Fat

embolism:
reaming
controversy
Basic
concepts the
relevant
to the
design and
development
of the Point Contact Fixator (PC-Fix)
Peter V Giannoudis1, Christopher Tzioupis2, Hans-Christoph Pape3
Stephan
M.Trauma
Perren
and
Department
& Orthopaedics,
School of Medicine, University of Leeds, Leeds, UK
2
Joy
S. Buchanan
Department
of Trauma & Orthopaedics, St Jamess University Hospital, Leeds, UK
1
3

Trauma & Orthopedic Surgery, Pittsburgh Medical School, Pittsburgh, USA

AO/ASIF Research Institute, Clavadelerstrasse, 7270 Davos, Switzerland
AO/ASIF Research Institute, Clavadelerstrasse, 7270 Davos, Switzerland
KEYWORDS:
Fat embolism;
KEYWORDS:
intramedullary nailing;
One silly fountain;
reaming;
adult resProgressive
dwarves;
piratory
distress
synUmpteen
mats;multidrome
(ARDS);
Fiveorgan
silly trailers;
ple
dysfunction
syndrome (MODS).

Summary1 Intramedullary nailing is the preferred treatment method for stabilizing femoral diaphyseal fractures. Despite its superior biomechanical advanSummary
bla bla
bla bla One
aardvark
marriesinthe
pawnbroker,
though five
tages
over1 other
implants,
its use,
particularly
selected
groupseven
of patients,
has
bourgeois
cats tickled
umpteen
but systemic
two obeseeffects
elephants
drunkenly
been
questioned
because
of the Macintoshes,
possible harmful
of intramedultowed
umpteen
almost
irascible
sheep. Two bureaux
easily telephoned
Paul, even
lary
reaming.
The
increase
in intramedullary
canal pressure
during intramedullary
though can
the result
wart hogs
gossips, butofone
elephant
partly
wart blood
hogs,
nailing
in intravasation
bone
marrowtastes
and fat
into putrid
the venous
because The
umpteen
purpleconsequences
botulisms kisses
the
subways (FES),
boughtadult
one
system.
subsequent
canMark,
be fatalthough
embolism
syndrome
extremely angst-ridden
lampstand,
obese
televisions
perused
respiratory
distress syndrome
(ARDS),even
and though
multiplefive
organ
failure.
The lung
seems
subways,
then fivetarget
progressive
auctioned
offfor
thethe
bureau,
although
two
trailto
be the primary
for fat mats
embolization
and
mediated
effects
primed
ers inflammatory
grew up, but irascible
Jabberwockies
untangles
speedy
fountains,
yet one
by
reactions.
In laboratory
studies,five
both
reamed
and unreamed
cat ran away, then
the trailer
veryshown
cleverly
two irascible
bureaux.
intramedullary
nailing
has been
to kisses
alter selected
pulmonary
variables.
Although transient, this effect appears to be more prominent with reamed than
unreamed techniques. Additional studies are required to determine whether a
subgroup of trauma patients is adversely affected by intramedullary reaming,
thus necessitating other fixation techniques.

Introduction
Intramedullary (IM) nailing, introduced by Kntscher
[1] in 1940, is currently the treatment of choice
for acute stabilization of femoral shaft fractures in
adults [27].
By successfully controlling both length and rotation, the interlocked intramedullary nail has
expanded the indications for IM nailing to include
virtually all fracture patterns of the femoral shaft,
regardless of the extent of comminution [3, 812].
Numerous authors have documented high success
rates treating femoral shaft fractures with reamed
intramedullary nails [4, 7, 1328].
Over the years, although it is considered as a safe
procedure, pulmonary complications have been reported in some groups of patients [29, 30]. Concerns
1

Abstracts in German, French, Italian, Spanish, Japanese,

and Russian are printed at the end of this supplement.

over fat embolization, adult respiratory distress

syndrome (ARDS), and sudden intraoperative death
have caused some authors to question whether the
benefits of reaming are outweighed by its potential
adverse affects to the patient [3138].
The increase in intramedullary pressure during
reaming is thought to cause venous fat infiltration
through the transcortical vessels, leading to pulmonary emboli and possibly ARDS [34, 39]. Efforts such
as different reamer head designs, venting during
nailing, and the unreamed nailing technique have
been used to minimize intramedullary pressure
changes [40, 41]. However, most data on the exacerbation of pulmonary dysfunction is intraoperative
(ie, very short-term end points). There is little data
to suggest a long-term clinical effect of reamed
femoral nails on the pulmonary status in patients
with fractured femurs.
While these problems are most commonly reported with medullary canal reaming [39], other
authors have demonstrated that inserting an un-

Fat embolism: the reaming controversy

reamed nail can also cause a significant increase in
intramedullary pressure and subsequent fat intravasation [4244]. Therefore, the decision on whether
to use reamed or unreamed nails has resulted in
controversy over the optimal method of nail insertion [45, 46] that centers on the systemic effects of
intramedullary reaming.
The purpose of this article is to present the currently available evidence relating to fat embolization following reamed and undreamed nailing to
stabilize femoral shaft fractures.

Fat embolism: an overview

Since 1860, more than 2,000 reports and articles
have been published on the process of fat embolization and the fat embolism syndrome (FES).
The relationship between a fracture of a long bone
and respiratory insufficiency in the form of FES was
described by Peltier in 1957 [51]. This syndrome has
since been described as a contributing source of
ARDS [52], in which progressive respiratory failure
often leads to death.
Even though the term FES does not accurately
describe the pathomechanics of this condition,
embolization of substances and fat from the marrow space has traditionally been thought to be the
source of embolic fat. However, recent studies suggest otherwise. Mudd et al [53] suggested that soft
tissue injury, rather than fractures, is the primary
cause of fat embolism syndrome. The occurrence
of fat embolisms in trauma patients is estimated to
be as high as 90% [54], although only 15% develop
FES [55]. However, 1226% of patients undergoing
reamed IMN in the area of the femur develop pulmonary complications [56].
Kntscher [1] was the first to observe the systemic
effects of IM nailing attributable to increased intramedullary pressures and fat embolization. There
is evidence that instrumentation of the femoral
medullary canal causes intravasation of bone marrow fat. Blood samples taken from cannulation of
the femoral vein during reaming contain marrow
tissue elements [57]. The use of intraoperative
transesophageal echocardiography (TEE) has also
shown intravasation of fat into the lung vasculature
[58, 59]. Several mechanisms have been suggested
regarding the true etiological factor for the systemic intravasation of fat. The pathophysiological
cause of intramedullary pressure increase has been
confirmed by several investigations. The normal
intramedullary pressure in the uninjured long bone
ranges from 2530 mm Hg in sheep [60], was reported to be 50 mm Hg in the dog, and goes up to

S51
65 mm Hg in man [61]. Experimentally, pressure
increases as high as 300 mm Hg have been reported
in animals [62]. In patients with fractured femurs,
elevations of intramedullary pressure between 140
and 830 mm Hg have been observed [63]. Other authors found evidence of a shunt mechanism between
the arterial and venous systems in bone and suggested that a rise in intramedullary pressure could
affect the precarious balance between the arterial
and venous systems resulting in embolization of fat
particles [64].
Fat embolization caused by the liberation of intramedullary contents from unstabilized fractures
and their surrounding tissues has given rise to various
explanatory theories, including the release of humoral mediators (thromboxane), the theory of toxic
effects, the theory of coagulation disturbances, and
the colloidal theory [31, 6567]. Indeed, bone marrow embolization in the lung may cause mechanical
obstruction and occlusion of pulmonary vessels. In
an animal study, pressures of 300400 mm Hg were
applied to the intact intramedullary femoral cavity
and blood collected from the vena cava showed
large emboli of bone marrow fat and thrombocytes
as long as 3 cm [68].
Several pathogenetic pathways have been suggested, such as a high thromboplastin content of bone
marrow causing coagulation of thrombocytes and fat
[69], changes of pulmonary artery pressure [35], and
stimulation of the alternative pathway of coagulation
by disrupted fat cells and the intramedullary debris
[70]. However, these mechanisms do not seem strong
enough to cause all the changes observed.
Some authors favor the idea that the toxic effects
of fat can lead to pulmonary endothelial damage
[71]. Others think that the hypoxic-induced endothelial damage can liberate humoral mediators
leading to acute changes in the pulmonary vascular
response [72].
The microvascular obstruction effect caused
by the intravasation of fat and the inflammatory
reactions is thought to modify neutrophil kinetics,
creating favorable conditions for neutrophil-mediated injury [73].
Some authors found evidence of an influence of
neutrophils in trauma-induced lung injury and in response to fat embolization. The pulmonary damage
induced by fat infusion was preventable by induction
of neutropenia [73, 74].
Willis et al [75] measured lung myeloperoxidase
activity to examine the contribution of leukocytes to
lung injury induced by femoral fracture and IMN.
In several studies [58, 76, 77], researchers analyzed lipid-laden cell counts or neutrophil counts
of bronchoalveolar lavage fluid obtained from patients who underwent reamed femoral nailing and

S52

suffered from FES to establish whether mechanical

obstruction by fat globules causes the development
of FES. More recent work has provided evidence of
important interactions between fat embolism, its
coagulative effect, and the inflammatory response,
which further confirms the complexity of the pathogenic mechanisms involved [7880].

Fat embolism: to ream or not to ream?

Reaming of the femoral canal has been shown to
cause substantial elevations in intramedullary pressures, inducing marrow fragment embolization into
the venous circulation that has been regarded as a
cause of FES and ARDS [42, 8183].
Intraoperative monitoring such as TEE suggests
that the incidence of pulmonary embolism may
be higher than estimated [84, 85], and also that
reaming triggers microembolic fat showers through
the pulmonary arteries [86, 87]. To avoid reaming-induced embolism, solid nails inserted with the
undreamed technique were developed, however,
these nails have also subsequently been associated
with fat intravasation [88, 89].
In 1993, Pape et al [34] reported a 10-year retrospective review of 766 critically injured patients
with femoral shaft fractures. The authors summarized that patients who had early fracture stabilization and significant chest trauma (AIS thorax
> 2) had a higher incidence of ARDS (33% versus
7%) and mortality (21% versus 4%) than those with
delayed nailing. Because of this tendency toward
a higher incidence of ARDS (although not statistically significant), they suggested that reaming the
femoral canal may have had a detrimental effect on
pulmonary function and recommended that femoral
fractures in patients with chest injuries be treated
with unreamed nails.
Pape et al [39] also compared the effects of intramedullary nailing with and without reaming in
a prospective investigation of a small group of 31
patients with femoral shaft fracture but no thoracic
injury. They reported a persistent and significant
decrease in the oxygenation ratio in patients who underwent reaming, and they concluded that a nailing
technique that does not involve reaming is indicated
for patients with preexisting lung injury.
Controversy concerning the recommendations of
Pape et al [34] led to multiple basic science and
clinical studies to analyze the impact of intramedullary reaming in patients with pulmonary injuries.
A number of animal studies were conducted referring to the deleterious effects of femoral IMN with
reaming on pulmonary function [37, 38, 46, 70, 75,
84, 87, 9094].

P V Giannoudis et al

Wolinsky et al [94] tried to get even closer to the

borderline conditions outlined by Pape et al [34]. Using an experimental animal model, they studied the
effect of IM reaming after drug-induced ARDS. Even
under those conditions, they reported no adverse
effects of reaming.
Willis et al [75] examined lung capillary leak in
rats with femoral fractures and reported an increase
in lung permeability and neutrophil content with
femoral fracture, which did not worsen with reaming. Elmaraghy et al [95] used an animal model to
assess the results of marrow content embolization.
They showed that marrow embolization in a physiologically normal animal lead from minimal to no
inflammatory changes in the lung tissue, indicating
that the significance of marrow content embolization depends on the patients physiological background inflammatory state.
Williams et al [93] showed that tissue plasminogen
activator inhibitor levels increased following femoral fracture in rabbits, which increased pulmonary
endothelial injury.
Duwelius et al [84], in a sheep model, showed peak
showers of microemboli occurred with cannulation
of the femoral canal with an awl, with secondary
peaks occurring during early passes of the reamer
and during insertion of the nail. Pulmonary physiological measurements and histological features
of lung tissue obtained from sheep with an experimental pulmonary contusion were compared with
equivalent data from healthy sheep. They reported
that reamed IM nailing did not increase the risk of
pulmonary dysfunction. This result was reproduced
by Wozasek et al [46] who reported similar lung permeability in sheep after IM nailing, with and without
associated pulmonary injury.
Schemitsch et al [96] induced fat embolism in a
canine experimental fracture model and then compared the effects of plate fixation with IM nailing
with and without reaming. They showed significant
changes in the alveolar arterial gradients in the
animals with and without reamed nailing when compared with using a plate. However, these changes
were temporary and the differences between the
three fixation methods were minimal after 24
hours. They summarized that the method of fracture
fixation had little influence on the development of
pulmonary dysfunction, which probably depended
on other factors.
Neudeck et al [97] calculated the intramedullary
pressure when using a reamed intramedullary nail,
an unreamed intramedullary nail, and a plate for the
stabilization of an experimental fracture of a sheep
femur. They reported similar intramedullary pressure increases during the reamed and the unreamed
techniques, whereas application of the plate did not

Fat embolism: the reaming controversy

cause any relevant increase in the intramedullary
pressure.
Buttaro et al [88] conducted a TEE study in a
pig model to quantify emboli phenomena during femoral nailing with both the reamed and
the unreamed technique. The authors concluded
that the pulmonary changes and fat embolization
during IM nailing occurred to the same degree in
reamed and unreamed femurs. This finding could
be explained by inferring that the amount of
intramedullary tension is independent of the IM
nailing technique.
Several authors have tried to quantify the degree
of fat embolization with the reamed and the unreamed nailing technique in clinical trials. Anwar
et al [98] prospectively randomized 82 patients with
femoral shaft fractures (two groups of 41 patients
each) applying a reamed or unreamed technique.
The authors calculated the alterations in arterial
blood gases, ratios of PaO2/FiO2, and alveolar arterial gradients; pulmonary complications (ARDS,
pneumonia, and respiratory failure) were also monitored. No significant differences were observed in
the ratio of PaO2/FiO2 ratios or alveolar arterial
(A-a) gradients before and after nailing. Although,
the overall incidence of pulmonary complications
was 14.6%, the rate in the reamed group was double
(eight patients who had reamed nailing and four
patients who had unreamed nailing). However, due
to inadequate statistical power they were unable to
document differences in pulmonary physiological response or clinical outcome between patients having
reamed and unreamed femoral nailing. They summarized that the severity of the initial pulmonary
injury is the most important factor in determining
which patients will have a pulmonary complication,
which is a view similar to other investigators Bosse
et al [99] and Stellin [100].
Krpfl et al [44], in a prospective consecutive
nonrandomized clinical trial, reported that insertion
of an unreamed nail is associated with a significant
intramedullary pressure increase. The same group
reported that the intramedullary pressure increased
significantly more in the reamed group than in the
unreamed group, and that bone marrow intravasation, which depended on the rise of intramedullary
pressure, occurred less frequently in femoral fractures stabilized with the unreamed technique than
the reamed one [101].
In a prospective randomized study of a group
of 153 patients with isolated femoral fractures,
Buckley et al [102] reported no difference in pulmonary complications for reamed versus unreamed
intramedullary nails. However, they showed a decrease in the PaO2/FIO2 ratio in multiply injured
patients who had reamed femoral nails.

S53
Weresh et al [103], in a prospective study of 50
patients with a femoral fracture, calculated alveolar
dead space (Vo/Vt) and alveolar arterial gradient (Aa D02) during IM nailing. The authors concluded that
intramedullary fixation of femoral shaft fractures
did not routinely generate a large enough burden of
pulmonary embolization to produce a noteworthy alteration in either parameter during reamed nailing,
even when comparing the number of reamer passes
or the presence of pulmonary injury.
Bosse et al [99] conducted a retrospective
comparative study of 453 patients with femur
fractures at two trauma centers, one of which
treated femoral fractures primarily with IM nails
and the other mainly with plates. They reported
no significant difference regarding the incidences
of ARDS, pneumonia, pulmonary embolism, multiorgan dysfunction, or death between the reamed
and unreamed groups. The overall incidence of
ARDS was only 2%. Their study suggested that
reamed nailing of femoral fractures did not increase the risk of pulmonary morbidity. Bone et al
[104, 105] and van der Made et al [106] confirmed
these findings and made a similar recommendation
that patients with pulmonary injuries and femoral
fracture should have reamed IM stabilization unless they are hemodynamically unstable, in which
case they still recommended early stabilization,
but with use of an unreamed nail or the plating
technique.
Helttula et al [107] compared pre- and immediate
postoperative central hemodynamic variables in 20
healthy adults with a unilateral simple tibial fracture
undergoing reamed or unreamed IM nailing. They
reported that unchanged cardiac performance but
pathologically altered pulmonary vascular tone were
unrelated to the type of nailing and concluded that
changes in cardiac and pulmonary hemodynamics
were already present after the trauma and before
the IM nailing procedure.
The Canadian Orthopaedic Trauma Society [108],
in a report on the results of a large prospective,
randomized, multicenter study, found no significant
difference between two groups of patients managed
with either reamed or unreamed nailing. They also
reported that the ARDS rate was too low to detect a
significant difference between the groups.
Giannoudis et al [109] reported that reamed
and unreamed femoral nailing provoked similar
increases in PMN elastase release and adhesion
molecule expression (plasma elastase- 1 antitrypsin
complex and CD11b), implying that fracture surgery
constitutes a significant proinflammatory stimulus.
The only patient in the study group who developed
ARDS showed a massive postoperative inflammatory
response shortly after reamed nailing.

S54

Nail shape and size have also been implicated in

the proliferation of embolic material. Mller et al
[41] reported on the effects of different reamer
systems and different reamer shaft diameters on
pressure dynamics in human femur specimens showing that a reduction in the reamer shaft diameter
led to a smaller intramedullary pressure increase.
Modification of the reamer design and size did not
significantly influence intramedullary pressure
changes in their study.
Moussavi et al [110] assessed the influence of
driving speed and revolution rate per minute of
two reamers on femoral intramedullary pressure
increase and fat intravasation exposing 24 animals
to hemorrhagic shock after midshaft osteotomy
and conducting controlled reaming. Reaming with
a smaller cored reamer and modified reaming parameters led to a lower increase in intramedullary
pressure and reduced the amount of fat intravasation measured with TEE. The authors concluded
that primary reamed IM nailing should be done after
resuscitation at a low driving speed and high revolutions per minute with a smaller cored reamer to
minimize the risk of pulmonary dysfunction. Their
findings suggested that fat intravasation seems to
be a cumulative phenomenon. In addition, reaming
the intramedullary canal with physical and reamercorrelated modifications to ameliorate or neutralize
fat embolism must be done within a certain time.
If it is not done within a certain time, additional
activation of inflammatory mediators plays a greater
role in pulmonary function impairment than do the
physical reaming parameters [109, 111].
Regarding the treatment of femoral metastases,
Assal et al [112] evaluated their experience of osteosynthesis of metastatic lesions of the proximal
femur using a solid femoral nail without reaming to
treat twelve pathological fractures in ten patients.
They reported one intraoperative death that was
diagnosed at autopsy as being a result of massive
pulmonary fat embolization. Broos et al [113] in
another prospective study of 67 cases of unreamed
femoral nailing, reported neither fat embolism nor
ARDS. The authors concluded that unreamed IM
nailing was safe and preferable as a technique for
treating patients with long bone metastases.
Tornetta and Tiburzi [23] reported that there is
no significant difference between the influence of
reamed and unreamed femoral nailing technique on
fat intravasation and pulmonary dysfunction. However, several studies have reported that intramedullary reaming and nailing of femoral fractures
could lead to serious pulmonary damage or death
[114116].
Finally, Bhandari et al [117] presented evidence
that reamed IM nailing did not incur greater risks

P V Giannoudis et al

of malunion, pulmonary emboli, compartment syndrome, and infection in their metaanalysis from a
pooled analysis of randomized trials.

Conclusion
There is no doubt that intravasation of fat particles
can cause severe lung damage. Animal studies that
show increased pulmonary endothelial permeability
associated with reaming and uncontrolled human
studies support the use of unreamed femoral nails
in patients with chest injuries.
Nevertheless, fat emboli are generated during nail
insertion with the unreamed technique. However,
advocates of the unreamed technique claim that
reaming could cause a cumulative effect (reamer
passages, nail insertion) that could be deleterious
to the patients pulmonary function. Despite the
contradictory results that have been published in
various studies, it seems that the clinical effects
of the embolization associated with intramedullary
manipulations and reaming are no longer as severe,
which can be attributed to the advances made
in pre-hospital care and transport, resuscitation,
critical care medicine, ventilation strategies, and
the increased awareness over the clinical entity.
In addition, careful surgical technique can limit
the medullary canal pressurization associated with
reaming.
The systemic effects of femoral nailing after polytrauma and particularly in selected patients at high
risk of complications is still a topic of animated discussion. It seems that the systemic response to femoral nailing includes the effects of fat and inflammatory reactions. As with any surgical procedure, the
decision to ream or not to ream the intramedullary
canal has to be based on several considerations, including the fracture pattern, concomitant injuries,
and the patients overall physiological status.
The new era that has begun as the result of the
coupling of basic science and applied orthopedics
has led to the alteration of the inherent characteristics of the known fixation methods. The efforts made
travel in two directions: altering the characteristics
of the technique itself and reevaluating the general
concepts of its application.
Our knowledge of the physiological changes between reamed and unreamed intramedullary nailing has increased over the years. The introduction
of damage control orthopedics is likely to have a
positive impact on treating femoral shaft fractures
in polytrauma patients without the risk of side effects. In this context, it appears to be an adequate
alternative for patients at high risk of posttraumatic
complications.

Fat embolism: the reaming controversy

S55

Bibliography

18. Hollmann MW, Horowitz M (1990) Femoral fractures secondary to low velocity missiles: treatment with delayed intramedullary fixation. J Orthop Trauma; 4(1):6469.

1. Kntscher G (1940) [Medullary nailing in fractures.] Arch F

Klin Chir; 200:443455.

19. Lhowe DW, Hansen ST (1988) Immediate nailing of open

fractures of the femoral shaft. J Bone Joint Surg Am;
70(6):812820.

2. Beckman SB, Scholten DJ, Bonneli BW, et al (1989) Long

bone fractures in the polytrauma patient. The role of early
operative fixation. Am Surg; 55(6):356358.
3. Bone LB, Johnson KD, Weigelt J, et al (1989) Early versus
delayed stabilization of femoral fractures: a prospective
randomized study. J Bone Joint Surg; 71A:336340.
4. Brumback RJ (1996) The rationales of interlocking nailing
of the femur, tibia, and humerus. Clin Orthop Relat Res;
324:292320.
5. Charash WE, Fabian TC, Croce MA (1994) Delayed surgical
fixation of femur fractures is a risk factor for pulmonary failure
independent of thoracic trauma. J Trauma; 37(4):667672.
6. Kropfl A, Naglik H, Primavesi C, et al (1995) Unreamed
intramedullary nailing of femoral fractures. J Trauma;38(5):717726.
7. Winquist RA, Hansen ST Jr, Clawson DK (1984) Closed
intramedullary nailing of femoral fractures: a report of 520
cases. J Bone Joint Surg Am; 66:529539.
8. Brumback RJ, Ellison TS, Poka A, et al (1992) Intramedullary nailing of femoral shaft fractures. Part III: Long-term
effects of static interlocking fixation. J Bone Joint Surg
Am;74(1):106112.
9. Kempf I, Grosse A, Beck G (1985) Closed locked intramedullary nailing. Its application to comminuted fractures of the
femur. J Bone Joint Surg Am; 67(5):709720.
10. Seiler JG III, Swiontkowski MF (1991) A prospective evaluation of the AO/ASIF universal femoral nail in the treatment
of traumatic and reconstructive problems of the femur.
J Trauma; 31(1):121126.
11. Thoresen BO, Alho A, Ekeland A, et al (1985) Interlocking
intramedullary nailing in femoral shaft fractures. A report of
forty-eight cases. J Bone Joint Surg Am; 67(9):13131320.
12. Wiss DA, Brien WW, Stetson WB (1990) Interlocked nailing
for treatment of segmental fractures of the femur. J Bone
Joint Surg Am; 72(5):724728.
13. Alho A, Stromsoe K, Ekeland A (1991) Locked intramedullary
nailing of femoral shaft fractures. J Trauma; 31(1):4959.
14. Benirschke SK, Melder I, Henley MB, et al (1993) Closed
interlocking nailing of femoral shaft fractures: assessment
of technical complications and functional outcomes by comparison of a prospective database with retrospective review.
J Orthop Trauma; 7(2):118122.
15. OBrien PJ, Meek RN, Powell JN, et al (1991) Primary intramedullary nailing of open femoral shaft fractures. J Trauma;
31(1):113116.
16. Butler MS, Brumback RJ, Ellison TS, et al (1991) Interlocking
intramedullary nailing for ipsilateral fractures of the femoral
shaft and distal part of the femur. J Bone Joint Surg Am;
73(10):14921502.
17. Grosse A, Christie J, Taglang G, et al (1993) Open adult
femoral shaft fracture treated by early intramedullary nailing. J Bone Joint Surg Br; 75(4):562565.

20. Nowotarski P, Brumback RJ (1994) Immediate interlocking

nailing of fractures of the femur caused by low-to mid-velocity gunshots. J Orthop Trauma; 8(2):134141.
21. Riquelme AG, Rodriguez AJ, Mino GL, et al (1992) Treatment
of the femoral and tibial fractures with Grosse and Kempf
locking nails. Clin Orthop Relat Res; 283:8689.
22. Rutter JE, de Vries LS, van der Werken C (1994) Intramedullary nailing of open femoral shaft fractures. Injury;
25(7):419422.
23. Tornetta P III, Tiburzi D (1994) Anterograde interlocked nailing of distal femoral fractures after gunshot wounds. J Orthop
Trauma; 8(3):220227.
24. Williams MM, Askins V, Hinkes EW, et al (1995) Primary
reamed intramedullary nailing of open femoral shaft fractures. Clin Orthop Relat Res; 318:182190.
25. Winquist RA (1993) Locked Femoral Nailing. J Am Acad Orthoped Surg; 1(2):95105.
26. Wiss DA, Brien WW, Becker V Jr (1991) Interlocking nailing for the treatment of femoral fractures due to gunshot
wounds. J Bone Joint Surg Am; 73(4):598606.
27. Wiss DA, Fleming CH, Matta JM, et al (1986) Comminuted
and rotationally unstable fractures of the femur treated with
an interlocking nail. Clin Orthop Relat Res; 212:3547.
28. Wright DG, Levin JS, Esterhai JL, et al (1993) Immediate
internal fixation of low-velocity gunshot-related femoral
fractures. J Trauma; 35(5):678682.
29. Goris RJ, Gimbrere JS, Van Niekerk JL, et al (1982) Early
osteosynthesis and prophylactic mechanical ventilation in the
multitrauma patient. J Trauma; 22(11):895899.
30. Levy D (1990) The fat embolism syndrome. A review. Clin
Orthop Relat Res; 261:281296.
31. Bradford DS, Foster RR, Nossel HL (1970) Coagulation alternations, hypoxemia, and fat embolism in fracture patients.
J Trauma; 10(4):307321.
32. Heim D, Schlegel U, Perren SM (1993) Intramedullary
pressure in reamed and unreamed nailing of the femur and
tibiaan in vitro study in intact, human bones. Injury; 24
Suppl 3:5663.
33. Henry SL, Adcock RA, Von Fraunhofer JA, et al (1987) Heat
of intramedullary reaming. South Med J; 80(2):173176.
34. Pape HC, AufmKolk M, Paffrath T, et al (1993) Primary intramedullary femur fixation in multiple trauma patients with
associated lung contusiona cause of posttraumatic ARDS?
J Trauma; 34(4):540547.
35. Pape HC, Dwenger A, Regel G, et al (1992) Pulmonary damage
after intramedullary femoral nailing in traumatized sheepis
there an effect from different nailing methods? J Trauma;
33(4):574581.
36. Pape HC, Regel G, Dwenger A, et al (1993) Influence of
thoracic trauma and primary femoral intramedullary nailing
on the incidence of ARDS in multiple trauma patients. Injury;
24 Suppl 3:82103.

S56

37. Schemitsch EH, Kowalski MJ, Swiontkowski MF, et al (1994)

Cortical bone blood flow in reamed and unreamed locked
intramedullary nailing: a fractured tibia model in sheep.
J Orthop Trauma; 8(5):373382.
38. Wozasek GE, Simon P, Redl H, et al (1994) Intramedullary
pressure changes and fat intravasation during intramedullary nailing: an experimental study in sheep. J Trauma;
36(2):202207.
39. Pape HC, Dwenger A, Grotz M, et al (1994) Does the reamer
type influence the degree of lung dysfunction after femoral
nailing following severe trauma? An animal study. J Orthop
Trauma; 8(4):300309.
40. Martin R, Leighton RK, Petrie D, et al (1996) Effect of
proximal and distal venting during intramedullary nailing.
Clin Orthop Relat Res; 332:8089.
41. Mller C, Frigg R, Pfister U (1993) Effect of flexible drive
diameter and reamer design on the increase of pressure in the
medullary cavity during reaming. Injury; 24 Suppl 3:4047.
42. Heim D, Regazzoni P, Tsakiris DA, et al (1995) Intramedullary nailing and pulmonary embolism: does unreamed nailing
prevent embolization? An in vivo study in rabbits J Trauma;
38(6):899907.
43. Hildebrand F, Giannoudis P, van Griensven M, et al (2005)
Secondary effects of femoral instrumentation on pulmonary
physiology in a standardised sheep model: what is the effect
of lung contusion and reaming? Injury; 36(4):544555.
44. Kropfl A, Berger U, Neureiter H, et al (1997) Intramedullary
pressure and bone marrow fat intravasation in unreamed
femoral nailing. J Trauma; 42(5):946954.
45. Browner BD, Burgess AR, Robertson RJ, et al (1984) Immediate closed antegrade Ender nailing of femoral fractures in
polytrauma patients. J Trauma; 24(11):921927.
46. Wozasek GE, Thurnher M, Redel H, et al (1994) Pulmonary reaction during intramedullary fracture management in traumatic shock: an experimental study. J Trauma; 37(2):249254.
47. Zenker FA. Beitrge zur Anatomie und Physiologie der Lunge.
Dresden, Germany: J Braunsdorf, 1861.
48. Von Bergmann E. Ein fall tdlicher Fettembolie. Berl Klin
Wochenschr 1873;10:385.
49. Peltier LF (1965) The diagnosis of fat embolism. Surg Gynecol
Obstet; 121:371379.
50. Oh WH, Mital MA (1978) Fat embolism: current concepts of
pathogenesis, diagnosis, and treatment. Orth Clin North Am;
9(3):769779.
51. Peltier LF (1957) An appraisal of the problem of fat embolism.
Surg Gynecol Obstet; 104(4):313324.
52. Weigelt JA (1984) The adult respiratory distress syndrome.
Meyers MH (ed), The multiply injured patient with complex
fractures. Philadelphia: Lea and Febiger, 4254.
53. Mudd KL, Hunt A, Matherly RC, et al (2000) Analysis of
pulmonary fat embolism in blunt force fatalities. J Trauma;
48(4):711715.
54. Palmovic V, McCarroll JR (1965) Fat embolism in trauma.
Arch Pathol; 80(6):630635.
55. Peltier LF, Sevitt S (1970) Trauma workshop report: fat embolism. J Trauma; 10(11):10741077.

P V Giannoudis et al

56. Schller W, Gaudernak T (1986) Lung complications after

intramedullary nailing. Unfallheilkunde; 1:273.
57. Danckwardt-Lilliestrom G (1969) Reaming of the medullary
cavity and its effect on diaphyseal bone. A fluorochromic,
microangiographic and histologic study on the rabbit tibia
and dog femur. Acta Orthop Scand Suppl; 128:1153.
58. Aoki N, Soma K, Shindo M, et al (1998) Evaluation of potential
fat emboli during placement of intramedullary nails after
orthopedic fractures. Chest; 113(1):178181.
59. Pell AC, Christie J, Keating JF, et al (1993) The detection
of fat embolism by transoesophageal echocardiography during reamed intramedullary nailing: A study of 24 patients
with femoral and tibial fractures. J Bone Joint Surg Br;
75(6):921925.
60. Rehm J (1956) [Measurement of pressure in the intramedullary space and determination of the total fat in efferent veins
in Kntschner nailing.] Langenbecks Arch Klin Chir Ver Dtsch
Z Chir; 283(4):452457.
61. Stein AH Jr, Morgan HC, Reynolds FC (1957) Variations
in normal bone-marrow pressures. J Bone Joint Surg Am;
39(5):11291134.
62. Strmer KM (1993) Measurement of intramedullary pressure
in an animal experiment and propositions to reduce the pressure increase. Injury; 24 Suppl 3:721.
63. Wenda K, Ritter G, Degreif J, et al (1988) [Pathogenesis of
pulmonary complications following intramedullary nailing
osteosyntheses.] Unfallchirurg; 91(9):432435.
64. Tothill P, Hooper G, Hughes SP, et al (1987) Bone blood flow
measured with microspheres: the problem of non-entrapment. Clin Phys Physiol Meas; 8(1):5155.
65. Baker PL, Pazell JA, Peltier LF (1971) Free fatty acids,
catecholamines, and arterial hypoxia in patients with fat
embolism. J Trauma; 11(12):10261030.
66. Meek RN, Woodruff B, Allardyce DB (1972) Source of fat
macroglobules in fractures of the lower extremity. J Trauma;
12(5):432434.
67. Watkins WD, Httemeier PC, Kong D, et al (1982) Thromboxane and pulmonary hypertension following E. coli endotoxin
infusion in sheep: effect of an imidazole derivative. Prostaglandins; 23(3):273285.
68. Nerlich ML, Wisner DH, Albes JM, et al (1985) Pulmonary
effects of IV injection of bone marrow fat and endotoxemia
in sheep. Langenbecks Arch Chir; 13:5558.
69. Strecker W, Gonschorek O, Fleischmann W, et al (1993)
Thromboxaneco-factor of pulmonary disturbances in intramedullary nailing. Injury; 24 Suppl 3:6872.
70. Pape HC, Bartels M, Pohlemann T, et al (1998) Coagulatory
response after femoral instrumentation after severe trauma
in sheep. J Trauma; 45(4):720728.
71. Manning JB, Bach AW, Herman CM, et al (1983) Fat release
after femur nailing in the dog. J Trauma; 23(4):322326.
72. Moncada S, Vane JR (1980) Prostacyclin in the cardiovascular
system. Samuelsson B (ed), Advances in prostaglandin and
thromboxane research. New York, Raven Press, 4350.
73. Doerschuk CM, Allard MF, Hogg JC (1989) Neutrophil kinetics
in rabbits during infusion of zymosan-activated plasma. J Appl
Physiol; 67(1):8895.

Fat embolism: the reaming controversy

S57

74. Andreasson S, Smith L, Aasen AO, et al (1989) Proteolytic

and lysosomal enzymes in acute trauma-induced lung injury
in sheep. Acta Chir Scand; 155(1):16.

91.

Neudeck F, Wozasek GE, Obertacke U, et al (1996) Nailing

versus plating in thoracic trauma: an experimental study in
sheep. J Trauma; 40(6):980984.

75. Willis BH, Carden DL, Sadasivan KK (1999) Effect of femoral

fracture and intramedullary fixation on lung capillary leak.
J Trauma; 46(4):687692.

92.

Pape HC, Dwenger A, Regel G, et al (1995) Intramedullary

femoral nailing in sheep: does severe injury predispose to
pulmonary dysfunction? Eur J Surg; 161(3):163171.

76. Chastre J, Fagon JY, Soler P, et al (1990) Bronchoalveolar

lavage for rapid diagnosis of the fat embolism syndrome in
trauma patients. Ann Intern Med; 113(8):583588.

93.

Williams JJ, Moalli R, Calista C, et al (1990) Pulmonary endothelial injury and altered fibrinolysis after femur fracture
in rabbits. J Orthop Trauma; 4(3):303308.

77. Vedrinne JM, Guillaume C, Gagnieu MC, et al (1992) Bronchoalveolar lavage in trauma patients for diagnosis of fat
embolism syndrome. Chest; 102(5):13231327.

94.

Wolinsky PR, Sciadini MF, Parker RE, et al (1996) Effects

on pulmonary physiology of reamed femoral intramedullary
nailing in an open-chest sheep model. J Orthop Trauma;
10(2):7580.

95.

Elmaraghy AW, Aksenov S, Byrick RJ, et al (1999)

Pathophysiological effect of fat embolism in a canine
model of pulmonary contusion. J Bone Joint Surg Am;
81(8):11551164.

96.

Schemitsch EH, Jain R, Turchin DC, et al (1997) Pulmonary

effects of fixation on a fracture with a plate compared with
intramedullary nailing. A canine model of fat embolism and
fracture fixation. J Bone Joint Surg Am; 79(7):984996.

97.

Neudeck F, Obertacke U, Wozasek G, et al (1994) [Pathophysiologic consequences of various osteosynthesis procedures in polytrauma patients. Part I: Experimental studies
of intramedullary pressure development in reamed and
unreamed intramedullary nailing and plate osteosynthesis
of the femur.] Aktuelle Traumatol; 24(4):114120.

98.

Anwar IA, Battistella FD, Neiman R, et al (2004) Femur

fractures and lung complications: a prospective randomized
study of reaming. Clin Orthop Relat Res; 422:7176.

99.

Bosse MJ, MacKenzie EJ, Riemer BL, et al (1997) Adult respiratory distress syndrome, pneumonia, and mortality following thoracic injury and a femoral fracture treated either
with intramedullary nailing with reaming or with a plate: A
comparative study. J Bone Joint Surg Am; 79(6):799809.

78. Burhop KE, Selig WM, Beeler DA, et al (1987) Effect of

heparin on increased pulmonary microvascular permeability
after bone marrow embolism in awake sheep. Am Rev Respir
Dis; 136(1):134141.
79. Coughlin SR (2000) Thrombin signalling and protease-activated receptors. Nature; 407(6801):258264.
80. Robinson CM, Ludlam CA, Ray DC, et al (2001) The coagulative and cardiorespiratory responses to reamed intramedullary nailing of isolated fractures. J Bone Joint Surg Br;
83(7):963973.
81. Blitzer CM, Hamilton L (1992) Oxygen saturation during reaming and intramedullary nailing of the femur. Orthopedics;
15(12):14031405.
82. Olerud S, Stromberg L (1986) Intramedullary reaming and
nailing: its early effects on cortical bone vascularization.
Orthopedics; 9(9):12041208.
83. Pape HC, Regel G, Dwenger A, et al (1993) Influences of
different methods of intramedullary femoral nailing on
lung function in patients with multiple trauma. J Trauma;
35(5):709716.
84. Duwelius PJ, Huckfeldt R, Mullins RJ, et al (1997) The effects
of femoral intramedullary reaming on pulmonary function in
a sheep lung model. J Bone Joint Surg Am; 79(2):194202.
85. Lafont ND, Kostucki WM, Marchand PH, et al (1994) Embolism detected by transoesophageal echocardiography during
hip arthroplasty. Can J Anaesth; 41(9):850853.
86. Peter RE, Selz T, Koestli A (1993) Influence of the reamer
shape on intraosseous pressure during closed intramedullary
nailing of the unbroken femur: a preliminary report. Injury;
24 Suppl 3:4855.
87. Wolinsky PR, Banit D, Parker RE, et al (1998) Reamed intramedullary femoral nailing after induction of an ARDS-like
state in sheep: effect on clinically applicable markers of
pulmonary function. J Orthop Trauma; 12(3):169176.
88. Buttaro M, Mocetti E, Alfie V, et al (2002) Fat embolism and
related effects during reamed and unreamed intramedullary
nailing in a pig model. J Orthop Trauma; 16(4):239244.
89. Coles RE, Clements FM, Lardenoye JW, et al (2000) Transesophageal echocardiography in quantification of emboli
during femoral nailing: reamed versus unreamed techniques.
J South Orthop Assoc; 9(2):98104.
90. Barie PS, Minnear FL, Malik AB (1981) Increased pulmonary
vascular permeability after bone marrow injection in sheep.
Am Rev Respir Dis; 123(6):648653.

100. Stellin G (1991) Survival in trauma victims with pulmonary

contusion. Am Surg; 57(12):780784.
101. Kropfl A, Davies J, Berger U, et al (1999) Intramedullary
pressure and bone marrow fat extravasation in reamed and
unreamed femoral nailing. J Orthop Res; 17(2):261268.
102. Buckley R, DeGroote R, Powell JP (1998) A prospective
randomized trial comparing reamed versus undreamed intramedullary nailing of femoral shaft fractures: Assessment
of pulmonary dysfunction. Final Program of the 1998 Annual
Meeting and Membership Directory of the Orthopaedic
Trauma Association. Vancouver, 111112.
103. Weresh MJ, Stover MD, Bosse MJ, et al (1999) Pulmonary
gas exchange during intramedullary fixation of femoral
shaft fractures. J Trauma; 46(5):863868.
104. Bone LB, Anders MJ, Rohrbacher BJ (1998) Treatment
of femoral fractures in the multiply injured patient with
thoracic injury. Clin Orthop Relat Res; 347:5761.
105. Bone LB, Babikian G, Stegemann PM (1995) Femoral canal
reaming in the polytrauma patient with chest injury: A clinical perspective. Clin Orthop Relat Res; 318:9194.
106. van der Made WJ, Smit EJ, van Luyt PA, et al (1996) Intramedullary femoral osteosynthesis: an additional cause of
ARDS in multiply injured patients? Injury; 27(6):391393.

S58

107. Helttula I, Karanko M, Gullichsen E (2002) Similar central

hemodynamics and oxygenation in reamed and unreamed
intramedullary nailing of tibial fractures. J Trauma;
52(2):30814.
108. Canadian Orthopaedic Trauma Society. Reamed vs unreamed
intramedullary nailing of the femur: comparison of pulmonary complications. J Orthop Trauma In press.
109. Giannoudis PV, Smith RM, Bellamy MC, et al (1999) Stimulation of the inflammatory system by reamed and unreamed
nailing of femoral fractures. An analysis of the second hit.
J Bone Joint Surg Br; 81(2):356361.
110. Mousavi M, David R, Schwendenwein I, et al (2002)
Influence of controlled reaming on fat intravasation after femoral osteotomy in sheep. Clin Orthop Relat Res;
394:263270.
111. Waydhas C, Nast-Kolb D, Trupka A (1996) Posttraumatic
inflammatory response, secondary operations, and late
multiple organ failure. J Trauma; 40(4):624631.

P V Giannoudis et al

116. Kerr PS, Jackson M, Atkins RM (1993) Cardiac arrest during

intramedullary nailing for femoral metastases. J Bone Joint
Surg Br; 75(6):972973.
117. Bhandari M, Guyatt GH, Tong D, et al (2000) Reamed versus
nonreamed intramedullary nailing of lower extremity long
bone fractures: a systematic overview and meta-analysis.
J Orthop Trauma; 14(1):29.
118. Behrman SW, Fabian TC, Kudsk KA, et al (1990) Improved
outcome with femur fractures: early vs. delayed fixation.
J Trauma; 30(7):792797.
119. Brumback RJ, Ellison PS Jr, Poka A, et al (1989) Intramedullary nailing of open fractures of the femoral shaft. J Bone
Joint Surg Am; 71(9):13241331.
120. Wenda K, Runkel M, Degreif J, et al (1993) Pathogenesis
and clinical relevance of bone marrow embolism in medullary nailingdemonstrated by intraoperative echocardiography. Injury; 24 Suppl 3:7381.

112. Assal M, Zanone X, Peter RE (2000) Osteosynthesis of metastatic lesions of the proximal femur with a solid femoral
nail and interlocking spiral blade inserted without reaming.
J Orthop Trauma; 14(6):394397.
113. Broos P, Reynders P (1998) The unreamed AO femoral
intramedullary nail, advantages and disadvantages of a
new modular interlocking system: A prospective study of
67 cases. Acta Orthop Belg; 64(3):284290.
114. Hall TM, Callaghan JJ (1994) Fat embolism precipitated
by reaming of the femoral canal during revision of a total
knee replacement: A case report. J Bone Joint Surg Am;
76(6):899903.
115. Hughes SP, Reichert IL, McCarthy ID (1993) Biological
effects of intramedullary reaming. J Bone Joint Surg Br;
75(6):845847.

Correspondence address:
Peter V Giannoudis
Professor Department of Trauma & Orthopaedics
St Jamess University Hospital
Beckett Street
Leeds, LS9 7TF, United Kingdom
Phone: +44 113 243 3144
Fax: +44 113 206 5156
e-mail: pgiannoudi@aol.com