Content uploaded by Avijit Datta
Author content
All content in this area was uploaded by Avijit Datta
Content may be subject to copyright.
doi: 10.1152/japplphysiol.01201.2005
100:2057-2064, 2006. ;J Appl Physiol
Avijit Datta and Michael Tipton
and asleep
pathways, interactions, and clinical consequences awake
Respiratory responses to cold water immersion: neural
You might find this additional info useful...
61 articles, 24 of which you can access for free at: This article cites
http://jap.physiology.org/content/100/6/2057.full#ref-list-1
6 other HighWire-hosted articles: This article has been cited by
http://jap.physiology.org/content/100/6/2057#cited-by
including high resolution figures, can be found at: Updated information and services
http://jap.physiology.org/content/100/6/2057.full
can be found at: Journal of Applied Physiology about Additional material and information
http://www.the-aps.org/publications/jappl
This information is current as of July 3, 2013.
http://www.the-aps.org/.
© 2006 the American Physiological Society. ISSN: 8750-7587, ESSN: 1522-1601. Visit our website at
year (monthly) by the American Physiological Society, 9650 Rockville Pike, Bethesda MD 20814-3991. Copyright
physiology, especially those papers emphasizing adaptive and integrative mechanisms. It is published 12 times a
publishes original papers that deal with diverse area of research in appliedJournal of Applied Physiology
by guest on July 3, 2013http://jap.physiology.org/Downloaded from
Invited Review
HIGHLIGHTED TOPIC A Physiological Systems Approach to Human and
Mammalian Thermoregulation
Respiratory responses to cold water immersion: neural pathways, interactions,
and clinical consequences awake and asleep
Avijit Datta
1,2
and Michael Tipton
1
1
Institute of Biomedical and Biomolecular Sciences, Department of Sport and Exercise Science,
University of Portsmouth, and
2
Portsmouth Hospitals National Health Service Trust, Portsmouth, United Kingdom
Datta, Avijit, and Michael Tipton. Respiratory responses to cold water immersion:
neural pathways, interactions, and clinical consequences awake and asleep. J Appl Physiol
100: 2057–2064, 2006; doi:10.1152/japplphysiol.01201.2005.—The ventilatory re-
sponses to immersion and changes in temperature are reviewed. A fall in skin
temperature elicits a powerful cardiorespiratory response, termed “cold shock,”
comprising an initial gasp, hypertension, and hyperventilation despite a profound
hypocapnia. The physiology and neural pathways of this are examined with data
from original studies. The respiratory responses to skin cooling override both
conscious and other autonomic respiratory controls and may act as a precursor to
drowning. There is emerging evidence that the combination of the reestablishment
of respiratory rhythm following apnea, hypoxemia, and coincident sympathetic
nervous and cyclic vagal stimulation appears to be an arrhythmogenic trigger. The
potential clinical implications of this during wakefulness and sleep are discussed in
relation to sudden death during immersion, underwater birth, and sleep apnea. A
drop in deep body temperature leads to a slowing of respiration, which is more
profound than the reduced metabolic demand seen with hypothermia, leading to
hypercapnia and hypoxia. The control of respiration is abnormal during hypother-
mia, and correction of the hypoxia by inhalation of oxygen may lead to a further
depression of ventilation and even respiratory arrest. The immediate care of patients
with hypothermia needs to take these factors into account to maximize the chances
of a favorable outcome for the rescued casualty.
cold shock; drowning; underwater birth; sleep apnea
THE VENTILATORY RESPONSE TO immersion is not purely of aca-
demic interest; it can be the precursor of drowning, a major
cause of global mortality. There are 500,000 drowning deaths
every year worldwide (59), and drowning is the second leading
cause of accidental death in the European Union and the United
States (79). In 2001, there were 3,281 unintentional drownings
in the United States, averaging nine people per day. This does
not include drownings in boating-related incidents (5). For
every child who drowns, three receive emergency department
care for nonfatal submersion injuries. More than 40% of these
children require hospitalization (5). Nonfatal incidents can
cause brain damage that result in long-term disabilities ranging
from memory problems and learning disabilities to the perma-
nent loss of basic functioning (i.e., persistent vegetative state).
Among children aged 1–4 yr, most drownings occur in resi-
dential swimming pools (8). Most young children who
drowned in pools were last seen in the home, had been out of
sight less than 5 min, and were in the care of one or both
parents at the time (60). Thus any factors which may modify
the mortality and morbidity of drowning would have a major
impact on global child health.
For those who survive the hazardous initial responses to
immersion and superficial cooling, hypothermia becomes an
increasing risk, particularly for those in remote areas, or when
search and rescue capabilities are limited, such as at times of
conflict.
In this paper we focus on the ventilatory response to immer-
sion and falling skin and deep body temperature.
VENTILATORY RESPONSE TO IMMERSION:
THERMONEUTRAL AND WARM WATER
The ventilatory responses to immersion in thermoneutral
water are a direct result of the high density of water compared
with air and the consequent differential hydrostatic pressure
over the immersed body. A negative transthoracic pressure of
⬃14.7 mmHg is established on immersion that results in
negative pressure breathing. A cephalad redistribution of blood
occurs within six heart beats of immersion and can increase
central blood volume by up to 700 ml. The increase in intratho-
racic blood volume engorges the pulmonary capillaries and
competes with air for space in the lung, resulting in a 30 –50%
Address for reprint requests and other correspondence: A. Datta, Institute of
Biomedical and Biomolecular Sciences, Dept. of Sport and Exercise Science,
St. Michael’s Bldg., Univ. of Portsmouth, White Swan Road, Portsmouth, UK
PO1 2DT (e-mail: avijit.datta@port.ac.uk).
J Appl Physiol 100: 2057–2064, 2006;
doi:10.1152/japplphysiol.01201.2005.
8750-7587/06 $8.00 Copyright
©
2006 the American Physiological Societyhttp://www. jap.org 2057
by guest on July 3, 2013http://jap.physiology.org/Downloaded from
reduction in static and dynamic lung compliance, whereas
pulmonary gas flow resistance is increased by 30–58% and
impedance by 90% (69). These shifts are thought to contribute
to a small and transient increase in oxygen consumption during
the first minute of immersion in water up to 40°C (51). The
increase in pulmonary capillary blood volume seen on immer-
sion in 34° and 40°C water, as a result of increased hydrostatic
pressure, is not significantly increased on immersion in water
at 25°C, suggesting that cold-induced vasoconstriction does
not augment the blood volume shifts caused by hydrostatic
pressure (11).
In conjunction with the increase in hydrostatic pressure
on the chest, the hemodynamic alterations result in a 65%
increase in the work of breathing. Vital capacity is reduced
by an average of 6%, maximum voluntary ventilation by
15%, and expiratory reserve volume is decreased by an
average of 66%, which results in a reduction in functional
residual capacity (16, 17, 37).
The decrease in functional residual capacity and the increase
in intrathoracic pooling of blood produces a small increase in
pulmonary shunting; a small but consistent fall in the arterial
partial pressure of oxygen has been reported by some authors
(16) but not others (12). Opposing some of these impairments
to lung function are improvements in both the ventilation-
perfusion ratio and diffusion capacity of the lung.
From the practical viewpoint there is little evidence that the
changes in lung function on immersion in thermoneutral or
warm water threaten respiration in fit individuals.
VENTILATORY RESPONSE TO COLD IMMERSION:
SKIN COOLING
Immersion of an unprotected body in cold water produces a
large and fast fall in skin temperature, which, in turn, evokes
the initial responses to cold immersion, given the generic name
“cold shock.” This is probably the most dangerous response
associated with immersion in cold water, having the potential
to be a precursor to drowning or cardiovascular problems. It
includes an “inspiratory gasp,” hyperventilation, hypocapnia,
tachycardia, peripheral vasoconstriction, and hypertension (see
Fig. 1; Refs. 40, 42, 70). The responses reach a peak within
30 s of immersion and adapt over the first 3 min of immersion
in most individuals. The inspiratory gasp occurs almost imme-
diately upon immersion, is usually between 2–3 liters in
volume, and results in a corresponding inspiratory shift in
end-expiratory lung volume (71). This results in breathing
(hyperventilation) taking place within 1 liter of total lung
capacity (26, 70). This shift, plus the large afferent drive to
breathe, is probably responsible for the sensation of dyspnea
experienced at this time, rather than bronchoconstriction or
altered lung mechanics (43). The time course of the inspiratory
shift corresponds with the period when subjects report being
breathless (41).
The method by which individuals enter cold water has a
significant effect on the pattern of respiratory responses, as the
cold shock response shows both spatial and temporal summa-
tion. During the first 10 s of a staged immersion, frequency can
Fig. 1. Cold shock response in a normal male subject following breath holding during naked, head-out immersion in cold water (11°C). From top downward
are shown the ECG (lead II), exhaled P
O
2
(FE
O
2
), exhaled PCO
2
(FE
CO
2
), and tidal volume (VT). Despite the subjects’ best efforts to voluntarily maintain apnea,
breath-hold time is only 23 s. Note the cardiac arrhythmias, hyperventilation, tachypnea, and hypocapnia following the resumption of breathing.
Invited Review
2058 RESPIRATORY RESPONSES TO COLD WATER IMMERSION
J Appl Physiol • VOL 100 • JUNE 2006 • www.jap.org
by guest on July 3, 2013http://jap.physiology.org/Downloaded from
increase by 41% and ventilation by 278%; however, with a
nonstaged immersion the increases are much greater: fre-
quency 115% and ventilation 644% (31).
The cold shock response can reduce maximum breath-hold
time to 25–30% of that seen before immersion, and breath
holding is followed by hyperventilation and resultant profound
hypocapnia (see Fig. 1 and Ref. 70). This hyperventilation
occurs notwithstanding the increase in airway resistance to
both inspiration and expiration on immersion noted above,
implying that the drive to breathe is vastly increased. The fact
that the ventilatory response is as large when immersion in cold
water follows voluntary hyperventilation to lower carbon di-
oxide tension (71) is further evidence that the drive to breath on
cold immersion is great and is not attenuated by the chemore-
ceptor pathways that normally influence ventilation. Cooper et
al. (15) reported that hyperventilation on cold water immersion
occurs without an alteration in the sensitivity of the central
chemoreceptors.
The initial respiratory responses to immersion in cold water
occur before there has been any change in core temperature and
the speed of the response indicates that they are neurogenic in
origin. That the responses are not seen on immersion in warm
water suggests that they are initiated by the cutaneous cold
receptors, the superficial subepidermal location of which
(depth ⬃0.18 – 0.22 mm) explains the speed of the response
and that fact that it is not influenced by subcutaneous fat
thickness.
The precise afferent pathways responsible for the respiratory
responses to cold water immersion remain to be elucidated. It
has been suggested that thermoafferents from the peripheral
cold receptors directly stimulate the respiratory center (26).
Keatinge and Nadel (43) concluded that the reflex respiratory
responses to cold water in the cat are mediated at midbrain
level and that the cerebrum is not essential for the response.
The earlier work of Lumsden (47) and St. John (66) sheds light
on the neural pathways responsible for gasping. In vagoto-
mized animals, eupnea is transformed to gasping following
removal of the pons or during hypoxia (48). Furthermore,
destruction of neurons in the rostral medulla with neurotoxins
leads to the elimination of gasping but not eupnea (65),
indicating that the neural pathways for gasping (an area in adult
cats extending from dorsomedial and ventrolateral medulla,
termed the pre-Bo¨tzinger complex, to the nucleus ambiguus)
may be distinct from those necessary for the generation of
eupnea. That the first respiratory response to immersion in cold
water is a gasp indicates that the cold thermoreceptor volley
elicited by cold immersion excites this area.
Using c-fos protein immunohistochemistry (9, 33), Tipton M
and Harris M (unpublished observations) have identified the
neuronal cell groups activated following the cold shock re-
sponse evoked (Figs. 2 and 3) by 60-s upright immersion to the
diaphragm of rats in 8°C water. The c-fos-positive neurons
were identified in the nucleus tractus solitarius, area postrema,
and dorsal motor nucleus, that is, areas known to process
cardiovascular and respiratory afferents. No expression was
Fig. 2. Cold shock response in a tracheostomized rat, anesthetized with
urethane. From top downward are shown arterial blood pressure (ABP),
ventilation (V
˙
E), VT, and respiratory frequency (f). The horizontal bar indicates
upright immersion to the diaphragm in cold (8°C) water, after which the rat is
transferred back into 37°C water (Tipton and Harris, unpublished observa-
tions).
Fig. 3. c-fos proto-oncogene staining in the dorsal medullary nuclei of a
urethane-anesthetized rat after immersion in cold water (8°C, 60 s, top) and
thermoneutral water (37°C, 2 h, bottom). There is marked staining only during
cold immersion in areas known to be responsible for cardiorespiratory inte-
gration. NTS, nucleus tractus solitarius; DMNX, dorsal motor nucleus of tenth
cranial nerve (vagus); VIV, fourth ventricle. (M. Tipton and M. Harris,
unpublished observations)
Invited Review
2059RESPIRATORY RESPONSES TO COLD WATER IMMERSION
J Appl Physiol • VOL 100 • JUNE 2006 • www.jap.org
by guest on July 3, 2013http://jap.physiology.org/Downloaded from
observed in animals immersed in water at 39°C (Fig. 3).
Analogous studies from other groups show the pathway for
noxious cold stimuli (hindlimb immersion in 4°C water) causes
c-fos activation of neurons in lamina I of the spinal dorsal horn
(1, 77). Another group showed that this c-fos immunoreactivity
coreacts with NK-1 receptor staining, indicating that those
receptors may mediate some of the noxious cold response (19).
Other studies show that facial immersion in 4°C water causes
c-fos activation of neurons in the dorsal horn of the medulla
(67). These neuroanatomic studies corroborate the hypothesis
that ascending neurons involved in transmitting the thermore-
ceptor volley following cold immersion are in the pons (4, 32)
very close to the neurons involved in the generation of gasping.
ANTICIPATION, ANXIETY, AND STRESS COMPONENTS OF
COLD SHOCK: POTENTIAL THERAPIES
The hyperventilation seen after the initial gasp of the cold
shock response probably also reflects a stress response, which
would be accompanied by a sympathetic overdrive (30). The
speed of this response, as with the respiratory response, again
suggests an uncomplicated neural pathway, thought to be
mediated through the tegmentum of the midbrain and the
hypothalamus (80).
The observation that many subjects display a tachycardia
and relative hyperventilation before they are immersed in the
cold water provides further evidence that an anticipatory anx-
iety and stress response is occurring (68) to the cold immer-
sion. Animal studies suggest that acclimation to this stress
response may involve endogenous opioid production (36).
Confirmation that there are neurogenic changes accompany-
ing the cold shock response comes from human studies mea-
suring cerebral blood flow velocity (76). Those authors dem-
onstrated that middle cerebral artery blood flow was reduced
during cold (12°C) water immersion compared with that re-
corded in water at 35°C (see Fig. 4B). However, if the hyper-
ventilation-induced hypocapnia induced by cold shock was
matched by voluntary hyperventilation either in warm air
(24°C; see Fig. 4A) or thermoneutral water (35°C), there was
an even lower cerebral blood flow velocity. In other words, the
cerebral blood flow velocities seen during cold shock are
higher than one would expect for a given level of arterial
carbon dioxide, suggestive of either increased cerebral neuro-
genic activity with an accompanying demand for increased
cerebral blood flow, or systemic sympathetic-induced hyper-
tension.
Recent evidence from our laboratory suggests that there is
also a marked and modifiable psychological component to the
breath-hold component of the cold shock response (6). Sub-
jects were asked to breath hold in air and then during immer-
sion into stirred cold water. As expected, the breath-hold times
were markedly reduced from 46 s to only 24 s despite subjects’
best efforts to maintain apnea volitionally. This was accompa-
nied by tachycardia and, after the break of breath hold in water,
a profound hyperventilation and hypocapnia (nadir P
CO
2
22
Torr), indicative of a powerful sympathetic overdrive. The
subjects were then split into two groups, matched for breath-
hold time. One group was given a battery of psychological
skills: goal setting (46), arousal regulation (58), mental imag-
ery (44), and positive self-talk (29) over 5 days. The mean
breath-hold time of this group increased to 44 s during a second
immersion 1 wk later, whereas that of the control group who
had not received the psychological skills training remained at
21 s. A corresponding change was not seen with the heart rate
response before or during immersion.
Thus the psychological skills had influenced the respiratory
but not the cardiac component of the cold shock response, the
obvious difference between the two being the degree to which
they are under conscious control. Breath holding requires the
voluntary suppression of a drive to breathe; in cold water this
drive comes from the cutaneous cold receptors. It is most likely
that the psychological skills improved the ability of subjects to
volitionally suppress the cold-evoked drive to breathe and
maintain voluntary apnea for longer. This implies an enhance-
ment of the descending inhibitory cortical pathways to the
respiratory centers.
The initial respiratory responses to immersion in cold water
can habituate. As few as five 3-min immersions in cold water
can reduce these responses by 50% (74), with the response still
being reduced by 25% 14 mo later (75). The extent to which
habituation of the initial respiratory responses to immersion is
a psychological phenomenon remains to be determined. That
the alterations that underpin habituation occur central to the
peripheral cold receptors has been established; repeatedly im-
mersing one side of the body habituates the respiratory re-
sponse evoked by a single immersion of the other, previously
Fig. 4. A: cerebral blood flow velocity (CBFV) of human middle cerebral
artery recorded with Doppler ultrasound in a normal adult male subject. Top:
CBFV recorded over5satrest. Bottom: CBFV during hyperventilation with
end-tidal PCO
2
(PET
CO
2
) matched to that seen in the same subject during cold
water immersion. B: group results of CBFV of human middle cerebral artery
over 3 min in 8 healthy adult volunteers. Data for immersion in thermoneutral
water (35°C,
䊐), cold water (12°C, {), room air (24°C, ‚) with PET
CO
2
matched
to cold water immersion, and immersion in thermoneutral water (35°C,
E) with
PET
CO
2
matched to cold water immersion are shown prior to intervention and
at 1, 2, and 3 min after the intervention. Note that cold water immersion (
{)
results in a decrease in CBFV secondary to hyperventilation and consequent
hypocapnia. However, this level of CBFV is greater than that seen in thermo-
neutral water and room air once the level of CO
2
is matched (76).
Invited Review
2060 RESPIRATORY RESPONSES TO COLD WATER IMMERSION
J Appl Physiol • VOL 100 • JUNE 2006 • www.jap.org
by guest on July 3, 2013http://jap.physiology.org/Downloaded from
unexposed, side of the body (73). Little has been done to
identify the neural pathways associated with the habituation of
the initial respiratory response to cold water immersion. More
is known about the habituation of the heart rate response to
repeated cold exposure. Glaser and Griffin (25) reported that
small bilateral frontal lesions of the cerebral cortex in rats
prevented the habituation seen in heart rate following repeated
cold water immersion of their tails. However, such lesions only
abolished established habituation in 25% of the rats tested.
They concluded that the frontal areas of the cerebral cortex
were necessary for the achievement but not the maintenance of
habituation. After experiments in which the blood pressure and
heart rate responses of leukotomized and control subjects were
examined during repeated immersion of the hand in 4°C water,
Griffin (28) concluded that the frontal areas of the cortex are
also important for the establishment of habituation in man. The
habituation of blood pressure, heart rate, and subjective re-
sponses induced by repeated hand immersion in 4°C water can
be abolished by 75 mg of chlorpromazine taken orally. How-
ever, the wide-ranging postsynaptic antagonistic effects of this
drug do not help elucidate the precise pathways responsible for
habituation.
CARDIAC ARRHYTHMIAS ON COLD IMMERSION:
AN INTERACTION BETWEEN RESPIRATORY
AND CARDIAC REFLEXES?
Ectopic cardiac beats have been noted during the initial
stages of head-out cold water immersions even in healthy
normal or elite divers (62) and even in water as warm as 25°C
(20). Cardiac arrest is a rare but documented cause of death
when water enters the nostrils (39), indicating that the cardiac
component of the cold shock response may be a precursor to
sudden death on immersion and requires further investigation.
Wet- and dry-suited subjects submerged under cold-water
experience supraventricular arrhythmias during and after
breath holding (62, 72). The interpretation of the results of
these studies is complicated by subjects being submerged and
hence subject to trigeminal nerve stimulation of the face,
eliciting the diving response of bradycardia, apnea, and hypo-
tension (34). Secondly, the subjects wore protective clothing,
so the cold stimulus to the subjects’ skin was attenuated.
Thirdly, the study could not address the question as to whether
the cardiac arrhythmias observed were in some way related to
the act of breath hold and its release. Lastly, the study could
also not exclude the possibility that the arrhythmias seen were
the result of a hydrostatic squeeze on the body from immersion
per se resulting in an increase in venous return to the heart and
consequent cardiopulmonary reflex activation. To overcome
these confounding variables, we recently investigated two
groups of subjects wearing just swimming trunks undertaking
head-out immersion in stirred cold water 1) during and after
breath holding and 2) during free breathing (18). Under these
circumstances, subjects were not submerged and therefore
there was no complication from the diving reflex, and the
absence of protective clothing meant that all subjects were
exposed to an unattenuated cutaneous cold stimulus. Further-
more, both groups of subjects experienced the same hydrostatic
squeeze but only in the first group did breath holding occur.
A tachycardia was seen before immersion in both groups,
which was ascribed to an anxiety- and anticipatory-related
sympathetic overdrive; both groups were also subject to a
tachycardia during immersion ascribed to a continuation of that
sympathetic overdrive. However, cardiac arrhythmias (pre-
dominantly supraventricular and junctional) were seen in over
60% of the first group after release of breath holding but not in
the free breathing group. This compares with an incidence of
81% of the submersions of Tipton et al. (72); the greater
prevalence with submersion is probably due to the greater
vagal drive seen with face immersion and trigeminal nerve
stimulation.
We conclude that the cardiac arrhythmias are the result of
the interaction of release of breath holding in a cold milieu and
not ascribable to a hydrostatic effect on the subject. This is
confirmed by previous work from our laboratory on horizontal
immersion in cold water, where hydrostatic effects on the
subject were minimal, yet ECG arrhythmias are also seen at the
break of voluntary breath holding (M. Tipton, unpublished
observations). It is also notable that the arrhythmias were often
time linked to respiration; this was also observed by Tipton et
al. (72) and interpreted as suggesting that the arrhythmias were
in part due to a cyclical vagal stimulus to the heart. We
therefore propose that immersion into cold water results in
three distinct patterns of response: 1) face-only stimulation by
water, even when cold, leading to a diving-reflex mediated
bradycardia; 2) anticipation, anxiety, and cold cutaneous stim-
ulation leading to a sympathetic overdrive and tachycardia; and
3) release of breath holding in cold water, producing supraven-
tricular and junctional arrhythmias in 60% of head-out immer-
sions and ⬃80% of submersions when the vagal tone is raised
still further. An integrated model of the cardiorespiratory
response to cold shock incorporating these elements has been
developed (21).
POSSIBLE APPLICATIONS AND ASSOCIATIONS: SURVIVAL,
BIRTH, SLEEP, AND SUDDEN DEATH
The marked reduction in breath-hold time (i.e., volitional
apnea) with cold water immersion and submersion has obvious
implication for escape from within vessels, helicopters, and
vehicles that have accidentally sunk, as a well as immersion in
rough water. The volume of the inspiratory gasp and the
minute volumes resulting from the uncontrollable hyperventi-
lation (minute ventilation ⬎100 liters) that occurs on immer-
sion in cold water should be compared with the lethal volume
for sea water aspiration, 22 ml/kg or ⬃1.5 liters for a 70-kg
human (52). The observation of the high incidence of cardiac
arrhythmias following the release of breath hold has implica-
tions for snorkeling and breath-hold diving, as well as for
survival following near drowning.
In many countries, water birth has become commonplace.
For example in the United Kingdom, the UK Central Council
for Nursing has stated that assistance at water birth is part of a
midwife’s duties and not “special treatment” (13, 78). Each
midwife needs to be confident that she has skills to help women
give birth in water. For some time it has been thought that the
vagally mediated triad of responses to trigeminal nerve stim-
ulation (apnea, bradycardia, and selective vasoconstriction)
that constitute the oxygen conserving “diving response” (7, 34)
provides protection against drowning for babies during under-
water birth by conserving oxygen (61). However, it is known
that the response in neonatal animals is markedly diminished in
Invited Review
2061RESPIRATORY RESPONSES TO COLD WATER IMMERSION
J Appl Physiol • VOL 100 • JUNE 2006 • www.jap.org
by guest on July 3, 2013http://jap.physiology.org/Downloaded from
the presence of hypoxemia, as can occur with a difficult
delivery (27), and recently underwater birth has been linked to
neonatal distress and mortality as part of a near-drowning
scenario with radiological evidence consistent with lung aspi-
ration of birthing pool water (38, 24). Thus it appears that the
apnea associated with the diving response is insufficient in
newborn babies to ensure that water is not inhaled during
underwater delivery.
The presumed increased sympathetic drive with tachycardia
and subsequent arrhythmias seen after the break of the voli-
tional apnea during cold immersion is analogous to the cardiac
changes observed in obstructive sleep apnea. Obstructive sleep
apnea is a common condition in adults and has been associated
with arrhythmias. There is a peak in sudden death of cardiac
cause between midnight and 6 AM. The severity of sleep apnea
is proportional to the risk of sudden cardiac death (22). Fur-
thermore, atrial fibrillation, ventricular ectopics, and second-
degree heart block and even complete heart block requiring
intervention of a pacemaker have been seen (45). Many of
these arrhythmias occur after the period of apnea, reminiscent
of the cardiac arrhythmias seen after breath holding during cold
immersion. Use of microneurography in patients with sleep
apnea confirms that there is a significant sympathetic overac-
tivity in sleep apnea (53), which may be responsible for both
the hypertension and the cardiac arrhythmias seen in patients
with sleep apnea to a far greater degree than in weight-matched
obese control patients (54). That the sympathetic hyperactivity
normalizes with elimination of apnea and regularization of
breathing after continuous positive airway pressure therapy
lends credence to this hypothesis (54). There is thus emerging
a credible chain of evidence linking apnea and its release, a
sympathetic overdrive and the generation of potentially life-
threatening arrhythmias with an increased risk of sudden death.
Finally, on the topic of the potentially harmful interaction of
respiratory and cardiac responses, it is worth noting the link
between immersion, the cardiac disorder of long QT syndrome
(LQTS), and sudden death. Over 4,000 people between the age
of 1–22 yr suffer sudden unexplained death each year in the
United States. LQTS is a genetic disorder for which multiple
genes have been identified, all of which encode cardiac ion
channels. In LQTS there is abnormal ventricular repolarization
and increased risk of malignant ventricular tachyarrhythmias
(e.g., Torsades de pointes). Swimming appears to be a gene-
specific arrhythmogenic trigger for the LQT1 genotype of
LQTS (2). Ishikawa et al. (35) reported that 51 of 64 children
with known arrhythmias developed significant arrhythmias
while swimming or diving. LQTS cannot be identified post-
mortem without molecular diagnoses. This leads to the possi-
bility that some unexplained immersion deaths could have a
genetic basis.
It remains to be determined how swimming triggers the
degeneration of a stable rhythm, but swimming combines
exertion, voluntary apnea with accompanying oxygen desatu-
ration, possible cold exposure, and face immersion. As noted
above, the combination of the cessation of breath holding and
vagal stimulation can represent a potent arrhythmogenic stim-
ulus in some situations, notably when the sympathetic nervous
system is coincidentally stimulated. This combination of stim-
uli may also have a role in the arrhythmias seen in LQTS.
Yoshinaga et al. (81) have reported that, in children with a high
probability of sporadic LQTS, cold water face immersion
results in much longer QT intervals than those seen in control
children.
VENTILATORY RESPONSE TO COLD IMMERSION: DEEP
BODY COOLING
In the absence of shivering, which increases metabolic rate
and ventilation, patients with accidental hypothermia fre-
quently demonstrate respiratory depression that leads to carbon
dioxide retention and acidosis (49). Most slowing of breathing
occurs with cooling from normothermia to deep body temper-
ature of 32–34°C. This suggests that some aspect of respiratory
control is abnormal during hypothermia. This abnormality does
not appear to be associated with the mechanical properties of
the respiratory system, which do not change significantly in
hypothermia down to a temperature of 29°C (63). Respiratory
rate, tidal volume, and minute volume all fall during hypother-
mia (3, 10) in proportion to the reduction in metabolism (57).
Vital capacity is also reduced, probably, as already noted,
because of filling of the pulmonary capacitance vessels.
Slowing of breathing is seen at deep body temperatures
above the threshold for blunting of the ventilatory response to
hypercapnia (55) and results in carbon dioxide retention and
acidosis. This suggests that the metabolically linked slowing in
breathing frequency during mild hypothermia is due to alter-
ations in the brain stem neuronal systems for the generation of
eupneic breathing per se rather than any alteration in the
response to the chemoreceptive drive.
Rewarming studies in anesthetized cats who were made
hypothermic (23) have explored further the differences in
temperature thresholds for effects on breathing frequency and
volume; as core temperature rose, the increase in ventilation
occurs via an increase in respiratory volume until core temper-
ature exceeded 30°C, when increases in ventilation are due
purely to increases in respiratory frequency.
Whole body cooling produces central vagal inhibition; this
results in a bronchodilation that overrides the bronchoconstric-
tion effect of airway cooling (64). In hypothermic humans, the
transfer of carbon dioxide from the pulmonary capillaries is
normal, and the single most important potential cause of
hypercapnia is the reduction in the rate of alveolar ventilation.
That alveolar P
CO
2
can be low during hypothermia is due to the
fact that carbon dioxide production can be suppressed more
than alveolar ventilation (the carbon dioxide production of the
body is approximately halved by an 8°C fall in deep body
temperature). However, below a deep body temperature of
⬃32°C, decreased spontaneous respiratory activity, plus in-
creased solubility of carbon dioxide in the body fluids, can
result in respiratory acidosis and severe hypercapnia (14). The
respiratory failure of hypothermia can also result in hypoxia,
sometime profound, with arterial P
O
2
as low as 3.3 kPa (25
Torr) (56). The hypoxia can be compounded by the increased
oxygen demand associated with shivering. Although the pro-
vision of pure oxygen can assist in correcting the hypoxia, it
also removes the hypoxemic stimulus to breathe; this may be
the primary drive to breathe in those with severe hypothermia
and its removal can result in respiratory arrest (50).
In conclusion, cold water immersion represents a potent
stimulus to the respiratory system, one that can override both
conscious and other autonomic respiratory controls to act as a
precursor to drowning. The combination of the reestablishment
Invited Review
2062 RESPIRATORY RESPONSES TO COLD WATER IMMERSION
J Appl Physiol • VOL 100 • JUNE 2006 • www.jap.org
by guest on July 3, 2013http://jap.physiology.org/Downloaded from
of respiratory rhythm after breath holding, hypoxemia, and
coincident sympathetic nervous and vagal stimulation appears
to be the arrhythmogenic trigger for potentially hazardous
response in a range of conditions, including those seen during
submersion, birth, sleep, and sudden death. Immersion in cold
water is the most common scenario in which these factors
coexist. It is concluded that the respiratory responses seen on
immersion can represents a significant threat to life.
ACKNOWLEDGMENTS
Thanks to Vicky Parry for assistance with this manuscript.
REFERENCES
1. Abbadie C, Honere P, and Besson JM. Intense cold noxious stimulation
of the rat hindpaw induces c-fos expression in lumbar spinal cord neurons.
Neuroscience 59: 457– 468, 1994.
2. Ackerman MJ, Tester DJ, and Oirter CJ. Swimming, a gene-specific
arrhythmogenic trigger for inherited long QT syndrome. Mayo Clin Proc
74: 1088 –1094, 1999.
3. Altman PL and Dittmer DS (Eds.). Environmental Biology. Bethesda,
MD: Federation of American Societies for Experimental Biology, 1966, p.
4 –5.
4. Amini-Sereshki L and Zarridanst MR. Brain stem tonic inhibition of
thermoregulation in the rat. Am J Physiol Regul Integr Comp Physiol 247:
R154 –R159, 1984.
5. Anderson RN, Minino AM, Fingerhut LA, Warner M, and Heinen
MA. Deaths: Injuries, 2001. National Vital Statistics Reports, Centers for
Disease Control, vol. 52, no. 21, 2004.
6. Barwood M, Dalzell J, Datta A, Thelwell R, and Tipton MJ. The
influence of psychological training on breath-hold performance during
cold water immersion. In: Environmental Ergonomics XI, edited by
Holmer I, Kuklane K, and Gao C. Ystad, Sweden: Lund University, 2005,
p. 243–246.
7. Bert P. Lecons sur la physiologie comparee de la respiration. Paris:
Bailliere, 1870, p. 526 –553.
8. Brenner RA, Trumble AC, Smith GS, Kessler EP, and Overpeck MD.
Where children drown, United States, 1995. Pediatrics 108: 85– 89, 2001.
9. Bullitt E. Expression of c-fos-like protein as a marker for neuronal activity
following noxious stimulation in the rat. J Comp Neurol 296: 517–530,
1990.
10. Choukroun ML, Kays C, and Varene P. Effects of water temperature on
pulmonary volumes in immersed human subjects. Respir Physiol 75:
255–265, 1989.
11. Choukroun ML, Guenard H, and Varene P. Pulmonary capillary blood
volume during immersion in water at different temperatures. Undersea
Biomed Res 10: 331–342, 1983.
12. Choukroun ML and Varene P. Adjustments in oxygen transport during
head-out immersion in water at different temperatures. J Appl Physiol 68:
1475–1480, 1990.
13. Cluett ER, Nikodem VC, McCandlish RE, and Burns EE. Immersion
in water in pregnancy, labour and birth. Cochrane Database Syst Rev:
CD000111, 2004.
14. Cooper KE. Temperature regulation and its disorders. In: Recent Ad-
vances in Medicine (15th ed.), edited by Baron DN, Compston N, and
Dawson AM. London: Churchill, 1968, p. 333–350.
15. Cooper KE, Martin S, and Riben P. Respiratory and other responses in
subjects immersed in cold water. J Appl Physiol 40: 903–910, 1976.
16. Craig AB and Dvorak M. Expiratory reserve volume and vital capacity
of the lungs during immersion in water. J Appl Physiol 38: 5–9, 1975.
17. Dahlback GO, Jonsson E, and Liner MH. Influence of hydrostatic
compression of the chest and intrathoracic blood pooling on static lung
mechanics during head-out immersion. Undersea Biomed Res 5: 71– 85,
1978.
18. Datta A, Barwood M, and Tipton MJ. ECG arrhythmias following
breathhold during head-out cold water immersion: putative neural mech-
anisms and implications for sudden death on immersion. In: Environmen-
tal Ergonomics XI: edited by Holmer I, Kuklane K, and Gao C. Ystad,
Sweden: Lund University, 2005, p. 247–250.
19. Doyle CA and Hunt SP. A role for spinal lamina I neurokinin-1-positive
neurons in cold thermoreception in the rat. Neuroscience 91: 723–732,
1999.
20. Ferrigno M, Ferretti G, Ellis A, Warkander D, Costa M, Cerretelli P,
and Lundgren CE. Cardiovascular changes during deep breath-hold
dives in a pressure chamber. J Appl Physiol 83: 1282–1290, 1997.
21. Ferrigno M and Lundgren CE. Breath-hold diving. In: Bennett and
Elliott’s Physiology and Medicine of Diving (5th ed.), edited by Brubakk
AO and Neuman TS. New York: Elsevier Science, 2005, chapt. 5, p.
153–180.
22. Gami AS, Howard DE, Olson EJ, and Somers VK. Day-night pattern of
sudden death in obstructive sleep apnea. N Engl J Med 352: 1206–1214,
2005.
23. Gautier H and Gaudy JH. Ventilatory recovery from hypothermia in
anesthetized cats. Respir Physiol 64: 329 –337, 1986.
24. Gilbert R. Water birth—a near-drowning experience. Pediatrics 110: 409,
2002.
25. Glaser EM and Griffin JP. Influence of the cerebral cortex on habitua-
tion. J Physiol 160: 429 – 445, 1962.
26. Goode RC, Duffin J, Miller R, Romet TT, Chant W, and Ackles A.
Sudden cold water immersion. Respir Physiol 23: 301–310, 1975.
27. Goodlin RC. Fetal cardiovascular responses to distress. A review. Obstet
Gynecol 49: 371–381, 1977.
28. Griffin JP. The role of the frontal areas of the cortex upon habituation in
man. Clin Sci 24: 127–134, 1963.
29. Hardy J, Gammage K, and Hall C. A descriptive study of athlete
self-talk. Sports Psychol 15: 306 –318, 2001.
30. Harver A and Lorig TS. Handbook of Psychophysiology (2nd ed.), edited
by Cacioppo JT, Tassinary LG, and Bertson GG. Cambridge, UK: Cam-
bridge University Press, 2000, chapt. 10, p. 265–293.
31. Hayward JS and French CD. Hyperventilation response to cold water
immersion: reduction by staged entry. Aviat Space Environ Med 60:
1163–1165, 1989.
32. Hinckel P and Schroder-Rosenstock K. Responses of pontine units to
skin-temperature changes in the guinea-pig. J Physiol 314: 189–194,
1981.
33. Hunt SP, Pina A, and Evan G. Induction of c-fos-like protein in spinal
cord neurons following sensory stimulation. Nature 328: 632–634, 1987.
34. Irving L. Comparative anatomy and physiology of gas transport mecha-
nisms. In: Handbook of Physiology, Respiration. Bethesda, MD: Am.
Physiol. Soc., 1964, sect. 3, vol. 1, chapt. 5, p. 177–212.
35. Ishikawa H, Matsushima M, Nagashima M, and Osuga A. Screening of
children with arrhythmias for arrhythmia development during diving and
swimming—face immersion as a substitute for diving and exercise stress
testing as a substitute for swimming. Jpn Circ J 56: 881–990, 1992.
36. Isom GE and Elshowihy RM. Interaction of acute and chronic stress with
respiration: modification by naloxone. Pharmacol Biochem Behav 16:
599 –603, 1982.
37. Jarrett AS. Effect of immersion on intrapulmonary pressure. J Appl
Physiol 20: 1261–1266, 1965.
38. Kassim Z, Sellars M, and Greenough A. Underwater birth and neonatal
respiratory distress. BMJ 330: 1071–1072, 2005.
39. Keatinge WR. Survival in cold water. Oxford, UK: Blackwell Scientific,
1969.
40. Keatinge WR and Evans M. The respiratory and cardiovascular response
to immersion in cold and warm water. Q J Exp Physiol 46: 83–94, 1961.
41. Keatinge WR and McCance RA. Increase in venous and arterial pressure
during sudden exposure to cold. Lancet ii: 123–138, 1957.
42. Keatinge WR, McIlroy MB, and Goldfien A. Cardiovascular responses
to ice-cold showers. J Appl Physiol 19: 1145–1150, 1964.
43. Keatinge WR and Nadel JA. Immediate respiratory response to sudden
cooling of the skin. J Appl Physiol 20: 65– 69, 1965.
44. Kendall G, Hrycaiko D, Martin G, and Kendall T. The effects of an
imagery rehearsal, relaxation, and self-talk package on basketball game
performance. J Sport Exerc Physiol 12: 157–166, 1990.
45. Koehler U, Fus E, Grimm W, Pankow W, Schafer H, Stammnitz A,
and Peter JH. Heart block in patients with obstructive sleep apnoea:
pathogenetic factors and effects of treatment. Eur Respir J 11: 434 – 439,
1998.
46. Locke EA and Latham GP. The application of goal setting to sports.
J Sport Exerc Physiol 7: 205–222, 1985.
47. Lumsden T. Observations on the respiratory centers in the cat. J Physiol
57: 153–160, 1923.
48. Lumsden T. Effects of bulbar anaemia on respiratory movements.
J Physiol 59: 1vii–1x, 1924.
49. McNicol MW. Respiratory failure and acid-base status in hypothermia.
Postgrad Med J 43: 674 – 676, 1967.
Invited Review
2063RESPIRATORY RESPONSES TO COLD WATER IMMERSION
J Appl Physiol • VOL 100 • JUNE 2006 • www.jap.org
by guest on July 3, 2013http://jap.physiology.org/Downloaded from
50. McNicol MW and Smith R. Accidental hypothermia. Br Med J i: 19–21,
1964.
51. Mekjavic IB and Bligh J. The increased oxygen uptake upon immersion.
Eur J Appl Physiol 58: 556 –562, 1989.
52. Modell JH. Pathophysiology and Treatment of Drowning. Springfield, IL:
Thomas, 1971.
53. Narkiewicz K, Kato M, Phillips BG, Pesek CA, Davison DE, and
Somers VK. Nocturnal continuous positive airway pressure decreases
daytime sympathetic traffic in obstructive sleep apnea. Circulation 100:
2332–2335, 1999.
54. Narkiewicz K and Somers VK. Sympathetic nerve activity in obstructive
sleep apnoea. Acta Physiol Scand 177: 385–390, 2003.
55. Natsui T. Respiratory response to hypoxia with hypocapnia or normocap-
nia and to CO
2
in hythermic dogs. Respir Physiol 7: 188 –202, 1969.
56. Nicolas F, Nicolas G, Heurtel A, Baron D, Rodineau P, and Lajartre
AY. Vingt-quatre observations d’hypothermies accidentelles. Anesth
Analg 31: 485–538, 1974.
57. Osbourne S and Milson WK. Ventilation is coupled to metabolic
demands during progressive hypothermia in rodents. Respir Physiol l92:
305–318. 1993.
58. Patrick DT and Hrycaiko DW. Effects of a mental training package on
an endurance performance. Sports Psychol 12: 283–299, 1998.
59. Peden M, McGee K, and Sharma K. The Injury Chart Book: A
Graphical Overview of the Global Burden of Injuries. Geneva: World
Health Organisation, 2002.
60. Present P. Child Drowning Study. A Report on the Epidemiology of
Drowning in Residential Pools to Children Under Age 5. Washington, DC:
US Consumer Product Safety Commission, 1987.
61. Reis DJ, Golanov EV, Galea E, and Feinstein DL. Central neurogenic
neuroprotection: central neural systems that protect the brain from hypoxia
and ischemia. Ann NY Acad Sci 835: 168 –186, 1997.
62. Scholander PF, Hammel HT, LeMessurier H, Hemmingsen E, and
Garey W. Circulatory adjustments in pearl divers. J Appl Physiol 17:
184 –190, 1962.
63. Sechzer PH. Effect of hypothermia on compliance and resistance of the
lung-thorax system of anesthetized man. J Appl Physiol 13: 53–56, 1958.
64. Severinghaus JW. Respiration and hypothermia. Ann NY Acad Sci 80:
384 –394, 1959.
65. St John WM, Bledsoe TA, and Sokol HW. Identification of medullary
loci critical for neurogenesis of gasping. J Appl Physiol 59: 1008–1019,
1984.
66. St John WM. Neurogenesis, control, and functional significance of
gasping. J Appl Physiol 68: 1305–1315, 1990.
67. Strassman AM, Vos BP, Mineta Y, Naderi S, Borsook D, and Burstein
R. Fos-like immunoreactivity in the superficial medullary dorsal horn
induced by noxious and innocuous thermal stimulation of facial skin in the
rat. J Neurophysiol 70: 1811–1821, 1993.
68. Suess WM, Alexander AB, Smith DD, Sweeney HW, and Marion RJ.
The effects of psychological stress on respiration: a preliminary study of
anxiety and hyperventilation. Psychophysiology 17: 535–540, 1980.
69. Taylor NA and Morrison JB. Static and dynamic pulmonary compliance
during upright immersion. Acta Physiol Scand 149: 413– 417, 1993.
70. Tipton MJ. The initial responses to cold-water immersion in man. Clin
Sci (Lond) 77: 581–588, 1989.
71. Tipton MJ, Stubbs DA, and Elliott DH. Human initial responses to
immersion in cold water at three temperatures and after hyperventilation.
J Appl Physiol 70: 317–322, 1991.
72. Tipton MJ, Kelleher PC, and Golden FStC. Supraventricular arrhyth-
mias following breath-hold submersions in cold water. Undersea Hyperb
Med 21: 305–313, 1994.
73. Tipton MJ, Eglin CM, and Golden FStC. Habituation of the initial
responses to cold water immersion in humans: a central or peripheral
mechanism? J Physiol 512: 621– 628, 1998.
74. Tipton MJ, Golden FStC, Mekjavic IB, and Franks CM. Temperature
dependence of habituation of the initial responses to cold water immer-
sion. Eur J Appl Physiol 78: 253–257, 1998.
75. Tipton MJ, Mekjavic IB, and Eglin CM. Permanence of the habituation
of the initial responses to cold-water immersion. Eur J Appl Physiol 83:
17–21, 2000.
76. Tipton M, Hetherington M, House CM, and Golden FStC. Cerebral
blood flow in man during cold immersion. In: Proceedings of Environ-
mental Ergonomics IX, edited by Werner J and Hexamer M. Aachen:
Springer Verlag, 2000.
77. Todd AJ, Spike RC, Young S, and Puskar Z. Fos induction in lamina
I projection neurons in response to noxious thermal stimuli. Neuroscience
131: 209 –217, 2005.
78. United Kingdom Central Council for Nursing, Midwifery, and Health
Visiting (UKCC). Position statement on water births. London, UK:
United Kingdom Central Council for Nursing, Midwifery, and Health
Visiting, 1994.
79. World Health Organisation. Atlas of Mortality in Europe. Geneva:
World Health Organisation, 1997.
80. Winters PM, McCabe PM, Green EJ, and Schneiderman N. Stress
responses, coping, and cardiovascular neurobiology: central nervous sys-
tem circuitry underlying learned and unlearned affective responses to
stressful stimuli. In: Stress, Coping and Cardiovascular Disease, edited by
McCade PM, Schneiderman N, Field T, and Wellens R. Mahwah, NJ:
Erlbaum, 2000, p. 1– 49.
81. Yoshinaga M, Kamimura J, Fukushige T, Kusubae R, Shimago A,
Nishi J, Kono Y, Nomura Y, and Miyata K. Face immersion in cold
water induces prolongation of the QT interval and T-wave changes in
children with nonfamilial long QT syndrome. Am J Cardiol 83: 1494–
1497, 1999.
Invited Review
2064 RESPIRATORY RESPONSES TO COLD WATER IMMERSION
J Appl Physiol • VOL 100 • JUNE 2006 • www.jap.org
by guest on July 3, 2013http://jap.physiology.org/Downloaded from
