Archives of Orthopaedic

Arch Orthop Traumat Surg 97 263-274 (1980)

and Traumatic Surgery
© J F Bergmann Verlag 1980

New Clinico-pathophysiological Studies on the Bone Cement Implantation Syndrome

H Rinecker
Chlrurglsche Klinik Dr Rinecker, Isartalstra Be 82, D-8000 Miinchen 70 Federal Republic of Germany

Summary Implantation of endoprostheses with bone endoprostheses employing bone cement have been
cement is followed by alterations of the circulation. reported in many publications The bone cement
Intoxication, caused by the monomer of bone cement implantation syndrome (BIS) can be recognized min-
or pulmonary embolism by intramedullary contents utes after implantation as an abrupt decrease of arterial
constitute the two mostly accepted pathophysiological blood pressure, or less frequently as an increase.
hypotheses Because of the lack of pulmonal and Occasionally, this is followed by irreversible cardiac
circulatory physiological data a clinical decision arrest and simultaneous hypoxemia The intraopera-
concerning the value of the hypotheses was not possible tive mortality ranges from 0 02 % to 6 6 % according to
until now Hip prosthesis implantation was analyzed in the literature l6, 8 l The risk is higher in patients
15 patients by measuring equipment controlled by an receiving hip endoprostheses in cases of fractures of the
on-line-computer The device allowed a high rate of femoral neck It is not clear whether the recent decrease
data retrieval The bone cement implantation syn- in number of published cases with fatal outcome just
drome reveals itself as cardiorespiratory sequelae of a results from a decrease in the number of respective
disseminated pulmonary embolism which is originating publications, or conversely, from a more intensive
in intramedullary contents, sqeezed intravasal Usual employment of empirically developed prophylactic
prophylactic methods are revisited. measures.
Experimental as well as clinical investigations have
Zusammenfassung Bei der Endoprothesenimplanta- led to a number of contradictory hypotheses on the
tion mittels Knochenzement treten Kreislaufreaktio- pathogenesis of the BIS:
nen auf Zwischen den verbreiteten pathologischen It was experimentally shown that manipulations in
Hypothesen hierfuir Knochenzement-Monomer-In- the medullary cavity of the tibia induce reflectory
toxikation und Markinhaltlungenembolie konnte neurogenic hpotension l33l in rabbits Raising the
bisher klinisch mangels lungen und kreislaufphysio- hydrostatic pressure in the exenterated medullary
logischer Daten nicht entschieden werden Mit Hilfe cavity has been used as a model to imitate implantation
einer proze 13rechnergesteuerten Me Banlage wird die of bone cement under pressure into the medullary
Huiftgelenkimplantation bei 15 Patienten mit hoher cavity l44 l.
Registrierfrequenz zahlreicher Parameter untersucht. Formation of heat due to polymerization of bone
Das Knochenzement-Implantations-Syndrom stellt cement as a pathogenetic factor can be ruled out, since
sich als cardiorespiratorische Folge einer disseminier- neither the amount of heat, nor the time course of heat
ten pulmonalen Embolie dar, die durch die intravasale production l4, 51 l concur with the development of BIS.
Einpressung von Markrauminhalt ausge16st wird Die It is, however, conceivable, that an accumulation of
iblichen Prophylaxema 13nahmen werden unter diesen heat affects the coagulatory system after a certain
Gesichtspunkten revidiert. latency, because the response of the coagulatory system
to an increase in temperature has not yet been
sufficiently explored l57 l Thus, generation of pul-
Threatening cardio-respiratory complications as side- monary microemboli due to heating cannot be ruled
effects secondary to implantation of hip or knee out completely.

0344-8444/80/0097/0263/$ 2 40
264 H Rlnecker: New Clinico-pathophyslologlcal Studies on the Bone Cement Implantation Syndrome

It was shown in animal experiments that bone tion procedure This involves on-line operation of a
cement monomer depresses circulation l 20l However, computerized data acquisition and processing system.
the doses necessary to induce circulatory depression are An attempt towards such a system has been made in the
about 10-20 times the concentrations which occur studies presented in this report where 20 digitalized
maximally under clinical circumstances In these parameters have been simultaneously recorded in
studies, a decrease of arterial blood pressure was found. intervals from 10 to 2 40 s.
However, the toxic dilatation of the resistance vessels
which has been postulated could not be demonstrated Methods
on the basis of direct calculations of the total peripheral The investigations were conducted in fifteen 38 to 86-year-old
resistance. patients (mean age: 71 years) Five patients received a total hip
Alternatively, it was suggested that monomer in- endoprosthesis 2 to 4 days after a transcervical fracture of the
duces cardiac depression either myogenic, or brady- femoral neck The other ten patients had coxarthrosis Hence, the
material consists of altogether thirty single bone cement
cardic in nature, leading to this decrease in arterial
Implantations Surgery was conducted in neuroleptanalgesia and
blood pressure l 13, 14 l Studies employing isolated volume controlled artificial ventilation' A standard protocol of
papillary muscle in cats have shown respective phe- alternating dextrane 2 and Ringer's solution was employed for i v.
nomena l2 l. infusions The patients received intraoperatively low-dose
Depression of respiratory activity, or bronchocon- heparin for prophylaxis of postoperative thrombosis Bruns-
wick-polyethylene cups, Lubminus prosthesis shafts and standard
striction induced by monomer do not sufficiently
packages of bone cement were used 3 A suction drainage of
explain the clinical symptoms which in mechanically maximal 75 cm H 2 0 was applied to the femoral cavity during the
ventilated patients are identical Hence, alterations in impaction of bone cement into the shaft.
type of respiration observed in animal experiments l27, Details of the measuring system have been published
28l using clinically occurring monomer concentrations elsewhere l 43 l For measurement a pulmonary function analyzer,
a blood-gas analyzer, and a cardio-vascular function analyzer
have limited significance.
were employed Hemoglobin was determined in venous blood
De-emulsification of fat secondary to high concen- samples prior to and after surgery Per-operatively, six mixed-
trations of monomer in blood l9 l has never been venous blood samples were drawn via a Swan-Ganz catheter
confirmed. localized in the pulmonary artery with respect to the stage of the
Disseminated pulmonary fat emboli following im- surgical procedure.
Pulmonary function analysis included a respiratory com-
plantation have been clinically demonstrated as well as
pliance computer4 , oxymetry 5, and carboxymetry 6.
in autopsy material It was assessed, that impaction of Arterial blood-gas analyses were performed by a blood-gas
bone cement under pressure into the medullary cavity analysis computer Automatic sampling of arterial blood
causes release of material such as fat, fat cells, bone occured "on-line" every 240 S from the radial artery.
marrow cells and thrombokinase into the vascular The cardio-respirator analysis system consisted of a
thermodilution cardiac-output computers, an electrocardio-
system l 49, 51l This induces formation of platelet
graph pressure strain-gauges, and temperature monitors" A
aggregates which are sequestered then in the pul- Swan-Ganz balloon catheter"' introduced into the pulmonary
monary vascular bed together with fibrin deposits l 35l. artery via subclavian vein was connected to the system The
Thus, an involvement of reflectory and thermal cardiac output determinations by injection of cold fluid into the
phenomena in BIS is conceivable, as is toxicity of right atrium were carried out automatically every 240 S as well as
the blocking of a pulmonary artery to obtain the pulmonary
monomer, although concentrations of monomer ex-
wedge pressure.
perimentally used by far exceeded concentrations The data sampled by the function analyzers were fed into an
observed under clinical circumstances On the other on-hne computer' for encoding and storage A second function of
hand, disseminated pulmonary embolization during
1 Engstrom ECS 2000, Jungner Instrument AB, Solna, Sweden
implantation has been clearly demonstrated, however,
2 Longasteril 75
occurence of cardiac, or respiratory complications 3 Refobacin Palacos, Merck, Darmstadt and Kulzer and Co.
could not be related with certainty to this process: Gmb H, Bad Homburg
Investigations conducted intraoperatively in man did 4 Megamed 0 5 2 2 D Megamed AG, Ziirich, Switzerland
not yet produce evidence to support one or the other 5 IBC Differential Oxygen Analyzer 145 B, Bentley Labora-
tories, Santa Ana, California, USA
hypothesis The cardiovascular and respiratory reac-
6 PM-20, Cavitron, Anaheim, California, USA
tions observed during implantation are very transitory 7 175 Automatic p H/Blood Gas System, Corning Glass
in nature, preventing because of the conventional Works, Medfields, Massachusetts, USA
circulatory and respiratory measurements with long 8 Cardiac Output Computer 9510, Edwards Laboratories,
intervals a statistical evaluation What is required, is Santa Ana, California, USA
9 Type 870 + P 3, Fa Datascope, Paramus, New Jersey, USA
a new methodical approach allowing for nearly con-
10 Type 93 A-118-7 F, Edwards Laboratories, Santa Ana,
tinuous registration of data of the pertinent respiratory California USA
and circulatory parameters in order to detect the brief 11 PDP-I I1 V03, digital equipment corporation, Maynard,
and transient abnormalities elicited by the implanta- Massachusetts, USA
H Rinecker: New Chnco-pathophyslological Studies on the Bone Cement Implantation Syndrome 265

the on-line computer was to eliminate recording artifacts %140- IM Pl I IMP 2

produced by the blood sampling, by injection of cold fluid for

cardiac output measurement, and by wedging the Swan-Ganz 120-

catheter Moreover, the computer activated cyclically the

sampling of blood specimen, the injection of cold fluid and the 100- _ \
p/;~=i7
balloon inflation of the Swan-Ganz catheter Finally, the
IL
computer controlled the consistency of the measurements and I' ~~
80-
activated warning signals, if values obtained exceeded given
limits The continuously registered data were stored every 10 Son I0 20 30 4oO S 60 7 860
O 90 10 110 mi

a floppy disc, the data collected every 4 min at time of

measurement. Patient Imp 1 Imp 1 Imp 1 Imp 1 Imp 2 Imp 2 Imp 2 Imp 2 Individual
Dlgltallzation of the raw data allowed postoperative 40 S 160 S 540S 40 S 160 S 540s
values

processing in a computer' 2 The data sampled with 4 mm-

intervals were interpolated linearly by the computer and 1 545 549 562 5 56 475 461 4 33 461

produced as 10-s values This was also to bridge nterruptions 2 360 376 428 5 07 415 4 20 5 70 5 08

caused by elihmnatlon of the recording artifacts This procedure 3 685 676 736 800 771 7 64 739 852
4 02 5 27 5 30 479
allowed for a virtually continuous presentation of 12 additional 4 397 367 249 517
480 491 493 417 5 02 495 468 457
parameters calculated from these data The individual measure- 5
6 462 471 507 462 4 65 4 95 499 481
ments initially taken were found to vary considerably Therefore,
7 760 746 692 6 93 6 97 7 06 7 28 561
control measurements were obtained during a period of 10 min 5 37 7 62
8 485 495 572 500 5 35 5 56
before surgery for calculation of the individual mean The 9 559 558 550 5 49 519 5 08 489 6 02
intraoperative changes were compared on a percentage base + 10 547 536 518 617 571 5 75 5 52 614
standard deviation with these initially obtained control values. 11 494 496 500 491 4 77 4 86 519 527
Since the time of the mplantations differed from patient to 12 454 468 443 4 40 3 66 3 60 3 99 513
patient, the computer had to correct the time axis in presen- 13 843 849 873 8 47 892 893 8 97 914
tations containing the accumulated data of all patients. 14 325 305 369 511 3 94 3 89 3 92 4 44
For statistical analyses, a distribution independent median 15 238 241 231 227 2 64 2 65 2 72 2 72
test for related samples (Wilcoxson test for paired data) l 21 l was
Mean 509 508 515 535 525 526 535 563 I/min
used The moment of onset of the implantation reaction can be
related only vaguely with the moment the bone cement made Significance
contact with the medullary cavity Therefore the statistical O,010
significance of every parameter during and after mplantation 0,025
was tested against the respective control 32 times within 300 s _O_
p oso

after the start of the mplantations.

-70 IMPl 100 +20 300 -0 o
IMP2 100 200 300 sec

Fig 1 Cardiac output Above: Time course over operation.

Results Percentage of individual control out of 10 min pre-surgery
control period Mean ± SEM of 15 patients IMP I and 2 = time
Clinical Observations of implantations Center: Original data during implantation
Because of infusion of plasma-volume expanders, mean reactions Below: Significance level for a de or increase of
cardiac output within 300 S after each implantation Here: no
hemoglobin concentration fell from initially 13 3 to significance reached in the Wilcoxson-test
8.7 g/100 ml at termination of surgery However,
clinical isovolemia was maintained as concluded from a
mean central venous pressure of 8 6 mm Hg, a mean
respective data of the mixed-venous blood samples.
pulmonary wedge pressure of 13 1 mm Hg, and a mean
The relative oxygen supply at termination of surgery
heart rate of 89/min found at the end of surgery.
was calculated as 385 ml/min m 2 implying main-
Cardiac output did not increase inspite of hemo-
tainance of oxygenation at sufficient levels in spite of
dilution A mean cardiac output of 5 71/min was found
hemodilution.
at termination which is only 1 1 ± 4 3 % above the
control value. Body temperature measured in the oesophagus
decreased after introduction of anesthesia during
The 02-content in the inspired air of 50 % led to an
washing to a mean of 35 3 °C It decreased further then
alveolar PO 2 of 226 to 327 mm Hg, an arterial P 0 2 of
114 to 271 mm Hg, and a corresponding right-to-left during surgery by O 60 C only.
shunt volume fraction of 0 022 to 0 113 Such values
can be expected considering the age distribution of the Clinical Significance of Monomer Intoxication
patients l46l Mild hyperventilation was deduced from
The monomer intoxication concept suggests develop-
an arterial PCO 2 ranging from 18 0 to 34 0 mm Hg The
ment of peripheral vasodilatation, or alternatively of
pH values of 7 40 to 7 60 ruled out even a slight
tendency of acidosis This was confirmed also by cardiac depression Peripheral vasodilatation is also
postulated by the medullary reflex-hypothesis In order
12 Tewldata, Munich to test the clinical significance of both hypotheses, the
266 H Rlnecker: New Chnlco-pathophyslologlcal Studies on the Bone Cement Implantation Syndrome

Mean arterial u 140. IM Pil IMP21 Total peripheral

%140- IMPl IMP2 pressure resistance
, I RA I
120-

120-
I
100 ?
100-
._, 80-
v I
l
jo_ '

so-

T i T i i i i i
10 20 30 40 50 60 70 80 90 100 110 mm
an_
V~ _ l l I
'

' 'l
' I i· 1
'
10 20 30 40 50 60 70 80 90 100 110 m-n

Patient Imp 1 Imp 1 Imp 1 Imp 1 Imp 2 Imp 2 Imp 2 Imp 2 Indwvidual
Patient Imp 1 Imp 1 Imp 1 Imp 1 Imp 2 Imp 2 Imp 2 Imp 2 Individual + + + + values
+ + + values 40 S 160 S 540S 40 S 160 S 540 s
40 S 160 S 540 S 40 S 160 S 540 s
1 1158 1325 1365 1710 1087 1172 1284 1091
1 85 96 104 125 70 74 75 68 2 1575 1870 2295 1997 1963 1866 1758 1621
2 74 91 129 131 106 101 128 104 3 1189 1209 1318 1256 1222 1223 1493 947
3 118 121 138 143 127 126 149 113 4 1852 2089 3038 1528 1055 1075 1013 1216
4 96 101 100 81 76 78 72 79 5 982 960 1231 1720 1162 1210 1437 1153
5 72 72 92 114 86 88 99 79 6 1831 1831 2097 2438 1614 1452 1644 1676
6 113 115 141 148 100 97 111 107 7 1093 1169 1373 1295 940 952 1273 1324
7 108 114 124 117 86 88 121 96 8 2246 2310 2740 1676 992 955 1264 1017
8 142 151 202 109 69 67 92 102 9 1417 1361 1448 1761 1462 1524 1616 1513
9 108 103 109 133 103 105 109 123 10 1127 1134 1341 1192 830 848 1128 1015
10 81 80 91 97 64 66 83 84 11 938 968 1198 1609 904 905 796 1000
11 62 65 80 106 59 60 58 72 12 1881 1814 2123 2286 1572 1596 1785 1541
12 115 116 128 139 78 80 96 108 13 597 583 924 944 744 734 891 745
13 75 73 116 113 92 91 109 95 14 1922 2094 1734 1877 1725 1747 1815 1507
14 86 87 89 134 91 92 96 94 15 1858 1935 2287 1779 1455 1670 2292 1469
15 72 75 83 85 73 75 94 67
Mean 1445 1510 1767 1671 1248 1262 1433 1256 dyn sec
Mean 939 974 1151 1183 853 859 995 927 mm Hg cm 5

I N oo005 nr r Significance
Il'
l
U LJIL 0,010
;I ir LI
L L F0,025
p 5 l U Significance I L L 0,025
Pl I I _ I
,050 lj if~~~ 0050
p0,050 d
-7 M L

-70 IMPl +100 +200 +300 -70 IMP2 +

100 200 300 sec -70 IMPl +100 +200 +300 -70 IMP2 +100 +200 300 sec

Fig 2 Mean arterial pressure Fig 3 Total peripheral resistant

time courses of the circulatory variables: cardiac out- tation control values were attained again Blood
put, arterial blood pressure and total peripheral resist- pressure was found to rise also during the second
ance were assessed after the bone cement implantations. implantation The elevations upon both implantations
Cardiac output (Fig 1) was found relatively un- were statistically significant (P < 0 005) A decrease in
stable, but individual deviations appeared to cancel out blood pressure was not observed.
each other as concluded from the accumulated mean Consequently, the totalperipheralresistance(Fig 3)
values An increase occuring 10 min after the first did not decrease during the critical post-implantation
implantation seems to be an exception, though No period when implantation reactions usually evolve To
significant changes in cardiac output were observed the contrary, the total peripheral resistance increased
during the test periods, neither after the first implan- by 20 % for 5 min in a bi-phasic mode The rise
tation, nor after the second This is in agreement with developed already during drilling the cup bed into the
the response of other cardiovascular parameters, the bone The increases are statistically significant (P<
heart rate and derived characteristics of the left and 0.005) Evidence for development of toxic vasodila-
right ventricle: Neither the ventricular work, nor tation could not be found in our patients.
function indices of the cardiac ventricles provided any
evidence for the presence of cardiac depression under Reactions Interpreted as Obstruction
the prevailing clinical circumstances. of the Pulmonary Vascular Bed
During the first implantation, mean arterialblood
pressure (Fig 2) increased by 23% This was followed The second cluster of hypotheses postulate systemic
by a subsequent decrease and later rise together with disturbances secondary to formation of pulmonary
the increase of cardiac output 20 min after implan- microemboli, which have been demonstrated so far on
H Rlnecker: New Clinco-patlhophysiological Studies on the Bone Cement Implantation Syndrome 267

%140- IMPl IMP21 Total respiratory °z in IMP1 IMP21 Artirlal nartlal

7/ iuo
compliance oxygen pressure

120- 110-

/' ^ . , _
I A -a
"-" 100 ' l I
1

.. I- ?\
l

V
i
80- o0-
-i
80, . -i_~T' ~
20
o 30 40 50 60 70 80 90 100 110 mn 1 20 O 40 so 60 70 8b 90 100 no mn

Patient Impl Imp'i Imp Imp1 lmp 2 Imp 2 Imp 2 Imp 2 Individual Patient Imp 1 Imp 1 Imp 1 Imp 1 Imp 2 Imp 2 Imp 2 Imp 2 Individual
-+ + + + values + + + + values
40 S 160 S 540S 40 S 160 S 540 s 40S 160 S 540 S 40S 160 S 540s

1 28 27 25 42 27 27 26 27 1 174 177 190 190 189 189 187 178

2 19 23 16 21 26 23 22 24 2 217 218 219 215 212 212 209 206
3 11 10 11 8 26 19 13 26 3 126 127 116 94 116 116 118 120
4 32 28 24 24 27 25 31 29 4 191 191 191 189 191 190 191 188
5 17 15 16 11 19 14 9 10 5 157 157 150 129 139 139 134 117
6 19 19 19 22 19 21 19 20 6 273 270 258 245 247 246 240 247
7 35 36 33 43 38 38 38 41 7 227 227 227 207 225 226 228 218
8 27 32 21 24 31 30 38 35 8 128 132 133 127 126 126 127 136
9 42 38 37 36 38 40 34 42 9 173 173 171 155 137 137 135 126
10 19 22 18 19 19 19 19 19 10 215 214 209 203 179 179 175 170
11 18 16 17 11 19 19 18 19 11 168 169 172 161 169 169 169 168
12 22 15 19 15 21 21 19 16 12 152 151 149 152 142 142 135 124
13 29 28 23 24 34 36 35 35 13 188 187 183 180 174 173 168 162
14 18 19 16 12 16 15 15 18 14 121 121 106 82 87 88 92 81
15 18 21 22 17 14 15 21 19 15 183 183 185 183 183 187 183 180

Mean 236 233 21 1 220 249 241 238 253 ml/ Mean 1795 1799 1773 1675 1678 1679 1660 1614 mmHg
cmHO20
l 020,005 rl Sgnifcance
J
:r-n r qI p
0 0 05
ooo Slgniflcance r 00 o
o r
U,I lb ' 1'n
r1 F 0,010.
*I U l IUIJ Ul 0,025 02
P r-

', U I1 1 0,050.
'J u L p
Loo
0 0 50
4 J LJ UL_____ -70 IMPl +100 +200 -700 MP2 100 20 300 sec

-70 IM Pl +100 +
200 +300 -70 IMP2 +100 +
200 +300 sec Fig 5 Arterial partial oxygen pressure
Fig 4 Total respiratory compl:

a qualitative basis only In the current study, the total implantation amounted to 17 % over the level prior to
respiratory compliance, arterial PO 2, mean pulmonary implantation Again, the differences are statistically
arterial pressure, and pulmonary vascular resistance significant (P< 0 005, and O 01, respectively).
were analyzed to assess possible functional conse- The increase in pulmonary arterial pressure can
quences of the pulmonary microembolization. only to a small part be explained by an increase in
At both implantations, total respiratorycompliance cardiac output A major part of it resulted from a
(Fig 4) decreased bi-phasically by 17 % which prevailed transient increase of the pulmonary vascular resistance
for 6 min after each implantation The decreases in (Fig 7) The pulmonary resistance started already to
compliance are statistically significant (P< O 005 and rise during preparation of the implantation beds The
0.01 respectively) During this period the airway increase occurred again in the polyphasic manner
resistance remained unchanged while the physiological mentioned above At first implantation pulmonary
dead space underwent minimal alterations only. vascular resistance increased by 33 % 140 S after the
The slightly but continuously decreasing arterial first implantation, the increase is statistically signifi-
PO2 (Fig 5) fell significantly immediately after both cant according to the Wilcoxon test (P<0 005) The
implantations by 7 % (P< O 01 and < 0 005 respective- second implantation led to another increase of pul-
ly) This is in agreement with respective changes of the monary resistance which, however, evolved only after
calculated alveolo-arterial PO 2-gradient and the right- termination of the brief test period An analysis of the
to-left shunt-volume fraction. trend of pulmonary resistance selectively studied in five
The mean pulmonary arterialpressure (Fig 6) rose patients (Fig 8) with the highest increase of pulmonary
after both implantations, after the first one in a bi- arterial pressure at first implantation, revealed clearly
phasic manner The increase to the first maximum after again the development of poly-phasic, superimposed
268 H Rinecker: New Clinico-pathophysiologlcal Studies on the Bone Cement Implantation Syndrome

%140-
. D- IMP2 Mean pulmonary %140- IMP1 IMP21 Pulmonary vascular
arterial pressure |;- ' - ' resistance
~~_ mr
I
-;Z~~w
120- 120-

_?%
'_ \_ -\_
'-N
mrl~
An EA/\U'''LL' L ; 4i ;, -
'__I , '* 1 1

,i-, , i i i i+ i 80
80 '
I -i
I a
60
. I I1
60
10
,
20
e S £
30
£A
40
An N 1
50 60 7 80 90 100 11 mn 10 o
20 30 40 50 60 7b o
8O o 16oO 10 mn

Patient Imp 1 Imp 1 Imp 1 Imp 1 Imp 2 Imp 2 Imp 2 Imp 2 Individual Patient Imp 1 Imp 1 Imp 1 Imp 1 Imp 2 Imp 2 Imp 2 Imp 2 Individual
+ + + + values + + + values
40 S 160 S 540 S 40 S 160 S 540 s 40 S 160S 540 S 40 S 160S 540 s

1 19 18 18 20 19 20 19 20 1 125 115 102 121 91 108 92 62

2 25 26 34 35 32 31 33 32 2 270 262 317 318 329 316 259 331
3 44 40 43 49 34 32 37 31 3 203 162 196 236 89 73 129 67
4 12 13 14 13 14 14 14 16 4 105 130 224 130 101 101 95 110
5 30 29 35 41 32 31 34 31 5 138 106 203 260 216 208 260 253
6 18 17 18 17 14 15 14 14 6 201 189 167 173 174 184 169 185
7 22 23 21 21 17 18 19 19 7 119 133 125 132 109 109 102 151
8 23 23 29 16 14 13 15 22 8 151 153 235 128 125 113 144 169
9 24 23 25 37 21 21 29 31 9 65 61 85 273 59 41 98 99
10 13 12 14 14 12 12 12 13 10 117 105 139 90 98 97 101 107
11 10 11 12 16 12 12 11 13 11 71 82 81 122 84 82 61 81
12 19 20 22 21 16 17 18 20 12 190 197 204 174 262 288 280 230
13 20 19 25 29 16 17 20 21 13 65 60 91 141 34 40 53 52
14 17 16 17 27 16 18 17 22 14 123 105 109 145 142 185 155 224
15 25 24 25 25 31 28 24 27 15 270 236 292 131 387 308 230 225

Mean 214 210 234 254 200 199 210 221 mm Hg Mean 148 140 172 172 153 150 149 157 dyn sec

0
',nn
1n F5 ce

l
1 Sigifcan
F l 132-'4000 Significance
"I 0,010 n
1
F hii 0,025 n Inr
r l rnIII |I o,oOo1
0,05
J
r Lb o oso r JLIUU
&_J L__ _ pqOP50 _J L
-J L -L___ o
1,050 I___
-70 IMPl +l C O +200 300 -70 IMP2 100 +200 +300 sec
-70 IM Pl +100 +200 +300 -70 IMP2 +100 +200 +300 sec
Fig 6 Mean pulmonary arterial pressure
Fig 7 Pulmonary vascular resistance

resistance-peaks (Table 1) At termination of surgery, Pulmonary vascular

the pulmonary vascular resistance fell to 88 1 % of resistance

control in this sub-group which is in agreement with the

total group studied.
%140- IMPe l IMP2

Comparison of Control Values Between Patients with

Sc/A,
Elective Surgery and Patients Suffering from 120-

TranscervicalFractures
7_77 ',
100-

The 5 patients suffering from a transcervical femoral

80-
fracture (Table 2) were older than the group subjected

II _II
.. ,-'
to elective surgery They had a lower cardiac output
inspite of a lower pre-operative hemoglobin concen-
tration The mean pulmonary arterial pressure was
60
-

10 20
I 30 40 50

Fig 8 Pulmonary vascular resistance of the sub-group of 5 pa-

60 70 8O 90 10 ~ lo I

higher in these patients, and so was the pulmonary tients with the highest pulmonary arterial pressure increases
after the first implantation
vascular resistance However, no differences were
found in pulmonary tests Moreover, this group did
respond similarly as far as implantation reactions are observed in electively operated patients, must be
concerned Nevertheless, since the pre-operative con- viewed as an extra burden of considerable significance
trol level of the pulmonary vascular resistance was for the right ventricle The maximal pulmonary
already up in these patients, an additional increase vascular resistance of patients with coxarthrosis was
following implantation, even if only equal to that 168 dyn s/cm s whereas patients with fractures reach-
H Rinecker: New Clinico-pathophysiological Studies on the Bone Cement Implantation Syndrome 269

Table 1 Development of pulmonary vascular resistance Sub- Discussion

group of 5 patients with the highest pulmonary arterial pressure
C _ C…'t
111 lctreas alr L Ilr t I iplaulLalu
LIU
The decrease in hemoglobin concentration resulted
% Resistance First Second from loss of blood which occured during surgery since
implantati on implantation electrocoagulation was avoided by purpose Hemo-
Pre -impl control 111 7 + 19 .1 83 3+ 18 1 dilution of this range lowers blood vicosity which,
according to the literature may account to 14-52% as
First peak after 150-240 S 166 8 +35
measured under in-vitro conditions l32, 47 l Further
Maximum (second peak) 192 2 + 23 .8 125 4 + 18 8 alterations of vital parameters were observed second-
ary to anaesthesia The arterial PO 2 had a tendency to
fall right after beginning of surgery This phenomenon
Table 2 Comparison of pre-surgery control data of elective and may be explained by an early start of formation of
posttraumatic patients microatelectasis in patients mechanically ventilated
C(ox Fracture without positive end-exspiratory pressure The in-
arrthrosis creases in pulmonary as well as arterial pressure within
30 min after initiation of anaesthesia are noteworthy.
Number 10 5 According to the computer plots, two mechanisms may
Mean age years 67,8 78,4 be involved: One is an increase in resistance of the
Preop hemoglobin g/100 ml 13.5 12 9 pulmonary and peripheral vascular system following
Cardiac output l/min 6.1 46 the wearing-off of the a-blocking effect of Droperidol
used during introduction of anaesthesia l19 l However,
Mean arterial
pressure mm Hg 99 111 then a general decrease of the total peripheral resist-
ance supervened prevailing for the remaining period
Mean pulmonary of surgery This decrease in resistance is likely to result
arterial pressure mm Hg
from the discussed decrease of blood viscosity by hemo-
Central venous dilution An increase of cardiac output may be con-
pressure mm Hg 8 10 sidered as another mechanism leading to the initial
Pulmonary wedge rise in blood pressure It is likely to have resulted from a
pressure mm Hg 14 14 volume replacement exceeding initially the volume
Pulmonary vascular which was lost In addition an influence of the
5
resistance dyn sec/cm I120 216 Droperidol/Fentanyl anaesthesia on the central ven-
Total peripheral ous pressure may be taken into consideration l 19l.
resistance dyn sec/cm 5
12230 1838 Employment of conventional recording techniques
Alveoloarterial 02 with long measuring intervals in lack of computer
gradient mmHg 79 82 support have so far prevented an adequate description
Deadspace and analysis of BIS This was due to the described
ventilation I/min 2.7 25 fluctuations combined with the transient nature of
Right-left shunt implantation reactions Correlation of a particular
volume fraction 0.058 0 063 reaction with implantation is possible only by coinci-
dence in time.

ed 302 dyn s/cm5 After implantation, pulmonary Lack of Clinical Evidence of Neurogenic Hvpotension,
resistance decreased only slowly in patients with Thermal Damage, or Monomer Intoxication
fractures At termination of surgery, pulmonary re- The results do not provide any evidence in patients
sistance was only 96 dyn s/cm 5 in patients with supporting the pressor-reflex observed in rabbits l44 l.
coxarthrosis, while 248 dyn s/cm5 in patients with If one accepts the studies in rabbits with the exenterated
femoral fractures The latter group developed con- tibial cavity as a relevant experimental model, some
gestion of the right ventricle in addition The central points merit critical discussion (I) Statistical analyses
venous pressure increased to 121 4 + 7 1 % during were not performed between the experimental group of
implantation as compared to a pre-implantation value 5 animals with nerves cut against the control group with
of only 89 9 + 10 5% The right-ventricular stroke work intact nerval supply (II) A decrease in blood pressure
did not fall secondary to hemodilution To the was also found to evolve in animals with nerves
contrary, after implantation it remained at, or above unsevered where, however, ligation of blood vessels led
the initial control-level. to anaerobic conditions in the respective limb The
270 H Rinecker: New Clinico-pathophysiological Studies on the Bone Cement Implantation Syndrome

results of this group seem to indicate that side-effects Another clinical study attempted to correlate the
like fat embolism have not been avoided during incidence of BIS to the amount of monomer uptake
administration of hydraulic pressure, neither by prepa- into the recipient l10l Implantation of bone cement
ration nor by rinsing in advance This agrees also with late after start of the polymerization process reduces
the histological findings. substantially the uptake of free monomer This
If one relates the time-course of the implantation procedure has been reported to lower frequency, but
response to the process of heat-discharge from the surprisingly not amplitude of the blood pressure fall.
polymerizing bone cement l48 l, it is obvious that Most of these studies analyzed the frequency of
thermal phenomena cannot be involved, since the occurence of a blood-pressure-fall event rather than the
implantation reactions occur prior to heating On the averaged pressure trend of the patients Occasionally,
other hand, only little information is available on the frequency histograms of the amplitudes of the different
influence of heat on the coagulatory system It is pressure falls were given l9 l Boundary conditions of
conceivable that heat prolongs changes of the coagu- time and pressure defining a pressure fall as such were
latory system induced by implantation. never included Many of the continously and intra-
The absence of a depression of the total peripheral operatively recorded parameters are subjected to
resistance after implantations in humans is a strong spontaneous deviations independent from implanta-
argument against monomer intoxication leading to tion Such a background activity would not allow
vasodilatation The respective hypothesis was based on recognition of changes of, e g , only 1% l10l as implan-
results obtained in animal experiments with injection of tation dependent.
methyl-methacrylat partially into the left cardiac The significance of fat de-emulsification by mo-
atrium l20, 31l Monomer concentrations of 1-2 mg/ nomer application has been questioned Experimen-
100 ml during implantation have been reported in tal observations of a decrease of the systemic blood
human venous blood l11,38, 49 l Gaschromatographic pressure after squeezing of plastilin into the medullary
studies suggest that probably most of the venous cavity together with administration of monomer
monomer is cleared during the first pulmonary passage: provided the basis of this hypothesis l9 l However, it
Concentrations in arterial blood were found to be remains open to debate whether administration of
below the detection threshold of O01 pg/ml l11l. essential phospholipids prevent a lethal outcome of
Hence, it is obvious that doses used in the above BIS Experimental studies have shown that such a
mentioned experiments are many times above those procedure does neither reduce histologically observed
encountered in clinical circumstances, rendering the fat embolism nor the number of fat droplets in venous
experimental data questionable Additionally, publish- blood draining the area of implantation l51l.
ed opinions vary, whether methyl-methacrylat alone,
or the polymerisation catalysts (hydrochinon, diben-
Embolism as a PathogeneticFactor
zoylperoxyd and dimethyl-p-toluidin) can be held of the Bone Cement Implantation Syndrome
responsible for the reactions l51 l Until now, conven-
tional techniques failed in animal experiments to Evidence for sequestration of fat in pulmonary tissue
register simultaneously the actual cardiac output, was obtained in autopsies of patients succumbing from
arterial and central venous blood pressure during the BIS l15, 18, 26, 53l However, the significance of this
brief phase of blood pressure fall Calculation of the phenomenon is somewhat limited, since fat emboli are
total peripheral resistance at this moment was not also found in pulmonary tissue in 80% of cases
feasible therefore. subjected to extracorporeal cardiac resuscitation l22l.
The fall in arterial pressure has been suggested to Nevertheless, clinical symptoms and laboratory find-
result from either myogenic l2, 13, 14 l or bradycardic ings, as e g , a reduction of the arterial PO 2, hyper-
l25, 54 l depression The results of this study do not pyrexia, failure of the right ventricle and confusion
support the concept of development of either cardiac observed in patients surviving massive BIS even
depressions Neither a decrease in cardiac output, without resuscitation, were indicative for fat embolism
stroke volume nor of heart rate was observed after l8, 53l Intraoperative filtration of venous blood drain-
implantation in our patients These results are in ing the implantation area showed fat droplet intra-
accordance with experimental studies in dogs, where vasation concurring with bone cement impaction l51 l.
monomer injections led to small and ambigous changes Moreover, drilling of the cup and opening of the
of the Veragut-Krayenbuihl contractility index only femoral shaft were also found to induce a release of fat
l51l Alterations in heart rate observed under respective l35 l The increase of intramedullary pressure during the
clinical circumstances may have resulted in the major- bone cement impaction into the cavity seems to be a
ity of cases from agonal hypoxemia. major determinant of intravasation of bone marrow
H Rinecker: New Chnlco-pathophysiologlcal Studies on the Bone Cement Implantation Syndrome 271

material In man, pressure peaks of up to 3000 mm Hg or posttraumatically l3l have been found to cause a
have been observed during manual cement impaction, decrease in arterial PO 2 The current studies demon-
whereas even higher pressures occured during hammer- strate a statistically significant reduction of the arterial
ing the prosthesis into the shaft l16, 50, 56 l By this PO 2 also after implantation of bone cement Since the
procedure, every material present in the medullary intraalveolar PO 2 was high, a reduction of the arterial
cavity may be pressed into the intravascular space: fat PO 2 must have resulted from an increase of the right-to-
droplets, fat cells, as well as air l37, 59l In histological left shunt volume fraction l41l This is supported by
studies, bone cells as well as spongy bone marrow calculation of respective shunt data.
material have been found in pulmonary vessels l59l. Experimental obstruction of the pulmonary vessels
Bone marrow is rich in thrombokinase activity. by embolization led to an increase of the pulmonary
Therefore, uptake of medullary contents into the vascular resistance together with an increase of the
vascular system leads to an activation of coagulation. pulmonary arterial pressure l51 l Now, identical phe-
The recalcification time, a measure of tissue thrombo- nomena have been demonstrated in man concerning
kinase activity in blood was found reduced l35l. the implantation of an artificial hip-joint Besides of
Coagulation starts already in veins leading to intravasal mechanically obstructing the capillaries, platelet aggre-
formation of thrombin, which in turn causes polymeri- gates were found to initiate pulmonary vasoconstric-
zation of fibrinogen and formation of platelet aggre- tion This has been attributed to a release of 5-
gates l 35l Studies using 125J-fibrinogen have demon- hydroxytryptamin from the aggregated platelets l58l.
strated deposition of fibrin in the lung l16, 36, 45 l The
platelets aggregating intravenously deposit subse- The present studies demonstrate development of
quently in the lung vessels This has been histologically cardio-respiratory alterations in man during artificial
confirmed as well as by transpulmonal differences in hip-joint implantation which are known to occur also
platelet count l51 l and by detection of pulmonary in experimental pulmonary embolism Moreover, our
sequestration of 5 Cr-labelled platelets l16, 36, 40 l. data agree with experimental findings in dogs subjected
Thus, overwhelming evidence for microembolization to simulated implantations which also led to an
after implantation has been provided on a morpho- increase of pulmonary arterial pressure l 51l Due to
logical basis This, however, does not necessarily mean technical limitations mentioned above, respective stud-
functional consequences for the cardio-respiratory ies in man have been conducted only occasionally.
system Embedding of pulmonary tissue for histolog- However, single observations obtained during these
ical analysis causes already changes in structural investigations had been interpreted likewise l 7, 34 l.
dimensions making quantitative generalizations ques- Taken together, the following pathogenetic mecha-
tionable l5 l. nism of BIS may emerge: Impaction of bone cement
The present studies have revealed a significant into the medullary cavity leads to high pressures there.
decrease in total respiratory compliance developing This results in a venous intravasation of medullary
after implantation Experimental studies have also contents A local hypercoagulation taking place in the
demonstrated a decrease of respiratory compliance draining veins causes platelet aggregation and fibrin
secondary to embolism Specific mechanisms have not deposition The combined effects are disseminated
been elucidated yet Toxic effects of free fatty acids pulmonary microembolism In a time-lapse fashion,
released from embolic material on surfactant metab- the sequence of pathogenetic steps of BIS is similar to
olism have been discussed l17, 39 l However, this may the sequence of processes involved in acute shock lung
not suffice to explain reduction of compliance occuring l3 l It causes a decrease of respiratory compliance and
already 90 S after implantation Changes of capillary of arterial PO2 as well as an increase of pulmonary
permeability have been reported to cause reduction of vascular resistance and of pulmonary arterial pressure.
compliance within 30 min after embolization l29 l. In a developed BIS, the final steps appear to follow
Explanations for the even more rapidly evolving identical rules: Development of right ventricular fail-
compliance changes following implantation of hip ure by peracutely elevated pulmonary vascular resist-
endoprosthesis remain for the moment purely specu- ance with ensuing relative hypovolemia of the left
lative: A decrease in elasticity because of constriction of ventricle The decrease of left atrial pressure may lead
the bronchial muscles may be considered The parallel to a decrease in cardiac output, even if myocardial
time courses of pulmonary arterial pressure and function is maintained This would explain the charac-
respiratory compliance may suggest a mechanical teristic decrease in blood pressure shortly after implan-
tissue stabilization effect through the overpressurized tation Maintenance, or recovery of arterial blood
lung vessels. pressure may depend on the capability of the right
Pulmonary embolization in animal experiments ventricle to compensate for the increase of pulmonary
l24 l, or occuring during lymphangiograms in man l12 l, vascular resistance.
272 H Rinecker: New Clinico-pathophysiological Studies on the Bone Cement Implantation Syndrome

However, this model does not explain the poly- Revision of Prophylaxis Recommendations
phasic nature of the implantation reaction as well as the
increase of total peripheral resistance Further investi- These investigations do not provide any evidence for an
gations are required Clinical studies report quite intoxication by monomer Therefore, the attempt to
frequently increases of arterial blood pressure second- reduce incorporation of monomer by using cement at a
ary to implantation l14, 52l. late phase of polymerization seems to be futile It may
also be dangerous, because of the haste then required
and of higher cement viscosity higher pressure peaks in
the medullary cavity are invariably produced If, to the
Implantation of Hip Endoprosthesis contrary, implantation is performed early duringpoly-
in TranscervicalFractures merization with bone cement still in low-viscosity
range, the cement may be sucked into the cavity
Provided the number of cases studied with transcervical by virtue of a suction drainage Experimentally, this
fractures warrant already an evaluation, the following procedure was found to substantially decrease intra-
conclusions may be drawn as to their higher risk for the vasation of medullary material into blood l 24l In the
development of BIS: In the posttraumatic phase, the present study after the first implantation, which was
pulmonary vascular resistance is already enhanced due performed in the pelvic bone without suction drainage,
to pulmonary fat embolism from the fracture which, the ensuing reactions were usually more severe than in
however, goes unnoticed clinically Obviously, such a the following implantation with drainage Hence,
patient is at higher risk then, if by the additional careful release of pressure in the medullary cavity can
surgical trauma disseminated microembolization oc- be considered the prophylactic measure with highest
curs again This conclusion calls in question to perform reliability against BIS.
surgery immediately, or early after trauma Indeed, The described pulmonary alterations in BIS let us
investigations in a large group of patients with abandon whole blood transfusions for volume substi-
transcervical fractures (n = 1000) did not find a reduc- tution and employ hemodilution by plasma-volume
tion of mortality by immediate surgery l42 l. expanders as another prophylactic measure against BIS
instead Hemodilution with dextran lowers the tendency
of platelet aggregation: Dextran interferes with factor
Severity of BIS in the Literature VIII which is known to stimulate platelet aggregation
and to stabilize thrombi l1 l In addition, dextran
The patients studied in this report had only mild forms reduces blood viscosity leading to a decrease in total
of BIS A difference in risk between various clinical peripheral resistance l32l Volume replacement with
reports cannot be explained by random effects only. plasma-volume expanders should therefore continue
Charnley had an intraoperative mortality of only until 5 min after the second implantation.
0.02% in a series of over 10,000 implantations l6l Our experience is that pre-operative administration
whereas other series report 3 lethal intraoperative of 5000 units s c heparin according to the protocol of
complications out of 395 cases l53 l, 4 out of 300 l30 l, or Kakkar l23l did not result in enhancement of blood
7 out of 246 l60l A study in knee-joint endoprostheses loss Low heparin doses are suggested to block factor X
reported 4 intra and postoperative lethal compli- thus preventing an activation of the coagulation cas-
cations taking the typical course described above in cade by tissue-thrombokinase l3l Moreover, low-dose
only 64 implantations l8 l. heparin is considered to attenuate consequences of
The prophylaxis against intravasation and subse- platelet aggregates l23l Furthermore, heparin blocks
quent hypercoagulation is likely to vary considerably at release of 5-hydroxytryptamin from aggregated plate-
different centers For example, suction drainage of the lets l55 l.
medullary cavity to attenuate pressure peaks at im- The present investigation makes obvious that the
plantation has not always been employed The coagula- bone cement-implantation-syndrome cannot be con-
tion potential can be assumed to vary between different sidered merely as an isolated, toxicological problem
patients, e g due to consumption of acetylsalicyclic caused by administration of methyl-methacrylate To
acid, or related compounds with anti-coagulatory the contrary, BIS which is most likely to result from
properties Often blood had been transfused without microembolization, must be viewed as an iatrogenic
employment of microfiltration. model of a peracutely developing respiratory insuf-
The current studies indicate that prevention, or at ficiency Such a definition places BIS among the large
least attenuation of embolic processes and their group of posttraumatic, or post-surgical respiratory
sequelae may be the most promising prophylactic and cardiovascular failures Consequently, treatment
measures against BIS. of severe forms of BIS is based on the same methods
H Rinecker: New Clinico-pathophysiological Studies on the Bone Cement Implantation Syndrome 273

used in acute postoperative respiratory insufficiency, 20 Holland CJ, Klm KC, Malik MJ, Ritter MA (1973) A histo-
e.g further heparinization, ventilation with positive logic and hemodynamic study of the toxic effects of
monomeric methyl methacrylate Clin Orthop Rel Res 90:
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conditions by a Swan-Ganz balloon catheter in the 21 Immich H (1974) Medizinische Statistik FK Schottauer,
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22 Jackson CT, Greendyke RM (1965) Pulmonary and cerebral
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