C O R R ESP O N D EN C E 269
life threatening hyp erkalem ia in a p reviou sly w ell 6-w eek-
old baby. The p atient u nd erw ent a m inor elective su rgical
p roced u re. Postop eratively they w ere com p letely anu ric
d esp ite m u ltip le i.v. flu id bolu ses. At 36 h p ostop eration a
blood sam p le w as sent for u rea and electrolyte analysis.
This revealed sod iu m 126 m M , p otassiu m 7.2 m M , u rea
11.2 m M , and creatinine 163 m M . An u ltrasou nd scan at
this tim e d em onstrated bilateral hyd ronep hrosis and
d ilated u reters. The blad d er w as not visu alized .
The p atient w as ad m itted to the PICU w here conservative
treatm ent for hyp erkalem ia consisted of nebu lised salbu ta-
m ol, bicarbonate infu sion and i.v. calciu m glu conate. The
p atient w as listed for an em ergency cystoscop y and inser-
tion of nep hrostom ies. When w e assessed the p atient, w ho
w as now 48 h p ostop eration, seru m p otassiu m had risen to
7.7 m M . Clinical exam ination revealed them to be ed em a-
tou s bu t otherw ise com fortable. The p arents rep orted ‘jerky’
m ovem ents. The electrocard iogram (ECG) w as norm al. We
w ere concerned that this acu te hyp erkalem ia, second ary to
an obstru ctive p ictu re, had been u nresp onsive to w hat w e
consid ered su b-op tim al m ed ical m anagem ent. The p atient
w as at risk of card iac arrhythm ias esp ecially if su rgery
resu lted in a d irect increase in the seru m p otassiu m .
After consu ltation w ith the intensive care and renal
p hysicians w e d ecid ed to p ostp one su rgery for 2 h w hile the
p atient w as com m enced on an insu lin ⁄ d extrose infu sion,
salbu tam ol infu sion, calciu m resoniu m enem a, and i.v.
m agnesiu m . This resu lted in seru m p otassiu m of 7.1 m M .
Peritoneal d ialysis w as not consid ered p ractical at this tim e.
The p atient w as taken to theatre and anesthetized
u neventfu lly w ith sevoflu rane, fentanyl, and atracu riu m .
The infu sions w ere continu ed p eriop eratively. Desp ite
this, the seru m p otassiu m increased to 7.7 m M . Within 2 h
of com p letion of the su rgery the seru m p otassiu m w as
w ithin norm al range. Over the next 6 h this w as accom -
p anied by a m assive d iu resis of 13 m lÆ kg )1Æ
h )1. The
p atient’s renal fu nction has now fu lly recovered .
We share the observation that conservative treatm ent of
hyp erkalem ia w as d isap p ointing bu t nevertheless need ed
to be op tim ized . This w as im p ortant given that su rgery
ap p eared to contribu te to a rise in the seru m p otassiu m .
Br u c e N e a r y
Ve s n a C o l o v i c
Department of Paediatric Anaesthesia,
Royal Manchester Children’s Hospital,
Hospital Road,
Pendlebury,
Manchester M27 4HA, UK
(email: docbruceter@hotmail.com)
Referen ce
1 Shu kry M, De Am end i A. Safe general anaestheisia in a
hyp erkalaem ic infant. Pediatric Anesthesia 2008; 18: 974–975.
2009 The Au thors
Jou rnal com p ilation 2009 Blackw ell Pu blishing Ltd , Pediatric Anesthesia, 19, 267–287
D yston ic reaction after Botox in jection
u n d er n itrou s oxid e ⁄ oxygen an d
sevoflu ran e an esth esia
d oi:10.1111/ j.1460-9592.2009.02927.x
In trod u ction
Botu linu m toxin is an extrem ely p otent neu rotoxin.
Botu linu m toxin typ e A (BTX-A; Botox, Allergan, Irvine,
CA, USA) has been ap p roved by the Food and Dru g
Ad m inistration for d ifferent u ses. In clinical p ractice, it has
been evalu ated and u sed ‘off-label’ for several other
ap p lications. We rep ort a d ystonic reaction in a p ed iatric
p atient after Botox injections.
Case rep ort
The p atient is a 14-year-old m ale, 72 kg, w ith a history of
cerebral p alsy and left sid ed hem ip aresis sched u led for
chem od enervation w ith Botox to the left u p p er and both
low er extrem ities. The ind ication w as to correct a p rogres-
sive contractu re. H is m ed ical history w as relevant for
p anhyp op itu itarism . H is m ed ications w ere L-thyroxine
100m cg by m ou th qd , H yd rocortisone (Cortef) 10 m g AM
and 5 m g PM , Som atrop in (N u trop in) 3.3 m g 6 d ays p er
w eek, Metform in 500 m g bid . The p atient w as com p liant
w ith his m ed ications intake and d osage w as op tim ized to
blood horm onal titles. Patient w as d escribed as being
ind ep end ent in p erform ing d aily tasks, had a flu ent sp eech
and d oing w ell in a sp ecial p rogram at school.
Anesthesia w as ind u ced and m aintained w ith oxygen ⁄
nitrou s oxid e and sevoflu rane ad m inistered throu gh a face
m ask, w ith the p atient breathing sp ontaneou sly. Botox
w as u sed w ith a concentration of 25 IU p er cu bic centi-
m eter. The p atient had 100 IU of Botox injected to his left
u p p er extrem ity, 75 IU into the brachial rad ialis, 25 IU into
the p ronator qu ad ratu s. H e also had 200 IU of Botox
injected in several sites in his m ed ial ham strings, bilater-
ally. The p roced u re lasted 14 m in and w as w ell tolerated
by the p atient. H e w as transferred to the recovery room in
a stable cond ition. Thirty m inu tes later, he w as noticed to
d evelop a sp astic reaction of his extrem ities, bu t p red om -
inantly his tongu e w hich w as com p letely p rotru d ing from
his m ou th, u nabling his sp eech. The p atient w as afebrile,
w ith no change in m ental statu s and his vital signs w ere
stable. A d ystonic reaction w as d iagnosed by a neu rologist
and 25 m g of Dip henhyd ram ine w as ad m inistered intra-
venou sly. A grad u al im p rovem ent w as observed and the
p atient w as d ischarged hom e 5 h after the p roced u re. H e
w as able to breathe and sw allow ad equ ately. The recovery
p rocess seem ed to be enhanced by m ovem ent and am bu -
lation and the p atient’s fam ily rep orted a retu rn to the
p atient’s baseline level of activity on the follow ing d ay.
There w as no fam ily history of d ystonia rep orted .
270 C O R RE SP O N D EN C E
Figu re 1
Molecu lar m achinery d riving exocytosis in neu rom ed iator release. The core SN ARE com p lex is form ed by fou r a-helices contribu ted by
synap tobrevin, syntaxin and SN AP-25, synap totagm in serves as a calciu m sensor and regu lates intim ately the SN ARE zip p ing.
D iscu ssion
Local injections w ith Botox seem to have effective short-
term resu lts in treating p ed iatric p atients w ith d ifferent
p athologies; how ever there are rep orted ad verse events
(1).
Docu m ented com p lications of Botox injections in ad u lts
have been either p roced u re-related , second ary to d ru g
effects, or id iosyncratic reactions. Ad verse events after
intram u scu lar local injection cou ld be exp lained by the
local d iffu sion of Botox in the ad jacent stru ctu res and are
thou ght to be related to techniqu e and d osage (2). An
im p ortant factor can be the interval betw een injections, as
the bind ing is irreversible, recep tors get satu rated and
fu rther u p take of Botox is im p aired .
Sp read in the nervou s stru ctu res throu gh retrograd e
axonal transp ort m ight be another p ossible m echanism of
d istant m u scle w eakness (3). Possibly, sm all am ou nts of
Botox entering the system ic circu lation can be an exp la-
nation for the generalized sid e effects after local injection.
Botox cleaves the synap tosom e-associated p rotein (SN AP-
25), a p resynap tic m em brane p rotein requ ired for fu sion of
Jou rnal com p ilation
neu rotransm itter-containing vesicles. Synap tobrevin, Syn-
taxin and SN AP-25 constitu te the solu ble N -ethylm alei-
m id e sensitive factor attachm ent recep tor (SN ARE)
com p lex, involved in the p rocess of qu antal transm itter
release (Figu re 1) (4). Dystonic reactions are m ore often
id iosyncratic, and ap p ear to resu lt from d ru g-ind u ced
alteration of d op am inergic–cholinergic balance in the
nigrostriatu m . Inhibitors of SN ARE d ecrease striatal 3, 4-
d ihyd roxyp henylalanine (DOPA) release (5), w hich m ay
exp lain the d ystonic reaction associated w ith Botox.
There are no know n interactions of Botox w ith the
m ed ications or anesthetic d ru gs ad m inistered to this
p atient. Dystonic reactions have been rep orted w ith
sevoflu rane (6) bu t only w hen ad m inistered in com bina-
tion w ith a neu rolep tic ⁄ antip sychotic m ed ication. In gen-
eral, d ystonic reactions occu r m ore often in m ales, and are
m ost com m on in child ren, teens and you ng ad u lts. In ou r
p atient, althou gh the cau sality of Botox in this m ovem ent
d isord er is not totally p roven, it is highly su sp ected
second ary to the tim ing of occu rrence and the absence of
another triggering m ed ication. The p ostop erative p ictu re
w as not com p atible w ith p ostanesthetic d eliriu m . Pred is-
2009 The Au thors
2009 Blackw ell Pu blishing Ltd , Pediatric Anesthesia, 19, 267–287

p osing factors to d ystonia su ch as viral infections cou ld
not be ru led ou t com p letely in this event.
Intravenou s anticholinergic agents are the treatm ent of
choice for these d ystonic reactions, how ever m ore than
one d ose m ay be necessary for com p lete resolu tion of
d ystonia. An ad d itional d ose of d ip henhyd ram ine m ay
have been beneficial in this p atient.
Althou gh u su ally self lim ited , com p lications after Botox
injections m ay be very d isabling. Patients w ith com m u ni-
cation p roblem s exp eriencing these com p lications p ose a
challenge for the care team , esp ecially in the context of
p resched u led p ed iatric am bu latory care. In ord er to avoid
these com p lications, op tim al d ose, injection volu m e, long-
term cu m u lative effect and injection techniqu es shou ld be
stu d ied fu rther.
Cl a u d e A bd a l l a h
Ra a f a t H a n n a l l a h
Division of Anesthesiology,
Children’s National Medical Center,
111 Michigan Ave, NW, Washington, DC, USA
(email: cabdalla@cnmc.org)
Referen ces
1 Li M, Gold berger BA, H op kins C. Fatal case of BOTOX-related
anap hylaxis? J Forensic Sci 2005; 50: 169–172.
2 Klein AW. Contraind ications and com p lications w ith the u se of
botu linu m toxin. Clin Dermatol 2004; 22: 66–75.
3 Olney RK, Am inoff MJ, Gelb DJ et al. N eu rom u scular effects
d istant from the site of botu linum neu rotoxin injection. Neurol-
ogy 1988; 38: 1780–1783.
4 Georgiev DD, Glazebrook JF. Su bneu ronal p rocessing of
inform ation by solitary w aves and stochastic p rocesses. In:
Lyshevski SE, (ed ). Nano and Molecular Electronics Handbook.
Boca Raton: CRC Press, 2007; 17: 36.
5 Zhu G, Okad a M, Yoshid a S et al. Determ ination of exocytosis
m echanism s of DOPA in rat striatu m u sing in vivo m icrod ial-
ysis. Neurosci Lett 2004; 367: 241–245.
6 Bernard JM, Le Rou x D, Pereon Y. Acu te d ystonia d u ring
sevoflu rane ind u ction. Anesthesiology 1999; 90: 1215–1216.
Prom p t an d p ow erfu l effect of a p ractice
gu id elin e on cau d al ad d itives
d oi:10.1111/ j.1460-9592.2009.02926.x
SIR—Cau d al blockad e is the m ost com m on regional tech-
niqu e in p ed iatric anesthesia. To p rolong the analgesic
effect of local anesthetics, p harm acological ad d itives are
frequ ently u sed . In sp ring 2006, C.E. cond u cted a non-
rep resentative international em ail su rvey on the u se of
cau d al ad d itives. Tw enty-five centres p articip ated , from
Germ any (12), United Kingd om (4), Sw itzerland (2),
Au stria (2), France (1), H u ngary (1), USA (1), Canad a (1),
and Au stralia (1), w ith a total nu m ber of m ore than 15,000
2009 The Au thors
Jou rnal com p ilation 2009 Blackw ell Pu blishing Ltd , Pediatric Anesthesia, 19, 267–287
C O R R ESP O N D EN C E 271
23
18
12
6
5
4
2
1
Clonidine Ketamine/S- Opioids None
Ketamine
Figu re 1
Clinical p ractice w ith cau d al ad d itives in 25 su rveyed p ed iatric
anesthetic centers in Germ any (12), UK (4), Sw itzerland (2), Au stria
(2), France (1), H u ngary (1), USA (1), Canad a (1), and Au stralia (1).
Com p arison of d ata from 2006 (left colu m ns) and 2008 (right).
annu al cau d al anesthetics. Clonid ine w as regu larly u sed in
18 centers, ketam ine or S-ketam ine in 12, and op ioid s
(m orp hine, d iam orp hine, fentanyl, and su fentanil) in five.
Tw o centers u sed no cau d al ad d itives at all (Figu re 1).
In Sep tem ber 2007 the Scientific Working Grou p for
Paed iatric Anaesthesia (WAKKA) of the Germ an Society of
Anaesthesiology and Intensive Care Med icine released its
p ractice gu id elines on regional anesthesia in child ren,
follow ing an ad visory statem ent on ep id u ral S-Ketam ine
p u blished earlier that year (1,2). Based on anim al d ata w hich
show ed neu rotoxicity after rep eated intrathecal ap p lication
of S-ketam ine in rabbits ‘no general recom m end ation’ on the
u se of ep id u ral (cau d al) S-ketam ine w as given (3).
In su m m er 2008, C.E. com p leted an u p d ated su rvey on
the u se of cau d al ad d itives w ith all 25 p articip ating centers
from 2006. The resu lts w ere as follow s: Clonid ine w as now
u sed in 23 centers (+5), op ioid s in 6 (+1), and S-keta-
m ine ⁄ ketam ine in fou r ()8) (Figu re 1). S-ketam ine ⁄ keta-
m ine as a cau d al ad d itive w as not u sed in any su rveyed
centre in Germ any, Sw itzerland , and Au stria. All rem ain-
ing fou r u sers w ere centres from the UK.
We conclu d e that this m arked change of attitu d e tow ard s
cau d al S-ketam ine ⁄ ketam ine has m ost likely been cau sed by
the p reviou sly p u blished WAKKA p ractice gu id elines as
clinical p ractice rem ained u nchanged in the p articip ating
British centres. This can be ap p raised as an ind ication for the
p rom p t and p ow erfu l effect of p ractice gu id elines.
C h r i s t o ph Ei c h *
Jo c h e n St r a u s s †
*Department of Anaesthesiology,
Emergency and Intensive Care Medicine,
University Medical Centre Göttingen, Germany
†Department of Anaesthesia,
Perioperative Medicine and Pain Therapy,
HELIOS Medical Centre Berlin-Buch, Germany
(email: ceich@med.uni-goettingen.de)