected just before each experiment, with the subject seated. It was not originally intended to collect samples before every experiment, but it soon became clear that the end-tidal pco2 of an individual before experiments was not constant, and that the variance of the changes during immersion could be decreased by a measurement before every immersion. Two samples were collected during immersion, the first between 21 and 51 min. (average 4 min.) and the second between 161 and 191 (average 18 min.). In the 40-min. immersions an additional sample was collected after min. Repeated measurements of alveolar air PCO2 were also made before immersions by the method of Haldane and Priestley [1905]; these gave values of P mm. Hg higher than the corresponding end-tidal samples. Pulmonary Ventilation.-During still immersions this was measured with a simple dry gas meter, taking readings every min. for 10 min., and every 2 min. for the second 10 min. Similar readings were made with the Max-Planck Institute Respirometer in the working experiments. All minute volumes are expressed as litres of dry air at 0 C. and 760 mm. Hg pressure. Electrocardiographs.-The skin contacts were silver discs 1 in. in diameter, coated with conducting jelly and strapped to the flexor surface of the wrists. Contact with the water was prevented by rubber cuffs sealed with vaseline round the wrist. The cuffs were cut from discarded surgical gloves. Counts were made for a period of 20 sec. before each still immersion with the subject sitting down, and over periods of 10 sec. starting at each minute after immersion. When the subject entered the water the amplitude of the record was immediately reduced by per cent presumably due to partial short-circuiting of the cardiac electrical impulses between his arms by the water. It was impossible to obtain a satisfactory trace 'while a subject was working. A record was obtainled on each subject while he paused for a few seconds during his first "working" experiment at 150 C.; as no abnormalities were observed, E.C.G. records were not attempted in subsequent working experiments. In the still experiments there was some interference to the record by muscle potentials due to shivering. This was occasionally serious enough to make counting difficult towards the end of the immersions but reasonable records could almost always be obtained by asking the subject to relax for a few seconds. RESULTS End-tidal pco2.-table I shows that the men's end-tidal pco2 was much the same before their first and their eighth immersion. In both of these they sat still unclothed in stirred water at 15 C. During the first their end-tidal pco2 fell significantly in the first 4 min. of immersion, but in the eighth immersion it rose a little. During the next 14 min. the end-tidal pco2 rose to the original level in the first immersion, and about 2 5 mm. above it in the eighth.

3 Reflex Responses to Immersion Table II shows that the men's end-tidal pco2 was much the same at the start of the remaining 150 C. immersions, although it was rather lower before the maximal work experiment than the others. On average it fell somewhat in the first 4 min. of the still stirred unclothed experiment and rose somewhat TABLE I.-THE EFFECT OF REPEATED IMMERSION IN WATER AT 150 C. ON THE END-TrDAL PCO2 (All figures means for twelve subjects) Before immersion Change in first 4 min.. Significance of change. Significance of difference Change between 4th and 18th min. (eleven subjects) Significance of change. Sitll stirred unclothed First immersion Eighth immersion 35* SI 1 10 Not significant P < 01 Sd 1-12 P < Sx P <* Si P < 05 during this time when the men worked (particularly when they worked maximally) or were clothed. It then tended to rise in the still stirred unclothed experiment, but to fall in the maximal work and the clothed immersions. TABLE II.-THE EFFECT OF WORK, CLOTHING AND AGITATION OF THE WATER ON THE END-TIDAL PCO2, 20 MIN. IMMERSIONS AT 15 C. (All figures means for twelve subjects) Before immersion - Change in first 4 min. of immersion Change between 4th and 18th min. of immersion Still Still Still Still Maxiral work stirred Working unstirred stirred Working unstirred unclothed unclothed unclothed unclothed clothed clothed clothed (eleven subjects) @05 36@63 36@96 37@ * * Differs from column 1, P < Table III shows that the men's end-tidal pco2 was much the same before the various immersions at 50 C. except before the maximal work ones, when it was rather low. Their mean end-tidal pco2 fell during the first 4 min. of the still stirred unclothed immersions at this temperature, but it did not change greatly during this time when the men worked or wore clothes. During the next 14 min. it rose to approximately its initial level in the still stirred unclothed immersion and did not change greatly in the other immersions. 85

4 86 Keatinge and Evans Table IV shows that the men's end-tidal pco2 was generally a little lower before working than still immersions at higher water temperatures. It rose significantly in the first 4 min. of both working and still experiments at TABLE III.-EFFECT OF WORK AND CLOTHING ON THE END-TIDAL pco2, 50 C. IMMERSIONS (All figures means for five subjects) Before immersion. Change in first 4 min. Change between 4th and 18th min. Still stirred unclothed Working Maximal work wr unclothed unclothed * * Difference from column 1, P < -05. t Difference from column 1, P < 01. TABLE IV.-EFFECT OF WORK ON THE END-TIDAL PCO2 OF UNCLOTHED MEN, HIGHER TEMPERATU-RE IMMERSIONS (All figures means for twelve subjects) Before immersion. Change in first 4 min. Change between 4th and 18th min. 250 C. Still stirred Working * t Water temperature 350 C. Still stirred Working * t * * Significance of rise or fall, P < -05. t Significance of rise or fall, P < -01. TABLE V.-EFFECT OF WORK AND CLOTHING ON THE END-TIDAL PCO2, 40 MIN. IMMERSIONS AT 150 C. Subject Before Change in first Change immersion 4 min. 4th-18th min. Still stirred unclothed Working unclothed Still stirred clothed Change 18th-38th min Working clothed t C. Still stirred and 350 C., and the rise was greater in the working than the still immersions. During the next 14 min. of the working and still immersions at 250 C. the PCO2 did not change appreciably, but it fell during this time in the 350 C. experiments and the C. immersion. Table V shows that there was no important change in end-tidal pco2 during the last half of the 40 min. unclothed immersions at 15 C.

5 Reflex Responses to Immersion 87 Pulmonary Ventilation.-Fig. 1 gives the men's pulmonary minute volumes in unclothed immersions at 5, 15, 25 and 350 C., both when working and when still in stirred water. The mean minute volume was only about in the first minute of the still stirred immersion at 350 C., and then fell to and remained near 10 1./min. (In the corresponding C. immersion it was about 1 1./min. higher throughout.) In the working experiment at STILL, IN STIRRED WATER WORKING I ~35~C 30] < l01 h \, T M E(minutes) FIG. 1.-Pulmonary ventilation during immersion at temperatures between 5 and 350 C. Volume expressed at S.T.P. dry. (All figures means of twelve men except 50 C. immersions which are means of seven men. Standard deviations are shown.) 350 C. it took 3 min. to rise to and remained near this level. The ventilation was slightly higher throughout the corresponding immersions at 25 than at 350 C., and in those at 150 C. it was substantially higher, particularly in the first few minutes of the immersions. The fig. also shows that the men's ventilation was higher throughout their first than their eighth immersion (both still in stirred water) at 150 C. This difference was significant in both the first 3 min. (Sd 1-163, P < -025) and last 2 min. (Sd 2-46, P < -025) of the immersions. The fig. also shows that the ventilation of seven men was high in the working and still experiments at 50 C., the main difference from the 15 C. immersions being a substantial rise towards the end of the still experiment at 50 C. Table VI shows that the men's pulmonary ventilation in the first 3 min. of

6 88 Keatinge and Evans the still experiments at 5 and 150 C. was lower when the men were clothed than when they were unclothed, and, at 150 C., when the water was unstirred than when it was stirred. Heart Rates.-Table VII shows that although the heart rates of eleven of TABLE VI.-EFFECT OF CLOTHING AND AGITATION OF THE WATER ON THE EXPIRED AIR VOLumE (EXPRESSED AS 1./min. AT S.T.P. DRY) IN THE FIRST 3 MIN. OF STILL IMMERSIONS AT 15 AND 50 C. Volume 1./min. - Water temperature 15 C. (means for twelve subjects) Still Still Still Still stirred unstirred stirred unstirred unclothed unclothed clothed clothed t 19.7* 18.lt * Difference from column 1, P < 05. t Difference from column 1, P < 01. I 50 C. (means for five subjects) I1 -A I Still Still stirred stirred unclothed clothed I the subjects rose in the 1st min. of the first immersion in which they were unclothed in stirred water at 150 C., their heart rates did not change appreciably under similar conditions in the same period of the eighth immersion. Nineteen minutes after the start of both experiments the heart rates were on average lower than before immersion, particularly in the eighth immersion. TABLE VII.-EFFECT OF REPEATED IMMERSION IN WATER AT 150 C. ON THE HEART RATE (All figures means for twelve subjects) Still stirred unclothed First Eighth Before immersion Change in 1st min. (eleven subjects) O015 Significance of change... SK 4.77 P < 05 Significance of difference... Sd 3.65 P < 005 Change during first 19 min. of immersion (ten subjects) Table VIII gives the heart rates of the subjects before and during the still, unclothed immersions in stirred water at 5, 15, 25, 35 and C. At 350 C. the rate rose only slightly during the 1st min., and quickly returned to the initial rate. In water at C. the rate increased significantly within a minute of immersion and continued to rise throughout the experiment, while at 250 C. the rate fell on average over 7 beats/min. in the 1st min. of immersion and remained at this lower rate. At 15 C. the rate rose in the 1st min., and then fell, until by the end of immersion it was slightly below the initial rate. The heart rates before the 50 C. immersions were usually

7 Reflex Responses to Immersion higher than before the other experiments, probably due to apprehension. They rose greatly during the 1st min. of immersion, fell nearly to the initial level by 7 min. and then rose slightly towards the end of the experiment. TABLE VIII.-EFFECT OF WATER TEMPERATURE ON THE HEART RATE, STILL STIRRED UNCLOTHED IMMERSIONS Water temperature Heart rate Min. after immersion Before A - I immersion C. (seven subjects) Difference Sa 6-78 P < C. (twelve subjects) Difference Sd 3-92 P < C. (twelve subjects) Differs from figure below Sd 5*74 P < C. (twelve subjects) C. (twelve subjects) Difference Sd 2-50 P < *001 Table IX shows that the heart rate rose less on average during the 1st min. of still immersions at 150 C. when the men were clothed than when they were unclothed, and when the water was unstirred than when it was stirred; TABLE IX.-EFFECT OF CLOTHING AND AGITATION OF THE WATER ON THE HEART RATE, STILL IMMERSIONS AT 15 AND 50 C. Rate before immersion Change in 1st mm.. Change in first 19 mm. of immersion Water temperature I -I^ 150 C. (means for twelve subjects) Still Still Still Still stirred unstirred stirred unstirred unclothed unclothed clothed clothed 50 C. (means for five subjects) Still stirred unclothed Still stirred clothed 79* * t * X28 * Difference from colunn 1, P < 05. t Difference from column 1, P < -01. it also rose less in the 1st min. of immersion at 50 C. when they were clothed than when they were unclothed. Table X shows that repeated immersion significantly reduced the men's metabolic rate in the water, but that it did not significantly alter their skin temperature before or after immersion, nor their rectal temperature or the rate at which it fell. 89

8 Keatinge and Evans Arrhythmias.-A series of ventricular extrasystoles originating in at least two sites was observed in the still unclothed immersion of Subject 7 in unstirred water at 150 C. (fig. 2, top). They were present both during the TABLE X.-EFFECT OF REPEATED IMMERSION AT 150 C. ON SKIN AND RECTAL TEMPERATURES AND METABOLIc RATE IN THE WATER. STILL STIRRED AND UN- CLOTHED IMMERSIONS FOR 20 MIN. (Means for twelve subjects) First Eighth imersion immersion Skin temperature C. Before immersion After immersion Rectal temperature 'C. Before immersion Fall during immersion Metabolic rate k.cal./min. (eleven subjects) Difference.. s 0236 P < 01 1 min. and the 2 min. readings and then ceased. In this and earlier experiments the E.C.G. had been operated for only sec. every min., but for subsequent experiments on the remaining four subjects it was turned on as soon as the man was in position in the tank, and was left running for the A*AL I FiG. 2.-Electrocardiographs (lead I) during still unclothed immersions at 15' C. Top-ventricular extrasystoles 1 mi. 40 sec. after immersion, Subject 7. Bottom-probable supraventricular extrasystoles 30 sec. after immersion, Subject 12. whole of the 1st min. A ventricular extrasystole appeared after 40 sec. of Subject 11's first unclothed immersion in stirred water at 150 C., and another after 35 sec. in Subject 10's unstirred, clothed immersion at the same temperature. Three isolated extrasystoles were observed in the middle of higher temperature immersions, two of them mm. after Subject 7's immersion at 35'0 C., and one 12 m. after Subject 10's immersion at 25' C., but no other runs of ventricular irregularities were seen. The heart rate was often very irregular during the 1st min. of immersion at 15 and 50 C. In some cases IP

9 Reflex Responses to Immersion this appeared to be sinus arrhythmia associated with the hyperventilation in the early stage of immersion. In others it seemed probable that the irregularity was due to supraventricular extrasystoles (fig. 2, bottom) but since P waves could seldom be distinguished clearly, it was impossible to be sure that these beats originated in an abnormal site. No subject who developed ventricular extrasystoles at 150 C. was immersed at 50 C., and no extrasystoles were observed in those who were immersed at this temperature. Apart from these irregularities, no significant abnormalities were detected in the electrocardiographs recorded during immersion. 91 DIscusSION Respiratory Changes during Immersion.-The principal respiratory change observed in these experiments was a fall in end-tidal pco2, associated with a high pulmonary ventilation, during the first few minutes of the men's first still, stirred unclothed immersion at 150 C. and the similar immersion at 50 C. The fall in true alveolar pco2 was probably rather greater than the fall in end-tidal pco2 measured during this time, since end-tidal samples collected before immersion underestimated alveolar pco2 by 2-3 mm. Hg and the samples collected during the immersions, when the ventilation was generally high, probably underestimated it by less (see Methods section, and Keatinge, 1958). The increase in ventilation in cold water began so rapidly after immersion that it must have been caused by a reflex from receptors in the skin rather than by a change in deep body temperature. It may have been due to a reflex affecting the respiratory centre directly, or indirectly through vascular pressure receptors, while the reflex release of adrenaline and noradrenaline probably contributed to it within a short time after immersion; these hormones are likely to be released on immersion and they cause hyperventilation [Whelan and Young, 1953; Barcroft, Basnayake, Celander, Cobbold, Cunningham, Jukes and Young, 1957]. The fall in pco2 was less (or converted to a small rise) when the men worked, but both the end-tidal pco2 and minute volume readings give evidence of hyperventilation in the first few minutes of the working unclothed immersions at 5 and 150 C. as compared to the corresponding experiments at 25 and 350 C. Haldane and Priestley [1905], and Cunningham and O'Riordan [1957] observed that men exposed to heat overbreathe and suffer a fall in alveolar pco2, or that they tend to underbreathe when exposed to cold, while Cotes [1954 and 1955] reported that for a given level of alveolar pco2, pulmonary ventilation increased linearly with a rise, and decreased with a fall in rectal temperature. However, Boycott and Haldane [1908] found that the hyperventilation caused by exposure to heat was not always associated with a rise in rectal temperature, and evidence that men exposed to cold may overbreathe was reported by Swift [1932], Dill and Forbes [1941] and Schneider [1957]. These observations, together with the findings in the

10 92 Keatinge and Evans present experiments, leave little doubt that strong cutaneous sensations of cold, and perhaps of heat, can greatly increase the pulmonary ventilation independently of changes in deep temperature or carbon dioxide production. Ventilation is clearly not dependent almost solely on the alveolar pco2 and the deep body temperature when cold is applied to the skin. Indeed moderate changes in deep body temperature had relatively little effect on ventilation in these experiments; the end-tidal pco2 was very little lower at the end of the C. still immersion when the mean rectal temperature had risen C., than at the end of the 350 C. still immersion when it had fallen C. The rapid decrease in the men's ventilation after their 1st min. of still stirred unclothed immersions in water at 5 and 150 C. was probably due to partial adaptation of their cutaneous cold receptors to the low skin temperature. The changes in their end-tidal pco2, a fall followed by a return to near the initial level, somewhat resembles the results obtained on dogs by Osborn [1953], who found evidence of hyperventilation followed by hypoventilation when aneesthetized animals were immersed in cold water. However, the men's end-tidal pco2 did not rise much above its resting level towards the end of the present cold immersions, even in the unclothed immersions at 50 C. and the 40 min. unclothed immersions at 150 C., when the falls in rectal temperature were substantial. Also, the men's mean end-tidal PCO2 in 20 min. unclothed immersions was lower at the end of both working and still experiments at 5 and 150 C. than those at 25 and 350 C. It is therefore probable that the factors causing overbreathing in the first few minutes of immersions at 5 and 150 C. continued to operate to some extent throughout these immersions. These results, therefore, do not support the prediction of Cotes [1954] that CO2 will accumulate to reach dangerous concentrations in men who exert themselves in cold water, at least in the majority of normal men under conditions of moderate hypothermia. Changes of Heart Rate in the Still Stirred Unclothed Immersions.-A rise of heart rate in warm, or a fall in cool, surroundings has often been observed [Barcroft and Verzar, 1931; Swift, 1932; Barcroft and Marshall, ; Bazett, Scott, Maxfield and Blithe, 1937; Cooper and Kerslake, 1955]; the last authors considered that the rapid increase in heart rate after exposure of men to radiant heat indicated that the change was a direct reflex response from the skin and not a result of vasodilatation, but the continuing rise in rate during the present C. immersions makes it likely that vasodilatation and perhaps an increase in the temperature of the heart played a part in this case. The men's immediate fall in heart rate in water at 250 C. must have been brought about either by a direct reflex from the skin or indirectly by vasoconstriction. Possibly an increase in central vascular pressures as a result of peripheral vasoconstriction was responsible; such increases take place during exposure to cold [Bondurant et al., 1957; Keatinge and McCance, 1957] and both an increase in arterial [Weiss and Baker, 1933] and venous [Aviado, Li Kalow, Schmidt, Turnbull, Peskin, Hess and Weiss, 1951] pressure may slow the heart by means of reflexes. The early increase in heart rate in

11 Reflex Responses to Immersion the 15 and 50 C. immersions may be due to the intense sensation of cold causing reflex release of adrenaline and noradrenaline into the general circulation and into the vicinity of the pacemaker of the heart. The changes in heart rate may also have been due in part to a direct effect of increases in filling pressure on the pacemaker of the heart; moderate increases in filling pressure increase the rate of denervated or isolated mammalian hearts [Tiitso and Tootson, 1935; Blinks, 1956] while larger increases cause a fall [Pathak, 1958] whose size depends on duration of the high pressure [Keatinge, 1959]. Cardiac Arrhythmias, and the Problem of Sudden Death in Cold Water.- The multiple ventricular extrasystoles that Subject 7 developed during the first few minutes of immersions at 15 'C. suggest that there was an increase in ventricular irritability during this time. Later experiments in which unclothed men were immersed repeatedly in water at 150 C. [Keatinge, 1960] have confirmed that ventricular extrasystoles are frequent in the first 70 sec. of cold immersion and this gives some support to the possibility that ventricular fibrillation is an occasional cause of sudden death in cold water. Several changes observed after cold immersion would tend to cause this; the venous pressure may rise briefly during sudden exposure to cold [Bondurant, Hickam and Isley, 1957; Keatinge and McCance, 1957] and an increase in filling pressure can precipitate ventricular fibrillation in isolated rabbit hearts [Keatinge, 1959], while it is well known that ventricular fibrillation can be precipitated by adrenaline [Levy, 1914; Goodford, 1958], which is probably released during cold immersion. The hyperventilation observed in these experiments is another possible factor, since a large fall in pco2 can cause ventricular fibrillation in dogs [Brown and Miller, 1952]. Effect of Repeated Immersion.-Both the rise in the men's heart rates and the fall in their end-tidal pco2 which took place in the first few minutes of their first still stirred unclothed immersions were greatly reduced or abolished by their eighth immersion at this temperature. The men usually found the eighth immersion less unpleasant than the first, they appeared to shiver less during it and their metabolic rates and pulmonary ventilation were lower in their eighth than their first immersion. Improved physical training decreases the metabolic response to cold [Keatinge, 1961] but it is unlikely that the two 20 min. experiments in which the present men worked at the standard rate, during the 14 days between their first and eighth immersion, significantly improved their physical fitness; they were all reasonably fit as a result of regular naval drill when they started the experiments. The heart rate and blood pressure response to brief immersion of a hand in painfully hot or painfully cold water is reduced by repetition and the reduction is probably due to central nervous rather than peripheral changes [Glaser and Whittow, 1957; Glaser, Hall and Whittow, 1959]. It seems likely that a similar central nervous change was responsible for the reduced responses in the present experiments. 93

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