Barriers to Rehab in Surgical Onc Patient

Journal of Surgical Oncology 2007;95:427–435

Barriers to Pain Management in the Rehabilitation of the Surgical Oncology Patient 1

JULIE SILVER, MD1,2,3* AND R. SAMUEL MAYER, MD4,5 Department of Physical Medicine and Rehabilitation, Harvard Medical School, Boston, Massachusetts 2 Spaulding Rehabilitation Hospital, New Hampshire, Massachusetts 3 Massachusetts General and Brigham and Women’s Hospitals, Boston, Massachusetts 4 Department of PM&R, Johns Hopkins University School of Medicine, Baltimore, Maryland 5 Inpatient Rehabilitation, Johns Hopkins Hospital, Baltimore, Maryland

Virtually every surgical oncology patient faces pain, and it can become a major barrier to rehabilitation and quality of life. Pain must be assessed as to its severity, etiology (somatic, visceral, or neuropathic), causation (directly from malignancy or from treatment side effects), and its impact on daily function. Treatments can include physical modalities, exercise, opioids, adjuvant medications, and interventional techniques. Barriers to treatment may include side effects, finances, and attitudes.

New technologies in medication delivery systems, intrathecal pumps, injections, and surgery have greatly strengthened the armamentarium available to manage pain.

J. Surg. Oncol. 2007;95:427–435.

ß 2007 Wiley-Liss, Inc.

KEY WORDS: cancer pain; surgical oncology; rehabilitation; opioid

INTRODUCTION Pain is almost a universal experience in the surgical cancer patient. However, post-operative pain specifically due to surgical interventions is but one type of pain that patients may experience. The various aspects of pain that include whether it is neuropathic, somatic, or visceral; whether it is malignant or non-malignant; whether it is acute or chronic; and whether it is mild, moderate, or severe, can all impact pain relief and function in the surgical oncology patient.

Though pain has always been a priority in the care of patients undergoing surgical procedures, recently, it has become of paramount importance. In fact, treating pain is now considered the ‘‘fifth’’ vital sign, and when hospitals undergo accreditation, they must show documentation that during the admission of a patient the vital signs— temperature, pulse, respiration, and blood pressure are taken along with a screening question on pain. According to the Comprehensive Accreditation Manual for Hospitals: The Official Handbook, ‘‘The following statement on pain management is posted in all patient care areas (patient rooms, clinic rooms, waiting rooms, etc.). . . All patients have a right to pain relief [1].’’ Medical personnel are now required to show that they work together with the patient and families to ‘‘establish a goal for pain relief and develop and implement a plan to ß 2007 Wiley-Liss, Inc.

achieve that goal.’’ These regulations are a very important step in trying to make pain relief a priority for every patient who enters the hospital.

Physicians must overcome a number of barriers to manage cancer pain, including treatment side effects, financial limitations, and negative attitudes. However, there exists a growing armamentarium of therapies available to cancer patients to better control pain and improve quality of life.

PREVALENCE OF PAIN IN CANCER SURVIVORS One can assume that the prevalence of immediate post-operative pain among surgical cancer patients is extremely high. In a random sample of 250 adults who Julie Silver is an Assistant Professor in Harvard Medical School, Attending Physician in Spaulding Rehabilitation Hospital, and an Associate in Physiatry in Massachusetts General and Brigham and Women’s Hospitals, Boston, Massachusetts; R. Samuel Mayer is a Clinical Associate in Johns Hopkins University School of Medicine and a Medical Director in Inpatient Rehabilitation, Johns Hopkins Hospital. *Correspondence to: Julie Silver, MD, 570 Worcester Road, Boston, MA. Fax: 508-872-1205. E-mail: jksilver@bics.bwh.harvard.edu Received 8 January 2007; Accepted 9 January 2007 DOI 10.1002/jso.20780 Published online 21 March 2007 in Wiley InterScience (www.interscience.wiley.com).

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had undergone various surgical procedures (not specifically cancer patients), a follow-up telephone survey revealed that approximately 80% experienced acute pain after surgery and of these, 86% had moderate, severe, or extreme pain with more patients experiencing pain after discharge than before discharge. The authors concluded, ‘‘Despite an increased focus on pain management programs and the development of new standards for pain management, many patients continue to experience intense pain after surgery’’ [2]. Clearly the management of pain in surgical oncology patients both perioperatively and during their post-operative rehabilitation needs much more attention from clinicians.

Although pain is a significant problem in cancer patients, its prevalence varies considerably. Approximately one-third of patients report pain during active therapy and in those with advanced disease, this number is approximately double at two-thirds [3–10]. Moreover, the undertreatment of cancer pain has been well documented.

According to the standards set by the World Health Organization (WHO), as many as 40% of ambulatory cancer survivors receive inadequate analgesia [11,12].

Pain after surgery can be due to a variety of factors including the type of procedure (e.g., lumpectomy versus mastectomy in breast cancer), follow-up cancer treatment (e.g., chemotherapy and radiation treatment can delay wound healing), and post-operative scarring, fibrosis, and loss of range of motion of soft tissues (e.g., frozen shoulder after mastectomy). Since pain is directly related to the type of surgery and the post-operative complications, it is imperative to carefully consider the surgical options in the context of both saving or extending a patient’s life and the quality of life post-operatively. For example, in a study done by van Wilgen and colleagues, a total of 137 patients with neck dissections were followed post-operatively up to at least 1 year, in order to identify shoulder complaints. Shoulder complaints were most common in those who had undergone postero-lateral neck dissection (66.7%) and least common in those who had undergone supraomohyoid neck dissection (20%) [13].

IDENTIFYING SOURCES OF PAIN IN CANCER PATIENTS In the immediate post-operative period, pain is often primarily due to the procedure itself. However, in the general cancer population, pain is usually due to one of three factors: (1) tumor invasion into pain-sensitive structures, (2) pain due to treatment, including surgical interventions, (3) pain that is unrelated to cancer or its treatment. Identifying the type of pain may help in assessing its underlying cause and then directing appropriate treatment. Common types of pain include the following [14].

Journal of Surgical Oncology DOI 10.1002/jso

Somatic Pain

This is often described as a dull, sharp, aching, or throbbing pain. Since this type of pain is often a result of bone metastasis, it follows that it is usually constant and well localized. This is typically seen in surgeries involving muscle and bone.

Visceral Pain

This type of pain is dull, aching, or a pressure sensation. Since it is often caused by the abnormal stretching or distention of the smooth muscle wall of the viscera or ischemia or irritation of the visceral muscles or mucosa, it is characterized (and differs from somatic pain) by its intermittent ‘‘colicky’’ nature. Abdominal surgery commonly causes visceral pain.

Neuropathic Pain

The presentation of this type of pain is considerably different from the others described in that it is a burning, shooting, electrical, or lancinating type of pain that is sometimes associated with paresthesias and numbness.

Neuropathic pain is a result of injury to nerve structures.

Etiologies include direct tumor invasion into peripheral nerves or plexusesl toxicity to peripheral nerves from chemotherapeutic agents, and surgical procedures, which cause injury to nerve, especially when large debulking of tumors is required.

IMPACT OF PAIN ON QUALITY OF LIFE The impact of pain on quality of life can be quite profound. The concept of quality of life, somewhat controversial and not easily defined, is measured in research studies in a variety of ways (listed in Table I).

The WHO definition of health is that it is a state of complete physical, mental and social well-being and not merely the absence of disease or infirmity. This definition considers, though doesn’t specifically state, that quality of life is an important aspect of health. Pain, regardless of its origin, not only impacts the physical functioning of a patient (e.g., someone with severe low back pain may not be able to sit at her desk and work in her usual manner), TABLE I. Measures of Quality of Life 67–76 Functional Assessment of Cancer Treatment (FACT) Cancer Rehabilitation Evaluation System (CARES) Visual Analog Scale Global Quality of Life (VASQOL) Sickness Impact Profile (SIP) Nottingham Health Profile (NHR) Medical Outcomes Study Short Form 36 (SF-36) European Organization for Research and Treatment of Cancer (EORTC) modular questionnaire Rotterdam Symptom Checklist (RSCL)

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but also many other aspects of daily life including attending to family, social and work obligations. Table II lists some of the important ways in which pain can interfere with quality of life.

Pain is a physical symptom with many psychological ramifications, particularly in cancer survivors. For example, in a study by Tishelman and colleagues [15] assessing symptoms in 400 patients who were newly diagnosed with inoperable lung carcinoma, the researchers found that breathing, pain, and fatigue were associated with the most distress. They concluded, ‘‘Breathing and pain appeared to function as icons representing threats associated with lung carcinoma, with distress described as related to the past and the present and to expectations for the future.’’ In another study by Rustoen and colleagues [16] in which they examined to what extent demographic and diseasespecific variables affected pain in cancer patients, they found that of the 1,435 patients who complete questionnaires, 60% reported some pain. Significant predictors of pain included the type of cancer, presence of metastases, and time until death. Interestingly sex, age, level of education, and co-habitation were not related to pain, but employment status was.

Another important pain issue is that in cancer it is often found as part of a ‘‘symptom cluster.’’ For example, fatigue, pain and depression are frequently simultaneously present and each contributes to the severity of the other two symptoms. In the case of a patient with pain as part of a cluster of other symptoms, this cluster can significantly negatively impact quality of life and it is important to address not only the pain, but the other symptoms as well.

PAIN RELIEF AS A DETERMINANT OF FUNCTION AND IMPROVED QUALITY OF LIFE The research in this area is quite deficient and it is difficult to draw generalized conclusions. Seemingly, improving pain in cancer patients would lead to better function and improved quality of life, though there is a distinct lack of literature to demonstrate this. For

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example, in one study Talbot and colleagues [17] evaluated surgery substantially improved functional and quality of life outcomes in 67 patients with nonspinal bone metastases. Their conclusions were, ‘‘There were no improvements in the Short Form-36 mental and physical summary scales of the patients. The number of patients using pain medication did not decrease. Patients had functional improvement after surgical treatment of bone metastases, even patients with a limited life expectancy.’’ This study was complicated by a high rate of attrition due to death and loss to follow-up. The authors of this study also noted, ‘‘. . .improvements in pain control and function occurred as early as 6 weeks postoperatively. . . Our findings support the rule of a 6-week life expectancy to consider surgery’’ [17].

In another study of 216 Chinese cancer patients with metastatic disease, the findings were that increasing severity of pain was associated with poorer functioning and that patients with well-controlled (mild) pain did not differ significantly from that of patients without pain [18]. Meurser and colleagues [19] surveyed the prevalence, etiology, and severity of pain in 593 cancer patients. These authors concluded that the ‘‘high prevalence and severity of many symptoms in far advanced cancer can be reduced, if pain treatment is combined with systematic symptom control.’’ Systemic symptoms included nausea, constipation, mood changes, fatigue, anorexia, and a host of others.

MEDICATIONS Physicians should tailor pain medications to individual patient’s needs. Certain drug classes can help more effectively treat specific pain generators—visceral versus musculoskeletal versus neuropathic origins [20] (NCCN category 1). Table III delineates these medications. One must, of course, also take into account side effects and contraindications. Furthermore, an accurate history of the patient’s previous pain medication use with the response and dosing can tremendously aid the physician in adjusting or modifying pain regimens.

Opioids

TABLE II. Pain Interfering With Quality of Life Interference with appetite, sleep, and other physical functions Reduced memory and concentration Decreased ability to work Loss of interest or other barriers to physical intimacy Difficulty participating in home activities (e.g., household chores, caring for children, etc.)

Limited social activity and engagements Decline in financial resources Change in spiritual connections (e.g., fear of dying, etc.)

Loss of autonomy and marginalized at home, work, and in social contexts Journal of Surgical Oncology DOI 10.1002/jso

Opioids act on several receptor sites in the brain and spinal cord (delta, kappa, mu, and others) by complex mechanisms, which are active areas of research in neuron-psycho-pharmacology [21]. While it is a gross over simplification for this brief overview, delta receptors primarily affect nocioception, kappa affect mood and dependence and mu affect gastrointestinal motility.

Pharmacologists are working to design new drugs, which preferentially bind to the intended receptor, but current opioids on the market are fairly indiscriminant in their bindings. This accounts for their side effects. The

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Uses

Examples

Opioids

Visceral, soft tissue, bone, neuropathic

NSAIDS*

Soft tissue, bone

TCAs**

Neuropathic, myofascial

SSRIs*** Anticonvulsants

Neuropathic, depressive component Neuropathic

Antispasmodics Benzodiazepines

Spasticity Muscle spasm, anxious component

Fentanyl, hydromorphone, methadone, morphine, oxycodone Celecoxib (COX-2), ibuprofen, nabumetone, naproxen Amitriptyline, desipramine, nortriptyline, cyclobenzaprine Duloxetine, tramadol**** Carbamazapine, clonazepam, gabepentin, pregabelin Baclofen, dantrolene, tizanidine Alprazolam, diazepam, lorazepam

*

Non-steroidal anti-inflammatory medications.

Tricylclic anti-depressant. *** Selective serotonin reuptake inhibitor; ****has properties of SSRI and opioid receptor agonist. **

differences in efficacy and tolerability among oral oxycodone, hydromorphone, and morphine are insignificant [22] (NCCN category 1); hence prescription for an individual patient may take trial and error. Genetic differences among individuals probably play a large role in the variable responsiveness seen.

Despite their side effects, opioids are highly effective in treating cancer pain, and generally well tolerated. In a well-designed RCT, early use of ‘‘strong’’ opioids in advanced cancer patients with mild to moderate pain showed better pain control, fewer changes in therapy and greater satisfaction than those treated with non-opioid or ‘‘weak’’ opioid analgesics [23] (NCCN category 1). This argues against the use of the 1986 World Health Organization’s guidelines for treatment of cancer pain, which had advocated a step-wise approach from ‘‘milder’’ medications to ‘‘strong’’ opioids [24].

Perhaps the most exciting advance in opioid medications in the last decade is the development of novel drug delivery systems. This allows medications to be delivered by numerous routes—oral, intravenous, intramuscular, sublingual, suppository, transdermal, epidural, and intrathecal. This not only allows flexibility in administration when one route of delivery is unavailable (e.g., the patient is NPO), but also flexibility in the onset and duration of the medication dose [25] (NCCN category 1).

Long-acting opioids include extended release forms of oral morphine, oxycodone, and tramadol (an opioid receptor agonist), as well as transdermal fentanyl. They vary in duration from 8 to 72 hr. This allows the patient a more even basal pain relief—‘‘getting ahead of the pain’’—and may reduce the total dose of medication and hence the side effects, while providing more effective relief. Short acting opioids are useful for breakthrough pain, especially during painful events such as wound care dressing changes, physical therapy, or diagnostic procedures. They have onset in 15 to 30 min, and duration Journal of Surgical Oncology DOI 10.1002/jso

of 1–4 hr, allowing quick ‘‘on–off’’ pain relief [26] (NCCN category 1). Intrathecal programmable pumps allow the ultimate in dosing flexibility with the capability of complex basal dosing or periodic boluses. Furthermore, since medication is delivered directly into the cerebral spinal fluid, there tends to be fewer systemic side effects. In one study of patients with intractable cancer pain, intrathecal pumps not only provided significantly better pain relief and less toxicity, but overall 6 month survival increased to 53.9% versus 37.2% in the control group [27] (NCCN category 1).

ADJUVANT MEDICATIONS Non-malignant pain, whether it is due to post-operative healing or other issues, can be treated with a variety of non-opioids including non-steroidal anti-inflammatories (NSAIDS), antidepressants (e.g., tricyclics and selective serotonin reuptake inhibitors), anticonvulsants, muscle relaxants and antispasmodics (refer to Table IV). The efficacy of a particular medication or class of medications may depend on the etiology and character of the pain.

Oral pain medications may be used in combination with TABLE IV. Chemotherapy Agents That Can Cause Peripheral Neuropathy Acetyl-L-carnitine Altretamine Amifostine Cytarabine Docetaxel Ifosfamide Methotrexate Methylene blue Mitotane Oxaliplatin Paclitaxel Thalidomide Vincristine

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each other or with other treatment such as physical modalities or injections.

PHYSICAL MODALITIES Most physical modalities have not been well studied in cancer patients due to the concern of exacerbating an underlying malignancy. Those which are generally believed to be safe include cryotherapy, biofeedback, iontophoresis (transdermal delivery of medication by electrical current), transcutaneous electrical nerve stimulation (TENS), and massage [28]. (NCCN category 2A) Electrical stimulation, regardless of how it is delivered, is generally not done directly over a tumor site. The same is true for massage therapy and superficial heat. Deep heat (e.g., ultrasound and phonophoresis) is usually contraindicated in cancer patients. Spinal traction is contraindicated in those patients with spinal metastases or with significant osteoporosis.

EXERCISE Exercise is certainly helpful in post-operative recovery and can assist with pain reduction if prescribed appropriately. In patients with head and neck cancers or breast cancer, gentle range of motion exercises can help patients resume their ability to function without developing excessive contractures and painful joint motion limitations. Exercise may help immune system functioning and post-operative healing [34] (NCCN category 2B). Cancer patients often become more sedentary during treatment and need encouragement and guidance when it comes to exercise. Exercise has also been shown to help prevent primary cancers from developing and more recently some evidence suggests that it may be helpful in preventing cancer recurrence [29–32]. (NCCN category 2A) The effects of obesity on survival have been well studied in breast cancer patients in more than three-dozen cohort studies [33]. Contraindications to exercise include severe cardiopulmonary limitations or blood dyscrasias.

Complementary and Alternative Medicine (CAM)

This is a huge field of medicine that covers a wide variety of treatments, some which have been studied quite extensively and found to be useful (e.g., meditation, acupuncture, and massage) and many others, which have not been well studied, and may in fact be harmful. In 1993, David Eisenberg and colleagues [35] published a report in the New England Journal of Medicine titled ‘‘Unconventional Medicine in the United States: Prevalence, Costs, and Patterns of Use.’’ They reported that approximately one out of three Americans were using CAM therapies and that approximately two out of three people were not sharing this information with their Journal of Surgical Oncology DOI 10.1002/jso

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primary health provider. Since cancer patients often use CAM therapies without confiding in their doctors or seeking medical advice, it is important for practitioners to take the initiative and inquire as to what treatments patients are already utilizing. This includes dietary regimens, supplements, mind-body therapies, etc. In an excellent review article titled ‘‘Advising Patients Who Seek Complementary and alternative Medical Therapies for Cancer,’’ acupuncture and massage therapy were acceptable CAM pain treatments that may be recommended based on the level of scientific evidence [36] (NCCN category 2A). The National Comprehensive Cancer Network guidelines recommend consideration of the following CAM therapies if pain scores remain 4 or above on a visual analog scale up to 10 points: massage, acupuncture, imager/hypnosis, and relaxation [37]. Of note is that they also recommend reevaulation of pharmacologic management simultaneously.

Interventional Techniques and Surgery

Pain control may warrant a more aggressive approach in some cases. Naturally, risks and benefits must be carefully weighed, particularly in terminally ill patients.

Nevertheless, interventional techniques are sometimes the only way to improve quality of life for these patients.

Implantable intrathecal pumps are discussed above as a delivery system for opioids. Percutaneous vertebroplasty may help some patients with pathologic compression fractures from spinal metastases [38] (NCCN category 2A). In some patients with radicular symptoms or complex regional pain syndromes, spinal cord stimulation may offer pain reduction and a decreased reliance on medications. Cordotomy, myelotomy, and dorsal root entry zone surgeries on the spinal cord are irreversible and reserved for the most desperate of situations [39] (NCCN category 2A).

BARRIERS TO PAIN MANAGEMENT IN THE SURGICAL ONCOLOGY PATIENT Pain itself is, of course, one of the major impediments in the rehabilitation of surgical oncology patients (NCCN category 1) [40]. Multiple barriers limit optimal pain management in surgical oncology patients. Factors, which make pain management so difficult include paucity of literature, side effects from cancer treatments and pain medications, depression, fatigue, and special precautions for cancer patients [41]. Sadly, attitudinal barriers among many health care providers and payers still exist. Wellintentioned governmental regulations to battle the war on drug abuse often catch cancer patients in the crossfire.

Financial barriers created by the dysfunctional American health care system exist both in the private and public sectors.

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Evidenced-Based Practice Barriers

One important barrier to understanding the results of pain treatment in cancer patients is that there is a lack of literature in this area and the studies that have been done have frequently focused on palliative measures for those with metastatic cancer. There is a great deal of research that needs to be done on pain control and quality of life in surgical patients who do not have metastases. Moreover, the research to date has focused primarily on pain relief with opioids, while rehabilitative measures have not been well studied.

Cancer Treatment Side Effects

Because cancer is usually life-threatening, physicians often prescribe aggressive treatments with many side effects, including pain. Surgery is almost by definition painful, despite the many advances in peri-operative anesthesia and post-operative pain management [42].

Newer minimally invasive techniques, for example, laparoscopic gastrectomy, certainly help minimize pain [43]. However, as many as one in four surgical oncology patients may suffer painful nerve damage from surgery, usually at the microscopic level [44]. Radiation therapy also can produce painful side effects including mucositis, headaches, avascular necrosis of the bone, and skin burns.

Chemotherapy can lead to painful peripheral neuropathy [45]. Table IV lists chemotherapy agents most often associated with peripheral neuropathy.

Pain Medication Side Effects

Management of cancer pain most often involves medications. Side effects of many of these medications often present barriers to treatment, and must be balanced with treatment efficacy. This is true of all classes of pain medications; thus prescriptions should be tailored to individual patient situations. Table V lists common side effects of various classes of drugs used for cancer pain.

Opioids are a mainstay of pain management in cancer patients, but often result in delirium, gastrointestinal distress, urinary retention, and, in rare cases, respiratory depression and death. Issues of tolerance, withdrawal, abuse, and divergence are important considerations as

TABLE V. Side Effects by Pain Medication Drug Classification Opioids

Delirium, somnolence, nausea, constipation, urine retention, respiratory depression NSAIDs, COX 2 Peptic ulcers, hypertension, renal insufficiency, cardiovascular events Anticonvulsants Delirium, somnolence, hepatic impairment, Stevens-Johnson, aplastic anemia, hyponatremia Antidepressants Orthostasis, drowsiness, dry mouth, urine retention, cardiac arrhythmias Journal of Surgical Oncology DOI 10.1002/jso

well when prescribing these medications. All of these side effects can be managed to some degree by experienced clinicians. Only rarely should that lead to a patient unable to tolerate enough medication to manage pain [46] (NCCN category 2A).

Delirium and somnolence frequently occur with opioids, particularly at higher doses and in elderly or debilitated patients. Delirium occurs in 26–44% of hospitalized cancer patients. It is important to exclude other causes of delirium such as dehydration or CNS metastasis. The cause is usually multi-factorial, but opioids are a factor in over 60% of delirious cancer patients [47]. Cognitive dysfunction often can be avoided with careful dose titration. When it does occur, doses can be reduced or the medication can be withdrawn as tolerated [48]. In these situations, the prescriber must set goals with the patient and family in terms of pain relief versus cognitive dysfunction. Some patients prefer pain relief at virtually any cost; others are willing to tolerate moderate pain in order to maintain their ‘‘faculties.’’

Alternative medications can sometimes be substituted.

Tramadol is a weak opioid analog that may produce less delirium than traditional opiates [49] (NCCN category 2B). Switching from sustained released morphine to transdermal fentanyl significantly reduced cognitive dysfunction among delirious patients in one open label trial [50] (NCCN category 2B). Opiate-induced somnolence has been counter-acted with methylphenidate in a small Phase 2 trial in breast cancer patients [51] (NCCN category 2B). Donepazil has also been used in a small trial of 40 patients [52] (NCCN category 2B). Neuroleptics such as haloperidol have been used in delusional patients [53] (NCCN category 2B).

Opioids can cause gastrointestinal dysmotility, frequently leading to nausea, emesis, and constipation. This is mediated by the Mu receptors in the gut [54]. Nausea and vomiting occur frequently with opioid use, usually in new use among opioid naive users or with rapid increase in dosage. In most cases, this can be controlled by more gradual dose increases. Anti-emetics are often useful, and are available in oral, parenteral, or suppository formulations. Emesis also can occur when the patient becomes constipated. Treating the constipation frequently relieves the upper gastrointestinal tract symptoms. It is important to prevent constipation among opioid users, and most of these patients should be on prophylactic stool softeners.

When constipation does result, a number of medication options are available. Senna in one RCT had similar efficacy to lactulose for opioid-induced constipation among cancer patients, but the cost was significantly lower [55] (NCCN category 1). Adding poletheylene glycol (MiralaxTM) in a step-wise approach to standard management was found to be effective in 78.4% of patients [56] (NCCN category 2B). A promising new

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experimental treatment is the use of Mu receptor antagonists (alvimopan and methylnatrexone), which are not readily absorbed in the gut [57] (NCCN category 3). There is some evidence that switching from oral opioids to transdermal fentanyl may reduce GI side effects [58] (NCCN category 2B).

Opioids not only impair GI motility, but also bladder detrussor contraction. Patients should be monitored for symptoms of urinary retention. Those patients at high risk of detrussor dysfunction (due to spinal cord or lumbosacral plexus compression from metastasis) or outlet obstruction (e.g., prostate or vulvar cancers) should be watched particularly closely. In these patients, consideration should be given to bladder scan post-void residuals, where available. Urinary retention can be managed by frequent toileting, preferably in the upright position on a commode, as gravity can aid in emptying. Pharmacotherapy may include sphincter relaxants (i.e., alpha receptor blockers such as tamusolin) or cholinergic agonists to increase detrussor contractility (e.g., bethanechol). Intermittent or Foley catherization may be needed in some circumstances.

Respiratory depression is perhaps the most feared of opioid side effects. Fortunately, it rarely occurs among chronic opioid users who have developed tolerance. It can occur in opioid na覺穡ve patients. Two situations are of particular concern, and have led to deaths among patients using long-acting opioid formulations. Patients who chew, either inadvertently or intentionally, sustained release capsules may receive the full 12 or 24-hr dose of medication immediately, leading to overdose. Transdermal patches have led to overdoses in patients with high fevers, and increased skin temperature hastens absorption [59].

Pain management experts have long advocated for the use of adjuvant medications along with opioids, since before the original WHO step-ladder. These medications may treat specific pain generators (e.g., bone or nerve) and enhance efficacy. In combinations with opioids, lower doses of each medication may reduce side effects.

However, it must be remembered that these medications, too, have serious side effects. Non-steroidal antiinflammatory medications and COX-2 inhibitors not only can cause peptic ulcer disease, but also may increase cardiovascular events. Anti-epileptics may cause as much, if not more, somnolence than opioids [60] (NCCN category 2B). Tricyclic anti-depressants can cause urinary retention and orthostatic hypotension.

Barriers to Physical Modalities and Exercise

Physical modalities and exercise certainly have fewer and less serious side effects than medications for pain management. However, other barriers may limit their use Journal of Surgical Oncology DOI 10.1002/jso

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as well. Most physical modalities cannot be used over open wounds (diathermy and infrared light are exceptions). Deep heating modalities should not be used near primary tumors or metastatic lesions as they may increase circulation to the area and increase the risk of tumor growth. Transcutaneous electrical nerve stimulation (TENS) should not be used in patients with pacemakers or implanted pumps. Manipulation and deep tissue massage must be used with extreme caution in patients with bony metastases as pathologic fractures may result.

Similarly weight-bearing precautions in patients with bone metastasis may limit exercise regimes (Category 2A). A bigger barrier to exercise is fatigue, often prominent among cancer symptoms. Furthermore, depression may limit motivation to exercise.

Financial and Attitudinal Barriers

In the American health care system, financial barriers to medications, therapies, and physician visits abound.

Nearly 46 million Americans are uninsured, and must pay out of pocket for all medical care. Even among those with private insurance or government coverage, large gaps exist with high deductibles and co-pays. Restrictive pharmaceutical formularies often limit access to pain medications, particularly newer drugs and formulation routes. Many insurers, including Medicare, have caps on coverage for physical therapy. Managed care plans often limit access to specialists. This behavior on the part of payers is regrettable, since guideline-based pain management in cancer patients only modestly increases costs (approximately $265) [61]. Furthermore, in minority neighborhoods, pharmacies are far less inclined to stock opioid medications, indeed 52 times less likely in one study of Michigan pharmacies by zip code [62].

The transition from hospital to rehabilitation center, nursing facility, and/or home can also be a barrier to pain management. Only recently have clinicians begun to recognize the importance of medication reconciliation when patients are transferred among levels of care, and careless errors can lead to unnecessary pain and suffering. Furthermore, some treatments may be unavailable in outside facilities or at home due to formulary restrictions, or intensity of nursing care required (e.g., patient controlled anesthesia pumps).

In pain management, perhaps the highest barriers of all to overcome are the attitudinal barriers [63]. Physicians, nurses and pharmacists are poorly trained in pain management [64]. This leads to unwarranted fears of side effects, and confusion about the meaning and incidence of tolerance and addiction [65]. The problem is further exacerbated by state and federal drug enforcement regulations aimed at decreasing illicit street use of

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prescription medications. This has generated considerable fear among physicians and pharmacist to prescribe and dispense opioids because of the perceived threat of wrongful prosecution [66].

CONCLUSION The prevalence of pain in the surgical oncology patient is extremely high and the importance of this topic is paramount. Pain is now considered the fifth vital sign and healthcare providers should go beyond simply documenting its presence and intensity. The relief of pain, whether it is complete or partial, is essential to improve quality of life and help patients to function optimally.

The rehabilitation model for treating pain is a multidisciplinary approach that utilizes a variety of treatments including medications, physical modalities, exercise, CAM, injections, and surgical interventions.

SUMMARY POINTS (1) Pain itself is a barrier to the rehabilitation of surgical oncology patients (NCCN category 1).

(2) Physical modalities, exercise, complementary medicine, medications, and surgical interventions can help manage pain in most patients (NCCN category 2A).

(3) Barriers to pain management include contraindications to certain modalities or exercises, medication side effects, and financial limitations (NCCN category 2B).

(4) Attitudinal barriers among clinicians, government officials, and even patients and their families, must be overcome (NCCN category 2B).

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