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Selected Instructional Course Lecture   |    
Controversies in Intramedullary Nailing of Femoral Shaft Fractures
Philip Wolinsky, MD; Nirmal Tejwani, MD; Jeffrey H. Richmond, MD; Kenneth J. Koval, MD; Kenneth Egol, MD; David J.G. Stephen, MD, FRCS(C)
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An Instructional Course Lecture, American Academy of Orthopaedic Surgeons

The Journal of Bone & Joint Surgery.  2001; 83:1404-1415 
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Intramedullary fixation with reaming is an excellent operative procedure that has revolutionized the treatment of fractures of the femoral shaft. Instead of being confined to bed in traction, patients can be mobilized on the first postoperative day. The expected union rate is between 95% and 99%, with infrequent malunion and infection, at least for closed fractures and for grade-1 and grade-2 open fractures. Stabilization of a femoral fracture within the first twenty-four hours after the injury has been shown to reduce morbidity and mortality in multiply injured patients. However, there are still controversial issues related to intramedullary femoral fixation. The present report addresses several of these issues, including the effect of intramedullary reaming on pulmonary complications and the rate of fracture union, whether a fracture table or a flat radiolucent table should be used for nail insertion, and whether the presence of a head injury alters the treatment selection.
Classically, intramedullary nailing is done with use of a fracture table. The table assists with fracture reduction by applying sustained longitudinal traction. A perineal post provides a fulcrum against which traction is applied. The design of most fracture tables allows circumferential access to the extremity for manipulation, surgical exposure, and imaging. When surgery is delayed and length has not been maintained, the mechanical advantage of a fracture table or a femoral distractor is needed to regain length.
Alternatively, intramedullary nailing can be performed on a radiolucent table1-4. Traction can be applied manually or with the use of a femoral distractor, although it takes almost as long to apply the distractor as it does to perform the entire nailing procedure and manual traction is usually sufficient to regain length. Manual traction works best when nailing is done within twenty-four hours after the injury; otherwise, muscle-shortening cannot be overcome with manual traction alone. If surgery is to be delayed, the patient should be placed in skeletal traction to maintain the normal length or even slight distraction of the fracture fragments. Radiographic documentation is suggested. The use of a flat radiolucent table keeps setup time to a minimum, and access to the piriformis fossa is improved by adduction of the limb. Disadvantages include difficulty in visualizing the hip and the proximal part of the femur in the lateral projection; difficulty in reducing and holding fracture alignment; and, if a distractor is used, risk to the femoral neurovascular structures and blockage of the operative field.
With either method, the patient can be placed in the lateral decubitus or supine position. An advantage of the lateral decubitus position is the improved access to the piriformis fossa, especially in obese patients or in those with ipsilateral hip disease associated with a decreased range of motion of the hip. The disadvantages of the lateral position include respiratory compromise in patients with pulmonary injuries, valgus angulation of the fracture, difficulty in determining proper rotation, and greater difficulty in insertion of distal locking screws.
Although femoral nailing with use of a fracture table has been associated with excellent results, there are problems with the technique. Obese patients are difficult to fit on a fracture table, and it can be extremely difficult to establish the correct starting hole. It is cumbersome to treat patients with multiple injuries on a fracture table since access to the chest, abdomen, contralateral limb, and the distal part of the ipsilateral limb is limited. These patients require table changes as well as multiple preparation and draping procedures, all of which add to the complexity of the operation and increase operative time. Unstable pelvic and spinal injuries make it difficult to use a fracture table as well. There are also several unique complications associated with the use of a fracture table, including compartment syndrome in the contralateral leg, perineal slough, and pudendal nerve palsy5-7.
More recently, surgeons have begun to utilize flat radiolucent tables to treat femoral shaft fractures. There are several advantages to placement of the patient in the supine position, including ease of setup, less respiratory compromise, better fracture alignment, and easier insertion of distal screws. Because the injured leg is draped free and can be adducted, it is easier to find the starting point, particularly in larger patients. Moreover, because the entire involved extremity as well as the contralateral lower extremity can be prepared and draped at the same time and because it is not necessary to reposition the patient and repeat the preparation and draping at the conclusion of femoral nailing, it is easier to address multiple fractures. The intramedullary nailing can be performed on the same table used for a laparotomy, eliminating the need for a table change. Two studies have shown that use of a radiolucent table rather than a fracture table results in a significant reduction (p < 0.05) in the time needed for preparation and draping; in the operative and anesthesia times; and, if multiple injuries are present, in the number of table changes and times that the patient needs to be prepared and draped in order to address all of the injuries1,4.
When a fracture table is used, a closed reduction is performed with use of traction applied through the fracture table combined with external manipulation of the leg by the surgeon. To minimize the risk of pudendal nerve palsy5, the traction is decreased during the preparation and draping of the patient and during proximal exposure. A small-diameter intramedullary nail can be placed in the proximal fragment and used as a joystick to manipulate the proximal fragment and reduce the fracture. This can be particularly useful for fractures of the proximal third of the femur. Many implant manufacturers include a device in the nailing sets for this purpose.
When a radiolucent table is used, the fracture is reduced with use of in-line manual traction combined with sterile bumps placed posteriorly to correct angulation in the sagittal plane. Percutaneously placed Schantz pins in the proximal or distal fragments may aid in the reduction of fracture fragments. A small-diameter nail can be used to correct angulation of short proximal segments. The most difficult fractures to reduce with this method are noncomminuted fractures of the isthmus in young patients with large thigh muscles. A small incision to allow direct reduction of the fracture with use of a bone-hook may be necessary.
A proper entry point is critical to ensure proper nail placement and fracture reduction. A 2-cm longitudinal incision is made one handbreadth proximal to the greater trochanter in line with the femoral shaft. The fascia of the gluteus maximus is incised, and the muscle is split bluntly in line with its fibers down to the piriformis fossa. A clamp is placed in the piriformis fossa, its position is confirmed with fluoroscopy, and then it is spread open upon withdrawal. A guide-pin is then placed into the piriformis fossa and checked on anteroposterior and lateral fluoroscopic views. Next, the guide-pin is overreamed. Medial portal placement should be avoided, as it may cause a femoral neck fracture. Lateral portal placement may lead to comminution and varus alignment in fractures of the proximal part of the femur. Alternatively, an awl may be placed in the piriformis fossa and the proximal part of the femur may be opened by creating a pilot hole. If this technique is chosen, a larger skin incision is required.
When a radiolucent table is used, judging the length of the femur can be problematic. The typical error when such a table is used is to fail to restore length fully, whereas the typical error when a fracture table is used is to overlengthen the limb. If the fracture is minimally comminuted, radiographic landmarks can be used to judge the proper length of the femur. If the fracture is so comminuted that radiographic landmarks cannot be used, it is critical to know the proper length before beginning the operation. Several methods can be used. A radiograph of the intact femur can be made with a radiopaque ruler placed along the thigh, and the distance between two reproducible landmarks, such as the tip of the greater trochanter and the adductor tubercle, can be used to determine length. In the operating room, the c-arm can be used to image nails of different lengths held over the intact femur until the proper length of nail is found. If both femora are fractured and comminuted, the length should be determined by measuring the less comminuted fracture and then making both femora the same length.
Radiographs of the contralateral limb also may be used to assess the diameter of the medullary canal and the degree of curvature of the intact femur. Patients with an extremely small medullary canal may require a special-size implant, which should be determined preoperatively to ensure implant availability.
The proper rotation is also difficult to judge. We find that it is easier to judge rotation when a radiolucent table is used, as it allows the use of several methods. External and internal rotation of the contralateral hip can be assessed prior to preparation and draping, and hip rotation on the injured side can be checked after proximal locking and placement of a drill-bit through a distal locking hole have been performed. Nearly symmetrical hip rotation indicates that proper rotation has been restored. Confirmation of proper rotation is performed by first making a perfect lateral fluoroscopic view of the knee with the image intensifier. Next, the image intensifier is slid proximally to the hip and the machine is rotated 15 to account for femoral anteversion. If the rotation at the fracture site is correct, this maneuver should produce a true lateral fluoroscopic view of the hip.
In conclusion, reaming and femoral intramedullary nailing can be performed safely and effectively on a flat radiolucent table. Operative and anesthesia times have been shown to be reduced, and the care of a multiply injured patient is facilitated.
Antegrade femoral nailing (passing the intramedullary nail from proximal to distal) is the gold standard for surgical treatment of diaphyseal femoral shaft fractures. It has a high rate of union (99%) and a low rate of infection and malunion (<1%)8,9. However, antegrade nailing is associated with a number of complications (including heterotopic ossification around the hip, abductor weakness resulting in a limp, and limited ability to walk or climb stairs), and its use is limited in certain situations10. If a fracture table is used, additional problems arise, including prolonged setup time, possible pudendal nerve palsy, and the inability to address other injuries simultaneously11,12. Recent clinical studies have shown that the results of retrograde nailing (passing the intramedullary nail from distal to proximal) are currently comparable with those of antegrade nailing13-15.

Indications for Retrograde Nailing

Retrograde nailing may be the treatment of choice for certain femoral fractures16. Distal femoral fractures with or without articular involvement are easier to reduce and stabilize with use of an implant that is inserted closer to the fracture site. For patients with fractures of the ipsilateral femoral neck and shaft, use of a retrograde nail allows the fracture of the shaft to be fixed with one implant and the fracture of the neck to be fixed with a separate implant, thus allowing each fracture to be treated optimally. Retrograde nailing is useful for the treatment of obese patients because the femoral intercondylar notch is easier to access than the piriformis fossa, and it is advantageous for pregnant patients because the radiation exposure to the fetus is reduced. Antegrade nailing can be problematic in patients who need operative fixation of an acetabular or pelvic fracture, as the incision for antegrade nailing is usually inappropriate for the fixation of these injuries. With use of an incision around the knee, it is possible to avoid a second approach in patients with an open knee joint, knee disarticulation, or a fracture of the ipsilateral tibia (a floating knee). Retrograde nails can also be used to stabilize femoral shaft fractures proximal to a knee replacement or distal to a total hip replacement. However, not all femoral components used for total knee replacement allow the passage of a nail and, if this is the case, a retrograde nail cannot be used.

Retrograde Nailing Technique

Retrograde nailing is performed with the patient placed in the supine position on a flat radiolucent table, with a bolster under the knee to allow approximately 60 of flexion. A medial parapatellar approach, either open or percutaneous, is used. The starting point is in the intercondylar notch, just anterior to the posterior cruciate ligament attachment and in line with the axis of the femoral shaft. Once the starting point is identified, a starting hole is made with a threaded guide-wire. This hole is then enlarged with use of a cannulated drill, followed by passage of the ball-tipped guide-wire. The fracture can be reduced with use of bolsters and manual traction. The femoral distractor can be used, if necessary, to achieve and maintain length and alignment. The ideal nail diameter is 1.5 to 2 mm less than the largest reamer used. The nail should be driven proximal to the level of the lesser trochanter and distally should be flush with or buried 1 to 2 mm deep to the articular cartilage to avoid impingement on the patella17.
Distal locking of the nail is done with use of the jig, and the length of the screws is carefully judged to avoid medial prominence, which can cause subsequent symptoms. In elderly patients with osteoporotic bones and poor screw purchase, washers are recommended. Proximal locking is done freehand in the anterior-posterior direction. The mass of the quadriceps muscle and the curved anterior femoral surface make this difficult. The proximal screw should be placed at or proximal to the level of the lesser trochanter to avoid damage to the neurovascular structures18.
It is essential that the fracture be reduced before the nail is inserted so that the correct length and rotation can be ascertained. The determination of appropriate length and rotation can be difficult, especially when indirect reduction techniques are used. The correct nail length should be determined preoperatively, particularly when the fracture is comminuted and radiographic markers cannot be used to judge length. Scanograms of the intact femur, fluoroscopic imaging of the actual implants over the intact femur, or an intraoperative modified scanogram measuring with a sterile electrocautery cord and c-arm are all methods that can be used to determine the proper length of the femur. Rotation is more difficult to judge. Comparing the cortical diameter of the femur proximal and distal to the fracture on the fluoroscopic image can help. Palpating the greater trochanter and comparing its position to that of the intact femur can also assist in obtaining the correct rotation.

Complications

Malunion is more frequent after retrograde nailing than it is after antegrade nailing. Malunion is a problem after the retrograde nailing of very proximal fractures because the capacious canal makes it difficult to judge and control length and rotation. It is important to reduce the distal femoral fracture prior to insertion of the nail. The nail holds the reduction but will not reduce the fracture. Retrograde nails are not the implant of choice for fractures of the proximal third of the femur. Early series19 demonstrated a higher prevalence of delayed union and nonunion after retrograde nailing; however, with improved technique and the use of canal-matched implants, the rate of union after retrograde nailing is currently comparable with that after antegrade nailing.

Clinical Studies

The early reports on the use of retrograde nails were retrospective, and the results were compared with those of historical controls. Swiontkowski et al. were the first, as far as we know, to report on the use of retrograde nails20. They used a cloverleaf femoral nail in seven patients who had an ipsilateral fracture of the femoral neck and shaft. The nail was inserted by means of an extra-articular portal through the medial femoral condyle. Sanders et al. expanded the indications for retrograde nailing to include ipsilateral acetabular, pelvic, or femoral neck fractures; polytrauma requiring multiple simultaneous procedures; and pregnancy21. Initial difficulties with insertion of the femoral nail necessitated a change to a tibial nail. The authors reported a healing rate of 92% (twenty-three of twenty-five fractures), with no instances of infection or nail failure. Patterson et al., in a study of seventeen fractures (eleven of which were open), were the first to report on the use of the intercondylar portal as a starting point22. They attributed the poor results in their study to the severity of the initial injury and the high proportion of open fractures. Herscovici and Whiteman also reported on a series in which this approach was used23.
Ostrum et al. recommended caution when retrograde nailing is used to treat type-IIIB open fractures19. They reported a healing rate of 95% (fifty-eight of sixty-one fractures) but noted that for seven fractures a secondary procedure was needed to obtain union. They recommended the use of canal-diameter-matched implants to increase rates of union and to decrease the need for secondary procedures.
In a follow-up to their earlier study24, Moed et al. reported that 94% (thirty-three) of thirty-five fractures united after retrograde nailing, with a shorter time to union and with excellent knee scores25.

Laboratory Studies

ElMaraghy et al., in a laboratory study, showed that retrograde femoral nailing after reaming led to a 52% decrease in anterior cruciate ligament perfusion and a 49% decrease in posterior cruciate ligament perfusion in adult dogs26. It is not known whether this decrease in perfusion occurs in humans or is clinically important for long-term knee function. Stubbs et al. examined rabbit knees at two, six, and twelve months after insertion of a stainless-steel implant and found that the insertion site was completely covered with fibrous tissue27. No histological difference was seen in the cartilage or synovial tissue compared with that on the contralateral side, and there was no evidence of metallosis.
Koval et al. found no significant difference during axial loading when the two nailing techniques were compared with regard to strength28.

Randomized Trials

The results of a number of randomized trials comparing antegrade and retrograde nailing have been published during the last several years. Tornetta and Tiburzi prospectively compared thirty-eight fractures treated with antegrade nailing and thirty-one fractures treated with retrograde nailing and found no difference in operative time, blood loss, or union rate29. They found that it was more difficult to judge rotation and length with use of the retrograde technique. In the most recent prospective, randomized trial of which we are aware, Ostrum et al. found no difference between antegrade nailing (forty-six fractures) and retrograde nailing (fifty-four fractures) with respect to the rate of union or the range of motion of the knee15. Knee motion improved more quickly and knee effusion resolved earlier in the group that had antegrade nailing. However, the group that had retrograde nailing had an increased need for distal hardware removal and conversion from a static to a dynamic construct as well as a longer time to union. These findings were attributed to undersizing of the nail diameter. Antegrade nailing was associated with an increased prevalence of hip and thigh pain. The prevalence of knee pain was similar in both groups.

Overview

The results of retrograde nailing of femoral shaft fractures are comparable with those of antegrade nailing. Retrograde nails are useful for fractures of the distal part of the femur with intra-articular involvement. Intra-articular fractures can be managed with compression lag screws before the nail is inserted. Fractures of the distal third of the femoral shaft may be better suited for retrograde nailing, and they have a lower rate of malalignment20.
Retrograde fixation may be better than antegrade fixation for the treatment of femoral shaft fractures associated with (a) fracture of the ipsilateral femoral neck, (b) obesity, (c) pregnancy, (d) knee disarticulation, (e) ipsilateral acetabular or pelvic fracture, (f) periprosthetic fracture, (g) a floating knee, or (h) an open knee joint. It is also better for the treatment of a femoral shaft fracture in a paraplegic patient with decubitus ulcers. The use of intercondylar portal nails designed for retrograde insertion and of larger-diameter nails has decreased the prevalence of complications, including malunion, nonunion, and implant failure. Retrograde nailing requires the creation of an intra-articular entry hole. There is concern about the long-term effect of such an entry hole in young patients as well as the potential for infection of the joint in patients with an open fracture, as the knee joint then communicates with the open fracture site. The long-term effects are still unknown, although the prevalence of knee pain and the limitation of range of motion in the short to medium term seem to be no higher than those associated with antegrade nailing. At present, antegrade nailing remains the gold standard for the treatment of isolated fractures of the proximal third of the femur and the femoral diaphysis. Studies with larger numbers and long-term follow-up are needed before the current recommendations for the use of retrograde nails can be extended.
Early-generation intramedullary nails were open-section devices designed to achieve a tight intramedullary fit in order to control rotation. Reaming was necessary to enlarge the canal sufficiently to maximize implant contact with the endosteum. Since the advent of locked intramedullary devices, a tight endosteal fit is less necessary because rotational control, as well as axial control, is achieved by means of proximal and distal locking bolts. These intramedullary devices behave more as rods than as nails30.
Reaming of the femoral canal prior to intramedullary nailing has a multitude of local and systemic effects. Some of the systemic effects are described in subsequent sections. Local effects have been classified as biological or mechanical31 and are discussed in this section.

Biological Factors

Rhinelander described the blood supply of the normal femoral diaphysis as coming from one or more nutrient arteries supplying the inner two-thirds of the cortex, with the outer third supplied by means of periosteal vessels derived from the abundant soft tissue surrounding the femoral shaft32. The cortical circulation is defined as centrifugal, with the predominant flow directed from the medullary canal toward the outer cortex. The medullary blood supply is disrupted by fracture, leading to necrosis of approximately 50% to 70% of the cortical bone near the fracture30. Fracture-healing is dependent on the reestablishment of blood flow to the disrupted cortical bone. This revascularization may be periosteal, endosteal, intracortical, or, additionally, by a transient extraosseous flow derived from the soft tissue surrounding the fracture. This extraosseous flow is particularly important in providing nutrients to callus as well as to detached fracture fragments33.
Trueta suggested that the overall direction of cortical blood flow after a fracture is reversed from centrifugal to centripetal34. This was confirmed by Strachan et al., who showed that ligation of the nutrient artery did not reduce blood flow to callus following diaphyseal osteotomy35. This reversal of flow takes place over approximately two weeks, demonstrating that the intramedullary and extramedullary circulations supplement each other through revascularization across the cortex of the bone36. Several animal studies have confirmed these findings37,38.
Placement of any intramedullary device, either with or without reaming, damages the endosteal blood supply. However, reaming of the medullary canal causes more substantial destruction of the endosteal circulation and may lead to necrosis of the inner one-half to two-thirds of the cortical bone39. This was well demonstrated in a fractured sheep tibia model with use of Doppler flowmetry40. Cortical perfusion was significantly decreased in the group that had nailing with reaming (p < 0.0009). Revascularization was established by six weeks in the group that had nailing without reaming compared with twelve weeks in the group that had nailing with reaming. Hupel et al. studied the effects of limited reaming on cortical blood flow in a canine model41. They demonstrated that minimal reaming, to allow easy passage of a small-diameter nail, had significantly less impact on the immediate postoperative cortical blood flow than did standard reaming (p = 0.009).
In addition to the destruction of endosteal blood flow, reaming causes a hyperemic response in the periosteum and the surrounding soft tissues. Reichert et al. demonstrated, with use of radiolabeled microspheres, a substantial increase in periosteal blood flow after reaming in sheep tibiae37. Schemitsch et al. showed that muscle perfusion is markedly increased following long-bone reaming42. Despite the reduced cortical blood flow that has been demonstrated after reaming, an experimental model demonstrated no difference between long bones treated with reaming and those treated without reaming with respect to the perfusion of callus and the early strength of union43.
Intramedullary nailing with reaming clearly disrupts endosteal blood circulation to a greater degree than nailing without reaming does. However, given the change in cortical circulation from centrifugal to centripetal following fracture, periosteal and extraosseous flow seems to be the dominant method of revascularization and healing after fracture fixation with intramedullary nails. This circulation is stimulated by reaming and is dependent on a more-or-less intact soft-tissue envelope surrounding the fracture. The excellent soft-tissue coverage of the femur likely provides a means for this revascularization, which may not be available after fractures of the tibia, particularly those associated with open injuries. Reaming of the femur in and of itself does not seem to have a deleterious effect on the revascularization necessary for the healing of a fracture treated with intramedullary nailing.
In addition to the circulatory effects, reaming is also thought to improve fracture-healing by means of autogenous bone-grafting through the deposition of bone from the reaming at the fracture site.

Mechanical Factors

Nails used without reaming of the femoral canal are typically of smaller diameter than are nails used with reaming. The moment of inertia of a nail is a component of its overall strength, increasing with the fourth power of the nail diameter. Reaming permits the insertion of a larger-diameter, hence, stronger, intramedullary nail, and a larger nail can accept larger locking bolts. A larger nail with larger locking bolts also may allow earlier or immediate weight-bearing44, even in the presence of a comminuted fracture. Reaming also increases the contact area between the nail and the endosteal bone, resulting in a stiffer fracture construct. However, reaming results in the removal of bone, theoretically decreasing the overall bone strength. Even so, the outer diameter of the cortex is the primary contributor of strength of the bone; thus, reaming removes the bone that contributes least to the overall strength yet allows a substantially stronger nail to be inserted45. Finite element analysis has demonstrated that, within clinical limits, it is not possible to ream a bone enough to substantially reduce its strength46.

Clinical Outcomes

Numerous studies have demonstrated that use of a locked intramedullary femoral nail after reaming leads to a union rate of 97% to 100%8,9,47,48. Kröpfl et al. reported a union rate of 100% in a study of eighty-one femoral fractures treated with an intramedullary device inserted without reaming49. However, several studies have demonstrated lower union rates25 and an increased need for secondary procedures50,51after nailing without reaming.
Clatworthy et al. performed a prospective, randomized study comparing femoral nailing with and without reaming52. They demonstrated that the group treated with reaming had a faster time to union (28.5 weeks compared with 39.4 weeks) and that the group treated without reaming required substantially more secondary procedures (conversion to a dynamic construct or bone-grafting) to achieve union. Tornetta and Tiburzi also demonstrated faster union with reaming (eighty days) than without reaming (109 days)53,54. Distal fractures had a more dramatic difference in time to union with reaming (eighty days) than without reaming (158 days). No significant difference was found between the groups with respect to operative time or transfusion requirements. The group treated with reaming had fewer technical complications. A meta-analysis of randomized trials has demonstrated similar findings55.
The use of reaming in the treatment of open tibial fractures is controversial because of concerns about the destruction of the endosteal blood supply in a bone with already compromised circulation. However, the femur has a more substantial soft-tissue envelope than the tibia does, so periosteal and extraosseous blood supply is better. Clinical studies of open femoral fractures treated with nailing after reaming have demonstrated excellent rates of union with a low risk of infection56,57.

Overview

Reaming of the medullary canal has been shown to disrupt the endosteal circulation. However, fracture-healing involves a reversal of the normal centrifugal blood flow across the cortex to a circulation dominated by periosteal and extraosseous flow. Reaming stimulates this flow. Despite the disruption of the nutrient vessel circulation, reaming seems actually to lead to increased circulation around a femoral shaft fracture in the presence of an adequate soft-tissue envelope. Reaming also permits the insertion of a larger, more stable nail, which is advantageous for fracture-healing. Numerous clinical studies have demonstrated that intramedullary nailing with reaming provides more reliable and faster healing with fewer complications than does nailing without reaming. Fixation with a femoral nail after reaming is the treatment of choice for most femoral fractures that are managed operatively.
The fat embolism syndrome is a multisystem disorder that results from fat embolization. Clinically, it causes dysfunction of the pulmonary and central nervous systems as well as fever and rash58. Almost all patients who sustain blunt trauma have some degree of pulmonary fat embolization as a result of the soft-tissue injury. The clinical severity of fat embolism syndrome ranges from subclinical symptoms to the adult respiratory distress syndrome (ARDS)59-64.
No consistent factors other than the number of long-bone fractures can be used to identify patients who are at risk. Pulmonary fat embolization apparently alters pulmonary hemodynamics, increases pulmonary vascular permeability, activates the fibrinolytic and coagulation systems, and causes pulmonary leukostasis58,59,65-67.
The clinical pulmonary effects are thought to occur as a result of an increase in pulmonary vascular resistance secondary to widespread vascular occlusion due to multiple small emboli. Larger fat emboli may obstruct the pulmonary circulation, causing a ventilation-perfusion mismatch and hypoxia. Death occurs as a result of right ventricular failure58,68,69.

Prevention of Pulmonary Complications

The best treatment of fat embolism syndrome and adult respiratory distress syndrome is prevention. Prior to the work of Riska et al.60,61 and Goris et al.70, fracture fixation was usually performed on a delayed basis. One reason given for the delay was to allow the peak dose of fat emboli to pass before fracture fixation was undertaken71. Riska et al. demonstrated that early stabilization of long-bone fractures in multiply injured patients decreased the prevalence of fat embolism syndrome61. They thought that fat embolization was an ongoing process that began at the time of injury. Early fracture stabilization stopped this process and prevented the development of related symptoms60,61. Goris et al. then showed that early fracture stabilization combined with mechanical ventilation not only decreased the prevalence of adult respiratory distress syndrome but also decreased the mortality rate in patients with an Injury Severity Score of >50 points70. Death was most often due to sepsis and multiple organ failure.
Bone et al., in a prospective, randomized trial, demonstrated that patients with femoral shaft fractures and an Injury Severity Score of >18 points benefited from fracture stabilization within twenty-four hours after injury72. Early stabilization led to a decrease in the rates of adult respiratory distress syndrome, fat embolism syndrome, and pneumonia and to a shorter length of stay in the intensive care unit. The authors hypothesized that the decreased fat embolization and the reduced need for narcotics associated with early stabilization, as well as the ability to position the patient with the torso upright, may explain these findings.

Femoral Intramedullary Nailing After Reaming: The Present Controversy

The results of these and other studies have led to the consensus that early stabilization of long-bone fractures is beneficial to the multiply injured patient. The current treatment of choice for fractures of the femoral shaft in adults is insertion of a statically locked intramedullary nail after reaming. When the nail is inserted with use of a closed technique, union rates of 95% to 99%, with low rates of infection and malunion, can be expected9,73. Several clinical studies have shown that early fixation with an intramedullary nail after reaming has a beneficial effect in this group of patients, leading to a decrease in pulmonary complications without an increase in other complications72,74,75. On the basis of the studies reported to date, it appears that trauma patients without thoracic injuries benefit from early nailing of a femoral shaft fracture, with a reduction in the prevalence of pulmonary complications. The potential downside of using a nail after reaming is the possibility that fat emboli generated during nail insertion are harmful. This issue was first raised, to our knowledge, by Pape et al., who analyzed a group of patients with thoracic injuries and femoral shaft fractures76. Those authors noted a trend toward an increase in pulmonary complications among patients in whom the fracture was stabilized with intramedullary nailing with reaming within twenty-four hours after the injury compared with those in whom the fracture was stabilized more than twenty-four hours after the injury. Although this finding was not significant, the authors concluded that nailing after reaming in the presence of thoracic trauma led to additional pulmonary damage.
There is no doubt that intramedullary nailing after reaming causes fat embolization. Numerous clinical and animal studies have demonstrated that pressurizing the medullary canal results in fat embolization that can be visualized with use of echocardiography58,77. The questions are whether this fat embolization has a clinically important effect and whether particular subgroups of patients are at risk. The study by Pape et al. suggested that patients with thoracic injuries are at an increased risk for postoperative complications when early intramedullary nailing with reaming is done76.
Since the cause of pulmonary dysfunction is multifactorial, it is hypothesized that an otherwise trivial pulmonary insult such as fat embolization may potentiate another noxious stimulus, leading to respiratory impairment. Evidence for this "second hit" phenomenon has been presented in animal studies66. In addition to the study by Pape et al.76, two other clinical studies have been performed to examine this issue. Charash et al. performed a study quite similar to that of Pape et al. and came to different conclusions78. They found that delayed femoral shaft stabilization in patients with thoracic trauma led to an increase in pulmonary complications. In fact, the more severely injured the patient, the more pronounced the difference. Bosse et al., in a report on femoral shaft fractures that were treated at two institutions, divided patients into groups on the basis of whether a thoracic injury was also present79. The fractures at one institution were stabilized with a plate, and those at the other institution were stabilized with an intramedullary nail after reaming. Presumably, the patients treated with a plate would have had no pulmonary fat embolization as a result of the femoral stabilization procedure, whereas those treated with intramedullary nailing after reaming would have had fat embolization. If fat embolization were harmful, the group treated with intramedullary nailing after reaming would have a higher prevalence of pulmonary complications. However, Bosse et al. found no difference between the two groups with respect to the prevalence of pulmonary complications.
In a study of sheep, Pape et al.80 subjected the animals to a lung crush injury and systemic hypotension on day 1. On day 3, the animals underwent nailing either with or without reaming. Pulmonary permeability increased in both groups, but only the group that had reaming had an increase in pulmonary arterial pressures. The authors concluded that nails inserted after reaming cause more pulmonary damage than do nails inserted without reaming. In contrast, Wozasek et al. found that intramedullary nailing after reaming alone did not cause an increase in pulmonary permeability, whereas nailing combined with systemic hypotension caused a transient increase81. This raises the question of whether it was the nailing with reaming or the hypotension that altered the pulmonary permeability in the study by Pape et al.80.
Since it is unclear what pulmonary permeability means clinically, one of us (P.W.) and colleagues used a sheep model to investigate the effects of intramedullary nailing after reaming on clinically applicable hemodynamic and oxymetric parameters82,83. Two groups of animals were used. The first had a lung crush injury, and the second had a chemically induced "ARDS-like" state. No alteration in pulmonary function was noted in either group after nailing with reaming was performed.
Current investigations are centered on the role of the inflammatory response in the development of adult respiratory distress syndrome. Trauma can cause the systemic inflammatory response syndrome (SIRS) early after injury. Hemorrhagic shock and the reperfusion injury can overstimulate the immune system and lead to complications, such as acute lung injury, adult respiratory distress syndrome, systemic inflammatory response syndrome, and multiple organ dysfunction syndromes. Oxygen free radicals released by activated neutrophils are thought to play a key role in this process by damaging endothelial tissues63,84-86. The SIRS score has been developed, and studies have shown that patients with blunt trauma and higher SIRS scores have an increased mortality rate and length of stay87. Presumably, these findings are related to the extent of the inflammatory reaction87.
The association between shock and the development of adult respiratory distress syndrome is well known. In fact, the likelihood of development of adult respiratory distress syndrome and the mortality rate have been found to be related to the initial base deficit, presumably reflecting the depth of the initial hypoxic event88,89. In a recent study, no relationship was found between the injury pattern (that is, chest injury, abdominal injury, fracture, and so on), patient age, Injury Severity Score on admission, Glasgow Coma Scale score, hypotension on admission, or time spent in the operating room and the development of adult respiratory distress syndrome88. However, the transfusion requirements in the initial twenty-four hours were substantially higher in the patients in whom adult respiratory distress syndrome developed. Those patients also had a lower base deficit in the initial twenty-four hours after the injury, and the deficit normalized more slowly than did the base deficit in those in whom adult respiratory distress syndrome did not develop. In addition, the magnitude of the lowest base deficit was found to correlate with the increase in cytokines on days 1 through 4, presumably reflecting an increased stimulation of the inflammatory cascade. It appears that the depth of the initial hypoperfusion correlates with the development of an early inflammatory response. The findings in that study suggest that the most effective prevention of adult respiratory distress syndrome is the early aggressive treatment of shock88.
It is hypothesized that the initial shock and resuscitation serve to prime the immune system so that a second, trivial stimulus can lead to an exaggerated inflammatory response. There are experimental and clinical data to support this hypothesis81,86,90,91. Wozasek et al., in a sheep model, demonstrated that only nailing with reaming and hypotension led to an increase in pulmonary permeability81. Other studies have shown that animals in shock can tolerate less of a fat load85,92.
The neutrophils of trauma patients have been found to be more responsive to stimuli to the release of superoxides than are the neutrophils of healthy donors90. Since neutrophils are thought to play a central role in the development of lung injury, this finding suggests that trauma patients who have had an initial stimulus of the inflammatory cascade as a result of hypoperfusion may be extremely sensitive to the stimulus of fat embolization that results from intramedullary nailing after reaming. Without the initial stimulus, this fat embolization may have had no significant detectable effect90.
In a recent clinical study, Crowl et al. investigated the effect of occult hypoperfusion on complications following intramedullary fixation of the femoral shaft within twenty-four hours after admission in patients with an Injury Severity Score of >18 points91. Patients were retrospectively divided into two groups on the basis of lactate levels. No patient had overt clinical signs of shock. The group with occult hypoperfusion had a higher complication rate and higher hospital costs. The authors hypothesized that all trauma patients have activation of the inflammatory process and that patients who have persistent occult end-organ hypoperfusion may be more susceptible to a second-hit injury. This suggests that the patients who may be harmed by early intramedullary nailing after reaming are those with inadequate resuscitation.

Overview

There is controversy with regard to whether intramedullary nailing after reaming can cause clinically important additional pulmonary damage in trauma patients. The studies to date have indicated that this is not an issue in trauma patients without chest injuries who have been well resuscitated. The bulk of the literature has indicated that intramedullary nailing after reaming does not seem to have a detrimental effect on patients with only a thoracic injury. The current controversy centers on the systemic inflammatory response syndrome in underresuscitated patients. It appears that the depth of initial hypoperfusion is an indicator of the extent of stimulation of the inflammatory cascade. This factor is thought to play a role in the development of endothelial injury, one aspect of which is the development of pulmonary dysfunction including adult respiratory distress syndrome. The already stimulated inflammatory reaction may exhibit inappropriate exuberance if stimulated again by factors such as the fat embolization generated during intramedullary nailing after reaming. Therefore, prior to intramedullary nailing with reaming, the patient must be fully resuscitated according to laboratory data (such as base deficit or lactate) to make sure that occult hypoperfusion is not present. If a patient is hemodynamically unstable or is not fully resuscitated, femoral fixation should be delayed or an alternative, less invasive procedure for stabilization, such as external fixation, should be used93. It seems that the extent of resuscitation rather than the presence or absence of a thoracic injury is the critical risk factor for further pulmonary damage as a result of intramedullary nailing after reaming.
The management of patients with a femoral fracture associated with a severe head injury is controversial94-101. A head injury is usually considered severe if the patient presents with a Glasgow Coma Scale score of £8 points or an Abbreviated Injury Scale score of 3 points102. It is postulated that patients undergoing early stabilization of a long-bone fracture in the presence of a severe head injury may be at risk for a secondary brain injury as a result of reduced cerebral perfusion pressure, hypoxemia, hypotension, and fat embolization59,95,99,103. This raises the question of whether the risk of secondary brain injury outweighs the benefits of early stabilization of a long-bone fracture in a patient with a severe head injury and a femoral fracture. If so, can traumatologists decide who should and who should not undergo early stabilization of a femoral fracture in the presence of a severe head injury?
After a severe head injury, numerous factors can lead to secondary ischemic brain injury, and ischemic brain injury has been shown to be the major determinant of long-term neurologic disability104. Hypotension on or before admission substantially increases the rate of poor neurologic outcomes104-106. Immediately after a severe head injury, the normal autoregulation that maintains a stable cerebral perfusion pressure (and thus cerebral blood flow and oxygen) is altered. This effect is most pronounced in the first twenty-four to forty-eight hours after injury107,108. During this time, cerebral perfusion pressure is directly proportional to mean arterial pressure. Thus, any hypotension during this period can lead to cerebral hypoperfusion and hypoxemia—that is, the so-called secondary brain injury104. The complicating issues are that the duration of altered autoregulation varies and that there can be regional cerebral ischemia up to forty-eight hours following the injury109.
Cerebral perfusion pressure reflects cerebral blood flow, and the current method of assessment is to monitor the intracranial pressure. In this way, once the mean arterial pressure is determined (by means of arterial line monitoring), the cerebral perfusion pressure is determined by subtracting the intracranial pressure from the mean arterial pressure. The generally accepted normal values are <20-25 mm Hg for intracranial pressure and >70 mm Hg for cerebral perfusion pressure110. This means that the mean arterial pressure should stay in the range of 90 mm Hg to avoid cerebral hypoperfusion and thus cerebral hypoxemia. Additional information concerning cerebral oxygenation can be obtained by sampling the central venous oxygen tension through a central venous catheter111. Thus, during the initial period following a severe head injury, protection against secondary brain injury requires aggressive resuscitation with crystalloid, blood products, and, if necessary, inotropic support as well as invasive monitoring of arterial, central venous, and intracerebral pressures to avoid systemic hypotension and cerebral hypoperfusion and ischemia.
Despite the known benefit of early stabilization of long-bone fractures and increased knowledge with regard to the treatment of patients with head injuries, there is no consensus on how best to manage a patient with both injuries. There are no large, prospective, randomized studies comparing early and delayed stabilization of long-bone fractures in the setting of a severe head injury. The advocates of each approach base their decision on small retrospective studies.
The advocates for delaying long-bone stabilization in patients with a head injury cite published reports indicating that hypotension leads to worse neurologic outcomes in patients undergoing an early operation (within the first twenty-four hours after injury)95,99,103. Jaicks et al. reported on a cohort of thirty-three patients who had blunt trauma associated with severe head injury (an Abbreviated Injury Scale score of >2 points) and femoral fracture95. Nineteen patients underwent early fracture fixation (within twenty-four hours after injury), and fourteen patients underwent late fixation (more than twenty-four hours after injury). The two groups were matched for age, Glasgow Coma Scale score, Injury Severity Score, and neurologic and orthopaedic Abbreviated Injury Scale scores. The early fixation group required significantly more fluids (p < 0.05) in the first forty-eight hours and tended toward a higher rate of intraoperative hypotension (observed in three patients who had early fixation and one who had late fixation) and intraoperative hypoxia (observed in two patients who had early fixation and one who had late fixation). Despite these findings, the neurologic complication rate was similar in the two groups. Although the mean Glasgow Coma Scale score on discharge was lower in the early-fixation group (13.5 3.7 points) than in the late-fixation group (15 0.0 points), the mean hospital stay was five days longer in the late-fixation group (27 13 days) than in the early-fixation group (22 20 days). No confidence intervals were given for these data. The authors concluded that early fracture fixation leads to greater fluid administration in patients with head injuries. They thought that prospective studies were required to evaluate the impact of the timing of fracture fixation on head injury.
The advocates of early stabilization cite an equal (if not greater) number of reports indicating that the severity of the initial head injury—not the timing of long-bone stabilization—determines the ultimate neurologic function96-98,100,101. McKee et al. reported on a group of forty-six patients with a femoral fracture and a severe head injury (mean Glasgow Coma Scale score, <8 points) who had early fracture stabilization (85% had stabilization within twenty-four hours after injury) and compared them with a cohort of ninety-nine patients with a severe head injury alone (mean Glasgow Coma Scale Score, 8 points; range, 3 to 13 points)98. There were no differences between the two groups with respect to demographic data or other injury patterns. No significant differences between the two groups were found in terms of early mortality, length of hospitalization, length of stay in the intensive-care unit, level of neurologic disability, or results of cognitive testing. The authors concluded that (1) femoral fractures in patients with head injuries should be aggressively managed with early fixation; (2) adequate oxygenation and cerebral perfusion pressure must be maintained during operative procedures, including femoral nailing after reaming; and (3) early femoral nailing after reaming did not negatively affect neurologic outcome in this subset of trauma patients98. Thus, each side of the argument is supported in the literature—albeit by small retrospective cohort studies—and the only solution may be to perform a large, multicenter, prospective, randomized study.
When faced with a patient with a severe head injury and a femoral fracture, it is imperative to adopt a multidisciplinary approach that includes the trauma service, the orthopaedic surgeon, the neurosurgeon, and the anesthesiologist. This approach will allow optimal resuscitation of the patient, establishment of the diagnosis and prognosis of the head injury, and placement of invasive monitors prior to orthopaedic intervention. The aggressive correction of hypothermia and coagulopathy, as well as timely use of inotropes to maintain optimal mean arterial pressure (and thus cerebral perfusion pressure), must be undertaken. The exact timing of long-bone stabilization is determined on the basis of the status of the patient, the results of the computerized tomography scan of the head, and the parameters made available by invasive monitoring. Prolonged orthopaedic interventions should be avoided, with timely fracture stabilization being the goal. A mass lesion, such as a subdural or epidural hematoma, seen on the computerized tomography scan of the head requires urgent neurosurgical intervention. A constellation of bad prognostic signs on the computerized tomography scan, such as extensive amounts of subarachnoid blood, a ventricular shift, and/or cerebellar herniation, may preclude any surgical intervention. Certainly, if the intracranial pressure or the cerebral perfusion pressure remains abnormal or labile, a delay in definitive stabilization of long-bone fractures is recommended. In these patients, external fixation for temporary fracture stabilization may be of benefit. This would be especially important in the presence of an open femoral fracture, in which case there is an urgency to get to the operating room. External fixation would then be followed by definitive stabilization with an intramedullary nail. The external fixator is usually applied as an anterior half-frame, with two pins in each fracture segment. In one series, this approach, called "damage control orthopedics," was required for 13% of 327 patients with a femoral fracture and multiple injuries who were treated at a level-I trauma center. This approach mirrors the experience with devastating abdominal injuries112 and is appropriate for patients who cannot tolerate additional blood loss, including those with head injuries and those who are not yet fully resuscitated. External fixation has been associated with a shorter operating-room time and less blood loss than has intramedullary nailing after reaming93. In rare cases, when the patient is in extremis, temporary skeletal traction may be required.
The timing of definitive stabilization with an intramedullary nail is determined by the status of the patient, but because of the risk of contamination of the external fixator pin site it is desirable to perform the procedure within five to seven days. In some cases, when the patient’s general or neurologic parameters do not stabilize, the external fixator can be used for definitive fixation93.
In summary, there is no evidence in the literature that early fixation of femoral fractures is deleterious in the presence of a severe head injury. However, aggressive resuscitation and invasive monitoring are required to achieve and maintain stable intracranial and systemic parameters. If these parameters remain unstable, temporization with external fixation or, rarely, skeletal traction may be required. A multidisciplinary approach must be adopted to allow an optimal outcome in this subset of trauma patients.
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