Treating pain in cancer and terminally ill patients (Proceedings)

When we consider and treat the population of patients we see who are dealing with cancer, or who have a terminal disease and are approaching the ends of their lives, we are really talking about providing palliative care. This is a concept borrowed from human medicine, and is defines as any form of medical care or treatment that concentrates on reducing the severity of the symptoms associated with disease, rather than providing treatment designed to delay or reverse the progression of disease or to provide a cure. It is the "gray zone" between withdrawing treatment of a disease, and the time for euthanasia. The goal is to prevent or relieve suffering and to focus on comfort care without providing heroic interventions.

In human medicine, the scope of palliative care is being actively expanded to include the comfort care provided to patients with chronic diseases other than cancer such as HIV, progressive neurological disorders, renal disease, and progressing heart disease to name but a few. Palliative care may also be applied to the treatments associated with relieving the discomfort associated with specific cancer therapies such as radiation treatment and certain chemotherapeutic regimens. The goals of palliative care are quite specific, and they all revolve around the concept of providing comfort care and support to the pet and to the humans providing day-to-day care at home.

Our obligations to the patient approaching the end of its life include:

• Relieving and preventing pain

• Maximizing mobility and comfort

• Relieving and preventing pain

• Empowering the client to have an active role in decision making

• Relieving and preventing pain

• Making a plan or algorithm to assist in the decision-making, actions, and interventions as disease progresses

• Relieving and preventing pain

Pain management has taken on a new imperative in veterinary medicine within the past decade. The pain physiologists have clearly articulated that our patients are "wired" for pain much as we are. In other words the principle of analogy holds, and if a procedure or condition would be painful for us, we can count on it being painful for our patients. Patients who have cancer and/or those who are approaching the ends of their lives are those patients who have the highest probability of suffering pain, and their pain may be from many sources throughout the body. They may have any or all of the following conditions (partial list): Osteoarthritis, immune-mediated polyarthritis, degenerative intervertebral discs, spinal bridging spondylosis, spinal stenosis, degenerative myelopathy

One of the most important tools in managing pain for cancer patients or those with terminal illness is a "Quality of Life Scale". Quality of life assessment goes way beyond simply palpating the patient to see if there is a withdrawal response or some other indication of pain. A QOL measurement tool allows us to place a semi-objective yardstick up to the patient's day-to-day life and ask the question, "How are we doing today?" Clients can and should be encouraged and educated to take an active participatory role in QOL assessment, for they really ARE our eyes and ears in the home. All veterinary healthcare team members have had the experience of the patient who sees us and exhibits a completely different set of behaviors than at home — sometimes I think they are "showing off" for us! More on a QOL assessment tool in a bit.

While there is a strong need to assess quality of life, it can be an elusive goal. Most pets in the "cancer patient" and "terminally ill" categories are dealing with multiple illnesses — co-morbidities — and these issues tend to progress with time, adding signs and symptoms to an ever-expanding list. All co-morbidities MUST be considered in creating a comfort-care (and subsequent end-of-life) plan for the pet. Is there renal failure? How will this affect medication decisions? What about the liver? Is the pet eating? Is the GI system working? Are there issues like increased acid production? Colitis? What medications do you have planned? How will they be given? Will the pet eat them in a treat or canned food? Will you use a liquid? What conditions is the pet experiencing that may contribute to a pain profile?

These are all questions to be asked and answered for the palliative care patient.

And now for a focus on the nervous system and some of its foibles...

An interesting twist that occurs in the nervous system that is subjected to ongoing, nociceptive input (chronic pain) is remodeling that is the result of relatively recently discovered/articulated neural plasticity. Over time the nervous system becomes more responsive to input. Previously innocuous input may now be perceived as noxious. This is known as "allodynia". Likewise, the patient may experience an exaggerated response to painful stimuli. This is known as "hyperalgesia" — literally, "too much feeling". . It is appropriate to recognize and respect these changes in the nervous system when putting together a pain management strategy for the terminally ill or cancer patient.

Both allodynia and hyperalgesia are part of a phenomenon known as "sensitization". And, both the peripheral and central nervous systems can become sensitized in the face of ongoing pain. In addition, patients with peripheral and central sensitization often experience expanded fields of altered sensation — areas beyond the sites of the original injury become painful

In peripheral sensitization, there is increased cell membrane excitability, production of increased numbers of action potentials in the nociceptors, and the threshold for firing of nociceptors is lowered. This combination of effects helps explain the transformation of innocent tactile stimulation into a painful experience. Likewise, it helps us understand the increased sensitivity to painful stimuli many of these patients possess. Sensitization also occurs commonly in the central nervous system, specifically in the dorsal horn. In the spinal cord, central sensitization amplifies and facilitates the transfer of information from the afferents to the dorsal horn neurons. Over time both chemical and genomic changes occur that lead to further facilitation and further exaggeration of the pain experience.

As a consequence of this phenomenon of "wind-up" our task to relieve pain is made more challenging. We have to think creatively about targeting specific receptors as we put our pain management plan in place. We also have to consider the patient's co-morbidities in choosing medications so that we do not relieve pain at the expense of prematurely terminating life. Fortunately, we have several excellent choices that can all work together for the comfort of the patient. It is important to become comfortable with a multi-modal approach due to the engagement of multiple pain mechanisms and the recruitment off multiple receptor types. The advantage of targeted therapy, is that we can aim for specific receptor targets, use more than one medication at a time to hit more than one target at a time, and (so long as we are aware of interactions and adverse event profiles, have decreased worry about collateral fallout.

NSAIDs

If the dog has reasonable renal function and is still eating, then NSAIDs to address inflammatory pain are not a bad choice. Occasionally, in the terminally ill patient with obvious inflammatory issues, I will reach for an NSAID. I generally try to balance that decision by having as good an understanding as possible about the animal's renal function. I have had chronic pain patients who, when their NSAID was discontinued, had significant pain relapses. In my experience, however, these patients come in my door fairly infrequently. I am generally able to create a pain management "package" that avoids the use of NSAIDs.

Gabapentin

Gabapentin remains a cornerstone of managing maladaptive pain in humans and is earning a place in the perioperative pain arena as well. It has the exquisitely specific target of the alpha-2 delta legend of the calcium channel in the dorsal horn of the spinal cord. By altering calcium permeability, it alters the modulation that occurs in the spinal cord of a chronically painful patient. In our pain referral practice, it has become a true cornerstone of managing chronic maladaptive pain in both dogs and cats. One distinct advantage is that gabapentin does not contribute to organ system problems or issues, making it a great choice for the pet with co-morbidities. Sedation is the dose-limiting side effect. If that happens, lower the dose. It should be given BID – TID, and we generally start at a dose of 5 – 15mg/kg. Non-linear pharmacokinetics means we can escalate our dose pretty aggressively to meet the patient's need. I have patients who take 50mg/kg per dose to stay comfortable. DO NOT stop gabapentin abruptly as you can have a serious pain rebound! Most chronic/maladaptive pain patients never come off gabapentin, as the remodeling in their spinal cords appears to be permanent.

Amantadine

Amantadine works at the NMDA receptor as an antagonist and tends to be the next drug I reach for in chronically painful patients. This is also where ketamine has its analgesic effects, but amantadine does not affect mentation as ketamine does. In chronic OA, amantadine has demonstrated its worth in ramping down central sensitization. I generally start patients at 2 – 5 mg/kg. It is a once a day medication.

Tramadol

Because of the exceptionally short half-life in dogs, tramadol generally lends itself best to use for "breakthrough" pain — that is, patients who have a pain protocol in place, but for whatever reason are experiencing spikes in their pain experiences. It must be given TID – QID in order for us to be able to count on its action against pain. I generally use it at 2 – 4 mg/kg/dose TID to start. It is exceptionally bitter, so be aware! I have had patients go completely anorectic after tasting tramadol just once! It does appear to have a slightly longer half-life in cats, so BID dosing may be appropriate. I find the taste to be a "deal-breaker" in cats.

Amitriptyline

Amitriptyline and other tri-cyclic antidepressants play an important role in the management of maladaptive pain in human pain patients. It has not yet been studied for this purpose in dogs and cats, though intuitively it makes sense that we could use it for pain in our patients since we already use it for brain-chemical driven behavior issues. Anecdotal reports suggest that pain patients need a smaller dose that those patients being treated for behavior issues, however, clinical trials need to be done.

Buprenorphine

Buprenorphine is a partial mu-agonist that works very well in my feline chronic pain patients who need more pain relief than the "package" up to this point can provide. I use it transmucosally, and to really consistent effect. There is ongoing work to look for sustained release formulations and for a high enough concentration to make it useful in the dog.

Morphine

Even with low bioavailability in its oral form, morphine remains a useful tool in the pain "pharmamentarium" I tend to reach for sustained release tablets in dogs, and start at 1 mg/kg per dose. Be sure to educate clients NOT to BREAK or CRUSH the tablets or they will create an overdose situation. Be careful to have in place a risk evaluation and mitigation strategy in place when using Schedule II drugs in outpatients. It is certainly do-able, but pay close attention to the laws in your state as well as following DEA guidelines carefully. I have used lots of oral morphine and still have not seen the side effect of constipation, which remains the single most important side-effect of morphine use in people, and a limiter to people getting opiates for their pain.

PSGAGs

PSGAGs certainly have a role in the end of life scenario if the patient has taken this for joint disease previously. The PSGAGs work best when the joints are still in motion and being used, and they have an indirect inti-inflammatory effect by acting to help support cartilage.

Nutraceuticals

Microlactin (milk protein extracted from the milk of hyper-immunized cows) appears to have a general anti-inflammatory effect in animals with OA, making it an option for joint inflammation in those patients who do not tolerate or shouldn't receive an NSAID. 40mg/kg BID is the ddose that is described, and that is the dose we currently use.

Omega 3 FA's have been demonstrated to have a significant positive impact on joints, provide immune system support, and have a positive effect on remission times iin many types of cancer.

As nutritional science continues to advance, there will be additional items fgor us to consider that may help our patients.

Physical Medicine

Acupuncture, medical massage techniques, Myofascial trigger point release, low-level laser, heat, cold, stretching, and various physiotherapy techniques have all been used to varying degrees to help the terminally ill be more comfortable. There are varying levels of evidence for each of these, so we must be cautious in making our recommendations and in the outcomes we imply.

One final consideration for the terminally ill pet, as well as those dealing with the effects of either cancer or cancer treatment, is to emphasize the role of good, consistent nursing care. Our clients want to do everything they can for their beloved animal family members, and there is so much that they can do at home to make everyday life more pleasant for the pet and for themselves. In human pain management, the psychological elements of our appearance and surroundings can play a big role in our ability to cope with chronic pain that may be difficult to control. Providing opportunities to "normalize" the life routine in the home can be of great comfort for both the pet and the client. Simple things like the following list should not be overlooked:

Good hygiene — the use of absorbent pads under non-ambulatory pets; cleaning away of stool and urine; equipping the client with an effective waterless shampoo

Padded bedding — be careful here, because some pets will do better with a firm memory foam while others will4 prefer the "cuddly" surface of soft quilts and blankets; keep an open mind when guiding your clients

Frequent potty opportunities — distended bladders can be quite uncomfortable, so be sure to guide clients to be creative about providing plenty of potty opportunities

Turning and moving immobilized pets — for those pets who have difficulty moving themselves around, teach clients to move and turn them on a regular basis; this prevents pressure sores and helps the patient with lung/chest expansion, muscle movement, etc.

Good grooming — encourage the client to continue regular grooming activities they have shared with the pet up to this point; very often, pets seem to "notice" when they are not looking their best.

Most clients welcome an opportunity to feel that they are actively engaged in the details of their pet's care and comfort. Take advantage of that desire by providing very specific guidance to them.

In closing, one QOL scale to consider is published in Dr. Alice Villalobos' book Canine and Feline Geriatric Oncology (Blackwell Publishing, 2007). It is easy for us and for clients to remember because it uses the pneumonic HHHHHMM. At whatever interval is decided upon — daily, weekly, biweekly — the patient is evaluated in each of the categories represented by HHHHHMM. Each category is scored 1 – 10 where 10 is best. 5 or better in each category is acceptable. And a total of 35 points or better generally means palliative care and hospice are going well.

The letters stand for:

• Hurt – Adequate pain control, including the ability to breathe

• Hunger – Is the pet eating enough? What about hand feeding? A feeding tube?

• Hydration – Is there dehydration? Consider SQ fluids for those not drinking enough

• Hygeine – Keep the patient clean and dry to avoid pressure sores

• Happiness – Does the pet express joy and interest? What about interacting with the environment asnd the family?

• Mobility – Can the patient get up and move without assistance? What about assistive devices like slings and carts? There are now carts for 4 legs not working.

• More Good Days Than Bad – When there are more bad days than good, QOL is seriously compromised and euthanasia should be considered. When a healthy human-animal bond can no longer be maintained, the end is near.

There is so much we can do for these patients when they need us the most. It is all about active advocating!