Colchicum autumnale L.

1. NAME
1.1 Scientific name
1.2 Family
1.3 Common name(s) and synonyms
2. SUMMARY
2.1 Main riss and tar!et or!ans
2.2 S"mmary of clinical effects
2.3 #ia!nosis
2.$ First%aid meas"res and mana!ement &rinci&les
2.' (oisono"s &arts
2.) Main to*ins
3. C+ARAC,ER-S,-CS
3.1 #escri&tion of t.e &lant
3.1.1 S&ecial identification feat"res
3.1.2 +a/itat
3.1.3 #istri/"tion
3.2 (oisono"s &arts of t.e &lant
3.3 ,.e to*in(s)
3.3.1 Name(s)
3.3.2 #escri&tion0 c.emical str"ct"re0 sta/ility
3.3.3 1t.er &.ysico%c.emical c.aracteristics
3.$ 1t.er c.emical contents of t.e &lant
$. USES2C-RCUMS,ANCES 1F (1-S1N-N3
$.1 Uses
$.1.1 Uses
$.1.2 #escri&tion
$.2 +i!. ris circ"mstances
$.3 +i!. ris !eo!ra&.ical areas
'. R1U,ES 1F E4(1SURE
'.1. 1ral
'.2 -n.alation
'.3 #ermal
'.$ Eye
'.' (arenteral
'.) 1t.ers
). 5-NE,-CS
).1 A/sor&tion /y ro"te of e*&os"re
).2 #istri/"tion /y ro"te of e*&os"re
).3 6iolo!ical .alf%life /y ro"te of e*&os"re
).$ Meta/olism
).' Elimination and e*cretion
7. ,14-N1813Y
7.1 Mode of action
7.2 ,o*icity
7.2.1 +"man data
7.2.1.1 Ad"lts
7.2.1.2 C.ildren
7.2.2 Rele9ant animal data
7.2.3 Rele9ant in 9itro data
7.3 Carcino!enicity
7.$ ,erato!enicity
7.' M"ta!enicity
7.) -nteractions
:. ,14-C1813-CA82,14-N1813-CA8 ANA8YSES AN#
6-1ME#-CA8 -N;ES,-3A,-1NS
:.1 Material sam&lin! &lan
:.1.1 Sam&lin! and s&ecimen collection
:.1.1.1 ,o*icolo!ical analyses
:.1.1.2 6iomedical analyses
:.1.1.3 Arterial /lood !as analysis
:.1.1.$ +aematolo!ical analyses
:.1.1.' 1t.er ("ns&ecified) analyses
:.1.2 Stora!e of la/oratory sam&les and s&ecimens
:.1.2.1 ,o*icolo!ical analyses
:.1.2.2 6iomedical analyses
:.1.2.3 Arterial /lood !as analysis
:.1.2.$ +aematolo!ical analyses
:.1.2.' 1t.er ("ns&ecified) analyses
:.1.3 ,rans&ort of la/oratory sam&les and s&ecimens
:.1.3.1 ,o*icolo!ical analyses
:.1.3.2 6iomedical analyses
:.1.3.3 Arterial /lood !as analysis
:.1.3.$ +aematolo!ical analyses
:.1.3.' 1t.er ("ns&ecified) analyses
:.2 ,o*icolo!ical Analyses and ,.eir -nter&retation
:.2.1 ,ests on to*ic in!redient(s) of material
:.2.1.1 Sim&le <"alitati9e ,est(s)
:.2.1.2 Ad9anced <"alitati9e Confirmation ,est(s)
:.2.1.3 Sim&le <"antitati9e Met.od(s)
:.2.1.$ Ad9anced <"antitati9e Met.od(s)
:.2.2 ,ests for /iolo!ical s&ecimens
:.2.2.1 Sim&le <"alitati9e ,est(s)
:.2.2.2 Ad9anced <"alitati9e Confirmation ,est(s)
:.2.2.3 Sim&le <"antitati9e Met.od(s)
:.2.2.$ Ad9anced <"antitati9e Met.od(s)
:.2.2.' 1t.er #edicated Met.od(s)
:.2.3 -nter&retation of to*icolo!ical analyses
:.3 6iomedical in9esti!ations and t.eir inter&retation
:.3.1 6ioc.emical analysis
:.3.1.1 6lood0 &lasma or ser"m
:.3.1.2 Urine
:.3.1.3 1t.er fl"ids
:.3.2 Arterial /lood !as analyses
:.3.3 +aematolo!ical analyses
:.3.$ -nter&retation of /iomedical in9esti!ations
:.$ 1t.er /iomedical (dia!nostic) in9esti!ations and t.eir inter&retation
:.' 19erall inter&retation of all to*icolo!ical analyses and to*icolo!ical
in9esti!ations
:.) References
=. C8-N-CA8 EFFEC,S
=.1 Ac"te &oisonin!
=.1.1 -n!estion
=.1.2 -n.alation
=.1.3 Sin e*&os"re
=.1.$ Eye contact
=.1.' (arenteral e*&os"re
=.1.) 1t.er
=.2 C.ronic &oisonin!
=.2.1 -n!estion
=.2.2 -n.alation
=.2.3 Sin e*&os"re
=.2.$ Eye contact
=.2.' (arenteral e*&os"re
=.2.) 1t.er
=.3 Co"rse0 &ro!nosis0 ca"se of deat.
=.$ Systematic descri&tion of clinical effects
=.$.1 Cardio9asc"lar
=.$.2 Res&iratory
=.$.3 Ne"rolo!ical
=.$.3.1 Central ner9o"s system (CNS)
=.$.3.2 (eri&.eral ner9o"s system
=.$.3.3 A"tonomic ner9o"s system
=.$.3.$ Seletal and smoot. m"scle
=.$.$ 3astrointestinal
=.$.' +e&atic
=.$.) Urinary
=.$.).1 Renal
=.$.).2 1t.er
=.$.7 Endocrine and re&rod"cti9e systems
=.$.: #ermatolo!ical
=.$.= Eye0 ear0 nose0 t.roat> local effects
=.$.1? +aematolo!ical
=.$.11 -mm"nolo!ical
=.$.12 Meta/olic
=.$.12.1 Acid%/ase dist"r/ances
=.$.12.2 Fl"id and electrolyte dist"r/ances
=.$.12.3 1t.ers
=.$.13 Aller!ic reactions
=.$.1$ 1t.er clinical effects.
=.$.1' S&ecial riss
=.' 1t.ers
=.) S"mmary
1?. MANA3EMEN,
1?.1 3eneral &rinci&les
1?.2 8ife s"&&orti9e &roced"res and sym&tomatic2s&ecific treatment
1?.3 #econtamination
1?.$ En.anced elimination
1?.' Antidote2antito*in treatment
1?.'.1 Ad"lts
1?.'.2 C.ildren
1?.) Mana!ement disc"ssion
11. -88US,RA,-;E CASES
11.1 Case re&orts from literat"re
12. A##-,-1NA8 -NF1RMA,-1N
12.1 S&ecific &re9entati9e meas"res
12.2 1t.er
13. REFERENCES
1$. AU,+1R(S)0 RE;-E@ER(S)0 #A,E(S) (-NC8U#-N3 U(#A,ES)0
C1M(8E,E A##RESS(ES)>
COLCHICUM AUTUMNALE
International Programme on Chemical Safety
Poisons Information Monograph 1!
Plant
1" NAME
1"1 Scientific name
Colchic#m a#t#mnale L"
1"! $amily
Colchicaceae
1"% Common name&s' an( synonyms
Common names)
A#t#mn croc#s &U*'+
a,afran sil-estre+
colchico &Italy'+
colchico a#t#mnale &Italy'+
colchico com#n colchic#m+
colchi.#e &$rance'+
(ame n#e+
fall croc#s &USA'+
Her/st/l#me &0ermany'+
Her/st,eitlose &0ermany'+
mea(o1 croc#s+
mea(o1 saffron &U*'+
Michel1#r, &0ermany'+
mysteria+
Nac2te 3#ngfer &0ermany'+
na2e( /oys+
na2e( la(ies &U*'+
p#rple croc#s+
safran (es pr4s+
t#e5chien+
-eille#se+
6iesensafran &0ermany'+
6interha#ch &0ermany'+
1on(er /#l/+
,afferano /astor(a &Italy'+
,afferano sal-atico &Italy'+
7eitlose &0ermany'"
Latin synonyms)
C" a#t#mnale s#/species pannonic#m &0rise/" 8 Schen2' Nyman+
C" a#t#mnale -ar" /#lgaric#m &9elen"' :omin+
C" /orisii Stef"+
C" /#garic#m 9elen"+
C" comm#ne Nec2"+
C" (reno1s2ii :egen 8 ;ech"f"+
C" haynal(ii He#ff"+
C" pannonic#m 0rise/" 8 Schen2+
C" polyanthon *er 0a1l"+
C" praeco< Spenn"+
C" rho(opae#m *o-"+
C" transsil-anic#m Sch#r+
C" -ernale Hoffm"+
C" -ern#m *#nth+ &Stri( 8 Tan= 1>>1+ T#tin et al"= 1>?@'"
!" SUMMA;A
!"1 Main ris2s an( target organs
Colchicine e<erts m#lti5organ to<icity" The main to<ic
effects are relate( to the effects of colchicine on mitosis
an( acco#nt for (iarrhoea= /one marro1 (epression=
car(ioto<icity= central ner-o#s system (ist#r/ances an(
alopecia" Other ac#te effects are hypo-olemia= shoc2 an(
coag#lation (ist#r/ances= 1hich may lea( to (eath"
!"! S#mmary of clinical effects
To<ic manifestations appear after a (elay of ! to 1!
ho#rs follo1ing ingestion or parenteral a(ministration"
Symptomatology progresses in three stages)

Stage I &:ays 15%' 0astrointestinal an( circ#latory
phase)

5Se-ere gastrointestinal irritation) na#sea= -omiting=
a/(ominal cramps= se-ere (iarrhoea"
Central ner-o#s system e<citation an(Bor (epression"

5:ehy(ration= hypo-olemia= shoc2" Car(iogenic shoc2 may
occ#r an( may res#lt in (eath 1ithin the C! ho#rs"

5Hypo-entilation= ac#te respiratory (istress syn(rome"

Stage II &:ays %51@' Done marro1 aplasia phase)

5Done marro1 aplasia 1ith agran#locytosis"

5Coag#lation (isor(ers 1ith (iff#se haemorrhages"

5;ha/(omyolysis"

5Polyne#ritis= myopathy= ascen(ing paralysis"

5Ac#te renal fail#re"

5Infectio#s complications"

Stage III &After 1@ (ays' ;eco-ery phase)

5Alopecia"
!"% :iagnosis
Colchicine le-els are not clinically #sef#l) /iological
samples m#st /e store( in airtight con(itions an( protecte(
from light"

Monitor the follo1ing)

5Electrolytes= partic#larly potassi#m= calci#m"

5Aci(5/ase /alance"

5$#ll /loo( co#nt an( platelets"

5Coag#lation parameters an( fi/rinBfi/rinogen (egra(ation
pro(#cts"

5Creatinine phospho2inase an( transaminases"
!" $irst5ai( meas#res an( management principles
Patients 1ith C" a#t#mnale poisoning sho#l( al1ays /e
a(mitte( as soon as possi/le in an intensi-e care #nit &an(
monitore( for at least ? ho#rs'"

Treatment may incl#(e)
5Early gastric emptying"
Acti-ate( charcoal in repeate( (oses"

5;ehy(ration= plasma e<pan(er inf#sion= inotropic an(
-asopressor (r#gs"

5Artificial -entilation"

5Correction of electrolyte an( aci(5/ase (isor(ers"Early
force( (i#resis"

5Pre-ention of infectio#s complications"
Monitor -ital signs &EC0= /loo( press#re= respiration=
central -eno#s press#re'= fl#i( an( electrolyte /alance=
haematological an( coag#lation parameters"
!"E Poisono#s parts
The acti-e principles are containe( in all parts of the
plant= especially in the see(s an( /#l/s"
!"F Main to<ins
The main to<in is colchicine" Se-eral other less to<ic
principles ha-e /een isolate( &0essner 8 Or,echo1s2i=
1>C'"
%" CHA;ACTE;ISTICS
%"1 :escription of the plant
%"1"1 Special i(entification feat#res
Colchic#m a#t#mnale is a small her/aceo#s
perennial plant 1@ to @ cm high= flo1ering typically
in the a#t#mn after the lea-es ha-e (isappeare("

Lea-es) lanceolate= (ar2 green= shiny &1E to %E cm < !
to C cm'" They appear in the spring= then (ie /ac2
/efore the flo1ers appear"

$lo1ers) sho1y pin2= p#rple to 1hite flo1ers in gro#ps
of 1 to F are pro(#ce( from an #n(ergro#n( /#l/" Each
petal is a/o#t % to "E cm long an( is f#se( /elo1
into a pale stal25li2e t#/e E5!@ cm long"

$r#it) an o/long to o-oi( green then /ro1n caps#le
containing many see(s &1?@ to !@@'"

D#l/) thic2ene(= -ertical= #n(ergro#n( stem= !"E to F
< ! to cm= co-ere( in a /ro1n t#nic"

:ifferent aspects of C" a#t#mnale may /e seen
thro#gho#t the year)

5in spring) lea-es 1ith fr#it &April to 3#ly'
5in a#t#mn) flo1ers" &A#g#st to Octo/er'

&H#<ley= 1>>!'"
%"1"! Ha/itat
C" a#t#mnale gro1s in 1et mea(o1s= 1oo(lan(
clearings an( sha(y roc2y ha/itats on non calcareo#s
s#/strates" It may /e fo#n( #p to an altit#(e of
!=@@@ metres"
%"1"% :istri/#tion
C" a#t#mnale is a nati-e plant of so#th= 1est
an( central E#rope= e<ten(ing to the eastern /an2s of
the Dlac2 Sea= in 0eorgia &Dr#neton= 1>>E+ T#tin et
al"= 1>?@'" The plant is c#lti-ate( thro#gho#t m#ch
of the 1orl(= primarily as an o#t(oor
ornamental"
%"! Poisono#s parts of the plant
All parts of the plant contain to<ins" The greatest
concentration of to<ins is fo#n( in the see(s an( the /#l/
&corm' &Cooper 8 3ohnson= 1>?+ $rohne 8 PfGn(er= 1>?%'"
Colchicine is present in the flo1ers &@"1 to @"?H in fresh
flo1ers+ #p to 1"?H in (rie( flo1ers'= in the see(s &@"! to
@"?H' in the /#l/ &corm' &@" to @"FH'" The lea-es contain
-ery lo1 amo#nts of colchicine &0essner 8 Or,echo1s2i=
1>C!'"
%"% The to<in&s'
%"%"1 Name&s'
C" a#t#mnale contains se-eral acti-e
principles" Colchicine= the maIor to<in= is an
al2aloi( 1hich 1as isolate( /y Pelletier an( Ca-ento#
in 1?!@ /#t at the time 1as tho#ght to /e -eratrine
1hich is similar in effect" It 1as 0eiger in 1?%%
that i(entifie( the to<in as colchicine &Ne#1inger=
1>>'" The other to<ins present= 1hich are closely
relate( to colchicine= incl#(e)
(esacetylmethylcolchicine= (esacetylthiocolchicine=
colchicosi(e= (emethyl (esacetylcolchicine"
%"%"! :escription= chemical str#ct#re= sta/ility
CAS n#m/er)

colchicine) F5?F5F
(esacetylmethylcolchicine) CC5%@5E
(esacetylthiocolchicine) !C%151F5@

Molec#lar 1eight)

colchicine) %>>"?
(esacetylmethylcolchicine) %C1"C
(esacetylthiocolchicine) %C%"E@

Chemical str#ct#re)

colchicine) C
!!
H
!E
NO
F
(esacetylmethylcolchicine) CHNO
E
(esacetylthiocolchicine) CH
!%
NO

S

The /iological acti-ity of colchicine is (#e to a
portion of its tricyclic molec#le= a se-en5mem/ere(
aromatic cyclopentatrieolone ring &tropolene'
&Ne#1inger= 1>>'"
%"%"% Other physico5chemical
characteristics
Colchicine is freely sol#/le in alcohol or
chloroform an( slightly sol#/le in petrole#m ether"
Sol#/ility in 1ater is 1B!E" On e<pos#re to light=
colchicine is transforme( to l#micolchicine"
Colchicine is not altere( /y (esiccation of the plant
an( it is thermosta/le"
%" Other chemical contents of the plant
No (ata a-aila/le"
" USESBCI;CUMSTANCES O$ POISONIN0
"1 Uses
"1"1 Uses
Miscellaneo#s pharmace#tical pro(#ct
Other therape#tic preparation
Other (r#g+ -eterinary
"1"! :escription
Me(ical)

Se-eral e<tracts of C" a#t#mnale ha-e /een #se( in
therape#tics) po1(er of see(s= tinct#re of see(s or
/#l/= alcoholic e<tracts"

!"E g of see(s an( !E g of tinct#re contain 1@ mg
colchicine" Altho#gh colchicine has /een #se( for
se-eral (iseases incl#(ing neoplastic an( allergic
(iseases= an( as a (i#retic= it is c#rrently almost
e<cl#si-ely #se( as a pharmace#tical in the treatment
of go#t attac2 an( familial Me(iterranean $e-er"

Homeopathic me(icine)

C" a#t#mnale is #se( for go#t an( polyarthritis"

9eterinary me(icine)

C" a#t#mnale is #se( for arthritis an( as a
(i#retic"
"! High ris2 circ#mstances
Poisoning /y C" a#t#mnale is a rare e-ent" Se-eral
circ#mstances of poisoning ha-e /een reporte( &0essner 8
Or,echo1s2i= 1>C'"

Acci(ental poisoning)

5ingestion of see(s /y chil(ren #sing the (rie( see( parts as
rattles+

5ingestion of lea-es as Jsala(J+

5ingestion of /#l/s in mista2e for onions+

5ingestion of po1(er of see(s+

5ingestion in or(er to in(#ce a/ortions+

5poisoning of n#rsing animals or of h#man /eings after #se of
mil2 from poisone( animals &goats= sheep'"

&Cooper 8 3ohnson= 1>?+ 0essner 8 Or,echo1s2i= 1>C+
*ings/#ry= 1>F'"

9ol#ntary into<ication)

5Ell1oo( an( ;o// &1>C1' reporte( a case of a 1F5year5ol(
girl 1ho ha( eaten a (o,en flo1ers"

Criminal into<ication)

5/y alcoholic e<tract has /een reporte( &0essner 8
Or,echo1s2i= 1>C'"
"% High ris2 geographical areas
See section %"1"%"
E" ;OUTES O$ EKPOSU;E
E"1" Oral
Into<ication is al1ays (#e to oral a/sorption of parts
of the plant or e<tracts"
E"! Inhalation
No (ata a-aila/le"
E"% :ermal
No (ata a-aila/le"
E" Eye
No (ata a-aila/le"
E"E Parenteral
No (ata a-aila/le"
E"F Others
No (ata a-aila/le"
F" *INETICS
F"1 A/sorption /y ro#te of e<pos#re
Oral)

;api(ly a/sor/e( from the gastrointestinal tract" Pea2
plasma concentration is reache( @"E to ! ho#rs after
ingestion &6allace 8 Ertel= 1>C%'"

Half time of a/sorption is 1E min#tes &0alliot= 1>C>'"

A/sorption may /e mo(ifie( /y pH= gastric contents=
intestinal motility &6allace et al"= 1>>@'

Colchicine is not totally a/sor/e(" There is an important
hepatic first pass effect"
F"! :istri/#tion /y ro#te of e<pos#re
Protein /in(ing is 1@ to !@H &Dennett et al"= 1>?@'"

Colchicine (istri/#tes in a space larger than that of the
/o(y" The apparent -ol#me of (istri/#tion is !"! LB2g
&6allace et al"= 1>C@'" In se-ere renal or li-er (iseases
the -ol#me of (istri/#tion is smaller &1"? LB2g'"

Colchicine acc#m#lates in the 2i(ney= li-er= spleen=
gastrointestinal 1all an( le#2ocytes /#t not in heart= /rain=
s2eletal m#scle"

Colchicine crosses the placenta an( has also /een fo#n( in
maternal mil2"
F"% Diological half5life /y ro#te of e<pos#re
a' Parenteral)

After a single ! mg intra-eno#s (ose the a-erage plasma half5
life is !@ min#tes &6allace et al"= 1>C@'" Plasma half5life
is increase( in se-ere renal (isease &@ min#tes' an(
(ecrease( in se-ere hepatic (isease &> min' &6allace et al"=
1>C@'"

/' Oral)

After oral a(ministration plasma concentrations reach a pea2
1ithin @"E to ! ho#rs an( after1ar(s (ecrease rapi(ly 1ithin
! ho#rs &6allace 8 Ertel= 1>C%'" The plasma half5life is F@
min#tes &0alliot= 1>C>'" Colchicine may remain in tiss#es
for as long as 1@ (ays"
F" Meta/olism
Colchicine #n(ergoes some hepatic meta/olism"
Colchicine is partially (eacetylate( in the li-er &Nai(#s et
al"= 1>CC'" Large amo#nts of colchicine an( of its
meta/olites #n(ergo enterohepatic circ#lation" This may
e<plain the occ#rrence of a secon( plasma pea2 concentration
o/ser-e( E to F ho#rs after ingestion &0alliot= 1>C>+
6alas,e2 et al"= 1>F@'"
F"E Elimination an( e<cretion
Colchicine is e<crete( #nchange( &1@ to !@H' or as
meta/olites"

*i(ney)

Urinary e<cretion amo#nt to 1F to CH of an a(ministere( (ose
&Heaney et al"= 1>CF'" E@ to C@H of colchicine is e<crete(
#nchange( an( %@ to E@H as meta/olites" !@H of the (ose
a(ministere( is e<crete( in #rine in the first ! ho#rs an(
!C"EH in the first !? ho#rs" Colchicine is (etecte( in #rine
#p to C to 1@ (ays after ingestion" Urinary e<cretion is
increase( in patients 1ith impaire( hepatic f#nction &6allace
et al"= 1>C@'"

Dile)

1@ to !EH of colchicine is e<crete( in the /ile &Heaney et
al"= 1>CF'"

$aeces)

Large amo#nts of the (r#g are e<crete( in the faeces" After
intra-eno#s a(ministration 1@ to EFH is e<crete( in the
faeces 1ithin the first ? ho#rs &6alac,e2 et al"= 1>F@'"

Dreast Mil2)

Colchicine may /e eliminate( in /reast mil2"
C" TOKINOLO0A
C"1 Mo(e of action
Colchicine /in(s to t#/#lin an( this pre-ents its
polymeri,ation into microt#/#les" The /in(ing is re-ersi/le
an( the half5life of the colchicine5t#/#lin comple< is %F
ho#rs" Colchicine impairs the (ifferent cell#lar f#nctions
of the microt#/#le) separation of chromosome pairs (#ring
mitosis &/eca#se colchicine arrests mitosis in metaphase'=
amoe/oi( mo-ements= phagocytosis"

To<ico(ynamics

Mitosis /loc2a(e acco#nts for (iarrhoea= /one marro1
(epression an( alopecia" Colchicine may ha-e a (irect to<ic
effect on m#scle= incl#(ing heart m#scle= central an(
peripheral ner-o#s system an( li-er" Inhi/ition of cell#lar
f#nction (oes not= ho1e-er= acco#nt for all the organ
fail#res seen in se-ere o-er(ose"

Pharmaco(ynamics

0o#t inflammation is initiate( /y #rate crystals 1ithin
tiss#es" The crystals are ingeste( /y ne#trophils /#t this
lea(s to the release of en,ymes an( the (estr#ction of the
cells" Chemotactic factors are release( an( attract more
ne#trophils" Colchicine may act /y pre-enting phagocytosis=
the release of chemotactic factors an( the response of
ne#trophils"

Colchicine= in therape#tic (oses= has other properties s#ch
as antipyretic effects= respiratory (epression=
-asoconstriction an( hypertension"
C"! To<icity
C"!"1 H#man (ata
C"!"1"1 A(#lts
E g see(s L E@ g tinct#re L !@ mg
colchicine is a lethal (ose"
C"!"1"! Chil(ren
The lethal (ose for chil( is sai( to
/e c" 1 to 1"Eg &$rohne 8 PfGn(er= 1>?%'"

Ell1oo( 8 ;o// &1>C1' reporte( a fatal
o#tcome in a 1F5year5ol( girl 1ho ha( eaten a
(o,en flo1ers of C" a#t#mnale &for (etails
see section 11"1'"
C"!"! ;ele-ant animal (ata
Li-estoc2 loss (#e to C" a#t#mnale has /een
reporte( in E#rope" In o<en= ingestion of ? to 1@ gB2g
fresh lea-es or !5% gB2g (rie( lea-es &in hay' 1as
lethal &*ings/#ry= 1>F'"

Poisonings in (ogs ha-e also /een reporte("
C"!"% ;ele-ant in -itro (ata
No (ata a-aila/le"
C"% Carcinogenicity
No (ata a-aila/le"
C" Teratogenicity
No (ata a-aila/le"
C"E M#tagenicity
No (ata a-aila/le"
C"F Interactions
No (ata a-aila/le"
?" TOKICOLO0ICALBTOKINOLO0ICAL ANALASES AN: DIOME:ICAL IN9ESTI0ATIONS
?"1 Material sampling plan
?"1"1 Sampling an( specimen collection
?"1"1"1 To<icological analyses
?"1"1"! Diome(ical analyses
?"1"1"% Arterial /loo( gas analysis
?"1"1" Haematological analyses
?"1"1"E Other &#nspecifie(' analyses
?"1"! Storage of la/oratory samples an( specimens
?"1"!"1 To<icological analyses
?"1"!"! Diome(ical analyses
?"1"!"% Arterial /loo( gas analysis
?"1"!" Haematological analyses
?"1"!"E Other &#nspecifie(' analyses
?"1"% Transport of la/oratory samples an( specimens
?"1"%"1 To<icological analyses
?"1"%"! Diome(ical analyses
?"1"%"% Arterial /loo( gas analysis
?"1"%" Haematological analyses
?"1"%"E Other &#nspecifie(' analyses
?"! To<icological Analyses an( Their Interpretation
?"!"1 Tests on to<ic ingre(ient&s' of material
?"!"1"1 Simple M#alitati-e Test&s'
?"!"1"! A(-ance( M#alitati-e Confirmation Test&s'
?"!"1"% Simple M#antitati-e Metho(&s'
?"!"1" A(-ance( M#antitati-e Metho(&s'
?"!"! Tests for /iological specimens
?"!"!"1 Simple M#alitati-e Test&s'
?"!"!"! A(-ance( M#alitati-e Confirmation Test&s'
?"!"!"% Simple M#antitati-e Metho(&s'
?"!"!" A(-ance( M#antitati-e Metho(&s'
Colchicine may /e analyse( in
/iological fl#i(s /y (ifferent metho(s)

5$l#orometric metho() $l#orescence of
organometallic &0alli#m' comple<es &Do#r(on
8 0alliot= 1>CF'"

5;a(ioimm#noassay) &Ertel et al"= 1>CF+
Scherrman et al"= 1>?@'

5High performance li.#i( chromatography)
&3ar-ie et al"= 1>C>+ Caplan et al"= 1>?@+
Hai,er= 1>?+ Lhermitte et al"=
1>?E'"
?"!"!"E Other :e(icate( Metho(&s'
?"!"% Interpretation of to<icological analyses
?"% Diome(ical in-estigations an( their interpretation
?"%"1 Diochemical analysis
?"%"1"1 Dloo(= plasma or ser#m
Plasma

5Do#r(on an( 0alliot &1>CF' reporte( plasma
le-els lo1er than !@ ngBmL at the Fth ho#r in
se-ere into<ications"

53ar-ie et al" &1>C>' in an o-er(ose 1ith C"E
mg= note( plasma le-els of !1 ngBmL at the
Fth ho#r an( /elo1 E mgBmL at the !th
ho#r"

5In se-ere into<ications plasma le-els
#s#ally range /et1een !@ to E@ ngBmL (#ring
the ! first ho#rs" After the !th ho#r only
small amo#nts of colchicine &N !@ ngBmL' are
(etecte( in plasma &Dism#th et al"= 1>CC+
Lam/ert et al"= 1>?1+ 3aeger et al"=
1>?E'"

5Hai,er &1>?' reporte( post5mortem ser#m
/loo( le-els of 1C@ an( !@ ngBmL &at the th
an( ?th ho#r' in ! heroin a((icts follo1ing
intra-eno#s inIection"

5Lhermitte et al" &1>?E' note( the follo1ing
plasma le-els in an o-er(ose 1ith %1 mg
orally) C!@= !1!= 1%!= an( 1!@ ngBmL at the
!@= 1!E= %@E= F@E min#tes respecti-ely"

Dloo(

Colchicine le-els in /loo( are higher than
those in plasma"

5In an o-er(ose 1ith !@ mg colchicine orally
Caplan et al" &1>?@' note( a /loo( le-el of
!E@ ngBmL at the !n( ho#r" No colchicine
co#l( /e (etecte( at the @th ho#r"
?"%"1"! Urine
Colchicine le-els in #rine range
/et1een !@@ an( !E@@ ngBmL o-er the first !
ho#rs &Dism#th et al"= 1>CC+ 3aeger et al"=
1>?E+ Lam/ert et al"= 1>?1'"

3aeger et al" &1>?E' st#(ie( #rinary
e<cretion in E cases" Concentrations in
#rine are ! to ?@ fol( higher than those in
plasma" to !E of the (ose ingeste( 1as
e<crete( in #rine o-er % to 1@ (ays"
E<cretion 1as specially high (#ring the first
! ho#rs follo1ing ingestion" Colchicine is
eliminate( in #rine #p to the 1@th
(ay"
?"%"1"% Other fl#i(s
0astric la-age fl#i()

In cases= gastric la-age performe( % to F
ho#rs post ingestion remo-e( C to !EH of the
(ose ingeste( &3aeger et al"= 1>?E'"

:iarrhoea)

In an o-er(ose 1ith !E mg colchicine orally=
1" mg 1ere eliminate( in (iarrhoea on the
!n( (ay &3aeger et al"= 1>?E'"
?"%"! Arterial /loo( gas analyses
?"%"% Haematological analyses
JDasic analysesJ
J:e(icate( analysesJ
JOptional analysesJ
?"%" Interpretation of /iome(ical in-estigations
?" Other /iome(ical &(iagnostic' in-estigations an( their
interpretation
?"E O-erall interpretation of all to<icological analyses an(
to<icological in-estigations
Colchicine may /e meas#re( in /iological fl#i(s /#t
le-els are not #sef#l or necessary for the management of
colchicine poisoning"

Sample collection
Dloo( samples for colchicine sho#l( /e (ra1n in plastic t#/es
1ith heparin" Colchicine may /e analyse( in 1hole /loo( or
plasma" Diological samples &/loo(= plasma= #rine"""' sho#l(
/e store( in airtight con(itions an( protecte( from light"
Concentrations in 1hole /loo( are mar2e(ly higher than those
in plasma" Concentrations in #rine are 1@ to ?@ fol( higher
than those in plasma"

Diome(ical analysis
A /iochemical profile 1ith gl#cose= DUN= electrolytes=
creatinine= /loo( cell co#nt= coag#lation parameters= li-er
an( m#scle en,ymes= an( /loo( gases sho#l( /e o/taine( on
a(mission an( repeate( e-ery 1! ho#rs" Samples for
/acteriological analysis sho#l( /e o/taine( at the stage of
aplasia or 1hen fe-er occ#rs"

To<icological analysis
Colchicine analysis in /iological fl#i(s is not necessary or
#sef#l for the management of the poisoning"

Other in-estigations
No other specific in-estigations are re.#ire(" Done marro1
/iopsy may /e in(icate( /#t it is not performe(
ro#tinely
?"F ;eferences
>" CLINICAL E$$ECTS
>"1 Ac#te poisoning
>"1"1 Ingestion
To<ic manifestations appear after a (elay of !
to 1! ho#rs follo1ing ingestion" The (elay may /e
increase( if other (r#gs (ecreasing gastrointestinal
motility ha-e also /een ingeste( &pheno/ar/itone=
psychotropic (r#gs= opi#m (eri-ati-es'"
Symptomatology progresses in % stages an( may
incl#(e)

Stage I &:ay 15%' 0astrointestinal an( circ#latory
phase)

5Se-ere gastrointestinal irritation) Na#sea=
-omiting= a/(ominal cramps= se-ere (iarrhoea"

5:ehy(ration= hypo-olemia= shoc2= prolongation of
prothrom/in time= le#cocytosis" Car(iogenic shoc2 may
occ#r an( may res#lt in (eath 1ithin the first C!
ho#rs"

5Hypo-entilation= ac#te respiratory (istress
syn(rome"

Central ner-o#s system e<citation an(Bor
(epression"

5Hypo-entilation= ac#te respiratory (istress
syn(rome"

Stage II &:ay %51@' Done marro1 aplasia phase)

5Done marro1 aplasia 1ith agran#locytosis"

5Coag#lation (isor(ers 1ith (iff#se haemorrhages"

5;ha/(omyolysis"

5Polyne#ritis= myopathy= ascen(ing paralysis"

5Ac#te renal fail#re"

5Infectio#s complications"

Stage III) &After 1@ (ays' ;eco-ery phase)

5Alopecia"
>"1"! Inhalation
Not rele-ant"
>"1"% S2in e<pos#re
Not rele-ant"
>"1" Eye contact
Not rele-ant"
>"1"E Parenteral e<pos#re
>"1"F Other
&Ellenhorn et al"= 1>>F+ 0a#ltier 8 Dism#th=
1>C?+ Stapc,yns2i et al"= 1>?1'"
>"! Chronic poisoning
>"!"1 Ingestion
Chronic a(ministration of colchicine may in(#ce
similar to<icity to that seen in ac#te poisoning)
gastrointestinal symptoms &-omiting= (iarrhoea'=
agran#locytosis= aplastic anaemia= myopathy &0oo(man 8
0ilman= 1>?E'"
>"!"! Inhalation
No (ata a-aila/le"
>"!"% S2in e<pos#re
No (ata a-aila/le"
>"!" Eye contact
No (ata a-aila/le"
>"!"E Parenteral e<pos#re
>"!"F Other
No (ata a-aila/le"
>"% Co#rse= prognosis= ca#se of (eath
Co#rse)

&see section >"1"1"'

Prognosis)

Prognosis is relate( to the (ose ingeste( &see section C"!"1'
an( therape#tic meas#res &especially early inter-ention'"

Occ#rrence of car(iogenic shoc2 in(icates a poor prognosis
&Sa#(er et al"= 1>?%'"

If the patient has reco-ere( from aplasia an( has not
(e-elope( ac#te respiratory (istress syn(rome or systemic
infectio#s complications= prognosis is #s#ally goo("

Ca#se of (eath)

At the early stage &(ay 1 to %'= ca#se of (eath 1ill /e (#e
to car(io-asc#lar shoc2 an(Bor ac#te respiratory (istress
syn(rome"

:eath (#e to haemorrhagic or infectio#s complications may
occ#r at the stage of /one marro1 aplasia &(ay % to
1@'"
>" Systematic (escription of clinical effects
>""1 Car(io-asc#lar
Shoc2)

Car(io-asc#lar shoc2 is al1ays present in se-ere
into<ications" Most (eaths res#lt form shoc2 1ithin
the first C! ho#rs"

Hypotension is #s#ally the res#lt of hypo-olemia (#e
to gastrointestinal fl#i( loss" Hypo-olemia 1ith
(ecrease( central -eno#s press#re is initially al1ays
present /#t some patients may (e-elop car(iogenic
shoc2 &Sa#(er et al"= 1>?%+ Dism#th 8 Se/ag=
1>?1'"

Haemo(ynamic st#(ies sho1e( t1o (ifferent profiles)
patients 1ith a hyper2inetic state &increase( car(iac
in(e< an( (ecrease( systemic -asc#lar resistances'+
patients 1ith car(iogenic shoc2 &(ecrease( car(iac
in(e< an( increase( systemic -asc#lar resistances'
&Sa#(er et al"= 1>?%'" Occ#rrence of car(iogenic
shoc2 in(icates a poor prognosis" Septic shoc2 may
occ#r (#ring the phase of aplasia"
>""! ;espiratory
Ac#te respiratory fail#re is #s#ally
concomitant 1ith circ#latory fail#re= altho#gh M#rray
et al"= 1>?%= reporte( a case 1ith ascen(ing paralysis
occ#rring more than ho#rs post5e<pos#re"

Ac#te respiratory (istress syn(rome (#e to (iff#se
interstitial an( al-eolar oe(ema has /een reporte( in
se-ere cases &:a-ies et al"= 1>??+ Hill et al"= 1>?F+
Ho/son et al"= 1>?F'"
>""% Ne#rological
>""%"1 Central ner-o#s system &CNS'
In se-ere cases= hypotension an(Bor
hypo<emia can lea( to conf#sion= agitation=
an( mental (epression" Coma an( sei,#res are
o/ser-e(" Profo#n( coma may /e (#e to
cere/ral complications s#ch as
haemorrhages"
>""%"! Peripheral ner-o#s system
Peripheral ne#ritis= ne#romyopathy
an( myopathy ha-e /een reporte(
&Dertran(=1>C>+ Dism#th= 1>CC+ Carr= 1>FE+
$a-arel50arrig#es et al"= 1>CE+ *ontos= 1>F!+
Mo#ren et al"= 1>F>'" Ascen(ing paralysis
may /e responsi/le for respiratory fail#re
&Carr= 1>FE+ M#rray et al"= 1>?%"
Polyne#ritis #s#ally reco-ers 1ithin one
month &Dertran(= 1>C>+ Dism#th et al"= 1>CC'
/#t may last longer &Mo#ren et al"=
1>F>'"
>""%"% A#tonomic ner-o#s system
No (ata a-aila/le"
>""%" S2eletal an( smooth m#scle
;ha/(omyolysis may occ#r 1ith an
increase in m#scle en,ymes an( myoglo/in#ria
&*ontos et al"= 1>F!+ Letellier et al"= 1>C>+
M#rray et al"= 1>?%'"
Letellier et al" &1>C>' reporte( a case of
rha/(omyolysis in a E?5year5ol( patient
treate( 1ith % mg colchicine (aily o-er F
(ays" The patient (e-elope( pro<imal
scap#lar 1ea2ness 1ith m#scle oe(ema an(
increase in m#scle en,ymes"
>"" 0astrointestinal
a' Ac#te)

0astrointestinal symptoms (e-elop after a (elay of !
to 1! ho#rs follo1ing ingestion an( incl#(e na#sea=
-omiting= a/(ominal pain an( se-ere (iarrhoea"
Us#ally (iarrhoea lasts for ? ho#rs an( may in(#ce
hypo-olemia an( electrolyte (ist#r/ances"
0astrointestinal symptoms also occ#r after colchicine
o-er(ose /y the intra-eno#s ro#te" Paralytic ile#s
may (e-elop &Heaney et al"= 1>CF'"

0astrointestinal (ist#r/ances may /e lac2ing or
(ecrease( if (r#gs (ecreasing gastrointestinal
motility &atropine= pheno/ar/itone= opi#m tinct#re'
ha-e also /een ingeste("

/' Chronic)

0astrointestinal symptoms are a common feat#re (#ring
colchicine treatment" Paralytic ile#s has /een
reporte( after intra-eno#s colchicine
treatment"
>""E Hepatic
Colchicine may e<ert (irect hepatic to<icity"
Hepatomegaly has /een reporte(" Hepatic (amage may
occ#r in se-ere poisoning an( incl#(e cytolysis an(
hepatocell#lar ins#fficiency= increase in gl#tamic
pyr#-ic transaminase &S0OT' &alanine amino
transferase= ALT' an( gl#tamic o<aloacetic
transaminase &S0OT' &aspartate amino transferase= AST'
an( in al2aline phosphatase= a (ecrease in coag#lation
factors" Histologic e<amination has sho1n necrosis
an( steatosis of hepatocytes"
>""F Urinary
>""F"1 ;enal
No (irect nephroto<ic effect has
/een reporte(" $#nctional renal
ins#fficiency is #s#ally o/ser-e( an( is
secon(ary to fl#i( an( electrolyte losses or
hypo-olemia"

Ac#te renal fail#re may occ#r follo1ing
car(io-asc#lar or septic shoc2" Protein#ria
an( haemat#ria ha-e /een reporte("
>""F"! Other
No (ata a-aila/le"
>""C En(ocrine an( repro(#cti-e systems
a' En(ocrine

Transient (ia/etes mellit#s has /een reporte( /y
Hilleman( et al" &1>CC' in a E? year ol( 1oman after
an o-er(ose 1ith !E mg"

Inappropriate anti(i#retic syn(rome has /een reporte(
/y 0a#thier et al" &1>CE'"

/' ;epro(#cti-e

Ac#te

Lam/ert et al" &1>?1' reporte( a case of colchicine
poisoning &@ mg' in a 1?5year5ol( pregnant 1oman"
The patient (e-elope( se-ere poisoning 1ith
coag#lopathy= ac#te respiratory (istress syn(rome
&A;:S' an( a/ortion on (ay C follo1ing ingestion" The
patient reco-ere("

Chronic

A re-ersi/le complete a,oospermia has /een reporte( in
a %F5year5 ol( man treate( 1ith colchicine for go#t
&Merlin= 1>C!'" T1o cases of :o1nOs syn(rome /a/ies
ha-e /een reporte(" Ehrenfel( et al" &1>?C' reporte(
the o/stetric histories of %F 1omen 1ith familial
Me(iterranean fe-er on long5term colchicine treatment
/et1een % an( 1! years" Se-en of !? pregnancies en(e(
in miscarriage" 1% 1omen ha( perio(s of infertility"
All 11F infants /orn to mothers 1ho ha( ta2en
colchicine (#ring pregnancy 1ere healthy" The a#thors
(o not a(-ise (iscontin#ation of colchicine /efore
planne( pregnancy /#t recommen( amniocentesis for
2aryotyping an( reass#rance"
>""? :ermatological
Ac#te

Alopecia /egins at a/o#t the 1!th (ay an( is complete
/y % 1ee2s after ingestion" Hair regro1th /egins
after the first month" Sometimes the colo#r of the
hair may change"

C#taneo#s an( s#/c#taneo#s haemorrhages are fre.#ent
in se-ere poisoning" They are (#e to coag#lation
(ist#r/ances"
>""> Eye= ear= nose= throat) local effects
Eyes) S#/conI#ncti-al haemorrhage may
occ#r"

Ear) :efiniti-e #nilateral (eafness (#e to an inner
ear haemorrhage has /een o/ser-e( &personal
e<perience'"

Nose) Nasal haemorrhages may occ#r especially after
local tra#ma (#e to insertion of tracheal or gastric
t#/es"

Throat) Stomatitis may also occ#r &Lam/ert et al"=
1>?1+ 6allace= 1>C'"
>""1@ Haematological
At to<ic (oses= colchicine in(#ces mar2e( /one
marro1 (epression"

Le#2ocytes)

At the initial stage= a peripheral le#2ocytosis occ#rs
fre.#ently" Ho1e-er= the le#cocytes seem at this
stage to /e f#nctionally (eficient" A le#copenia 1ith
agran#locytosis /egins at the thir( (ay an( reaches a
ma<im#m at (ay E to C" 6hite /loo( cells &6DC' ret#rn
to normal -al#es at a/o#t the 1@th to 1!th (ay"

Erythrocytes

Anaemia is fre.#ent in se-ere cases an( may /e (#e to
(ifferent factors)

5Hypoplastic anaemia (#e to /one marro1 s#ppression
may /e o/ser-e( /#t is rarely important"

5Haemolytic anaemia 1ith Hein, /o(y has /een rarely
reporte( &Heaney et al"= 1>CF'"

5Ac#te intra-asc#lar haemolysis 1ith haemoglo/inemia
an( haemoglo/in#ria has /een o/ser-e( in F se-ere
cases &Lam/ert et al"= 1>?1'"

5Se-ere anaemia is mostly secon(ary to m#ltiple
(iff#se haemorrhages"

Dlee(ing (iatheses an( coag#lopathy)

5A ten(ency to1ar(s /lee(ing is al1ays present in
se-ere cases" It appears ! to % (ays follo1ing
ingestion an( may last for ? to 1@ (ays"

5Us#ally the earliest clinical sign of coag#lopathy is
persistent /lee(ing from -eno#s or arterial p#nct#re
sites an( s#/c#taneo#s haemorrhages"

5Other types of /lee(ing incl#(e epista<is= gingi-al=
conI#ncti-al an( gastrointestinal haemorrhages"
Dlee(ing may /e (#e to throm/ocytopenia or a
intra-asc#lar coag#lopathy"

5A cons#mpti-e coag#lopathy 1ith prolongation of
coag#lation time= hypoprothrom/inaemia= a (ecrease in
fi/rinogen= ele-ate( fi/rin (egra(ation pro(#cts an(
throm/ocytopenia is o/ser-e( in se-ere into<ication
&Dism#th et al"= 1>CC+ Cra/ie et al"= 1>C@+ Lam/ert et
al"= 1>?1'"
>""11 Imm#nological
No (ata a-aila/le"
>""1! Meta/olic
>""1!"1 Aci(5/ase (ist#r/ances
Meta/olic aci(osis (#e to
(ehy(ration an(Bor shoc2 may /e
seen"
>""1!"! $l#i( an( electrolyte (ist#r/ances
The gastrointestinal syn(rome often
res#lts in mar2e( (ehy(ration an(
hypo-olaemia 1ith haemoconcentration an(
f#nctional renal fail#re"

Hypo2alaemia (#e to gastrointestinal losses
is also fre.#ent at the initial stage"

Hypocalcaemia may /e seen an( can persist for
se-eral (ays" $rayha et al" &1>?' reporte(=
in a !@5year5ol( girl 1ho ha( ingeste( !@ mg=
con-#lsions an( paralytic ile#s 1hich 1ere
relate( to a hypocalcaemia &1"!E mmolBL'"
Hypocalcaemia may /e (#e to a (irect to<ic
effect of colchicine &Heath et al"=
1>C!'"
>""1!"% Others
Hyperglycaemia) Hilleman( et al"
&1>CC' reporte( a E?5year5ol( 1oman 1ho
ingeste( !E mg an( (e-elope( transient
(ia/etes mellit#s"

Hyperlipaemia) A transient hyperlipaemia has
/een reporte( &Hilleman( et al"= 1>CC'"

Hyper#ricaemia) A transient hyper#ricaemia
as also /een note( &Hilleman( et al"=
1>CC'"

Hyperthermia5fe-er) occ#rrence of fe-er may
/e relate( to an infectio#s complication=
especially (#ring the stage of
aplasia"
>""1% Allergic reactions
No (ata a-aila/le"
>""1 Other clinical effects"
No (ata a-aila/le"
>""1E Special ris2s
Pregnancy

T1o cases of :o1nOs syn(rome /a/ies ha-e /een
reporte(" Ehrenfel( et al" &1>?C' reporte( the
o/stetric histories of %F 1omen 1ith familial
Me(iterranean fe-er on long5term colchicine treatment
/et1een % to 1! years" Se-en of !? pregnancies en(e(
in miscarriage" 1% 1omen ha( perio(s of infertility"
All 1F infants /orn to mothers 1ho ha( ta2en
colchicine (#ring pregnancy 1ere healthy" The a#thors
(o not a(-ise (iscontin#ation of colchicine /efore
planne( pregnancy /#t recommen( amniocentesis for
2aryotyping an( reass#rance"

Dreast5fee(ing

As colchicine is eliminate( in the /reast mil2 /reast5
fee(ing sho#l( /e a-oi(e("
>"E Others
No (ata a-aila/le"
>"F S#mmary
1@" MANA0EMENT
1@"1 0eneral principles
Patients 1ith C" a#t#mnale poisoning sho#l( al1ays /e
a(mitte( to an intensi-e care #nit" Treatment (epen(s on the
(ose ingeste(= the symptomatology an( the (elay follo1ing
ingestion" It incl#(es gastric emptying= acti-ate( charcoal=
early force( (i#resis= an( s#pporti-e treatment 1ith
correction of the shoc2= artificial -entilation= treatment
an( pre-ention of haemorrhagic coag#lation an( infectio#s
complications" 9ital signs &EC0= /loo( press#re= central
-eno#s press#re= respiration' sho#l( /e monitore(" De
caref#l a/o#t -eno#s an( arterial p#nct#res if there is a
se-ere coag#lopathy"
1@"! Life s#pporti-e proce(#res an( symptomaticBspecific treatment
a' O/ser-ation an( monitoring)

Monitor systematically -ital signs= EC0= /loo( press#re an(
central -eno#s press#re" ;epeate( monitoring of central
-eno#s press#re is essential to a-oi( circ#latory o-erloa(
(#ring plasma e<pan(er inf#sion"

If shoc2 is present= insertion of a p#lmonary artery catheter
for monitoring of haemo(ynamic parameters may /e #sef#l for
g#i(ing the treatment in the initial phase"

The patient remains at ris2 #ntil at least ? ho#rs after
e<pos#re"

/' :iarrhoea)

:iarrhoea sho#l( not /e treate( /eca#se some colchicine is
eliminate( in faeces"

c':ehy(ration 5 Electrolyte (ist#r/ances 5 Aci(osis)

0i-e intra-eno#s fl#i(s an( electrolytes accor(ing to
clinical an( /iological stat#s" If meta/olic aci(osis is
present gi-e intra-eno#s /icar/onate" Monitor potassi#m
le-els an( /loo( gases" Maintain a(e.#ate #rinary o#tp#t
&8gt1@@ mLBho#r'"

('Hypotension= shoc2)

Hypotension sho#l( /e anticipate( an( treate( 1ith a(e.#ate
fl#i( replacement an( -asoacti-e (r#gs" Monitor /loo(
press#re" Early instit#tion of haemo(ynamic monitoring is
-ery helpf#l for a(e.#ate treatment of shoc2"

Hypotension an( shoc2 are (#e primarily to hypo-olaemia"
Car(iogenic shoc2 may occ#r"

5Plasma e<pan(ers)