Femoral intramedullary nail fixation is currently considered the “gold standard” for treatment of femoral shaft fractures in the adult population. Advances in design, technique, and biologic implications have further expanded the indications for the use of intramedullary implants.
Reports exist of intramedullary implants in use as early as the late 19th century, in the form of bone or ivory pegs. However, it was the work by Gerhardt Küntscher in the 1930s, which was instrumental in the later progression to modern day intramedullary nailing systems. His concept of endosteal intramedullary interference fit for fracture fixation ultimately led to development of reaming techniques, secondary to the physiologic variation in canal diameter among the population. This advancement permitted standardized enlargement of the intramedullary canal for improved implant contact and the resultant benefits of larger diameter nails. The 1950s and 1960s marked the shift from nonoperative management toward intramedullary fixation; however, it was not until the 1980s that the technique enjoyed widespread acceptance after the advent of locked intramedullary nails by Klemm and Schellmann. This innovation increased the application for fractures beyond the isthmus as the implant design controlled length and rotational alignment through interlocking technology, relying less on an endosteal interference fit.1
Closed intramedullary nailing with modern interlocking implants can be performed with or without reaming. Fracture healing of 98% has been reported with closed nailing techniques. Unreamed nailing allows for better maintenance of the endosteal circulation at the expense of smaller diameter implants; in contrast, reamed applications permit a larger diameter nail, resulting in stronger fixation constructs and earlier fracture union.2 Although it is clear that interlocking intramedullary nailing is the standard of care for fractures of the femoral shaft, debate exists regarding technical aspects of the procedure, particularly the role of medullary reaming with regard to local and systemic physiologic consequences and ultimately the impact upon clinical practice within certain patient populations. The purpose of this review is to discuss intramedullary reaming with respect to problems associated with its use and the evolution of treatment modalities and clinical advances.
BIOLOGY OF INTRAMEDULLARY REAMING
Long bone circulation is composed of 3 interactive components. The nutrient artery arises from the peripheral circulation, entering the diaphysis through a nutrient foramen. These further subdivide into arteries and arterioles once within the medullary canal. The metaphyseal circulation stems from the periarticular plexus, penetrating the metaphysis and then anastomosing with the endosteal supply originating from the nutrient artery. Finally, the periosteal capillary network comprises the remaining vascular supply. Rhinelander et al described the vascular supply of the diaphyseal cortex. The inner two-thirds are supplied by the endosteal arteries, whereas the periosteum supplies the outer one-third.3 Under normal physiologic conditions, the cortical circulation is centrifugal. It has been experimentally shown that with removal of the endosteal blood supply, cortical flow reverses to a centripetal pattern.4
Intramedullary reaming has a detrimental effect on the local environment of the medullary canal, by obliterating the endosteal blood supply. Hupel et al evaluated cortical blood flow after intramedullary reaming before interlocking nail fixation of tibial osteotomies in a canine model. Cortical perfusion was decreased by 83% and returned to baseline at 11 weeks after fixation.5 Smith et al6 have demonstrated that when compared with other forms of fixation, intramedullary implants cause significantly lower blood flow to cortical bone during the healing process but without any significant difference in bone remodeling. Schemitsch et al reported the effects of reamed versus unreamed locked nailing on the blood flow in fracture callus and the strength of union in a sheep tibia model. They revealed that reaming resulted in a significant decrease of endosteal perfusion compared with the unreamed group; however, fracture callus perfusion and strength of union were not different whether reaming was performed or not.7 Further animal studies have shown that reaming increases cortical porosity, but no differences were identified regarding new bone formation at 2, 6, or 12 weeks between reamed and unreamed comparisons.8 In addition to the effects of reaming on cortical perfusion, the soft tissue envelope in a fracture environment is also altered by reaming. Animal investigations, using a fractured sheep tibia model, have shown that muscle perfusion is significantly greater after reaming.9
Cortical temperature alterations after reaming have been described, and concerns regarding thermal necrosis and its resultant impact on healing exist. Henry et al investigated temperature alterations after intramedullary reaming of cadaveric femoral and tibial specimens. Results revealed direct correlation with temperature and incremental increase in reamer size.10 Baumgart et al11 recommended sequential reaming in 0.5-mm increments, well-judged utilization of hand reamers for restricted canal diameters, and maintenance or replacement of reamers as necessary to minimize heat generation. There exists direct correlation between temperature elevation and amount of reaming in the tibia. Tibial canal diameters of 8 mm reamed to greater than 10 mm showed statistically significant temperature increases compared with those with larger diameters, yet no thermal necrosis or osseous healing problems were noted.12 The authors noted that reaming a normal size canal did not seem to produce any adverse clinical events but cautioned that preparation of smaller diameter canals could potentially produce significant heat production. Historically, thermal necrosis as a complication of reaming has been implicated particularly with tourniquet usage during reaming procedures of the tibia. Tourniquet use has been presumed to negate the physiologic cooling effect of blood and tissue fluid flow in the extremity. However, recent evidence has questioned this practice. Results from a canine study revealed similar temperature changes both with and without a tourniquet; the authors showed that the risk of thermal necrosis was due to the practice of intramedullary reaming.13 In a prospective randomized trial of tibial intramedullary fixation, Giannoudis et al14 demonstrated transient temperature increases (20 seconds) and no effect upon temperature was reached whether a tourniquet was applied when reaming at least 1.5 mm above the selected nail diameter.
Reaming has been associated with intramedullary pressure increases and bone marrow embolization. The intramedullary canal is characterized by a physiologic positive pressure, which is found to be up to 65 mm Hg in humans.15 Passage of a reamer affects intramedullary pressure, a mechanism analogous to a piston within a cylinder. There is agreement that the most significant pressure spikes occur during the primary reamer passage. Furthermore, pressure increases are greatest when the reamer engages the distal fracture fragment, particularly if the fracture is noncomminuted and proximal as there is less probability that venting can occur through the fracture.15 Experimentally, reaming has been associated with pressure increases ranging from 300 to 1000 mm Hg in animal models, and in clinical evaluations of patients with femur fractures, pressures have been noted to range from 140 to 830 mm Hg.16 Danckwardt-Lillieström et al,17 in a microangiographic study of rabbit tibia, observed that the increased intramedullary pressures after reaming resulted in bone marrow occlusion of the intracortical vascular channels, thus impairing circulation resulting in variable depth of cortical necrosis. Wozasek et al experimentally evaluated intramedullary pressure changes and fat intravasation after reamed nailing using pressure monitoring and echocardiography in a sheep model. They concluded that although reaming significantly increased the intramedullary pressure, fat intravasation was greatest during nail insertion.18 Further experimental evidence suggests that marrow content embolization was associated with the rise in intramedullary pressure and occurred to a lesser degree with unreamed procedures.19 In a clinical trial, Kröpfl et al exhibited a significant increase in intramedullary pressure after reamed nailing in contrast to unreamed procedures. Furthermore, they concluded that bone marrow embolization correlated with the escalation of intramedullary pressure and was less common with unreamed nailing group compared with the reamed control group.20 Therefore, rises in intramedullary pressure after reaming likely, in part, contribute to embolization of marrow contents.
The potential autograft phenomenon deserves mention. Frölke et al21 displayed that 24% of intramedullary reaming debris was deposited at an artificial gap created in the femora of sheep. Reaming debris is composed of bone trabeculae and bone marrow stroma, histologically. Hoegel et al22 indicated sheep osteoblast survival after reaming in a laboratory culture. Human reaming contents contain multipotent stem cells capable of growth and propagation in vitro, based on recent evidence.23 Inverse correlation exists between extent of reaming and the viability of reaming debris, reaming to 1 mm below the canal diameter results in a greater viable bone mass percentage.24 Considerable increase in growth factors has been demonstrated after intramedullary reaming. Giannoudis et al25 recorded increased intramedullary levels of vascular endothelial growth factor, platelet-derived growth factor-betabeta, insulin-like growth factor-I, and transforming growth factor-I after reaming compared with unreamed samples. The autograft effect is likely multifactorial, taking into consideration local delivery of reaming debris in combination with increased growth factors believed to be instrumental in bone healing.
Recent attention has focused on the biologic systemic complications of reamed intramedullary nailing, particularly upon the pulmonary system. Several authors have documented bone marrow emboli in the pulmonary system through the use of echocardiography.26-30 The pathophysiology of pulmonary damage seems to be multifactorial. Mechanical occlusion of the pulmonary vasculature, changes in pulmonary artery pressure, and coagulation incited by intramedullary debris and fat have all been proposed as potential pathways for pulmonary damage.16,31,32 Others believe pulmonary damage to be potentiated by detrimental effects of fat molecules upon the pulmonary endothelium, leading to further inflammatory activation.16 Furthermore, Pape et al32,33 showed reaming to be associated with increased polymorphonuclear leukocyte activation and triglyceride embolization in a traumatized sheep model. The authors concluded that in the face of lung injury and hemodynamic shock, alternative methods of fixation could avoid further injury. Hildebrand et al34 reported their findings that reamed nailing in a lung contusion animal model resulted in significant increases in lung edema, pulmonary vascular permeability, and polymorphonuclear leukocyte activation compared with femora stabilized with an external fixator. In contrast, other animal studies have concluded that intramedullary reaming caused mild transient increase in pulmonary vascular resistance; however, it did not further impair sheep in a pulmonary contusion model.35
Other authors have provided insight into the stimulatory effect that reaming imparts upon the immune system. Giannoudis et al36 found elevated serum interleukin (IL)-6 and elastase during nailing procedures, but there was no statistical significance between reamed and unreamed groups. In addition, increased IL-10 levels and decreased HLA-DR expression have been demonstrated after reamed intramedullary femoral fixation.37 Elevated prothrombin time, activated partial thromboplastin time, prothrombin fragments, D-dimers, and decreased fibrinogen levels after reamed intramedullary nailing of the femur and tibia provide evidence for alteration of coagulation and fibrinolytic mechanisms.38 Intravascular fat generates a complex interaction of immune modulation and mechanical consequences that cumulatively manifest as furthered pulmonary injury, which is the major disadvantage of intramedullary reaming.
CLINICAL COMPLICATIONS ENCOUNTERED IN FEMORAL NAILING
Fat embolism syndrome is typically characterized by acute hypoxia, confusion, and petechial rash. It is well established that intramedullary reaming and instrumentation result in increased canal pressures, with subsequent extravasation of marrow contents into the systemic circulation. Schemitsch et al39 have shown that intravascular fat continues in the circulation of the lungs, kidneys, and brain for 72 hours after canal reaming and pressurization in their canine model. The origin of fat emboli syndrome has been called into question by Mudd et al40 who revealed no myeloid tissue in lung sections of patients suffering from blunt trauma. They concluded that soft tissue injury is the foremost source. Fat emboli occur in approximately 90% of trauma patients, although only 1%-5% of patients display clinical fat embolism syndrome.41 Bilateral femoral fractures and pathologic fractures of the femur pose higher risks for development of fat embolism syndrome.42 Several hypotheses have been proposed to explain the neurologic findings in patients with fat emboli syndrome. These include hypoxia, paradoxical embolization, changes in the blood-brain barrier, and cerebral edema.43,44 Additionally, activation of coagulation pathways and microvascular occlusion are felt to contribute to the inflammatory response through direct interaction with the pulmonary endothelium.41
Adult respiratory distress syndrome (ARDS) is another potential complication after intramedullary fixation of the femur, particularly in the multiply injured patient. This devastating acute respiratory failure is currently defined by pulmonary edema without pulmonary hypertension and acute onset hypoxemia (PaO2:FiO2 ratio ≤ 200 mm Hg) by the American-European Consensus Conference.45 With an incidence of greater than 100,000 cases per year in the United States, mortality rates range from 30% to 40%.45 Similar to fat emboli syndrome, much attention has been focused on whether intramedullary reaming produces a “second-hit” phenomenon, placing multiply injured patients at risk for end-pulmonary damage such as ARDS. Data presented by Pape et al46 in 1993 suggested that in patients with severe chest trauma, there was a 33% increased incidence of ARDS and 21% mortality versus 7.7% and 4%, respectively, in trauma patients without chest injury who underwent stabilization of femoral shaft fractures with primary reamed intramedullary nailing. This sparked further animal and clinical investigations, which, at times, demonstrated conflicting reports. In a sheep model with induced pulmonary insult, Wolinsky et al47 found no clinically significant effect of reamed intramedullary nailing procedures when monitoring markers of pulmonary function. Some authors maintain that reamed intramedullary nailing is not a major cause of ARDS or multiorgan system failure in patients with concomitant thoracic injuries.48 In a comparison of reamed nail versus plate fixation of femoral shaft fractures, Bosse et al49 showed no difference with respect to ARDS, pneumonia, pulmonary emboli, multiorgan failure, or death in patients with a chest injury.
Systemic inflammatory response syndrome is characterized by an altered host systemic immune defense after trauma, which predisposes to increased vulnerability to infection, sepsis, and organ failure. Increased understanding of the body's physiologic response to trauma has led to development of the first- and second-“hit” models. Patients sustaining severe trauma (first hit) are therefore theoretically in danger of further systemic insults (second hit) from a variety of stresses including prolonged surgical procedures. This massive hyperinflammatory response is orchestrated through complex interactions and activations of the innate immune system, which can result in unbiased injury to host tissue after severe trauma.50 With respect to intramedullary nailing, reaming has been postulated as the causative agent in intramedullary pressurization, fat embolization, and subsequent activation of immune mechanisms. Authors have correlated elevated IL-6 levels and systemic inflammatory response score with greater risk for systemic complications and are useful additions to clinical assessment in polytraumatized patients.51 Furthermore, increased IL-6 levels have been demonstrated locally after intramedullary reaming.52 The feasibility of routine serum monitoring of these inflammatory markers is yet to be determined.
Traumatic brain injuries account for significant morbidity and mortality among trauma patients, and these patients pose a dilemma with regard to femoral fracture fixation as well. Controversy exists regarding optimal timing for fracture care in this patient population. Stahel et al53 cautioned that patients with brain injuries are particularly susceptible to further insult precipitated by hypotension or hypoxia, and therefore, a damage control approach is advocated. These second hits may be in the form of early definitive fracture fixation. In contrast, other authors recommend early total care with intramedullary nailing during the first 24 hours after injury, citing no increase in neurologic disability.54,55
EVOLUTION OF VARIOUS TREATMENT MODALITIES TO ADDRESS CLINICAL PROBLEMS WITH REAMING
Skeletal traction deserves historical mention as a definitive treatment option. Traction is associated with prolonged hospitalization, increased costs, malalignment, extended time to union, and complications stemming from extensive bed rest. There are no current universal indications, in the adult population, for treatment of femoral shaft fractures to union with traction. Its application may permit temporization until definitive fixation is achieved, but its use confines patients to bed and makes general care difficult. With the accepted benefits of early mobilization, operative stabilization has decisively surpassed the routine use of traction for definitive treatment.
Reaming permits enlargement of the intramedullary canal in preparation for a larger diameter nail than would be otherwise possible. Controversy exists regarding the systemic consequences of reaming, and this has fostered discussion of the advantages and disadvantages of intramedullary preparation. Proponents argue that reaming is advantageous because it allows for larger diameter implants and theoretical “autografting” at the fracture site. Larger nails provide greater torsional and bending rigidity, have better stability as a result of greater canal fill, and decreased time to union.1 Traditionally, stainless steel unreamed nails were of small diameter and therefore had a higher probability of implant failure from decreased biomechanical properties. Clatworthy et al compared 23 patients without reaming and 22 with reaming. All nails were 10 mm in diameter, and a 13% implant failure rate was discovered, recommendations were offered for larger diameter nails to minimize this complication.56 A multicenter, randomized, prospective study by the Canadian Orthopaedic Trauma Society compared nonunion rates between femoral nailings performed with and without reaming. Their data revealed a 4.5 times greater chance of nonunion when reaming was not employed.57 Others have shown a decreased healing time, reaming averaged 20.5 weeks and, in contrast, nonreamed healing with a mean of 26.9 weeks.58
Nonetheless, unreamed nailing has gained popularity secondary to the potential deleterious systemic effects of reaming the canal. Increases in intramedullary pressure and subsequent fat embolization are major drawbacks to the reaming process. In an isolated injury, this may not upset the immune balance and no untoward systemic effects may be realized. In multiply injured patients who have already sustained a substantial “first hit,” avoidance of reaming might minimize hyperstimulation of a primed immune system after trauma. Therefore, in certain instances, the risk to benefit ratio must be contemplated to determine whether a surgeon is willing to accept minimizing systemic risks at the expense of prolonged healing and increased likelihood of nonunion.
Reaming results in elevated temperature and pressure within the intramedullary cavity, which may adversely affect bone healing. Advancements in reamer understanding led to design improvements in an effort to minimize complications. Biomechanical data have shown that that blunt reamers cause increased positive and negative intramedullary pressure peaks, increased torsional strain, and 2.8 times greater cortical heat generation.59 Typically, the thermal energy generated during reaming is below the threshold that produces bone necrosis.60 In addition, mechanical loading of the femur is optimized by using narrow reamer shafts, long lead head taper, and enlarged cutting flutes.61 The design features reduced intramedullary pressure by 37% and as high as 58% with hollow reamers in biomechanical experiments.62 Addition of a flexible narrow drive shaft further reduces intramedullary pressure.63 Reaming to a lesser degree or with smaller diameter reamers does not avoid intramedullary pressure increases.64 Data also suggest that reaming at slow driving speeds and high revolutions results in the least intramedullary pressure increase.65
Reduction of intramedullary pressure gave way to investigations centered on suction and venting of the canal during reaming, in hopes to reduce pressure and ultimately the embolic load inherent in standard reaming practices. Intramedullary pressure is dependent upon the flow rate of the medullary cavity contents, as the reamer/canal relationship functions as a hydraulic piston, as described by Stürmer.64 Venting, examined in animal studies, decreases canal pressure during reaming, yet the clinical effectiveness for trauma patients remains unknown as the pressure threshold for embolization of marrow contents in humans is yet to be established.66,67
Intramedullary viscosity was reduced by the irrigation-suction technique, resulting in a significant decrease in canal pressures.64,68 Joist et al69 discovered significantly less pulmonary resistance, intravenous fat, and lower pulmonary fat load histologically with a rinsing-suction reamer.
Building on the success of medullary irrigation and suction, development of the reamer-irrigator-aspirator (RIA) (Synthes, Paoli, PA) ensued in the 1990s,70 designed as a single-pass reamer with capability to irrigate and simultaneously aspirate reaming debris for collection.70 Husebye et al71 exhibited significantly decreased intramedullary pressures with RIA compared with a standard reamer. In contrast, Higgins et al72 generated greater pressures with RIA application, which the authors attributed to possible outflow obstruction. Biomechanical data suggest that, despite no differences in healing, callus formed from RIA aspirates resulted in marked improvement in stiffness and strength.73 Pape et al compared standard reaming and RIA with regard to pulmonary dysfunction of lung-injured sheep receiving intramedullary fixation. The RIA cohort demonstrated no significant increase in polymorphonuclear leukocyte activation or D-dimer levels, concluding that evacuation of the canal debris minimizes fat intravasation and the associated systemic alterations upon immune and coagulation pathways, which are implicated in end-organ damage after trauma.74
Introduction of the RIA has impacted the practice of intramedullary nailing. Although it is not in routine use for femoral nailing procedures, RIA may prove advantageous for certain applications. Its role as a bone graft harvester is now becoming a viable alternative to traditional autograft procedures.70 Experimentally, aspiration of the medullary canal results in decreased intramedullary pressure and lower embolization of marrow contents. Given the inflammatory potential for extravasated intramedullary fat, RIA may serve as an alternative to standard reaming for femoral fracture fixation in patients at risk for systemic complications, but maintaining the benefits of a reamed intramedullary device. However, validity of this function clinically remains to be determined.
CONCLUSIONS AND SUMMARY OF BEST PRACTICES FOR INTRAMEDULLARY FEMORAL NAILING
Reamed intramedullary fixation has matured into the treatment of choice for femoral shaft fractures. With regard to reaming, it is imperative that surgeons pay close attention to technique and the equipment, always considering the biologic implications both locally and systemically. Reaming should be performed at slow driving speeds and high revolutions with sharp reamer heads to avoid inadvertent intramedullary heat and pressure generation. Routine use of RIA, though theoretically advantageous, has yet to be thoroughly investigated in prospective randomized studies and cannot be recommended for routine fracture care.
The ideal algorithm for femoral shaft fractures should adhere to several principles based on current literature. Orthopaedic clinical evaluation of injured patients requires identification and understanding of injuries outside the musculoskeletal system. The general condition of the patient after trauma needs to be kept in mind during clinical decision making regarding fracture fixation. For the isolated fracture, surgeons should subscribe to a treatment algorithm of early total care as this has been shown to be beneficial. In the multiply injured patient, however, caution must be exercised to ensure that further injury caused by iatrogenic intervention be minimized. Therefore, in the face of multisystem trauma, identification of the “at risk” patient is paramount. In these circumstances, damage control with temporary stabilization by external fixation allows for further resuscitative efforts before definitive treatment.
1. Brumback RJ, Virkus WW. Intramedullary nailing of the femur: reamed versus nonreamed. J Am Acad Orthop Surg
2. Chapman MW. The effect of reamed and nonreamed intramedullary nailing on fracture healing. Clin Orthop Relat Res
3. Rhinelander FW. Effects of medullary nailing on the normal blood supply of diaphyseal cortex. Instr Course Lect
4. Reichert IL, McCarthy ID, Hughes SP. The acute vascular response to intramedullary reaming
. Microsphere estimation of blood flow in the intact ovine tibia. J Bone Joint Surg Br
5. Hupel TM, Aksenov SA, Schemitsch EH. Effect of limited and standard reaming on cortical bone blood flow and early strength of union following segmental fracture. J Orthop Trauma
6. Smith SR, Bronk JT, Kelly PJ. Effect of fracture fixation on cortical bone blood flow. J Orthop Res
7. Schemitsch EH, Kowalski MJ, Swiontkowski MF, et al. Comparison of the effect of reamed and unreamed locked intramedullar nailing on blood flow in the callus and strength of union following fracture of the sheep tibia. J Orthop Res
8. Schemitsch EH, Turchin DC, Kowalski MJ, et al. Quantitative assessment of bone injury and repair after reamed and unreamed locked intramedullary nailing. J Trauma
9. Schemitsch EH, Kowalski MJ, Swiontowski MF. Soft-tissue blood flow following reamed versus unreamed locked intramedullary nailing: a fractured sheep tibia model. Ann Plast Surg
10. Henry SL, Adcock RA, Von Fraunhofer JA, et al. Heat of intramedullary reaming
. South Med J
11. Baumgart F, Kohler G, Ochsner PE. The physics of heat generation during reaming of the medullary cavity. Injury
. 1998;29(Suppl 2):B11-B25.
12. Giannoudis PV, Snowden S, Matthew SJ, et al. Temperature rise during reamed tibial nailing. Clin Orthop Relat Res
13. Karunaker MA, Frankenburg EP, Le TT, et al. The thermal effects of intramedullary reaming
. J Orthop Trauma
14. Giannoudis PV, Snowden S, Matthews SJ, et al. Friction burns within the tibia during reaming. Are they affected by use of a tourniquet? J Bone Joint Surg Br
15. Pape HC, Giannoudis P. The biological and physiological effects of intramedullary reaming
. J Bone Joint Surg Br
16. Giannoudis P, Pape HC, Cohen AP, et al. Review: systemic effects of femoral nailing: from Küntscher to the immune reactivity era. Clin Orthop Relat Res
17. Danckwardt-Lillieström G, Lorenzi L, Olerus S. Intracortical circulation after intramedullary reaming
with reduction of pressure in the medullary cavity. J Bone Joint Surg Am
18. Wozasek GE, Simon P, Redl H, et al. Intramedullary pressure changes and fat intravasation during intramedullary nailing: an experimental study in sheep. J Trauma
19. Kröpfl A, Davies J, Berger U, et al. Intramedullary pressure and bone marrow fat extravasation in reamed and unreamed femoral nailing. J Orthop Res
20. Kröpfl A, Berger U, Neureiter H, et al. Intramedullary pressure and bone marrow fat intravasation in unreamed femoral nailing. J Trauma
21. Frölke JP, Van de Krol H, Bakker FX, et al. Destination of debris during intramedullary reaming
. An experimental study on sheep femurs. Acta Orthop Belg
22. Hoegel F, Mueller CA, Peter R, et al. Bone debris: dead matter or vital osteoblasts. J Trauma
23. Wenisch S, Trinkaus K, Hild A, et al. Human reaming debris: a source of multipotent stem cells. Bone
24. Kouzelis AT, Kourea H, Megas P, et al. Does graded reaming affect the composition of reaming products in intramedullary nailing of long bones? Orthopedics
25. Giannoudis PV, Pountos I, Morley J, et al. Growth factor release following femoral nailing. Bone
26. Wenda K, Runkel M, Degreif J, et al. Pathogenesis and clinical relevance of bone marrow embolism in medullary nailing-demonstrated by intraoperative echocardiography. Injury
. 1993;24(Suppl 3):S73-S81.
27. Christie J, Robinson CM, Pell AC, et al. Transcardiac echocardiography during invasive intramedullary procedures. J Bone Joint Surg Br
28. Coles RE, Clements FM, Lardenoye JW, et al. Transesophageal echocardiography in quantification of emboli during femoral nailing: reamed versus unreamed techniques. J South Orthop Assoc
29. Pell ACH, Christie J, Keating JF, et al. The detection of fat embolism by transoesophageal echocardiography during reamed intramedullary nailing. J Bone Joint Surg Br
30. Aoki N, Soma K, Shindo M, et al. Evaluation of potential fat emboli during placement of intramedullary nails after orthopedic fractures. Chest
31. Pape HC, Regel G, Dwenger A, et al. Influences of different methods of intramedullary femoral nailing
on lung function in patients with multiple trauma. J Trauma
32. Pape HC, Dwenger A, Regel G, et al. Pulmonary damage after intramedullary femoral nailing
in traumatized sheep-is there an effect from different nailing methods? J Trauma
33. Pape HC, Dwener A, Regel G, et al. Intramedullary femoral nailing
in sheep: does severe injury predispose to pulmonary dysfunction? Eur J Surg
34. Hildebrand F, Giannoudis P, van Griensven M, et al. Secondary effects of femoral instrumentation on pulmonary physiology in a standardised sheep model: what is the effect of lung contusion and reaming? Injury
35. Duwelius P, Huckfeldt R, Mullins R, et al. The effects of femoral intramedullary reaming
on pulmonary function in a sheep lung model. J Bone Joint Surg Am
36. Giannoudis PV, Smith RM, Bellamy MC, et al. Stimulation of the inflammatory system by reamed and unreamed nailing
of femoral fractures. J Bone Joint Surg Br
37. Smith RM, Giannouodis PV, Bellamy MC, et al. Interleukin-10 release and monocyte human leukocyte antigen-DR expression during femoral nailing. Clin Orthop Relat Res
38. Robinson CM, Ludlam CA, Ray DC, et al. The coagulative and cardiorespiratory responses to reamed intramedullary nailing of isolated fractures. J Bone Joint Surg Br
39. Schemitsch EH, Turchin DC, Anderson GI, et al. Pulmonary and systemic fat embolization after medullary canal pressurization: a hemodynamic and histologic investigation in the dog. J Trauma
40. Mudd KL, Hunt A, Matherly RC, et al. Analysis of pulmonary fat embolism in blunt force fatalities. J Trauma
41. Giannoudis PV, Tzioupis C, Pape HC. Fat embolism: the reaming controversy. Injury
42. Kontakis GM, Tossounidis T, Weiss K, et al. Fat embolism: special situations, bilateral femoral fractures and pathologic femoral fractures. Injury
43. Kallina C, Probe R. Paradoxical fat embolism after intramedullary rodding: a case report. J Orthop Trauma
44. Gray AC, Torrens L, White TO, et al. The cognitive effects of fat embolus syndrome following an isolated femoral shaft fracture. J Bone Joint Surg Am
45. Phua J, Stewar TE, Ferguson ND. Acute respiratory distress syndrome 40 years later: time to revisit its definition. Crit Care Med
46. Pape HC, Auf'm'Kolk M, Paffrath T, et al. Primary intramedullary femur fixation in multiple trauma patients with associated lung contusion-a cause of posttraumatic ARDS
? J Trauma
47. Wolinsky P, Banit D, Parker R, et al. Reamed intramedullary femoral nailing
after induction of an “ARDS
-like” state in sheep: effect on clinically applicable markers of pulmonary function. J Orthop Trauma
48. van der Made WJ, Smit EJ, van Luyt PA, et al. Intramedullary femoral osteosysthesis: an additional cause of ARDS
in multiply injured patients? Injury
49. Bosse MJ, Mackenzie EJ, Reimer BL, et al. Adult respiratory distress syndrome, pneumonia, and mortality following thoracic injury and a femoral fracture treated with either intramedullary nailing with reaming or with a plate. A comparative study. J Bone Joint Surg Am
50. Stahel PF, Smith WR, Moore EE. Role of biological modifiers regulating the immune reponse after trauma. Injury
51. Giannoudis PV, Harwood PJ, Loughenbuy P, et al. Correlation between IL-6 levels and the systemic inflammatory response score: can an IL-6 cutoff predict a SIRS state? J Trauma
52. Morley JR, Smith RM, Pape HC, et al. Stimulation of the local femoral inflammatory response to fracture and intramedullary reaming
: a preliminary study of the source of the second hit phenomenon. J Bone Joint Surg Br
53. Stahel PF, Ertel W, Heyde CE. Traumatic brain injury: impact on timing and modality of fracture care. Orthopade
54. Brundage SI, McGhan R, Jurkovich GJ, et al. Timing of femur fracture fixation: effect on outcome in patients with thoracic and head injuries. J Trauma
55. McKee MD, Schemitsch EH, Vincent LO, et al. The effect of a femoral fracture on concomitant closed head injury in patients with multiple injuries. J Trauma
56. Clatworthy MG, Clark DI, Gray DH, et al. Reamed versus unreamed femoral nails. A randomized prospective trial. J Bone Joint Surg Br
57. Canadian Orthopaedic Trauma Society. Nonunion following intramedullary nailing of the femur with and without reaming. J Bone Joint Surg Am
58. Giannoudis PV, Furlong AJ, MacDonald DA, et al. Reamed against unreamed nailing
of the femoral diaphysis: a retrospective study of healing time. Injury
59. Müller C, McIff T, Rahn BA, et al. Intramedullary pressure, strain on the diaphysis and increase in cortical temperature when reaming the femoral medullary cavity-a comparison of blunt and sharp reamers. Injury
. 1993;24(Suppl 3):S22-S30.
60. Garcia OG, Mombiela FL, De La Fuente CJ, et al. The influence of the size and condition of the reamers on bone temperature during intramedullary reaming
. J Bone Joint Surg Am
61. Peindl RD, Harrow ME, Banks DM, et al. Comparison of mechanical loads produced by current intramedullary reamer systems. J Orthop Trauma
62. Müller CA, Baumgart F, Wahl D, et al. Technical innovations in medullary reaming: reamer design and intramedullary pressure increase. J Trauma
63. Müller C, Frigg R, Pfister U. Effect of flexible drive diameter and reamer design on the increase of pressure in the medullary cavity during reaming. Injury
. 1993;24(Suppl 3):S40-S47.
64. Stürmer KM. Measurement of intramedullary pressure in an animal experiment and propositions to reduce the pressure increase. Injury
. 1993;24(Suppl 3):S7-S21.
65. Mousavi M, David R, Ehteshami J, et al. Pressure changes during reaming with different parameters and reamer designs. Clin Orthop Relat Res
66. Martin R, Leighton R, Petrie D, et al. Effect of proximal and distal venting during intramedullary nailing. Clin Orthop Relat Res
67. Dalgorf D, Borhoff CM, Stephen DJ, et al. Venting during prophylactic nailing for femoral metastases: current orthopedic practice. Can J Surg
68. Mueller CA, Rahn BA. Intramedullary pressure increase and increase in cortical temperature during reaming of the femoral medullary cavity: the effect of draining the medullary contents before reaming. J Trauma
69. Joist A, Schult M, Ortmann C. Rinsing-suction reamer attenuates intramedullary pressure increase and fat intravasation in a sheep model. J Trauma
70. Stafford PR, Norris B. Reamer-irrigator-aspirator
as a bone graft harvester. Techniques Foot Ankle Surg
71. Husebye EE, Lyberg T, Madsen JE, et al. The influence of a one-step reamer-irrigator-aspirator
technique on the intramedullary pressure in the pig femur. Injury
72. Higgins TF, Casey V, Bachus K. Cortical heat generation using an irrigating/aspirating single-pass reaming vs. conventional stepwise reaming. J Orthop Trauma
73. Hammer TO, Sudkamp MP, Wieling R, et al. Effect of re-implanted particles from intramedullary reaming
on mechanical properties and callus formation. J Bone Joint Surg Br
74. Pape HC, Zelle BA, Hildebrand F, et al. Reamed femoral nailing in sheep: does irrigation and aspiration of intramedullary contents alter the systemic response? J Bone Joint Surg Am