Postoperative Pain Relief

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Chapter 7 Postoperative Pain Relief

Carmel F. Martin

Introduction and background

The goal of postoperative pain relief is to achieve optimal analgesia, facilitating a quick return to normal activities with minimal side effects. In addition, the effective treatment of acute postoperative pain may reduce the incidence of chronic pain after surgery. Acute postoperative pain differs from chronic or cancer pain because it is more transitory and there may be an affective component relating to anxiety about the outcome of the surgical procedure and concern for suboptimal analgesia. Studies have shown that for patients awaiting surgery the possibility of severe acute postoperative pain is a major concern.¹ In addition, uncontrolled postoperative pain can lead to delayed recovery from surgery, pulmonary dysfunction and hypoxia, together with restriction of mobility and subsequent increased risk of thromboembolism. Surveys in the UK, the USA and Europe have identified an unacceptable prevalence of poor pain control after surgery.^2,³ However, in recent years the introduction of acute pain management services in hospitals has promoted improvements in postoperative pain.⁴ In addition, the use of ‘multimodal’ or ‘balanced’ analgesia – a combination of opiates, non-steroidal antiinflammatory drugs (NSAIDs), local anaesthetics and other adjuvants have been recommended to manage postoperative pain. Recently, White and Power reviewed the evidence for such pain management. They showed that multimodal analgesia improves the efficacy of pain relief, decreases the risk of side effects and is an evidence-based, established effective strategy for postoperative pain management.^5,⁶

Treatment options

1. Paracetamol

2. NSAIDs

3. Opiate drugs

4. Local anaesthetic drugs

5. Peripheral nerve blocks

Assessment of pain

The international Association for the Study of Pain defines pain as ‘an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage’.

Pain is a very individual experience, and many factors including previous pain experiences, cultural background, disease or surgical prognosis, coping strategies, fear, anxiety and depression, will interact to produce what the patient then describes as pain. There is, however, often a poor correlation between the patient’s assessment of the pain and that of the nursing or medical staff.

Measurement of pain

In adults, three common methods of self-reported pain measurement are used.

1. Visual analogue scale

2. Verbal numerical rating scale

3. Categorical rating scale.

Each of these methods of measurement is reasonably reliable as long as the endpoints and adjectives employed are carefully selected and standardized.

Visual analogue scale

The visual analogue scale (VAS) uses a 10 cm line with endpoint descriptors such as ‘no pain’ marked at the left end of the line and ‘worst pain imaginable’ marked at the right end (Fig. 7.1). Patients are asked to mark a point on the line that best represents their pain. The distance from ‘no pain’ to the patient’s mark is then measured and this equals the VAS score.

Figure 7.1 Visual analogue scale.

The disadvantages of the VAS system are that it can be more time consuming than other simple scoring methods and some patients may have difficulty understanding or performing this score, especially in the immediate postoperative period.

Verbal numerical rating scale

The verbal numerical rating scale (VNRS) is very similar to the VAS. Patients are asked to imagine that ‘0 equals no pain’ and ‘10 equals the worst pain imaginable’ and then to give a number on this scale that would best represent their pain.

Available methods of pain relief

Summary Box 7.2 Side effects of NSAIDs

Gastrointestinal	Gastric erosions
Renal	Decreased renal blood flow
	Acute renal failure
Haematological	Prolonged bleeding time
Respiratory	Bronchospasm
Others	Skin rashes

Adverse effects/complications

Gastrointestinal

Erosions of the gastrointestinal tract (especially the stomach) can develop. They are due to local irritation of the mucosa as well as a decrease in mucus production and mucosal blood flow and increased gastric acid secretion, mediated by a reduction in prostaglandin levels. These problems may be lessened but not avoided altogether if the drugs are given by parenteral or rectal routes. Gastric irritation, dyspepsia and ulceration may develop at any time, but are less likely with short-term treatment. Pre-existing peptic ulcer disease can be exacerbated and indeed may be a contraindication to the use of these drugs.

Renal

The reduction in prostaglandin levels due to NSAID administration may also result in a decrease in renal blood flow and acute renal failure. Pre-existing renal impairment may increase this risk. In the healthy patient renal blood flow is not normally prostaglandin dependent. However, renal blood flow may be altered during anaesthesia.

NSAIDs can also cause sodium, potassium and water retention, which may lead to oedema in some patients.

Haematological

Aggregation of platelets depends on a balance between prostacyclin (from endothelial cells) and thromboxane A2 (from platelets). The former is a vasodilator and inhibits platelet aggregation; the latter is a vasoconstrictor which stimulates platelet aggregation. NSAIDs inhibit the synthesis of both these factors and the net balance will determine the tendency to bleed. NSAIDs also inhibit platelet COX, although the effect lasts only as long as the drug remains in the blood (five half-lives). An increase in operative bleeding has been reported as a result of the use of NSAIDs and surgeons should be aware of this risk. A meta-analysis of several randomized controlled trials showed a higher risk of postoperative bleeding after tonsillectomy with the postoperative use of NSAIDs.¹⁰ However, others have disagreed with this analysis, citing poor surgical technique and that in some patients the bleeding occurred at a time when the drug had been eliminated from the body.¹¹

Respiratory

Bronchospasm, related to COX inhibition, can occur in some asthmatic patients. As a consequence, NSAIDs should be used with caution in these people. Up to 20% of adult asthmatics may develop aspirin-induced bronchospasm, and a cross-sensitivity does exist between aspirin and other NSAIDs.

Liver

Abnormalities in liver function tests may occur but are usually transient.

Skin reactions

Skin reaction is the second most common unwanted effect of NSAIDs. Patients may present with a variety of skin conditions ranging from mild rashes, urticaria and photosensitivity, to occasionally more serious and potentially fatal varieties.

Cox-2 inhibitors

In an effort to minimize the potential for bleeding at the surgical site and to reduce the incidence of serious gastrointestinal adverse effects and renal dysfunction associated with traditional NSAIDs, selective COX-2 inhibitors, also named ‘coxibs’, such as rofecoxib and celecoxib, were developed . Other novel COX-2 inhibitors with improved biochemical selectivity recently developed include etoricoxib, valdecoxib, parecoxib and lumiracoxib. These ‘coxibs’ have similar analgesic efficacy to that of NSAIDs, with reduced risk of bleeding and less gastrointestinal toxicity. However, large outcome and epidemiological studies suggest that while COX-2 inhibitors do confer improved gastrointestinal safety, they are not devoid of gastrointestinal effects during long-term use. Two of these drugs have already been withdrawn because of safety concerns: rofecoxib because of cardiovascular problems and valdecoxib because of serious subcutaneous adverse reactions.¹²

Concerns have also been raised regarding the increased incidence of thrombotic complications (leading to myocardial infarction and stroke) associated with selective COX-2 compounds.¹³ COX-2 inhibition with coxibs may increase the risk of vascular thrombus formation by upsetting the balance between pro- and anti-platelet aggregation effects: thromboxane A2 synthesis is primarily a COX-1-induced effect, and prostaglandin I2 synthesis a COX-2 effect.

Current practice

The new COX-2 inhibitors, despite the sound pharmacological basis for their development, are not ‘miracle’ drugs. They also seem to be associated with adverse effects and, although they may represent a safer alternative to non-selective NSAIDs, their role in postoperative pain management is still not clearly defined. There is also a cost implication as they are considerably more expensive than the older non-selective NSAIDs.

Pre-emptive use

Analgesics given before surgical trauma are thought to have a pre-emptive effect. This implies that analgesia will start before the surgical stimulus, leading to a reduction of CNS input and hence reducing pain. This is commonly referred to as controlling the ‘wind-up’ phenomenon. There have been many studies done using different NSAIDs pre-emptively and, while there have been some mixed results (some showing a benefit, others showing no benefit), it is common practice in orthopaedic patients to commence NSAIDs pre-emptively either orally, sublingually or intravenously using standard drugs (naproxen, piroxicam, ibuprofen or diclofenac).^14,¹⁵

Opiates

Opioid drugs are effective postoperative analgesics and are the principal drugs used to combat moderate to severe pain. The most commonly used drugs are morphine, codeine, oxycodone and tramadol. Pethidine is no longer recommended for postoperative analgesia because repeat doses may lead to accumulation of its metabolite, norpethidine, which can lead to confusion and seizures. It also has a very high incidence of nausea and vomiting. Opioids can be given orally, intravenously, subcutaneously, transdermally, intra-articularly, transmucosally and by the intramuscular (i.m.) route. They can also be administered by anaesthetists through the spinal or epidural route. Oral dosing of opioids is usually the most convenient and least expensive route of administration; it is appropriate as soon as the patient can tolerate oral intake and is the mainstay of pain management in the ambulatory surgical population. Intravenous PCA, in which the patient has control over the timing of each dose, has become the standard method of providing postoperative analgesia after major surgery.

Pharmacology

Morphine and codeine are alkaloids of opium. These naturally occurring substances are called opiates. All drugs that have morphine-like actions, naturally occurring or synthetic, are called opioids. Unlike less potent drugs, opioids influence the emotional aspects of pain such as anxiety and fear as well as altering the actual pain threshold, making pain more tolerable. Despite all the advances in developing new analgesics, morphine remains the ‘gold standard’ against which all new analgesics are compared.

Opioid receptors

Opioids produce their effect by binding to opioid receptors located in the brain and spinal cord. A number of different opioid receptor types have been identified: mu (µ), delta (δ), kappa (κ) and sigma (σ). There are two subtypes of µ receptors – µ1 and µ2 – with subtype µ₁ mediating analgesia and µ₂ responsible for respiratory depression. All currently available µ receptor agonist opioids activate both subtypes.

Summary Box 7.3 Side effects of opioids

Respiratory	Respiratory depression
Central nervous system	Sedation, euphoria
	Nausea and vomiting
Cardiovascular	Vasodilation, bradycardia
	Myocardial depression
Genitourinary	Urinary retention
Gastrointestinal	Delayed gastric emptying
	Constipation
	Pruritus

Side effects (complications) of opioid drugs

All of the opioid drugs that we commonly use for pain management in the postoperative setting act primarily at the µ receptor sites and all have a fairly similar spectrum of side effects. In equianalgesic doses and in most patients, the incidence of side effects is generally very similar regardless of the opioid used (Table 7.1).

Table 7.1 Side effects of opioid drugs

1. Respiratory	Respiratory depression
2. Central nervous system	Sedation, euphoria (or dysphoria)
	Nausea, vomiting, miosis, muscle rigidity
3. Cardiovascular	Vasodilatation, bradycardia, myocardial depression
4. Pruritus	Common with morphine
5. Genitourinary	Urinary retention
6. Gastrointestinal	Delayed gastric emptying constipation
7. Allergy	Allergic reactions to opioid drugs are very uncommon

The most important side effects of opioids are respiratory depression, which may be severe and result in hypoxia. Sedation is routinely monitored postoperatively using a sedation score and, while respiratory rate is also monitored, it is routine practice to use continuous pulse oximetry in all postoperative patients in the recovery room or postanaesthetic care unit (PACU). Opioids are implicated as one of the risk factors in postoperative nausea and vomiting (PONV) and are assigned 1 point in the Apfel risk scoring system.¹⁶ In all cases where opioids are used intraoperatively or postoperatively, antiemetics should be given as prophylaxis. Combination antiemetic prophylaxis with drugs having different mechanisms of action have been shown in many studies to markedly reduce the incidence of PONV. Ondansetron and cyclizine have been shown to achieve a response rate of 95%.¹⁷

Methods of administration

Intramuscular administration

Traditionally, i.m. opioids, particularly morphine prescribed 4-hourly ‘p.r.n.’, provides the mainstay of postoperative analgesia. However, opioids given by intermittent injection generally are not able to maintain steady analgesic plasma levels for between 2 and 4 h. As a consequence, i.m. regimens are no longer recommended for the following reasons:

• i.m. injections are painful

• Steady blood concentrations are difficult to sustain

• There are prolonged intervals where the patient experiences pain

• The patient may be unaware that pain relief is available

• There may be delays between request for relief and the actual time of administration

• Considerable input from nursing/ancillary staff is required (often a scarce resource).

Intravenous route

For an opioid to be effective, it must reach a certain concentration in the blood. Therefore, titration of opioids is needed to individualize treatment for each patient. The best way to monitor the effectiveness of opioid treatment is the pain score. The aim of pain management is to make the patient comfortable while keeping the sedation score below 2. Analgesia is usually obtained more rapidly if an i.v. bolus dose is administered to ‘load’ the patient in the first instance. Usually, in the recovery room a bolus dose of 0.1 mg/kg of morphine is given in divided doses until the patient is comfortable.

Patient-controlled analgesia

PCA using opioids (usually morphine) has become the standard of care at many hospitals, for the management of postoperative pain. The term ‘PCA’ is used to describe a method of analgesia which employs sophisticated infusion devices which allow patients to self-administer opioids, usually intravenously. Most PCA systems incorporate microprocessor-driven syringe pumps that, within preset limits, will deliver a bolus dose of morphine when the patient presses a demand button connected to the pump. Access to the syringe and the microprocessor program are only possible using a key or an access code. Certain variables are prescribed and programmed into the PCA pump which control how much opioid the patient can receive. Most machines can also deliver a continuous or ‘background’ infusion. Patients using PCA are instructed to push the demand button whenever they are uncomfortable. Where the patient is unable to use either hand, other mechanisms have been devised to enable the patient to use the machine in a ‘demand’ mode (pneumatic device, pressure-sensitive pad, etc.). The inherent safety of the PCA technique lies in the fact that as long as the machine is in PCA mode only (i.e. there is no continuous infusion) no further doses of opioid will be delivered should the patient become sedated, because no further demands will be made.

PCA variables

Loading dose

PCA is a maintenance therapy and will not be effective if moderate or severe pain is present before it commences. To make the patient comfortable before the PCA is started, a loading dose of morphine is needed. As there is such an enormous variation between patients in the amount of morphine required as a loading dose, the amount is individualized for each patient and titrated against the pain score.

Bolus dose

The bolus dose is the amount of opioid (in milligrams) that the PCA machine will deliver when the demand button is pressed. The commonly used initial dose of morphine is 1 mg. However, in the very elderly, for example in patients over 70 years old, it is sensible to start with a smaller incremental dose (0.5 mg). Conversely, in a 20-year-old the opioid requirements will be higher and a bolus dose of 2 mg may be needed.

Lock-out interval

The time from the end of the delivery of one dose until the machine will respond to another demand is called the ‘lock-out’ interval. This is to allow the effect of one dose to be felt before another can be given and is one of the safety features of the machine. A lock-out interval of 5 min has become the standard used today.

Continuous (background) infusion

Although most PCA machines can deliver a continuous infusion, this feature is rarely used in the postoperative setting as it has been shown to increase the risk of side effects, with no improvement in the quality of analgesia.

Effectiveness of PCA

Many studies have been carried out comparing PCA to conventional methods of analgesia. Systemic reviews in 1992 and 2001 (Acta Anaesth Scand 2001) found conflicting results regarding the effectiveness of PCA compared to traditional analgesia. However, a Cochrane review in 2007 of 55 studies involving a total of 3861 patients found that, overall, more patients were satisfied with the analgesia provided by the PCA pump. Also, pain intensity during the first 24 h was 8 points lower in the PCA group than in the group receiving conventional analgesia, 9 points lower between 25 and 48 h and 13 points lower between 49 and 72 h.¹⁸

Oral analgesics

The most commonly used drugs for mild to moderate pain in the postoperative period are codeine, or codeine plus paracetamol combinations. Oxycodone and tramadol are also increasingly used.

Codeine

Codeine is a naturally occurring alkaloid like morphine. It is metabolized in the liver, where 5–10% of the dose is converted to morphine, which accounts for its main analgesic effect. Codeine is usually given for the treatment of mild to moderate pain by the oral route. Codeine plus paracetamol preparations are the most commonly used opioid analgesics for day surgery procedures. However, with fixed-dose combinations of paracetamol plus codeine there is a relatively flat dose–response curve and a clear ceiling effect. Added to this, the analgesic potential of fixed-dose combinations is limited by unacceptable side effects associated with the paracetamol component. Fixed-dose combination preparations must be given every 4–6 h and any delay in administration, especially when ordered on an ‘as needed’ (p.r.n.) basis, may result in lower plasma opioid concentrations and thus the re-emergence of pain.

Oxycodone

Oxycodone is a thebaine derivative and is used for the management of moderate to severe pain. A sustained-release preparation of oxycodone has been developed which has been shown to be very effective in postoperative pain relief. The biphasic pattern of absorption of the drug following oral administration results in an initial rapid absorption of approximately 40% of the dose, with rapid onset of analgesia (at about 1 h), which is then followed by sustained release of drug and stable plasma levels over a further 12 h period; therefore twice daily dosing is all that is required. A trial of this drug in orthopaedic patients showed that it provided effective analgesia, shortened hospital stay and reduced the frequency of analgesic administration after hip and knee arthroplasty.¹⁹

Tramadol

Tramadol provides effective analgesia in patients undergoing minor or intermediate surgery. It provides analgesia by two mechanisms: an opioid effect and an enhancement of the serotonergic and adrenergic pathways. It is a weak opioid and thus has fewer of the typical opioid side effects. Little respiratory depression occurs unless given in large doses. In addition, it causes less constipation and has less addiction potential. It can be given orally or intravenously, usually in a dose of 100 mg. As nausea is common after i.v. administration, antiemetics should be given prior to intravenous usage.

Clinical Pearl 7.1

• The goal of pain management is the ‘three Ls’:

• Lowest dose

• Longest duration

• Least side effects

Adjuvant analgesic agents

A number of other adjuvant analgesic drugs, anticonvulsants, ketamine, clonidine, neostigmine and magnesium, have been shown in clinical trials to be useful in controlling postoperative pain.²⁰ However, these modalities are not yet used in routine clinical practice and are best managed by specialist anaesthetists and pain medicine practitioners.

Summary Box 7.4 Regional or topical options

Topical local anaesthesia

Surgical infiltration

Regional blocks such as axillary, supra- or infraclavicular, interscalene

Local anaesthetic techniques

1. Local infiltration

2. Intra-articular joint injections/catheter techniques

3. Peripheral nerve blocks.

Local Infiltration

Single injections of local anaesthetic drugs into wounds can provide effective analgesia following minor operations. Bupivacaine as a long-acting local anaesthetic is the most commonly used drug in this setting. However, as bupivacaine is potentially more cardiotoxic than the other local anaesthetic drugs it is now being replaced by its isomer, levobupivacaine, a drug which has a better safety profile.

Intra-articular joint Injections/catheters

Intra-articular local anaesthetic infiltration has been used for many years in arthroscopic knee surgery with improved pain relief demonstrated in the postoperative period. Similarly in shoulder and elbow arthroscopies intra-articular injection of local anaesthetic appears superior to surgical wound infiltration. Intra-articular catheter techniques have recently been developed where at the end of surgery a 20-gauge catheter is inserted by the surgeon into the joint under direct visualization. Dilute solutions of local anaesthetics are then infused through the catheter postoperatively. While intra-articular local anaesthetic infiltration has the potential advantages of better preservation of motor function and technical simplicity, a study comparing this technique to perioperative interscalene block in shoulder surgery demonstrated superior analgesia in the interscalene group.²¹

Peripheral nerve blocks

The use of single-shot or continuous peripheral nerve blocks is becoming increasingly popular for postoperative analgesia following major upper limb surgery. Peripheral nerve blocks provide excellent analgesia with minimal motor blockade. This facilitates early and more effective joint mobilization and physiotherapy, while limiting reflex muscle spasm. They also avoid the side effects of PCA morphine (sedation, PONV). In addition, with the increased use of day case facilities and minimally invasive surgery, e.g. arthroscopic elbow surgery, more procedures are being carried out under regional anaesthesia as a sole technique.

Innervation of the elbow

The elbow is innervated by four major nerves – the median, musculocutaneous, ulnar and radial nerves – which are the terminal branches of the three cords of the brachial plexus. Brachial plexus block is the most frequently performed major peripheral nerve block and, although over 40 techniques have been described in the literature, they are all modifications of the four major approaches, which can be categorized as:

No one technique is ideal, as they have different advantages and complications and their use depends on which is most appropriate for the intended surgery. The interscalene approach is best suited for shoulder and upper arm surgery but has the potential for serious complications. For elbow surgery, either the supraclavicular or infraclavicular (vertical infraclavicular block) approaches can be used. The vertical infraclavicular technique is easy to perform, and has a high success and low complication rates. The axillary approach is easy to learn and has the lowest incidence of complications; as such it is ideally suited for hand surgery. However, the musculocutaneous nerve can be missed with axillary blocks. It is advised therefore that an additional block of this nerve is undertaken to avoid tourniquet pain.

Continuous peripheral nerve blocks

This technique involves the percutaneous insertion of a catheter directly adjacent to the peripheral nerve(s) innervating the surgical site (as opposed to a ‘wound’ catheter placed directly at a surgical site). Infusing local anaesthetic via the perineural catheter then provides potent, site-specific and continuous analgesia. Since the 1990s, advances in needle technology, placement techniques (e.g. nerve stimulators, ultrasound guidance) catheter design and infusion pump mechanics have resulted in widespread use of this technique. Particularly for painful shoulder surgeries, continuous perineural catheters provide superior analgesia, limit opioid-related side effects and improve patient satisfaction.²² This technology has also proven useful and safe for outpatient use using disposable elastomeric pumps.²³

Clinical Pearl 7.2

• Whenever a regional anaesthetic is performed, detailed instructions must be given to the patient, offering an expectation of the duration and extent of their block, the requirement to protect the insensate limb, and the need to begin analgesic medications prior to his/her experiencing severe pain.

Ultrasound-guided regional nerve block

The use of ultrasound guidance has become increasingly popular in regional anaesthesia over the past few years. The advantages of ultrasound guidance include the real-time visualization of anatomical structures and the spread of anaesthetic.²⁴ Peripheral nerve stimulation relies on placing the needle close to the target nerve, but cannot make allowances for individual anatomical variation or reliably predict the spread of the local anaesthetic. Using high-resolution real-time ultrasound visualization during peripheral nerve block may further increase success rates, decrease latency of the block, reduce the volume of local anaesthetic used, shorten time to perform the blocks and has the potential to reduce or eliminate the risk of accidental intravascular or intraneural injection. A number of recent studies support these claims.

A study by Chan et al, reporting a retrospective analysis of 662 axillary blocks, found that in the ultrasound-guided group the block success rate was higher compared to the traditional group (91.6% versus 81.9%). The US-guided axillary block group also required a lower volume of local anaesthetic and had a shorter time in the block room.²⁵ Combined ultrasound and nerve stimulation guided techniques are now being used more frequently with high success rates. Finally, National Institute for Health and Clinical Excellence (NICE) guidelines (January 2009) also supported the increased efficacy and safety profile of ultrasound-guided nerve blocks.²⁶

Summary Box 7.5 Complications of brachial plexus block

Vertebral artery injection

Subarachnoid injection

Phrenic nerve palsy

Recurrent laryngeal nerve palsy

Stellate ganglion block

Pneumothorax