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Efforts are made to ensure the accuracy and agreement of these guidelines. However, we cannot guarantee this. This guidance does not override the individual responsibility of healthcare professionals to make decisions appropriate to the circumstances of the individual patient, in consultation with the patient and/or guardian or carer, in accordance with the mental capacity act, and informed by the summary of product characteristics of any drugs they are considering. Practitioners are required to perform their duties in accordance with the law and their regulators and nothing in this guidance should be interpreted in a way that would be inconsistent with compliance with those duties
The use of corticosteroids in palliative care varies considerably from unit to unit and physician to physician. Traditionally they have been used to reduce oedema, to promote appetite and well being; and for their specific use in disease processes such as asthma or chronic lymphatic leukaemia or in emergency situations where their use can buy time until a more definitive treatment can be instituted.
Corticosteroids are produced by the adrenal gland and have a number of physiological roles including catabolic effects on protein, carbohydrate and fat metabolism, and anti-inflammatory effects. They influence water and electrolyte balance and suppress immunity.
Dexamethasone is the corticosteroid of choice in palliative care since compared with prednisolone it causes less fluid retention and the tablet burden for a given dose is less.
bone marrow involvement causing pancytopenia (normocytic)
•bleeding (microcytic if chronic)
bone marrow suppression from chemotherapy
general reaction to advanced malignancy, anaemia of chronic disease (usually normocytic)
iron deficiency (microcytic)
Management of clinical anaemia
Treat mild iron-deficient (microcytic) anaemia with ferrous sulphate
Transfusion is unlikely to give benefit if the Hb is 10 g/dl or more, but symptoms may be better predictors of response
Transfusion must be considered to be likely to help
dyspnoea (more often due to lung pathology) or
weakness (more often due to tumour cachexia)
and thus improve quality of life
It is important to document if the transfusion has been effective in the notes. This helps plan future transfusions.
If repeated transfusion is required, the frequency of transfusion, symptomatic benefit, and patient's desires regarding prolonging life need to be carefully reviewed.
Bleeding in cancer may be due to local pathology e.g. tumour, peptic ulcer, haemorrhoids or varices.
Systemic causes of bleeding may exacerbate local factors, or present as more diffuse mucosal bleeding:
liver disease or jaundice
vitamin C deficiency (scurvy)
Medications (other than anticoagulants) may have a causative / contributory role e.g. NSAIDs, SSRIs
Important to distinguish acute life-threatening bleeding from chronic bleeding, and reversible from irreversible causes, as well as clarifying patient preference for management and ceiling of care.
Non-acute haemorrhage may be treated by oncological, systemic and local measures. Palliative radiotherapy is very useful for superficial tumours and those of the bronchus and genito-urinary tract. Radiotherapy, which causes a radiation thrombosis, can be helpful to reduce bleeding from tumour sites, including ulcerating skin tumours, haemoptysis and haematuria
If radiotherapy is not appropriate, coagulation should be enhanced with oral tranexamic acid 1g t.d.s., but caution is necessary with haematuria since clots may form in the bladder resulting in further problems. Caution is also required if there is a history of stroke / IHD.
General medical management will include assessment of blood loss, appropriate fluid replacement or transfusions.
If bleeding tendency is present, attention should be paid to optimise:
Acute haemorrhage which may be caused by malignant erosion of a major artery may be a rapidly terminal event, e.g. erosion of a head and neck cancer into the carotid artery. It may be possible to anticipate such an occurrence and appropriate medication and a red/green blanket to reduce the visual impact should be readily available. Relatives or others who witness such an event will need a great deal of support. If the haemorrhage is not immediately fatal such as with a haematemesis or bleeding from the rectum, vagina or superficially ulcerated wound, the aim of treatment is local control if possible and sedation of a shocked, frightened patient.
In the case of suspected bleeding from a non-malignant cause e.g. gastric erosions, active management may be appropriate depending on patient circumstances.
The palliative care team need to balance the anxiety of alerting the family to the possibility of an acute bleed, with the likelihood of such an event occurring and the need for the family to be prepared. If the patient chooses to be looked after at home, the issues of managing acute haemorrhage need to be discussed with the family and the home care team and a clear plan worked out.
Continuous bleeding due to low platelet count (rare unless < 20) may occur in pancytopenia from bone marrow infiltration, leukaemia, chemotherapy etc.
may be appropriate if bleeding is distressing
will only raise the platelet count in the patient for a matter of days
only indicated if active bleeding
5 units IV over 1 hour
may need to be repeated every few days
tranexamic acid (or aminocaproic acid) can control mucosal bleeding (nose, uterus, GI tract) in thrombocytopenia of various aetiologies.
Liver Disease & Jaundice
Clotting factors may be reduced in advanced liver disease and lead to bleeding from mucosal surfaces.
Obstructive jaundice will lead to fat malabsorption and thus reduced vitamin K absorption. Abnormal clotting may be normalised by giving vitamin K:
vitamin K given IV or orally
needs to be water soluble (Menadiol) if given orally
10mg PO or by slow IV injection daily
Hepatocellular damage will prevent many clotting factors being manufactured; this may only be reversed by fresh frozen plasma.
Fresh frozen plasma needs to be given daily, but may very rarely be appropriate in late stage disease to reduce severe distress from oral bleeding, haemoptysis, etc.
Haemorrhage on warfarin
Poorly controlled anticoagulation with warfarin is a particular problem in cancer patients.
However these patients also carry a higher risk of venous thromboembolism.
British Society for Haematology Guidelines:
Major bleeding - stop warfarin. Phytomenadione (vitamin K1) 5mg by slow IV injection; FFP 15mL/kg
INR > 8.0, no bleeding or minor bleeding - stop warfarin, restart when INR < 5.0. If other risk factors for bleeding give Phytomenadione (vit K1) 0.5mg by slow IV injection or 5mg orally. Repeat phytomenadione after 24h if INR still >5.0
INR 6.0-8.0, no bleeding or minor bleeding - stop warfarin, restart when INR <5.0
Haemorrhage on heparin
If bleeding occurs on heparin, it is usually sufficient to stop the heparin. Protamine is a specific antidote, but is only partially effective against low molecular weight heparins.
Heparins (unfractionated and low molecular weight) can cause thrombocytopenia. Immune reaction, seen after 5 days or more of treatment. Stop heparin if this occurs.
Chronic renal failure
Renal failure causes complex disturbances of blood clotting.
Tranexamic acid shortens bleeding time in chronic renal failure.
Conjugated oestrogens shorten prolonged bleeding times in renal failure. Daily IV infusion 0.6mg/kg daily for 4-5 days, or 50mg daily for 7 days (duration of effect 10-15 days).
Vitamin C deficiency (scurvy)
Scurvy is usually due to dietary insufficiency and is most common in elderly people, living alone, or dependent on alcohol. Its frequency is probably underestimated in cancer patients.
It should be suspected in cases of unexplained haemorrhage, especially with intramuscular haemorrhage or haemorrhagic gingivitis, ecchymoses and purpura. 'Corkscrew hairs' due to failure of hair follicle eruption may be seen.
Diagnosis is made on a mixture of clinical findings and serum vitamin C level (though these reflect recent dietary intake). Treatment is with vitamin C 1g daily for 2 weeks, then 60-100mg daily. Clinical signs should resolve within 1-2 weeks.
Some degree of venous thromboembolic disease (VTE) is extremely common in patients with cancer and to a lesser extent with other advanced disease.
Suspect pulmonary emboli in patients with episodic and otherwise unexplained breathlessness or confusion.
Serological tests such as D-Dimers are unhelpful in advanced cancer.
Doppler scans will reveal DVTs in large veins.
CT pulmonary angiography can detect even small pulmonary emboli.
Cancer patients carry a high risk of venous thromboembolism overall.
However, poorly controlled anticoagulation with warfarin is a particular problem in palliative care.
Decisions about management of venous thromboembolism in cancer must be made on an individual basis weighing up the benefits and risks, and taking individual circumstances into account. Increased bleeding risk should be taken into account e.g. thrombocytopenia or liver failure.
Management of DVT or PE
Treatment goals should be:
Symptomatic relief of acute event :
DVT: consider leg elevation, compression garment and analgesia for swelling and tenderness.
PE: consider oxygen, opioids ± benzodiazepine for dyspnoea and fear.
Resolution of thrombus, if possible:
If pelvic DVT due to external tumour compression or infiltration, this may not be achievable.
Low molecular weight heparin treatment for 7-14 days can be given quite safely, even as an outpatient, without blood monitoring.
Fibrinolytic therapy (e.g. streptokinase) may be appropriate for selected patients e.g. with central venous catheter-related SVC thrombosis.
Prevention of further DVT or more serious PEs.
Offer LMWH to patients with active cancer and confirmed proximal DVT or PE, and continue the LMWH for 6 months. At 6 months, assess the risks and benefits of continuing anticoagulation.  CG144
For active cancer, anticoagulation therapy can include treatment with LMWH or rivaroxaban given in accordance with the summary of product characteristics. Quality Standard 29
Hypercalcaemia occurs as a result of increased osteoclastic activity (which releases calcium from bone) and decreased excretion of urinary calcium. This is attributed to locally active substances produced by bone metastases or by factors such as ectopic parathyroid hormone related protein (PTHrP) or cytokines, and occurs in 10% of the cancer population. The tumours most commonly associated with hypercalcaemia include squamous cell carcinoma of the bronchus, carcinomas of the breast and prostate, multiple myeloma and other squamous cell tumours.
Hypercalcaemia is the most common tumour-induced metabolic disorder of malignancy
Other associated cancers include renal, genitourinary and lymphoma.
A corrected plasma calcium concentration above 2.6 mmol/L defines hypercalcaemia. It is often mild and asymptomatic and significant symptoms usually only develop with levels above 3.0 mmol/L (although some patients may have significant symptoms at lower levels). It is probable that the rate of rise determines symptoms. Levels of 4.0 mmol/L and above will cause death in a few days if left untreated. 80% of hypercalcaemic patients with cancer survive less than one year.
Symptoms include drowsiness, confusion, nausea, vomiting, thirst, polyuria, weakness and constipation.
PTHrP-secreting tumours, eg carcinoma of lung
dehydration, renal impairment
Management should include supportive management and symtom control e.g. anti-emetics
Treatment is only necessary if there are symptoms or there is a high likelihood of symptoms developing and may be unnecessary if the patient is very near to death.
A high oral intake of fluid is essential if this is possible. Extra fluid intravenously is necessary especially if the patient is significantly dehydrated, which is likely.
Bisphosphonates inhibit osteoclast activity and thereby inhibit bone resorption. Because of poor alimentary absorption, they are usually given intravenously initially. Bisphosphonates are effective in 70-80% of patients for an average of two to three weeks.
Zoledronic acid 4mg in 100mL sodium chloride 0.9%
It may have a longer (4 weeks) period of action and has a shorter (15 minute) period of administration than disodium pamidronate which is also used commonly
60-90mg in sodium chloride 0.9%,
500ml over 2-4h
Sodium clodronate 1.5g in sodium chloride 0.9%,
500mL over 4h
The dose and rate of bisphosphonate infusion may need to be reduced if there is renal impairment. Bisphosphonates should be avoided if GFR less than 30. Plasma calcium levels start to fall after 48 hours and fall progressively for the next 6 days. Oral ibandronate has been reported to delay the recurrence of hypercalcaemia and may be important for maintenance.
If calcium remains high or rises again shortly following a bisphosphonate infusion it may be useful to try an alternative bisphosphonate. If it is not possible to reduce the calcium levels, attention should be paid as ever to the management of symptoms particularly pain, confusion and constipation.
If poor renal function limits use, or if calcium doesn't respond satisfactorily to bisphosphonate, an alternative such as denosumab may be appropriate - seek specialist advice.
Normocalcaemia should be achieved after 3-7 days. Mean length of response for pamidronate is 2-4 weeks, and for zoledronate 4-6 weeks.
Consider maintenance treatment e.g. pamidronate 90mg iv or zoledronate 4mg iv 4 weekly.
Fine control of blood glucose levels is no longer an appropriate treatment goal in patients in the last weeks and days of illness and in some patients, particularly those with liver metastases, the pursuit of fine control may not be possible and may be a distracting burden for the patient and family. However symptomatic hyperglycaemia must not be ignored, even in patients who are not receiving active treatment, as raised blood sugars can result in patients being very symptomatic.
Factors affecting diabetic control in the palliative care setting include:
medications (e.g. corticosteroids)
chemotherapy causing nausea and vomiting
patients receiving high calorie or Percutaneous Endoscopic Gastronomy (PEG) feeding
reduced activity levels
medications other than corticosteroids such as ondansetron
For more information go to the attached Diabetes UK documents:-