1. Introduction

Doctors have a rather scruffy track record of pain management. Take the following quote from Axel Munthe (who worked in the famous La Salpêtrière with Charcot in about 1900):

"The old nun had told me that I was committing a terrible sin, that Almighty God in His inscrutable wisdom had willed it so, that the more suffering He inflicted at the hour of death the more forgiving would He be on the Day of Judgement. Even sweet Soeur Philomene had looked at me disapprovingly when, alone among my comrades, I had come with my morphia syringe after the old padre had left the bed with his Last Sacrament".

A hundred years later, we are no better than Munthe's colleagues. A recent survey of British Hospitals found a third of randomly selected patients to be in severe, poorly managed pain. As in past centuries, many, perhaps most doctors today neither listen to their patients nor manage their pain adequately.

This lecture briefly tries to address the nitty-gritty of pain. It is merely an introduction to a vast subject.

2. What is pain?

Most pain lectures begin with a ritual incantation, the IASP definition of "pain". I will not repeat it here, as I consider it an anachronism - pain is not merely an elusive 'subjective experience' but a complex physiological response to harmful stimulation, that has been around for hundreds of millions of years and profoundly affects the whole nervous system and indeed the whole organism.

There is a great danger in confining our definition of pain to the reporting of a subjective experience. A patient under anaesthesia or someone with a head injury, who appears to be in pain as shown by, for example hypertension and tachycardia, can be virtuously ignored if we subscribe to the 'subjective experience' myth. Yet we know that examination of the spinal cord of a rat subjected to similar indignities will show expression of c-fos, our "molecular marker for pain", and that opiate analgesia will partially ablate this response. Giving suitable neuraxial anaesthesia (a spinal or epidural) can totally suppress the c-fos response to inflicted pain.

We have relatively few weapons in our fight against pain, but carefully used, they can control most pain. Let us learn to use some of these weapons.

3. Local anaesthetic

In previous lectures you learned the difference between ester and amide local anaesthetics, and details of their pharmacology. We will try and look at more practical aspects. Most contemporary local anaesthetics are amide based - among these we consider lignocaine, bupivacaine and ropivacaine, which share many similar properties. The most important thing to consider when administering local anaesthetic agents is toxicity.

Toxicity and complications of local anesthetic administration

Toxic Doses

These are usually expressed on a per-kilogram basis, a gross oversimplification because toxicity depends not only on the individual and his metabolism of the drug, but also on how the drug is administered.

Toxic doses
Drug Toxic dose (mg/kg)
Lignocaine (without a vasoconstrictor) 3
Lignocaine with a vasoconstrictor 7
Bupivacaine 2
Ropivacaine 3 to 4
Note that by some the above maximum doses might be considered conservative. It is always wise to be conservative when dealing with local anaesthetics. You kill fewer people.
Features of toxicity

Local anaesthetics are a safe and effective and highly desirable means for achieving analgesia. However, if you use them enough, despite your best precautions, you will encounter toxicity. If you are not prepared to deal with it, this toxicity may result in serious harm or death. The first step is to recognise toxicity, which takes two major forms:

  1. Neurotoxicity
  2. Cardiotoxicity

Lignocaine, bupivacaine and ropivacaine are all more likely to cause neurotoxicity than cardiac toxicity. This relative risk has been estimated at 7 to 10 times for lignocaine, four times for bupivacaine, and somewhere in between for ropivacaine.

Neurotoxicity often starts with a change in mentation, followed by perioral paraesthesia, a feeling that the subject's whole body is flushing, tinnitus and other neurological symptoms culminating in generalised seizures. The initial neurological manifestation is often missed by the incautious doctor, as it may manifest as:

The first and most important rule of local anaesthesia is thus clear:

Keep the patient talking at all times!

Cardiotoxicity This is a rightly feared consequence of high blood levels of local anaesthetic. There may be extrasystoles, brady- or tachyarrhythmias, culminating in cardiac arrest.

Management of toxicity

Most important is to be prepared to resuscitate the patient, and know your 'ABC'. Prolonged cardiopulmonary resuscitation may be required, especially with bupivacaine which has a longer half-life than lignocaine. It has been said that you may need to continue CPR for several hours! There is no specific antidote, although adrenaline may be administered with caution if deemed necessary by a competent and experienced resuscitator.

Prevention of toxicity

Toxicity often results from excessive doses, or inadvertent intravenous administration of local anaesthetic. The latter can occur at any site, but is particularly common where large vessels are near the site of administration.

There is no merit in 'sucking back' on the syringe when administering local anaesthetic subcutaneously, but this should be routinely done when performing major nerve blocks e.g. brachial plexus, femoral, or sacral. Here one should repetitively withdraw to prevent inadevertent intravascular administration.

Testing of epidurals is important. Administration of a test-dose of lignocaine with added adrenaline (e.g. 5 µg/ml) will fairly reliably elevate the heart rate if the dose is accidentally given intravenously, even in children with a baseline tachycardia, but in some circumstances this is of no value. For example, in women in labour, a substantial increase in heart rate might just as likely be related to a contraction! There is also much dissent about the amount of lignocaine that should be put into a test dose. Conventionally many anaesthetists give only "2ml of 2%", that is, forty milligrams, which is probably inadequate. Eighty to 100 milligrams is probably a more realistic dose, followed by careful checking for sensory loss.


Allergy to amide local anaesthetics is extremely uncommon, if it exists. Ester local anaesthetics, which are infrequently used, are much more often associated with allergy because they are metabolised to para-amino benzoic acid, which acts as a hapten.

Toxicity related to additives

Multi-use vials

These are a cost-saving abomination. They usually contain methyl paraben as a preservative, which is neurotoxic. There are thus several good reasons why you should never use a multi-use vial, including:


Mistrust doctors who make complex concoctions, especially for epidural or spinal use. Next time you have the opportunity, check the pH of dextrose (a common additive) - you will find it to be surprisingly acidic. This, if added to carefully pH-adjusted solutions like lignocaine or marcaine, will totally muck up the pH balance.

Local complications

To a certain extent these depend on site. Important concerns are:

Preventing complications of local anaesthesia

There are five basic rules to performing local anaesthesia. If you ignore these, you will imperil the patient, your career, and your medical protection society. They are:

  1. Know the patient and the indications for the procedure. Make sure that the procedure is appropriate for the patient. Examine the patient before the procedure paying particular attention to neurological function, especially in the area affected by the local anaesthetic procedure.

  2. Use the correct monitoring. A minimum requirement is someone who knows what they are doing - don't do a procedure first time without competent supervision. Monitoring is always dependent on what is available. An ECG (although never shown to improve outcome) is always available and must be used. Easy to use, it also provides an auditory AND visual input - a major plus! There must be some means of repeatedly and regularly checking the blood pressure, even if this is 'just' a dedicated person with a sphygmomanometer and stethoscope. Automated blood pressure devices are great. The use of a "finger on the pulse" is generally frowned on, as it is really impossible to concentrate and not miss abnormalities. A pulse oximeter is a beautiful method of monitoring saturation and heart rate, and even gives you an idea of blood pressure.(It is not however without its faults). The golden rules of monitoring are:

    1. Trust your equipment!

    2. Trends are more important than absolute values

    3. Multiple monitors give security

    Practically, what the above mean is that if the monitor says there is a problem (eg the ECG shows asystole) don't spend ages mucking around trying to find a loose lead while the patient accumulates brain damage. Similarly, a downward trend on the pulse oximeter from a saturation of 99% to 95% is as worrying as a saturation of under 90%. And clearly if you have several monitors and they all indicate a problem, there definitely is a problem.

  3. Have good IV access. Don't play silly buggers with local. Have a functioning intravenous line.

  4. Have the correct resuscitation equipment there in the room with you. This should as a minimum include:
    1. oxygen
    2. An airway
    3. Decent suction (not a fiddly little device)
    4. An Ambu bag
    5. An endotracheal tube, laryngoscope, and a 'largyngoscopist' - someone who can put the darn thing in!
    6. Adrenaline.

  5. Know what you're doing. Ask what you don't know of real people - don't learn off a website! Actively seek knowledge - be a helpful pest, and people will teach you!

Onset and duration of local anaesthesia

It is difficult to attach numbers to the rapidity with which local anaesthetic agents start working, and how long they continue working. In general, the onset of action of lignocaine is quicker than that of bupivacaine (about 5 min as opposed to fifteen minutes), and the duration of action less (about one to one and a half hour, as opposed to approximately three hours).

An important concept is that of motor versus sensory dissociation. Especially with epidurals, it's extremely desirable to block sensory fibres, but spare the larger motor fibres. One can to a certain degree do this by using lower concentrations of local anaesthetic. A claimed advantage of ropivacaine is that it allows just this - predominant sensory block.


Nobody but nobody waits 5' for lignocaine to work! This is baaad.

4. Non-steroidal anti-inflammatories & paracetamol

As opposed to most medical therapy, with pain control it is often a good idea to combine a variety of different analgesics to maximise effect and minimise side-effects. The value of paracetamol and nonsteroidal anti-inflammatories (NSAIDs) is often underestimated.


This analgesic is often underused. An appropriate loading dose is 20mg/kg (3 x 500mg tablets in a 70kg adult). Thereafter, four-hourly doses of approximately 10-15 mg/kg may be administered. It is generally advisable to limit the daily dose to under 10g (in an adult), as there is a potential for hepatotoxicity at doses higher than this.

Paracetamol administration may be combined with NSAIDs.


These are excellent for mild to moderate pain, especially bone pain. There may be synergy with other agents such as opiates. Of interest is the fairly recent advent of ketorolac, which is a non-steroidal shown to be equipotent with opiates for acute pain, when given parenterally. It shares the side effects of other NSAIDs.

Side effects of NSAIDs

Although excellent agents for pain, all non-steroidals share worrisome side effects, that include:

These side effects are of particular concern in the elderly, where gastrointestinal bleeding following even a single dose of NSAID is extremely common. We have recently seen the arrival of selective COX-2 inhibitors, but their role in acute pain is not yet well-defined, although they seem set to revolutionise the management of, for example, chronic arthritis. The mechanisms of action of NSAIDs are numerous, and beyond the scope of this talk.

5. Opiates

There is a variety of opiates, but our 'gold standard' is still morphine. Speaking of gold, here are a few comparative prices and 'equivalent' doses:

Opiate prices
Agent/Opiate (name) Amount Price (approximate)
Gold 1 oz (about 31.1 g) R1800
Morphine 15mg R0.17
Sufentanil 10µg R10.00
Fentanyl (generic) 100 µg R1.70
It can be seen that (a) Morpine is a very inexpensive drug and (b) sufentanil is vastly more expensive than gold, at R~31 million/oz (for what this is worth)!

Most opiates appear to have their analgesic effect predominantly through stimulation of mu opiate receptors. Onset of action is generally within minutes, depending on mode of administration, and time to peak effect depends on the opiate - for example, with morphine, it's about ten to fifteen minutes when given intravenously. Morphine should not only be regarded as a prototype drug, but still among the best we have - it's a brilliant analgesic.

Opiate side effects

All opiates have substantial side effects. Your name doesn't have to be Shipman for you to realise that large doses are potentially lethal. Opiates must be administered with care. Side effects include:

Different opiates

There is a variety of opiates. Generally it is a good idea to use the one(s) that you are familiar with. The newer (and more expensive) opiates have both benefits and problems to offer. They are generally devoid of histamine release, and are remarkably haemodynamically stable, although one should remember that large doses of morphine were commonly used in cardiothoracic surgery (with good results) prior to the advent of say fentanyl. There has been much fuss made about the greater potency of certain agents - this is completely irrelevant. What really counts is efficacy. If you use agents such as fentanyl, you should be aware of the complex kinetics. Remifentanil is an interesting new agent with an ultrashort duration of action. The unfortunate consequence is that if you turn off the infusion, the patient will wake in agony unless you give a longer acting agent such as - wait for it - morphine!

There are few indications to give agents such as pethidine repetitively, although once-off dosages may be useful, for example in tonsillectomies in children. Pethidine is a particularly 'dirty' drug, with one major side effect - with chronic repeated doses, especially in renal failure, the metabolite normeperidine accumulates, and eventually causes generalised seizures.

Certain opiates should be mentioned only to be condemned. A nasty opiate mixture is papaveretum (trade name e.g. 'Omnopon'). This is about 50% morphine, and 50% other rubbish. There is in our opinion never an indication to administer this "drug". If you want an opiate that has been cut with rubbish, perhaps you should contact your local street-corner pusher!

Opiate doses

One of the greatest crimes we regularly commit is to give a fixed amount of opiates at a fixed interval. Opiates should ideally be titrated according to the needs of the individual, which vary widely from person to person. This can equally well be done by an attentive and concerned nursing sister (or even doctor!) with the morphine drawn up and ready, or using patient controlled analgesia. If a patient is in pain, then opiates should be titrated in until the pain is controlled. Individual responses to opiates vary widely.

Doses are in their conservative infancy when opiates are administered epidurally or intra-thecally. Extreme care and diligent monitoring for 24 hours after the last dose are pre-requisites for these therapies, to detect and manage potentially life-threatening respiratory depression which may occur. Despite much hype and nonsense that has been written, the only opiate that is of value given by these routes is morphine. Opiates such as fentanyl and sufentanyl are of no merit given epidurally or intra-thecally, and might just as well be given intravenously.

The maximum epidural dose of morphine that should be given at any one time is 1mg. (3mg epidurally is equivalent to 45 to 60mg intravenously)! Intrathecally one only has one chance, and should give a maximum of 200 micrograms, which may work for twenty four hours.

Monitoring opiate administration

Monitoring facilities should be similar to those used for local anaesthesia. Remember that respiratory rate alone may not show the true picture. Dose and interval should be adjusted according to individual requirements, preferably using PCA.

All too often, nurses will refuse to administer opiates to someone in pain because "It's written up four hourly and only three and a half hours have elapsed". An atrocity!

Other opiates

Mention should be made of codeine. Codeine is a pro-drug which has no effect itself. It is metabolised by cytochrome P450 (2D6) to morphine. It's effect may therefore be extremely variable. In patients deficient in 2D6 (up to 10% of Caucasians), the drug is ineffective. In those who are 'super-metabolisers', the opposite may occur, with massive production of morphine resulting in severe abdominal discomfort (a recognised effect of morphine in large doses)!

6. Patient-controlled analgesia (PCA)

Just as morphine is the gold-standard analgesic, PCA is our gold-standard for analgesic administration. Remember that PCA is no better than a really good nurse. The basic idea is that the patient self-administers analgesic boluses, with a "lock-out" time to prevent excess doses in too small a time. Most devices also have the facility to limit the total hourly dose.

Important is that the patient understands the PCA device. The concept and device should be explained pre-operatively to the patient - if this is done, then most patients can use PCA, including many older children.

Our principles of PCA are:

  1. There is absolutely no point in giving a basal infusion. This is out of date.
  2. Bolus doses should be large enough for the patient to feel and respond to the dose, thereby giving good 'feedback' that something is happening. We're talking 1.5 to 2mg.
  3. Lock-out time should be adjusted appropriately. We often start at 6 minutes, but this may need to be adjusted upwards. Remember to tell the patient preoperatively that morphine doesn't work immediately, but "takes 5 to 10 minutes to work, so there's no point in pressing the button several times a minute". Stress that the patient is in control of their pain, and that even if the pain is initially severe, it will be controlled.
  4. PCA must be given by a dedicated line. Can you work out why?
  5. Intravenous and subcutaneous PCA appear equivalent, although there is generally much resistance to the latter. S/C PCA is particularly valuable in paediatrics. Local injection site reactions are rare. Considerable fuss has been made about concentrations: generally higher concentrations with lower volumes are used for S/C administration, the reverse for IV. For IV we use a standard mix of 1mg/ml of morphine.
  6. Patient monitoring should be appropriate, ideally in a high-care area.

7. The value of pain, and other quibbles

We know that those rare individuals with congenital insensitivity to pain live miserable lives. They are prone to mutilating injuries, and generally become progressively debilitated. Likewise, patients with acquired insensitivity, for example those with syringomyelia or leprosy. In contrast, there is no evidence that acute pain related to injury or surgery is anything other than a scourge. Isolated individuals have argued unconvincingly that pain subserves some function in promoting an immune response in acute infection or injury.

Another topic that is frequently broached is that of addiction. There is again absolutely no evidence that a person in acute pain has ever become an addict following adequate administration of analgesics. The 'potential for addiction' is never an excuse to withold opiates or other pain killers.

8. Cancer Pain

Perhaps the single defining characteristic of the pain associated with advanced malignancy is how badly it is managed by medical staff. The topic is complex, but basic principles of pain management still apply. Most cancer pain can be managed using conventional strategies.

Most important is to keep the patient informed about their disease, and to get the patient on your side in managing the pain - a positive attitude that the pain will be controlled goes half way towards controlling the pain. Here more than anywhere, the strategy of combining different modes of analgesia pays off.

If the patient is in severe pain, this must be addressed immediately. Perhaps the easiest way to do so is to take a 15mg (1ml) ampoule of morphine and make it up to 15 ml, and then titrate in 2 mg boluses every 5 to 10 minutes until the pain is controlled. You can then usually convert to oral morphine syrup. Because the biovailability of oral morphine is under 40%, you will have to titrate the doses to effect - start with an oral dose about twice that required intravenously to achieve initial pain control.

The rules for morphine administration are:

1. Make friends with your pharmacist! Morphine syrup has to be made up to the concentration you specify. This is a pain, especially as it's a schedule 7 drug.

2. Stick to the rules for writing S7 medication. Document all management meticulously.

3. Titrate dose and interval to effect. Explain the principles to the patient. Approximately four-hourly dosing often works well, with little "break-through" pain, but allow the patient to be flexible. It's a great idea to interlace doses of different agents - a dose of morphine can be taken; an hour later a dose of paracetamol; and then an hour later again, a dose of non-steroidal anti-inflammatory, and so on..

4. Give antemetics such as cyclizine, metoclopramide. Be aware of the potential toxicities of these agents, especially in higher dosages.

5. Give aperients Walk the wards and you will seldom find a patient on opiates who has passed stool in the preceding three weeks - as many doctors ignore this simple rule.

6. Slow release morphine sulphate is available and can be used once the pain is controlled and a dosage has been established. It's convenient, but supplemental morphine syrup may still be beneficial. Do not simply plonk someone on a convenient dose of "MST" without sitting down and establishing their morphine needs.

7. Analgesic needs vary and may increase with time. Concerns about 'addiction' in the patient with advanced cancer are irrelevant.

8. When confronted by intractable pain, consult an expert.


The most important aspect of all pain control is to communicate with the patient. Be aware of those in pain (even when they cannot tell you about it, eg with head injury) and address the pain aggressively. Keep the patient informed and reassured.