JURNAL READING

Ondansetron Given Intravenously

Attenuates Arterial Blood
Pressure Drop Due to Spinal
anesthesia: A Double-Blind,
Placebo-Controlled Study

SITI ROHIMAH JAMALUDIN

11-2009-217
Background and
Objectives
 Spinal anesthesia :
 arterial hypotension
 bradycardia
 induced by sympathetic nerve mediated by
peripheral serotonin
 The aim of this study was to verify the hypothesis that
blockade of type 3 serotonin receptors by
intravenous ondansetron administration might
reduce hypotension and bradycardia induced by
spinal anesthesia.
Methods
 71 patients
 36 in the ondansetron group (receiving 8 mg IV
ondansetron)
 35 in the placebo group (receiving isotonic NaCl
solution).
 Measurements of heart rate and arterial blood
pressure were taken every 5 minutes after
spinal anesthesia was performed with 4 mL
0.5% hyperbaric bupivacaine solution.
Results
 in both groups Decreases in mean, systolic, and
diastolic arterial pressure as well as in heart rate,
compared with baseline values.
 Minimal systolic and mean blood pressure values
obtained over a 20-minute observation period were
significantly higher in the ondansetron group.
 There were no significant differences in diastolic
blood pressure and heart rate values between the
groups.
Conclusions

 Ondansetron IV attenuates the fall of

systolic and mean blood pressure, but
does not have an influence on diastolic
blood pressure or heart rate.
Spinal anesthesia (SA)
 Efficient method of providing intraoperative analgesia
and a safe alternative to general anesthesia
 SA is not flawless or free from adverse effects, which
include unwanted cardiovascular events
 arterial hypotension (33%) and minor bradycardia
(13%) in the nonobstetric population.
 Drop in arterial pressure results primarily from
decreased vascular resistance caused by blockade of
sympathetic nerves.
 Bradycardia parasympathetic system,
increased baroreceptor activity, or to the
Bezold-Jarisch reflex (BJR)triggered by
stimulation of intracardiac receptors
bradycardia, vasodilatation, and hypotension.
 Receptors triggering the Bezold-Jarisch reflex
 systemic responses to hyper- and hypovolemia
 chemoreceptors sensitive to serotonin
 Although mechanoreceptors located in all
cardiac chambers are normally sensitive to
distension, diminished venous return of
blood, induces deformation of the cardiac
wallirritation of mechanoreceptors 
BezoldJarisch reflex.
 Chemoreceptors are activated by
serotonin released from activated
thrombocytes
 The aim of the present study was to verify
the hypothesis that blockade of type 3
serotonin receptors by ondansetron IV
administration would reduce hypotension
and bradycardia induced by spinal
anesthesia.
Method
 Patients gave their written consent.

 Inclusion criteria :
1. (ASA) I or II
2. 20 to 70 years.
 Priori excluded
1. classic contraindications to subarachnoidal block
2. hypersensitive to ondansetron
3. history of allergy to local anesthetic agents.
4. arterial hypertension, coronary heart disease, cvs insufficiency
5. persons taking medication that may result in hypotension.

 Neither selective serotonin reuptake inhibitors nor serotonin-

related migraine medication were used in any of the examined
Patients were randomized into 2
groups
the ondansetron group the placebo group
 receiving 8 mg IV  10 mL of isotonic sodium
ondansetron (Zofran®, chloride solution.
GlaxoSmithKline
Manufacturing S.p.A.,
Parma, Italy)
 diluted in 10 mL of
isotonic sodium chloride
solution
 The content of the syringe was infused 5
minutes before performing the subarachnoid
anesthesia; the time of the content
administration was 1 minute.
 The person who administered the solution was
blind to the content of the syringe
 The person who prepared the solution and
knew its composition was directly available on
the phone
 Standardized anesthesiological
management
 Patients fasted for 8 to 10 hours before anesthesia.
 no patient was hydrated intravenously before the procedure.
 Patients were medicated 60 minutes before anesthesia with
7.5 mg oral midazolam.
 Upon patient arrival to the operating room, pulse oximetry,
ECG monitoring, and noninvasive arterial pressure
measurement was started
 Heart rate was calculated automatically from
electrocardiographic curves presented on the monitor.
 Systolic and diastolic blood pressure values were measured
directly.
 MAP was calculated using the following formula: MAP = ([2
× diastolic blood pressure] + systolic blood pressure) / 3.
 A cannula was introduced into a peripheral
vein, and slow infusion of 0.9% sodium
chloride solution was commenced so as not to
exceed the volume of 200 mL during the study
period.
 Baseline measurements were performed
before ondansetron administration, about 5
minutes before patients were positioned for
spinal anesthesia.
 Lumbar puncture was performed with the patient in a
sitting position, and the subarachnoid space was punctured
at the L3-L4 or L4-L5 level.
 Whitacre pencil-point 25-, 26-, or 27-gauge needles were
used.
 After identification of the subarachnoid space
(cerebrospinal fluid outflow), 4 mL of 0.5% hyperbaric
bupivacaine solution (Marcaine® Spinal 0.5%) was
administered
 Immediately after completing the subarachnoid injection,
patients were positioned supine on the operating table.
 From this moment on, the level of anesthesia was
evaluated 4 times (every 5 minutes) with cold
sensation (using alcohol swab).
 At the same time points, the level of motor blockade
was assessed (according to the Bromage scale) and
heart rate and arterial pressure were measured.
 Atropine (0.5 mg intravenously) was administered in
cases of bradycardia, and ephedrine (10 mg
intravenously) in cases of hypotension,
 Hemodynamic parameter values before
anesthesia and values recorded after the
blockade were used for analysis.
 A double analysis method was used:
 values obtained at every time point of the
study were compared
 the minimal values recorded within the 20-
minute period after the blockade.
 No surgical procedures were performed
during the study period.
Statistical Analysis

 In 4 cases, anesthesia was abandoned

because the operation was; in 1 patient
there were no signs of subarachnoid block
following bupivacaine administration.
 There were no significant differences in
patient age, body weight, height, sex, or
ASA classification between the groups.
Characteristics of the
Blockade

 Blockade distribution (number of anesthetized

segments above Sl) is presented in Figure 1.
 Numbers of anesthetized segments at
respective time points did not differ between
the groups
 Bromage scores of motor block showed no
significant differences between the groups at
the respective time points. Characteristics of
the motor block are presented in Table 2.
Hemodynamic Parameter
Variation
 Minimal MAP and SAP values were significantly higher in
the ondansetron group, while no significant differences
in minimal DAP and HR values between the groups were
detected.
 A SAP drop below 90 mm Hg was recorded in 7 patients
in the placebo group, and in 1 patient in the
ondansetron group (20% vs. 2.8%), and the difference
was statistically significant (P = .028).
 Relations between a significant systolic blood pressure
drop (below 90 mm Hg), and age and sex of patients
were not detected (P values respectively .07 and .54).
Discussion
 The most important finding in the present study is the
observation of higher minimal systolic and mean blood
pressure
 Drop in arterial pressure accompanying subarachnoid
blockade is a common side effect of this procedure
 This complication results mainly from hyperactivity of
the vagal nerve.
 the mechanisms of blood pressure drop  decrease in
systemic vascular resistance and central venous
pressure, which originates from incomplete sympathetic
block, and blood redistribution
 severe bradycardia and cardiac arrest a consequence
of BezoldJarisch reflex and an increase in baroreflex
activity.
 Sympathovagal balance (parasympathetic system
predomination) may provoke both kinds of side effects.
 Methods of decreasing the extent of cardiovascular
consequences of spinal anesthesia include:
1. preloading with intravenous fluid infusion
2. administration of vasoconstricting agents
3. placing patients in positions facilitating venous return
4. administration of atropine.
 Spinal anesthesia-related triggering of Bezold-Jarisch
reflex, demonstrated by hypotension, bradycardia, and
vasodilatation, is known to result from stimulation of 5-
HT^sub 3^ receptors in vagal nerve endings.
 Usage of 5-HT^sub 3^ blockers results in an
incidental clinically relevant response from the
cardiovascular system.
 In the present study, a lower decrease in SAP
and MAP was observed following administration
of ondansetron, without any influence upon
diastolic blood pressure.
 As mentioned, bradycardia connected with spinal
blockade occurs at a rate almost 3 times less than
hypotension, so in an observed group of patients,
frequency of the event was too small to observe
significant differences.
 Lack of concurrent variations in HR and DAP values
may suggest that related to the 5-HT^sub 3^
receptor blockade limiting SAP and MAP drop, there
might be changes in cardiac output and vascular
response.
 Serotonin is known to influence systolic
activity of the heart, but through the
binding to 5-HT4 receptors.
 suppressed vasodilatation, explain the
decreased extent of SAP dropping in the
ondansetron group observed in the
present studyrelated to diminished
restriction in venous return.
 It may be suspected that such an event occurs
primarily in the venous part of the vascular
system, augmenting the amount of blood
coming to the heart and thus increasing its
output
 This speculation is supported by the absence of
significant differences in DAP values between
the 2 study groups, because DAP reflects the
tonus of arterial vessel walls
 Ondansetron poorly penetrates the blood-brain
barrierdoes not have much influence on
central serotoninergic mechanisms, even though
it does play a role in the observed changes in
blood pressure.
 These agents are primarily used in the
treatment of post-operative nausea and
vomiting and for prevention of shivering in
patients undergoing SA.
 This study revealed the fact that a fall in
systolic and mean blood pressure may be
reduced by ondansetron usage prior to
spinal anesthesia.