39 Acute pain

Analgesic drugs 1092

Patient-controlled analgesia 1100

Epidural analgesia 1102

Continuous peripheral nerve blockade 1106

Stimulation-produced analgesia: TENS and acupuncture 1107

The opioid-dependent patient 1108

The patient with a substance abuse disorder 1110

Acute neuropathic pain following surgery 1111

RS—abdominal/thoracic pain results in diaphragmatic splinting and weakened cough. Reduction in lung volumes, atelectasis, and sputum retention cause chest infections and hypoxaemia.

GI—delayed gastric emptying and reduced intestinal motility. This can be a direct effect of pain or as a side effect of opioids and surgery.

GU—urinary retention.

Metabolic/endocrine—release of vasopressin, aldosterone, renin, angiotensin, cortisol, glucagon, growth hormone, and catecholamines, and reduction in insulin and testosterone lead to increased protein breakdown, impairment of wound healing/immune function, sodium and water retention, increased fibrinogen and platelet activation, and increased metabolic rate.

Chronic pain—there is some evidence that patients who suffer acute pain are more likely to develop chronic pain.

Psychological—poor acute pain management can lead to patient anxiety, sleeplessness, fatigue, and distress well into the postoperative period.

Numerical rating scales—take the two extremes of the pain experience and have a numerical scale in-between ‘no pain’ and ‘worst imaginable’, for example. These scales are robust and reproducible and easy for patients to understand. A disadvantage is that a digital scale reduces the capacity to detect subtle changes as the digits act as anchoring points.

Visual analogue scales—similar to numerical rating scales with two extremes of the pain experience on either end of the scale. The patient is asked to mark across the line of standard length (usually 100mm). The distance along this line is used. The continuous data generated make analysis easier than with verbal or numerical rating scales.

Excreted renally after glucuronide and sulphate conjugation in the liver. A hepatotoxic metabolite N-acetyl-p-benzoquinoneimine is normally inactivated by conjugation with hepatic glutathione. In paracetamol overdose, this pathway is overwhelmed, leading to hepatic cell necrosis.

Usually given PO or PR but available as IV preparation—Perfalgan^®.

Recommended dose—4g/d in adults. Most effective when prescribed regularly rather than prn.

Two types of COX: COX-1 is normally present in the kidney, gastrointestinal mucosa, and platelets where prostaglandin contributes to normal organ function. COX-2 is associated with inflammatory mediators following tissue damage. COX-2 inhibitors may be associated with fewer adverse effects than COX-1 and COX-2 inhibitors (but see p. 1093 and below).

NSAIDs have some central as well as peripheral activity. Absorption from the upper gastrointestinal tract is rapid. Metabolised in the liver, excreted in the kidney.

Opioid sparing effect of between 20 and 40%. May be used as the sole analgesic for mild to moderate pain. Side effects with NSAIDs are relatively common.

The Royal College of Anaesthetists published guidelines¹ for the use of NSAIDs in the postoperative period, suggesting a number of precautions and contraindications.

The VIGOR study,² in which patients on low-dose aspirin were excluded, found an increased risk of myocardial infarction for patients given rofecoxib compared to naproxen. Rofecoxib and some other COX-2 inhibitors have been withdrawn from clinical practice because of further concerns about the risks of cardiovascular events including myocardial infarction and stroke.³

Isonox (isoflurane 0.2–0.75% in Entonox). Lower concentrations of isoflurane produce less drowsiness.⁴

Ideal for procedures of short duration such as dressing changes, removal of drains, catheterisation, labour pain, and application of traction.

Side effects of Entonox include drowsiness, nausea, excitability, and augmentation of respiratory depressant drugs.

Entonox diffuses rapidly into and increases gas-containing cavities. Contraindications thus include pneumothorax, decompression sickness, intoxication, bowel obstruction, bullous emphysema, and head injury.

κ—analgesia, sedation, dysphoria, diuresis. Endogenous agonists are dynorphins.

δ—analgesia. Endogenous agonists are enkephalins.

Intermittent SC or IM opioids. Traditional route of administration ordered 4-hourly PRN. A reluctance to give opioids more frequently than 4-hourly often leads to failure of regimens. Blood levels of an opioid need to reach minimum effective analgesic concentration (MEAC) before any relief of pain is perceived. This requires an adequate initial dose. The only way to achieve good pain relief is to titrate the dose of opioid for each patient.

Intermittent IV opioids. To achieve sustained pain relief without excessive drowsiness and respiratory depression, small doses of opioids should be given often. This technique of opioid administration is suitable for recovery wards but not for routine maintenance of analgesia by untrained staff. Commonly used regimens are 1–3mg morphine or 20–60µg fentanyl every 5min until the patient is comfortable. Morphine can take up to 15min to exhibit its full effect.

Continuous IV infusion. To avoid ‘peaks and troughs’ in blood opioid concentrations associated with intermittent administration, continuous opioid infusions are sometimes used. Close observation and monitoring of the patient is essential. Patients are best made comfortable with IV boluses to ‘load’ the patient.

Intrathecal opioids. Intrathecal opiates are administered at the same time as the intrathecal local anaesthetic during spinal anaesthesia. Fentanyl 10–30µg has a rapid onset (10–20 min) and a short duration of action (4–6hr). After single administration, it can be used in day-case arthroscopic surgery to enhance analgesia without prolonging hospital stay. Diamorphine 0.3–0.4mg is used for analgesia after elective Caesarean section. Doses up to 1mg diamorphine have been used. Intrathecal morphine 0.1–0.2mg has been shown to give good postoperative pain relief following hip arthroplasty; 0.3–0.5mg morphine similarly provides good postoperative relief following knee arthroplasty.

Intranasal diamorphine. Very effective in children (>1yr) needing acute analgesia. A suitable dosing regime is 0.1mg/kg in 0.2ml saline (0.1ml to each nostril). To prepare solution, add 10mg diamorphine to 20/weight (kg) of saline (ml) and draw up 0.2ml.

Transmucosal administration. Fentanyl lollipops (oral transmucosal fentanyl citrate) allow absorption from the oral mucosa. More frequently used for anaesthetic premedication in children. Can be used for ‘breakthrough’ analgesia in opioid-tolerant patients with cancer.

Transdermal administration. Very lipid-soluble opioids are absorbed through skin. Fentanyl patches are available in five sizes (12–100µg/hr) and patches are replaced every 72hr. Buprenorphine patches are available as low-dose 7d release patches or in higher dose patches replaced every 72hr. Steady plasma concentrations occur on average 12hr after application of the transdermal patch. Dangerously high plasma concentrations can occur if patients are actively warmed whilst wearing a transdermal patch. Although not suitable for acute pain management, in chronic pain the recommended dose based on daily parenteral morphine dose is shown in the table below.

The optimal bolus dose consistently results in analgesia without side effects. Initial values for PCA variables are given below.

For paediatric use of PCA see p. 828.

Operator error is much more common. Programming errors, the use of the wrong drug or incorrect drug concentrations, and incorrect background infusions have all been reported and have led to fatalities due to respiratory depression.

Side effects related to opioid use such as nausea and vomiting, pruritus, sedation, respiratory depression, urinary retention, confusion, constipation, and hypotension.

Breakthrough pain: add regular NSAID and paracetamol if not contraindicated. Increase bolus dose or consider background infusion if severe.

Respiratory depression: this is caused by direct action of opioids on the respiratory centre. All opioids, given in equianalgesic doses, have the same potential for respiratory depression. This is a relatively uncommon side effect and if doses are properly titrated, the risk is small. The best early clinical indicator of respiratory depression is increasing sedation. Opioid doses are adjusted so that the sedation score remains below 2. Respiratory depression (respiratory rate <8/min) is reversed with IV naloxone (100–400µg).

The incidence of postoperative atelectasis and pulmonary infection is reduced, improving oxygenation.² Effective pain relief allows the patient to cough, breathe deeply, and cooperate with physio.

The incidence of postoperative myocardial infarction is reduced. The myocardial oxygen supply:demand ratio is improved by the reduction of sympathetic activity, improved pulmonary function, and reduced thrombotic tendency.

The hypercoagulable response to surgery is attenuated and fibrinolytic function is improved by attenuation of the stress response. This has been shown to be of benefit for graft survival in patients undergoing lower limb revascularisation.

Increased postoperative mobility reduces the incidence of DVT.

Epidural analgesia improves intestinal motility by blocking nociceptive and sympathetic reflexes as well as limiting systemic opioid use. The duration of postoperative ileus is reduced so permitting earlier feeding.

Intraoperative neuraxial block reduces postoperative blood transfusion requirements.

There is, however, no survival benefit in high-risk patients despite being beneficial in terms of pain relief and respiratory function.³

Untrained staff—staff must have a good understanding of the techniques used and be able to recognise and treat complications.

Contraindications to catheter or needle placement include local or general sepsis, hypovolaemia, coagulation disorders, concurrent treatment with anticoagulant drugs, and some central neurological diseases (see p. 739, p. 784, pp. 1174–1177).

0.1% bupivacaine with 5µg/ml fentanyl or 100µg/ml diamorphine.

0.0625% bupivacaine with 2µg/ml fentanyl or 50µg/ml diamorphine.

Pethidine has local anaesthetic as well as opioid properties. It can be used as the sole drug for spinal anaesthesia (requires higher doses).

Delayed or late respiratory depression can occur with the less lipid-soluble drugs (particularly morphine). Increasing patient age, high doses of opioid administered intrathecally, concurrent use of sedatives, and systemic opioids are associated with increased risk of respiratory depression.

Diamorphine (if available) offers the best combination of duration of analgesia with fewest side effects.

Incoming noxious pain signals are reduced by presynaptic and postsynaptic inhibition in laminae 1–5 in the dorsal horn of the spinal cord. Modulatory input arrives via descending pathways and lateral branches from myelinated afferent A-fibres. A-fibres arise in low-threshold mechanoreceptors activated by transcutaneous electrical nerve stimulation (TENS) and in high-threshold mechanoreceptors responsive to low-frequency needle manipulation (acupuncture).

A-fibres are recruited at 50–200Hz and respond to low-intensity stimulation. Pain relief occurs immediately but lasts only as long as stimulation continues. A-fibre stimulation increases levels of inhibitory neurotransmitters dynorphin A and B in the dorsal horn.

A-fibres are recruited at 2–4Hz and respond to high-intensity stimulation. Pain relief takes 20–30min but lasts hours or days. A-fibre stimulation also increases inhibitory neurotransmitter metenkephalin levels in the dorsal horn.

Symptoms and signs of withdrawal include yawning, sweating, anxiety, rhinorrhoea, lacrimation, tachycardia, hypertension, diarrhoea, nausea, vomiting, abdominal pain, and cramps. On average, these symptoms peak at 36–72hr after the last dose. Aims of treatment must be provision of analgesia, prevention of opioid withdrawal, and management of abnormal drug-taking behaviour. Non-opioid analgesics such as paracetamol and NSAIDs should be prescribed regularly if possible.

Opioid-dependent patients normally fall into one of three groups: opioid addicts, chronic non-cancer pain, and cancer pain. The principles of management are the same for each group.

Opioid-tolerant patients are at risk of opioid withdrawal if non-opioid analgesic regimens or tramadol are used.

PCA settings may need to include a background infusion to replace the usual opioid dose and a higher bolus dose.

Total dose should be increased until acceptable analgesia is achieved or until side effects prohibit any further dose increases. PCA with larger than average bolus doses is the preferred means of administrating opioids.¹,² Opioid rotation may be of use particularly with an agent of higher intrinsic opioid agonist activity.³

The aim is to eventually discharge the patient on no more opioid than was used before admission. Normally dose reductions of 20–25% every day towards the pre-admission opioid intake will avoid symptoms of withdrawal.

Oral or SC clonidine (50µg tds) can be used to treat symptoms of opioid withdrawal.

An objective assessment of function, i.e. ability to cough, may be a better guide to opioid requirements than pain scores. Patients with an addiction to opioids tend to exaggerate pain in the hope of receiving increased dosages.¹,²,³

Whenever possible, regional analgesic techniques should be used (e.g. continuous lumbar plexus, brachial plexus, or epidural infusions).

Liaise with all clinicians involved in the treatment of these patients.

Presence of the drug of abuse.

Presence of tolerance, physical dependence, and the risk of withdrawal.

Medications used to assist with drug withdrawal or rehabilitation.

Complications related to drug abuse including organ impairment.

Effective analgesia.

Symptomatic treatment of affective and behavioural problems.

Naltrexone—pure opioid antagonist administered orally. Binds to opioid receptors for 24hr following a single dose. May create difficulties in the acute pain setting. It is recommended that naltrexone is stopped 24hr before surgery. Usual maintenance dose is 25–50mg daily.

Buprenorphine—partial opioid agonist used in the treatment of opioid addiction. Commonly prescribed doses are 8–32mg. Continuation of buprenorphine presurgery has been suggested although it may be difficult to obtain good analgesia with full agonist opioids. Multimodal analgesic strategies should be used.

Patients may complain of an unusual type of pain different from the usual postoperative nociceptive pain. Patients often describe the pain as burning or shooting in nature. Pain may extend beyond the territory of a single peripheral nerve.

The pain is often poorly responsive to opioid analgesia despite high doses being administered.

Allodynia (pain following a normal innocuous stimulation), hyperalgesia (pain disproportionate to a noxious stimulus), and dysaesthesias (spontaneous unpleasant abnormal sensations) are often seen.

The presence of a neurological deficit such as brachial plexus avulsion or spinal cord injury makes the presence of acute neuropathic pain more likely.

Tricyclic antidepressants or anticonvulsant drugs (carbamazepine, gabapentin, or pregabalin) can be used to supplement treatment. These drugs are commonly used in established chronic pain conditions. Common side effects are drowsiness, dizziness, and gait disturbance.

Acute neuropathic pain after surgery is well recognised but poorly studied. Clinical trials are required to confirm the efficacy of treatments.