Aims. Tourniquets have potential adverse effects including postoperative thigh pain, likely caused by their ischaemic and possible compressive effects. The aims of this preliminary study were to determine if it is possible to directly measure intramuscular pH in human subjects over time, and to measure the intramuscular pH changes resulting from tourniquet ischaemia in patients undergoing knee arthroscopy. Methods. For patients undergoing short knee arthroscopic procedures, a sterile calibrated pH probe was inserted into the anterior fascial compartment of the leg after skin preparation, but before tourniquet inflation. The limb was elevated for three minutes prior to tourniquet inflation to 250 mmHg or 300 mmHg. Intramuscular pH was recorded at one-second intervals throughout the procedure and for 20 minutes following tourniquet deflation. Probe-related adverse events were recorded. Results. A total of 27 patients were recruited to the study. Mean tourniquet time was 21 minutes (10 to 56). Tourniquet pressure was 300 mmHg for 21 patients and 250 mmHg for six patients. Mean muscle pH prior to tourniquet inflation was 6.80. Muscle pH decreased upon tourniquet inflation, with a steeper fall in the first ten minutes than for the rest of the procedure. Change in muscle pH was significant after five minutes of tourniquet ischaemia (p < 0.001). Mean muscle pH prior to tourniquet release was 6.58 and recovered to 6.75 within 20 minutes following release. No probe related adverse events were recorded. Conclusion. It is possible to directly measure skeletal muscle pH in human subjects over time. Tourniquet ischaemia results in a decrease in human skeletal muscle pH over time during short procedures. Cite this article: Bone Joint Res 2021;10(6):363–369

Aims. Glucose-insulin-potassium (GIK) is protective following cardiac myocyte ischaemia-reperfusion (IR) injury, however the role of GIK in protecting skeletal muscle from IR injury has not been evaluated. Given the similar mechanisms by which cardiac and skeletal muscle sustain an IR injury, we hypothesized that GIK would similarly protect skeletal muscle viability. Methods. A total of 20 C57BL/6 male mice (10 control, 10 GIK) sustained a hindlimb IR injury using a 2.5-hour rubber band tourniquet. Immediately prior to tourniquet placement, a subcutaneous osmotic pump was placed which infused control mice with saline (0.9% sodium chloride) and treated mice with GIK (40% glucose, 50 U/l insulin, 80 mEq/L KCl, pH 4.5) at a rate of 16 µl/hr for 26.5 hours. At 24 hours following tourniquet removal, bilateral (tourniqueted and non-tourniqueted) gastrocnemius muscles were triphenyltetrazolium chloride (TTC)-stained to quantify percentage muscle viability. Bilateral peroneal muscles were used for gene expression analysis, serum creatinine and creatine kinase activity were measured, and a validated murine ethogram was used to quantify pain before euthanasia. Results. GIK treatment resulted in a significant protection of skeletal muscle with increased viability (GIK 22.07% (SD 15.48%)) compared to saline control (control 3.14% (SD 3.29%)) (p = 0.005). Additionally, GIK led to a statistically significant reduction in gene expression markers of cell death (CASP3, p < 0.001) and inflammation (NOS2, p < 0.001; IGF1, p = 0.007; IL-1β, p = 0.002; TNFα, p = 0.012), and a significant reduction in serum creatine kinase (p = 0.004) and creatinine (p < 0.001). GIK led to a significant reduction in IR-related pain (p = 0.030). Conclusion. Systemic GIK infusion during and after limb ischaemia protects murine skeletal muscle from cell death, kidneys from reperfusion metabolites, and reduces pain by reducing post-ischaemic inflammation. Cite this article: Bone Joint Res 2023;12(3):212–218

Aims: The pathomechanism of avascular necrosis of the femoral head (AVN) is still debated. Hip joint synovitis and effusion may impair blood ßow to the femoral head. The critical ischemia time is around 6 hours, but repeated ischemic episodes may impair reperfusion and elicit AVN. The aims of this study were to investigate the value of dynamic MRI in femoral head after ischemia and during reperfusion. Methods: In 15 domestic pigs, 3–4 months old, femoral head ischemia was achieved by raising the joint pressure to 250 mmHg by dextran infusion through a hole in the acetabular wall. MRI was performed (Philips gyroscan S15, 1.5 T, Gd-DTPA enhancement, dynamic imaging interval 39 sec.) before ischemia, after 6 hours of ischemia, and again after 4 hours of reperfusion. Results: Signal intensity versus time (SI/t) plots were constructed from 347 MR studies. By regression analysis of SI/t curves an index (enhancement/decrease) was developed as criterion for arterial or venous circulatory disturbance. Index values < 1.1 signiþed arterial impairment, > 100 venous disturbance. Values between 1.1 and 100 were considered normal. The positive predictive value for disturbed osseous blood ßow was 96%. Conclusions: Early detection of intraosseous circulatory disturbance was possible with a mathematical model for dynamic MRI results. The method is reproducible and may be employed in the early diagnosis of AVN and during treatment for monitoration of revascularisation

Purpose: Near-infrared spectroscopy (NIRS) detects changes in chromophore concentrations of oxygenated (O2Hb) and deoxygenated hemoglobin (HHb) in target tissues approximately 2 to 3 cm below the skin. The main purpose of this study was to non-invasively measure skeletal muscle oxygenation in the leg during and after tourniquet (TQ)-induced ischemia using continuous wave NIRS. Secondarily, we aimed to assess the sensitivity, specificity, and reliability of this optical technique for detection and continuous monitoring of changes in muscle oxygenation and hemodynamics during TQ-induced ischemia throughout orthopedic surgery. Method: Consented patients aged 19–69 (n=21) with unilateral ankle fracture requiring emergency or elective surgery at our institution were recruited. All patients underwent standard general anesthetic. A pair of NIRS probes was fixed over the midpoint of the tibialis anterior muscle (TA) of both the fractured and healthy legs. A thigh TQ was applied to the injured leg and inflated to 300 mmHg. Using the NIRS apparatus coupled to a laptop with data acquisition software, changes in O2Hb, HHb, and total hemoglobin (tHb) levels in the TAs of both legs were measured at 10 Hz before and during TQ inflation, and after release until values returned to baseline. In each surgery the TQ was released when arterial obstruction was no longer required by the clinical team. Data are reported as mean±SD. Results: Changes in O2Hb, HHb, and tHb were successfully collected, stored and transmitted for graphic display in all subjects. TQ time (ischemia interval) varied among subjects, from 1245 s to 4431 s (2753±854). NIRS measured a progressive increase in HHb (2.6±2 μmol/L) during the first minute of TQ inflation and a sharp increase in O2Hb (23.3±12 μmol/L) during the first minute of leg muscle reperfusion (after deflation). Following TQ inflation a progressive increase in HHb (24.2±10.3 μmol/L) with a concomitant decrease in O2Hb (mean – 24.4±8 μmol/L) in the under-TQ TA were consistent across subjects. These changes in ΔHHb and ΔO2Hb began to reverse immediately after TQ deflation. Significant correlations were observed between ischemia interval and, respectively, oxygenation recovery time (r2=0.84) and changes of deoxygenated hemoglobin (r2=0.57). Conclusion: We demonstrated that, following TQ inflation and deflation respectively, NIRS can sensitively monitor muscle deoxygenation and reoxygenation. Consistent patterns of ΔHHb and ΔO2Hb occurred during TQ-induced ischemia in all subjects. These data confirm that near infrared spectroscopy is useful for the non-invasive detection and monitoring of muscle ischemia. These results indicate that it may be useful to investigate the efficacy of NIRS in the early detection of muscle ischemia or hypoxemia in conditions such as compartment syndrome. FUNDING: MSFHR, COF, BC Lung

Tourniquet induced ischemia-reperfusion syndrome (IRS) may trigger systemic inflammatory response following a total knee arthroplasty. The IRS will be studied in a prospective randomized controlled study in humans undergoing total knee arthroplasty, by measuring blood inflammatory mediators and blood gases. Materials and Methods: Forty four (n=44) patients (female/male: 35/9 male) with a mean age of 72 years, undergoing primary total knee arthroplasty for osteoarthritis, were prospectively randomized in two groups. 22 patients operated with tourniquet [tourniquet group (TG)] and 22 patients operated without a tourniquet [non-tourniquet group (NTG)]. The mean overall ischemia time was 90 minutes. Arterial and venous blood samples were collected preoperatively, and at 1, 2, 3, 6, 24, 48 hours postoperatively. The pro-inflammatory (IL-1b, IL-6) and anti-inflammatory cytokines (IL-10) as well as the adhesion molecules (ICAM, VCAM), the CRP and blood counts were measured and correlated with the blood gases. Results: Patients in TG had higher cytokine and inflammatory mediators values, compared to the NTG group especially during the sixth postoperative hour and the first postoperative day. The most abrupt changes were evident in the patients with the highest preoperative levels of cytokines and inflammatory mediators especially when the ischemia time was more than 90 minutes. Male patients demonstrated the most significant changes. Discussion: The use of the tourniquet triggers the systemic inflammatory response. The most remarkable changes in inflammatory mediators are evident during the sixth postoperative hour and the first posoperative day. Tourniquet may be used for Total knee Replacement but care should be taken to decrease the ischemia time to the absolutely necessary specifically in males

Aims: Pharmacological modulation of skeletal muscle reperfusion injury after trauma associated ischaemia may improve limb salvage rates and prevent the associated systemic sequelae. Resuscitation with hypertonic saline restores the circulating volume and has favourable effects on tissue perfusion and blood pressure. The purpose of our study was to evaluate the effects of hypertonic saline on skeletal muscle ischaemia reperfusion (I/R) injury and the associated endorgan injury. Methods: Adult male Sprague Dawley rats (n=24) were randomised into three groups: control group, I/R group treated with normal saline and I/R group treated with hypertonic saline. Bilateral hind-limb ischaemia was induced by rubber band application proximal to the level of the greater trochanters for 2.5 hours. Treatment groups received either normal saline or hypertonic saline prior to tourniquet release. Following twelve hours reperfusion, the tibialis anterior muscle was dissected and muscle function assessed electrophysiologically by electrical field stimulation. The animals were then sacrificed and skeletal muscle harvested for evaluation. Lung tissue was also harvested for measurement of wet-to-dry ratio, myeloperoxidase content and histological analysis. Results: Hypertonic saline significantly attenuated skeletal muscle reperfusion injury as shown by reduced twitch and tetanic contractions of the skeletal muscle (Table). There was also a significant reduction in lung injury as demonstrated by differences in wet-to-dry ratio, myeloperoxidase content and histological analysis. Conclusion: Resuscitation with hypertonic saline may have a protective role in attenuating skeletal muscle ischaemia reperfusion injury and its associated systemic sequelae

Introduction: Intra-uterine vascular deficiency of the upper limbs is very rare. Materials & Methods: Thirty two cases collected by 118 paediatric surgeons (GEOP) over the last 20 years were presented. Results: This series illustrates the large range of presentations of vascular deficiencies, from total ischaemia of both upper limbs to small scars of the hand. Three infants had diabetic mothers; nine children had a cerebral infarction; non disturbed haematologic screening was found; three new born had an intra-uterine thrombotic event. Discussion: Our hypothesis is that such an intra-uterine thrombotic pathology can lead to thromboembolism. The embolus passing through the foramen ovale, arrives in the high pressure circulation and is transported directly to the upper limbs and brain. The size of embolus corresponds with the extent of the necrosis

Introduction: Perioperative blood losses in TKR (total knee replacement) are significant and it has been determined that hidden blood loss is frequently more significant than visible blood loss. The aim of this study is to determine if there were any differences in blood loss due to the timing of ischemia cuff release during TKR. Materials and methods: We studied 103 patients divided into 2 groups; in group A, of 41 patients, the cuff was released when all the bon cuts had been carried out, hemostasis of bleeding blood vessels was carried out and pressure was elevated until the end of surgery and placement of the compressive bandage. In group B, of 62 patients, once the prosthesis was cemented the cuff was released, hemostasis was applied, the wound was sutured and the compressive bandage was put in place without elevating the cuff pressure. In both groups we recorded intraoperative blood loss, both external blood loss and through the drainage, which was removed at 36–48 hours. Hidden blood loss was determined using the formula of Naddler et al that considers sex, weight, height and preoperative hemoglobin and hemoglobin 4 days after surgery. Results: In group A the mean volume drained was 502 ml, hidden blood 928 ml, with a total loss of 1429 ml. In group B the mean volume drained was 567 ml, hidden blood 764 ml and total loss of blood 1331. There were no significant differences between both groups. Conclusions: The significance of blood loss in TKR is therefore confirmed, especially hidden blood loss. There were no statistically significant differences according to the moment at which the ischemia cuff was released

Aims: Pharmocological modulation of skeletal muscle reperfusion injury after an ischaemic insult may improve limb salvage rates and prevent the associated systemic sequelae. Activated Protein c (APC) is an endogenous anti-coagulant with anti-inflammatory properties. The purpose of our study was to evaluate the effects of APC on skeletal muscle ischaemia reperfusion injury and to examine the direct effects of APC on neutrophil activation. Methods: Adult male Sprague Dawley rats (n=30) were randomised into three groups: control group, I/R group treated with normal saline and I/R treated with APC. Bilateral hind-limb ischaemia was induced by rubber ban application proximal to the level of the greater trochanters for two hours. Treatment groups received either normal saline or APC prior to tourniquet release. Following twelve hours reperfusion, the tibialis anterior was dissected and muscle function assessed electrophysiologically by electrical field stimulation. The animals were then sacrificed and skeletal muscle harvested for evaluation. Skeletal muscle injury was assessed based on myeloperoxidase content, wet-to-dry ratio and histological analysis. The effect of APC on TNF-α stimulated human peripheral blood neutrophils was also examined by measuring CD 18 expression and reactive oxygen species (ROS) generation. Results: APC significantly attenuated skeletal muscle reperfusion injury as shown by reduced myeloperoxidase content, wet-to-dry ratio and electrical properties of skeletal muscle. These findings were supported by our histological findings. Our in-vitro work demonstrated a reduction in CD 18 expression and ROS generation. Conclusion: Activated Protein C may have a protective role in the setting of skeletal muscle ischaemia reperfusion injury and this is in part mediated by a direct inhibitory effect on neutrophil activation

Purpose: Several variables related to tourniquet (TQ) inflation contribute to ischemic muscle injury. Among these the duration of ischemia has been identified as a primary factor. The purposes of this study were to investigate the following during and after TQ-induced ischemia during orthopedic trauma surgery:. muscle oxygenation changes measured by near infrared spectroscopy (NIRS);. muscle protein oxidation; and. correlations between muscle oxygenation / hemodynamics and oxidative changes. Method: Consented patients aged 19–69 yrs (n=18) with unilateral ankle fracture requiring surgery at our institution were recruited. A pair of NIRS probes was fixed over the midpoint of the tibialis anterior muscle (TA) on both the injured and healthy legs. A thigh TQ was applied to the injured leg and inflated to 300 mmHg. Using the NIRS apparatus coupled to a laptop with data acquisition software, changes in oxygenated (O2Hb), deoxygenated (HHb), and total hemoglobin (tHb) levels in the TA of both legs were measured before and during TQ inflation, and after release until values returned to baseline. PRE surgical biopsies were collected from the peroneus tertius muscle (PT) immediately after TQ inflation and incision. POST biopsies were collected from the same PT immediately before TQ deflation. Oxidation of PT myosin, actin, and total protein was quantified using Western blot analysis of 4-hydroxynonenal (4-HNE) modified proteins. Data are reported as mean±SD. Results: In PRE biopsies compared to POST biopsies there were large and statistically significant increases in the PT content of 4-NE modified myosin (174.4±128%; P< 1×10-6), actin (223.7±182%; P< 5×10-9), and total protein (567.5±378%; P< 5×10-7). There was a greater increase in PT protein oxidation in male subjects than in female subjects (50.8% difference; P< 0.05). In the TA of the fractured side, there were moderate to strong linear correlations between total protein oxidation and: the relative change in tHb (r=−0.704) and O2Hb (r=−0.415) during the period of TQ inflation and the rate at which the muscle became reoxygenated following TQ release (r=0.502). There was no relationship between muscle protein oxidation and TQ time, nor between muscle protein oxidation and age of patients. Conclusion: TQ-induced muscle ischemia for 21 to 74 min during lower extremity surgery leads to oxidative muscle injury as measured according to myofibrillar contractile protein oxidation. Importantly, we observed that when the TQ was “leaky,” local increases in muscle tHb were associated with a lower magnitude of protein oxidation, however, when local decreases in muscle O2Hb were observed, perhaps due to local blood loss below the TQ, more oxidative changes resulted. Intriguingly, gender appeared to influence the extent of muscle oxidative injury, but age did not. Surprisingly, there was no significant correlation between muscle oxidative injury and the TQ-induced ischemia interval. FUNDING: MSFHR, COF, BCLA

Introduction and Aims: To determine whether taurine influences skeletal muscle ischaemia-reperfusion injury in a rat hindlimb model. Method: Twenty-three rats in five groups were subjected to right hindlimb ischaemia-reperfusion injury. The right femoral vein was exposed and cannulated, and a tourniquet applied to the right hindlimb. The left hindlimb acted as a control in each animal. In group 1 there was no treatment, group 2 had normal saline injected into the femoral vein distal to the tourniquet, group 3 had taurine 200mg/Kg injected distal to the tourniquet, group 4 had taurine 200mg/Kg injected proximal to the tourniquet, and group 5 had taurine 100mg/Kg distally and 100mg/Kg proximally. After ischaemia (four hours) and reperfusion (30 minutes), right and left gastrocnemius biopsies were taken and their contraction strength in response to a standardised electrical impulse was measured. Results: Histology of all right-sided biopsies confirmed inflammatory changes consistent with ischaemia-reperfusion injury. In groups 1, 2, 4, and 5, the mean contraction strength of the right (ischaemia-reperfusion injury) biopsies was significantly less than that of the left (control) biopsies. In group 3 (taurine distal to the tourniquet) the difference in strength between right and left was an order of magnitude less than in the other groups, and was not statistically significant. Conclusion: These data suggest that taurine during ischaemia confers some protection against ischaemia-reperfusion injury mediated functional impairment in rat skeletal muscle

Introduction: The aim was to evaluate the outcome of orthopaedic intervention in children who sustained peripheral ischaemia from meningococcal septicaemia and assess the benefit of fasciotomies within this group. Methods: From 1994–2004 there were 190 admissions to paediatric intensive care unit (PICU) with meningococcal septicaemia. 12 had significant Orthopaedic/Plastic Surgical input. Case notes were examined to establish admission patterns, limb progress, operative intervention and outcomes. All presented with viral symptoms and developed rapidly spreading purpuric rashes within 24hours. 8 were admitted from A& E, 4 transferred from other hospitals. All received antibiotics, fluid resuscitation, ventilation and inotropic support. One child died within 14 hours of PICU admission. Haemofiltration was used in 11 children (mean 14.8 days, range 2–60 days). We were able to follow up 8 of the survivors clinically. Results: All children had surgical treatment. 9 children had one or more amputations. Two children did not require amputations. Seven of the 12 children had fasciotomies performed (mean 34 hours after admission, range 2–96 hours). The child who died had multiple fasciotomies at 9 hours post admission. The remaining children had varying amputations. The other five children did not have fasciotomies. Of these one child did not require any amputations, three children had partial amputation of a single limb and one child had partial amputations of two limbs.. All five within this group required additional split-skin grafts. 8 children were followed clinically. 7 were mobile with walking aids with a mean of 1.3 prosthetic lower limbs (range 0–2). Conclusion: There is no evidence from our study that early fasciotomies are detrimental to survival, limb function or subsequent wound healing after definitive amputation. In other published series fasciotomy has been advocated within 24hours. In 2 of 7 patient, after fasciotomy the demarcation level receded distally leading to more distal amputation levels

Introduction. Ischaemia reperfusion injury (IRI) is a very common metabolic insult in orthopaedics. It is often a subtle clinical event such as after brief tourniquet use, however severe injury, even multi-organ failure or death may result from prolonged tourniquet-use, crush injuries, vascular trauma or the release of compartment-syndrome. IRI is mediated by leukocyte infiltration and oxidatively-induced endothelial disruption. Antioxidants clearly attenuate or prevent this effect in animal models. Hypothesis. That the antioxidant medications ascorbate and n-acetyl-cysteine attenuate IRI in the setting of elective knee arthroscopy. Methods & Materials. A EudraCT-registered, prospective, randomized-controlled trial was performed. Patients undergoing elective knee arthroscopy (n=24) were randomized to one of 3 groups (IV NAC/oral ascorbate/placebo). Full blood counts, cytokines, adhesion molecules, physiological response, pain scores and analgesia were recorded pre-operatively and at 3 post-operative time-points. Results. Physiological response, analgesia and VAS did not differ. NAC inhibited VCAM-1 (p=0.003) and tended to inhibit ICAM-1 (p=0.094). NAC tended to increase circulating leukocytes (p=0.093), neutrophils (p=0.12) and monocytes (p=0.04) and also induced a transient early increase in IFN-gamma (p=0.022). Conclusions. NAC attenuates the IRI resulting from tourniquet use in elective knee arthroscopy by apparently reducing adhesion molecule expression and leukocyte trapping in the post-ischaemic limb. The potential systemic benefits of NAC warrant further study in the setting of a more extensive ischaemic insult

In primary total knee arthroplasty (TKA) performed under ischemia the antibiotic prophylaxis is administered 15’ before inflating the tourniquet. The infection rate in TKA is higher than in hip arthroplasty. We hypothesise that ischemia could impair the efficacy of the antibiotic. The objective of our study was to compare the effectiveness of two schedules of antibiotic administration. We conducted a randomised and a double blind study. Patients were assigned to receive placebo 15’ before inflating tourniquet and cefuroxim 1.5 g 10’ before releasing the tourniquet (experimental arm) or cefuroxim 1.5 g 15’ before inflating tourniquet and placebo 15’ before releasing tourniquet (standard arm). In both arms cefuroxime 1.5 g was administered 6 hours after finishing surgery. The variables gathered were: age, sex, indication for TKA, co-morbidity, ASA score, duration of the operation, number of blood transfusions, days of hospitalisation and number of surgical site infections after 3 months of surgery. Categorical variables were compared using the χ. 2. test or the Fisher exact test and quantitative variables using Student-t test. Nine hundred and eight patients were randomised and 466 and 442 patients were allocated to experimental and standard arms respectively. Both groups were similar and there were no differences in deep and superficial infection rates, 1.39% and 4.18% for experimental arm and 3.39% and 3.17% for standard arm (p> 0.05). The experimental arm had a lower global and deep infection rate than the standard arm when the length of surgery was lower than the 75th percentile (global: 4.03 vs 7.93%, p=0.04, deep: 1.72% vs 4.44%, p=0.07). The administration of antibiotic prophylaxis 10’ before releasing the tourniquet decreases the surgical site infection rate when the duration of surgery is lower than the 75th percentile

Aims: Evaluate the outcome of orthopaedic intervention in children who sustained peripheral ischaemia resulting from meningococcal septicaemia and to assess the benefit of fasciotomies within this group. Introduction: There have been only two published series on the orthopaedic management of meningococcal septicaemia in children. We carried out a retrospective review of all patients who had undergone this intervention in RHSC. Methods: Between 1994 and 2004 there were 190 admissions to paediatric intensive care unit (PICU) with meningococcal septicaemia. 12 had significant Orthopaedic/Plastic Surgical input. Case notes were examined to establish admission patterns, limb progress, subsequent operative intervention and eventual outcomes. All presented with vague viral symptoms and developed rapidly spreading purpuric rashes within 24hours. 8 children were admitted from A& E and 4 were transferred from other hospitals. All received antibiotics, fluid resuscitation, ventilation and inotropic support. One child died within 14 hours of PICU admission. Haemofiltration was used in 11 children (mean 14.8 days, range 2–60 days). We were able to follow up 8 of the survivors clinically. Results: All children had some form of surgical treatment. 9 children had one or more amputations. Two children did not require amputations. Seven of the 12 children had fasciotomies performed (mean 34 hours after admission, range 2–96 hours). The child who died from overwhelming sepsis had multiple fasciotomies at 9 hours post admission. The remaining children had varying amputations. The other five children did not have fasciotomies. Of these one child did not require any amputations, three children had partial amputation of a single limb and one child had partial amputations of two limbs. All five within this group required additional split-skin grafts. 8 children were followed clinically. 7 were mobile with walking aids with a mean of 1.3 prosthetic lower limbs (range 0–2). Conclusion: There is no evidence from our study that early fasciotomies are detrimental to survival, limb function or subsequent wound healing after definitive amputation. In other published series fasciotomy has been advocated within 24hours. In our study 2 of our 7 patients who underwent fasciotomy the demarcation level receded distally post decompression leading to more distal amputation levels

Introduction. The concept and method of repeatedly connecting an extracorporeal blood pump to produce elevated pancycle inflow pressures to ischaemic limbs is presented. The aim of this study was to determine if intermittent increased perfusion would improve the clinical picture in peripheral arterial disease. Methods. Animal studies—to determine the safety and efficacy of the pumping and the access device were performed on 12 sheep. Following successful completion of that study, pilot studies of 18 patients were treated using the Peripheral Access Device (PAD) and Hypertensive Extracorporeal Limb Hyperperfusion (HELP). Treatment was offered to patients who had no other alternative than major amputation. Patients were treated for less than 100 hours of total pumping, broken over three or less treatment periods over approximately one week. Improvement was measured by pain scores, clinical examination and digital thermography. Results. In all cases access and desired flow parameters were shown to be reliably achieved. In all cases an improvement was found to peripheral circulation, with the longest follow up at more than three years and mean CFI improving from 0.6 to 1.1. Mortality and infection rates in the pilot study were lower than expected for amputation, with a third of patients retaining their limbs. Conclusion. It is shown that blood flow through collaterals can be very significantly augmented by the HELP treatment and that pancycle hyperperfusion can be safely repeated by implantation of the PAD arterial access device, offering a potential new treatment modality for Critical Limb Ischaemia

Objectives: Ischaemia reperfusion injury (IRI) is one of the most common metabolic insults in orthopaedic clinical practice. Oral ascorbate and both oral and intravenous n-acetylcysteine (NAC) have shown definitive beneficial effects in animal skeletal muscle IRI models. The authors hypothesized that a similar protective effect could be demonstrated in a well designed clinical trial. Materials and Methods: A EudraCT registered, prospective, randomized, controlled, double blind trial was performed to assess the hypothesis. Ethical approval was obtained from the competent authority. Patients (n=18) undergoing elective knee arthroscopy were randomised to one of 3 groups. The NAC group received IV NAC and preoperative oral placebo. The ascorbate group received oral ascorbate and IV placebo. The placebo group received both oral and IV placebo. Anaesthetic protocols were standardized across all groups. Phlebotomy was performed preoperatively and at 3 post-operative time points. IL-1, 2, 6 and 10, ICAM, VCAM, Selectins, TNF-alpha and malondialdehyde (MDA) were measured in systemic and local blood samples. Physiological parameters were recorded in the peri-operative period. Post-operative analgesic requirements and visual analogue scores were recorded. Leg oedema was measured using volumetric analysis and figure-of-eight tape measurement. Results: There were no differences between the groups pre-operatively. In the post-operative period the analgesic requirements were lower in the NAC group compared to ascorbate and placebo groups. CRP and d-dimers were found to peak in the early post operative period. White cell counts decreased in all groups in the early post-operative period, with a lesser reduction in the NAC and ascorbate groups. Elevation of MDA was noted in all groups but was significantly less in the NAC group. There was a trend towards increasing IL-6 and IL-8. There was a trend towards decreasing TNF-alpha and IL-1. Conclusions: Ascorbate and NAC appear to attenuate the inflammatory response to IRI in a clinical model. These cheap, readily available medications which are acceptable to patients and doctors alike appear offer a potential benefit to patients. Further studies are required to clarify the extent of the benefit and to examine the role of these medications in trauma and in the setting of more extensive ischaemic insults

Purpose: To investigate the mode of presentation, management and outcome of ischaemic contracture following a supracondylar fracture with a pink, pulseless hand.

Methods: We reviewed the database at our tertiary referral unit to identify cases over a 20 year period who had been referred for complications of a supracondylar fracture and/or a Volkmann’s ischaemic contracture.

Results: We identified 20 children with Volkmann’s ischaemic contracture following a supracondylar fracture. Of these, 4 patients (mean age 5, range 2–11) were referred to us with evidence of an ischaemic contracture but they had always had a pink albeit pulseless hand. Two of these 4 had undergone vascular exploration at 48 hours and at 72 hours but despite this developed an ischaemic contracture.

The 2 patients with the most severe contractures have undergone surgical intervention for their contracture, and 2 were managed conservatively with splinting. All 4 cases have residual problems with hand function (mean follow-up 5.5 years, range 2–11).

Conclusions: Volkmann’s ischaemic contracture should be a preventable condition. The pink albeit pulseless hand is at increased risk of ischaemic muscle and nerve damage and should not be ignored as the consequences are potentially devastating.

Significance: Clinicians must consider whether they feel that their management protocols for the pink, pulseless hand are robust and defensible.

Aims: Increased intraarticular hip joint pressure has been considered a pathomechanism in femoral head necrosis. The aim of this study was to investigate histopathological femoral head changes in an immature big animal model of arterial hip joint tamponade. Methods: Out of a total of 15 domestic pigs, 11 animals were randomly chosen to undergo 6h unilateral hip joint tamponade at an intraarticular pressure of 250mmHg while 4 animals underwent a unilateral sham operation serving as controls. 4h after the end of hip joint tamponade, the animals were killed with potassium chloride, the femoral heads were excised, and þxed in Schafferñs solution for undecalciþed Goldnerñs, alcianblue-PAS, Krutsay, methyl green pyronine, toluidin blue O, and standard Giemsa staining. Results: A great number of congested sinus and vessels of the terminal vascular system showed inclusions of blood cells dominantly in the tamponaded hip side. Congestion also be documented by dilated sinus with deformed blood cells. Bone remodeling of normal osteoblast and osteoclastic lacuna activity was noted in all trabeculae. None of the known signs of osteonecrosis were found. Conclusions: Our acute histological study in immature pigs shows the early microcirculatory disturbances which may precede femoral head necrosis. Future research is needed to investigate histologic changes after a longer time interval following hip joint tamponade, and into the duration of the joint tamponade.

Introduction: Ischaemia-reperfusion-injury (IRI) is one of the most common metabolic insults in orthopaedic practice. It is often a mild insult after brief tourniquet use with minimal clinical implications; but much more severe insults may result from excessive tourniquet-times, vascular trauma or release of compartment-syndrome. It is mediated largely by oxidatively-induced endothe-lial disruption and leukocyte infiltration. Antioxidants attenuate or prevent this effect in animal models.

Hypothesis: That IRI can be attenuated using established antioxidant medications (ascorbate and n-acetyl-cysteine) in the controlled setting of elective knee arthroscopy.

Methods: A EudraCT registered, prospective, randomized-controlled trial was performed. Patients (n=24) undergoing elective knee arthroscopy were randomized to one of 3 groups (IV NAC/oral ascorbate/placebo). Full blood counts, a broad array of cytokines and adhesion molecules, physiological response, pain scores and analgesia were recorded pre-operatively and at 3 postoperative time-points (10mins, 2hours, 4hours).

Results: Physiological response, analgesia and VAS did not differ. Systemic leukocytes and neutrophils were increased (p=0.001) indicating a measurable reperfusion injury. Ascorbate tended to inhibit ICAM-1 (p=0.10) and IFN-gamma (p=0.080). NAC inhibited VCAM-1 (p=0.003) and tended to inhibit ICAM-1 (p=0.094). Selectins responded in a similar pattern but not significantly. NAC tended to increase circulating leukocytes (0.093), neutrophils (0.12) and monocytes (0.04) and also induced a transient early increase in IFN-gamma (p=0.022).

Conclusions: Elevated circulating leukocytes indicate reduced leukocyte trapping and infiltration due to reduced adhesion molecule expression. NAC attenuates IRI resulting from tourniquet use in knee arthroscopy. The study was underpowered to confirm the efficacy of ascorbate in this setting. Further studies are necessary on the effects of these substances in more extreme ischaemic insults in which they may confer significant local and systemic benefits for the patient. Ascorbate and NAC act at different points in the inflammatory cascade and their potential synergistic effects warrant investigation.