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Acute pain 

Acute pain
Chapter:
Acute pain
Author(s):

Keith G. Allman

, Iain H. Wilson

, and Aidan O’Donnell

DOI:
10.1093/med/9780199584048.003.0039
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Subscriber: null; date: 17 September 2019

  • Adrian Dashfield

    Introduction [link]

  • Analgesic drugs [link]

  • Patient-controlled analgesia [link]

  • Epidural analgesia [link]

  • Continuous peripheral nerve blockade [link]

  • Stimulation-produced analgesia: TENS and acupuncture [link]

  • The opioid-dependent patient [link]

  • The patient with a substance abuse disorder [link]

  • Acute neuropathic pain following surgery [link]

Introduction

Benefits of acute pain management

Severe postoperative pain and the stress response to surgery cause increased morbidity and mortality.

  1. CVS—tachycardia, hypertension, and increased peripheral vascular resistance cause increased myocardial oxygen consumption/demand and myocardial ischaemia. Altered regional blood flow (sympathetic stimulation), reduced mobility, venous stasis, and increased clotting cause venous thrombosis.

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

  3. 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.

  4. GU—urinary retention.

  5. 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.

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

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

Measurement of pain

  1. Verbal rating scales—stratify pain intensity according to commonly used adjectives such as ‘mild’, ‘moderate’, and ‘severe’. They are widely applied and easy for patients to use. The semiquantitative nature makes them less suitable for research purposes.

  2. 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.

  3. 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.

Analgesic drugs

Paracetamol

  1. Action is thought to be inhibition of prostaglandin synthesis within the CNS. Analgesic and antipyretic without anti-inflammatory activity.

  2. 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.

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

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

Non-steroidal anti-inflammatory drugs (NSAIDs)

  1. Analgesic, anti-inflammatory, antiplatelet, and antipyretic action is due to inhibition of the enzyme cyclo-oxygenase (COX) and consequently the synthesis of prostaglandins, prostacyclins, and thromboxane A2 from arachidonic acid.

  2. 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 [link] and below).

  3. 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.

  4. 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.

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

  6. 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

Contraindications of NSAIDs

Relative contraindications

Absolute contraindications

Impaired hepatic function, diabetes, bleeding or coagulation disorders, vascular disease

Operations with a high risk of intraoperative haemorrhage (e.g. cardiac, vascular, and hepatobiliary surgery)

Operations where an absence of bleeding is important (eye surgery, neurosurgery)

Non-aspirin-induced asthma

Concurrent use of ACE inhibitors, potassium-sparing diuretics, anticoagulants, methotrexate, ciclosporin, antibiotics such as gentamicin

Pregnant and lactating women

Age >65yr (risk of renal impairment)

History of gastrointestinal bleeding or ulceration

Known hypersensitivity to NSAIDs

Severe liver dysfunction

Cardiac failure (NSAIDs cause sodium, potassium, and water retention)

Dehydration, hypovolaemia, hypotension

Hyperkalaemia

Pre-existing renal impairment

Uncontrolled hypertension

Aspirin-induced asthma

Comparison of NSAIDs and COX-2

NSAIDs

COX-2

Efficacy for moderate to severe acute pain (numbers needed to treat—NNT)

Diclofenac 50mg (2.3)

Ibuprofen 400mg (2.4)

Ketorolac 10mg (2.6)

Celecoxib 200mg (4.5)

Parecoxib 20mg (3.0)

Valdecoxib 20mg (1.7)

Renal function

Can affect renal function postoperatively

Similar adverse effects on renal function

Gastrointestinal

Acute gastroduodenal damage and bleeding can occur. Risk increased with higher doses, history of GI ulceration, long-term use, and elderly

Less clinically significant peptic ulceration than NSAIDs (VIGOR and CLASS studies)

Platelet function

Inhibit platelet function but do not significantly increase surgical blood loss in normal patients. Associated with higher incidence of post-tonsillectomy haemorrhage

Do not impair platelet function

Aspirin-exacerbated respiratory disease

10–15% of asthmatics affected when given aspirin. Cross-sensitivity with NSAIDs

Do not produce bronchospasm

Bone healing

Impaired in animal models. No good evidence that clinically important

Similar to NSAIDs

Inhalational analgesia

  1. Entonox (50% nitrous oxide, 50% oxygen) is a quick-acting, potent analgesic of short duration which relies on patient self-administration.

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

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

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

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

Opioids

Opioid drugs act as agonists at opioid receptors found mainly in the brain and spinal cord but also peripherally. There are three principal classes of opioid receptor:

  1. µ—analgesia, nausea and vomiting, bradycardia, respiratory depression, miosis, inhibition of gut motility, pruritus. Endogenous agonists are β-endorphins.

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

  3. δ—analgesia. Endogenous agonists are enkephalins.

Morphine—remains the ‘gold’ standard against which all new analgesics are compared. It is the least lipid-soluble opioid in common use. Metabolised in the liver, with only 10% excreted unchanged by the kidney. Metabolite morphine 6-glucuronide is more potent than morphine. Other main metabolite is morphine 3-glucuronide which has no analgesic activity. Both metabolites are excreted in the kidney. Accumulation can occur after prolonged use in patients with impaired renal function. Dose ranges and dose intervals vary according to route of administration.

Diamorphine—a prodrug (diacetylmorphine) rapidly hydrolysed to 6-monoacetylmorphine and then morphine. Diamorphine is much more lipid soluble than morphine and thus has a more rapid onset of action than morphine when given by epidural or IV route.

Fentanyl—highly lipid-soluble synthetic opioid with a short duration of action because of rapid tissue uptake. The high lipid solubility makes it suitable for transdermal administration. Metabolites of fentanyl are inactive. Fentanyl is commonly administered IV, epidurally, or intrathecally.

Pethidine—analgesic with anticholinergic and some local anaesthetic activity. Primarily metabolised in the liver with metabolites excreted in the kidney. One of the main metabolites is norpethidine with a half-life of 15–20hr. Norpethidine is a potent analgesic. High blood concentrations can lead to central nervous system excitation. Patients with impaired renal function are at risk. Pethidine can be used to treat postoperative shivering associated with volatile anaesthetic agents, epidural and spinal anaesthesia.

Codeine is a prodrug for morphine. Usually administered for the treatment of mild to moderate pain. About 10% of the dose is converted to morphine. Metabolism to morphine requires an enzyme (CYP2D6) which is part of the cytochrome P450 system; 8–10% of Caucasians lack this enzyme, obtaining little or no benefit.

Tramadol—synthetic centrally acting opioid-like drug. Less than half of its analgesic activity is at the µ-opioid receptor. It inhibits noradrenaline and serotonin uptake at nerve terminals. Lower tolerance and abuse potential, less respiratory depression, and constipation compared to other opioids reported. Metabolised in the liver and excreted in the kidney. Main metabolite of tramadol is O-desmethyltramadol (M1) which is more potent. Formation of M1 also depends on the presence of CYP2D6 within the cytochrome P450 system (see codeine).

All opioids are equianalgesic if adjustments are made for dose and route of administration. Allowance should be made for long-term opioid therapy, incomplete cross-tolerance between opioids, differing half-lives, and interpatient variability.

Equianalgesic dosages

Opioid

IM/IV (mg)

Oral (mg)

Morphine

10

25

Diamorphine

5

Fentanyl

0.15–0.2

Pethidine

100

250

Codeine

175

Tramadol

100

100

Opioids have a similar spectrum of side effects. There is considerable interpatient variability and some patients may suffer more side effects with one particular drug compared to another.

Side effects include respiratory depression (decreased respiratory rate, tidal volume, and irregular respiratory rhythm), sedation, euphoria, dysphoria, nausea and vomiting, muscle rigidity, miosis, bradycardia, myocardial depression, vasodilatation, delayed gastric emptying, constipation, and pruritus.

Opioid antagonists act at all opioid receptors. Naloxone is the most commonly used. By titrating the dose of naloxone administered, it is possible to reverse side effects such as respiratory depression, nausea and vomiting, and sedation without antagonising the analgesic effects. It must be remembered that naloxone is effective for about 60min.

Opioids—routes of administration

  1. Oral. Oral bioavailability of most opioids is limited due to first-pass metabolism The slower onset and longer duration of controlled-release formulations make rapid titration impossible. Immediate-release oral opioids (e.g. morphine syrup, oxycodone) are preferred for early management of acute pain.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

Transdermal administration of opioids

Transdermal fentanyl dose (µg/hr)

Oral morphine dose in 24hr

Parenteral morphine dose in 24hr

12

45

4–11

25

90

8–22

50

180

23–37

75

270

38–52

100

360

53–67

125

450

68–82

150

540

83–97

Transdermal buprenorphine dose (µg/hr)

Oral morphine dose in 24hr

Parenteral morphine dose in 24hr

5

9

1–3

10

18

2–5

20

35

4–9

35

60

6–15

52.5

90

8–22

70

120

14–22

The Oxford league table of analgesic efficacy. (Courtesy of Pain Research Unit, Oxford—www.ebandolier.com.)

Analgesic

Number of patients in comparison

At least 50% pain relief (%)

NNT

Lower confidence interval

Higher confidence interval

Valdecoxib 40mg

473

73

1.6

1.4

1.8

Valdecoxib 20mg

204

68

1.7

1.4

2.0

Diclofenac 100mg

411

67

1.9

1.6

2.2

Rofecoxib 50mg

1900

63

1.9

1.8

2.1

Paracetamol 1000mg + codeine 60mg

197

57

2.2

1.7

2.9

Parecoxib 40mg (IV)

349

63

2.2

1.8

2.7

Diclofenac 50mg

738

63

2.3

2.0

2.7

Ibuprofen 600mg

203

79

2.4

2.0

4.2

Ibuprofen 400mg

4703

56

2.4

2.3

2.6

Ketorolac 10mg

790

50

2.6

2.3

3.1

Paracetamol 650mg + tramadol 75mg

679

43

2.6

2.3

3.0

Ibuprofen 200mg

1414

45

2.7

2.5

3.1

Diclofenac 25mg

204

54

2.8

2.1

4.3

Pethidine 100mg (IM)

364

54

2.9

2.3

3.9

Morphine 10mg (IM)

946

50

2.9

2.6

3.6

Parecoxib 20mg (IV)

346

50

3.0

2.3

4.1

Ketorolac 30mg (IM)

359

53

3.4

2.5

4.9

Paracetamol 500mg

561

61

3.5

2.2

13.3

Paracetamol 1000mg

2759

46

3.8

3.4

4.4

Paracetamol 600/650mg + codeine 60mg

1123

42

4.2

3.4

5.3

Aspirin 600/650mg

5061

38

4.4

4.0

4.9

Tramadol 100mg

882

30

4.8

3.8

6.1

Tramadol 75mg

563

32

5.3

3.9

8.2

Paracetamol 300mg + codeine 30mg

379

26

5.7

4.0

9.8

Tramadol 50mg

770

19

8.3

6.0

13.0

Codeine 60mg

1305

15

16.7

11.0

48.0

Patient-controlled analgesia

Patient-controlled analgesia (PCA) refers to self-administration of IV opioids and helps overcome the marked variability in response to postoperative opioids. Patients titrate their plasma opioid concentration to remain in the analgesic window [above the minimum effective analgesic concentration (MEAC) and below the minimum toxic concentration (MTC)]. The inherent safety of PCA lies in the fact that excessive doses of opioid will not be delivered should the patient become sedated. No-one but the patient is allowed to operate the PCA demand button.

PCA regimens

  1. The most commonly used opioid is morphine. Fentanyl, pethidine, tramadol, and other opioids have also been used. No opioid is noticeably superior to any other, although a greater incidence of pruritus may be seen with morphine; on an individual basis one opioid may be better tolerated than another.

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

  3. For paediatric use of PCA see [link].

PCA regimes

PCA variable

Drug and dose

Comments

Loading dose

0mg

Patients should be comfortable before starting PCA

Bolus dose

Morphine 1mg

Pethidine 10mg

Fentanyl 20µg

Diamorphine 0.5mg

Tramadol 10mg

Patients over the age of 70yr may require half this amount

Concentration

Varies depending on pumps used and hospital protocols

Should be standardised in hospital protocols for each drug

Lock-out interval

5min is usual

Background infusion

0mg/hr

If used, the background infusion rate (mg/hr) usually should not exceed the bolus dose (mg)

Dose limit

30mg morphine or equivalent in 4hr

No clear opinion on how this facility should be used. Often no dose limit is set

Complications

  1. Equipment malfunction is rare. Interference in pump operation has been reported following current surges and static electricity. Modern PCA pumps have a number of ‘fail-safe’ design features where the program defaults to the lowest setting possible for a bolus dose. Most machines have a battery back-up lasting up to 8hr. Failure of antireflux valves has led to cases of respiratory depression.

  2. 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.

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

Troubleshooting

  1. Nausea and vomiting—consider:

    1. Adding antiemetic to the PCA (ondansetron 4mg, cyclizine 50–100mg, haloperidol 2mg).

    2. Prescribe antiemetic on a regular basis.

    3. Change opioid.

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

  3. 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).

Sedation score

0

Patient wide awake

1

Mild drowsiness. Easy to rouse

2

Moderate drowsiness. Easy to rouse

3

Severe drowsiness. Difficult to rouse

S

Asleep but easy to rouse

Epidural analgesia

Epidural analgesia is considered by many to be the ‘gold standard’ analgesic technique for major surgery. It can provide complete analgesia for up to 3d. Patients can mobilise and resume normal activities more quickly compared to parenteral opioids. Beneficial effects of epidural analgesia result from attenuation of the ‘stress response’ following surgery.

  1. The efficacy of epidural analgesia, regardless of agent used, location of catheter, type of surgery, time or type of pain assessment, has recently been demonstrated.1

  2. 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.

  3. 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.

  4. 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.

  5. Increased postoperative mobility reduces the incidence of DVT.

  6. 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.

  7. Intraoperative neuraxial block reduces postoperative blood transfusion requirements.

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

Contraindications

  1. Patient refusal—a full explanation of the risks and benefits of the technique must be given to every patient.

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

  3. 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 [link], [link], pp. [link][link]).

Troubleshooting

  1. Breakthrough pain—consider:

    1. Adding regular PO/PR/IV NSAID and paracetamol if not contraindicated.

    2. Bolus dose (3–5ml) followed by increased infusion rate.

    3. Check all connections and insertion site.

    4. Check block level (with ice or touch). If block patchy or unilateral, withdraw catheter to 2cm in space.

    5. Bolus dose of opioid only (fentanyl 50–100µg, diamorphine 2–3mg).

    6. Pruritus—give naloxone (50–100µg) and consider adding 300µg to infusion fluids, or removing opioid from epidural infusion. Antihistamines may give some relief.1,2,3

    7. Hypotension—check fluid status of patient, probably relatively hypovolaemic. Check block height. Consider reducing infusion rate. If acute/severe raise legs, give fluid bolus ± ephedrine (6mg boluses).

    8. Motor block—reduce infusion rate. Consider reducing local anaesthetic concentration.

Complications of epidural anaesthesia4 (see also pp. [link][link])

Complication

Incidence (%)

Management

Dural puncture

0.16–1.3

Bed rest, analgesia, hydration, blood patch (see [link])

Headache

16–86

Bed rest, analgesia, hydration, suspect dural puncture

Nerve or spinal cord injury

0.016–0.56

Immediate neurological assessment (see [link] and [link])

Catheter migration

0.15–0.18

Remove catheter and resite if appropriate

Epidural haematoma

Epidural abscess

0.0004–0.03

0.01–0.05

MRI or CT scan. Immediate neurosurgical assessment. Antibiotics (see also [link] and [link])

Respiratory depression

0.13–0.4

Decrease in opioid concentration may be required

Hypotension

3–30

IV fluids ± vasopressors. Temporarily reduce or stop infusion

Pruritus

10

Naloxone IV (50–100µg) ± antihistamine

Urinary retention

10–30 (in males)

Catheterisation

Motor block

3

Check for catheter migration. Temporarily cease infusion. Consider epidural haematoma ([link] and [link])

Other

Possible increased risk of anastomotic leakage after bowel surgery. No evidence to support this

Drugs used for epidural analgesia

To minimise the side effects of each class of drug and provide optimal analgesia a combination of an opioid and a low concentration of local anaesthetic solution is given by continuous infusion. Commonly used mixtures are:

  1. 0.125% bupivacaine with 5µg/ml fentanyl or 100–125µg/ml diamorphine.

  2. 0.1% bupivacaine with 5µg/ml fentanyl or 100µg/ml diamorphine.

  3. 0.0625% bupivacaine with 2µg/ml fentanyl or 50µg/ml diamorphine.

There is no universally accepted optimal combination of drugs. Infusion rates vary according to the concentration, surgical site, and dermatomal level of epidural catheter placement. Usual infusion rates for the above solutions are 8–15ml/hr for adult patients and reduced rates of 4–8ml/hr in patients over 70yr of age. Some anaesthetists reduce or avoid epidural opioids in the very elderly and use local anaesthetic solutions only.

Intrathecal opioids

Opioids can be administered intrathecally in combination with local anaesthetic during spinal anaesthesia. The opioid is delivered directly into the CSF, so avoiding distribution into epidural fat and blood vessels. Consequently the doses used are much smaller compared to epidural or parenteral routes.

Opioid

Intrathecal dose

Onset (min)

Duration (hr)

Epidural dose

Morphine (preservative free)

0.1–0.2mg

15–30

8–24

2–3mg

Pethidine (preservative free)

10–25mg

<5

1–2

10–50mg

Fentanyl

10–25µg

<10

1–4

50–100µg

Diamorphine

0.25–0.5mg

<10

10–20

2.5–5mg

  1. The more lipid soluble the drug, the more rapid the onset and the shorter the duration of action.

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

  3. 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.

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

Spinal infection5

Extreme vigilance is needed for all patients who have had epidural analgesia. Pyrexia and/or backache are the most common signs and symptoms but are not invariable. Only 13% of patients with epidural abscess present with the classical triad of fever, backache, and neurological signs and symptoms. Back pain is the initial symptom in 75% of cases. Fever occurs in 66% of cases. Only two out of three patients have a leucocytosis. A raised ESR (>30mm) is a consistent finding. A normal CRP does not exclude spinal infection. Monitoring trends is more important than relying on a single measurement. If there is a suspicion of infection, a full infection screen and blood cultures are mandatory. The epidural catheter should always be removed immediately and sent to the laboratory for microbiological investigation. Ninety percent of spinal infections are bacterial, mainly Staphylococcus aureus. MRI with gadolinium is the investigation of choice. The whole spine should be scanned early before neurological signs and symptoms occur. Once muscle weakness is present, only 20% of patients regain full function, even after spinal surgery. Poor recovery is predicted by patient age (older patients do worse), extent of cord compression, and duration of neurological symptoms (<36hr has better prognosis). Mortality from epidural abscess is 10%. Treatment is based on surgical or percutaneous abscess drainage and antibiotics. Steroids are contraindicated.

Continuous peripheral nerve blockade

There are many potential benefits of continuous peripheral nerve blockade. The quality of analgesia is better compared with opioids and the incidence of postoperative side effects including nausea and vomiting is decreased. Compared with epidural analgesia for knee joint arthroplasy, analgesia is of equal quality, but the side-effect profile is better with peripheral nerve catheters. A recent development is the use of ultrasound to direct peripheral nerve catheter placement. Successful catheter placement relies on a high degree of skill in a practitioner who is already very familiar with single shot peripheral nerve blockade.

The chart below suggests typical bolus and infusion rates for peripheral nerve blockade: 0.5% or 0.25% ropivacaine or levobupivacaine is commonly used for the initial bolus; 0.1–0.25% levobupivacaine or ropivacaine is used for the continuous infusion. Safe doses must be calculated on a per kilogram basis for every patient. Do not exceed 0.6mg/kg/hr for either levobupivacaine or ropivacaine.

Absolute contraindications for this technique include: patient refusal, skin infection at or near the puncture site, systemic infection, pyrexia, bleeding diathesis (including systemic anticoagulation), peripheral neuropathy, and compartment syndrome.

Catheter site

Initial bolus (ml)

Basal rate (ml/hr)

Patient-controlled bolus (ml)

Interscalene

25–35

3–5

3–5

Axillary

30

5–10

5

Femoral/fascia iliaca

30

4–6

5–10

Sciatic

15–20

2–4

2–4

Complications include: bruising, haematoma, local anaesthetic toxicity, peripheral nerve damage, infection, catheter kinking, and catheter migration.

Stimulation-produced analgesia: TENS and acupuncture

  1. Stimulation techniques activate the body's pain-modulation systems. The gate control theory of pain by Melzack and Wall in 1965 provided a model to explain this phenomenon.

  2. 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).

  3. 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.

  4. 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.

The opioid-dependent patient

The principles of acute pain management in the opioid-dependent patient are similar to those previously described. The aim is to bring acute pain under control. Involvement of a multidisciplinary team will often be necessary to manage behavioural, psychological, psychiatric, and medical problems encountered in this group of patients.

  1. Tolerance, dependence, addiction, and pseudoaddiction—tolerance is a decrease in sensitivity to opioids resulting in less effect from the same dose. Physical dependence is a physiological phenomenon characterised by a withdrawal reaction when the drug is withdrawn or an antagonist is administered. Addiction is a pattern of drug abuse characterised by compulsive use to experience a psychological effect and to avoid withdrawal reaction. Pseudoaddiction is iatrogenic drug-seeking behaviour normally due to undertreatment of acute pain by the physician.

  2. 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.

  3. 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 requirements will in general be much higher than in non-opioid-dependent patients. The initial dose prescribed should take the patient's current opioid requirement into account. It may be difficult to judge current opioid use when illicit drugs have been taken. The GP, local pharmacist, or drug rehabilitation centre may provide helpful information.

  1. Opioid-tolerant patients report higher pain scores and have lower incidence of opioid-induced nausea and vomiting.

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

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

  4. 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

  5. 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.

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

  7. 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

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

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

The patient with a substance abuse disorder

A substance abuse disorder (SAD) exists when the extent and pattern of substance use interferes with the psychological and sociocultural integrity of the person.1

Effective management of acute pain in patients with SAD may be complicated by:

  1. Psychological and behavioural characteristics.

  2. Presence of the drug of abuse.

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

  4. Medications used to assist with drug withdrawal or rehabilitation.

  5. Complications related to drug abuse including organ impairment.

Ethical dilemmas can arise as a result of the need to balance concerns of undermedication against anxieties about safety and possible abuse or diversion of the drugs.

Management of pain in patients with SAD should focus on:

  1. Prevention of withdrawal.

  2. Effective analgesia.

  3. Symptomatic treatment of affective and behavioural problems.

Patients with SAD may be abusing CNS depressant drugs (alcohol, benzodiazepines, opioids) or CNS stimulant drugs (cocaine, amphetamines, ecstasy, cannabinoids).

Drugs used in the treatment of SAD include:

  1. Methadone—long-acting pure opioid agonist. In the acute pain setting methadone should be continued at the same dose. If the patient is unable to take methadone orally, substitution with parenteral methadone or other opioids may be required in the short term.

  2. 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.

  3. 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 in drug-free recovery may be concerned about the risk of relapse into active SAD if given opioids for acute pain management. Use of multimodal analgesic strategies, reassurance that the risk of reversion is small, and information that ineffective analgesia can paradoxically lead to relapses in recovering patients help avoid undertreatment.

Acute neuropathic pain following surgery

The occurrence of persistent pain following surgery is becoming increasingly recognised. Acute postoperative neuropathic pain does not usually occur in isolation; there will also be nociceptive pain as a result of tissue damage/inflammation.

  1. Approximately 14% of patients presenting to the pain clinic attribute their pain to surgery, with the pain beginning acutely.

  2. 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.

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

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

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

Treatment

There is currently no published evidence to guide treatment of acute neuropathic pain.

Mechanisms of neuropathic pain involve central nervous system changes and increased peripheral nerve excitability. Drug therapy focuses on reducing neuronal hyperexcitability and reducing activity of the NMDA receptor in an attempt to reverse neuronal changes.

  1. Parenteral ketamine (NMDA receptor antagonist, 5mg/hr) and lidocaine (neuronal membrane stabilisation, 5mg/kg over 30–40min followed by 0.5–1.5mg/kg/hr) can be given in the acute phase to alter both peripheral and central neuronal plasticity. Treatment may take up to a week or more. This should be supervised by a suitably qualified pain specialist.

  2. 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.

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

Notes:

1 Royal College of Surgeons and College of Anaesthetists (1990). Report of the Working Party on Pain after Surgery.

2 Bombardier C, Laine L, Reicin A, et al. (2000). Comparison of upper gastrointestinal toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis. VIGOR Study Group. New England Journal of Medicine, 343, 1520–1528.

3 FDA (2004). FDA Public Health Advisory: Safety of Vioxx. US Food and Drug Administration. www.fda.gov/cder/drug/infopage/vioxx/pha_ioxx.htm.

4 Ross JAS (2000). Isoflurane Entonox mixtures for pain relief during labour. Anaesthesia, 55, 711–712.

1 Block BM, Liu SS, Rowlingson AJ, et al. (2003). Efficacy of postoperative epidural analgesia: a meta-analysis. JAMA, 290, 2455–2463.

2 Ballantyne JC, Carr DB, deFerranti S, et al. (1998). The comparative effects of postoperative analgesic therapies on pulmonary outcome: cumulative meta-analyses of randomized, controlled trials. Anesthesia and Analgesia, 86, 598–612.

3 Rigg JRA, Jamrozik K, Myles PS, et al. (2002). Epidural anaesthesia and analgesia and outcome of major surgery: a randomised trial. Lancet, 359, 1276–1282.

4 National Audit of Major Complications of Central Neuraxial Block in the United Kingdom. Report and Findings 2009. http://www.rcoa.ac.uk/index.asp?pageid=717.

5 Joshi SM, Hatfield RH, Martin J, et al. (2003). Spinal epidural abscess: a diagnostic challenge. British Journal of Neurosurgery, 17, 160–163.

3 De Leon-Casasola OA, Lema MJ (1994). Epidural bupivacaine/sufentanil therapy for postoperative pain control in patients tolerant to opioid and unresponsive to epidural bupivacaine/morphine. Anesthesiology, 80, 303–309.

1 American Psychiatric Association (1994). Diagnostic and Statistical Manual of Mental Disorders, 4th edn. Washington, DC, American Psychiatric Association.