Appendix 3: Special Medication Delivery Systems
This article is Appendix 3 of the book "How Cancer Pain is Treated: A non-technical guide for patients and their carers". You will find links to the other articles in the series at the bottom of this page. Alternatively, you may download the whole book in various formats HERE. (All downloads are free.)
This article, written by a senior medical practitioner with considerable experience in palliative medicine and hospice care, is offered purely for educational purposes. Nothing in it should be taken as therapeutic advice for any particular patient. Mention of any trade (brand) name should not be taken as an endorsement of the brand or its manufacturer.
If you read the articles in this series carefully, and think about the information in them, in relation to a particular pain management problem affecting you or someone you love, you may sometimes be able to think of modifications to the current treatment which might be expected to improve the situation.
However, it is very dangerous to make changes to a patient's medication without first discussing them with the prescribing doctor. The doctor must always know exactly what the patient is taking, as virtually all medications can cause unwanted side effects and interact in various ways with other medications.
Importantly, this also applies to "natural", "alternative" or "complementary" therapies, many of which have significant interactions with prescribed medications. Therefore, even if you feel that the current pain management is not optimal, never make any changes without first discussing them with the doctor.
Syringe drivers are very useful for delivering medication by continuous infusion, often via a "butterfly" needle which is sited subcutaneously somewhere convenient, such as the anterior surface of the chest or abdomen. If a single analgesic medication is being infused continuously, extra doses of a predetermined size can be added to that infusion by the patient or nursing staff if breakthrough pain occurs, or if incident pain is expected, simply by pressing a button on the device.
A syringe of suitable size is filled with the medication which is to be administered, placed in the device, and connected to a butterfly needle by a flexible tube. After expelling air from the system, the butterfly needle is inserted subcutaneously at the chosen site and covered with sterile adhesive film, which keeps it in place and also protects the entry point from contamination.
The plunger of the syringe is then moved along very slowly by the drive mechanism of the device, over a number of hours, at a rate set by the doctor, nurse or pharmacist. This rate is, of course, calculated so that the medication in the syringe will be administered exactly as fast as is necessary in order to provide that particular patient's baseline analgesia.
Although this sounds simple, the end result depends on quite a number of steps, each of which must be carried out correctly in order to achieve the desired effect. Therefore, anyone who is responsible for the use of this type of medication delivery system must obviously be familiar with the particular device in use, as well as the general principles involved, and must have received suitable training and supervised experience.
The devices themselves can be quite temperamental. There have been some welcome advances in their engineering in recent decades, but they are still far from foolproof, so close monitoring of their function is essential. If, for example, the plunger jams and therefore fails to advance at the set rate, baseline analgesia will fail, and the patient's pain will return. Alternatively, if the rate is set incorrectly high, the patient will receive a progressively worsening overdose of the medication.
When necessary, multiple medications can be combined in a single subcutaneous infusion, though more frequent re-siting of the subcutaneous needle is then usually necessary. Morphine sulphate, hyoscine, haloperidol, metoclopramide, promethazine and midazolam are usually compatible together in a syringe.
Importantly, when there is more than one medication in the syringe, extra opioid doses for breakthrough or incident pain cannot be given from that syringe, as an extra amount of each other medication in the syringe would be received by the patient, as well as the desired extra dose of opioid.
Some medications, such as diazepam and prochlorperazine, cause irritation when infused subcutaneously. Morphine tartrate (which has the sometimes considerable advantage of greater solubility than morphine sulphate) is inclined to form a precipitate when mixed with various other useful medications. The assistance of a pharmacist is therefore invaluable when more than one medication is to be loaded into the syringe.
Patient-Controlled Analgesia Pumps
Although Patient-Controlled Analgesia (PCA) is primarily used for post-operative pain management, usually by the intravenous or epidural route, the same type of pump can be used as an alternative to a syringe driver when baseline analgesia is being provided by continuous subcutaneous infusion.
In addition, PCA itself is sometimes used as a temporary measure when a patient is admitted to hospital for the purpose of achieving rapid control of pain and then determining a suitable maintenance regimen. In this case, the intravenous route is often used initially, converting to a more suitable route for long term use when the correct dosage has been established.
As discussed in previous articles in this series (see the series links near the bottom of this page), the longer term use of intravenous opioids should be avoided whenever possible, partly because of the inevitable complications associated with venous cannulae, and partly because there is anecdotal evidence of excessive dose escalation when extra doses are frequently given intravenously.
Neuraxial Delivery Systems
Neuraxial administration usually means injection or infusion near the spinal cord, either inside (intrathecal) or just outside (epidural) its membranous coatings. However, the term can also be applied to an infusion into the cerebral ventricles (inside the brain).
Neuraxial delivery systems are sometimes used for the intrathecal administration of opioids, local anaesthetics and various other medications. The opioid most often chosen for intrathecal delivery is morphine. The local anaesthetic usually chosen for intrathecal delivery is bupivacaine. Two other agents which have an established role in intrathecal analgesia are the alpha-2 adrenergic receptor antagonist clonidine, and the GABAB receptor agonist baclofen. Various other medications, such as ketamine, midazolam and ziconotide, are also being evaluated for possible use as intrathecal analgesics.
The last agent mentioned, ziconotide, which is marketed under the trade name Prialt, is rather interesting. It is a synthetic analogue of a substance found naturally in a marine snail called Conus magus. Its therapeutic action is the result of selective blockade of a neuronal transmission channel called the N-type voltage-sensitive calcium channel, so it is the first example of a new class of analgesics called N-type calcium channel blockers (NCCBs). Ziconotide could provide another option for patients whose pain has not been satisfactorily controlled by the methods currently in regular use, but it is too early to predict how often, or how effectively, it might come to be used.
However, it should be remembered that intrathecal infusions and other neuraxial delivery methods are only very occasionally appropriate in the management of cancer pain. They have the potential to provide very powerful analgesia with minimal drug side effects, but they also have risks of their own, some of which can be serious, so they should not be used if less invasive alternatives are available and effective.
When neuraxial analgesia really is necessary, a catheter can be tunnelled under the skin to a convenient site and connected to a suitable infusion pump. Totally implanted systems (with a subcutaneous portal for the addition of medications to a reservoir) are probably the only satisfactory way of providing long term neuraxial analgesia.
Declaration of Interest
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Articles in the Cancer Pain Series
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