Independent predictors of moderate to severe postoperative pain are summarised in Table 6.2. These may prove valuable in the development of a risk stratification tool for postoperative pain and the selection of an appropriate pain management strategy. It may also be possible to specifically target and modify individual risk factors.

The observation that the severity of preoperative pain predicts the severity of postoperative pain supports a theory of central pain sensitisation that may become irreversible with time [8]. It is possible that earlier surgery might prevent irreversible neuronal changes and hence reduce postoperative pain; however, this must be considered alongside evidence that outcomes from joint arthroplasty are poor in early osteoarthritis. An alternative strategy is aggressive pain management prior to surgery, yet analgesic use also predicts postoperative pain. It is important to recognise that patients taking opiates prior to surgery will have developed a degree of tolerance and dosing regimes must be adjusted accordingly. Preoperative patient education focusing on pain science may significantly improve arthroplasty outcomes by reducing patient fear and anxiety. Educational sessions focusing on anatomy, biomechanics, and pathology have not shown to be effective in improving postoperative pain and may even enhance patient apprehension [9].

Pre-emptive analgesia traditionally refers to analgesia that is more effective when administered prior to surgery than when the same analgesia is administered after surgery. Increasingly the term is used to describe any analgesia given prior to surgery in order to improve postoperative pain and is sometimes also termed preventative analgesia. Incisional pain is different to other pain states, and regional hyperalgesia results from sensitisation of Aδ-fibre and C-fibre nociceptors [1]. It is hoped that administering analgesics immediately prior to surgery may prevent peripheral and central sensitisation. Pre-emptive nonsteroidal anti-inflammatories, cyclooxygenase-2 inhibitors, and the neuropathic agents gabapentin and pregabalin have all shown promise [10], although the optimal dose, time of administration, and whether further benefit is gained by continuing the analgesics during intraoperative and postoperative care remain unknown.

The optimal method of anesthesia during TKA remains to be established. The techniques most frequently adopted are spinal anesthesia or general anesthesia with or without nerve blocks. Spinal anesthesia alone remains the most common approach recorded in the UK National Joint Registry [11]. This trend has in part originated from studies showing superiority of spinal anesthesia over general anesthesia in terms of morbidity and mortality [12, 13]. Subsequent studies focusing on TKA report mixed and often contradictory findings. Although most continue to favour spinal anesthesia for a range of outcomes including perioperative complications, the differences between groups are small [14, 15]. Considering postoperative pain, it is difficult to draw conclusions from studies comparing general anesthesia with spinal anesthesia as they only form part of a plethora of different multimodal anaesthetic regimes. Good postoperative pain control can be achieved using either technique as part of a multimodal anaesthetic approach, and both are recommended for use in TKA [16]. Spinal anesthesia complication rates are low but include post-dural puncture headache, neurological injury, and spinal or epidural infection or haematoma, which is especially salient given the current drive towards thromboprophylaxis anticoagulation [17]. Epidural anesthesia is not recommended given the increased risk of complications without conferring a benefit over alternate modalities [18].

General anesthesia and spinal anesthesia must be combined with additional analgesic strategies in order to provide adequate postoperative pain relief. Traditional methods such as parenteral opioids have inadequate efficacy and are limited by adverse effects when used alone. Postoperative nausea and vomiting and sedation are particularly troublesome and impede early mobilisation [19]. Nerve blocks have proven to be a valuable adjunct and efficacy and reliability are improved with the introduction of ultrasound guidance and stimulating catheters. Femoral nerve blocks are the most widely used for TKA and provide superior analgesia to opioid patient-controlled analgesia (PCA) [20]. Nerve blocks can be delivered as a single-shot injection or continuously through an indwelling catheter. While continuous infusion may provide more efficacious analgesia of longer duration, the procedure is more technically challenging and requires additional time and expertise for insertion and management [20]. A postulated complication of femoral nerve blockade is an increased risk of falls in the postoperative period due to quadriceps weakness; however, recent studies have not supported this observation [21]. Quadriceps weakness may still delay postoperative rehabilitation and consequently the ability to instead perform a conduction block on the sensory branches of the femoral nerve in the adductor canal has been explored. It currently remains unclear whether this confers any clinical benefit over conventional femoral nerve blockage [19]. The femoral nerve provides sensory innervation to the anteromedial knee, and blockade does not offer analgesia for pain arising from the posterior knee that is innervated by the sciatic nerve. A sciatic nerve block may therefore be used in combination with femoral nerve blockade, but whether this confers clinically important analgesic benefit remains uncertain and the possible exacerbation of motor weakness delaying rehabilitation must be addressed [20, 22]. The obturator nerve provides variable cutaneous innervation to the medial knee, and blocks do not appear to offer any benefit for postoperative pain management [23].

Local infiltration anesthesia (LIA) is a further strategy for enhancing postoperative analgesia. The composition, concentration, and volume of infiltrate vary widely but typically comprise a long-acting local anaesthetic, nonsteroidal anti-inflammatory, and adrenaline. The adrenaline causes vasoconstriction that aids haemostasis and reduces systemic absorption of drugs that prolongs action and reduces the risk of toxicity. The infiltrate is distributed throughout the layers of the knee joint intraoperatively in volumes exceeding 150 mL. It is an attractive modality given the simplicity and speed of administration. LIA may offer postoperative analgesia that is comparable to nerve blockade but without motor weakness, allowing earlier rehabilitation and a reduced length of stay [24], but conclusions are limited by the heterogeneous comparators used in different studies. The optimal composition and delivery of LIA remains undetermined and is subject to ongoing investigation. A limitation of LIA is the short duration of action; however, this may be addressed with longer-acting agents such as liposomal bupivacaine, which has a reported duration of action of up to 72 h. Liposomes are artificial lipid vesicles that can be used for gradual drug release to extend the duration of action. Despite the theoretical advantages, there is not yet sufficient evidence of clinical benefit over conventional LIA regimes [25]. There is also insufficient evidence to support the use of continuous LIA infusions postoperatively [26], although studies have demonstrated that this can provide effective analgesia [27]. As with continuous nerve blockage, additional healthcare resource is necessary for wound catheter management and there is a postulated increased risk of infection.

Clonidine is an α₂-adrenergic agonist that improves postoperative pain for up to 24 h after knee replacement when co-administered with intrathecal local anaesthetic and opiate during spinal anesthesia [28]. Clonidine is thought to act at the level of the dorsal horn to potentiate the effect of local anaesthetics and opiates but can give rise to postoperative hypotension. Clonidine has also been included in nerve blocks and LIA, although the benefit remains uncertain.

Postoperative analgesia must provide a seamless transition from the intraoperative anesthesia and any nerve blocks or LIA. General and spinal anesthesia usually employ opiates in combination with non-opioids to provide analgesia, either via the intravenous or intrathecal routes. The effects of the nerve block and LIA can be extended using continuous infusions through perineural or wound catheters. These techniques offer improved postoperative analgesia with fewer side effects than systemic opiate analgesia [20, 39]; however, they require greater technical expertise and healthcare resource. Slow release liposomal local anaesthetic agents may overcome these limitations, but further evidence is required of clinical effectiveness. The mainstay of postoperative pain management remains via parenteral or oral routes. Anaesthetic regimes have traditionally centred on opiate medication attempting to strike a seemingly impossible balance between efficacy and tolerability. New multimodal analgesic strategies reduce the dependence on opiate medication. Employing several different agents at low doses improves analgesic efficacy with few adverse effects.