Paul Harwood

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.

Severe and multiple trauma in older patients; incidence and mortality

OBJECTIVE To examine the differences between severely injured older patients (aged over 65 years) compared with similarly injured younger adults in terms of incidence, inpatient mortality and factors predicting outcome. METHODS Data prospectively entered into the Trauma Audit and Research Network (TARN) database from our level I trauma unit over a 5-year period were retrospectively examined, with 3172 patients included in the final analysis. RESULTS Older patients accounted for 13.8% of those with severe injuries (Injury Severity Score 16 or more) and almost 2% of our trauma admissions overall. High energy injuries were responsible for the majority of these injuries though relatively minor trauma became increasingly important in older patients. Mortality rates in the older patients were more than twice those seen in the adult population (19% in the under 40s to almost 50% in the over 75s). Age, Injury Severity Score and Glasgow Coma Score continued to be predictive of mortality in older patients but other factors relevant in younger adults were not. CONCLUSIONS Patients in the older group without physiological derangement on admission were still at a relatively high risk of inpatient mortality. This was in contrast to the younger patients, suggesting that it might be more difficult to predict which older patients might benefit from more aggressive monitoring or treatment. Despite increased mortality in older patients, significant survival rates were achieved even in the oldest. Active treatment should not be withdrawn on the basis of age alone.

The Risk of Local Infective Complications After Damage Control Procedures for Femoral Shaft Fracture

Objectives To determine infection rates after damage control orthopaedics (DCO) and primary intramedullary nailing (1′ IMN) in multiply injured patients with femoral shaft fracture. Design Retrospective case analysis. Setting Level I trauma center. Patients All patients with New Injury Severity Score (NISS) >20 and femoral shaft fracture (AO 32-) treated in our unit between 1996 and 2002. Intervention Damage control orthopaedics, defined as primary external fixation of the femoral shaft fracture and subsequent conversion to an intramedullary nail, or primary IMN. Main Outcome Measurements Rates of infection classified as contamination (positive swabs with no clinical change), superficial, deep (requiring surgery), and removal of hardware (those requiring removal of femoral instrumentation or amputation). Results A total of 173 patients with 192 fractures were included; 111 fractures were treated by DCO and 81 by primary IMN. Mean follow-up was 19.1 months [median, 16.7, range, 1 (patient died)–67 months]. DCO patients had a significantly higher NISS and more grade III open fractures (P<0.001). IMN procedures took a median of 150 minutes compared with 85 minutes for DCO (P<0.0001). Although wound contamination (including contaminated pin sites) was more common in the DCO group (P<0.05), the risk of infectious complications was equivalent (P=0.86). Contamination was significantly more likely when conversion to IMN occurred after more than 14 days (P<0.05); however, this did not lead to more clinically relevant infections. Logistic regression analysis showed that although a DCO approach was not associated with infection, delay before conversion in the DCO group might be [P=0.002 for contamination and removal of hardware, P=0.065 for serious infection (deep or worse), not significant for other infection outcomes]. Grade III open injury also was significantly associated with serious infection in all patients (P<0.05). Conclusions Infection rates after DCO for femoral fractures are comparable to those after primary IMN. We see no contraindication to the implementation of a damage control approach for severely injured patients with femoral shaft fracture where appropriate. Pin-site contamination was more common where the fixator was in place for more than 2 weeks. For patients treated by using a DCO approach, conversion to definitive fixation should be performed in a timely fashion.

Application of bone morphogenetic proteins in orthopaedic practice: their efficacy and side effects.

Bone morphogenetic proteins (BMPs) have been extensively studied since the discovery of agents within bone that could induce bone formation at ectopic sites by Urist in the 1960s. Extensive preclinical research has been carried out showing the efficacy of these products in promoting bone healing. Clinical trials are encouraging, with meta-analysis of results revealing better rates of healing than treatment with autologous bone grafting (risk ratio [RR]: 0.845; 95% confidence interval [CI]: 0.772 – 0.924; p < 0.001 for clinical outcome and RR: 0.884; 95% CI: 0.825 – 0.948; p < 0.001 for radiological outcome). Preclinical and clinical safety assessments have revealed little evidence of toxic effects and there have been few reports of adverse events related to their use. A small rate of immunological reaction following administration, resulting in antibody formation, has been observed in some patients, without clinical consequence, although the long-term implications of this are unknown. Ongoing research is revealing that BMPs act on an extremely wide range of body tissues in a variety of manners and this is far from fully understood. It should be noted, however, that given the role of BMP as a differentiation factor, the production of undifferentiated neoplastic tissue seems unlikely. It has also been shown in an animal model that artificially administered BMP can cross the placenta and subsequently be detected in the growing embryo. As this area has been little investigated, use in pregnancy is currently contraindicated. Until the long-term safety profile is more fully documented it would seem sensible to continue to carefully control use and monitor patients closely. However, the current evidence is very promising.

The multiply injured child.

The treatment of multiple traumas in children requires knowledge of common injury patterns, incidence, mortality, and the consequences and differences between these injuries in children and adult patients. However, epidemiological studies concerning pediatric multiple trauma are rare. To address this, data were collected and analyzed from 682 multiple trauma patients treated at a Level I trauma center. The patients were divided into four age-related groups (< 6 years, 6-12 years, 13-18 years, and 18-40 years) and were evaluated for trauma mechanism, injury distribution, and cause of death. Children aged 6 to 17 years mostly were injured as pedestrians and cyclists whereas infants, preschoolers, and adults more commonly were injured as car passengers. Pediatric patients suffered a significantly higher mortality than adults, with a threefold increased risk of death when injured as passengers in car accidents. Injuries to the head and the legs were most common. A lower incidence of thoracic (28% versus. 62%), abdominal (20% versus 36%), pelvic (22% versus 35%), and upper limb (32% versus 43%) trauma was observed in children (< 18 years) than in adults (18-40 years). Nevertheless, trauma to the thorax, abdomen, and head were associated with a high risk of death in all groups. Spinal cord injuries, especially in the cervical region, also carried a high risk of mortality (36.8 in the group of patients younger than 18 years and 18.9 in the group of patients 18-40 years). Children younger than 6 years had the most severe head injuries. The data show that there are important differences in incidence, mortality, and injury patterns between pediatric and adult patients with multiple traumas.

Restoration of long bone defects treated with the induced membrane technique: protocol and outcomes

This prospective study was undertaken at a regional tertiary referral centre to evaluate the results of treatment of bone defects managed with the induced membrane (IM) technique. Inclusion criteria were patients with bone defects secondary to septic non-union, chronic osteomyelitis and acute fracture with bone loss. Pathological fractures with bone loss were excluded. Data collection included patient demographics, pathology, previous surgical intervention, size of bone defect, type of graft implanted, time-to-union and complications/reinterventions. The minimum time of follow up was 12 months. Forty-three patients (32 males) met the inclusion criteria with a mean age of 47.9 years (range 18-80 years). 22 patients had an acute traumatic bone loss associated with open fracture and 21 presented with an infected non-union or underlying osteomyelitis requiring bone excision. The most common microorganisms grown were staphylcoccous aureus and coagulase negative staphylococcous. The mean length of the bone defect area was 4.2 cm (range 2-12 cm). All patients were managed with the two stage technique receiving composited grafting (Autologous bone graft (Iliac crest/RIA), graft expander as required, osteoprogenitor cells, growth factor) during the second stage. There was one failure (humeral infected non-union) in a previous background of bone radiation that necessitated reconstruction with a free fibula vascularized graft. One patient had a fall and sustained implant failure (humeral defect) 3 months after reconstruction and following re-plating progressed to union 4 months later. Two patients required re-grafting due to failure of healing in one of the defect sides. One patient presented with a discharging sinus 2 years after successful healing of a tibial defect that was treated successfully with soft tissue and bone debridement without necessitating further interventions. One patient despite union (distal 1/3 tibia) underwent a below knee amputation due to a dysfunctional ankle/foot (previous foot compartment syndrome-regional pain syndrome). Of those patients, with lower limb injuries, 4 patients had leg length discrepancies of 1 cm, 1.5 cm, 2 cm (two patients) respectively. The mean time to radiological union was 5.4 months (range 2-12 months). The average time of healing of 1 cm bone defect was 1.24 months. Patients with upper limb reconstruction recovered earlier than those with lower limb injuries. At the latest follow up all patients were able to mobilize full weight bearing without residual pain. The induced membrane technique appears to be an alternative good option for the management of large bone defects secondary to acute bone loss or infected non-unions. The incidence of re-interventions was low in this challenging cohort of patients. The technique should be considered in the surgeons armamentarium as it is effective and is associated with a low rate of complications.

The safety and efficacy of linezolid in orthopaedic practice for the treatment of infection due to antibiotic-resistant organisms

Linezolid is the first of a new class of antibacterial agents, the oxazolidinones. It is particularly effective against Gram-positive infections and little resistance has been reported, even amongst methicillin- and vancomycin-resistant bacteria. The compound’s excellent oral bioavailability and reasonable safety profile, along with the increasing incidence of resistant infections, means that linezolid offers a valuable alternative to more traditional therapies such as vancomycin. Although no large randomised trials have been carried out in patients with orthopaedic infections such as osteomyelitis and septic arthritis, early results are encouraging. However, the apparent increase in observed adverse events, particularly bone marrow suppression, seen with prolonged administration, means that treatment of such patients must be undertaken with careful surveillance, at least until these complications are better understood.

Pattern of release and relationship between HMGB-1 and IL-6 following blunt trauma

BACKGROUND High mobility group box-1 (HMGB-1), a recently identified inflammatory cytokine, is implicated in the pathogenesis of several inflammatory, infective and neoplastic processes. Patterns of expression following blunt trauma have not been adequately reported in the literature. This study aimed to quantify the serum concentrations of HMGB-1 following blunt trauma, and assess its relationship with the more established interleukin 6 (IL-6). PATIENTS AND METHODS 20 patients with median injury severity score 17 (range 9-36) sustaining closed diaphyseal fractures of the femur treated by intramedullary nailing were included in the study. Serum concentrations of HMGB-1 and IL-6 were measured at several time points during their treatment. RESULTS A strong correlation was observed between admission and day 1 post-op concentrations of IL-6 and both the injury severity score (ISS) and the requirement for intensive care unit treatment. Serum concentrations of HMGB-1 did not demonstrate such a correlation. Around day 3 when IL-6 concentrations begin to fall, serum HMGB-1 concentrations were observed to increase. CONCLUSIONS IL-6 concentration measured early after admission is again shown to be strongly associated with overall injury severity and requirement for intensive care unit treatment. In contrast, HMGB-1 appears to be a late inflammatory mediator with levels becoming elevated once serum concentrations of IL-6 begin to fall. However, we were unable to demonstrate any relationship with injury severity or requirement for ICU care at any stage. These preliminary findings may form the basis for future research in this area.

Are alterations of lymphocyte subpopulations in polymicrobial sepsis and DHEA treatment mediated by the tumour necrosis factor (TNF)-α receptor (TNF-RI)? A study in TNF-RI (TNF-RI–/–) knock-out rodents

Sepsis is associated with depression of T cell‐dependent immune reactivity with proinflammatory cytokines, such as tumour necrosis factor (TNF)‐α, playing an important role. Recent investigations describe an association between these immunological alterations and disturbances of the endocrine system, related most frequently to sex steroid hormones. Dehydroepiandrosterone (DHEA), one of the most abundant adrenal sex steroid precursors, seems to have a protective immunological effect towards septic insults. In this study, both the role of TNF‐receptor I (RI) and possible interactions in the protective role of DHEA were investigated in a murine model of polymicrobial sepsis. Polymicrobial sepsis was induced by caecal ligation and puncture (CLP) in a murine model. The effects of DHEA on survival, clinical parameters and cellular immunity (T lymphocytes and natural killer (NK) cells) were investigated. CLP was performed in genetically modified TNF‐RI knock‐out (TNF‐RI–/–) and genetically unmodified (wild‐type, WT) mice. DHEA application was associated with a decrease in the mortality rate in WT animals. A mortality rate of 91·7% was observed in TNF‐RI–/– mice after CLP. This mortality rate was reduced to 37·5% by the application of DHEA. In sham‐operated TNF‐RI–/– animals, a significantly higher proportion of NK cells within the lymphocyte population was measured compared with the corresponding WT group. After CLP, a significant increase in the percentage cell count of NK cells was recorded in WT mice. Overall, following DHEA application in WT mice, an alteration in the cellular immune response was characterized by a reduction in the percentage counts of CD4+, CD8+ and NK cells. In the group of TNF‐RI–/– mice treated with DHEA, no increase in the percentage cell count of NK cells was observed after CLP. No data for cell analysis were available from the CLP‐TNF‐RI–/– mice treated with saline, due to the high mortality rate in these animals. DHEA reduces the complications of sepsis in a TNF‐RI‐independent manner. Our study suggests that NK cells are involved in the protective mechanism of DHEA in WT mice. It would therefore seem that DHEA represents a feasible alternative therapy for the dysregulated immune system in sepsis.

Calculation of Different Triage Scores Based on the German Trauma Registry

Background and Purpose:Exact, prehospital, on-scene grading is crucial in patients with life-threatening injuries. For blunt trauma, early patient grading continues to represent a challenge. In Europe, the ratio between heart rate and blood pressure (Shock Index [SI]) was frequently used in the 1980s, but was later discarded as irrelevant due to improved rescue times. The current study reevaluates the usefulness of this index based on the German Trauma Registry.Methods:Patients documented in the German Trauma Registry between 1993 and 2001 were investigated. The registry lists patients with multiple injuries. From these patients, inclusion criteria were multiple injuries with complete on-scene documentation. A subgroup analysis was performed for patients who have minor injuries (Injury Severity Score [ISS] < 16, no requirement of intensive care therapy) and patients who died in the emergency room (ER). The association between pathologic values of the SI and later complications (organ failure and death) was investigated. Also, associations between pathologic shock indices and the clinical diagnoses as made by the physician on scene and special injuries diagnosed after hospital admission were calculated.Results:6,346 patients were included in the study and demonstrated the following demographic parameters: mean age 33.4 (16–81) years, male gender 76.4%; mean admission Glasgow Coma Scale (GCS) 9.8 (4–15) points, mean alert time 14.4 (6.3–73) min, mean rescue time 43.5 (22–91) min; mean prehospital crystalloids 954.9 (200–4,300) and colloids 773 (150–3,100). A receiver operating characteristic (ROC) analysis regarding the association between a score and the likelihood of complications was calculated and provided the following results: Revised Trauma Score (RTS), 0.633; SI, 0.684; pulse rate, 0.579; blood pressure, 0.564; respiratory rate, 0.377. An odds ratio was calculated, describing the likelihood of organ failure in specific patient subgroups. The highest values were obtained for patients who died in the ER (6.3), patients in whom the cause of death was hemorrhagic shock (6.1), and patients who sustained predominantly abdominal (5.3) and pelvic injuries (4.5).Conclusion:The data of this study supports previous findings that the ratio between pulse and systolic blood pressure is sensitive in detecting shock states in patients with multiple injuries. In the current population, the value of the SI as a field screening tool was better in patients who died of shock and those who sustained abdominal or pelvic injuries when compared with those who had extremity fractures only. It was improvable by adding the presumed major clinical prehospital diagnosis. The score is easily accessible and may be used for estimation of the blood volume status on scene.