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1Critical Care Group – Portex
Unit, Institute of Child Health,
University College London,
London, UK
2 APHP, Service de
Réanimation et Surveillance
Continue Pédiatriques, Hôpital
Robert Debré et Université
Paris-Diderot Paris VII,
Paris, France
Correspondence to
Dr Peter Jones, Critical Care
Group – Portex Unit, Institute
of Child Health, University
College London, 30 Guilford
Street, London WC1N 1EH, UK
peter.jones@rdb.aphp.fr
Accepted 8 April 2011
Published Online First
28 May 2011
Arch Dis Child 2012;97:139–144. doi:10.1136/adc.2010.210518
Bradycardia during critical care intubation:
mechanisms, significance and atropine
Peter Jones,1 Stéphane Dauger,2 Mark J Peters1
ABSTRACT
Bradycardia occurs during the intubation of some
critically ill children as a result of vagal stimulation
due to hypoxia and/or laryngeal stimulation; such
‘stable’ bradycardia is accompanied by selective
vasoconstriction. Some induction drugs also
induce bradycardia which may be accompanied
by vasodilatation which is also a feature of certain
pathologies, which influence the progression to
‘unstable’ bradycardia, which does not respond
to re-oxygenation and a pause in laryngoscopy.
Preintubation atropine diminishes the overall incidence
of stable bradycardia during routine anaesthesia.
However, clinical studies of critical care intubation
show that atropine does not prevent all episodes of
bradycardia and specifically cannot affect vasodilatation.
As such, there is insufficient evidence to support a
recommendation for the indiscriminate use of atropine
for intubation during critical care illness, including
simple neonatal respiratory distress. Atropine is
appropriate during septic or late stage hypovolaemic
shock where abnormal vasomotor tone and bradycardia
may potentially set up a negative feedback loop of
cardiac hypo-oxygenation and hypoperfusion and during
premedication when using suxamethonium.
INTRODUCTION
The majority of bradycardias occurring during
intubation, whether in routine anaesthesia or
in the critical care setting, are benign. Probably
the most frequent cause is activation of the vagal
afferent-efferent ‘reflex’ loop, either by hypoxia1
and/or laryngoscopy. 2 – 4 Such bradycardias can be
described as ‘stable’ because they can be corrected
by a pause in laryngoscopy and re-oxygenation.
In the 1950s the use of ‘vagolytic’ atropine, as part
of induction premedication, was proposed to limit
bradycardia, which was often associated with the
use of suxamethonium or other relatively car-
diotoxic inhalation anaesthetic agents, such as
halothane. 5 The subsequent transition away from
suxamethonium to less toxic drugs, such as sevo-
flurane and non-depolarising muscle relaxants,
led anaesthetists to question the continued use-
fulness of atropine.6 – 9 Today, the use of atropine
has been almost entirely abandoned for routine
paediatric premedication.10
In critical care settings bradycardias do not
always respond to a pause in laryngoscopy and
re-oxygenation because they are ‘unstable’. They
often require epinephrine and are associated with
severe haemodynamic disturbance and progres-
sion to the slow, terminal rhythm that is most
frequently observed in dying children.11 12 Adult
studies of intubation in critical care settings have
Review
What is already known on this topic
▶ Vagally mediated bradycardia can occur during
critical care intubation and is accompanied
by selective vasoconstriction to conserve
perfusion in vital organs.
▶ Induction drugs may induce bradycardia and/
or vasodilatation which may also be a feature
of some pathologies, such as septic and late
hypovolaemic shock.
▶ Atropine diminishes bradycardia but has no
effect on vasodilatation.
What this study adds
▶ The transformation from stable (responding
to re-oxygenation and a pause in laryngos-
copy) to unstable (associated with haemody-
namic instability) bradycardia is mediated by
vasodilatation.
▶ Atropine is unnecessary for non-infectious
pathologies, including the majority of neonatal
intubations, if judicious oxygenation and intu-
bation technique are used.
▶ Atropine should be used in the presence of
vasodilatation and with suxamethonium.
described up to 3% mortality, with hypotension
being an important associated risk factor.13 –15 In
contrast, the limited number of paediatric stud-
ies have restricted themselves to describing the
frequency of bradycardia without associating a
clinical outcome.16 –18 As such we do not know
the frequency of paediatric mortality, and its
associated risk factors, during critical care intu-
bation. In recent years atropine has been recom-
mended for use during critical care intubations
in neonates,19 –21 children under 5 years of age22
and for children in septic shock. 23 The intention
is not necessarily to diminish the frequency of
stable bradycardia but to prevent progression to
unstable bradycardia. These recommendations
have appeared without evidence in critically
ill children undergoing intubation. It remains
unknown if atropine influences progression to
unstable bradycardia.
We discuss the mechanisms and significance of
bradycardia during critical care intubation and the
factors that influence the progression from stable
to unstable bradycardia before giving our recom-
mendations for the use, or not, of atropine.
139
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Review

MECHANISMS OF BRADYCARDIA
Reflex bradycardia: hypoxia
There are two sources of vagal ‘reflex’ bradycardia during intu-
bation. The fi rst occurs when the aortic body senses lowered
oxygen tension, and transmits via an afferent branch of the
vagus nerve to the medulla oblongata which in turn uses an
efferent branch of the vagus to lower heart rate by the secre-
tion of acetylcholine on muscarinic receptors in the sino-atrial
node (see figure 1). The resulting bradycardia is ‘compensated’
by the selective vasoconstriction of non-vital organs. 24 –28 The
overall effect is one of redistribution of blood flow to maintain
availability of oxygen to the brain and other vital organs while
generally reducing consumption.
Reflex bradycardia probably developed as a survival mecha-
nism by early aquatic organisms who needed to cope with cur-
rents of hypo-oxygenated water. Later in evolution the same
reflex bradycardia protected fi sh from oxygen deprivation dur-
ing the temporary collapse of their gills during terrestrial explo-
ration. 28 Reflex bradycardia is strongly conserved in evolution
and persists in crabs, 29 trout 30 and carp, 31 and is enhanced to
deal with a return to water by amphibious and diving animals
such as frogs, 32 turtles, 33 ducks34 35 and elephant seals, 36 and
in armadillos experimentally covered in soil. 37 Interestingly
we fi nd the same reflex again exploited by certain mammals to
adapt circulatory and metabolic needs during the early euther-
mic stage of hibernation. 38
The capacity to induce reflex bradycardia is retained by ter-
restrial mammals39 including human children1 and adults,40 41
probably as an evolutionary vestige. Prior to birth and during the
first 3–6 months of life humans possess an autonomic imbalance
due to the dense vagal innervation of the sino-atrial node and
poor sympathetic innervation of the ventricles and conduc-
tion bundles.42 This disequilibrium allows the fetus to mount
a defence against hypo-oxygenation due to placental hypoper-
fusion which accompanies contractions during birth. A further
manifestation of this is the higher frequency of reflex bradycar-
dia in the young during routine anaesthetic intubation.43
Reflex bradycardia: laryngoscopy
The second source of reflex bradycardia during intubation is
the manipulation of the laryngopharynx. During laryngos-
copy, 2 – 4 bronchoscopy,44 insertion of a gastric catheter45 or
during oesophagogastroduodenoscopy,46 mechanical stimula-
tion of the laryngopharynx provokes efferent vagal nerves in
the laryngopharynx. The number of attempts at intubation47
and speed of gastric catheter insertion,45 which are both indi-
rect measures of vigour of laryngopharyngeal stimulation, are
associated with more frequent bradycardia (figure 1).
Drug induced bradycardia
Induction drugs can induce bradycardia due to their capacity to
alter autonomic balance and/or by direct effects on the heart.
The important difference between drug-induced bradycardia
and reflex bradycardia is the maintenance of preload by vaso-
constriction which preserves ventricular fi lling25 48 (figure 1).
‘Vagomimetic’ bradycardia, which can be so severe as
to provoke asystole, is probably the most important drug-
induced bradycardia and is a well-known complication of
suxamethonium. 5 49 Conversely, the use of non-depolarising

Pathology

Intubation

Hypoxaemia Mechanical
stimulation Induction drugs

Blocked by atropine Diminished by atropine

Reflex Drug induced

Vasoconstriction Vasodilatation
bradycardia bradycardia

Observed
bradycardia

Reduces risk Increases risk

Severe
haemodynamic
disturbance

Figure 1 Intubation can activate reflex bradycardia which is accompanied by vasoconstriction, which tends to negate the effects of bradycardia
on the progression to severe haemodynamic disturbance, whereas certain pathologies and drug-induced vasodilatation tend to favour the
progression to haemodynamic disturbance.

140 Arch Dis Child 2012;97:139–144. doi:10.1136/adc.2010.210518

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muscle relaxants, such as vecuronium, and rocuronium has
been shown to have a tendency to attenuate oculocardiac
vagal reflex bradycardia. 50 During anaesthetic use of propofol,
a 12% frequency of bradycardia has been noted in children
aged less than 4. 51 Fast acting morphine-like sedation agents
such as sufentanyl, and particularly remifentanil, can also
induce bradycardia in both adults 52 and children. 53 Thiopental
does not have an effect on heart rate, 54 although it should be
noted that both thiopental and propofol have negative iono-
tropic properties. 51 54 Contractility may also be reduced when
using ketamine. 55
Those induction anaesthetics which have no effects on heart
rate include ketamine in experimental situations 56 and eto-
midate, whose use in the emergency department setting has
been shown to increase heart rate in children by 10 beats/min,
although this may be due to an insufficient analgesic effect. 57
Even if induction drugs do not provoke bradycardia, they can
have important effects on the circulation by inducing vasodi-
latation as is the case for propofol, 58 59 thiopental 58 60 and for
the opiates morphine,61 sufentanyl62 and remifentanil.63
THE SIGNIFICANCE OF BRADYCARDIA
There is no consensus on the defi nition of bradycardia prior
to intubation. During routine anaesthesia, heart rates can
be compared reliably to the normal for age. However, what
constitutes the defi nition of ‘normal’ or ‘abnormal’ heart rate
before and during emergency intubation is a more complex
issue because of the influence of the state of the vasculature,
myocardial force and metabolic needs, which are themselves
influenced by pathology. A good example would be that of a
sick child with tachycardia of 200 beats/min who experiences
a reduction to an age-related ‘normal’ heart rate of 100 beats/
min during intubation but cannot be considered to have a nor-
mal heart rate.
Many arbitrary defi nitions of bradycardia during intuba-
tion have been proposed. These are most frequently based
on an absolute change in heart rate,64 – 66 but any bradycardic
event,43 67 a fall below 2 SDs of the mean heart rate for age,17
three or more beats at <60 beats/min, 68 69 at <100 beats/
min 69 70 or percentage reductions in base rate such as 20%8
or 25%,18 have also been proposed. Such non-agreement over
any defi nition of what constitutes bradycardia during intu-
bation inevitably obscures the true frequency of the event.
Carroll et al16 recently looked at a retrospective cohort of emer-
gency intubations using yet another defi nition of bradycardia
(<80 beats/min for children <2 years of age or <60 beats/min
for children ≥2 years of age) and found a frequency of 10%
for emergency intubation. The most obvious reason for this
extraordinary lack of consensus is that none of the above
authors have tried to link their particular defi nition to a spe-
cific clinical outcome. Sing et al18 considered that a fall of 25%
from baseline was a “haemodynamically significant event”
without any justification or the establishment of a relation-
ship with a defi ned clinical outcome.
Tolerance of bradycardia is very much affected by the pres-
ence or absence of vasoconstriction. Other mechanisms which
can be found in animals, and maybe present in humans,
include postbradycardia tachycardia, 71 which plays a role in
metabolite washout, 72 tolerance of metabolic acidosis by buff-
ering73 and cellular hypometabolism to varying degrees.74
These adaptive mechanisms are also influenced by the pres-
ence of certain pathologies.
Vasoconstriction is influenced by the presence of cer-
tain pathologies which potentially play a pivotal role in the
Arch Dis Child 2012;97:139–144. doi:10.1136/adc.2010.210518
Review
conversion from stable to unstable bradycardia and general
haemodynamic disturbance (figure 1). The vasoplegia that is
associated with septic shock has an influence on the capac-
ity of the vascular bed to maintain preload which deter-
mines myocardial fibre stretching and thus ejection volume.75
Vasoplegia also accompanies the late ‘decompensated’ phase
of hypovolaemic shock.76
Isolated cerebral hypoperfusion is an important clinical out-
come to consider. In states of raised intracranial pressure (ICP)
a reduction in perfusion pressure can be translated directly into
a decrease in brain perfusion pressure77 which represents an
important risk for secondary ischaemia after cranial trauma.78
Another special group is that of preterm infants who are sus-
ceptible to absent cerebral end diastolic flow during sponta-
neous ‘central’ bradycardia 79 with reductions in overall flow
of as much as 80%.80 The hypothesis that cerebral perfusion
is diminished during bradycardia is contradicted by a study
by Marshall et al3 of 10 premature infants which recorded
a significant rise in systemic blood pressure despite a fall in
heart rate. The rise in blood pressure was probably due to pain
related to ineffective sedation and/or as a manifestation of the
vasoconstrictive component of reflex bradycardia.
CLINICAL STUDIES AND SIDE EFFECTS OF ATROPINE
Atropine is a non-specific antagonist of acetylcholine on mus-
carinic receptors and prevents reflex bradycardia by inhibit-
ing vagal activation of the sino-atrial node. Atropine can also
relieve vagal tone which diminishes drug-induced bradycar-
dia. Atropine has a proven efficacy of reducing falls in heart
rate in prospective ECG studies during routine anaesthesia
of infants,81 small82 and older children and adolescents.8 68
In critical care settings a similar trend has been repeated in
neonates69 83 and in one retrospective out-of-hospital study.18
However, another retrospective study of children in an emer-
gency department showed a 4% rate of bradycardia with or
without atropine.17
The trend of atropine reducing falls in heart rate in ECG
studies has been reproduced when looking at the cardiac index
during routine anaesthesia using halothane maintenance 65
and immediately after induction intubation with halothane, 65
thiopentone/suxamethonium 54 and sevofluorane/remifenta-
nil.64 A recent study in adults shows a fall in blood pressure
during propofol anaesthesia due to vasodilatation despite atro-
pine use, notwithstanding conservation of the heart rate. 59 It
is important to bear in mind that there are no similar studies
in intensive care to determine if atropine maintains perfusion
during intubation where cardiac output and vascular resistance
are already compromised.
Cardiac side effects of atropine at normal doses (10–20 μg/kg
intravenous) in anaesthetic studies are benign in the nor-
mal heart and are generally limited to sinus tachycardia.
Nevertheless, sinus tachycardia due to atropine increases oxy-
gen consumption84 and reduces ventricular fi lling and left ven-
tricular end diastolic pressure in normal dogs,85 both of which
are potentially important in a critical care setting. In an abnor-
mal heart there is one case report which describes a 9-year-old
girl who had previously identified spontaneously occurring
bigeminism that converted to ventricular tachycardia after
administration of atropine.86
In a normal heart atropine has been shown to be a safe drug.
During the First Gulf War at least 240 children in Israel were
injected with adult dose ‘automatic atropine injector’ organo-
phosporous nerve agent antidotes but no fatalities resulted.87
Accidental or intentional poisoning by naturally occurring
141
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Review
anticholinergic molecules occurs regularly and cardiac toxic-
ity beyond sinus tachycardia is not a feature.88 – 91 Similarly,
the absence of cardiac toxicity in three children who received
more than a thousand times the normal dose illustrates just
how safe atropine can be in a normal child.92
Non-cardiac, or ‘peripheral’, side effects in normal children
are well documented and include dilated pupils, dry hands and
mouth93 and pro-hyperthermia.94 At least one paper has reported
a fatal association with atropine poisoning, probably related to
fever.95 Other side effects include reduced micturation,90 96 the
relaxation of the oesophageal sphincter 97 98 and a reduction
in gastric and colonic motility.99 ‘Central anticholinergic syn-
drome’ occurs more frequently in adults than children, with
lethargy or excitatory behaviour, hallucinations, coma92 and
pro-convulsant activity100 being described.
DISCUSSION
The majority of intubations where atropine has been given as
premedication fall into two categories: those where no bra-
dycardia would have occurred and those where stable brady-
cardia would have taken place. Indeed, the concept of using
bradycardia to assess the outcome of intubation leads us to
overlook not only the importance of the vasoconstrictive com-
ponent of vagal activation in maintaining the perfusion pres-
sure of vital organs but also the vasodilatation of certain drugs
and pathologies that can destabilise the circulation (figure 1).
If the intubation is being performed using induction drugs
for a pathology where neither is associated with vasodilata-
tion, the bradycardia observed is likely to be vagal in origin
(figure 1). Under such circumstances it is accompanied by
vasoconstriction which maintains organ perfusion, and will
respond to simple re-oxygenation and a pause in laryngos-
copy, so it is not justifiable to pretreat with atropine even if the
efficacy of atropine in reducing the frequency of reflex vagal
activation is not in question. Reflex bradycardia will not prog-
ress from stable to unstable unless there is excessive use of the
laryngoscope and/or desaturation.
Relatively few pathologies are associated with vasodilata-
tion, the most conspicuous being septic shock, and relatively
few drugs induce important levels of vasodilatation. Atropine
can also diminish drug-induced bradycardia but importantly
will not have any effect on vasodilatation as a consequence of
pathology or drugs (figure 1). W here atropine use is judicious is
in the context of vasodilatation. Under such circumstances, it
is rational to prevent or diminish reflex bradycardia that could
indirectly influence progression to unstable bradycardia by
inducing a negative feedback loop of cardiac hypoxaemia and/
or hypoperfusion. Suxamethonium is an important exception
because even in the absence of vasodilatation it can induce
severe bradycardia or asystole independently of pathology or
concomitant use of drugs.
We know that the side effect profi le of atropine is benign
in normal children, but for children with critical care ill-
nesses we have very little information. In particular, the
pro-hyperthermic effects of atropine should not be underes-
timated. As such, where vascular reactivity is not jeopardised
by pathology or drugs, the benefits of atropine are probably
outweighed by the potential risks. Most neonatal respiratory
distress, ear, nose and throat (ENT) pathologies and non-
infectious non-neonatal respiratory pathologies fall outside
of the category requiring atropine if suxamethonium is not
used for induction. Special cases of raised ICP and extremely
premature babies may warrant particular consideration for
their enhanced risks of neurological sequelae. The possibility
142
that atropine can confound pupillary assessment should be
considered in cases where raised ICP may be an issue.
We need to progress away from seeing fluctuations in the
heart rate during intubation as being significant. Stable brady-
cardia does not inevitably evolve to unstable bradycardia and
is not associated with severe haemodynamic disturbance, cere-
bral hypoperfusion and neurological sequelae and death. The
challenge for future research is to move away from using the
outcome of bradycardia per se as a measure of successful criti-
cal care intubation towards using other clinical indicators.
CONCLUSION
The indiscriminate use of atropine during emergency intuba-
tion is not justified because clinical studies have focused on
altered heart rate and not the progression from stable to unsta-
ble bradycardia or other clinical outcomes. Indirect evidence
leads the authors to recommend the use of atropine during
septic and late hypovolaemic shock, when using suxametho-
nium. Children with non-infectious respiratory pathologies
(which includes the majority of neonatal intubations), ENT or
non-raised intracranial neurological pathologies do not neces-
sarily need atropine during intubation if judicious oxygenation
and careful intubation techniques are assured. The direction
of future research needs to focus on the relationship between
bradycardia and clinical outcomes rather than variation in
physiological parameters.
Atropine should be used when intubating in the presence
of vasodilatation from septic or late hypovolaemic shock and
when using suxamethonium.
Competing interests None.
Provenance and peer review Not commissioned; externally peer reviewed.
REFERENCES
1. Wennergren G, Hertzberg T, Milerad J, et al. Hypoxia reinforces laryngeal reflex
bradycardia in infants. Acta Paediatr Scand 1989;78:11–17.
2. Sutera PT, Smith CE. Asystole during direct laryngoscopy and tracheal
intubation. J Cardiothorac Vasc Anesth 1994;8:79 – 80.
3. Marshall TA, Deeder R, Pai S, et al. Physiologic changes associated with
endotracheal intubation in preterm infants. Crit Care Med 1984;12:501– 3.
4. Doyle DJ, Mark PW. Laparoscopy and vagal arrest. Anaesthesia 1989;44:448.
5. Leigh MD, McCoy DD, Belton MK, et al. Bradycardia following intravenous
administration of succinylcholine chloride to infants and children. Anesthesiology
1957;18:698 –702.
6. Blanc VF. Atropine and succinylcholine: beliefs and controversies in paediatric
anaesthesia. Can J Anaesth 1995;42:1–7.
7. Guyton DC, Scharf SM. Should atropine be routine in children? Can J Anaesth
1996;43:754 – 5.
8. McAuliffe G, Bissonnette B, Boutin C. Should the routine use of atropine before
succinylcholine in children be reconsidered? Can J Anaesth 1995;42:724 – 9.
9. Jöhr M. Is it time to question the routine use of anticholinergic agents in
paediatric anaesthesia? Paediatr Anaesth 1999;9:99 –101.
10. Parnis SJ, van der Walt JH. A national survey of atropine use by Australian
anaesthetists. Anaesth Intensive Care 1994;22:61– 5.
11. Samson RA, Nadkarni VM, Meaney PA, et al.; American Heart Association
National Registry of CPR Investigators. Outcomes of in-hospital ventricular
fibrillation in children. N Engl J Med 2006;354:2328 – 39.
12. Walsh CK, Krongrad E. Terminal cardiac electrical activity in pediatric patients.
Am J Cardiol 1983;51:557– 61.
13. Schwartz DE, Matthay MA, Cohen NH. Death and other complications of
emergency airway management in critically ill adults. A prospective investigation
of 297 tracheal intubations. Anesthesiology 1995;82:367–76.
14. Jaber S, Amraoui J, Lefrant JY, et al. Clinical practice and risk factors for
immediate complications of endotracheal intubation in the intensive care unit: a
prospective, multiple-center study. Crit Care Med 2006;34:2355 – 61.
15. Griesdale DE, Bosma TL, Kurth T, et al. Complications of endotracheal intubation
in the critically ill. Intensive Care Med 2008;34:1835 – 42.
16. Carroll CL, Spinella PC, Corsi JM, et al. Emergent endotracheal intubations
in children: be careful if it’s late when you intubate. Pediatr Crit Care Med
2010;11:343 – 8.
Arch Dis Child 2012;97:139–144. doi:10.1136/adc.2010.210518
 Downloaded from http://adc.bmj.com/ on February 5, 2015 - Published by group.bmj.com
17. Fastle RK, Roback MG. Pediatric rapid sequence intubation: incidence of reflex
bradycardia and effects of pretreatment with atropine. Pediatr Emerg Care
2004;20:651– 5.
18. Sing RF, Reilly PM, Rotondo MF, et al. Out-of-hospital rapid-sequence induction
for intubation of the pediatric patient. Acad Emerg Med 1996;3:41– 5.
19. Kelleher J, Mallya P, Wyllie J. Premedication before intubation in UK neonatal
units: a decade of change? Arch Dis Child Fetal Neonatal Ed 2009;94:F332– 5.
20. Wyllie JP. Neonatal endotracheal intubation. Arch Dis Child Educ Pract Ed
2008;93:44 – 9.
21. Chaudhary R, Chonat S, Gowda H, et al. Use of premedication for intubation in
tertiary neonatal units in the United Kingdom. Paediatr Anaesth 2009;19:653 – 8.
22. Bledsoe GH, Schexnayder SM. Pediatric rapid sequence intubation: a review.
Pediatr Emerg Care 2004;20:339 – 44.
23. Brierley J, Carcillo JA, Choong K, et al. Clinical practice parameters
for hemodynamic support of pediatric and neonatal septic shock: 2007
update from the American College of Critical Care Medicine. Crit Care Med
2009;37:666 – 88.
24. Pendergast DR, Lundgren CE. The physiology and pathophysiology of the
hyperbaric and diving environments. J Appl Physiol 2009;106:274 – 5.
25. Joulia F, Lemaitre F, Fontanari P, et al. Circulatory effects of apnoea in elite
breath-hold divers. Acta Physiol (Oxf) 2009;197:75 – 82.
26. Blix AS, Gautvik EL, Refsum H. Aspects of the relative roles of peripheral
vasoconstriction and vagal bradycardia in the establishment of the ‘diving reflex’
in ducks. Acta Physiol Scand 1974;90:289 – 96.
27. Blix AS, Wennergren G, Folkow B. Cardiac receptors in ducks – a link between
vasoconstruction and bradycardia during diving. Acta Physiol Scand 1976;97:13 –19.
28. Gooden BA. The evolution of asphyxial defense. Integr Physiol Behav Sci
1993;28:317– 30.
29. Gannon AT, Henry RP. Oxygen and carbon dioxide sensitivity of ventilation in
amphibious crabs, Cardisoma guanhumi, breathing air and water. Comp Biochem
Physiol, Part A Mol Integr Physiol 2004;138:111–17.
30. Wood CM, Shelton G. The reflex control of heart rate and cardiac output in the
rainbow trout: interactive influences of hypoxia, haemorrhage, and systemic
vasomotor tone. J Exp Biol 1980;87:271– 84.
31. Vornanen M, Tuomennoro J. Effects of acute anoxia on heart function in
crucian carp: importance of cholinergic and purinergic control. Am J Physiol
1999;277:R465 –75.
32. Jones DR. Factors affecting the recovery from diving bradycardia in the frog.
J Exp Biol 1966;44:397– 411.
33. Hicks JW, Wang T. Cardiovascular regulation during anoxia in the turtle: an
in vivo study. Physiol Zool 1998;71:1–14.
34. Borg KA, Milsom WK, Jones DR. The effect of O2 and CO2 on the dive
behavior and heart rate of lesser scaup ducks (Aythya affinis): quantification
of the critical PaO2 that initiates a diving bradycardia. Respir Physiol Neurobiol
2004;144:263 –79.
35. Butler PJ, Jones DR. Onset of and recovery from diving bradycardia in ducks.
J Physiol (Lond) 1968;196:255 –72.
36. Andrews RD, Jones DR, Williams JD, et al. Heart rates of northern elephant
seals diving at sea and resting on the beach. J Exp Biol 1997;200:2083 – 95.
37. Casanave EB, García Samartino L, Affanni JM. Bradycardia in armadillos
experimentally covered with soil. Arch Physiol Biochem 1995;103:51– 3.
38. Milsom WK, Zimmer MB, Harris MB. Vagal control of cardiorespiratory function
in hibernation. Exp Physiol 2001;86:791– 6.
39. Fewell JE, Taylor BJ. Level of ventilation influences the cardiovascular response
to hypoxemia in lambs. Can J Physiol Pharmacol 2004;82:1113 –17.
40. Foster GE, Sheel AW. The human diving response, its function, and its control.
Scand J Med Sci Sports 2005;15:3 –12.
41. Lemaître F, Bernier F, Petit I, et al. Heart rate responses during a breath-holding
competition in well-trained divers. Int J Sports Med 2005;26:409 –13.
42. Chow LT, Chow SS, Anderson RH, et al. Autonomic innervation of the
human cardiac conduction system: changes from infancy to senility – an
immunohistochemical and histochemical analysis. Anat Rec 2001;264:169 – 82.
43. Keenan RL, Shapiro JH, Kane FR, et al. Bradycardia during anesthesia in infants.
An epidemiologic study. Anesthesiology 1994;80:976 – 82.
44. Hasdiraz L, Oguzkaya F, Bilgin M, et al. Complications of bronchoscopy for foreign
body removal: experience in 1,035 cases. Ann Saudi Med 2006;26:283 –7.
45. Haxhija EQ, Rosegger H, Prechtl HF. Vagal response to feeding tube insertion in
preterm infants: has the key been found? Early Hum Dev 1995;41:15 –25.
46. Gilger MA, Jeiven SD, Barrish JO, et al. Oxygen desaturation and cardiac
arrhythmias in children during esophagogastroduodenoscopy using conscious
sedation. Gastrointest Endosc 1993;39:392– 5.
47. Mort TC. Emergency tracheal intubation: complications associated with
repeated laryngoscopic attempts. Anesth Analg 2004;99:607–13.
48. Pendergast DR, Lundgren CE. The underwater environment: cardiopulmonary,
thermal, and energetic demands. J Appl Physiol 2009;106:276 – 83.
49. Sørensen M, Engbaek J, Viby-Mogensen J, et al. Bradycardia and cardiac
asystole following a single injection of suxamethonium. Acta Anaesthesiol Scand
1984;28:232– 5.
Arch Dis Child 2012;97:139–144. doi:10.1136/adc.2010.210518
Review
50. Karanovic N, Jukic M, Carev M, et al. Rocuronium attenuates oculocardiac reflex
during squint surgery in children anesthetized with halothane and nitrous oxide.
Acta Anaesthesiol Scand 2004;48:1301– 5.
51. Steur RJ, Perez RS, De Lange JJ. Dosage scheme for propofol in children under
3 years of age. Paediatr Anaesth 2004;14:462–7.
52. Arnold RW, Jensen PA, Kovtoun TA, et al. The profound augmentation
of the oculocardiac reflex by fast acting opioids. Binocul Vis Strabismus Q
2004;19:215 –22.
53. Tirel O, Chanavaz C, Bansard JY, et al. Effect of remifentanil with and without
atropine on heart rate variability and RR interval in children. Anaesthesia
2005;60:982– 9.
54. Tibballs J, Malbezin S. Cardiovascular responses to induction of anaesthesia
with thiopentone and suxamethonium in infants and children. Anaesth Intensive
Care 1988;16:278 – 84.
55. Gelissen HP, Epema AH, Henning RH, et al. Inotropic effects of propofol,
thiopental, midazolam, etomidate, and ketamine on isolated human atrial muscle.
Anesthesiology 1996;84:397– 403.
56. Riou B, Viars P, Lecarpentier Y. Effects of ketamine on the cardiac papillary
muscle of normal hamsters and those with cardiomyopathy. Anesthesiology
1990;73:910 –18.
57. Guldner G, Schultz J, Sexton P, et al. Etomidate for rapid-sequence intubation
in young children: hemodynamic effects and adverse events. Acad Emerg Med
2003;10:134 – 9.
58. Robinson BJ, Ebert TJ, O’Brien TJ, et al. Mechanisms whereby propofol
mediates peripheral vasodilation in humans. Sympathoinhibition or direct vascular
relaxation? Anesthesiology 1997;86:64 –72.
59. Maruyama K, Nishikawa Y, Nakagawa H, et al. Can intravenous atropine prevent
bradycardia and hypotension during induction of total intravenous anesthesia with
propofol and remifentanil? J Anesth 2010;24:293 – 6.
60. Klockgether-Radke AP, Frerichs A, Kettler D, et al. Propofol and thiopental
attenuate the contractile response to vasoconstrictors in human and porcine
coronary artery segments. Eur J Anaesthesiol 2000;17:485 – 90.
61. Afshari R, Maxwell SR, Webb DJ, et al. Morphine is an arteriolar vasodilator in
man. Br J Clin Pharmacol 2009;67:386 – 93.
62. Ebert TJ, Ficke DJ, Arain SR, et al. Vasodilation from sufentanil in humans.
Anesth Analg 2005;101:1677– 80.
63. Ouattara A, Boccara G, Köckler U, et al. Remifentanil induces systemic
arterial vasodilation in humans with a total artificial heart. Anesthesiology
2004;100:602–7.
64. Chanavaz C, Tirel O, Wodey E, et al. Haemodynamic effects of remifentanil in
children with and without intravenous atropine. An echocardiographic study.
Br J Anaesth 2005;94:74 – 9.
65. McAuliffe G, Bissonnette B, Cavallé-Garrido T, et al. Heart rate and cardiac
output after atropine in anaesthetised infants and children. Can J Anaesth
1997;44:154 – 9.
66. Tibballs J, Malbezin S. Cardiovascular changes during deep halothane
anaesthesia in infants and children. Anaesth Intensive Care 1988;16:285 – 91.
67. Tramèr MR, Moore RA, McQuay HJ. Propofol and bradycardia: causation,
frequency and severity. Br J Anaesth 1997;78:642– 51.
68. Shorten GD, Bissonnette B, Hartley E, et al. It is not necessary to administer
more than 10 micrograms.kg-1 of atropine to older children before succinylcholine.
Can J Anaesth 1995;42:8 –11.
69. Venkatesh V, Ponnusamy V, Anandaraj J, et al. Endotracheal intubation in a
neonatal population remains associated with a high risk of adverse events.
Eur J Pediatr 2011;170:223 –7.
70. Simon L, Trifa M, Mokhtari M, et al. Premedication for tracheal intubation: a
prospective survey in 75 neonatal and pediatric intensive care units. Crit Care
Med 2004;32:565 – 8.
71. Elliott NM, Andrews RD, Jones DR. Pharmacological blockade of the dive
response: effects on heart rate and diving behaviour in the harbour seal
(Phoca vitulina). J Exp Biol 2002;205:3757– 65.
72. Elsner R, Millard RW, Kjekshus JK, et al. Coronary blood flow and
myocardial segment dimensions during simulated dives in seals. Am J Physiol
1985;249:H1119 –26.
73. Reese SA, Crocker CE, Carwile ME, et al. The physiology of hibernation in
common map turtles (Graptemys geographica). Comp Biochem Physiol, Part A Mol
Integr Physiol 2001;130:331– 40.
74. Jackson DC. Hibernating without oxygen: physiological adaptations of the
painted turtle. J Physiol (Lond) 2002;543:731–7.
75. Feltes TF, Pignatelli R, Kleinert S, et al. Quantitated left ventricular systolic
mechanics in children with septic shock utilizing noninvasive wall-stress analysis.
Crit Care Med 1994;22:1647– 58.
76. Evans RG, Ludbrook J, Ventura S. Role of vagal afferents in the haemodynamic
response to acute central hypovolaemia in unanaesthetized rabbits. J Auton Nerv
Syst 1994;46:251– 60.
77. Stiefel MF, Udoetuk JD, Storm PB, et al. Brain tissue oxygen monitoring
in pediatric patients with severe traumatic brain injury. J Neurosurg
2006;105:281– 6.
143
 Downloaded from http://adc.bmj.com/ on February 5, 2015 - Published by group.bmj.com
Review
78. Narotam PK, Burjonrappa SC, Raynor SC, et al. Cerebral oxygenation in major
pediatric trauma: its relevance to trauma severity and outcome. J Pediatr Surg
2006;41:505 –13.
79. Perlman JM. Neonatal cerebral blood flow velocity measurement. Clin Perinatol
1985;12:179 – 93.
80. Ramaekers VT, Casaer P, Daniels H. Cerebral hyperperfusion
following episodes of bradycardia in the preterm infant. Early Hum Dev
1993;34:199 – 208.
81. Friesen RH, Lichtor JL. Cardiovascular depression during halothane
anesthesia in infants: study of three induction techniques. Anesth Analg
1982 ;61:42– 5.
82. Shaw CA, Kelleher AA, Gill CP, et al. Comparison of the incidence of
complications at induction and emergence in infants receiving oral atropine vs no
premedication. Br J Anaesth 2000;84:174 – 8.
83. Oei J, Hari R, Butha T, et al. Facilitation of neonatal nasotracheal intubation
with premedication: a randomized controlled trial. J Paediatr Child Health
2002;38:146 – 50.
84. Rautakorpi P, Manner T, Kanto J, et al. Metabolic and clinical responses to
different types of premedication in children. Paediatr Anaesth 1999;9:387– 92.
85. Bishop VS, Horwitz LD. Effects of altered autonomic control on left ventricular
function in conscious dogs. Am J Physiol 1971;221:1278 – 82.
86. Tsou CH, Chiang CE, Kao T, et al. Atropine-triggered idiopathic ventricular
tachycardia in an asymptomatic pediatric patient. Can J Anaesth
2004;51:856 –7.
87. Amitai Y, Almog S, Singer R, et al. Atropine poisoning in children during the
Persian Gulf crisis. A national survey in Israel. JAMA 1992;268:630 –2.
144
88. Ceha LJ, Presperin C, Young E, et al. Anticholinergic toxicity from nightshade
berry poisoning responsive to physostigmine. J Emerg Med 1997;15:65 – 9.
89. Caksen H, Odabas D, Akbayram S, et al. Deadly nightshade (Atropa belladonna)
intoxication: an analysis of 49 children. Hum Exp Toxicol 2003;22:665 – 8.
90. Djibo A, Bouzou SB. [Acute intoxication with ‘sobi-lobi’ (Datura). Four cases in
Niger]. Bull Soc Pathol Exot 2000;93:294 –7.
91. Tiongson J, Salen P. Mass ingestion of Jimson Weed by eleven teenagers.
Del Med J 1998;70:471– 6.
92. Arthurs GJ, Davies R. Atropine – a safe drug. Anaesthesia 1980;35:1077– 9.
93. Kozer E, Mordel A, Haim SB, et al. Pediatric poisoning from trimedoxime (TMB4)
and atropine automatic injectors. J Pediatr 2005;146:41– 4.
94. Magbagbeola JA. The effect of atropine premedication on body temperature of
children in the tropics. Br J Anaesth 1973;45:1139 – 42.
95. Purcell MJ. Atropine poisoning in infancy. Br Med J 1966;1:738.
96. Gatti JM, Perez-Brayfield M, Kirsch AJ, et al. Acute urinary retention in children.
J Urol 2001;165:918 –21.
97. Opie JC, Chaye H, Steward DJ. Intravenous atropine rapidly reduces lower
esophageal sphincter pressure in infants and children. Anesthesiology
1987;67:989 – 90.
98. Fang JC, Sarosiek I, Yamamoto Y, et al. Cholinergic blockade inhibits gastro-
oesophageal reflux and transient lower oesophageal sphincter relaxation through
a central mechanism. Gut 1999;44:603 –7.
99. Gattuso JM, Kamm MA. Adverse effects of drugs used in the management
of constipation and diarrhoea. Drug Saf 1994;10:47– 65.
100. Wright BD. Exacerbation of akinetic seizures by atropine eye drops.
Br J Ophthalmol 1992;76:179 – 80.
Arch Dis Child February 2012 Vol 97 No 2
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Bradycardia during critical care intubation:

mechanisms, significance and atropine
Peter Jones, Stéphane Dauger and Mark J Peters

Arch Dis Child 2012 97: 139-144 originally published online May 28, 2011
doi: 10.1136/adc.2010.210518

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http://adc.bmj.com/content/97/2/139

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Collections Arrhythmias (69)
Drugs: cardiovascular system (443)
Child health (3364)
Neonatal and paediatric intensive care (329)
Neonatal health (584)
Surgery (248)
Surgical diagnostic tests (236)

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