Michelle Keenan and Helen Kerr Cancer and its treatment can cause multiple symptoms, which may lead to significant distress for patients and their families. Clinical nurse specialists (CNS)s have a vital role in the delivery of cancer care by providing supportive care and symptom advice. This requires CNSs to have the knowledge and skills to accurately assess, safely manage and evaluate interventions to alleviate symptoms. This can be challenging in cancer care due to patient complexity, multiple drug regimens and symptom burden. This chapter will discuss the role of the CNS in the assessment and management of four common symptoms that may be experienced by individuals with cancer: pain, breathlessness, nausea and vomiting and constipation. It will also highlight the need for CNSs to carefully consider contra‐indications and side effects before advising on any pharmacological treatment and the importance of seeking additional support when symptoms are persistent or complex. Patients with cancer often experience symptoms that are disease or treatment‐related and that can be complex and debilitating and may negatively affect quality of life (Verkissen et al. 2019). Patients with advanced cancer may present with multiple symptoms such as pain, fatigue, nausea, anorexia, depression and insomnia (Deshields et al. 2014; Grotmol et al. 2019). These symptoms can be challenging to treat, with 66% of patients in the last month of life requiring hospitalisation for acute management (Hjermstad et al. 2013). Clinical nurse specialists (CNS) play a vital role in the delivery of cancer care as they provide expertise in the management of symptoms while providing holistic and supportive care to patients and their families (Fulton et al. 2016; Kerr et al. 2021). The first author, Michelle Keenan, is employed as a CNS in a hospital specialist palliative care team in Northern Ireland, which requires a high level of knowledge and skill in assessing and managing complex symptoms in patients with life‐limiting conditions. The second author, Helen Kerr, is a senior lecturer at the School of Nursing and Midwifery, Queen’s University Belfast, with a clinical nursing background in cancer and palliative care. This chapter will highlight the role of the CNS in the assessment, management and evaluation of four symptoms: pain, breathlessness, nausea and vomiting and constipation. Pain is highly prevalent in individuals with cancer, affecting 66% of people with advanced disease (Van den Beuken‐van Everdingen et al. 2016). The aetiology of cancer pain is often complex and multi‐factorial due to disease burden, side effects of treatment and co‐morbidities (Caraceni and Shkodra 2019). The experience of cancer pain is multidimensional and individual to the patient (Hui and Bruera 2014). Existential distress in individuals with cancer can often exacerbate their experience of pain (Huysmans et al. 2020). This requires CNSs to complete a holistic assessment, which should identify not only the physical symptoms but also the emotional, psychosocial and spiritual needs of the patient. This ensures that the experience of total pain is acknowledged and addressed. Various tools are available that provide a structured pain assessment in determining the source of pain using mnemonics (Rayment and Bennett 2015; Quinn et al. 2017), such as PQRST (provocation, quality, radiation, severity and timing). When identifying the source of pain (e.g. nociceptive, neuropathic or combined), it is important to consider location, radiation, intensity, onset and duration of pain. In addition, exacerbating and alleviating factors should be considered, along with associated symptoms such as anxiety, depression and insomnia (Li et al. 2017). An effective assessment should also include a detailed medical treatment and analgesic history. A clinical examination, review of scans and consideration of appropriate investigations are also essential in determining or excluding the source of pain (Caraceni and Shkodra 2019). For people with cognitive impairment, such as dementia, CNSs must also rely on observing emotional and behavioural manifestations of pain, as individuals may lose their ability to accurately self‐report pain (Achterberg et al. 2020). A number of validated tools are available for assessing pain in cognitive impairment, such as the Abbey pain scale or Pain Assessment in Advanced Dementia (PAINAD) scale (Warden et al. 2003; Abbey et al. 2004); however, it is reported that these are underutilised in clinical practice (Burns and McIlfatrick 2015). Untreated pain can manifest into behavioural disturbances such as agitation or aggression (Sampson et al. 2015), which causes distress not only to the individual but also to their family and caregivers (Lichtner et al. 2016). Therefore, it is vital that a CNS completes an effective, holistic and individualised pain assessment, as this will determine appropriate treatment options and analgesic choices. When devising a treatment plan, it should be discussed, negotiated and agreed upon with the individual; their expectations and concerns should be addressed, as a lack of communication between the patient and healthcare professionals has been identified as a barrier to effective pain management (Zuccaro et al. 2012). This will include the CNS discussing treatment options, potential benefits and side effects with patients and, when consented, with their families if appropriate. The pharmacological management of cancer pain should be a step‐wise approach using the World Health Organisation (WHO) analgesic ladder (World Health Organisation 2003). Opioids are recommended in the pharmacological management of moderate to severe cancer pain and should be considered in combination with non‐opioid analgesics, adjuvants and non‐pharmacological therapies (National Institute for Health Care Excellence (NICE) 2021), such as transcutaneous electrical nerve stimulation (TENS), complementary therapies, relaxation or distraction (Hökkä et al. 2014). Unlike most analgesics, opioids have no ceiling dose and can be up‐titrated without maximum dosing (Varilla et al. 2015). Oral opioids are often available in slow‐ and immediate‐release preparations and provide pain relief within a 30–60 minute onset (Joint Formulary Committee 2022). Immediate‐release opioids are used in the management of breakthrough pain, and the recommended dosing is normally one‐sixth of the total 24‐hour slow‐release dose (Back et al. 2021). When adjusting the dose of slow‐release opioids, the amount of breakthrough analgesia administered and the effectiveness and potential side effects should be considered. It is recommended that the up‐titration of opioids should not exceed 30–50% of the total daily dose in 24 hours (Back et al. 2021). The up‐titration of opioids should stop when pain is controlled or the individual is experiencing intolerable side effects (NICE 2012; Varilla et al. 2015). Morphine sulphate is considered the gold standard opioid in the management of cancer pain (NICE 2012) and is considered cost‐effective, easily accessible and available in various oral preparations. Common side effects include constipation, nausea, vomiting and drowsiness (Joint Formulary Committee 2022). Therefore, it is advisable to ensure that patients have access to an antiemetic and regular prophylactic laxative therapy (Back et al. 2021). Opioid‐induced nausea will likely subside within five to seven days; however, opioid‐induced constipation can remain problematic and should be reviewed daily. Morphine is metabolised by the liver and excreted by the kidneys (Smith 2009), so careful titration should be considered in individuals with renal impairment or moderate to severe hepatic impairment (Wilcock et al. 2020). Renal impairment can increase the number of active morphine metabolites, which may lead to neurotoxicity such as myoclonus, confusion or drowsiness (Joint Formulary Committee 2022). It is vital that CNSs carefully monitor cerebral activity in opioid treatment and consider a dose reduction or opioid rotation to avoid these side effects, as severe opioid toxicity can lead to respiratory depression (Back et al. 2021). A dose reduction and careful titration may be required in older people or those who are opioid naïve. Morphine should be avoided in individuals with moderate to severe renal impairment and consideration given to alternative opioids, depending on the degree of impairment. Opioid rotation should also be considered in patients who experience intolerable adverse effects and unsuccessful pain control despite increasing titration (Back et al. 2021). Opioid conversion guidance should be used when switching opioids (NICE 2012), and it is recommended that clinicians dose‐reduce by 25–50% for the first 24–48 hours when introducing an alternative opioid (Back et al. 2021). It is also important to ensure that patients have appropriate breakthrough analgesia when advising or prescribing a slow‐release opioid. Oxycodone is considered a ‘second‐line’ opioid in the management of severe pain and has similar action and side effects to morphine (Guo et al. 2018). Similar to morphine, it is metabolised by the liver and excreted by the kidneys. Due to the risk of drug accumulation, it should be cautiously titrated in patients with mild to moderate renal impairment and avoided in patients with severe renal impairment (Ackroyd and Aman 2012). It is also contraindicated in moderate to severe hepatic impairment (Joint Formulary Committee 2022). Oxycodone is twice as potent as morphine; therefore, the CNS should always refer to opioid conversion guidance when considering switching from one opioid to another (McKie 2016; Back et al. 2021). The presence of renal impairment should not delay the treatment of cancer pain. A CNS must recognise the risks of analgesic use and make adjustments to minimise potential side effects developing. This requires close monitoring of renal function and careful consideration of opioid choice, dose and frequency reduction. Acute kidney injury (AKI) can be common in individuals with cancer and is reported to affect 50% of individuals (Cosmai et al. 2021). It often significantly affects prognosis and length of hospitalisation (Candrilli et al. 2008). In clinical practice, it is often observed in patients receiving systemic anticancer treatment due to nephrotoxic side effects or as a result of direct tumour invasion of the kidneys (Kitchlu et al. 2019). Other causes include dehydration due to sepsis, vomiting or diarrhoea, nephrotic syndrome and obstructive uropathy secondary to disease (Rosner and Dalkin 2012; Lameire et al. 2016; Folkard et al. 2020). For patients with rapidly deteriorating renal function, the CNS must assess for any reversible causes and consider a pre‐emptive change in opioids and adjuvants. The use of codeine, morphine or diamorphine is not recommended for severe pain in patients with renal failure (Ashley and Dunleavey 2019; Joint Formulary Committee 2022). Tramadol can be considered for mild to moderate pain (Coluzzi et al. 2020); and for severe pain, oxycodone or alfentanil should be considered (Back et al. 2021). The choice of opioid will be dependent on clinical condition and degree of renal impairment. Alfentanil is safe to administer in severe renal impairment as it is metabolised in the liver to non‐toxic metabolites, which are excreted renally (Klees et al. 2005). However, alfentanil can only be administered parentally and has a short duration of action when given as breakthrough analgesia. Therefore, in clinical practice, it is often administered via continuous subcutaneous infusion with oxycodone for breakthrough analgesia. This can be problematic for patients who have ongoing cancer pain or chronic pain conditions or do not wish to have a syringe driver. A CNS should always seek guidance from specialist palliative care teams in the management of complex pain for patients with renal failure, for consideration of alternative opioids such as hydromorphone, subcutaneous fentanyl, transdermal fentanyl or buprenorphine. A CNS should also be mindful of the use of adjuvant analgesics in renal failure, such as non‐steroidal anti‐inflammatory drugs (NSAIDs), which are contra‐indicated in patients with renal impairment (Ashley and Dunleavey 2019), and a dose reduction should be considered in neuropathic agents such as pregabalin or gabapentin (Lee et al. 2011; Ashley and Dunleavey 2019). For individuals with cancer, liver impairment can be related to disease progression, anticancer treatment or other underlying conditions such as cirrhosis or hepatitis (Pinter et al. 2016). Liver metabolism is the main route of elimination for many drugs. Impairment can cause abnormal metabolism resulting in the accumulation of drug metabolites, increasing drug side effects. There are several factors to consider before choosing an analgesic, such as the patient’s prognosis, the severity of the liver disease, liver function, internationalised normalised ratio (INR), and albumin and bilirubin levels (Bridgewater et al. 2014). Currently, there is no clear guidance on analgesic use in individuals with hepatic impairment; therefore, the CNS should seek guidance under the relevant drug in the British National Formulary (Joint Formulary Committee 2022). A systematic review of the use of opioids in patients with cancer with hepatic impairment found that morphine is the preferred choice of opioid (Hughes et al. 2022); however, there is limited evidence to support this. As there is no clear guidance, all opioids should be used with caution in patients with hepatic impairment. The general approach to pain management is to avoid hepatotoxic drugs such as NSAIDS, consider opioid reduction with extended dose intervals, and ensure close monitoring and regular review (Back et al. 2021). In acute liver failure, the use of regular immediate‐release opioids, instead of controlled‐release, should be used until the pain or liver function is stable (Joint Formulary Committee 2022). The use of transdermal patches should also be avoided until the liver function has stabilised (Soleimanpour et al. 2016). A CNS should also be mindful that although paracetamol is a relatively safe non‐opioid analgesic, a dose reduction must be considered in hepatic impairment (Joint Formulary Committee 2022). For patients experiencing intolerable side effects or unresolved pain, the CNS should seek guidance from specialist palliative care for consideration of alternative opioids such as subcutaneous fentanyl. For the management of pain in patients with both renal and hepatic impairment, the CNS and medical team should always seek advice from specialist palliative care. Neuropathic pain refers to ‘pain caused by a lesion or disease of the somatosensory system’ (Bouhassira 2019, p. 16). It is often characterized as paraesthesia, numbness and allodynia (Bouhassira 2019). Neuropathic pain is common in advanced cancer due to the direct invasion, compression, or irritation of peripheral or central nerves (Tomita et al. 2013). It is often difficult to treat as it does not normally respond to standard analgesics such as opioids (Jung et al. 2020). The NICE guidelines for the management of neuropathic pain recommend amitriptyline, duloxetine, pregabalin or gabapentin in pharmacological treatment (Tan et al. 2010). In clinical practice, pregabalin is often used first‐line in specialist palliative care due to its efficacy and ease of titration. Pregabalin is a gabapentinoid licensed for the treatment of neurological disorders. In 2004, it was approved for the treatment of diabetic peripheral neuropathy and postherpetic neuralgia (Arnold et al. 2017), and it is now widely used in the treatment of other neuropathic pain. Due to drug misuse and increased mortality associated with pregabalin (Skopp and Zimmer 2012), it is now a class C controlled drug in the United Kingdom (UK). Clinicians must be cautious about prescribing gabapentinoids and consider whether the potential risks outweigh the benefits (Derry et al. 2019); therefore, it is important that CNSs carefully evaluate for signs of drug abuse or dependence. The dosage of gabapentinoids such as pregabalin can be up‐titrated depending on response and tolerability. The side effects include dizziness, headache, confusion, tremor, blurred vision, vertigo, ataxia and incoordination (Zaccara et al. 2011). The frequency and intensity of these effects are often increased in higher doses (Bafna et al. 2014). CNSs must also be aware of less common side effects such as peripheral oedema (Calkins et al. 2014), and caution must be taken with a patient with severe congestive heart failure (Ho et al. 2013). Abrupt withdrawal or rapid down‐titration of pregabalin can cause insomnia, nausea, headache and diarrhoea (Naveed et al. 2018); therefore, it should be gradually down‐titrated over a minimum of one week. In clinical practice, regular review should be arranged to assess effectiveness and tolerability with every dose titration. Clinical judgement should be used when deciding to titrate slowly, and a dose reduction must be considered in individuals with renal impairment or receiving haemodialysis (Lee et al. 2011). If first‐line treatment is not effective or intolerable, the CNS should seek advice from the medical team to consider switching to other recommended neuropathic agents. Pain secondary to nerve compression may benefit from corticosteroids such as dexamethasone (Wilcock et al. 2020; Back et al. 2021). CNSs should seek advice from specialist palliative care teams for pain management that is complex or persistent. In specialist palliative care, ketamine is often used under specialist supervision for complex neuropathic pain (Back et al. 2021). Ketamine is an N‐methyl D‐aspartate (NMDA) receptor antagonist used when neuropathic pain has been unresponsive or poorly responsive to first‐line conventional therapies. Although the efficacy of ketamine in the treatment of chronic and cancer pain has been widely debated (Velzen et al. 2021), it is often used in specialist palliative care. It is prescribed under the recommendation of a palliative medicine consultant and requires close monitoring of the individual, guided by the specialist palliative care team. Possible side effects include dysphoria, vivid dreams, hallucinations, hypertension, anxiety, tachycardia and cystitis (Joint Formulary Committee 2022). It is contraindicated in patients with raised intracranial pressure, uncontrolled hypertension, severe cardiac disease or cerebrovascular accident (CVA). Patients commencing ketamine will likely be on existing regular opioids; therefore, CNSs must be vigilant, as the introduction of ketamine can restore opioid sensitivity, increasing the risk of opioid toxicity (Lilius et al. 2015; Jonkman et al. 2017). Breathlessness is one of the most distressing symptoms for individuals with cancer (Solano et al. 2006), with intensity increasing in the last weeks to days of life (Hui et al. 2015). It is highly prevalent in advanced lung cancer, affecting 90% of individuals (Chan and Hughes 2015). There is a wide range of aetiology relating to disease progression, effects of cancer treatment, underlying co‐morbidities, fear and anxiety (Cachia and Ahmedzai 2008
8
Symptom Management
Abstract
8.1 Introduction
8.2 Pain
8.2.1 Renal Impairment
8.2.2 Hepatic Impairment
8.2.3 Neuropathic Pain
8.3 Breathlessness
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