Monday, 9 April 2007

The Pain Relief Pyramid

In my career so far, I have noticed that patients on occasion have their pain relief poorly managed by junior physicians.

Patients in the UK and Japan all experience pain of some sort, depending upon their underlying condition. However, the expression of the pain can be different.

I have noticed that when patients complain of pain, the pain relief provided may sometimes be inadequate either because the pain is simply not appreciated by the doctor, the patient expresses their pain and their treatment wishes poorly and the doctor's knowledge and experience in treating pain may be limited.

In order to treat pain effectively, it must be understood what is actually causing the pain.

Is the pain organic or functional? Is it inflammatory (Sharp)? Is it bone pain (deep and aching)? Is it cardiac pain (central chest, severe and heavy)? Is the pain muscular? Is the pain like a lightning bolt? Does it come on at night and feel like burning and associated with 'pins and needles' (neuropathic)? Is the pain the result of a problem elsewhere (radiating pain)?

For example, inflammatory pains such as pleuritis and tenosynovitis are effectively treated with acetaminophen and NSAIDs.

However, ischaemic chest pain from an acute myocardial infarction is not going to be treated effectively from these mild analgesic agents and morphine is required in this setting.

I recently was teaching residents that pain relief must be given to patients suffering from an acute myocardial infarction rather than just calling the cardiologists and hoping the pain will just go away as the patient leaves the ER department (and out of your sight and responsibility) as they go to the catheter lab for PTCA and stenting ! When I mentioned using morphine or diamorphine, the residents looked astounded and said that this was only used in terminal disease. Well, the UK guidance for treating AMI is pain relief with morphine/diamorphine and from my experience, it is extremely effective and calms patients down as well, in an otherwise very painful and stressful situation.

Pain from cancer is again effectively treated with opioid or opiate therapy but some pains are also helped in combination with acetaminophen and / or NSAIDs and even neuropathic pain therapies (detailed later). Radiotherapy and bisphosphate use in bone pain conditions can also be very useful.

There are less strong opiate therapies such as codeine phosphate, which is an effective analgesic agent used in situations when acetaminophen and / or NSAIDs are still providing ineffective to suppress pain. However, they can cause constipation so are generally given with lactulose / senna or magnesium hydroxide.

In the UK, we generally use an analgesic pyramid for treating pain such that pain can be effectively treated. Hence, in severe pain of any type we use oral morphine or even intravenous diamorphine, unless contra-indicated, and not just for terminal cancer patients.

For example, a patient with pericarditis may have a sharp-type pain. Acetaminophen should be given first and if ineffective, a non-steroidal drug (NSAID) can be added or substituted. If however, the pain gets worse despite treatment, an opioid such as codeine phosphate can be added to the above regimen.

Another example is in myeloma with bone pain; if the pain got worse despite the above three drugs, the codeine could be stopped and oral morphine liquid could be given instead. The advantage of using morphine orally is that a total daily amount can be estimated which controls pain, and following this a dose of Morphine Sulfate (MST) can be estimated and given instead of the oral morphine. Lets say a patient requires 20mg of oral morphine per day to control their severe chronic back pain, an estimated daily dose of long acting MST can be given at 10mg twice daily as an initial starting dose and increased if the pain is still problematic.

Morphine naive patients can safely be given 5-10mg every 3-4 hours and those on long term doses may require larger amounts to control their pain (UpToDate 15.1)

Of course, if morphine sulfate doses escalate further, transdermal opiod patches can be used such as Fentanyl which provides a much smoother delivery of the drug and avoid having to take lots of MST tablets and are changes after 72 hours.

Pethidine which is a tablet, intramuscular and intravenous opioid therapy, can sometime be given for pain relief. Its main advantage is that it is not supposed to cause contraction of the duodenal papilla (Ampulla of Vater / Sphincter of Oddi) unlike morphine, and it is therefore useful in conditions such as biliary colic and pancreatitis.

The downside of such therapy in the long term is addiction and 'professional' patients in the UK sometimes ask specifically for pethidine if they get a return of their 'pain'. I have experienced such patients who do not have clinical pain but manufacture their condition in order to obtain pethidine or morphine like compounds to feed their physical and psychological addiction.

However, short term use (days) of opiate/opioid use, for example, in an acute MI will not lead to addiction, and chronic pain syndromes are likely to need such therapies in any case.

Buprenorphine is a partial agonist with a high binding affinity for opiate receptors and it is used in acute pain. It is excreted mainly in the faeces and some in the urine unchanged.

Non-Traditional Analgesic Therapies

Sometimes, Tricyclic antidepressant therapy can be used for chronic headache or neuropathic pain. Traditionally, amitryptilline 10mg as a starting dose has been used and incrementally increased until effective pain relief is achieved. However, tricyclic agents although having antidepressant properties, are fraught with side effects from their anti-histamine, anti-muscarinic blocking properties. These agents cannot treat acute pain as they are pain modulators and in fact, take several weeks before the patients experience a reduction in their pain.

Perhaps better therapies are Gabapentin or Pregabalin, which are effective therapies for neuropathic pain syndromes, and in the UK are typically used in Diabetic patients who can develop severe nocturnal pain due to diabetic neuropathy.

Another very new development is with the drug Duloxetine which is a dual SNRI anti-depressant which is effective in neuropathic pain syndromes and is also used in diabetic patients. In is approved in more than 70 countries for use in severe depression, but as I understand it, Japan will be marketing the drug for use in incontinence.

Of course, non-drug treatment of pain can be with TENS (Transcutaneous Electrical Nerve Stimulation) which can be effective for 'gating' pain and is used in pregnant patients and chronic back pain conditions in the UK. Basically, this consists of stick-on pads that deliver an electrical current onto the skin of the affected area thereby stimulating the local nerves and making them refractory to the conduction of painful stimuli from the area downstream causing the painful condition.

Salmon Calcitonin is an effective therapy used in the UK and USA for treating osteoporotic fractures. It is given subcutaneously until the pain level is reduced by approximately 50%. It is usually given for a week or thereabouts, but it is frequently associated with nausea and vomiting. However, it is an effective therapy for such bony conditions and is combined with oral bisphosphonate treatment and traditional analgesic agents.

Protecting Your Patients When Giving Analgesia

Always be very careful when prescribing NSAIDs. Adverse side effects include asthma in susceptible individuals, GI bleeding and renal failure to name but a few.

Always take a careful drug and allergy history to ensure that patients have not experienced adverse effects from these drugs in the past.

In the elderly, if you do consider NSAID therapy, please consider adding a Proton Pump Inhibitor (not H2 blocker) especially in the elderly as this is the most effective acid-suppressant therapy and this may prevent a patient developing an ulcer with prevention being better than cure!

Check BUN and Creatinine a few times a week to ensure that the patient does not develop renal failure. If the patient has underlying renal disease and / or is taking diuretic therapy or other potentially nephrotoxic agents, then be warned as NSAIDs reduce renal blood flow through abolition of vasodilatory prostaglandins and renal failure can ensue.

NSAIDs can be substituted by using the above combination of acetaminophen and codeine phosphate but please be careful in patients with liver dysfunction as codeine / morphine compounds require the liver ( and kidneys) to be eliminated. Remember, morphine has the addition of two glucuronic acid side chains (morphine diglucuronide) to be excreted in the bile / urine. Renal failure can slow the excretion of morphine as well, dependent on the creatinine clearance, so dose reductions for opioid/opiates may be necessary.

The elderly are also very sensitive to opiates / opioids in who may benefit the most from having their pain controlled and hence, a smaller starting dose may be necessary.

Specific major side effects include reduced respiratory rate, pin-point pupils, confusion, unconsciousness, hallucinations and the classical 'opiate twitch' seen in opiate toxicity. Luckily, the reversal agent is Naloxone (Narcan), given intravenously and intramuscularly or as a constant infusion and I have personally seen over-treated and unrousable patients suddenly start breathing and open their eyes after seconds of an injection of the anti-dote. Unfortunately, NSAID side effects cannot be reversed as easily! However, please remember that naloxone's effects are short lived and sometimes an infusion is necessary and hence, in patients with hepatic and/or renal failure this may need to be prolonged.


For a full analgesic explanation, side effect profile and indications and contra-indications, please refer to a pharmacology text before prescribing. Some major information on drugs can also be found in UpToDate 15.1

So, I hope that the above gives you a better idea of how to treat pain, and your patients will feel better as a result.

Please let me have your feedback.

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