Bradycardia in acute haemorrhage
BMJ 2004; 328 doi: https://doi.org/10.1136/bmj.328.7437.451 (Published 19 February 2004) Cite this as: BMJ 2004;328:451
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EDITOR-Sixty three years after the first publication in the Br Med J
(1), Thomas and Dixon once more bring the absense of tachycardia to
maintain blood pressure in some haemorrhagic patients to our attention
(2). Triggered by a reduced venous return, the circulatory response
changes from normal maintenance of arterial pressure to parasympathetic
activation and sympathetic inhibition, resulting in bradycardia in some
subjects. In our view, it should be added that this phenomenon is also
known as the Bezold Jarisch reflex and treatment with atropin may have
deletorious consequences in these patients.
Von Bezold described a similar bradycardia as a response to injection
of various alkaloid compounds and later discovered that this was mediated
by chemoreceptors in the heart (3). The non-myelinated, type C vagal
fibers are heterogeneous in terms of their responsiveness to mechanical
(pressure, inotropism, volume) and chemical (veratrum alkaloids and
various other substances) stimuli. Therefore, the Bezold-Jarisch reflex
also includes reactions triggered by cardiac mechanoreceptor activation by
left ventricular distension or hypovolemia. The decrease in peripheral
resistance coupled with decreased venous return triggers bradycardia,
presumably to preserve cardiac filling. Other clinical conditions include
the syncope associated with aortic stenosis, perioperative bradycardia,
hypotension during exercise, bradycardia observed during utrafiltration in
patients on hemodialysis, myocardial infarction involving the inferior
posterior wall of the ventricle, and bradycardia due to the use of
nitroglycerin or amyl nitrite.
Theoretically, the observed bradycardia can be treated by
compensation of the volume depletion or repressing vagal tonus by the
administration of atropine. However, there are indications that
administration of atropin may be deletorious in these patients. In the
referenced study of Barriot (4), 27 cases experienced bradycardia that was
succesfully treated with volume loading. Only 2 patients received
atropine, of which 1 patient developed ventricular fibrillation. This
suggests that in hemorrhagic shock administration of atropine may have
potential deleterious effects. Therefore, treatment of choice is generous
fluid administration.
Peter Pickkers, internist-intensivist
p.pickkers@ic.umcn.nl
Department of Intensive Care Medicine
University Medical Centre St. Radboud,
PO Box 9101, 6500HB Nijmegen, The Netherlands
Lucas van Eijk, medical student
Department of Intensive Care Medicine
University Medical Centre St. Radboud,
PO Box 9101, 6500HB Nijmegen, The Netherlands
Hans van der Hoeven, internist-intensivist
Department of Intensive Care Medicine
University Medical Centre St. Radboud,
PO Box 9101, 6500HB Nijmegen, The Netherlands
No competing interests.
(1) Grant RT, Reeve EB. Clinical observations on air-raid casualties.
BMJ 1941; ii: 293-297.
(2) Thomas I, Dixon J. Bradycardia in acute haemorrhage. BMJ 2004;
328(7437):451-453.
(3) von Bezold A, Hirt L. über die physiologischen Wirkungen des
essigsuren Veratrins. Untersuchungen aus dem physiologischen Laboratorium
Wurzburg. 1867: 75-156.
(4) Barriot P, Riou B. Hemorrhagic shock with paradoxical bradycardia.
Intensive Care Med 1987; 13:203-207.
Competing interests:
None declared
Competing interests: No competing interests
It is indeed a misconception that acute haemorrhage and bradycardia
are incompatible (1). Similarly in a related clinical scenario, that of
acute thoracic aortic dissection, bradycardia is not uncommon.
In the biggest post-mortem review of patients with aortic dissection
by Hirst and colleagues (2) who analysed the heart rate of 196 patients,
they found that 20 patients (10.2%) had a bradycardia of 40-60 bpm, 117
(59.7%) had a normal heart rate and only 48 patients (24.5%) were
tachycardic with a pulse rate exceeding 100bpm. Bradycardia occurring in
the dissecting aorta can be the result of stimulation of the depressor
nerves, the carotid sinus or as a result of a haematoma in the atrial
septum near the AV node (2).
Consequently, absence of tachycardia should not prevent radiological
imaging if the clinical suspicion is high for either acute haemorrhage or
(1) or acute thoracic dissection.
References
1. Thomas I, Dixon J. Bradycardia in acute haemorrhage. BMJ 2004;
328: 451-3
2. Hirst AE Jr, Johns VJ Jr, Kime SW Jr. Medicine 1958; 37: 217-279
Competing interests:
None declared
Competing interests: No competing interests
Dear Editor,
We would agree with Thomas and Dixon (1) that for patients with acute
haemorrhage and hypovolaemia lack of a tachycardia is more common than
previously thought. We recently had a clinical case illustrating this
point.
A 74-year-old man presented to our Accident and Emergency department
with a history of sudden onset severe left sided abdominal pain and marked
hypotension (blood pressure 73/43 mm Hg), hypothermia (35.4oC) and cool
peripheries. He denied any recent trauma. Pulse was 73 beats / min. He was
not beta blocked. Abdominal examination revealed signs of generalised
peritonitis. There was no clinical evidence of an abdominal aortic
aneurysm. Admission haemoglobin was 107 g/l. With intravenous fluid
resuscitation the blood pressure eventually came up to 123 / 82 mm Hg. At
laparotomy 1500ml of intra-peritoneal blood mixed with clots was
aspirated. There was a large peri-splenic haematoma and a decapsulated
spleen. Splenectomy and peritoneal lavage was carried out. The patient
made a quick recovery.
It transpired that this man had forgotten to tell us that he slipped
on a frosty step 5 days previously, landing heavily on his left side. The
diagnosis was a delayed rupture of splenic haematoma. Despite marked
hypotension and obvious hypovolaemia this patient’s pulse did not rise
above 75 beats / min.
Ref: Thomas I, Dixon J. Bradycardia in acute haemorrhage. BMJ 2004;
328: 451-3. (21 February).
Garth Beattie, Specialist Registrar, General Surgery.
Ian Garstin, Consultant General Surgeon.
Antrim Area Hospital, Bush Rd, N Ireland.
garthbeattie@yahoo.co.uk
Competing interests: None declared.
Editorial note
The patient whose case is described has given his signed informed consent to publication.
Competing interests: No competing interests
I believe that the lesson of the week ‘Bradycardia in acute
haemorrhage’ is potentially misleading and am confused as to what lesson
or lessons the authors are trying to convey. Are they saying that it is
not well recognised that relative bradycardia may be associated with
hypovolaemic shock? This lack of recognition may be true.
What is not true is that ‘tachycardia occurs in the initial stage of
a biphasic cardiovascular response …’ It is well known that tachycardia is
a relatively late sign of haemorrhagic hypovolaemia. I quote two human
studies of progressive haemorrhage1;2. Price found that healthy volunteers
could have 10 to 15% of their blood volume removed with no significant
change in heart rate, blood pressure, cardiac output or blood flow to the
splanchnic bed. However, splanchnic blood volume was reduced by 40%. The
subjects in his study had essentially auto-transfused and were maintaining
the systemic circulating volume at the expense of the splanchnic
circulating volume. More recently Hamilton-Davies et al. performed a
similar experiment on healthy volunteers. They found that approximately
25% of the blood volume could be removed with no effect on the commonly
measured cardiovascular variables but, consistent with Price’s findings,
the gastric mucosal PCO2 rose immediately followed by a fall in cardiac
stroke volume.
Were in fact these three case scenarios actually hypovolaemic and
relatively bradycardic. The authors seem to suggest that the anaemia and
hypotension indicate that the cases presented were not adequately
resuscitated and hence might be expected to be tachycardic due to ‘acute
central hypovolaemia’. They may however have had their circulating volume
adequately resuscitated and were haemo-diluted. If that is the case a
normal heart rate would be expected. Hypotension, following anaesthesia
and subsequent epidural or opiate analgesia, is relatively common. If the
systemic vascular resistance is low, cardiac output may of course be low,
normal or high in the presence of hypotension. They make no mention of
markers of inadequate end organ perfusion-for example lactate, base excess
and urine output. Nor do they mention causes, other than hypovolaemia, of
hypotension. This is despite one patient experiencing perioperative
myocardial ischaemia.
Two very important lessons I believe may therefore be added to the
relatively rare scenario of true bradycardia in the face of acute
haemorrhagic hypovolaemic shock. First, tachycardia, especially in the
young, is a very late sign in hypovolaemia and indicates potentially
imminent cardiovascular collapse. Second, we know that in the face of
hypovolaemia the physiological responses of the patient seek to maintain
pressure at the expense of flow. Initially this means stealing volume from
regional beds -gut, skin, kidneys etc. This may lead to occult
hypovolaemia which unless recognised and treated may lead to an increase
in morbidity and mortality.
Given the three clinical scenarios, the patients’ mental state,
capillary refill, respiratory rate, urine output and analgesia and volume
requirements together with a fall in haemoglobin concentration may have
suggested that a return to theatre were indicated. If these clinical
assessments were inadequate to make the diagnosis then either measure flow
to assess resuscitation or surrogates of inadequate perfusion-poor urine
output, base excess, lactate or gastric tonometry to guide diagnosis and
appropriate treatment. Reliance on either bradycardia or tachycardia to
diagnose concealed haemorrhagic hypovolaemia is not a good lesson to
impart.
Reference List
1. Hamilton-Davies C, Mythen MG, Salmon JB, Jacobson D, Shukla A,
Webb AR. Comparison of commonly used clinical indicators of hypovolaemia
with gastrointestinal tonometry. Intensive Care Medicine 1997;23:276-81.
2. Price HL, Deutsch S, Marshall BE, Stephen GW, Behar MG, Neufeld
GR. Hemodynamic and metabolic effects of hemorrhage in man, with
particular reference to the splanchnic circulation. Circulation Research
1966;18:469-74.
Competing interests:
None declared
Competing interests: No competing interests
Editor--The authours, in the Lesson of the week entitled :
Bradycardia in acute haemorrhage BMJ 2004;328:451-453, failed to indicate
in their discussion that another important phenomenon occurs i.e.
Triphasic response to haemorrahage. It has been recognised relatively
recently that the bradycardic phase of haemorrhage can be followed by a a
massive increase in heart rate and further falls in mean arterial pressure
as blood losses exceed about 40% of the total blood volume.
The triphasic response has been reported following animal experiments
and during clinical practice. The bradycardic phase appears to be
reversible with prompt fluid resuscitation, but patients developing
tachycardia and further hypotension are far more resistant to therapy.
This third and potentially irreversible phase of haemorrhage response is
associated with increased sympathetic activity. Cerebral hypoferfusion and
hypoxia are thought to to be partly responsible.
It is important to note that the cardiovascular response to
haemorrhage is different in haemorrhage with tissue injury vs haemorrhage
alone(i.e. venesection in experimental animals).Anaesthetized animals
subjected to haemorrhage and associated electrical stimulation of the
sciatic nerve(injury simulation) show lower rate of survival compared with
those subjected to haemorrhage alone. Furthermore, nerve stimulation or a
real tissue injury superimposed on haemorrhage produces greater falls in
cardiac index and systemic oxygen delivery than those produced by a
haemorrhage alone(2).
It is a mistake to assume that there is a linear pattern in the
sequence of tachycardia followed by bradycardia. This may be so in the lab
under controlled rate blood loss. In the real world blood loss in not
linear and often a small loss may be followed by a sudden loss of large
volume of blood,the result of many factors including initial vasospasm and
tamponade.
In the cases described by the authours,the Heart Rate (HR) and Blood
Pressure (BP) were checked in 15 mins to 1/2 hrly intervals. A lot can
happen in that time and perhaps the
patients did have a tachycardia,albeit transient,not noted.
In young healthy patients the onset of tachycardia takes longer due
to cardiovascular compensation. However, following the threshold of
compensation there is often a sudden fall in BP associated with immediate
and dramatic increase in HR. These patients often exhibit sudden
tachycardia which if not corrected will lead to bardycardia and
death.Although hypovolemic shock is most often associated with an increase
in HR, the increase is modest and a paradoxical bradycardia develops in
severe but potentially reversible hypotensive hypovolemic shock(2).
The phenomenon of relative bradycardia may probably be due to
hyperresponsiveness of vagal cardiac afferents. The common denominator in
almost all the published literature is a massive blood loss. Perhaps the
threshold for triggering vagal cardiac afferents is lower for this subset
of patients.This phenomenon has been described in as high as 50% of
patients with acute blood loss(3). Tachycardia may not be a reliable sign
of hypovolemic shock when defined by blood pressure criteria in patients
(3)(4).The haemodynamic response to a fixed volume haemorrhage passes
through three distinct phases: a normotensive, compensatory phase; a
hypotensive, decompensatory phase; and a post-haemorrhage, recompensatory
phase (5).
The role of the forebrain and midbrain in regulating the triphasic
response to a 'fast' (1.5%/min) or 'slow' (0.75%/min) rate of blood
withdrawal (30% haemorrhage)
was evaluated by Troy et al(5)who compared,in unanaesthetised rats, the
effects of pre-collicular (PCD) vs. pre-trigeminal decerebrations (PTD).It
was found that pre-trigeminal decerebration attenuated the decompensatory
(hypotensive) phase to either a fast or slow haemorrhage. In contrast, pre
-collicular decerebration attenuated the compensatory and recompensatory
phases of the response to a 'fast' (but not a slow) haemorrhage. These
results suggest that the integrity of (i)forebrain structure(s)are
critical for compensatory and recompensatory responses to 'rapid' blood
loss; and (ii) midbrain structure(s) are critical for the decompensatory
response to progressive blood loss irrespective of rate.
These findings suggest that we do not understand the full concept of
blood loss and compensation. However we should all take note of the fact
that the assumption that initial tachycardia is the only haemodynamic
response to acute central hypovolaemia is incorrect, and a failure to
recognise bradycardia as a sign of acute haemorrhage is potentially
dangerous. Also these cases together with those described in the
literature illustrate that BP used alone is dangerous and often
misleading.The use of the Shock Index (SI) is a more sensitve indicator of
blood loss than BP and HR as independent parameters. Other potential means
of better monitoring is Doppler aortograghy which has been validated as a
non-invsive method when used suprasternally.
Respectfully,
Sashi Kommu.
(1)Dark PM, Little RA. Surgery 2000.
(2)Secher NH, Sander Jensen K,Werner C, Warberg J, Bie
P.Bradycardia during severe but reversible hypovolemic shock in man.Circ
Shock.1984;14(4):267-74.
(3)Snyder HS, Dresnick SJ. Lack of tachycardic response to
hypotension in penetrating abdominal injuries. J Emerg Med. Jul-Aug 1989
;7(4):335-9.
(4)Adams SL, Greene JS. Absence of a tachycardic response to
intraperitoneal hemorrhage. J Emerg Med.1986;4(5):383-9.
(5)Troy BP, Heslop DJ, Bandler R, Keay KA. Haemodynamic response to
haemorrhage: distinct contributions of midbrain and forebrain structures.
Auton Neurosci.2003 Oct 31;108(1-2):1-11.
Competing interests:
None declared
Competing interests: No competing interests
The development of bradycardia in a fetus is interpreted as evidence
of fetal distress and in a neonate as a harbinger of cardiorespiratory
arrest. Yet bradycardia is the normal response in breath-holding human
divers (1). In aquatic animals, such as seals, several enzymatic
adaptations support their ability to survive for long periods underwater
(2,3). These data suggest that bradycardia may be one of several
physiological adaptations, well developed in the fetus and neonates and
trained breath-holding divers, to limit the degree of tissue damage
induced in hypoxia.
Xanthine dehydrogenase may be converted to xanthine oxidase in
hypoxia. Not only does this set the stage for the generation of free
radicals and free radical-induced tissue injury but it also sets the stage
for the irreversible degradation of ATP into uric acid and the depletion
of adenine nucleotide and nucleoside pools. These are needed to replenish
ATP pools when normoxia is resumed. In cultured enterocytes exposed to
cytokines free radicals are released which deplete intracellular levels of
NAD(+)/NADH secondary to activation of the nuclear enzyme poly(ADP-ribose)
polymerase (PARP) (4). This inhibits oxygen consumption by the enterocytes
and may also be interpreted as a cytoprotective rather than a cytopathic
response.
Paradoxically organs withstand complete anoxia better than they do
partial anoxia. Gut mucosa, for example, is destroyed by free radicals
after one hour of ischaemia followed by reperfusion. Yet surgical
specimens washed of adherent digestive juices develop no such evidence of
mucosal damage for many hours.
Might, therefore, bradycardia in haemorrhagic shock be a
cytoprotective response to hypoxia induced by the generation of free
radicals?
1. Andersson JP, Liner MH, Runow E, Schagatay EK. Diving response and
arterial oxygen saturation during apnea and exercise in breath-hold
divers.
J Appl Physiol. 2002 Sep;93(3):882-6.
2. Elsner R, Oyasaeter S, Almaas R, Saugstad OD. Diving seals,
ischemia-reperfusion and oxygen radicals.
Comp Biochem Physiol A Mol Integr Physiol. 1998 Apr;119(4):975-80.
3. Fuson AL, Cowan DF, Kanatous SB, Polasek LK, Davis RW. Adaptations
to diving hypoxia in the heart, kidneys and splanchnic organs of harbor
seals (Phoca vitulina).
J Exp Biol. 2003 Nov;206(Pt 22):4139-54.
4. Khan AU, Delude RL, Han YY, Sappington PL, Han X, Carcillo JA,
Fink MP.Liposomal NAD(+) prevents diminished O(2) consumption by
immunostimulated Caco-2 cells.
Am J Physiol Lung Cell Mol Physiol. 2002 May;282(5):L1082-91
Competing interests:
None declared
Competing interests: No competing interests
The information from your paper is applicable to all post-operative
patients. However you did not mention if any of your patients had RBC
transfusions during their resuscitation. For euvolemic anaemic post-
operative patients blood transfusions may no longer be justified in many
cases and the Haemoglobin/haematocrit levels for triggering RBC
transfusions has continued to be lowered. While there may still be debate
about the best type of fluid to use for acute resuscitation, if a patient
is deemed to be hypovolemic and is believed to have had significant blood
loss there should be a low threshold for RBC replacement to resuscitate
them instead of the continued usage of crystalloids or colloids.
Competing interests:
None declared
Competing interests: No competing interests
I observed the same, apparently paradoxical, bradycardic response to
acute hameorrhage frequently among trauma patients in Africa. The patients
I saw were typically fit young men, and many of them seemed to maintain a
low pulse rate prior to circulatory collapse. In that setting, with low
numbers of medical staff, nurses made initial and ongoing observations.
Both doctors and nurses were frequently lulled into a false sense of
security by the low/normal pulse rate. This typically led to less urgent
resuscitation than necessary and may have contributed to some deaths.
Furthermore, I also observed several fit young men who maintained
apparently normal blood pressure and pulse rate after obviously massive
haemorrhage, and who frequently then suffered circulatory collapse and who
then typically could not be resuscitated. I quickly learned not to rely on
pulse and blood pressure under these circumstances, but noted the history,
type of injury, amount of blood on clothes etc and maintained a very high
index of suspicion. It seemed to me that at least some fit young men were
able to maintain apparently normal pulse and blood pressure until prior to
complete circulatory collapse.
Competing interests:
None declared
Competing interests: No competing interests
Tachycardia: The Shock Sign that may never come.
Dear Sirs:
This article and the relevant responses are some of the best that I
have come across on the topic of relative bradycardia to hypotension in
the intra-abdominal hemorrhage patient. I became personally interested in
this topic only recently. On April 26, 2004, I temporarily exchanged my
role as an Emergency Room Nurse of 15 years for the role of a patient. I
had a Total Abdominal Hysterectomy and Bilateral Salpingo-oophorectomy.
The physician and nurses taking care of me missed the fact that I had bled
approximately 60% of my blood volume into my abdomen, apparently most of
it within 9.5 hours of surgery. Six weeks after a morbid and eventful
recovery (I was never returned to the OR), I reviewed my medical records.
What struck me as odd was my pulse of 79 bpm associated with a blood
pressure of 82/55. Despite drops in hemoglobin and hematocrit of 40% and
42% on Post Op day 1, the physician noted me as "remaining hemodynamically
stable" (there were also signs and symptoms of lethargy,
confusion,oliguria of under 20cc/hr, and the blood pressure afore
mentioned). He repeated a hematocrit 24 hours later on the morning of Post
Op Day 2, and my count was down 60% (most likely attributed to
hemodilution). However, urine output increased and my pulse was now 120
bpm. He transfused me with 2 units PRBC's on this day. The interesting
thing to me at the time was that I felt BETTER when my pulse was 120 pbm.
I went from lethartic and obtunded to able to stand. The significant
change to me on Post Op Day 2 was the onset of a splitting headache. After
reviewing my chart, I questioned my (former) physician regarding his care.
He remained convinced that the thing that separated a stable versus an
unstable patient was tachycardia. The nurses had the same
misunderstanding of cardiac output. I had to put it into simple terms of:
Remember CO = SV x HR? Who is sicker? A patient loosing over 50% of their
blood who responds to the loss with an increased heart rate to compensate
for the low stroke volume or the patient who does not? Imagine what the
cardiac output would have been had this been appropriately monitored? From
the literature available, and there is not that much, I understand that
the presence of blood in the peritoneal cavity triggers a parasympathetic
tone that blocks the usual, life-saving sympathetic reponses of increased
heart rate and narrowing pulse pressure. This phenomena (seemingly
paradoxical) occurs because of the predominance of vagal receptors in the
abdominal viscera over those of the sympathetic nervous system. Not only
did my heart rate not increase for 2 days, but the diastolic numbers fell
with the systolic. This is usually a terminal event when rapid
intervention does not take place. In fact, I am not able to locate another
patient in the literature who survived this severe and rapid a blood loss
who did not return to surgery, and did not receive prompt fluid
resuscitation and blood transfusion who lived. I cannot explain why I
survived. One result of my survival that it I am compelled to spread the
word that tachycardia is not shock and, more importantly, shock is NOT
tachycardia. I am writing an article on this in my MSN curriculum. Anyone
with additional information/observations they would like to share? Also,
it appears to me that recommending Atropine as an adjunct to fluid therapy
may be a good thing in instances such as this--further discussion here
would be appreciated. Thanks for your contributions.
Sincerely, Greer
Marshall, RN at overheadslam@msn.com.
Competing interests:
None declared
Competing interests: No competing interests