CALCIUM GLUCONATE FOR

POST PARTUM HEMORRHAGE

THERAPY ETCAUSA UTERINE
ATONY
DR. dr. KUSNARMAN KEMAN, SP.OG-K
DEPARTMENT OBSTETRIC AND GYNECOLOGY
DIVISION FETAL AND MATERNAL MEDICINE
MEDICAL FACULTY OF BRAWIJAYA UNIVERSITY/SAIFUL ANWAR HOSPITAL
MALANG

1ST MALANG COMBINED CLINICAL MEETING

ARIA GAJAYANA HOTEL, MAY 23RD 2016

Every minute of every day a women

dies from complication of pregnancy
and childbirth
Global maternal mortality ratio is
402/ 100 000 births , 99% in
developing
countries (Finland 1.6/100 000 )
Haemorrhage accounts for 30% of
cases and is a leading cause of
maternal death
Should we be concerned?
YES !!!!
In UK annually 17 maternal deaths
due to maternal haemorrhage and
the number is increasing !
Cca 75% of near misses cases in
Scotland due to haemorrhage
( 5/1000), 50% substandard care !

Uterine atony

Uterine atony failure of the uterus to contract adequately

following delivery

The most common cause of postpartum haemorrhage (PPH)

A critical step in the prevention of PPH is the simultaneous

contraction of myometrial fibers during and after the third stage
of labour
(Wray, 2007)

Uterine contractility
Our knowledge still insufficient !
Uterine contractility regulated by:
- Ca++ (nifedipine as first line
medication for treatment of
premature contractions
- progesterone ( im injections weekly
in cases of previous premature birth)
- oxytocin (induction of labor,
prophylactic administration
immediately after second stage of
labor completed, treatment of atony,
- prostaglandines (misoprostol,
sulprostone)
From: Aguilar et al. Physiological pathways and
molecular mechanisms regulating uterine contractility.
Human Reproduction Update,2010

Uterine atony risk factors

Uterine atony management options

Uterine atony
management
options

from: Ahonen J, Stefanovic V, Lassila R :

Management of post-partum haemorrhage, Acta Anaesthesiologica Scandinavica, 2010

Uterine atony management

Identifying ris factors and prevention

Surgical management of lacerations

Medical

Surgical ( pelvic arterial ligation, uterine brace suture)

Other (balloon tamponade, embolization)

(Wray, 2007)

Uterine atony
Identifying

risk factors
Prophylactic oxytocin immediately after
delivery of infant (10 IU bolus im or iv),early
clamping of umbilical cord and controlled cord
traction RR 0.5
Oxytocin or ergometrine? No statistical
difference.
Calcium gluconate

Uterus Contraction
Physiology

The change of myometrium condition that still calm

during pregnancy then become actively contractive
approach to the labor, successively called as
activation period, stimulation period and involution
period soon after the baby birth.
(Challis and Lye, 2003).

2+
Mechanism of Ca2+
in The Uterine
Muscle Contraction

Interaction of action-myosin at
the muscle contraction process
Ion Ca2+ has role in phosphorilation
of mysofibrile protein that involved
in the muscle contraction.

Role of Calcium in Cross-Bridge Formation

During relaxed state

Human physiology by Lauralee Sherwood, 7th edition

Role of Calcium in Cross-Bridge Formation

Excited

Human physiology by Lauralee Sherwood, 7th edition

Sliding Filament
Mechanism
Cross-bridge interaction between actin
and myosin brings about muscle
contraction by means of the sliding
filament mechanism.

Sliding Filament
Mechanism

Increase in Ca2+ starts filament sliding

Decrease in Ca2+ turns off sliding process

Thin filaments on each side of sarcomere slide inward over

stationary thick filaments toward center of A band during
contraction

As thin filaments slide inward, they pull Z lines closer together

Sarcomere shortens

Sliding Filament
Mechanism

All sarcomeres throughout muscle fibers length

shorten simultaneously

Contraction is accomplished by thin filaments from

opposite sides of each sarcomere sliding closer
together between thick filaments.

Calcium Release
in ExcitationContraction
Coupling

Human physiology
by Lauralee
Sherwood, 7th
edition

CROSS-BRIDGE
CYCLE

Human physiology
by Lauralee
Sherwood, 7th
edition

Intracellular calcium store in myometrium

Intracellular calcium is normally stored in a special intracellular

organelle known as sarcoplasmic reticulum (SR)

The main physiological function of myometrial SR is to actively take up

the cytosolic calcium against Ca2+ gradient and store it until needed.

Calcium ions can be released from the SR via two main channels present
on the SR membrane.
(Broderick and Broderick, 1990).

Mechanism of calcium ions released from

SR

IP3 channels
(mainly activated by
IP3 second
messenger)

ryanodine
receptors (RyRs)
(activated mainly
by Ca2+ itself),
leading to a
phenomenon
known as Ca2+
induced Ca2+
release (CICR).

It is suggested that there is no or little role for CICR in myometrium

(Taggart and Wray, 1998, Holda et al., 1996)

Electrophysiology of myometrium
(excitation-contraction coupling)

The sequence of events, between the generation of action potential

and the initiation of muscle contraction, is known as excitationcontraction coupling (ECC)

Resting membrane potential of uterine smooth muscle cells falls

between -35 to -80 mV

As uterine smooth muscle is spontaneously active, changes in

membrane potential are necessary for the contraction to occur.
(Sanborn, 2000)

Similar to most other excitable tissues, the excitability of uterine

smooth muscle is largely determined by the movement of sodium
(Na), calcium (Ca) and chloride (Cl) ions into the cytoplasm
and the movement of potassium (K) ions into the extracellular
space.

The former three ions are concentrated outside the myometrium

whereas the latter are concentrated inside the myometrial
cytoplasm.
(Jain et al., 2000).

Two main mechanisms of excitationcontraction coupling in myometrium

Electrochemical
mechanism

(Taggart, 2001).

Schematic diagram showing calcium entry and initiation

of contraction in uterine smooth muscle (Taggart, 2001).

pharmacomechanical coupling

(Taggart, 2001).

EFFECTS
UTERINE

OF CALCIUM GLUCONATE TO
CONTRACTION

Chemical formula of ca gluconate

C12H22CaO14H2O = molecular weight 448,4

Calcium gluconate

The usageof calcium gluconate is replacement of electrolit,

positive inotropic, hyperkalemia treatment, hypermagnesia, and
dosage excess of calcium antagonist.

Dosage IV: 10% in 10 cc not more then speed of 1 ml/minute

Elimination: kidney

Package: solution injection 10%

Pharmacology

Calcium is important to maintain functional integrity of

Nerve system

Skeletal system

Cell membrane

Capillary permeability

Heart muscle contraction

Smooth muscle and skeleton

Renal function

Respiration

Blood coagulation.

Pharmacokinetic

Onset of action : IV less than 30 seconds (electrolyte replacement

and inotropic effect)

Peak effect: IV less than 1 minute (electrolyte replacement and

inotropic effect)

Duration of action : IV 10-20 minutes (inotropic effect)

Calcium Gluconate For

Calcium Gluconate For
Uterine Atony Therapy
Uterine Atony Therapy

Several literatures stated that Ca gluconate intravena is able to be given

for post partum hemorrhage caused by uterine atony because of
magnesium or nifedipin excess.

Magnesium work as Ca2+ competitor so with the Mg2+ presence, normal

activities of muscle contraction will not occur.

Nifedipin is the drug that inhibit calcium channel, inhibit the entry of Ca 2+
ion intracellular, so prevent the threshold achievement of Ca 2+ to cause
muscle contraction.
(Brown, 2011)

Calcium Gluconate For Uterine

Calcium Gluconate For Uterine
Atony Therapy
Atony Therapy

Ca gluconate work as the Ca2+ source.

The increase of Ca2+ concentration give muscle

contraction signal through protein precursor
movement that is bound at the actin filament:
tropomyosin and troponin.
(Brown, 2011)

Calcium Gluconate For Uterine

Calcium Gluconate For Uterine
Atony Therapy
Atony Therapy

Interaction of action-myosin at
the muscle contraction process
Ion Ca2+ has role in phosphorilation
of mysofibrile protein that involved
in the muscle contraction.

Calcium Gluconate For Uterine

Calcium Gluconate For Uterine
Atony Therapy
Atony Therapy

Because concentration of Ca2+ increase (from Ca gluconate),

reticulum sarcoplasma will open quickly and release Ca 2+ into
sarcoplasma.

Concentration of Ca2+ ion in the sarcoplasma increase quickly up

to 105 mol/L. The binding place of Ca2+ at TpC in thin filament
quickly filled by Ca2+. Complex of TpC-4Ca2+ interacts with Tpl
and TPT to change the interaction with tropomyosin lead to
muscle contraction
(Brown, 2011)

Calcium Gluconate For Uterine

Calcium Gluconate For Uterine
Atony Therapy
Atony Therapy

At the hypermagnesermia condition (magnesium sulfate excess),

with high Ca2+ concentration come from Ca gluconate, Ca2+ ion
able to place its receptor, so physiological activities of muscle
contraction able to recover again.

At the excessive effect of calcium channel blocker, ca gluconate

as the source of Ca2+ ion can cause the increase of Ca2+ ion.

With the increase of Ca2+, Ca2+ able to open voltage dependent

gate at the cell membrane, so Ca2+ ion able to enter into
intracellular and cause muscle concentration.
(Brown, 2011)

Calcium Gluconate For Uterine

Atony Therapy

The sample taking randomly from 116 birth by using control

group.

At the sample group, at the cervical opening 10 cm

intravenous infusion of 100 ml glucose 10% add with 10 ml ca
gluconate 10%.

Control group withaout drug

At both group still given oxytocin injection after baby delivery

Postnatal
observation 2 hour and 24 hour, average blood loss
10 IU and intravenous infusion of oxytocin 20 IU.
post partum at sample group was significantly lower than control
group.

Calcium gluconate intravenous help in the uterus contraction,

significantly prevent post partum hemorrhage.
(Luo Changhua and Wang Huajing,
2012)

CONCLUSION

The usage of calcium gluconate intravenous able to help uterus

contraction, and significantly able to prevent post partum
hemmorrhage, especially in the case of uterin atony caused by
the excessive use of magnesium sulphate and nifedipine.

The used dosage at several research: drip 10 ml calcium

gluconate 10% in 100 ml glucose 10%.

Tnan vga!
Thank U!
Kiitos!