Contrast Media Questions RSP v1.1.2 Technician

CONTRAST MEDIA
PROF. M. TAMEEM AKHTAR

MCPS; FCPS
DIRECTOR, RADIOLOGY DEPTT
ZIAUDDIN MEDICAL UNIVERSITY HOSPITAL
KARACHI
CONTRAST MEDIA
“Contrast Medium” or “dye” is a liquid/solid

substance that is used during a radiological
examination for the purpose of
delineating internal structures
or
an organ
that is being studied, this would otherwise not
be possible
OR
CONTRAST MEDIA
are agents used in radiology to
enhance
or
create
the necessary visual contrast in an image b/w
the organ, vessel or tract in which they are
present & the surrounding tissues in the
body
OR
CONTRAST MEDIA
When natural contrasts are not sufficient to

allow visualization of desired anatomic
structures, structures can be enhanced
through the use of an artificial contrast
CONTRAST MEDIA
Substances that can modify absorption of

CM are divided into negative CM &
positive CM
CONTRAST MEDIA
Types of Contrast Media
Positive CM Negative CM
absorb more x-rays absorb less x-rays

than the surrounding than the surrounding
structures & tissues structures & tissues
& therefore enhance & therefore do not
visualization enhance visualization
(= white). (= dark or black).
Contrast Media
Types of lodinated Contrast Media

Contrast Media
Types of lodinated Contrast Media

4 major types of iodinated compounds are currently
used as CM:
3. Conventional ionic iodinated compounds or
high osmolar ionic iodinated agents:
• = Ionic Monomer
4. Low osmolar ionic iodinated agents:
• = Ionic Dimer
5. Nonionic iodinated compounds
• = Nonionic Monomer
6. Isotonic nonionic iodinated agents
• = Nonionic Dimer
CONTRAST MEDIA
CLASSIFICATION
OF CONTRAST MEDIA
Iodinated CM
THE
"IDEAL"
INTRAVENOUS CONTRAST
THE "IDEAL" INTRAVENOUS CONTRAST AGENT
1. Water-soluble
2. Heat / Chemical / Storage Stability
3. Non-antigenic
4. Low viscosity
5. Lower or same osmolarity compared to
plasma
6. Selective excretion
7. Safety :LD50 should be high
8. Low cost
GOLDEN
RULES
GOLDEN RULES CONCERNING
CONTRAST MEDIA ADMINISTRATION
Check:
emergency trays
(is everything there, & is it still current?), &
- O2 supply (reservior still full?) frequently!
does everybody in your department know:
who to call in case of emergency?
how to work with the necessary equipment (e.g.,
the O2 bottle?!) ?
Remember:
always be prepared
to treat adverse side effects,
i.e., have emergency equipment
& potential help available!
Remember:
use dosage ampoules on the emergency tray
do not require "a lot of calculations"!
knowing, that one ampoule is the normal dose
for an adult can be easier to remember than mg
or ml
Remember:
always use a stable, & safe injection site &
needle
do not remove the i.v. access immediately after
CM is injected
keep it - you may need it later!
Remember:
majority of CM side effects occur in the 1st 10-
20” after CM injection.
do not leave the pt unattended!
if something happens, get help / assistance
immediately, even if the problem seems to be
only a minor one!
Remember:
drastic reactions sometimes start with slight
symptoms, like nausea & emesis!
stop the CM administration if the problem is
not absolutely minor !
Remember:
whatever the reaction, check the ABC first:
Airway free or compromised?

Blood pressure OK?
Circulation OK? (pulse?)
Remember:
make sure the pt's airway is free &
maintained
remove any obstacles
watch the tongue
it might fall back & also cause obstruction.
give O2 if necessary or if in doubt
Remember:
in case of cardiovascular collapse, or
Cardiac arrest,
immediately start cardiopulmonary
resuscitation!
in case of respiratory problems:
Oxygen is (nearly) always good!
UNIVERSAL
PRE-TREATMENT
OPTIONS
ADVERSE REACTIONS
TO CONTRAST MEDIA
CATEGORIZATION OF IDIOSYNCRATIC REACTION
Categorization
Of idiosyncratic reactions
Mild Immediate
Moderate Seriousness Time Early Reaction
Severe Late Reaction

Immediate adverse reaction

…………..occurs within seconds to few
minutes after injection
Early adverse reaction

…………..occurs within upto 15 minutes
after injection
Late adverse reaction

…………..occurs within hours to a couple
of days after injection
ADVERSE REACTIONS
TO CONTRAST MEDIA
ADVERSE REACTIONS TO CONTRAST MEDIA
• Hematological changes
• Nausea & vomiting
• Sloughing of skin
• Headache
• Sneezing • Cardiac arrest
• Abdominal pain • Arm Pain, may be local
• Rigors ?? Extra-vasation of
contrast
• Broncho-spasm
• Hypotension • Thrombophlebitis &
thrombosis (late
• Convulsions
reaction)
Muco-cutaneous reaction:
1. Flushing
2. Pallor
3. Urticaria
4. Angioneurotic edema (in severe cases)
Rhinorrhoea
Onset may be
immediate or
delayed upto 3 days
BRAIN TEASERS
ABOUT
CONTRAST MEDIA
ARE ARs TO CM DOSE DEPENDENT OR
INDEPENDENT
Physiochemical reactions are directly related to

the dose
Are primarily due to:
Hypertoxicity
Viscosity of CM
ARE ARs TO CM DOSE DEPENDENT OR
INDEPENDENT
Idiosyncratic reactions are not dose

related
Can occur with so call small doses of 1 ml
or less of CM
?? ADVERSE REACTIONS TO
CM ARE DOSE
22.13
?? DO LATE REACTIONS
OCCUR MORE FREQUENTLY
?? DO LATE ARs OCCUR MORE FREQUENTLY
AFTER ADMINISTRATION OF NON-IONIC CM
No difference b/w the frequency of late reactions

b/w ICM & NICM
Venous problems lessened with LOCM but still
seen in 10%
Less pain after extravasation
Less frequent skin necrosis
Rashes & parotitis more common with NICM
?? DO LATE OCCURRING
CM ARs NECESSITATE
?? DO LATE OCCURRING ARs CM
NECESSITATE LONGER SUPERVISION OF PT.
Definition of delayed (late occurring reactions)

that occurs after the pt has left the
department*
Variable
*Panto P, Davies P (1986): Delayed reactions to urographic contrast

?? DO LATE OCCURRING ARs CM NECESSITATE
LONGER SUPERVISION OF PT.
TYPES OF DELAYED
(LATE OCCURRING REACTIONS)
3. Venous problems:
• Thrombosis
• Skin necrosis
4. Rashes
5. A flu like syndrome
6. Parotitis
7. Cardiac syndrome:
• Worsening of heart failure
• Cardiac arrest

?? DO LATE OCCURRING ADVERSE REACTIONS CM
NECESSITATE LONGER SUPERVISION OF PT.
TIME OF ONSET OF ACUTE REACTIONS*

ARs are clearly those that occur in the deptt
while the a pt is under observation
Acute death & severe life threatening reactions
with HOCM occur early mostly within 15”
Abt. 10% occur after > 60”

?? DO LATE OCCURRING ADVERSE REACTIONS
CM NECESSITATE LONGER SUPERVISION OF PT.
TIME OF ONSET OF ACUTE REACTIONS

Abt 2/3 occur within 5” of injection
Observation very important
Some pts may suffer cardiac arrest which may
occur any time

CAN THE “AR” RATE BE
REDUCED BY
CAN THE “AR” RATE BE REDUCED BY
ADMINISTRATION OF CORTICOSTEROIDS
Pts with known allergy 2-6x rise in side effects

Reactions are largely dose independent
CAN THE AR RATE BE REDUCED BY
WHAT'S THE ROLE OF CORTICOSTEROIDS ??

HOW IT WORKS
Counter acts permeability impairment of cell
membranes
Checks compliment-induced lyses of RBC
Lower the serum compliment levels
Counteracts both release of histamine &
hemolysis
WHAT'S THE ROLE OF CORTICOSTERIODS ??

HOW IT WORKS
Results in slow onset of these side effects of CM,
Not the immediate dose, but hrs before the test
WHAT’S THE DOSE OF CORTICOSTEROIDS ??

2 parts 32 mg each methylprednisolone
12 hr &
2 hr
prior to administration of CM
leads to significant lowering of side effects
Lasser EC et al (1977) Theoretical & experimental basis for utilization of in

prevention of contrast media reactions. Radiology 125: 1-9
ARE DELAYED
REACTIONS
ARE DELAYED REACTIONS SERIOUS OR
FATAL
NO STUDY HAS SHOWN

THIS
ARE DELAYED REACTIONS SERIOUS
OR FATAL
That is why select pts carefully

Late reactions cannot be predicted or avoided
but careful observation for 1st 5” are important
ARE CM HEATED TO
BODY TEMPERATURE
ARE CM HEATED TO BODY TEMPERATURE
BETTER TOLERATED
CM in high concentration & large doses are

better tolerated if given at body temperature
Warmer at 37º
Ansell G (1987) Radiological Contrast Media: Inman WHW (ed) Monitoring for
BETTER TOLERATED
WHAT HAPPENS TO CM
reduces viscosity
making injection easier particularly with small
needles & catheters
BETTER TOLERATED
WHAT HAPPENS TO CM
pain & heat sensation in angiographies
are associated with viscosity,
therefore CM at body temp. are better
tolerated
DOES THE INJECTION RATE
AFFECT THE TOLERANCE
DOES THE INJECTION RATE AFFECT THE
TOLERANCE
If CM is to be injected in large doses & volume

like in interventional
rapid injection will be less tolerated
ECG changes occur during rapid injection due
to histamine release
therefore rapid injections are less desirable than
slower injections
?? CAN MAXIMUM DOSE
CAN BE EXCEEDED
CAN MAXIMUM DOSE CAN BE EXCEEDED
CM related toxicity has 2 aspects:

Anaphylactic reactions are dose related to some
extent
May occur with small dose even with
subcutaneous
High dose toxicity ?? high dose ?? maximum
permissible not defined
High dose toxicity ?? high dose ?? maximum

permissible:
Dependent on:
Time period during which the whole dose was given
It may be moderate doses for some & disastrous
for some
Several 100 ml CM might be acceptable for some

over a period of 2-3 hrs
May not be acceptable if given by rapid IV over a
period of < 1 min.
GUIDE LINES
Those at risk from CM overdose are:
• Poor cardiac reserve pts
• Poor renal function pts
GUIDE LINES
LOCM & NICM are preferred in such pts. & in
those where large quantities of CM is expected to
be used
Renal function is always the concern
Caution after high dose procedures for renal
function
STORAGE OF CONTRAST
MEDIA
STORAGE OF CONTRAST MEDIA
expiry date mentioned

at 0º C crystallization occurs
dissolved again in unopened bottle to about 80º C
> 30º C (like hot sun for prolong hrs can cause
decomposition)
decomposition increases by exposure to light &
radiation
STORAGE OF CONTRAST MEDIA
Recommendation!
CM should be placed in
dark &
away from radiation
MIXING CONTRAST
MEDIUM
MIXING CONTRAST MEDIUM
should not be mixed with other drugs

results in precipitations
like:
1. Tolazolin
2. Papverin
3. Cimetidine
4. Diphenhydramine
5. Protamine
MIXING CONTRAST MEDIUM
thoroughly flush the I/V lines catheters with saline

before injecting any substance through pre-
existing I.V. line
CAN LAB TESTS BE
INFLUENCED BY CM
CAN LAB TESTS BE INFLUENCED BY CM
ADMINISTRATION
sure they can !!

thyroid function tests even upto 2-6 wks
specific gravity of urine increases
iron & copper blood levels may be disturbed
ADMINISTRATION
some CM may disturb:

BUN
Creatinine
Cholesterol
Triglycerides
Liver enzymes like
GOT
GPT
ADMINISTRATION
therefore urine & blood samples should

be taken after
24 hours
IS THERE ANY CONSIDERATION
BEFORE BLOOD DONATION
AFTER CM EXAMINATION
IS THERE ANY CONSIDERATION BEFORE
BLOOD DONATION AFTER CM
CM may remain in the body for much longer

time due to 50% reduction in GFR
10% of CM remain intra-corporeal even after 6
days
IS THERE ANY CONSIDERATION BEFORE
BLOOD DONATION AFTER CM
it is not to wise to donate blood earlier than
14 days
after CM administration
WHAT SHOULD BE DONE IN CASE
OF CM EXTRAVASATION WITH
PARAVASCULAR INJECTION
WHAT SHOULD BE DONE IN CASE OF CM
EXTRAVASATION WITH PARAVASCULAR
extravasation of NICM may not cause any

serious problems
pain resulting in extravasation draws your
attention
it results in chemical cellulitis;
max peak 24-48 hrs after the event
INJECTION
?? EFFECTS:
injection of hyaluronidase, thought to increase
the distribution may increase the tissue
damage
local injection of corticosteroids no
convincing results
extravasation in worst conditions may lead to

gangrene (in compromised vascular state)
injection in confined place results in increase in
tissue pressure may impair perfusion
INITIAL
Elevate extremity
Ice pack 3 x day
Observe for 2-4 hours if volume > 5ml
Surgical Consultation
ionic > 30 ml
nonionic > 100 ml
skin blistering
altered tissue perfusion
increasing pain after 2-4 hours
change in sensation distal to site of
extravasation
MEASUREMENTS
2. elevation of extremity
3. application of warm compresses
4. immobilization to improve & speed up
restoration
?? ROLE OF CM DURING
PREGNANCY & LACTATION
?? ROLE OF CM DURING PREGNANCY &
LACTATION
still controversial
small amounts of CM entering the fetal & infant
circulation; no known side effects
thyroid function of fetus may be significantly
altered by iodine containing CM passing freely
through the placental barrier resulting in
hypothyroidism
result in iodine mumps
same in infants
I blood levels increases
I excess can cause hypothyroidism, transiently
Stubbe P, Heidmemann P, Schrnbrand P et
LACTATION
CM may enter milk after oral or

intravascular administration
blood milk barrier is crossed by diffusion
it depends on:
the dose given
properties of CM
CM clearance from the mother’s body
LACTATION
0.5% was detected in mother’s milk in 24 hrs

nursing child with normal GIT will absorb only
0.5%
free iodide can be absorbed
may result in blocked thyroid hormone
synthesis……..leading to hypothyroidism
if untreated will lead to cerebral & cardio-
pulmonary maldevelopment

LACTATION
mothers may be asked therefore to refrain

from nursing for about
3-5 days
after CM administration

?? ARE CM INDUCED SIDE
EFFECTS AGE DEPENDENT
?? ARE CM INDUCED SIDE EFFECTS AGE
DEPENDENT
age one of the factors

more prevalent b/w 3rd & 4th decade
lowest at the either ends of the age
highest minor reactions b/w 20-29 yrs
fatal reactions most common in 6th & 7th
decades due to CVS collapse
?? WHY IS PRE-EXISTING LUNG
DISEASE A RISK
?? WHY IS PRE-EXISTING LUNG DISEASE A
RISK FOR THE CM ADMINISTRATION
CM can result in:

1. increase in interstitial pulmonary water
2. impairment of compliance
3. impairment of diffusion
4. sub-clinical bronchospasm
5. dramatic bronchospasm
?? WHY IS PRE-EXISTING LUNG DISEASE A
RISK FOR THE CM ADMINISTRATION
THOSE AT RISK ARE:

2. already impaired diffusion & compliance
3. tendency of bronchospasm
4. asthmatics
5. COPD with an element bronchospasm
DOES UNDERLYING CVS
DISEASE CONSTITUTE AN
DOES UNDERLYING CVS DISEASE
CONSTITUTE AN INCREASED RISK OF CM
CM produces marked peripheral vasodilatation..

therefore fall in systemic BP
pts without CVS disease can tolerate reflex
tachycardia without difficulty
angina may follow in pt. with IHD
DOES UNDERLYING CVS DISEASE
CONSTITUTE AN INCREASED RISK OF CM
ADMINISTRATION
pts with IHD are therefore at more risk

with IHD pts CM can affect pump function &
electrophysiological changes therefore leading
to cardiac fibrillation
more common in elderly age group
DOES GA PREVENT
OCCURRENCE OF CM
INDUCED SIDE EFFECTS
DOES GA PREVENT OCCURRENCE OF CM
does not provide absolute protection
can not be alternative to prophylaxis

DOES GA PREVENT OCCURRENCE OF CM
eliminates CM induced pain & defense

mechanism & restlessness
protective effects against undesirable CM
reactions
skin reaction occur equally
IS SEDATION INDICATED
BEFORE CM
IS SEDATION INDICATED BEFORE CM
ADMINISTRATION
↓↓ anxiety as it is one of the common factors in

CM reaction
fear is the most common cause of mild, &
undesirable side effects
IS SEDATION INDICATED BEFORE CM
ADMINISTRATION
main cause of severe reactions like shock;

pulmonary & CVS problems
due to direct effects on CNS
nausea; & vomiting urticaria reduced due to
hypnotic effects prior to CM introduction
reduces agitation to avoid vaso-vagal reactions
THANK YOU
SOME COMMENTS ON DRUGS
USED FOR TREATMENT
OF CM REACTIONS
USED FOR TREATMENT
OF CM REACTIONS
Epinephrine
acts upon
α-receptors; effect: peripheral vasoconstriction
ß-receptors, which are of 2 types
ß-1 receptors effect:
increased rate, &
contractility of heart
ß-2 receptors; effect:
smooth muscle relaxation, esp.
bronchodilation,
arteriolar dilation
USED FOR TREATMENT
OF CM REACTIONS
EPINEPHRINE
USED FOR TREATMENT
OF CM REACTIONS
Epinephrine
large amounts of epinephrine may
cause:
high blood pressure &
cardiac problems, like
dysrhythmias &
even infarction
USED FOR TREATMENT
OF CM REACTIONS
Epinephrine
in pts, in whom hypotension is the primary
problem, try volume replacement by
vigorous hydration first
if this does not work sufficiently, then go
to pharmacologic therapy
USED FOR TREATMENT
OF CM REACTIONS
Epinephrine
Be cautious in:
elderly pts.,
pts with hypoxia
pts on ß-blockers
USED FOR TREATMENT
OF CM REACTIONS
Epinephrine
start with a small dose of epinephrine, &
give additional amounts depending on
the initial effect!
USED FOR TREATMENT
OF CM REACTIONS
Epinephrine
Dose & administration:
subcutaneous injection (only if
circulation is not drastically impaired,
otherwise uncontrollable effect due to
varying absorption!)
USED FOR TREATMENT
OF CM REACTIONS
Epinephrine
dose 0.1-0.2 mg in adults
i/v injection: slow injection
0.1 mg diluted in 10 mL of saline,
given over a few minutes (= about 10
g min).
USED FOR TREATMENT
OF CM REACTIONS
ANTIHISTAMINES
USED FOR TREATMENT
OF CM REACTIONS
ANTIHISTAMINES
have a beneficial effect
due to their competitive action with
the histamine at the Hl & H2-receptors
circulating histamine may be
inactivated
USED FOR TREATMENT
OF CM REACTIONS
ANTIHISTAMINES
?? should be given
in pts with urticaria:
give Hl-receptor blockers (e.g.
diphenhydramine)
if no response, then an H2-receptor
blocker (Cimetidine)
USED FOR TREATMENT
OF CM REACTIONS
ANTIHISTAMINES
with more severe anaphylactoid
reactions, give Hl- & H2-blockers.
do not give H2-receptor blockers alone
to pts. with heart disease!
USED FOR TREATMENT
OF CM REACTIONS
ANTIHISTAMINES
Diphenhydramine:
25-50 mg per orally/i.m. / i.v.
Cimetidine:
300 mg i.v., diluted & slow.
USED FOR TREATMENT
OF CM REACTIONS
ATROPINE
USED FOR TREATMENT
OF CM REACTIONS
ATROPINE
Occ. required in pts with vasovagal
reactions (hypotension & bradycardia!) if
elevation of legs & i.v. fluid
administration is unsuccessful.
USED FOR TREATMENT
OF CM REACTIONS
ATROPINE
Initial dose in adults is abt l mg
injected slowly i.v.
(NB: smaller doses may accentuate
dysrhythmias!).
USED FOR TREATMENT
OF CM REACTIONS
BRONCHODILATORS
USED FOR TREATMENT
OF CM REACTIONS
BRONCHODILATORS
bronchodilation is mediated by ß-
adrenergic effects.
with slow injection of epinephrine these
ß-adrenergic effects predominate
can also be treated by inhalation of ß-
adrenergic agonists through metered-dose
inhalers (e.g. metaproterenol, terbutaline)!
USED FOR TREATMENT
OF CM REACTIONS
BRONCHODILATORS
2 to 3 inhalations of metaproterenol,
terbutaline or other (by metered dose inhaler).
USED FOR TREATMENT
OF CM REACTIONS
NITROGLYCERIN
USED FOR TREATMENT
OF CM REACTIONS
NITROGLYCERIN
may be given in case of episodes of
suspected angina pectoris, which can be
precipitated by stress.
improves coronary perfusion, & reduces
oxygen demand.
USED FOR TREATMENT
OF CM REACTIONS
NITROGLYCERIN
Capsule (0.4 mg), sublingual
USED FOR TREATMENT
OF CM REACTIONS
DIAZEPAM
USED FOR TREATMENT
OF CM REACTIONS
DIAZEPAM
convulsions or seizures may be due to
several mechanisms
if they persist, they may be effectively
treated by diazepam
useful to calm down excited patients.
USED FOR TREATMENT
OF CM REACTIONS
DIAZEPAM
5 to 10 mg, slowly i.v.!
USED FOR TREATMENT
OF CM REACTIONS
CORTICOSTEROIDS
USED FOR TREATMENT
OF CM REACTIONS
CORTICOSTEROIDS
in high doses are probably always given in
severe anaphylactoid reactions
do not have an immediate effect, but rather
one with a slow onset
probably stabilize cell membranes
reduce the production of mediator substances
USED FOR TREATMENT
OF CM REACTIONS
CORTICOSTEROIDS
Hydrocortisone or methylprednisolone,
500-1000 mg i.v.
USED FOR TREATMENT
OF CM REACTIONS
FUROSEMID
(LASIX)
USED FOR TREATMENT
OF CM REACTIONS
FUROSEMID
(LASIX)
Useful in case of acute pulmonary edema.
Approx. 20-40 mg i.v.
Acute Reaction to Contrast Media:
Treatment Outline
Treatment Outline
Treatment Outline
Treatment Outline
Treatment Outline
Treatment Outline

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CONTRAST MEDIA

PROF. M. TAMEEM AKHTAR

“Contrast Medium” or “dye” is a liquid/solid

When natural contrasts are not sufficient to

Substances that can modify absorption of

absorb more x-rays absorb less x-rays

Types of lodinated Contrast Media

Types of lodinated Contrast Media

Airway free or compromised?

Moderate Seriousness Time Early Reaction

Severe Late Reaction

Immediate adverse reaction

Early adverse reaction

Late adverse reaction

Physiochemical reactions are directly related to

Idiosyncratic reactions are not dose

No difference b/w the frequency of late reactions

Definition of delayed (late occurring reactions)

*Panto P, Davies P (1986): Delayed reactions to urographic contrast

*Panto P, Davies P (1986): Delayed reactions to urographic contrast

TIME OF ONSET OF ACUTE REACTIONS*

*Panto P, Davies P (1986): Delayed reactions to urographic contrast

TIME OF ONSET OF ACUTE REACTIONS

*Panto P, Davies P (1986): Delayed reactions to urographic contrast

Pts with known allergy 2-6x rise in side effects

WHAT'S THE ROLE OF CORTICOSTEROIDS ??

WHAT'S THE ROLE OF CORTICOSTERIODS ??

WHAT’S THE DOSE OF CORTICOSTEROIDS ??

Lasser EC et al (1977) Theoretical & experimental basis for utilization of in

NO STUDY HAS SHOWN

That is why select pts carefully

CM in high concentration & large doses are

If CM is to be injected in large doses & volume

CM related toxicity has 2 aspects:

High dose toxicity ?? high dose ?? maximum

Several 100 ml CM might be acceptable for some

expiry date mentioned

should not be mixed with other drugs

thoroughly flush the I/V lines catheters with saline

sure they can !!

some CM may disturb:

therefore urine & blood samples should

CM may remain in the body for much longer

it is not to wise to donate blood earlier than

extravasation of NICM may not cause any

extravasation in worst conditions may lead to

CM may enter milk after oral or

0.5% was detected in mother’s milk in 24 hrs

Stubbe P, Heidmemann P, Schrnbrand P et

mothers may be asked therefore to refrain

Stubbe P, Heidmemann P, Schrnbrand P et

age one of the factors

CM can result in:

THOSE AT RISK ARE:

CM produces marked peripheral vasodilatation..

pts with IHD are therefore at more risk

does not provide absolute protection

can not be alternative to prophylaxis

eliminates CM induced pain & defense

↓↓ anxiety as it is one of the common factors in

main cause of severe reactions like shock;

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