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Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_II | Pages 72 - 72
1 Feb 2012
Gray A White T Clutton R Hawes B Christie J Robinson C
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Damage Control techniques involve primary external fracture fixation to reduce the ‘second hit’ of surgery. This study used a large animal (ovine) trauma model to compare pathophysiological responses of primary external femoral fixation and intramedullary stabilisation.

Under terminal anaesthesia bilateral femoral fractures and hypovolaemia were produced using a pneumatic ram. 24 sheep were randomised into 4 groups and monitored for 24 hours. Group 1 – Control; Group 2 – Trauma only; Group 3 – Trauma and external fixation; Group 4 – Trauma and reamed intramedullary stabilisation. Outcome measures: pulmonary embolic load (transoesophageal echocardiography); plasma coagulation markers; bronchoalveolar lavage differential cell counts (neutrophils, lymphocytes and macrophages).

Total embolic load was significantly higher (p<0.001) in the intramedullary fixation group (median score 42 versus 20). All trauma groups had a significant increase (p < 0.05) in prothrombin time with a fall in antithrombin III and fibrinogen levels. No significant differences occurred between trauma groups with any coagulation or alveolar lavage marker.

Intramedullary femoral fracture fixation produced a relatively higher pulmonary embolic load. However, the initial fracture fixation method did not affect any of the changes seen in the measured coagulation or inflammatory markers during the first 24 hours of injury.


Orthopaedic Proceedings
Vol. 88-B, Issue SUPP_III | Pages 413 - 414
1 Oct 2006
Gray A Torrens L Christie J Graham C Robinson C
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Background: Transcranial Doppler Ultrasound has been used to detect cerebral micremboli following long bone fractures and intramedullary stabilization. However the clinical effects in terms of cognitive function remain unclear. We aim to measure the cerebral embolic load and to clarify clinical cognitive function following lower limb long bone fractures stabilised by reamed intramedullary fixation.

Methods: 27 femoral and tibial diaphyseal fractures (median age 36 years) were cognitively assessed 3 days following surgery and compared to the normal age and intelligence matched population. A wide range of cognitive tests assessed: global cognitive function; verbal fluency and speed; immediate and delayed memory recall; attention and mental processing speeds. 20 patients had intra-operative transcranial Doppler ultrasound monitoring of the middle cerebral artery for embolic signals. In addition a marker of neuronal injury (S-100B protein) was measured pre-operatively and at 0, 24 and 48 hours following surgery. One sample Wilcoxon signed rank test compared median (percentile) cognitive scores for the fracture patient cohort to a value of 50 representing the normal population.

Results: A significant deterioration in immediate memory recall of unstructured material was noted following surgery. Using established criteria, 4 patients had detectable cerebral emboli with a median count of 3 (range 2–9). Scatter plot graphs indicated no correlation between cerebral embolic events and clinical cognitive dysfunction. S-100B protein levels increased from a pre-operative median (interquartile range) of 0.20 (0.23) to a peak immediately following surgery of 0.51 (0.97) with no correlation to clinical cognitive dysfunction

Conclusions: A small number of cerebral embolic events occur during intramedullary fracture stabilisation but with no direct correlation made to cognitive dysfunction on detailed testing. Recent concerns over the specificity of S100B protein due to extracerebral tissue release appear to be confirmed.

Significance: Clarify cognitive function following intramedullary fracture stabilisation and correlate with cerebral (systemic) embolic load.


Orthopaedic Proceedings
Vol. 88-B, Issue SUPP_II | Pages 250 - 250
1 May 2006
Gray A Christie J Howie C Torrens L Shetty A Robinson C
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Study Purpose To assess clinical cognitive function and measure cerebral embolic load following primary cemented hip arthroplasty.

Methods 34 primary cemented hip arthroplasty patients (mean age 69.9 (SD 11.0)0 and no history of cerebrovascular disease, underwent cognitive assessment before and after (day 4) surgery. Testing included: Verbal fluency and speed (Control Oral Word Association Test); Working memory to assess immediate and delayed recall (Weschler Memory Scale III); Attention and mental processing speeds (Colour Trails 1& 2). A one sample Wilcoxon signed rank test compared median differences before and after surgery. A sub-group of 20 patients had intra-operative transcranial Doppler ultrasound monitoring of the middle cerebral artery for embolic signals. A marker of neuronal injury (S-100B protein) was measured pre-operatively and at 0, 24 and 48 hours following surgery.

Results A significant difference was noted in Colour Trails tests 1& 2 following hip arthroplasty with P values (C.I.) of 0.002 (−21, −4) and 0.023 (−15.5, −1.0) respectively.

Using established emboli criteria 10 (50%) patients had true cerebral emboli with a range from 1 to 550 signals (median 2.5 interquartile range (IQ) 2 to 12.5). S-100B levels increased from a pre-operative median (IQ) of 0.15 microg/L (0.12 to 0.20) to a peak immediately following surgery of 1.88(1.36 to 4.24) returning to 0.26(0.18 to 0.37) by 48 hours (normal range: 0.03–0.15). Plotted scatter charts indicated no correlation between embolic load and cognitive dysfunction or with S-100B levels following surgery.

Conclusion Cognitive testing indicates deterioration in early measured attention, visual searching and mental processing speed shortly following hip arthroplasty. No direct correlation was found between cognitive dysfunction and cerebral embolic load.


Orthopaedic Proceedings
Vol. 88-B, Issue SUPP_I | Pages 186 - 186
1 Mar 2006
Gray A Torrens L Christie J Howie C White T Carson A Robinson C
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Background: Long bone fractures and intramedullary stabilisation can result in the extravasation of fat and marrow emboli into the venous circulation. The effects of these emboli can become systemic causing neurological features.

Aim: To establish the cerebral microembolic load following femoral and tibial diaphyseal fractures treated by intramedullary fixation and to specify any neurological impairment with the application of a series of cognitive tests and a serum marker of neuronal injury.

Methods: 20 femoral and tibial fractures treated with intramedullary fixation had intra-operative transcranial doppler ultrasound monitoring of the middle cerebral artery with emboli detection software set to established guidelines. Cognitive testing (day 3), following surgery with an I.Q. assessment (PFSIQ) allowing comparison with age specific normative data. This included: verbal fluency and speed (COWAT – Control Oral Word Association Test); working memory with assessment of immediate and delayed recall; mini-mental state examination; executive function, attention and mental processing speeds (Colour Trails 1& 2). Beta S-100 levels measured pre-operatively, 0, 24 and 48 hours following surgery as a marker of neuronal injury.

Statistical Analysis: One sample Wilcoxon signed rank test to compare median of the cognitive scores with age matched normative data. Multiple regression analysis used to correlate embolic load with cognitive function.

Results: Mean age (SD) for the group is 32 (5.8). Mean PFSIQ of 52.8%, SD 21.4 [median 59.5, IQ range 28.3, 71.3]. No significant difference detected in cognitive testing compared with normative data. Cerebral microemboli detected in 17 of 20 patients with a count median (range) of 6 (0, 29). The mean pre-operative beta S-100 level was 0.36 micro g/l (normal range 0–0.15). This increased to a peak mean of 0.88 micro g/l immediately following surgery with a poor correlation to cerebral embolic load.

Discussion: Detailed clinical testing indicates no significant deterioration in cognitive function following intramedullary stabilisation of these fractures. A variable cerebral micro-embolic load was seen but with no detectable clinical effect. No direct correlation was found between the elevated levels of Beta S-100 seen following surgery and cerebral embolic load. This appears to correlate with previous concerns in the literature regarding the specificity and sensitivity of this established marker of neuronal injury.


Orthopaedic Proceedings
Vol. 88-B, Issue SUPP_I | Pages 171 - 171
1 Mar 2006
Gray A White T Clutton E Hawes B Christie J Robinson C
Full Access

Introduction Damage Control orthopaedic techniques have been proposed in the seriously injured with primary external fixation of long bone fractures, reducing the ‘second hit’ of surgery. We have developed a large animal (ovine) model for the study of major trauma.

Aim To clarify the sequence of pulmonary and systemic physiological responses over a 24-hour period following injury, comparing the effects of primary external femoral fixation to intramedullary stabilisation to better quantify the ‘second hit’ of these surgical techniques.

Methods Under terminal anaesthesia bilateral femoral diaphyseal fractures were produced using a mechanical pneumatic actuator (ram). Hypovolaemic shock was maintained for 4 hours before fluid resuscitation and surgical stabilisation.

24 sheep were randomised into 4 groups and monitored for 24 hours following injury:

Group 1 – Control Group (effects of general anaesthesia only)

Group 2 – Control Group for Trauma (injury but no long bone stabilisation)

Group 3 – Damage control group (Injury and external fixation)

Group 4 – Early total care (Injury and reamed intra-medullary stabilisation)

Outcome measures: Embolic load (Mayo score) using transoesophageal echocardiography; serum markers of coagulation (prothrombin time, activated partial thromboplastin time and fibrinogen levels) and inflammation (interleukin 6). Bronchoalveolar lavage to assess total cell count and cell differential to quantify the proportion of neutrophils present.

Results A sustained embolic shower was detected with each femoral fracture (mean Mayo score of 5 and 5.5 respectively). Intramedullary reaming and nailing produced further embolic events with a mean score of 2.5 and 1.5 respectively. Mean prothrombin time increased from a pre-fracture mean of 12 in each group to 18.8 (group 1) 20.7 (group 2); 24.8 (group 3); 31.1 (group 4). Alveolar lavage samples taken at 0, 4 and 24 hours following injury indicated a progressive neutrophilia developing in each group with a count pre-fracture of 4.3 increasing to 55.75 (group 1); 40 (group2); 49 (group3) and 31.7 (group 4) by 24 hours following injury.

Discussion The effects of damage control techniques in this model appear to be a reduced stimulation of the extrinsic coagulation system. An additional embolic hit was detected secondary to intramedullary reaming and nail insertion. Localised lung inflammation seems to develop in all groups with no significant differences seen due to treatment.