Christian Krettek

Impact of intramedullary instrumentation versus damage control for femoral fractures on immunoinflammatory parameters: prospective randomized analysis by the EPOFF Study Group.

BACKGROUND Damage control orthopedic surgery has recently been advocated for the management of femoral shaft fractures in severely injured patients because surgical procedures were found to represent a second-hit phenomenon regarding the operative burden. It has been attempted to determine the operative burden by means of proinflammatory cytokines. In this study in clinically stable patients with multiple injuries, the effects induced by different types of primary fracture stabilization on the systemic release of proinflammatory cytokines were evaluated. METHODS This was a prospective, randomized, multicenter intervention study. Inclusion criteria were long bone shaft fracture of the lower extremity; age 18 to 65 years; Injury Severity Score > 16 or more than three extremity injuries (Abbreviated Injury Scale [AIS] score of 2 or more) in association with another injury (AIS score of 2 or more); and thoracic AIS score < 4. After informed consent, randomization for the treatment of the femoral shaft fracture was performed at admission. Groups were as follows: group I degrees FN (primary, < 24 hours) intramedullary nailing, and group DCO (DCO, I degrees ex.fix.) damage control orthopedic surgery and external fixation. In DCO patients, measurements were also performed at the time of conversion to the intramedullary procedure (DCO II degrees FN). Parameters included clinical parameters and complications (acute respiratory distress syndrome, multiple organ failure, sepsis). From serially sampled central venous blood, the perioperative concentrations of interleukin IL-1, IL-6, and IL-8 were determined. RESULTS Thirty-five patients were included (I degrees FN, n = 17; DCO, n = 18). In I degrees FN-patients, a perioperative increase of IL-6 levels was measured (preoperatively, 55 +/- 33 pg/dL; 24 hours postoperatively, +254 +/- 55 pg/dL; p = 0.03), which was not found in subgroup DCO I degrees Ex.fix.: preoperatively, 71 +/- 42 pg/dL; 24 hours postoperatively, 68 +/- 34 pg/dL; not significant [NS] or in group DCO II degrees FN: preoperatively, 36 +/- 21 pg/dL; 24 hours postoperatively, +39 +/- 25 pg/dL; NS. Likewise, in I degrees FN patients, a perioperative increase of IL-8 levels was measured only at the 7-hour time point (preoperatively, 35 +/- 29 pg/dL; 7 hours postoperatively, 95 +/- 23 pg/dL; p < 0.05), which was not found in group DCO I degrees Ex.fix.: preoperatively, 43 +/- 38 pg/dL; 24 hours postoperatively, 69 +/- 39 pg/dL; NS or in group DCO II degrees FN: preoperatively, 25 +/- 20 pg/dL; 24 hours postoperatively, 36 +/- 29 pg/dL; NS. There were no differences in the complication rate in terms of acute respiratory distress syndrome, sepsis, or multiple organ failure. CONCLUSION In this prospective, randomized, multicenter study, a sustained inflammatory response was measured after primary (<24 hours) intramedullary femoral instrumentation, but not after initial external fixation or after secondary conversion to an intramedullary implant. These findings may become clinically relevant in patients at high risk of developing complications. It confirms previous studies in that damage control orthopedic surgery appears to minimize the additional surgical impact induced by acute stabilization of the femur.

Comparison of human bone marrow stromal cells seeded on calcium-deficient hydroxyapatite, beta-tricalcium phosphate and demineralized bone matrix.

The aim of this study was to compare three resorbable biomaterials regarding seeding efficacy with human bone marrow stromal cells (BMSCs), cell penetration into the matrix, cell proliferation and osteogenic differentiation. Calcium-deficient hydroxyapatite (CDHA), beta-tricalcium phosphate (beta-TCP), and demineralized bone matrix (DBM) were seeded with human BMSCs and kept in human serum and osteogenic supplements for 3 weeks. Morphologic and biochemical evaluations were performed on day 1, 7, 14 and 21. The allograft DBM and CDHA exhibited both an excellent seeding efficacy while the performance of beta-TCP was lower when compared. The total protein content and the values for specific alkaline phosphatase (ALP) increased on all matrices and no significant difference was found for these two markers. BMSCs in monolayer had a significant increase of protein, but not of ALP. Osteocalcin (OC) values increased significantly higher for BMSC in cultures on DBM when compared to CDHA and beta-TCP. The OC levels decreased significantly in the BMSC monolayer culture. BMSCs were found inconsistently within the synthetic materials, whereas in DBM they were found more homogeneously distributed throughout the matrix. All three matrices promoted BMSC proliferation and differentiation to osteogenic cells. DBM allografts seem to be more favorable with respect to cell ingrowth tested by histology, and osteogenic differentiation ascertained by an increase of OC. CDHA with its high specific surface area showed more favorable properties than beta-TCP regarding reproducibility of the seeding efficacy.

Biochemical changes after trauma and skeletal surgery of the lower extremity: quantification of the operative burden.

OBJECTIVE To quantify changes in variables of inflammation, coagulation, and fibrinolysis in blunt trauma patients with lower extremity fractures who underwent different types of surgical procedures. DESIGN Prospective, cohort study. SETTING Level I university trauma center. PATIENTS We allocated 83 blunt trauma patients in stable condition and 22 patients eligible for elective hip replacement to four treatment groups. INTERVENTIONS In 34 multiply traumatized patients with femoral fracture (group PTFF) and in 28 patients with an isolated femoral fracture (group IFF), primary unreamed intramedullary nailing for stabilization of the femoral shaft fracture was performed. In 22 patients, an elective uncemented total hip arthroplasty (group THA) was inserted for osteoarthritis, and in 21 control patients, an isolated ankle fracture (group AF) was acutely stabilized. MEASUREMENTS AND MAIN RESULTS From serially sampled central venous blood, the perioperative concentrations of interleukin (IL)-6, of tumor necrosis factor-alpha, of prothrombin fragments 1 + 2, and of D-dimer cross-linked fibrin degradation products were evaluated. Intramedullary instrumentation for an isolated femur fracture caused a significant perioperative increase in the concentrations of IL-6 (preoperative IL-6, 52 +/- 12 pg/mL; IL-6 30 mins postinsertion, 78 +/- 14 pg/mL; p = .02). This increase was comparable with group THA (preoperative IL-6, 46 +/- 16 pg/mL; IL-6 30 mins postinsertion, 67 +/- 11 pg/mL; p = .03). A positive correlation occurred between both groups (r = .83, p < .0004). Multiple trauma patients demonstrated significantly (p = .0002) higher IL-6 concentrations than all other groups throughout the study period and showed a significant increase after femoral nailing (preoperative IL-6, 570 +/- 21 pg/mL; IL-6 30 mins postinsertion, 690 +/- 24 pg/mL; p = .003), whereas no perioperative change was seen in group AF. The highest IL-6 increases were associated with a longer ventilation time (group PTFF) and a longer period of positive fluid balances (groups PTFF, IFF, THA). The coagulatory variables demonstrated similar perioperative increases in groups IFF and THA, but not in groups PTFF and AF. The IL-6 concentrations and the prothrombin fragments 1 + 2 concentrations correlated between groups THA and IFF at 30 mins and at 1 hr after surgery (r2 = .64, p < .02). In all patients the clinical variables were stable perioperatively. CONCLUSIONS Major surgery of the lower extremity causes changes to the inflammatory, fibrinolytic, and coagulatory cascades in patients with stable cardiopulmonary function. The inflammatory response induced by femoral nailing is biochemically comparable to that induced by uncemented total hip arthroplasty. In multiple trauma patients, increases, which occurred in addition to those induced by the initial trauma, were measured. Definitive primary femoral stabilization by intramedullary nailing imposes an additional burden to the patient with blunt trauma. A careful preoperative investigation is required to evaluate whether primary definitive stabilization can be performed safely.

Impact of the Method of Initial Stabilization for Femoral Shaft Fractures in Patients With Multiple Injuries at Risk for Complications (Borderline Patients)

Objectives:The timing of definitive fixation for major fractures in patients with multiple injuries is controversial. To address this gap, we randomized patients with blunt multiple injuries to either initial definitive stabilization of the femur shaft with an intramedullary nail or an external fixateur with later conversion to an intermedullary nail and documented the postoperative clinical condition. Methods:Multiply injured patients with femoral shaft fractures were randomized to either initial (<24 hours) intramedullary femoral nailing or external fixation and later conversion to an intramedullary nail. Inclusion: New Injury Severity Score >16 points, or 3 fractures and Abbreviated Injury Scale score ≥2 points and another injury (Abbreviated Injury Scale score ≥2 points), and age 18 to 65 years. Exclusion: patients in unstable or critical condition. Patients were graded as stable or borderline (increased risk of systemic complications). Outcomes:Incidence of acute lung injuries. Results:Ten European Centers, 165 patients, mean age 32.7 ± 11.7 years. Group intramedullary nailing, n = 94; group external fixation, n = 71. Preoperatively, 121 patients were stable and 44 patients were in borderline condition. After adjusting for differences in initial injury severity between the 2 treatment groups, the odds of developing acute lung injury were 6.69 times greater in borderline patients who underwent intramedullary nailing in comparison with those who underwent external fixation, P < 0.05. Conclusion:Intramedullary stabilization of the femur fracture can affect the outcome in patients with multiple injuries. In stable patients, primary femoral nailing is associated with shorter ventilation time. In borderline patients, it is associated with a higher incidence of lung dysfunctions when compared with those who underwent external fixation and later conversion to intermedullary nail. Therefore, the preoperative condition should be when deciding on the type of initial fixation to perform in patients with multiple blunt injuries.

Fractures and Fracture Dislocations of the Midfoot: Occurrence, Causes and Long-term Results

Etiology and outcome of 155 patients with midfoot fractures between 1972 and 1997 were analyzed to create a basis for treatment optimization. Cause of injuries were traffic accidents (72.2%), falls (11.6%), blunt injuries (7.7%) and others (5.8%). Isolated midfoot fractures (I) were found in 55 (35.5%) cases, Lisfranc fracture dislocations (L) in 49 (31.2%), Chopart-Lisfranc fracture dislocations (CL) in 26 (16.8%) and Chopart fracture dislocations (C) in 25 (16%). One hundred and forty eight (95%) of the midfoot fractures were treated operatively; 30 with closed reduction, 115 with open reduction, 3 patients had a primary amputation. Seven (5%) patients were treated non-operatively. Ninety seven (63%) patients had follow-up at an average of 9 (1.3–25, median 8.5) years. The average scores of the entire follow-up group were as follows: AOFAS – sum of all four sections (AOFAS-ET): 296, AOFAS-Midfoot (AOFAS-M): 71, Hannover Scoring System (HSS): 65, and Hannover Questionnaire (Q): 63. Regarding age, gender, cause, time from injury to treatment and method of treatment no score differences were noted (t-test: p > 0.05). L, C or I showed similar scores and CL significantly lower scores (AOFAS-ET, AOFAS-M, HSS, Q). The highest scores in all groups were achieved in those fractures treated with early open reduction and operative fixation. Midfoot fractures, particularly fracture dislocation injuries, effect the function of the entire foot in the long-term outcome. But even in these complex injuries, an early anatomic (open) reduction and stable (internal) fixation can minimize the percentage of long-term impairment.

Comparison of Surgical Repair or Reconstruction of the Cruciate Ligaments versus Nonsurgical Treatment in Patients with Traumatic Knee Dislocations

Background: Studies of traumatic knee dislocations have failed to provide a consensus regarding the best method of treatment. Purpose: Our purpose was to evaluate the results after surgical repair or reconstruction versus nonsurgical treatment and to compare the influence of prognostic factors. Study Design: Retrospective study. Methods: Eighty-nine patients were treated for traumatic knee dislocation. Surgical repair or reconstruction of the cruciate ligaments was performed in 63 patients (repair, 49; reconstruction, 14). In 26 patients, nonsurgical treatment was undertaken. Results: At an average follow-up of 8.2 years, the mean Lysholm and Tegner scores were 75 and 3.7, respectively. The outcome in the surgical group was better than in the nonsurgical group. The scores were higher in patients who were 40 years of age or younger, who had sports injuries rather than motor vehicle accident injuries, and who had undergone functional rehabilitation rather than immobilization. Conclusions: Surgical repair or reconstruction of the cruciate ligaments was superior to nonsurgical treatment. Functional rehabilitation was the most important positive prognostic factor. Surgical repair or reconstruction of the cruciate ligaments is mandatory to achieve sufficient stability for functional rehabilitation. In cases of cruciate ligament avulsion, repair with transosseous fixation is a reasonable alternative to reconstruction, provided that it is performed within 2 weeks of trauma.

Alterations in the systemic inflammatory response after early total care and damage control procedures for femoral shaft fracture in severely injured patients.

BACKGROUND Recently, there has been a move away from early total care in patients with severe, multiple injuries to damage control orthopedics (DCO) in an attempt to limit the physiologic insult resulting from operative treatment after trauma. For femoral shaft fracture, this entails initial external fixation and subsequent conversion to an intramedullary nail (IMN). We sought to quantify the inflammatory response to initial surgery and conversion and link this to subsequent organ dysfunction and complications. METHODS Patients with femoral shaft fracture and a New Injury Severity Score of 20 or more were included. Data were retrospectively collected for 4 days at admission and at exchange procedure (external fixation to intramedullary nail), and the Systemic Inflammatory Response Syndrome (SIRS) score and the Marshall multiorgan dysfunction score were calculated. RESULTS One hundred seventy-four patients met the inclusion criteria. The DCO group had significantly more severe injuries (New Injury Severity Score of 25.4 vs. 36.2, p < 0.0001) and significantly more head and thoracic injuries (both p < 0.0001). The mean SIRS score was significantly higher in the IMN group, from 12 hours until 72 hours postoperatively (p < 0.05). The mean peak postoperative SIRS score was significantly higher in the IMN group than in the DCO group, at the primary procedure and at conversion, as was the time with an SIRS score greater than 1. At conversion in the DCO group, the preoperative SIRS score correlated with magnitude and duration of elevation in the SIRS and multiorgan dysfunction scores (p < 0.0001). CONCLUSION It would appear that despite more severe injuries in the DCO group, patients had a smaller, shorter postoperative SIRS and did not suffer significantly more pronounced organ failure than the IMN group. DCO patients undergoing conversion while their SIRS score was raised suffered the most pronounced subsequent inflammatory response and organ failure. According to these data, DCO treatment was associated with a lesser systemic inflammatory response than early total care for femur fractures. The inflammatory status of the patient may be a useful adjunct in clinical decision making regarding the timing of conversion to an intramedullary device.

Influence of sex and age on mods and cytokines after multiple injuries.

Although salutary effects of female sex steroids have been demonstrated not only in proestrus females but also in male animals treated with estradiol in different models of trauma, it remains unknown whether sex hormones influence post-traumatic immune response in humans. We therefore investigated the effect of sex and age on organ dysfunction and clinical course in patients with multiple injuries. Polytraumatized patients (injury severity score > 16) between 16 and 65 years old admitted to the Hannover Medical School Level 1 trauma center between January 1997 and December 2001 were included. Marshall Score for multiple organ dysfunction syndrome (MODS) was calculated for at least 14 days. The length of stay in intensive care unit and the ventilator days were recorded in addition to the number of transfusions the patient received. A total of 106 males and 37 females were included in the study. Patients with MODS had increased plasma levels of IL-6, IL-8, and IL-10. Furthermore, patients with organ dysfunction had more frequent sepsis and higher mortality rates. In addition, MODS was associated with extended length of stay in the intensive care unit and increased ventilator days. Females not older than 50 years with an injury severity score greater than 25 suffered significantly less MODS and sepsis compared with age-matched males. Moreover, they had significantly lower plasma cytokines. Thus, in this prospective study, sex difference was confirmed in MODS and sepsis, with a benefit observed in females. Although the levels of sex steroids were not measured, it seems that the protective effects may be due to estrogen effects on plasma cytokines. This suggestion is based on the fact that such salutary effects were apparent predominantly in premenopausal females.

Timing of fixation of major fractures in blunt polytrauma: role of conventional indicators in clinical decision making.

Grading of the clinical status in patients with multiple trauma is important regarding the treatment plan. In recent years, 4 different clinical conditions have been described: stable, borderline, unstable, in extremis. Clinical parameters have been widely used in patients with penetrating injuries, and 3 categories were found to be important: shock, hypothermia, coagulopathy. However, in blunt trauma patients, the role of conventional parameters for decision making regarding the timing of fracture treatment is poorly described. After blunt trauma, additional factors seem to play a role, because the injuries affect multiple body regions. These additional factors are summarized under the term, “soft-tissue injuries,” which may include the soft tissues of the extremities, lung, abdomen, and pelvis. The study describes four pathophysiologic cascades that are relevant to the clinical conditions listed above. Threshold values for separation of the patient conditions are documented, leading to a staged surgical strategy.

30 years of polytrauma care: An analysis of the change in strategies and results of 4849 cases treated at a single institution.

The quality and progress of treatment of 4849 multiple trauma patients treated at one institution was reviewed retrospectively. Three periods, 1975-1984 (decade I; n=1469) and 1985-1994 (decade II; n=1937) and 1995-2004 (decade III; n=1443) were compared. 65% of multiple trauma patients had cerebral injuries, 58% thoracic trauma and 81% extremity fractures (37% open injuries). Injury combinations decreased during all decades with head/extremity injuries being the most common combination. Throughout the three decades pre-hospital care became more aggressive with an increase of intravenous fluid resuscitation (I: 80%, II: 97%, III: 98%). Chest tube insertion decreased after an initial increase (I: 41%, II: 83%, III: 27%) as well as intubation (I: 82%, II: 94%, III: 59%). Rescue times were progressively shortened. For initial clinical diagnosis of massive abdominal haemorrhage ultrasound (I: 17%, II: 92%, III: 97%) replaced peritoneal lavage (I: 44%, II: 28%, III: 0%). CT-scans were used more frequently for the initial diagnosis of head injuries and other injuries to the trunk throughout the observation time. With regard to complications, acute renal failure decreased by half (I: 8.4%; II: 3.7%; III: 3.9%), ARDS initially decreased but increased again in the last decade (I: 18.1%, II: 13.4%, III: 15.3%), whereas the rate of multiple organ dysfunction syndrome (MODS) increased continuously (I: 14.2%, II: 18.9%, III: 19.8%) probably due to a decline of the mortality rate from 37% in the first to 22% in the second and 18% in the third decade and parallel increase of the time of death. These treatment results summarise the enormous clinical effort as well as medical progress in polytrauma management over the past 30 years. Further reduction of mortality is desirable, but probably only possible when immediate causal therapy of later posttraumatic organ failure can be established.