This PhD project developed the femoral 3-in-1 nerve block to provide safe, effective regional analgesia to the 60,000 patients admitted annually to UK hospitals with a fractured neck of femur. The hospital mortality for patients with a fractured hip in a large UK study was 14.3% with cardiac aetiologies predominating in the first 2 days (Bottle & Aylin 2006). In contrast to the marked improvements in mortality for elective surgery, the overall mortality from emergency surgery and in particular surgery for fractured neck of femur patients has remained unchanged (Roberts & Goldacre 2003). Development of the femoral 3-in-1 nerve block for fractured neck of femur patients will provide analgesia but may also improve outcome. A relationship between effective pain analgesia and improved cardiac morbidity and reduced mortality in patients with a fractured neck of femur was demonstrated by Matot et al using epidural analgesia in 2001 but this is not the current clinical standard in the UK (Matot et al. 2003). The femoral 3-in-1 nerve block (also called the fascia iliacus block or anterior psoas compartment block) offered a viable solution to provide analgesia to patients with a fractured neck of femur prior to surgical fixation. The femoral 3-in-1 nerve block is technically undemanding and requires a minimum of extra training and resources. In contrast to epidural analgesia which requires extensive training of practitioners and continuous cardio-respiratory monitoring of patients and an increased level of nursing care, ultrasound guided nerve blocks have been associated with an increased success rate, need less local anaesthetic and have shorter onset times than traditional techniques (Marhofer et al. 1997;Marhofer et al. 1998). Ultrasound guidance may increase the nerve block success rate and lower complication rates but it is associated with the extra cost of the ultrasound machine, disposables and staff training. In contrast, needle guidance using loss of resistance for a femoral 3-in-1 block is technically simple and cheap but is potentially inaccurate and, as a result, may be less effective. Anaesthetists currently utilise the femoral 3-in-1 nerve block to provide effective pain after surgical fixation of the femur but these techniques use large doses of local anaesthetic. Further information on dosing based on efficacy and duration of action will allow a reduction in dose and hence an improvement in safety of the femoral 3-in-1 nerve block. The information needed to develop the femoral 3-in-1 nerve block to provide analgesia for patients with a fractured neck of femur was provided by undertaking one prospective observer-blinded muticentre randomised controlled study, a clinical trial of an investigational medicinal product and a cadaveric dissection study. A multicentre randomised controlled study compared the efficacy of using ultrasound, nerve stimulator and loss of resistance techniques to guide the needle for a femoral 3-in-1 nerve block in elective primary total hip arthroplasty patients. This initial study recruited patients scheduled for a similar operation to fracture neck of femur patients (elective primary total hip arthroplasty) as it was impossible to recruit and assess a large number (>100) elderly, frail emergency patients. The use of the nerve stimulator is the current gold standard for elective femoral 3-in-1 nerve blocks but if used on patients with a fractured neck of femur it will cause unnecessary discomfort in a limb with an unfixed fracture. In order to determine the comparative efficacy of ultrasound, nerve stimulator and loss of resistance techniques, we performed femoral 3-in-1 nerve blocks on 180 patients scheduled for elective primary total hip arthroplasty. The efficacy of these three techniques was measured by assessing femoral nerve sensory and motor response at 30 minutes after the femoral 3-in-1 nerve block. The use of ultrasound and nerve stimulator (US+NS) for the femoral 3-in-1 femoral nerve block for elective total hip replacement was statistically significantly more effective than loss of resistance (LOR-59.5%, US+NS-80.3%, p=0.0159 (p≤0.025)) with a number needed to treat of 5. There was no statistically significant difference in the effectiveness of using the nerve stimulator(NS) and ultrasound(US) to guide the insertion of a femoral 3-in-1 nerve block (NS-77.5, US-83.1%, p=0.527 (p≤0.025). Since the use of nerve stimulator would result in significant unnecessary discomfort in patients with an unfixed fracture it was concluded that ultrasound was the optimal technique to guide femoral 3-in-1 nerve blocks for analgesia in patients with a fractured neck of femur. The dosing and safety of the femoral 3-in-1 nerve block was determined in patients with a fractured neck of femur. Levobupivacaine dosing was estimated by a Dixon’s up/down sequential methodology. Femoral 3-in-1 nerve blocks were performed and the concentration of levobupivacaine was increased or decreased (using a fixed volume) for an ineffective or effective nerve block respectively, as a result the concentration tended towards the EC50 (effective concentration in 50% of patients). The EC50 and the EC95 (effective concentration in 95% of patients) for 30 ml of levobupivacaine was estimated using a binary probit regression model; in which the probability of an effective nerve block was modelled against the concentration of levobupivacaine. The second part of this clinical trial assessed the pharmacokinetics (to ensure that serum levels were within the safe range) and pharmacodynamics (to assess duration of analgesia). The estimated EC95 concentration of levobupivacaine for the femoral 3-in-1 nerve block was 30mls of 0.036% with 95% confidence interval of 0.0332% to 0.0383%. The EC95 concentration of levobupivacaine gave a mean duration of analgesia of 166 minutes with a standard error of the mean of 35 minutes and peak median plasma level of 52 ng/ml 30 minutes after the femoral 3-in-1 nerve block. The measured plasma levobupivacaine concentrations were below the threshold (2100ng/ml) associated with toxicity. The clinical anatomy of the femoral 3-in-1 nerve block was determined by dissection. We investigated the distribution of 30 ml of black 10% latex injected lateral to the femoral nerve under the fascia iliacus membrane in two unembalmed adult cadavers. In all four dissections the lateral cutaneous and femoral nerves were stained at the inguinal ligament and the latex travelled distally in the adductor canal into the popliteal fossa to stain the sciatic nerve and its terminal branches.