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Other Symptoms and Emergencies in Palliative Care

Other Symptoms and Emergencies in Palliative Care. Module 4. Patients with advanced cancer have a high prevalence of multiple symptoms. Walsh et al. 2000. Nausea & Vomiting. Associated with GIT, gynae and breast primary cancer Metastases to lung, pleura, peritoneum

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Other Symptoms and Emergencies in Palliative Care

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  1. Other Symptoms and Emergencies in Palliative Care Module 4

  2. Patients with advanced cancer have a high prevalence of multiple symptoms Walsh et al. 2000

  3. Nausea & Vomiting • Associated with • GIT, gynae and breast primary cancer • Metastases to lung, pleura, peritoneum • Female, <65 years of age • Opioid treatment • Worsening performance status • Many causes, frequently multi-factorial Walsh et al. 2000; Mannix 2005

  4. Nausea & Vomiting • Causes of nausea • Constipation • Gastric outlet obstruction, SBO • Hepatomegaly • Autonomic failure, gastric stasis • Medications (chemotherapy, analgesia, antibiotics, etc.) • Metabolic derangement, e.g. hypercalcaemia, uraemia • Raised ICP

  5. Nausea & Vomiting • Physiology (in brief) • Vomiting is controlled by the Vomiting Centre (VC) • A number of adjacent, co-ordinated sites located in the lateral reticular formation of the medulla • Physiology of nausea is not well understood, may arise when stimuli excite the VC without sufficient amplification to trigger the vomiting cascade.

  6. The Vomiting Centre (VC) • Afferent input to the VC • 1. Chemoreceptor Trigger Zone (CTZ) • 2. Vagal viscera • 3. Other sympathetic afferents from viscera • 4. Labyrinth of the inner ear • 5. Cerebral cortex & limbic system • Important neurotransmitters: • H1, M, 5HT3

  7. The Chemoreceptor Trigger Zone (CTZ) • Located in the floor of the 4th ventricle • Effectively, no blood brain barrier • Chemo-sensitive nerve cell endings are bathed in CSF which is in chemical equilibrium with blood • Important neurotransmitters are: • D2, 5HT3

  8. Other afferents • Vagal and Sympathetic afferents • Activated by gastric irritation, gastric distension, intestinal obstruction, constipation, liver disease etc. • Important neurotransmitters are: D2, 5HT4 • Vestibular nuclei • Motion & position sickness, labyrinthitis • Important neurotransmitters: M, H1

  9. Other afferents continued • Higher centres / CNS • Anxiety, fear, raised ICP, cerebral lesion, meningitis, senses (taste, smell). • Neurotransmitter: H1

  10. Lichter, 1993

  11. Choosing an anti-emetic • Identify the probable cause(s) • Treat reversible causes • Pharmacological measures • Consider the likely pathway and neurotransmitters involved in order to select the most appropriate agent • Ensure delivery via an appropriate route • Titrate and review regularly • If symptoms persist, re-evaluate

  12. Anti-emetic choice • Butyrophenones • Haloperidol, droperidol • D2 receptor antagonists • Uses: opioid induced nausea, chemical or metabolic causes • Prokinetics • Metoclopramide, domperidone • D2 peripheral receptor antagonists • Uses: gastric stasis, ileus

  13. Anti-emetic choice, cont. • Phenothiazines • Prochlorperazine, chlorpromazine, levomepromazine • Useful for CNS causes, general measure. • Antihistamines • Cyclizine, diphenhydramine, promethazine • Mainly active centrally • Uses: Intestinal obstruction, peritoneal irritation, raised ICP, vestibular causes.

  14. Anti-emetic choice, cont. • 5HT3 antagonists • Ondansetron, tropisetron • Uses: chemotherapy, radiotherapy, post-operative nausea & vomiting. • Other drugs • Corticosteroids • Benzodiazepines • Substance P neurokinin-1 receptor antagonist Mannix 2005; Tramer 1997

  15. Malignant Bowel Obstruction • Well recognised complication of advanced abdominal/pelvic malignancy • 5-51% in ovarian cancer • 4-28% in colorectal cancer • Relapsing, remitting • Partial or complete obstruction • Small, large bowel or both involved • Single or multiple levels of obstruction Jatoi et al. 2004; Mercandante et al. 2007

  16. Pathophysiology of MBO • Intra-luminal obstruction • Intra-mural extension • Extramural compression / obstruction • Motility disorder, directly by tumour infiltration or indirectly drugs, constipation • Benign causes - 11-32% Feuer et al. 2000; Ripamonti and Bruera 2002; Jatoi et al. 2004

  17. Is intervention appropriate? • Even in very advanced cancer, interventional approaches may provide best palliation eg. Surgery for bowel obstruction, radiotherapy for haemoptysis • Important to evaluate carefully – no place for nihilism. Instead require careful decision-making. Miller et al. 2000

  18. Evidence for surgery in MBO • Cochrane Review 2000: retrospective case series, unable to draw any conclusions • Helyer et al 2007, retrospective review. ? More optimistic. 80% tolerating solid food and returning home. Feuer et al. 2000; Helyer et al. 2007

  19. Predictors of poor outcome with surgery in MBO • Compromised nutrition / LOW • Heavy tumour burden • Ascites • Extensive prior / or recent chemo • Previous XRT • Low albumin • Palpable abdominal tumour • Advanced age • Multiple levels of obstruction / carcinomatosis

  20. Role of stents in MBO • Accepted alternative for definitive palliative management, ‘bridge to surgery’ in the acute setting • Used in gastric outlet, proximal small bowel and colonic obstruction • Limited role if obstruction multilevel Tsuramaru et al. 2007; Khot et al. 2000

  21. Decompression in MBO • Nausea and vomiting control 83-93% • NGT - Cx nose and throat pain, abscess, nasal cartilage erosion, social isolation • Gastrostomy - Cx tube obstruction/replacement, skin break down, abscess, pain Jatoi et al. 2004

  22. Irreversible bowel obstruction in advanced cancer • Is there a role for surgery or for stents? • Is it medically reversible? • Disordered motility • Bowel rest • Corticosteroids • Prokinetic agents – metoclopramide • Stool softeners / enemas • Symptom control

  23. Corticosteroids in MBO • Anti-emetics (central action) • Co-analgesic • Anti-inflammatory • ?Anti-secretory • Cochrane review (updated 2006) • trend (NS) towards resolution MBO, 6-16mg dexamethasone. Minimal SE’s. • ? Role in motility disorder obstruction Mercandante 2007; Feuer and Broadley 2000

  24. Symptom ControlLandmark paper - Baines et al. 1985 Jatoi et al. 2004

  25. Anticholinergics • Hyoscine butylbrombide (Buscopan), glycopyrolate • Antisecretory • Action via competitive inhibition muscarinic receptors inhibit neural transmission in the bowel wall

  26. Somatostatin Analogs • Octreotide • Anti-secretory • Reduced gastric and intestinal secretion and bile flow by complex endocrine mechanisms (including VIP) • 3 RCT’s confirm superiority over hyoscine in a total of 103 patients Ripamonti et al. 2000; Mercandante et al. 2007

  27. Analgesics • Morphine cornerstone • Ensure absorption reliable • Buscopan for colic / spasmodic pain

  28. Centrally acting antiemetics • Cyclizine (antihistamine) and hyoscine scopolamine (anticholinergic) act on the vomiting centre • Haloperidol (D2 antagonist) action on chemoreceptor trigger zone • Ondansetron (5HT3 antagonist) also on CTZ - constipation, expensive • Corticosteroids

  29. Daily care if irreversible MBO • Assessment, institution of symptomatic measures and monitor response • Mouth care • General nursing care • Careful fluid administration as appropriate • Many patients will choose to have an oral intake for comfort, even if that leads to vomiting • Not necessary to measure electrolytes

  30. Decision points in MBO • Is surgery /stenting appropriate? • Is decompression needed? Should a gastrostomy be considered? • Is this potentially medically reversible? • What drugs are appropriate for symptom control and what route?

  31. Dyspnoea • “a term used to characterize a subjective experience of breathing discomfort that is comprised of qualitatively distinct sensations that vary in intensity. The experience derives from interactions among multiple physiological, psychological, social and environmental factors, and may induce secondary physiological and behavioural responses” • Implications: • Subjective • Responsive to physiological, and other factors. • Not dependent upon oxygen saturations American Thoracic Society, 1999

  32. Dyspnoea in advanced illness • Common: • Cancer: ranges from 19-64% • Non-malignant: very common, about 70% on general medical wards • Associated with poor prognosis • Qualitative aspects to dyspnoea: Group of 51 patients with dyspnoea • wheezy (57%) • rattling (25%) • Also affective adjectives: • constricting (22%), • disabling (61%) • distressing (51%) • Also extreme terms: • stifling (14%) • suffocating (16%) and asphyxiating (2% or 1 patient). Chan et al. 2005; Solano et al. 2006; Sigurdardottir and Haugen 2008; Mercandante 2000; Philip 2008 (personal comm.)

  33. Possible causes of dyspnoea in advanced cancer • Cancer related (directly): eg. pulmonary metastases, parenchymal infiltration, airway obstruction, pleural effusion, pericardial effusion. • Cancer treatment related: eg. radiation pneumonitis, bleomycin lung, PCP secondary to immunosuppression • Indirectly cancer related: eg. Anaemia, cachexia • Related to co-morbidities: eg. LVF, COPD

  34. Approach to dyspnoea in advanced illness • Thorough multidimensional assessment • History, examination, appropriate investigations • Evaluation of severity according to patient reports: quantitative and qualitative reports • Development of differential diagnosis • Reverse potential reversible causes • (where possible) • Consideration of symptomatic treatments

  35. Role of opioids in treatment of dyspnoea • Effect acknowledged • Cochrane Systematic Review 2001 • Mechanism unknown • Lack of data about routes, starting dose, optimal dosage • No good evidence of clinical benefit with nebulised morphine Jennings et al. 2001; Ben - Aharon et al. 2008

  36. Other pharmacological treatments of dyspnoea • Benzodiazepines • Widely used in clinical practice • Very little evidence (only one RCT) • Corticosteroids • Bronchodilators • (Local anaesthetic agents) • (Nebulised frusemide) Navigante et al. 2006; Chan et al. 2005

  37. Non-pharmacological treatments of dyspnoea • Behavioural approaches: • Psycho-social support and empowerment • Controlled breathlessness techniques • Emotional and problem-focused coping • Evidence of benefit in the literature Ben-Aharon et al. 2008; Chan et al. 2005

  38. Role of oxygen in treatment of dyspnoea • Evidence of benefit in hypoxic patients • BUT, response does not correlate with oxygen saturations • Therefore SpO2 not useful to monitor response, use a symptom based assessment • Reasonable to trial if the patient is hypoxic or dyspnea improves • Remember the burdens of O2 therapy Philip et al. 2006; Ben-Aharon et al. 2008

  39. Palliative Emergencies • Require prompt diagnosis and treatment • Examples: • Spinal cord compression • Major haemorrhage • Acute airway obstruction • Agitated delirium in the dying patient • Acute pain crisis • Seizures • Cardiac tamponade, etc….

  40. Spinal cord compression • Assume until proven otherwise in a patient with back pain and cancer; known or likely bony involvement • Aim is early detection • 4mg QID dexamethasone • Imaging , usually MRI • Radiation oncology, neurosurgery referrals Falk and Fallon 1997; Caraceni et al. 2005

  41. Airway Obstruction • Subacute presentations (eg. with stridor) may be managed with radiotherapy or interventional procedures such as laser and stenting. Commence steroids. • In acute presentations, there may be limited reversibility and/or interventions may be inappropriate • Aggressive symptom palliation • Oxygen, morphine, benzodiazepines (for sedation)

  42. Major haemorrhage • Bleeding may have a reversible cause, which should be addressed as appropriate • Consider radiotherapy, tranexamic acid, embolisation, surgery • In the case of major bleeding where intervention is not appropriate and/or clearly a terminal event • Aggressive symptom palliation • Green towels • Provide comfort, clam and reassurance

  43. Agitated delirium in the dying patient • Common, very distressing • Deserves its place amongst ‘emergencies’ • While often multifactorial, reversal should be considered when / if appropriate • However in the actively dying patient, aggressive and timely management is essential • Anti-psychotics first line • Palliative sedation therapy may be necessary

  44. General considerations • Anticipation of problems and plan for care accordingly • Focus on patient directed goals not disease directed goals • Time critical • Accurate and careful clinical skills with willingness to reassess and reconsider

  45. When might additional palliative care advice be sought? • Palliative care could offer: • Skills in pain /symptom management • Advanced communication skills • Determining what is important to the individual patient aims & goals • Assistance with clinical decision making • Discharge planning incorporating patient goals and mobilising appropriate hospital and community based supports. • Needs-based referral, not prognosis dependent

  46. References • American Thoracic Society: medical section of the American Lung Association Dyspnea: Mechanisms, assessment, and management: a consensus statementAmerican Journal of Respiratory and Critical Care Medicine 1999;159:321-340 • Ben-Aharon I, Gafter-Gvili A, Paul M, Leibovici L, Stemmer SM Interventions for alleviating cancer-related dyspnea: a systematic reviewJournal of Clinical Oncology 2008;26(14):2396-2404 • Caraceni A, Martini C, Simonetti F Neurological problems in advanced cancer IN Oxford Textbook of Palliative Medicine 3rd Edition Edited by Doyle D, Hanks G, Cherny N and Calman K 2005:702-726 • Chan K, Sham MMK, Tse DMW, Thorsen AB Palliative medicine in malignant respiratory diseases IN Oxford Textbook of Palliative Medicine 3rd Edition Edited by Doyle D, Hanks G, Cherny N and Calman K 2005:587-618 • Escalante CP, Martin CF, Elting LS, Price KJ, Manzullo EF, Weiser MA, Harle TS, Cantor SB, Rubenstein EB Identifying risk factors for imminent death in cancer patients with acute dyspneaJournal of Pain and Symptom Management 2000:20(5):318-325 • Falk S, Fallon M ABC of palliative care: emergenciesBritish Medical Journal 1997;315:1525-2528 • Feuer DJ, Broadley KE Corticosteroids for the resolution of malignant bowel obstruction in advanced gynaecological and gastrointestinal cancerThe Cochrane Database Systematic Review 2000;2:CD001219 • Feuer DJ, Broadley KE, Shepherd JH, Barton DP Surgery for the resolution of symptoms in malignant bowel obstruction in advanced gynaecological and gastrointestinal cancer The Cochrane Database Systematic Review 2000;4:CD002764 • Helyer LK, Law CHL, Butler M, Last LD, Smith AJ, Wright FC Surgery as a bridge to palliative chemotherapy in patients with malignant bowel obstruction from colorectal cancerAnnals of Surgical Oncology 2007;14(4):1264-1271 • Jatoi A, Podratz KC, Gill P, Hartmann LC Pathophysiology and palliation of inoperable bowel obstruction in patients with ovarian cancerJournal of Supportive Oncology 2004;2(4):

  47. References • 323-337 • Jennings AL, Davies AN, Higgins JP, Broadley K Opioids for the palliation of breathlessness in terminal illnessThe Cochrane Database Systematic Review 2001;4:CD002066 • Khot UP, Lang AW, Murali K, Parker MC Systematic review of the efficacy and safety of colorectal stents British Journal of Surgery 2002;89:1096-1102 • Lichter I, Which Antiemetic?Journal of Palliative Care 1993;9(1):42-50 • Mannix, KA Palliation of Nausea and Vomiting IN Oxford Textbook of Palliative Medicine 3rd Edition Edited by Doyle D, Hanks G, Cherny N and Calman K 2005:459-468 • Mercandante S, Casuccio A, Fulfaro F The course of symptom frequency and intensity in advanced cancer patients followed at home Journal of Pain and Symptom Management 2000:20:104-112 • Mercandante S, Casuccio A, Mangione S Medical treatment for inoperable malignant bowel obstruction: a qualitative systematic reviewJournal of Pain and Symptom Management 2007:33(2):217-223 • Miller G, Boman J, Shrie I, Gordon PH Small-bowel obstruction secondary to malignant disease: an 11-year auditCanadian Journal of Surgery 2000;43(5):353-358 • Navigante AH, Cerchietti LC, Castro MA, Lutteral MA, Cabalar ME Midazolam as adjunct therapy to morphine in the alleviation of severe dyspnea perception in patients with advanced cancerJournal of Pain and Symptom Management 2006;31(1):38-47 • Ripamonti C and Bruera E Palliative management of malignant bowel obstructionInternational Journal of Gynaecological Cancer 2002;12:135-143

  48. References • Ripamonti C, Mercandante S, Groff L, Zecca E, De Conno F, CasuccioA Role of octreotide, scopolamine butylbromide and hydration in symptom control of patients with inoperable bowel obstruction and nasogastric tubes: a prospective randomised trialJournal of Pain and Symptom Management 2000;19(1):23-34 • Singurdardottir KR and Haugen DF Prevalence of distressing symptoms in hospitalised patients on medical wards: a cross-sectional study BMC Palliative Care 2008;7:16 • Solano JO, Gomes, B and Higginson IJ A comparison of symptom prevalence in far advanced cancer, AIDS, heart disease, chronic obstructive pulmonary disease and renal diseaseJournal of Pain and Symptom Management 2006;31(1):58-69 • Steinhauser KE, Christakis NA, Clipp EC, McNeilly M, McIntyre L, Tulsky JA Factors considered important and the end of life by patients, family, physicians and other care providers Journal of the American Medical Association 2000;284(19):2476-2482 • Tsurumaru D, Hidaka H, Okada S, Sakoguchi T, Matsuda H, Matsumata T, Noiyama H, Utsunomiya T, Irie H, Honda H Self expandable metallic stents as palliative treatment for malignant colorectal obstructionAbdominal Imaging 2007;32(5):619-23 • Tramer MR, Moore RS, Reynolds DJM, McQuay HJ A quantitative systematic review of ondansetron in established post-operative nausea and vomitingBritish Medical Journal 1997;314:1088-1092 • Walsh D, Donnelly S, Rybicki L The symptoms of advanced cancer: relationship to age, gender, and performance status in 1,000 patientsSupport Care Cancer 2000;8(3):175-179

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