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CLINICAL
Until the chemist opens
PRACTICE
Pal iation from the doctor's bag MBBS, is a registrar, Southern Adelaide Palliative Services, Repatriation General Hospital, South Australia.
BA, BMBS, MPH, FRACP, is People with a life limiting il ness may have unpredictable exacerbations of their symptoms requiring after hours care by a Research Fellow, Southern general practitioners using medications that are readily accessible. Al doctors are provided with injectable ‘doctor's Adelaide Palliative Services, bag' emergency drugs for use in such a crisis.
Repatriation General Hospital, South Australia.
OBJECTIVE
This article aims to: identify which medications from the doctor's bag can be used in the pal iative care crises that are
most frequently encountered, present the best possible evidence for these indications, and to provide GPs caring for PhD, FRACGP, is Associate Professor, Centre for General pal iative care patients after hours with management strategies so, whenever appropriate, they can continue to be Practice, University of managed at home.
DISCUSSION
David C Currow
The clinical context, including disease trajectory and patient and caregivers' wishes, must be assessed in pal iative care MPH, FRACP, is Professor, crises. Having excluded reversible problems, symptoms can be treated using doctor's bag medications. Attention must Department of Palliative and be given to route of administration, duration of effect, and appropriate doses for effective pal iation. Supportive Services, Flinders University, and Director, Southern Adelaide Palliative Services, Repatriation General Hospital, South Australia. Australian general practitioners treat a median of
The doctor's bag contains injectable emergency 5–7 palliative patients each year1 – a small part of
medications, some of which have off-license but wel their total clinical practice. However, it is care that
accepted indications for pal iative care, that can provide patients and their families value greatly and, if
excel ent symptom control (Table 1, 2). Appropriate use done well, stands out in people's minds as a very
of these medications for pal iation in a crisis requires special encounter. Patients with end stage disease
consideration of route of administration, appropriate may have unpredictable crises requiring emergency
doses, knowledge of the duration of effect, and of assessment and treatment after hours. Frequently
adverse effects relevant in the emergency setting. The encountered acute problems may include nausea,
preferred parenteral route of administration for pal iative vomiting, dyspnoea, delirium and pain, which occur
medications is subcutaneous. It is worthwhile to carry in many life limiting illnesses including cancer, HIV/
subcutaneous butterfly needles in the emergency bag AIDS, end stage organ failure and neurodegenerative
as inserting a butterfly for repeated doses is less diseases such as multiple sclerosis or motor
traumatic for the patient. Suggested dosages are taken, wherever possible, from the Therapeutic guidelines for pal iative care.2 Decision making as the end of life approaches can Nausea and vomiting
be chal enging. Patients may no longer want active investigation and management, or may be unrealistic Nausea and vomiting are common, unpleasant about what is still achievable, especially at home. symptoms in patients with cancer and other end Assessment of the patient's disease trajectory and stage diseases. Assessment aims to identify an potential y reversible pathologies may be difficult in the underlying cause. Causes may relate to the disease after hours setting. Nonetheless, the clinical imperative process (eg. cerebral metastases), to treatment (eg. is to relieve acute, distressing symptoms, and offer the chemotherapy), or be unrelated (eg. gastroenteritis).3 possibility of appropriate management at home if the It is often multifactorial. Assessment should focus patient and caregiver wish, and when appropriate. on distinguishing potential y reversible presentations Reprinted from Australian Family Physician Vol. 35, No. 4, April 2006 225
CLINICAL PRACTICE Until the chemist opens – palliation from the doctor's bag requiring more urgent attention (eg. bowel The doctor's bag carries several drugs death approaches, and in some patients no obstruction, raised intracranial pressure) from with antiemetic activity: metoclopramide, reversible causes wil be identifiable (Table 4). those that can be managed symptomatical y prochlorperazine, chlorpromazine, haloperidol, Several randomised control ed trials using oral pending further review. It also guides dexamethasone, hydrocortisone, and or parenteral opioids for dyspnoea in people medication choice. For example, prokinetic promethazine. Parenteral forms can be with a range of life limiting il nesses have effects of metoclopromide are helpful in administered subcutaneously rather than shown beneficial effect.7,8 Pain and dyspnoea gastric stasis but are likely to worsen vomiting intramuscularly except prochlorperazine and are potent stimulants of respiratory drive; by and colicky pain in complete gastrointestinal chlorpromazine, which may only be given modulating the respiratory drive, morphine obstruction.4 Unheralded vomiting suggests intravenously or intramuscularly.
lessens distress associated with severe the possibility of cerebral metastases or very dyspnoea, reducing respiratory effort without high bowel obstruction, and steroids may be changing respiratory rate.9 Benzodiazepines appropriately used5,6 (Table 3). Dyspnoea may be insidious, often worsens as are sometimes recommended to treat Table 1. Doctor's bag medications and their indications for palliation
Medication and form
Pal iative care indication
Mode of action
Malignant bleeding Vasoconstriction Can be used topical y (ie. adrenaline soaked gauze) for smal volume Injection 1 mg/mL (1 in 1000) bleeding at superficial sites otherwise difficult to control (eg. fungating wounds) Noisy breathing/terminal secretions (‘death rattle') Anticholinergic – may reduce bronchial secretions Side effects of atropine can be distressing for conscious or semiconscious patients. Injection 600 µg in 1 mL Terminal secretions do not always require treatment. Treatment is often ineffective once secretions are wel established. Repositioning may reduce breathing noises Antipsychotic with antiemetic action via dopamine Haloperidol preferred as it can be given subcutaneously and is less sedating than Injection 50 mg in 2 mL Delirium/acute confusional state antagonism at the chemoreceptor trigger zone chlorpromazine, and (unlike metoclopromide) has no prokinetic effect Injection 5 mg in 1 mL Central causes of nausea and vomiting, raised intracranial Corticosteroids – act to reduce malignant Dexamethasone is the more commonly used drug for these indications, but Injection 4 mg in 1 mL pressure, malignant spinal cord compression, neuropathic inflammation and cytokine production, reduce equipotent dose of hydrocortisone is a reasonable alternative. pain or other poorly control ed pain, superior vena cava perineural oedema, mechanism of antiemetic High dose dexamethasone (16 mg daily) may prevent long term neurological obstruction, dyspnoea caused by lymphangitis effect not known consequences of some spinal cord compressions if started immediately. If Injection 100 mg in 2 mL active treatment of cord compression or raised intracranial pressure is appropriate, it should be instituted without delay and further investigations urgently arranged Agitation and restlessness, myoclonus, seizures, muscle spasm Benzodiazepine – GABA agonist, effective as Benzodiazepines can worsen delirium. If delirium is suspected an antipsychotic Injection 10 mg in 2 mL anxiety from dyspnoea or other difficult symptoms anticonvulsant, muscle relaxant and anxiolytic should be used in preference to a benzodiazepine initial y. Myoclonus suggests renal or hepatic encephalopathy or neuroexcitatory effects of medications including accumulating opioid metabolites. Further investigation may be appropriate depending on the stage of the patient's disease. Benzodiazepines may precipitate or worsen hepatic encephalopathy due to cirrhotic liver disease Antiemetics which act by dopamine antagonism Metoclopramide is preferred as it can be given subcutaneously; contraindicated in Injection 10 mg in 2 mL at the chemoreceptor trigger zone; metoclopramide suspected high bowel obstruction is also prokinetic and increases tone in the Prochlorperazine gastro-oesophageal sphincter Opioid agonist – mode of action in relieving dyspnoea Morphine has been shown to relieve dyspnoea in end stage respiratory disease and Injection 15 mg in 1 mL Dyspnoea, acute pulmonary oedema not known, may act by modulating ventilatory should not be withheld from distressed patients because of underlying lung disease. Nebulised morphine has not been shown to be effective18 – the parenteral route is most appropriate in an emergency Nausea (vestibular type in particular) Antihistamine – acts on vestibular apparatus and Sedating effects of promethazine can also be beneficial in contributing to symptom Injection 50 mg in 2 mL vomiting centre by H1 receptor antagonism control for selected patients. Considerable patient variability in response 226 Reprinted from Australian Family Physician Vol. 35, No. 4, April 2006
Until the chemist opens – palliation from the doctor's bag CLINICAL PRACTICE anxiety associated with refractory dyspnoea person. Anticholinergic medications are the end stage of life limiting illnesses, is in the terminal y il .10 Their use can only be traditional y used, as an extension of their underdiagnosed, and is associated with poor extrapolated from their anxiolytic role and use in anaesthesia for managing airway prognosis.12 A simple tool for the detection of have not been formal y studied in this setting.
secretions. The side effect profile of atropine delirium is the Confusion Assessment method Patients with lymphangitis carcinomatosis can be distressing to a conscious patient (dry (Table 5). Delirium is often multifactorial and present with severe dyspnoea which may mouth, tachycardia, urinary retention). It may less than half of cases occurring at the end progress rapidly, often unrelieved by oxygen worsen confusion and delirium, because it of life are reversible.13 Delirium is distressing or morphine. It is most often seen in breast, crosses the blood-brain barrier. Repositioning for patients, families and caregivers. It may lung and gastric cancers. Steroids may be the patient may be almost as beneficial.11 be hyperactive (two-thirds), hypoactive, or tried in this situation.6 Delirium/acute confusional states
both, and is characterised by fluctuating Noisy respirations at the end of life (‘death poor concentration, confusion, and easy rattle') may upset the caregivers of a dying Delirium is common in patients approaching distractibility, making assessment of other Table 1. Doctor's bag medications and their indications for palliation
Medication and form
Pal iative care indication
Mode of action
Malignant bleeding Vasoconstriction Can be used topical y (ie. adrenaline soaked gauze) for smal volume Injection 1 mg/mL (1 in 1000) bleeding at superficial sites otherwise difficult to control (eg. fungating wounds) Noisy breathing/terminal secretions (‘death rattle') Anticholinergic – may reduce bronchial secretions Side effects of atropine can be distressing for conscious or semiconscious patients. Injection 600 µg in 1 mL Terminal secretions do not always require treatment. Treatment is often ineffective once secretions are wel established. Repositioning may reduce breathing noises Antipsychotic with antiemetic action via dopamine Haloperidol preferred as it can be given subcutaneously and is less sedating than Injection 50 mg in 2 mL Delirium/acute confusional state antagonism at the chemoreceptor trigger zone chlorpromazine, and (unlike metoclopromide) has no prokinetic effect Injection 5 mg in 1 mL Central causes of nausea and vomiting, raised intracranial Corticosteroids – act to reduce malignant Dexamethasone is the more commonly used drug for these indications, but Injection 4 mg in 1 mL pressure, malignant spinal cord compression, neuropathic inflammation and cytokine production, reduce equipotent dose of hydrocortisone is a reasonable alternative. pain or other poorly control ed pain, superior vena cava perineural oedema, mechanism of antiemetic High dose dexamethasone (16 mg daily) may prevent long term neurological obstruction, dyspnoea caused by lymphangitis effect not known consequences of some spinal cord compressions if started immediately. If Injection 100 mg in 2 mL active treatment of cord compression or raised intracranial pressure is appropriate, it should be instituted without delay and further investigations urgently arranged Agitation and restlessness, myoclonus, seizures, muscle spasm Benzodiazepine – GABA agonist, effective as Benzodiazepines can worsen delirium. If delirium is suspected an antipsychotic Injection 10 mg in 2 mL anxiety from dyspnoea or other difficult symptoms anticonvulsant, muscle relaxant and anxiolytic should be used in preference to a benzodiazepine initial y. Myoclonus suggests renal or hepatic encephalopathy or neuroexcitatory effects of medications including accumulating opioid metabolites. Further investigation may be appropriate depending on the stage of the patient's disease. Benzodiazepines may precipitate or worsen hepatic encephalopathy due to cirrhotic liver disease Antiemetics which act by dopamine antagonism Metoclopramide is preferred as it can be given subcutaneously; contraindicated in Injection 10 mg in 2 mL at the chemoreceptor trigger zone; metoclopramide suspected high bowel obstruction is also prokinetic and increases tone in the Prochlorperazine gastro-oesophageal sphincter Opioid agonist – mode of action in relieving dyspnoea Morphine has been shown to relieve dyspnoea in end stage respiratory disease and Injection 15 mg in 1 mL Dyspnoea, acute pulmonary oedema not known, may act by modulating ventilatory should not be withheld from distressed patients because of underlying lung disease. Nebulised morphine has not been shown to be effective18 – the parenteral route is most appropriate in an emergency Nausea (vestibular type in particular) Antihistamine – acts on vestibular apparatus and Sedating effects of promethazine can also be beneficial in contributing to symptom Injection 50 mg in 2 mL vomiting centre by H1 receptor antagonism control for selected patients. Considerable patient variability in response Reprinted from Australian Family Physician Vol. 35, No. 4, April 2006 227
Until the chemist opens – palliation from the doctor's bag CLINICAL PRACTICE Table 2. Suggested emergency management strategies for acute symptom control and palliation from the doctor's bag
Nausea and vomiting
• Metoclopromide 10–20 mg subcutaneously, dose may be repeated if necessary, up to 120 mg over 24 hours OR
• Haloperidol* 0.5–2.5 mg subcutaneously, up to 5 mg over 24 hours OR
• Promethazine 10–25 mg subcutaneously, up to 100 mg over 24 hours
• Suspected central causes of vomiting: dexamethasone 8–16 mg subcutaneously as a single dose
Dyspnoea
• Opioid naïve patient: morphine 1–2 mg subcutaneously, repeat half hourly if needed
• Patients on regular opioids: morphine, statim dose should be calculated based on 30–50% increase on the fourth hourly dose of opioid1
• Persistent distress unrelieved by morphine: diazepam 2–5 mg intravenously, repeated half hourly if needed until agitation settles
Delirium
• Haloperidol 2.5–5.0 mg subcutaneously,2 titrate at half hourly intervals up to 15 mg in 24 hours OR
• Chlorpromazine 10–25 mg intravenously, titrate at half hourly intervals, up to 100 mg in 24 hours is a more sedating option
• If the patient is agitated, distressed, and/or a risk to themselves or their caregivers, sedation may be required in addition to
antipsychotic medication • Diazepam 2.5–10.0 mg intravenously,2 repeated in half an hour if needed, until sedation is achieved
Pain
• Opioid naïve: morphine 1.0–2.5 mg subcutaneously (frail, elderly) or 2.5–5.0 mg subcutaneously as an initial dose. In a crisis, the
patient should be frequently reviewed and the dose titrated up or down by 30–50% according to effect • On opioids already, experiencing an acute exacerbation that is likely to be opioid sensitive: increase background and breakthrough doses of opioid by 30–50% and convert to parenteral morphine3 1. On opioids already, with an acute change less likely to be opioid sensitive (eg. visceral or neuropathic pain): a single dose of dexamethasone 4–16 mg subcutaneously can be added to opioid 2. Use lower end of dose range initial y in those who are medication naïve, the frail and elderly to minimise side effects3. Breakthrough doses are one-sixth to one-twelfth of total daily dose. Conversion from oral to parenteral morphine is based on oral bioavailability of 30–50%. Parenteral doses must therefore be calculated as half to one-third of the oral morphine dose symptoms with a subjective component morphine use, and treatment of acute pain in pain, especial y in calculating an appropriate difficult (eg. pain or dyspnoea). Confusional the opioid naïve patient. Difficulties arise with crisis dose when the usual medication is states most likely to be reversible at the assessing opioid needs in patients already different, or is taken by a different route (eg. end of life are those related to medications, using regular opioids who have escalating transdermal fentanyl patch, methadone, or oral sepsis, dehydration, and treatable metabolic abnormalities such as hypoxaemia.13 Table 3. Bowel obstruction – an emergency management strategy from the doctor's bag
Haloperidol is the first line medication Assessment
for treating delirium and can be given Often partial/subacute rather than complete. Symptoms vary depending on level and subcutaneously.14 Benzodiazepines have no completeness of obstruction. Gastric splash suggests high level of obstruction. Bulky primary role in treating delirium and may hepatomegaly can sometimes cause gastric outlet obstruction worsen it.15 However, severe agitated delirium Management
occurring in the last hours to days of life Aim is to reduce gastric secretions, pain, nausea and vomiting, and inflammation sometimes requires a sedating antipsychotic at site of obstruction, using parenteral medications. A combination of medications and the addition of a benzodiazepine, which usually needed for optimal comfort. Overhydration (>1 L/day) should be avoided as may act synergistical y. it increases volume of gastrointestinal secretions. Effective medical management is usually possible without use of nasogastric drainage in end stage disease Pal iative care patients with significant pain Haloperidol 0.5–5.0 mg subcutaneously is the most appropriate antiemetic as it will not worsen colicky pain (0.5–2.5 mg in the frail elderly) will require a strong opioid for adequate Dexamethasone 8–16 mg subcutaneously reduces peritumour oedema and nausea, symptom relief. The doctor's bag contains has been shown to speed resolution of malignant bowel obstruction injectable morphine and tramadol. Morphine Parenteral opioid should be titrated for analgesia is the preferred medication for palliation (Table 6).16 Most doctors are familiar with Reprinted from Australian Family Physician Vol. 35, No. 4, April 2006 229
CLINICAL PRACTICE Until the chemist opens – palliation from the doctor's bag sustained release preparations of oxycodone, 30–50% increase in the total daily dose and conversion table can be consulted for the morphine or tramadol). These patients are also in the breakthrough dose of a patient conversion to parenteral morphine.2 often undertreated in an acute pain crisis. A on regular opioids is general y safe, and a Corticosteroids can be helpful in patients with pain due to acute nerve compression, Table 4. Possible causes of dyspnoea in terminally ill patients
visceral distension, raised intracranial pressure and soft tissue infiltration.6,17 Related to the disease
Dexamethasone can be given subcutaneously. • Lung tumour or metastases In a crisis an immediate dose is appropriate, • Lymphangitis carcinomatosis however ongoing steroids should not be given • Pleural or pericardial effusion after midday as they have the potential for • Cardiac tamponade significant sleep disturbance.
• Superior vena cava obstruction• Pulmonary embolism • Muscle weakness Patients with end stage disease may progress into organ failure, and be frail and cachexic. • Psychological distress Many are also elderly. Dose selection should Related to treatment of the disease
take these factors into account, often starting • Chemotherapy induced lung injury (eg. bleomycin, taxanes) at the lower end of the dose range. Arranging • Radiation pneumonitis (a late effect – months to years) to review the effect of the initial dose and Comorbid or intercurrent problems
titrate medications is the safest way to assure • Congestive cardiac failure good symptom control.
• Exacerbation of chronic obstructive pulmonary disease • Pneumonia Conclusion
• Multifactorial Some exacerbations may be intermittent or self limiting, but new symptoms can also herald progression of disease and sometimes Table 5. The Confusion Assessment method19
the onset of the terminal phase. Patients and their families often have clear ideas 1. Acute onset and Usually obtained from a family member or nurse about where they wish care to be provided fluctuating course and shown by positive responses to the following at this time. For some people with a good questions: ‘Is there evidence of an acute change in level of function and an acute, unexpected mental status from the patient's baseline?' ‘Did the deterioration, transfer to a hospital for abnormal behaviour fluctuate during the day, ie. tend to come and go, or increase and decrease in severity?' investigation and management may be Shown by a positive response to the following: ‘Did the appropriate. For others, it may result in patient have difficulty in focusing attention, eg. being needless hospitalisation for a problem that easily distracted or having difficulty keeping track of could have been effectively managed in the what was being said?' community setting. The option of care at 3. Disorganised thinking Shown by a positive response to the following: ‘Was home is often grateful y received, and good the patient's thinking disorganised or incoherent such as emergency symptom control contributes to rambling or irrelevant conversation, unclear or illogical this being a possibility. The chal enging aspect ideas, or unpredictable switching from subject to subject?' of patient assessment as death approaches 4. Altered level of Shown by any other than ‘alert' to the following: however is in judging the disease trajectory, ‘Overall, how would you rate this patient's level of and helping people weigh up the benefits and burdens of medical interventions that might be offered for potential y reversible symptoms, Hyperalert = vigilant so they can make their own choices. Drowsy, easily aroused = lethargic Most palliative care services provide Difficult to arouse = stupor advice around the clock and can assist general Unarousable = coma practitioners. Referral for acutely uncontrol ed symptoms allows urgent follow up from The diagnosis of delirium requires the presence of 1 and 2 plus either 3 or 4 the local palliative care team for ongoing 230 Reprinted from Australian Family Physician Vol. 35, No. 4, April 2006
Until the chemist opens – palliation from the doctor's bag CLINICAL PRACTICE Table 6. Choice of parenteral opioid from the doctor's bag for palliation in a crisis
Advantages
Morphine
May be given subcutaneously If there is a history of intolerance, give with an antiemetic. Avoid if possibility of hypersensitivity Is also effective for dyspnoea Renally cleared – dose reduce in renal failure Clinical effect lasts 3–4 hours Upper dose only limited by side effects, and considered titration minimises these effects Can be used to initiate continuing analgesia with regular oral or ongoing subcutaneous morphine (regularly or by continuous infusion) Tramadol
Can be used if morphine sensitivity or intolerance Has an upper ceiling on dose, therefore not Acts via serotonin and noradrenaline reuptake, therefore the ideal agent for palliation may have a role in complex and neuropathic pain Dose reduce in renal failure, hepatic failure, Duration of effect 6–9 hours and in the elderly Potential interaction with other analgesics, antidepressants and serotonergic agents – may precipitate seizures or serotonergic syndrome management, and additional support for those 10. Man GCW, Hsu K, Sproule BJ. Effect of alprazolam caring for dying people at home.
on exercise and dyspnoea in patients with chronic obstructive pulmonary disease. Chest 1986;90:832–6. 11. Wildiers H, Menten J Death rattle: prevalence, pre- Conflict of interest: none.
vention and treatment. J Pain Symptom Manage 2002;23:310–17.
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