Pain management for the cancer patient (Proceedings)

One of the primary goals for all personnel involved with managing veterinary cancer patients is to preserve quality of life. In human oncology patients more than 50% report experiencing moderate to severe pain associated with their disease; obviously our patients can not voice their pain in words. It is crucial to develop and utilize a systematic method to rate/score pain in veterinary medicine. There are many forms of pain that are associated with companion animal cancer patients. Pain can either result directly from the pathology of cancer or indirectly from our treatment modalities such as chemotherapy, radiation therapy or surgery. There are many viable methods that we employ to control and/or eliminate much of the pain we see in these patients.

Sources of cancer pain

Pain can be attributed indirectly to malignancies as a result of the following: associated edema, ascites, intestinal obstruction, infection (cellulitis or deep abscess formation) or immobility due to limb paralysis. These types of pain are not to be confused with pain primarily caused by the malignancy.

Pain which is caused directly from malignancies is categorized as pathologic pain. Bony metastases, nerve compression and soft tissue infiltration are among the most common reasons that we see pain as the result of neoplastic pathology. These are readily identifiable as osteosarcomas [OSA], which result in bone fractures or deformities and soft tissue sarcomas (nerve sheath tumors, fibrosarcomas [FSA], and infiltrative lipomas) which result in deep muscle pain and nerve compression.

A third category of cancer pain is that which is caused by our therapeutic interventions. We commonly observe acute post- operative pain, chronic post-operative pain, radiation tissue burns, tissue necrosis (from extravascular chemotherapy administrations), gastric ulceration, pancreatitis and mucosal sloughing all caused directly from the methods that we use to treat the various types of cancer that we see in our patients.

Physiologic processes of pain

There are four distinct physiologic processes that are identifiable when dealing with pain. The first is transduction. Transduction is the translation of physical energy (noxious stimuli) into electrical activity at the peripheral nociceptor. This is the first step in sensing pain. The second process involves the sensory nerves; also referred to as transmission. Transmission is the movement of nerve impulses through the peripheral nervous system to the spinal cord. The third process is called modulation. Modulation occurs in the spinal cord and is, in simple terms, the movement and alteration of impulses through the spinal cord towards the brain. Lastly, the fourth process is perception. Perception results from the successful completion of the other three processes as the brain subsequently recognizes the pain.

Blueprint for pain management in the cancer patient

There are multiple areas that should be reviewed when formulating a plan to manage the pain that our patients may encounter. For an optimal outcome there are four steps that should occur. We must 1) educate ourselves on the most current techniques to alleviate pain (this includes available drugs, possible complications and interventional techniques), 2) educate the pet owners realistically and involve them in the overall plan, 3) use a systematic approach to score the pain throughout treatment so as to "stay ahead of the game"; not identifying pain only when it is severe and we have "fallen behind" and 4) have the full support of the practice you are at to utilize controlled substances and progressive techniques as needed.

The role of the veterinary technician in managing pain is a crucial one. Technicians are typically the first people to greet the clients and assess the patient. Many times pet owners have a separate relationship with veterinary technicians and convey different degrees of information to them than they do the doctor. It is imperative to communicate this information to the clinicians to help identify the degree of pain the animal may be feeling at home. To be effective as technicians we need to be able to assess the pain timely and accurately and effectively communicate this to the clinician. We should be able to identify the effectiveness and/or any side effects that may be occurring as a result of treatment, as well as being proactive in educating the clients on the process.

Managing indirect pain associated with malignancies

At times we see our patients develop pain secondary to the malignancy. This pain may be in the form of edema from decreased circulation. An excellent form of treatment for pain resulting from edema is massage therapy. Another form of indirect pain may be ascites or pleural effusion (an abnormal accumulation of fluid). The first step in alleviating the pain felt with ascites or pleural effusion is to evacuate the fluid via centesis (the removal of fluid from a body cavity via a needle). It is important when draining fluid to minimize the risk of re-expansion from removing too large a volume at once. It should also be noted that this type of management is usually short lived and poses risks without a long term plan to control the malignancy. Yet another type of indirect pain we occasionally see is associated with deep abscesses. Common treatment for a deep abscess is to drain it. We also at times see cellulitis. The most common treatment is antibiotics combined with hot packing the effected area 3-4 times daily (for 20 minutes) to help reduce swelling and increase circulation.

Managing pathologic pain

Often the management of pathologic pain comes in the form of surgery, radiation therapy, chemotherapy or some combination of the three. Frequently, we do not consider these to be forms of pain management when in reality they are. For example, bone pain associated with OSA can be alleviated with common treatments such as amputation combined with chemotherapy, palliative radiation therapy or limb-sparing with follow-up chemotherapy. Nerve sheath tumors which can cause severe neuropathic pain may be treated with surgery, radiation therapy and/or chemotherapy. The same can be said for most types of invasive tumors. Some other pharmacologic treatments that can be employed are NSAIDS, steroids and opioids.

Managing pain caused by therapeutic intervention

The most common type of pain that is seen in cancer patients is pain that is a result of our therapeutic intervention. However, it is largely preventable and most times inexcusably under managed. There are many reasons that pain is under managed in our patients. Many clinicians are concerned about unwanted side effects such as respiratory depression, decreased cardiac output or dysphoria. These unwanted side effects can be eliminated for all practical purposes through education, close monitoring and the use of reversal agents. Another reason for under managing pain is the amount of time and paperwork it takes to prescribe controlled drugs. Other reasons include: fear of masking physiologic signs (hypotension, ↓HR, ↓RR, etc), fear of overdosing, the belief that cats are too sensitive to opioids to chance using them, the myth that some animals are just stoic and don't need analgesics and lastly, the concern of speaking with clients regarding the of added cost of analgesics. When considering that all of these concerns are fairly easily dealt with and the fact that managing pain is ethical, cost effective and even profitable there is no reason to under manage pain any longer.

Post-operative pain management

When dealing with pain caused from surgery we have multiple options at our disposal. The best approach is a multi-modal one. For amputations and thoracic surgeries we can place epidural catheters and use periodic infusions of morphine, lidocaine or bupivacaine. This method is effective for up to 12 hours per injection and can be maintained for 3-5 days safely. We can also treat most surgical systemic pain with pharmacologic agents either as scheduled treatments or with a CRI (constant rate infusion) of opioids, ketamine or lidocaine. **We should never use PRN orders as an effective method to treat pain; this method allows for severe windup pain to occur and runs the risk of uncontrollable pain**. If the patients' renal and hepatic functions are within normal limits we can add an NSAID to reduce inflammation. Other modalities for dealing with post-operative pain are ice packing the incision site (15min q4hrs for the 1st 24 hr period) and utilizing physical therapy. Transdermal fentanyl patches are a good method of delivering the opioid fentanyl continuously for several days at home. Some clinicians also opt to use oral analgesics when sending patients home. The use of oral acetaminophen with codeine can be useful after the pain is reduced to a moderate level. The use of buprenorphine in cats sublingually is also an effective method to control moderate to minor pain. The use of butorphanol is considered an ineffective analgesic (duration of 45-60minutes) and is extremely costly for most forms of immediate post-operative pain.

Chronic post-operative pain

Chronic pain should be treated much like acute pain in the sense that it should be assessed quantitatively and monitored closely. The goal in managing terminally ill patients is to sustain good quality of life with minimal adverse effects. Initially when managing either acute or chronic pain conventional analgesia should be used. As we evaluate pain progression and begin to see altered CNS processing and/or hyperalgesia then we need to look at alternative therapies. These therapies can include NMDA receptor antagonists (ketamine), GABA agonists (gabapentin), tricyclic antidepressants (Prozac) along with acupuncture and chiropractics. It is crucial to listen to pet owners and incorporate their daily observations into the overall analgesic plan. As part of the medical team we should not be discouraged by having to change protocols frequently to keep unwanted side effects at a minimum. It is imperative to educate owners on the difficulty of managing chronic pain and that it may take several different approaches before the most effective treatment is discovered. Every patient reacts to each drug (or combination of drugs) differently.

Radiation burns

An unwanted but often times, unpreventable side effects of radiation therapy are tissue burns and mucositis. These too are treatable with a variety of modalities. The current treatments include: oral opioids, sucrafate, viscous lidocaine, green tea rinses, epidurals, transdermal patches, TCM (Traditional Chinese Medicine) and acupuncture. Another method which can be used is to apply a barrier film (Cavilon or Nexcare) to the radiation site to delay tissue burns. By delaying tissue burns we can provide a better quality of life throughout already stressful daily treatments.

Tissue necrosis

Many anti-neoplastic agents cause significant injury if administered extra vascular. Typically these occurrences are painful and begin to show signs in the affected area within 1-10 days. Treatment options include local corticosteroid injections, surgical debridement and reconstruction (in severe cases) and oral opioids and NSAIDS if needed.

Gastrointestinal related pain

The most common types of GI pain that we see in cancer patients are associated with vomiting, diarrhea or pancreatitis. The degree of pain for these three ranges from mild to severe. For vomiting or nausea we mainly utilize trademark anti-emetics such as Tagamet, Pepcid, Zantac, Anzemet, Zofran, Carafate, and Reglan to name a few. Many of these drugs are 5-HT3 receptor antagonists and have proven to reduce and/or eliminate most chemotherapy induced vomiting. This class of drugs works by effectively blocking 5-HT3 receptors which are activated by serotonin (which can be released from chemotherapy administration). 5-HT3 receptors are located on the vagal afferents and, in turn, initiate the vomiting reflex. Some clinicians also prescribe butorphanol as an anti-emetic / analgesic which can be effective. It should be noted that studies have shown that general anesthesia alone causes pin-point GI ulcers and so this too should be considered with patients that require daily anesthesia. Lastly we may also choose to include intraperitoneal injections of lidocaine to control severe pain in patients with pancreatitis.

Tissue biopsy related pain

It is also very common to see pain resulting from our need to determine what type of cancer we are dealing with and at times whether or not the mass we may be seeing is neoplastic at all. There are several different methods by which we can acquire tissue samples. Among them are: fine needle aspirates, punch biopsies, endoscopic biopsies, Tru-cut biopsies, bone marrow aspirates, surgical biopsies and wedge biopsies. Most cause some form of pain. Among the more common are nasal endoscopic biopsies which can be easily managed with a combination of opioids along with a regional infraorbital block and punch or wedge biopsies which can be also pain free with a local block and an NSAID/opioid combo. Bone marrow aspirates should be performed under anesthesia and have been reported to be pain-free with the exception of the point of aspiration. When performing bone marrows on an awake animal a local block and some form of opioid should be used. Surgical biopsies are usually managed pain wise as any surgery with a combination of NSAID, opioid +/- epidural or CRI.

Doses—how much and when

There are many reference guides out there to use when dosing drugs. It is easiest to put together a quick reference chart to use for the particular setting you are in. This is usually a combination of references but can be most useful in tracking effectiveness and to keep uniformity amongst staff. It is also crucial to establish a universal pain scoring system that you may refer to for each patient to have preset guidelines and be able to review each patient throughout time and change your analgesic plan as needed. There are pain scale models available in most analgesia texts. It is often times, that we see pain being treated after the patients are vocalizing and distraught instead of preemptively and continuously. It must be the goal of all veterinary practitioners, technicians included, to see that we continue to strive to eliminate pain and provide the highest quality of life possible in our animal companions.

References

1. Haskell C. Cancer Treatment W.B. Saunders; 2001: 360.

2. Tranquilli W, et.al. Pain Management Teton Press; 2000: 14.

3. Withrow S, et.al. Small Animal Clinical Oncology W.B. Sanders; 2001: 183.