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Ac a O hopaedica
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Risk ac o s o pe iope a i e hype glycemia in
p ima y hip and knee eplacemen s
Esa Jämsen, Pasi I Ne alainen, An i Eskelinen, Ja kko Kallio alkama &
Teemu Moilanen
To ci e his a icle: Esa Jämsen, Pasi I Ne alainen, An i Eskelinen, Ja kko Kallio alkama &
Teemu Moilanen (2015) Risk ac o s o pe iope a i e hype glycemia in p ima y hip and knee
eplacemen s, Ac a O hopaedica, 86:2, 175-182, DOI: 10.3109/17453674.2014.987064
To link o his a icle: h p://dx.doi.o g/10.3109/17453674.2014.987064
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Ac a O hopaedica 2015; 86 (2): 175–182 175
Risk ac o s o pe iope a i e hype glycemia in p ima y hip
and knee eplacemen s
A p ospec i e obse a ional s udy o 191 pa ien s wi h os eoa h i is
Esa JämsEn1, Pasi I nE AlAInEn2, An i EskElInEn1, Ja kko kAllIo AlkAmA1, and Teemu moIlAnEn1
1 Coxa, Hospi al o Join Replacemen , Tampe e; 2 Depa men o In e nal medicine, Tampe e Uni e si y Hospi al, Tampe e, Finland.
Co espondence: esa.jamse[email p o ec ed]
submi ed 2014-02-21. Accep ed 2014-09-08.
Open Access - This a icle is dis ibu ed unde he e ms o he C ea i e Commons A ibu ion Noncomme cial License which pe mi s any noncomme cial use,
dis ibu ion, and ep oduc ion in any medium, p o ided he sou ce is c edi ed.
DOI 10.3109/17453674.2014.987064
Backg ound and pu pose — Pe iope a i e hype glycemia has
been associa ed wi h ad e se ou comes in se e al ields o su -
ge y. In his obse a ional s udy, we iden i ied ac o s associa ed
wi h an inc eased isk o hype glycemia ollowing hip and knee
eplacemen .
Pa ien s and me hods — We p ospec i ely moni o ed changes
in glucose ollowing p ima y hip and knee eplacemen s in 191
pa ien s wi h os eoa h i is. Possible associa ions o pa ien cha -
ac e is ics and ope a ion- ela ed ac o s wi h hype glycemia
(de ined as glucose > 7.8 mmol/L in 2 consecu i e measu emen s)
and se e e hype glycemia (glucose > 10 mmol/L) we e analyzed
using bina y logis ic eg ession wi h adjus men o age, sex,
ope a ed join , and anes hesiological isk sco e.
Resul s — 76 pa ien s (40%) de eloped hype glycemia, and
48 o hem (25% o he whole coho ) had se e e hype glycemia.
Glycemic esponses we e simila ollowing hip eplacemen and
knee eplacemen . P e iously diagnosed diabe es was associa ed
wi h an inc eased isk o hype glycemia and se e e hype gly-
cemia, compa ed o pa ien s wi h no mal glucose me abolism,
whe eas newly diagnosed diabe es and milde glucose me abolism
diso de s had no e ec . In pa ien s wi hou p e iously diagnosed
diabe es, inc eased alues o p eope a i e glycosyla ed hemoglo-
bin (HbA1c) and as ing glucose on he day o ope a ion we e
associa ed wi h hype glycemia. Highe anes hesiological isk
sco e—bu none o he ope a ion- ela ed ac o s analyzed—was
associa ed wi h an inc eased isk o hype glycemia.
In e p e a ion — Pe iope a i e hype glycemia is common in
p ima y hip and knee eplacemen s. P e iously diagnosed diabe-
es is he s onges isk ac o o hype glycemia. In pa ien s wi h
no his o y o diabe es, p eope a i e HbA1c and as ing glucose
on he day o ope a ion can be used o s a i y he isk o hype -
glycemia.

S ess-induced insulin esis ance and consequen pe iope a-
i e hype glycemia ha e been ecognized as impo an isk
ac o s o ad e se ou comes ollowing majo su gical in e -
en ions (Ljungq is e al. 2007, Akh a e al. 2010, Riz i e
al. 2010). In join eplacemen s, pe iope a i e hype glycemia
is a ela i ely common phenomenon (Pili-Flou y e al. 2009)
and i has been epo ed be associa ed wi h an inc eased isk
o p os he ic join in ec ion (PJI) (M ao ic e al. 2011) and
enous h omboembolism (Cohn e al. 2012).
Al hough he e is deba e abou how in ensi ely pe iope a-
i e hype glycemia should be managed (G iesdale e al. 2009),
i is easonable o expec ha con olling se e e hype glyce-
mia would be bene icial (Ljungq is e al. 2007, Jämsen e al.
2010). This is impo an because, unlike mos isk ac o s o
PJI (Jämsen e al. 2010, Bozic e al. 2012, Chen e al. 2013),
hype glycemia can be modi ied. Un o una ely, he e is li le
in o ma ion abou ac o s ha a e p edic i e o hype glycemia
in o hopedic pa ien s.
Diabe es is a well-es ablished isk ac o o PJI (Dowsey
and Choong 2009, Malinzak e al. 2009, Bozic e al. 2012,
Jämsen e al. 2012, Chen e al. 2013) and pe iope a i e hype -
glycemia (Akh a e al. 2010, Masla e al. 2011, Jämsen e
al. unpublished da a), al hough i is impo an o no e ha
pe iope a i e hype glycemia may also de elop in he absence
o an es ablished glucose me abolism diso de (Ljungq is e
al. 2007, Dona elli e al. 2008, Gus a sson e al. 2009, Pili-
Flou y e al. 2009). Mo eo e , a conside able p opo ion o
pa ien s wi h ype 2 diabe es a e undiagnosed (Meding e al.
2007, Saa is o e al. 2008). O he s udies ha e sugges ed ha
exis ing insulin esis ance (Dona elli e al. 2007), me abolic
synd ome (Dona elli e al. 2008), gene al anes hesia a he
han epidu al (Dona elli e al. 2007), and he se e i y o issue
auma (Tho ell e al. 1999) a e associa ed wi h pe iope a i e
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176 Ac a O hopaedica 2015; 86 (2): 175–182
hype glycemia. Howe e , only 1 o hese s udies conce ned
join eplacemen s (Dona elli e al. 2007).
We analyzed he cou se o pe iope a i e hype glycemia in
a se ies o 191 p ima y hip and knee eplacemen s pe o med
o os eoa h i is, and ied o iden i y pa ien cha ac e is ics
and ope a ion- ela ed ac o s associa ed wi h pe iope a i e
hype glycemia. We hypo hesized ha p eope a i e hype gly-
cemia and g ea e su gical s ess (e.g. du a ion o su ge y and
amoun o issue auma) would inc ease he isk o pe iope a-
i e hype glycemia.
Pa ien s and me hods
The pa ien s o his p ospec i e obse a ional s udy we e col-
lec ed a a single publicly unded o hopedic hospi al be ween
Decembe 2009 and May 2011. Pa ien s o all ages unde go-
ing p ima y hip o knee eplacemen o os eoa h i is we e
eligible o inclusion. Pa ien s wi h and wi hou diabe es we e
included. Exclusion c i e ia we e egula co icos e oid ea -
men . Based on a p e ious s udy (Pili-Flou y e al. 2009), i
was es ima ed ha a con enien sample o 200 ope a ions
would be su icien o de ec a 1.5- old di e ence in he isk
o hype glycemia be ween di e en pa ien subg oups (each
ep esen ing ≥ 20% o he ma e ial) a he 5% signi icance
le el wi h ≥ 80% powe . A pos -hoc analysis indica ed ha he
powe calcula ions allowed 5% loss o s udy pa ien s.
S udy p o ocol
Fo he de ailed s udy p o ocol see Supplemen a y da a.
B ie ly, he pa ien s we e ec ui ed a e hey we e scheduled
o su ge y. A esea ch nu se egis e ed hei medical his o y
and made an h opome ic measu emen s. In addi ion o ou-
ine p eope a i e labo a o y es s, he pa ien s had hei lipid
alues, as ing plasma glucose, and glycosyla ed hemoglobin
(HbA1c) measu ed. Pa ien s wi h no his o y o diabe es also
unde wen a 2-h 75-g o al glucose ole ance es , which is
a commonly used and sensi i e means o diagnosing ype 2
diabe es (Ame ican Diabe es Associa ion 2013) and o he dis-
o de s o glucose me abolism (i.e. inc eased as ing glucose
(IFG) and impai ed glucose ole ance (IGT)). Du ing he hos-
pi al s ay, glucose was measu ed 4–6 imes a day om capil-
la y blood samples using a bedside glucose moni o (P ecision
Xceed; Abbo Labo a o ies, Abbo Pa k, IL), acco ding o a
p ede ined scheme. Sho -ac ing insulin (Ac apid; No o No -
disk A/S, Bags ae d, Denma k) was adminis e ed acco ding
o he ea ing anes hesiologis ’s ins uc ions o keep glucose
below 10 mmol/L.
Cha ac e is ics o he s udy popula ion
O he 200 pa ien s ec ui ed ini ially, 191 comple ed he s udy
p o ocol (Figu e 1). The pa ien s included we e compa able o
he whole popula ion o os eoa h i is pa ien s ea ed a ou
hospi al du ing he same pe iod, wi h espec o age (mean 66
(43–89) yea s in he s udy sample and 69 (18–93) yea s in all
o he pa ien s; p = 0.002), sex (65% emales s. 63% emales,
espec i ely; p = 0.6), and ope a ed join (p opo ion o knee
eplacemen s: 61% s. 57%; p = 0.3).
74 s udy pa ien s (39%) unde wen hip eplacemen and 117
s udy pa ien s (61%) unde wen knee eplacemen . Pa ien
demog aphics, como bidi ies, and ope a i e da a a e p esen ed
in Table 1. The majo i y o ope a ions (89%) we e unila e al,
and excep o 9 unicompa men al knees, a o al join eplace-
men was implan ed. A g ea e p opo ion o knee eplace-
men ecipien s han hip eplacemen ecipien s we e obese
(BMI ≥ 30) (56% s. 38%; p = 0.02), bu he p e alences o
diso de s o glucose me abolism, me abolic synd ome, and
sel - epo ed como bidi ies we e simila (da a no shown).
Cemen ed ixa ion was used in he majo i y o knee eplace-
men s (87 o 117, 74%) whe eas 55 o he 74 hip eplacemen s
(74%) we e cemen less. Blood loss was g ea e in hip eplace-
men s han in knee eplacemen s (mean 415 (200–3100) mL
s. 50 (5–800) mL; p < 0.001), and blood ans usions we e
mo e common a e hip eplacemen han a e knee eplace-
men (22% s. 6%; p = 0.001).
Ope a i e de ails
Almos all he pa ien s a i ed a he hospi al on he day o
ope a ion. Spinal anes hesia was used in all ope a ions. In a-
ope a i e luid eplacemen s we e pe o med using ace a ed
Ringe ’s solu ion, which was changed o 5% glucose solu-
ion ( o a oid hypoglycemia and ca abolic me abolism) a e
su ge y and con inued un il he pa ien esumed no mal ood
in ake. A single 3.0-g bolus o ce u oxime was used as an i-
bio ic p ophylaxis (bu when con aindica ed, clindamycin
was used ins ead). An ibio ic-imp egna ed cemen was used
in all cemen ed join eplacemen s. A pneuma ic ou nique
Figu e 1. Collec ion o pa ien s.
Pa ien s ec ui ed o his s udy
n = 200
Pa ien s ope a ed
n = 193
Pa ien s included
n = 191
Hip eplacemen s, 74
Knee eplacemen s, 117
Excluded (n = 7):
– cancelled hei consen o pa icipa e, 2
– wi hd ew om su ge y, 2
– su ge y cancelled due o heal h- ela ed easons, 3
Excluded (n = 2):
– inadequa e pos ope a i e glucose moni o ing, 2
Hip and knee eplacemen s o
os eoa h i is pe o med be ween
Decembe 2009 and May 2011
n = 2,756
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Ac a O hopaedica 2015; 86 (2): 175–182 177
was used in all knee eplacemen s. Closed suc ion d ains (i
used) we e emo ed on he i s pos ope a i e day. Subcu ane-
ous enoxapa in o o al i a oxaban was used as h ombop o-
phylaxis. The median leng h o hospi al s ay was 4 (1–6) days,
and app oxima ely wo- hi ds o he pa ien s we e discha ged
o home di ec ly.
S a is ics
The p ima y ou come was occu ence o hype glycemia
du ing he hospi aliza ion. Hype glycemia was de ined as glu-
cose > 7.8 mmol/L in 2 consecu i e measu emen s o glucose
> 10 mmol/L a any ime poin . The 7.8 mmol/L cu o poin
was based on he de ini ion o hype glycemia by he Ame i-
can Diabe es Associa ion (2013). Glucose > 10 mmol/L (la e
e e ed o as “se e e hype glycemia”) is conside ed o be
he h eshold o ea ing hype glycemia (Ame ican Diabe es
Associa ion 2013), and i has been associa ed wi h pos ope a-
i e complica ions in se e al s udies (Akh a e al. 2010). Thus,
e en a single occu ence o glucose exceeding 10 mmol/L was
conside ed o be clinically signi ican . Occu ence o se e e
hype glycemia was analyzed as a seconda y ou come.
We analyzed possible associa ions o pa ien demog aphics,
medical his o y, esul s o p eope a i e labo a o y es s and
ope a ion- ela ed da a wi h hype glycemia. Da a ela ed o
medical his o y we e based on pa ien epo ing. Diagnoses o
hype ension and (p e iously diagnosed) diabe es we e con-
i med om pa ien eco ds and medica ion da a. The Ame i-
can Socie y o Anes hesiologis s (ASA) isk sco e (Owens e
al. 1978) was used o assess como bidi y and was analyzed
as a ca ego ized a iable. BMI was analyzed bo h as a con-
inuous a iable and a ca ego ized a iable as ollows: no mal
(< 25.0), o e weigh (25–29.9), obese (30.0–34.9), se e ely
obese (35.0–39.9), and mo bidly obese (≥ 40.0).
Diabe ic s a us was ca ego ized as ollows: no mal glucose
me abolism, IFG and/o IGT, and diabe es (diagnosed ei he
p e iously o using OGTT in his s udy). HbA1c was ca e-
go ized in 3 g oups using 6.0% (median alue o he whole
se ies) and 6.5% (which has been accep ed as a means o
diagnosing diabe es by he Ame ican Diabe es Associa ion
(2013)) as cu o poin s. HbA1c was analyzed also as a con-
inuous a iable. Analyses conce ning HbA1c, p eope a i e
as ing glucose, and baseline glucose (a as ing sample aken
a he induc ion o anes hesia) we e pe o med sepa a ely o
pa ien s wi h and wi hou a p e ious diagnosis o diabe es.
Me abolic synd ome was diagnosed acco ding o he consen-
sus c i e ia (Albe i e al. 2009). Pa ien s whose p eope a i e
hemoglobin was below he local labo a o y e e ence alues
(i.e. < 117 g/L in women and < 136 g/L in men) we e consid-
e ed o ha e anemia. Renal unc ion was es ima ed using he
Cockc o -Gaul o mula (Cockc o and Gaul 1976), based
on p eope a i e c ea i ine, and was ca ego ized as no mal
(es ima ed glome ula il a ion a e ≥ 90 mL/min) o as mild
(60–89 mL/min), mode a e (30–59 mL/min), o se e e (< 30
mL/min) enal insu iciency.
Changes in glucose a e su ge y we e simila ollowing hip
eplacemen and knee eplacemen (Figu e 2), so he ma e ials
we e analyzed as a whole o maximize s a is ical powe . In
desc ip i e analyses, c oss- abula ion and he chi-squa e es
we e used o compa ison o ca ego ical a iables and inde-
penden -samples - es o analysis o a iance was used o
compa ison o con inuous a iables.
The a es o hype glycemia and se e e hype glycemia a e
epo ed as pa ien numbe s and pe cen ages. The associa-
Table 1. Pa ien demog aphics, medical s a us, and ope a i e da a
Pa ien demog aphics and como bidi y
Median age a su ge y ( ange), yea s 66 (43–89)
Sex, no.
Female 124 (65%)
Male 67 (35%)
Median body mass index ( ange), kg/m2 30 (21–50)
ASA isk sco e, no.
I 16 (8%)
II 92 (48%)
III 82 (43%)
IV 1 (1%)
Sel - epo ed como bidi ies, n
Hype ension 106 (55%)
Ca dio ascula disease 42 (22%)
Pulmona y disease 31 (16%)
De ma ological disease 28 (15%)
Gas oin es inal disease 22 (12%)
Geni ou ina y disease 17 (9%)
Cance o his o y o cance 14 (7%)
Neu ological disease 6 (3%)
Smoking, n 22 (12%)
Ea lie join eplacemen s, n
None 150 (79%)
Any 41 (21%)
Clinical e alua ion in his s udy
S a e o glucose me abolism, n
No mal 91 (48%)
IFG and/o IGT (“p e-diabe es”) 47 (24%)
Newly diagnosed diabe es 17 (9%)
P e iously diagnosed diabe es 36 (19%)
Me abolic synd ome, n 85 (45%)
P eope a i e anemia, n 10 (5%)
Renal unc ion, n a
No mal 100 (52%)
Mild insu iciency 74 (39%)
Mode a e insu iciency 17 (9%)
Se e e insu iciency 0
Ope a i e da a
Simul aneous bila e al su ge y, no. 21 (11%)
To al join eplacemen , no. 182 (95%)
P os hesis ixa ion, no.
Cemen ed 101 (53%)
Hyb id 7 (4%)
Cemen less 83 (43%)
Median du a ion o su ge y ( ange), min 85 (44–225)
Median ou nique ime ( ange), min 50 (0–129)
Median blood loss ( ange), mL 150 (5–3100)
Blood ans usions, n 24 (13%)
Closed suc ion d ains, n 114 (60%)
a Es ima ed, based on p eope a i e c ea inine acco ding o he
Cockc o -Gaul o mula.
SD: s anda d de ia ion; ASA: Ame ican Socie y o Anes hesiologis s;
IFG: inc eased as ing glucose; IGT: impai ed glucose ole ance.
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178 Ac a O hopaedica 2015; 86 (2): 175–182
ions be ween po en ial isk ac o s o hype glycemia we e
analyzed using bina y logis ic eg ession wi h adjus men o
age, sex, ope a ed join (hip, knee), and ASA isk sco e. In
he adjus ed analyses, all con inuous a iables we e ea ed
as such, i.e. no as ca ego ized. The a iables o adjus men
we e selec ed based on clinical judgmen , because hey we e
hough o be po en ially associa ed wi h bo h in e en ion
and de elopmen o hype glycemia. Fu he mo e, all a iables
we e associa ed wi h he p e alence o glucose me abolism
diso de s, i.e. he baseline isk o hype glycemia (da a no
shown). The espec i e esul s a e p esen ed as adjus ed odds
a ios (ORs) wi h 95% con idence in e als (CIs). Because
odds a ios exagge a e he inc ease in he isk when he ini ial
isk is high (o e 20–30%) (Da ies e al. 1998), we ad ise he
eade o look a he ac ual di e ences in he occu ence o
hype glycemia (i.e. pe cen ages) and o conside he ORs and
hei CIs only as indica o s o s a is ical signi icance, no as
indica o s o how much he isk is inc eased.
E hics
This s udy was pe o med in acco dance wi h he Wo ld Medi-
cal Associa ion Decla a ion o Helsinki. The esea ch plan was
app o ed by he E hics Boa d o Pi kanmaa Hospi al Dis ic ,
Tampe e, Finland (R09207; No embe 24, 2009). All pa ien s
ga e in o med consen o pa icipa e. The s udy has been eg-
is e ed a clinical ials.go (NCT01021826).
Resul s
Al oge he , 76 pa ien s (40%) de eloped hype glycemia and
48 o hem (25%) had se e e hype glycemia. These p opo -
ions we e simila in hip and knee eplacemen s (37% s. 45%
(p = 0.3) o hype glycemia and 30% s. 22% (p = 0.2) o
se e e hype glycemia, espec i ely), as was he o e all glyce-
mic esponse o su ge y (Figu e 2).
P e iously diagnosed diabe es, and inc eased ASA sco e,
p eope a i e HbA1c, and baseline glucose—bu none o he
ope a ion- ela ed ac o s analyzed—we e associa ed wi h
hype glycemia and se e e hype glycemia in he adjus ed
analyses (Table 2). The incidence o bo h hype glycemia and
se e e hype glycemia inc eased wi h age, bu a e adjus -
men s he e we e no s a is ically signi ican di e ences
be ween he age g oups (Table 2). The e ec o ASA sco e
(compa ing ASA sco es III–IV wi h I–II) was p onounced
in pa ien s wi h diabe es (32/38 s. 7/15; adjus ed OR = 6
(1.3–31)) and in pa ien s wi h HbA1c ≥ 6.5% (24/25 s. 3/7;
adjus ed OR = 10 (1.3–82)). ASA sco e was no associa ed
wi h hype glycemia in pa ien s wi hou diabe es (adjus ed OR
= 1.4 (0.66–3.4)) and in hose wi h HbA1c < 6.5% (adjus ed
OR = 1.7 (0.66–4.5)).
None o he sel - epo ed como bidi ies we e associa ed wi h
an inc eased isk o hype glycemia (da a no shown). Pa ien s
wi h a his o y o o he join eplacemen s (n = 41) had hype -
glycemia mo e equen ly han hose ha ing hei i s -e e
join eplacemen (n = 150) (56% s. 35%), bu a e adjus -
men s he e was no s a is ically signi ican di e ence (adjus ed
OR = 1.7 (0.60-4.8)). Smoking had no e ec (Table 2).
Diabe es was s ongly associa ed wi h hype glycemia
(Table 2). All 9 pa ien s who we e on insulin p eope a i ely
p esen ed wi h se e e hype glycemia du ing he hospi aliza-
ion, as compa ed o 19 o 27 o pa ien s ea ed wi h o al
an i-diabe ic agen s (p = 0.06). Pa ien s wi h newly diagnosed
diabe es o p ediabe ic s a es (IFG and/o IGT) we e simila o
he pa ien s wi h no mal glucose me abolism in he adjus ed
analyses (Table 2). Me abolic synd ome was associa ed wi h
an inc eased isk o hype glycemia and se e e hype glycemia
(Table 2), bu in he absence o co-p e alen diabe es i had
no e ec (13/43 s. 24/95; adjus ed OR = 1.3 (0.61–2.8) o
hype glycemia, and 4/43 s. 13/95; adjus ed OR = 0.9 (0.33–
2.6) o se e e hype glycemia). BMI, p eope a i e anemia,
and enal unc ion we e no associa ed wi h pe iope a i e
hype glycemia (Table 2).
The e was also a s ong associa ion be ween HbA1c and
bo h hype glycemia and se e e hype glycemia, independen
o diabe ic s a us (Table 3). In pa icula , 21 o he 22 pa ien s
wi h p e iously diagnosed diabe es and HbA1c ≥ 6.5% we e
hype glycemic pe iope a i ely and 20 o hem de eloped
se e e hype glycemia. In pa ien s wi hou p e iously diag-
nosed diabe es, e en sligh ly inc eased HbA1c (6.1–6.4%)
appea ed o double he isk o hype glycemia (Table 3), bu
he di e ence did no each s a is ical signi icance (adjus ed
OR = 1.7 (0.77–3.9) compa ed o HbA1c ≤ 6.0%). HbA1c ≥
6.5% ins ead showed a signi ican e ec (adjus ed OR = 4.3
(1.1–17).
P eope a i e as ing glucose was no associa ed wi h he
isk o hype glycemia in pa ien s wi h o wi hou a p e ious
diagnosis o diabe es (adjus ed ORs: 1.7 (0.69–4.0) and 1.6
(0.92–2.7), espec i ely). Baseline glucose ins ead inc eased
he isk o hype glycemia in pa ien s wi hou a p e ious diag-
nosis o diabe es (adjus ed OR = 2.4 (1.4–4.3) o an inc ease
o 1 mmol/L). Baseline glucose ≥ 7.0 mmol/L in pa icula ,
compa ed o ≤ 5.5 mmol/L, ma kedly inc eased he odds o
Figu e 2. Mean glucose (wi h 95% CIs) ollowing p ima y hip and knee
eplacemen in pa ien s wi h os eoa h i is.
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Ac a O hopaedica 2015; 86 (2): 175–182 179
Table 2. The e ec s o di e en pa ien - and ope a ion- ela ed ac o s on he incidence o hype glycemia
and se e e hype glycemia. The odds a ios (oRs) we e adjus ed o age, sex, ope a ed join (hip o knee),
and he Ame ican socie y o Anes hesiologis s isk sco e
Hype glycemia Se e e hype glycemia
Adjus ed Adjus ed
n n (%) OR (95% CI) n (%) OR (95% CI)
Gende
Male 67 26 (39) 1 17 (25) 1
Female 124 50 (40) 1.4 (0.70–2.7) 31 (25) 1.3 (0.60–2.6)
Age a 1.0 (0.99–1.1) 1.0 (0.97–1.1)
< 55 yea s 20 5 (25) 1 4 (20) 1
55–64 yea s 68 20 (29) 0.7 (0.22–2.5) 10 (15) 0.4 (0.11–1.6)
65–74 yea s 72 32 (44) 1.0 (0.79–7.3) 20 (28) 0.7 (0.18–2.7)
≥ 75 yea s 31 19 (61) 1.7 (0.42–6.7) 14 (45) 1.2 (0.28–5.5)
ASA isk sco e
I 16 1 (6) 1 1 (6) 1
II 92 27 (29) 5.0 (0.61–41) 15 (16) 2.6 (0.31–22)
III 82 48 (59) 15 (1.8–125) 32 (39) 8.0 (0.93–69)
IV 1 0 (0) - 0 (0) -
Body mass index, kg/m2 a 1.0 (0.94–1.1) 1.0 (0.95–1.1)
< 25.0 28 12 (43) 1 9 (32) 1
25.0–29.9 71 27 (38) 1.0 (0.37–2.5) 11 (16) 0.4 (0.14–1.2)
30.0–34.9 60 24 (40) 1.0 (0.36–2.6) 19 (32) 1.1 (0.39–3.0)
35.0–39.9 20 8 (40) 1.0 (0.28–3.7) 6 (30) 1.0 (0.26–3.9)
≥ 40.0 12 5 (42) 0.8 (0.19–3.8) 3 (25) 0.6 (0.12–3.3)
S a e o glucose me abolism
No mal 91 20 (22) 1 10 (11) 1
IFG and/o IGT 47 17 (36) 1.8 (0.79–4.1) 7 (15) 1.4 (0.48–4.2)
Newly diagnosed diabe es 17 8 (47) 2.4 (0.79–7.5) 3 (18) 1.5 (0.34–6.1)
P e iously diagnosed diabe es 36 31 (86) 18 (5.7–59) 28 (78) 29 (9.1–97)
Me abolic synd ome
Wi hou 106 31 (29) 1 18 (17) 1
Wi h 85 45 (53) 2.2 (1.1–4.2) 30 (35) 2.1 (1.03–4.4)
Smoking
No 169 67 (40) 1 42 (25) 1
Yes 22 9 (41) 1.59 (0.52–4.83) 6 (27) 1.6 (0.52–4.8)
P eope a i e anemia
Wi hou 181 69 (38) 1 44 (24) 1
Wi h 10 7 (70) 3.9 (0.91–17) 4 (40) 2.0 (0.50–8.1)
Renal unc ion
No mal 100 39 (39) 1 26 (26) 1
Mild insu iciency 74 29 (39) 0.6 (0.28–1.2) 15 (20) 0.5 (0.22–1.2)
Mode a e insu iciency 17 8 (47) 0.5 (0.12–1.6) 7 (41) 1.0 (0.27–3.7)
Ope a ion- ela ed da a
La e ali y
Unila e al 170 72 (42) 1 45 (27) 1
Bila e al 21 4 (19) 0.5 (0.14–1.5) 3 (14) 0.7 (0.17–2.5)
Time o induc ion o anes hesia
Be o e 10 am 95 41 (43) 1 25 (26) 1
A e 10 am 96 35 (37) 0.7 (0.40–1.4) 23 (24) 0.9 (0.43–1.7)
Du a ion o su ge y × 10 min a 191 0.95 (0.86–1.1) 1.03 (0.92–1.2)
Blood loss × 100 mL a 191 1.0 (0.88–1.1) 1.0 (0.90–1.2)
Tou nique ime × 10 min
(incl. knees only) a 117 1.0 (0.84–1.2) 1.2 (0.99–1.5)
Cemen used o ixa ion b
None 83 36 (43) 1 21 (25) 1
Any 108 40 (37) 0.8 (0.37–1.6) 27 (25) 1.3 (0.56–2.9)
Blood ans usion
None 167 63 (38) 1 38 (23) 1
Any 24 13 (54) 1.3 (0.48–3.3) 10 (42) 1.8 (0.66–4.7)
Closed suc ion d ains
None 77 31 (40) 1 21 (27) 1
Any 114 45 (40) 2.0 (0.67–5.8) 27 (24) 1.4 (0.44–4.2)
a Con inuous
b Fully cemen less s. ully cemen ed and hyb id join eplacemen s.
ASA: Ame ican Socie y o Anes hesiologis s; IFG: inc eased as ing glucose;
IGT: impai ed glucose ole ance.
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180 Ac a O hopaedica 2015; 86 (2): 175–182
hype glycemia (adjus ed OR = 17 (1.6–178)). In pa ien s wi h
a p e ious diagnosis o diabe es, baseline glucose showed a
simila , bu s a is ically insigni ican associa ion (Table 3).
Fewe pa ien s unde going simul aneous bila e al su ge y
han hose unde going unila e al su ge y had hype glycemia
(4/19 s. 72/170) bu a e adjus men s, he e was no s a is i-
cally signi ican di e ence (Table 2). None o he 9 pa ien s
unde going unicompa men al knee eplacemen p esen ed
wi h hype glycemia, bu 40% o hose who ecei ed o al knee
eplacemen s did (43 o 108) (p=0.02). The o he ope a ion-
ela ed a iables a ailable ( ime o su ge y, du a ion o su -
ge y, ou nique ime, blood loss, use o bone cemen o p os-
hesis ixa ion, use o closed suc ion d ains, allogenous blood
ans usion) we e no associa ed wi h occu ence o hype gly-
cemia (Table 2). These esul s we e simila o hip and knee
eplacemen s, and o unila e al and simul aneous bila e al
ope a ions (da a no shown).
Discussion
One- hi d o he pa ien s had hype glycemia ollowing ou ine
p ima y hip o knee eplacemen o os eoa h i is. In a qua e
o hem, glucose exceeded 10 mmol/L—which is abo e he
ange ecommended o hospi alized pa ien s i espec i e o
hei diabe ic s a us (Moghissi e al. 2009, Umpie ez e al.
2012), and which is also conside ed he h eshold o s a -
ing insulin ea men (Ame ican Diabe es Associa ion 2013).
Occu ence o hype glycemia was s ongly ela ed o exis ing
diso de s o glucose me abolism, pa icula ly o he p esence
o diabe es and o p eope a i e glucose con ol, as measu ed
by HbA1c. None o he ope a ion- ela ed pa ame e s was
independen ly associa ed wi h hype glycemia.
The main s eng hs o ou s udy we e i s p ospec i e na u e
and he s udy popula ion, which ep esen ed he gene al popu-
la ion equi ing join eplacemen o os eoa h i is well. The
de ailed p eope a i e e alua ion allowed de ailed es ing o he
s a e o p eope a i e glucose me abolism and o he me abolic
abno mali ies. A ou ins i u ion, pe iope a i e ca e is highly
s anda dized and i emained essen ially unchanged du ing he
s udy pe iod. The ope a ions we e pe o med by expe ienced
join eplacemen su geons wi h high numbe s o ope a ions
annually. Thus, di e ences in he ea men would no bias
he esul s much. Fu he mo e, he co e age o glucose moni-
o ing was good—e en hough wa d s a pe o med i along
wi h hei daily wo k.
The key inding was he s ong associa ion be ween exis -
ing diso de s o glucose me abolism and pe iope a i e hype -
glycemia. Ou s udy shows ha diabe es, milde diso de s
o glucose me abolism, and me abolic synd ome a e e y
common in hip and knee eplacemen ecipien s. Gi en he
high p e alence o obesi y in pa ien s who unde go join
eplacemen su ge y (Bou ne e al. 2009, Jämsen e al. 2012),
his is no su p ising. One- hi d o pa ien s wi h diabe es had
no been diagnosed p io o scheduling o su ge y. Howe e ,
hype glycemia was less equen in newly diagnosed diabe es
pa ien s han in p e iously diagnosed diabe es pa ien s and, in
he adjus ed analysis, only p e iously diagnosed diabe es was
associa ed wi h hype glycemia.
A clinically impo an obse a ion in ou s udy was he
alue o HbA1c in s a i ying he isk o pe iope a i e hype -
glycemia, bo h in pa ien s wi h and in hose wi hou a p e ious
diagnosis o diabe es. Almos all pa ien s wi h diabe es and an
HbA1c o ≥ 6.5% p esen ed wi h hype glycemia. Based on
ou igu es, i can be es ima ed ha he incidence o pe iope a-
i e hype glycemia could be educed by almos hal i pa ien s
wi h diabe es we e ea ed p eope a i ely o HbA1c ≤ 6.0%.
To ou knowledge, howe e , he e ha e no been any s udies
ha ha e examined he e ec i eness o p eope a i e glucose
con ol in he p e en ion o pe iope a i e hype glycemia o
pos ope a i e complica ions. Mo eo e , in a e ospec i e sin-
gle-cen e s udy o 4,241 hip and knee eplacemen s (Io io e
al. 2012), HbA1c le els a ied ma kedly in diabe ic pa ien s
bo h wi h and wi hou in ec ion, and he a e age HbA1c was
no signi ican ly di e en be ween hese 2 g oups. This sug-
ges s ha , in pa ien s wi h diabe es, ac o s o he han HbA1c
also con ibu e o he occu ence o PJI.
In e es ingly, non-diabe ic HbA1c alues also appea ed o
inc ease he isk o hype glycemia in pa ien s wi h no p e i-
ous diagnosis o diabe es (Figu e 3). Sa o e al. (2010) ha e
demons a ed he associa ion be ween p eope a i e HbA1c
and pe iope a i e insulin esis ance in ca diac ope a ions, bu
in con as o ou esul s, such an associa ion was no ound
o pa ien s wi h no p e ious diabe es diagnosis. Al oge he ,
HbA1c appea s o be an easily applicable ool o s a i ying
he isk o pe iope a i e hype glycemia in join eplacemen s,
i espec i e o diabe ic s a us. Gi en he associa ion be ween
baseline glucose and hype glycemia, measu ing glucose a
induc ion o anes hesia also seems easonable, bu i one elies
Table 3. Associa ion o p eope a i e HbA1c and baseline glucose
(on he day o ope a ion) wi h occu ence o hype glycemia in
pa ien s wi h and wi hou a p e ious diagnosis o diabe es
Pa ien s wi h p e iously Pa ien s wi hou a p e ious
diagnosed diabe es diagnosis o diabe es
Hype - Hype -
glycemia glycemia
n n (%) p a n n (%) p a
HbA1c
≤ 6.0% 7 4 (57) - 96 20 (21) -
6.1–6.4% 7 6 (86) 0.3 49 19 (39) 0.01
≥ 6.5% 22 21 (95) 0.002 10 6 (60) 0.04
Baseline glucose
< 5.6 mmol/L 6 4 (67) - 88 18 (20) -
5.6–6.9 mmol/L 12 10 (83) 0.4 60 22 (37) 0.03
> 6.9 mmol/L 18 17 (94) 0.1 5 4 (80) 0.02
a p- alues a e om pai wise uni a ia e compa isons agains he
lowes HbA1c/glucose ca ego y.
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Ac a O hopaedica 2015; 86 (2): 175–182 181
on his measu e only, he oppo uni y o con ol hype glyce-
mia p eope a i ely is los .
In addi ion o ma ke s o diso de s o glucose me abo-
lism, he ASA sco e was associa ed wi h an inc eased isk
o hype glycemia. Impo an ly, he associa ion be ween
ASA sco e and pe iope a i e hype glycemia was seen
among pa ien s wi h diabe es o wi h a high HbA1c, so dia-
be es as such and glucose con ol do no explain he esul .
The occu ence o diabe es- ela ed complica ions (such as
neph opa hy and concomi an ca dio ascula disease) migh
be a possible explana ion, bu his could no be con i med
wi h he p esen da a.
We hypo hesized ha ope a ion- ela ed ac o s such as
blood loss migh be measu es o su gical auma and co ela e
wi h he hype glycemic eac ion. Con a y o expec a ions, he
e ec s o all he ope a ion- ela ed ac o s analyzed we e sligh
a bes and none showed a s a is ically signi ican associa ion
wi h hype glycemia. The only excep ion—and suppo o ou
hypo hesis—was he obse a ion ha none o he pa ien s who
unde wen unicondyla knee eplacemen had hype glycemia,
bu he e we e only 9 such pa ien s. Pa ien selec ion p ob-
ably explains he ac ha he occu ence o hype glycemia
is lowe in bila e al su ge y han in unila e al. In ou se ies,
he ope a ions we e highly homogenous, which could explain
he nega i e esul s. In e ision join eplacemen s and auma
su ge ies (Richa ds e al. 2012) g ea e hype glycemia and
mo e a ia ion would be expec ed.
Compa ed o an ea lie pape epo ing on pe iope a i e
hype glycemia ollowing hip o knee eplacemen (Pili-Flou y
e al. 2009), he incidence o pe iope a i e hype glycemia in
he p esen s udy was much lowe , al hough we also included
pa ien s wi h diabe es. In he ea lie s udy, he ope a ions we e
pe o med unde gene al anes hesia, leading o mo e di i-
cul s ess- ela ed insulin esis ance (Dona elli e al. 2007),
whe eas we used spinal anes hesia. In addi ion, Pili-Flou y
e al. (2009) had p opo ionally mo e pos p andial glucose
measu emen s han we did. Simila ly, in a e ospec i e s udy
in which only as ing samples we e analyzed, only 3% o
pa ien s had glucose le els o > 11.1 mmol/L (> 200 mg/dL)
(M ao ic e al. 2011). In in e p e ing ou esul s, i should be
acknowledged ha s a is ical powe was calcula ed expec -
ing a g ea e incidence o hype glycemia. Hence, he lowe
incidence o hype glycemia ( oge he wi h he loss o 9 o he
ec ui ed 200 pa ien s) may ha e led o alse-nega i e esul s
in some compa isons.
I appea s likely ha he ex en o su gical s ess- ela ed
pe iope a i e insulin esis ance is smalle in mode n hip
and knee eplacemen s han in, o example, ca diac o open
abdominal su ge y (Tho ell e al. 1999, Dona elli e al. 2007).
The op imal pos ope a i e glucose le el in o hopedic su -
ge y is unknown. Al hough glucose exceeding 7.8 mmol/L is
conside ed o be hype glycemia, ecen guidelines (Ame ican
Diabe es Associa ion 2013) and s udies in he ield o ca dio-
ho acic su ge y (Bhamidipa i e al. 2010) sugges ha keep-
ing pos ope a i e glucose le els be ween 7.8–8.1 and 10.0
mmol/L may be sa is ac o y. In ac , con ol o hype glycemia
ha is oo s ic may be ha m ul—especially in pa ien s wi h
se e e como bidi ies (G iesdale e al. 2009). Thus, he clinical
signi icance o hype glycemia be ween 7.8 and 10.0 mmol/L,
as de ined in ou s udy, is unclea pa icula ly in pa ien s wi h-
ou diabe es.
Highe glucose alues ha e also been associa ed wi h su gi-
cal si e in ec ions a e o hopedic p ocedu es. In a e ospec-
i e s udy o 1,948 p ima y hip o knee eplacemen s, pos op-
e a i e as ing glucose > 200 mg/dL (11.1 mmol/L) doubled
he isk o PJI (M ao ic e al. 2011). Using he same cu o
o glucose, Richa ds e al. (2012) demons a ed a 3- old
isk o su gical si e in ec ion ollowing su gical ea men o
o hopedic auma. Taking in o accoun ha clinical guide-
lines (Moghissi e al. 2009, Umpie ez e al. 2012, Ame ican
Diabe es Associa ion 2013) sugges ea men o hype gly-
cemia > 10.0–11.1 mmol/L, pa ien s wi h such pos ope a i e
glucose alues—e.g. he pa ien s wi h se e e hype glycemia
in ou s udy—should also be iden i ied and ea ed a e join
eplacemen . In addi ion, i should be acknowledged ha
in hese s udies as well as in ou s, hype glycemia was i s
ea ed a e i had occu ed (insulin was adminis e ed on a
so-called sliding scale basis), which leads o in e io ou comes
compa ed o ea men wi h long-ac ing basal-bolus insulin
(Umpie ez e al. 2011).
In conclusion, pos ope a i e hype glycemia occu s e-
quen ly in p ima y hip and knee eplacemen , and in one-
qua e o pa ien s i equi es in e en ion. Mos pa ien s wi h
p e iously diagnosed diabe es de elop hype glycemia, which
is o en se e e, and hey he e o e need close glucose moni o -
ing du ing hei hospi al s ay. In pa ien s wi h no his o y o
diabe es, p eope a i e HbA1c and as ing glucose on he day
o su ge y can be used o es ima e he isk o hype glycemia.
Supplemen a y da a
Fo S udy p o ocol, see www.ac ao hop.o g, iden i ica ion
numbe 7276.
EJ, PIN, JK, and TM designed he s udy. EJ and JK pa icipa ed in collec ing
he ma e ials. EJ pe o med s a is ical analysis, w o e he i s d a o he
manusc ip , and ook ca e o e isions. All he au ho s con ibu ed o in e p e-
a ion o he esul s and p epa a ion o he manusc ip .
We acknowledge inancial suppo o his s udy om he Compe i i e
Resea ch Funding o Tampe e Uni e si y Hospi al, Tampe e, Finland (g an s
9M026 and 9N020) ( ep esen ing go e nmen al unding) and om he Emil
Aal onen Founda ion, Tampe e, Finland.
AE has ecei ed lec u e ees om DePuy and S yke and cong ess paymen s
om DePuy (all un ela ed o he p esen wo k). TM has ecei ed lec u e ees
om Roche and MSD and cong ess paymen s om DePuy (all un ela ed o
he p esen wo k). The o he au ho s ha e no hing o disclose.
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