Multiple Symptoms and Multiple Illnesses

The term comorbidity has been defined as follows:

The presence of coexisting or additional diseases with reference to an initial diagnosis or with reference to the index condition that is the subject of study.

Comorbidity may affect the ability of affected individuals to function and also their survival; it may be used as a prognostic indicator for length of hospital stay, cost factors, and outcome or survival.

In the past, the term was not used to define the interplay of specific diseases and multiple symptoms. Here, the term is used to encompass both.

Patients who have advanced, progressive illness and those who are at the end of life rarely present with just one illness or symptom. Many of us will die with or of two or more chronic illnesses. In 1999, 65% of elderly persons in the United States had two or more types of chronic illnesses. Elderly patients comprise most of those in need of palliative and end-of-life care. In 2002, three fourths of the deaths in the United States occurred in persons aged 65 years and older. Five of the six leading causes of death in this age group were chronic illnesses, including cancer, neurodegenerative diseases such as Alzheimer’s disease, and organ (particularly cardiac) or system failure. The frequency and mortality rate of cancer increase with advancing years. The incidence of neurodegenerative diseases and advanced pulmonary, cardiovascular, and renal diseases also increases dramatically with age. Patients with diagnoses other than cancer often have less predictable and longer illness trajectories. As a result, accurate prognostication, goals of care, and therapies are more difficult, and the issues of comorbidity are more prevalent.

Many patients who are at the end of life are also elderly persons who have experienced considerable changes in their function, drug pharmacokinetics, and social situations that also complicate management. Moreover, many clinical research studies exclude patients with significant comorbidities, thus making the application of the results of these studies less effective in the palliative care population. Underreporting of symptoms is a well-documented phenomenon in the elderly that makes symptom management difficult. Concern about being a burden on one’s family may be one reason that symptoms are underreported.

Comorbid illnesses and symptoms may make prognosticating that much more difficult, may drastically change the prognosis of an illness such as cancer, may interfere with responses to therapy, and may pose a significant, independent threat to high-quality end-of-life care. Patients with comorbid conditions also have a variety of lifestyles, economic capabilities, families, and other psychosocial and spiritual issues that they bring with them into the terminal phase of their illnesses, and these factors can affect suffering and management of the illnesses.

The cost of care is also considerably affected by comorbid conditions. In one study of congestive heart failure, costs increased with each comorbid condition, especially diabetes and renal failure. In 1999, 65% of the U.S. elderly population had two or more types of chronic medical conditions. Per capita annual expenditures were $1154 for those with one type, $2394 for those with two types, $4701 for those with three, and $13,973 for those with four or more chronic medical conditions.

Superimposed on this multiple illness background and the age factor is the prevalence of many symptoms produced by these illnesses in addition to a superadded terminal illness such as cancer. Pain as a symptom has been the major focus of attention in palliative and end-of-life care. Poor pain treatment continues to be documented. Uncontrolled pain can add to suffering in multiple ways, and compliance with therapeutic regimens may decrease. Depression, loss of function, anxiety, and family problems may result. Pain management that also overlooks the need to manage its common adverse effects such as constipation, sedation, and decreased concentration or cognitive dysfunction can end up adding to suffering rather than reducing it.

Pain is rarely the only symptom, however. Other physical symptoms are common in patients near the end of life and are often not assessed adequately. This deficiency contributes substantially to suffering in terminally ill patients. One recent large study of patients with advanced cancer assessed the prevalence of symptoms. The results are detailed in Table 6-1 .

Table 6-1

Symptom Prevalence in 922 Patients with Advanced Cancer *

Symptom	Number	Percent
Pain	775	84
Easy fatigue	633	69
Weakness	604	66
Anorexia	602	65
Lack of energy	552	60
Dry mouth	519	56
Constipation	475	52
Early satiety	473	51
Dyspnea	457	50
Sleep problems	456	50
Weight loss	447	49
Depression	376	41
Cough	341	37
Nausea	329	36
Edema	262	28
Taste change	255	28
Hoarseness	220	24
Anxiety	218	24
Vomiting	206	22
Confusion	192	21
Dizzy spells	175	19
Dyspepsia	173	19
Belching	170	18
Dysphagia	165	18
Bloating	163	18
Wheezing	124	13
Memory problems	108	12
Headache	103	11
Hiccup	87	9
Sedation	86	9
Aches/pains	84	9
Itch	80	9
Diarrhea	77	8
Dreams	62	7
Hallucinations	52	6
Mucositis	47	5
Tremors	42	5
Blackout	32	4

* From Walsh D, Rybicki L: Symptom clustering in advanced cancer, Support Care Cancer 14:831–836, 2006.

A systematic search of medical databases and textbooks identified 64 original studies reporting the prevalence of 11 common symptoms among patients with end-stage cancer, acquired immunodeficiency syndrome, heart disease, chronic obstructive pulmonary disease, or renal disease. This review consistently showed a high prevalence of almost all considered symptoms: pain, confusion, delirium, cognitive failure, depression, low mood, sadness, anxiety, dyspnea, fatigue, weakness, anorexia, nausea, diarrhea, constipation, insomnia, and poor sleeping.

Most symptoms were found in one third or more of patients, and multiple symptoms occurred for all five diseases. However, two symptoms, pain and fatigue, were common in all five diseases, occurring in 34% to 96% and 32% to 90%, respectively. Breathlessness was common in most conditions, but it was most consistently found among patients with chronic obstructive pulmonary disease (minimum, 90%) and heart disease (minimum, 60%).

Another recent study reviewed the prevalence of symptoms in 90 older U.S. adults. In this group, 42% had a diagnosis of chronic obstructive pulmonary disease, 37% had a diagnosis of congestive heart failure, and 21% had a diagnosis of cancer. The prevalence of symptoms, as measured by the Edmonton Symptom Assessment Scale, ranged from 13% to 87%. Limited activity, fatigue, physical discomfort, shortness of breath, pain, lack of well-being, and problems with appetite were experienced by the majority (>50%) of participants. Smaller proportions of participants experienced feelings of depression (36%), anxiety (32%), and nausea (13%).

The prevalence of these symptoms in palliative care patients varied widely in other reports and depended on the trajectory of the patients’ illnesses, the assessment tools used, and the selection of patients. These symptoms are often either undertreated or not recognized across care settings. More systematic assessments using multiple tools will uncover more symptoms, but options for effective treatment of these symptoms may be limited and often require numerous medications that can pose significant risks and added suffering because of adverse drug effects and interactions.

There is growing literature around the issues of multiple symptoms and clusters of symptoms. Research on symptoms has generally been focused on single symptoms. Patient age, gender, performance status, primary disease, race, symptom severity and distress, and symptom assessment method influence symptom prevalence and epidemiology. Symptom prevalence may also have socioeconomic factors. Symptom clusters such as pain, depression, and fatigue seem to be linked clinically and may have similar interdependent, pathophysiological processes. Patients with cancer who have multiple symptoms have worse outcomes. The synergistic effect of symptoms that constitute a symptom cluster remains to be determined. Palliative care has traditionally understood the need to address multiple issues, but the comorbidities engendered by these multiple symptoms, comorbid illnesses, and multiple care systems provide new challenges in management.

Illustrative Case Studies

Case Study 6-1

Albert is a 62-year-old man with advanced, non–small cell lung cancer with liver and bone metastases. He also has a 30-year history of diabetes mellitus and is insulin dependent. Diabetic complications include increased creatinine (175 mg/L), peripheral neuropathy, hypertension, hyperlipidemia, and mild macular degeneration. He was quite obese (at least 20 kg overweight) until recently and has severe osteoarthritis in one knee. He has developed increased, burning pain in both feet since undergoing chemotherapy. His bone pain and knee pain have been difficult to control with opioids (oxycodone), and he has had two episodes of toxicity from his opioids. Other symptoms include decreased appetite with a weight loss of 10 kg, several hypoglycemic episodes, a sacral ulcer (stage 2), and generalized weakness. He is taking multiple medications, including atorvastatin, ramipril, insulin, sustained-release oxycodone, immediate-release oxycodone, desipramine, sennosides, and lactulose. He was referred to the palliative care service for pain management.

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