Introduction

Pain is defined as an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage. Pain in the post-operative period is one of the major factors that impede recovery from anaesthesia and surgery. Total abdominal hysterectomy is commonly performed via a Pfannenstiel incision and causes significant moderate to severe pain that requires multimodal post­operative pain management.

Pain after hysterectomy is often multifactorial and arises from different sources. The sources of pain may include a combination of incision pain, pain from deeper visceral struc­tures, and dynamic pain or pain on movement, such as during straining, coughing, or mobilizing that may be severe. The main aim of multimodal analgesia is to obtain synergistic or additive analgesia, allowing a smaller dose of each drug with improved safety profile and less side effects. This can be achieved by combining analgesics acting at different locations of the pain pathway.

Pain Assessment

The essential prerequisite to comprehensive pain management is reliable and accurate assessment of pain. This should include history of the site of pain, pain characteristics, pain intensity, associated symptoms such as nausea and effect of pain on activities, and sleep.

A number of scales are available to quantify and measure pain intensity, such as the verbal descriptor scale and numerical rating scale. These can be used together with self-reporting, as pain is itself a subjective experience. The verbal descriptor scale uses words to describe the magnitude of pain using terms such as none, mild, moderate, and severe pain. This is quick and simple but may be limited by personal, cultural and language differences in interpretation by patients and doctors. The numerical rating scale is used by asking patients to rate their pain intensity on a scale of 0 to 10, with 0 being no pain and 10 being the worst pain imaginable. This scale can be done both in a verbal and written manner.

Post-operative pain management should also include monitoring the adverse effects of therapy and haemodynamic monitoring such as blood pressure, pulse rate and respiratory rate. The availability of an acute pain service would also be beneficial to better manage pain by dedicated staff including anaesthetists and nurse clinicians.

Opioid Analgesia

Opioids remain the cornerstone for treatment of moderate to severe pain for post-operative pain management. However, they should not be the sole analgesic of choice. The use of opioids by patient-controlled analgesia is popular but limited by side effects, and certain types of pain such as neuro­pathic pain respond poorly to opioids.1 Neuropathic pain is defined as pain arising as a direct conse­quence of a lesion or disease affecting the soma­tosensory system. The consumption of morphine is often high, particularly in the initial post-operative period, leading to marked opioid adverse effects.2,3

Morphine, pethidine and tramadol are the most frequently used drugs for post-operative pain manage­ment.2,4 In patients undergoing abdominal hysterectomy, the administration of intravenous morphine, pethidine and tramadol via patient-controlled analgesia resulted in equivalent pain scores and side effects.5 Intravenous opioid patient-controlled analgesia provides better anal­gesia than conventional intramuscular or subcutaneous opioid regimens, although the magnitude of the differ­ence in analgesia is small.6 Opioid consumption may be greater though. There are no differences in duration of hospital stay or opioid-related adverse effects other than pruritus. Intravenous patient-controlled analgesia is associated with increased pruritus but higher patient satisfaction compared with most conventional opioid regimens.

Morphine remains the most widely used opioid for the management of pain and is considered the gold standard against which other opioids are compared. Morphine-6-glucuronide and morphine-3-glucuronide, the main metabolites, are formed by morphine gluc­uronidation in the liver. Morphine-6-glucuronide is an active metabolite and may contribute to respiratory depression. Both are dependent on renal excretion. Impaired renal function, higher doses and increased age may lead to higher concentration and thus potential risk of sedation and respiratory depression.

Tramadol is commonly referred to as an atypical, centrally acting opioid often used as an adjuvant in pain management. Its efficacy is a result of two complemen­tary mechanisms of action that include stimulation of opioid µ receptors and inhibition of the noradrenaline and serotonin reuptake in the pain pathway.7 Although an effective analgesic, it may not provide adequate pain relief if used as the sole agent for management of moderate to severe pain.8 The adverse effect profile is different from those of other opioids. The risk of respiratory depression is significantly lower compared with other opioids at equianalgesic doses.9–11 Nausea and vomiting are the most common adverse effects and occur at rates similar to other opioids.12

Pethidine is a synthetic opioid still widely used even though there are several disadvantages. Pethidine induced more nausea and vomiting than morphine in the first 2 hours after gynaecological surgery.13 Accumula­tion of its active metabolite, norpethidine, is associated with neuroexcitatory effects including nervousness, tremors, twitches, myoclonus, and seizures. This is especially evident with renal impairment. Intramuscu­lar pethidine is a popular choice even though there are drawbacks, such as pain on injection and unpredictable duration of analgesia especially with multiple dosing.14 Overall, the use of pethidine should be discouraged in favour of other opioids.15

Oral opioids are a viable option owing to the short time to feeding after abdominal hysterectomy. Common options include tramadol and oxycodone. Oxycodone is a potent opioid agonist derived from the opium alka­loid thebaine. It is metabolized in the liver primarily to noroxycodone and oxymorphone, but these metabolites have clinically negligible analgesic effects.16 Animal studies have suggested that oxycodone is thought to act as a . receptor agonist, and these receptors may play an important role in the treatment and mediation of visceral pain.17,18

Dextropropoxyphene has low analgesic efficacy and should be discouraged in favour of other opioids. It is often combined with paracetamol, but this combi­nation does not lead to superior analgesia and there is an increased incidence of dizziness.19 Furthermore, there are other adverse effects of dextropropoxyphene, including risk of abuse, risk of accumulation in the elderly, and cardiac arrhythmia from prolonged QT inter­val. There is a current phase withdrawal of dextropro­poxyphene in the UK of dextropropoxyphene-containing medications.20

Opioid administration is associated with adverse effects such as pruritus, urinary retention, sedation, constipation, paralytic ileus, and nausea and vomit-ing. Because of the multiple mechanisms involved in post-operative pain, a multimodal analgesic regimen, with a combination of opioid and non-opioid analgesic drugs, is often used to enhance analgesic efficacy, and reduce opioid requirements and opioid side effects. In many institutions, this would involve combining patient-controlled opioid analgesia with paracetamol and non-steroidal anti-inflammatory drugs (NSAIDs). There are several adjuvants that have been added to patient-controlled opiod analgesia. Dexmedetomidine, an α2 agonist, has been shown to improve analgesia and be opioid-sparing, and may reduce opioid adverse effects.21,22 Ketamine has not been useful to reduce opioid consumption after abdominal hysterectomy.22

Non-opioid Analgesia

Paracetamol is a commonly used analgesic, act­ing via cyclooxygenase inhibition in the central nerv­ous system. It is a simple analgesic for treatment of mild to moderate pain. The role of paracetamol is in its morphine-sparing effect. Recently, intravenous paracetamol has become available and is useful in the peri-operative setting. Pre-emptive intravenous paracetamol, 1 g, provided good-quality analgesia and decreased morphine consumption with minimal side effects compared with administration of intra­venous paracetamol just before skin closure.23 Rectal paracetamol has a significant morphine-sparing effect after abdominal hysterectomy, with a 36% reduction in patient-controlled morphine consumption.24 In fact, a combination of rectal paracetamol and diclofenac was shown to have the greatest effect in reducing morphine consumption after abdominal hysterectomy compared with either drug used alone.25

Non-selective NSAIDs are used for post-operative pain management. The effects of NSAIDs are due to the inhibition of prostaglandin synthesis in peripheral tissues, nerves and the central nervous system. Pros­taglandins are produced by prostaglandin synthases, which have cyclooxygenase and hydroperoxidase sites. Two subtypes of cyclooxygenase (COX) enzymes are identified: constitutive cyclooxygenase 1 (COX-1) and inducible cyclooxygenase 2 (COX-2). Physiological roles such as gastric mucosal protection, renal tubular func­tion and vasodilatation, bronchodilation, and platelet function are mainly regulated by COX-1 and contribute to the adverse effects of COX inhibition. Tissue damage resulting in inflammation and pain induces COX-2, the target of COX inhibition for pain relief.

Diclofenac is an NSAID that may reduce morphine consumption after abdominal hysterectomy.24,26,27 Total pain, sedation and nausea scores were significantly lower in the diclofenac group compared with placebo in one study.26 Another NSAID, intravenous ketorolac, 30 mg, has been shown to reduce morphine consumption and sedation in the first post-operative day.28 However, because of their significant gastrointestinal toxicity and antiplatelet effects, their use has been limited. Renal dysfunction and reactive airway disease are also contraindications to NSAID use.

Parecoxib sodium is a parenteral anti-inflam­matory analgesic agent that acts through selective inhibition of COX-2. Parecoxib sodium is the prodrug of valdecoxib sodium that is much more selective for COX-2 than for COX-1. Intravenous parecoxib, 40 mg, given at induction of anaesthesia is recommended by patients undergoing total abdominal hysterectomy.29 Parecoxib, being the only available intravenous selec­tive COX-2 inhibitor, is suitable for the peri-operative period. The analgesic efficacy was found to be supe­rior to intravenous morphine, 4 mg, and comparable to intravenous ketorolac, 30 mg, for both magnitude and duration.30,31 There is also rapid onset of pain relief within 10 minutes. Parecoxib provides morphine-spar­ing analgesic effects and reduced pain on sitting up. There were no differences in pain scores at rest or on deep inspiration. There were also no significant differ­ences in adverse effects including nausea, vomiting and sedation.29

Gabapentin, a structural analogue of γ-aminobutyric acid, was initially developed as an anti­convulsant drug. Gabapentin binds to the α2δ subunit of the voltage-gated calcium channels, thus preventing the release of nociceptive neurotransmitters including glutamate, substance P and noradrenaline.32 Pretreat­ment with gabapentin can block the development of hyperalgesia or increased pain sensitivity. Mechani­cal hyperalgesia surrounding the wound and central sensitization contribute to post-operative pain. Central sensitization involves increased responsiveness of noci­ceptive neurons in the central nervous system to normal or below threshold nociceptive inputs. Gabapentin has a selective effect on the nociceptive pain pathway involv­ing central sensitization.33 Pre-operative single dose gabapentin, 1,200 mg, before surgery was associated with decreased post-operative pain scores at rest and on movement after total abdominal hysterectomy.34,35 Gabapentin reduced opioid consumption and did not increase the side effects when compared with placebo. Gabapentin also significantly decreased morphine consumption and pain in patients after mastectomy.36 It may be useful in post-operative patients who have contraindications to NSAIDs due to the adverse renal, gastrointestinal and haemostatic effects. However, gabapentin is less well established and likely to be more expensive. Gabapentin in a total dose of 3,000 mg before and during the first 24 hours after abdominal hysterectomy reduced morphine consumption by 32%, with no significant effects on pain score and no differ­ences in side effects.37

Regional Anagesia

With the Pfannenstiel incision used for total abdominal hysterectomy, peripheral nerve blocks may be a viable option for post-operative analgesia. Bilateral ilioin­guinal nerve block has been used for post-caesarean delivery analgesia and post-hysterectomy analge­sia.38–40 In a prospective, randomized, controlled tri­al, a combination of ropivacaine and clonidine was compared with saline used for bilateral ilioinguinal nerve block. The block was performed immediately after surgery with the patient anaesthetized. There was a 50% decrease in cumulative morphine con­sumption during the first 48 hours post-operatively.

There was no significant difference in pain scores and there was less nausea in the bilateral ilioin­guinal block group. This procedure is easy to per­form and easy to learn, and few complications have been reported in the literature. The main complica­tions described are rare and include intravascular and intraperitoneal injection of local anaesthetics.

Continuous wound infiltration through prolonged administration via a multi-orifice catheter positioned by the surgeon at the end of surgery increases the duration of action as compared with single injections and may thereby improve the efficacy of local wound infil­tration.41 A systematic review supported the benefits and safety of continuous wound infiltration, showing very low incidence of complications. A randomized controlled trial showed that bupivacaine wound infu­sion above the superficial abdominal fascia provides better post-operative analgesia compared with infusion below the fascia in the immediate post-operative period after abdominal hysterectomy.42 There was significant reduction in pain scores at rest and coughing. Opioid-sparing effects were also demonstrated.

Another technique is the transversus abdomi­nis plane block to provide analgesia to the anterior abdominal wall. This is targeted at the abdominal inci­sion which is one of the components of post-operative pain. The abdominal wall sensory afferents course through the neurofascial transversus abdominis plane superficial to the transversus abdominis muscle. Local anaesthetics are administered to block these sensory nerves before they leave this plane via the bilateral lumbar triangles of Petit, which is termed the transver­sus abdominis plane block. The transversus abdominis plane block with ropivacaine reduced the post-operative pain scores and the mean total morphine requirements in the first 48 hours after abdominal hysterectomy.43 Furthermore, there were no complications attribut­able to the transversus abdominis block. Hence, it is an effective analgesic technique when used as part of a multimodal analgesic regimen. This technique is operator-dependent especially when performed under ultrasound guidance, and some degree of technical variability may exist. With practice, the transversus abdominis block is simple, effective and reliable espe­cially with ultrasound guidance.

Centroneuraxial Anagesia

For many years, there has been interest in the ef­ficacy and safety of spinal and intrathecal morphine to relieve post-operative pain.44 Spinal anaesthesia has become the gold standard for caesarean sec­tion.45,46 However for abdominal hysterectomy, gen­eral anaesthesia is still the most widely used. Spi­nal anaesthesia using bupivacaine with intrathecal morphine and fentanyl has been shown to decrease the morphine requirement with patient-controlled analgesia for pain control and shorten hospital stay, after abdominal hysterectomy with a low transverse incision.47 One would, of course, need to tailor and individualize the anaesthetic plan.

Epidural analgesia is a viable option especially for patients with co-morbidities such as chronic respira­tory dysfunction. A meta-analysis of systemic patient-controlled opioid analgesia versus epidural analgesia concluded that epidural analgesia provides better pain relief at rest and with movement using local anaesthetics and lipophilic opioids such as fentanyl.48 Thoracic epidu­ral placement was associated with reduced pulmonary complications and pulmonary infections. Side effects of epidural infusion included a higher incidence of nausea and motor blockade compared with intravenous anal­gesia. Pruritus was, however, lower in incidence with epidural analgesia. The provision of epidural analgesia would require dedicated acute pain services and nursing expertise for post-operative monitoring.

Other

Local anaesthetic wound infiltration is widely rec­ognized as a useful adjunct in the multimodal ap­proach to pain management.49,50 Local anaesthetic wound infiltration without infusion, however, pro­vides no opioid-sparing effect after abdominal hys­terectomy.51 This may suggest that the pain aris­ing from viscera and deeper peritoneal layers is of greater significance than that from the cutaneous, subcutaneous and muscular layers of a wound in­cision. The pain afferents from deeper structures would be unaffected by wound infiltration.

Transcutaneous electrical nerve stimulation decreased post-operative opioid analgesic require­ments and opioid-related side effects when utilized as an adjunct to patient-controlled analgesia after abdominal hysterectomy. Complementary and alternative medicines have also been investigated with conflicting results. Homeopathy was ineffective for pain relief after abdominal hysterectomy.52 Local post-operative cooling showed no benefits in pain relief or opioid requirements after abdominal hysterectomy.53

Development Chronic Pain

Chronic pain prevalence is reported to be 5–32% after hysterectomy.54 This chronic pain is the presence of pain in the surgical site present for at least 3 months after surgery. In most women, the pain was present pre-opera­tively with a minority developing new-onset chronic post­surgical pain. Post-operative pain signals have the capac­ity to initiate prolonged changes in both the peripheral and central nervous system that lead to the amplification and prolongation of post-operative pain. Peripheral and central sensitization contributes to the post-operative hypersensitivity state which is responsible for a decrease in the pain threshold, both at the site of injury (primary hyperalgesia) and in the surrounding uninjured tissues (secondary hyperalgesia).55

The mechanisms underlying chronic post-operative pain are incompletely understood, but either nerve damage during surgery or continuous inflammatory response may lead to an altered pain perception. Further­more, other reasons for pelvic pain, such as chronic infec­tion, adhesions, endometriosis, and bowel and ovarian diseases, should be excluded before diagnosis of the chronic post-hysterectomy pain is made.56

One should identify the pre-operative risk factors to risk-stratify patients. The risk factors for chronic post-surgical pain include moderate to severe pain last­ing more than 1 month, repeat surgery, psychological vulnerability, pre-operative anxiety, and younger age.57,58 This would then allow interventions, such as pre­operative education and appropriate medications, to be administered to prevent development of chronic postsur­gical pain.

Gabapentin has been shown to reduce the inci­dence of chronic pain after abdominal hysterectomy.35 Pregabalin is another gabapentin-like drug that has good oral bioavailability, with a convenient dosing of twice a day and more predictable plasma concentrations at higher doses.59 Increasingly, pregabalin is used for treat­ment of chronic post-surgical pain. Peri-operative gaba­pentin and post-operative ropivacaine wound infusion resulted in lower opioid requirements after hysterectomy and less pain at 1 month compared with subjects given placebo, although there was no difference in pain scores in the first 7 post-operative days.60

Interestingly, spinal anaesthesia in comparison with general anaesthesia reduced the risk of chronic post­surgical pain after hysterectomy, reflecting the potential extended beneficial effects of regional anaesthesia.61 However, there was no difference in the risk of chronic pain between abdominal and vaginal hysterectomy.

Conclusion

Pain management after abdominal hysterectomy should involve regular pain assessment and mul­timodal analgesic regimens. Multimodal analgesic regimens allow the optimization of the benefits for each analgesic technique, whilst reducing the adverse effects. Opioid analgesics form the cor­nerstone in treating moderate to severe pain after

abdominal hysterectomy. However, the side effects of opioids, such as nausea and vomiting, pruritus, and urinary retention, may be significant. Hence, non-opioid analgesia, regional analgesia and cen­troneuraxial analgesia are good options for post­operative pain management. Use of ultrasound guidance in bilateral ilioinguinal blocks and trans-versus abdominis plane block are additional options to reduce opioid-related adverse effects.


About the Authors

Dr Sng is Consultant, Department of Women’s Anaesthesia, KK Women’s and Children’s Hospital, Singapore. Associate Professor Sia is Division Chairman, Clinical Support Services, Head and Senior Consultant, Department of Women’s Anaesthesia, KK Women’s and Children’s Hospital, Singapore.


Acknowledgement

This paper was made possible through a collaboration between KK Women’s and Children’s Hospital (KKH) and the Journal of Paediatrics, Obstetrics and Gynaecology. KKH is the largest medical facility in Singapore which provides specialized care for women, babies and children.


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A complete list of references is available on request to the editorial office.

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