Patient Controlled Analgesia (PCA) became popular when it was realised that individual requirements for opioids varied considerably. Therefore a system was devised whereby patients could administer their own intravenous analgesia and so titrate the dose to their own end-point of pain relief using a small microprocessor - controlled pump. A variety of commercial devices are now available for this purpose. When pain is experienced, the patient self-administers a small bolus dose of opioid and experiences the benefit of this action. Thus they can adjust the level of analgesia required, according to the severity of the pain. In theory, the plasma level of the analgesic will be relatively constant and side effects caused by fluctuations in plasma level will be eliminated.

To achieve successful and safe analgesia with PCA requires that the patient understands what is required and this should be explained in detail before the operation. Almost every opioid drug has been used for PCA. In theory, the ideal drug should have rapid onset, moderate duration of action (to prevent the need for frequent demands) and have a high margin of safety between effectiveness and troublesome side effects. Choice usually depends upon availability, personal preference and experience. Once a selection has been made other parameters need to be set including the size of the bolus dose, the minimum time period between doses (the lock-out period) and the maximum dose allowed. Some devices permit the use of a continuous background infusion but for the reasons stated in the section on intravenous administration it will not be considered here.

see table 4

PCA need not be administered intravenously and intramuscular, subcutaneous and epidural routes have all been employed. Patients using PCA usually titrate their analgesia to a point where they are comfortable rather than pain free. The reasons for this are not clear but are probably related to fears of overdosage, the need for contact with members of the hospital staff and the expectation of some pain after surgery. The normal pattern of use is for frequent demands to be made in the initial postoperative period and for these to decrease with time. The total amount of opioid used is less with PCA than with intramuscular delivery. The overall incidence of side effects is about the same with the two techniques but the incidence of respiratory depression is less with P.C.A. Where this has occurred it has usually been due to incorrect programming, device malfunction or inappropriate use by third parties. Because of this, devices should be tamperproof and activated only by the patient. The pump should normally be attached to a dedicated intravenous cannula. If it is attached to an existing intravenous infusion it must be through a one way valve to prevent increments of opioid collecting in the giving set which may be delivered later as a large bolus if the infusion rate is increased.
 
Intrathecal and epidural opioids have been used following a wide variety of surgical procedures and other acutely painful conditions see table 5). Intrathecal opioids are easy to administer either to provide surgical anaesthesia or as an additional technique when general anaesthesia is given. Many patients will remain comfortable for 24 hours or more after a single injection of intrathecal morphine. The epidural route has been used even more extensively although the reason for this is not clear. It may be that anaesthetists are more familiar with the epidural route for the delivery of long term analgesia and because of the potential advantages in terms of long term catheter use and freedom from post -spinal puncture headache.

Side effects are common using these routes of delivery. They include nausea, vomiting, itching (which is much more common with morphine than other drugs) and urinary retention. Of most concern however, as with any opioid, is the possibility of respiratory depression. Early respiratory depression may be caused by systemic drug absorption. Late respiratory depression is from rostral (towards the head) spread in the cerebrospinal fluid and the incidence is increased by factors such as dose, age, posture, aqueous solubility of the drug administered, positive pressure ventilation and increased intra-abdominal pressure

It should be assumed that all patients are at risk of this occasional complication and a high level of care and vigilance should be maintained. Many centres recommend that patients receiving analgesia by these methods should be in a high dependency or intensive therapy unit. Trained personnel should be present at all times to check on the rate and depth of respiration and level of consciousness of the patient at regular intervals, protocols should be available for immediate treatment of complications and medical staff have received appropriate training. Respiratory rate alone is insufficient to measure the status of respiration. A more global assessment is necessary particularly during the first 24 hours of treatment. Any patient receiving intrathecal or epidural opioids whose level of consciousness drops must be assumed to have respiratory depression until proved otherwise. Where available, the use of supple-mentary oxygen has been recommended.

It is particularly dangerous to prescribe other opioids to patients receiving intrathecal or epidural opioids as this increases the likelihood of clinically significant respiratory depression.

Opioid/local anaesthetic mixtures have been adopted in some centres in an attempt to reduce the frequency and severity of side effects seen with infusions of pure local anaesthetics. Dilute concentrations of these agents have been combined with opioids and delivered by infusion through an epidural catheter. These mixtures appear to produce a synergistic effect. Bupivacaine appears to be most suitable for this purpose as dilute solutions produce a very limited motor block. A mixture of bupivacaine 0.1% and morphine 0.01% infused at 3/4ml/h gives good pain relief and permits the patient to walk without the risk of hypotension.

Other routes of delivery Transdermal, inhaled and intranasal opioids are among the routes of drug delivery currently under development.

 
Opioid analgesic agents (narcotics)

Opioid analgesic drugs act at receptors within the central nervous system. Initially three distinct receptor groups were described (mu, kappa and sigma) on the basis of their binding characteristics. The opioid drugs have differing affinities for these receptors and are described by their receptor affinities. Thus morphine and related compounds are known as mu agonists. Other analgesic agents have differing receptor affinities giving them different clinical properties.

Morphine remains the gold standard by which other analgesics are judged. Morphine has a short half life and poor bioavailability. It is metabolised in the liver and clearance is reduced in patients with liver disease, in the elderly and the debilitated. Major side effects include nausea, vomiting, constipation and respiratory depression. Tolerance may occur with repeated dosage but this is highly unlikely to become apparent during the first week of continuous treatment.

Parenteral doses range from 2.5mg to a maximum of 20mg. Morphine may need to be prescribed as frequently as 2 hourly.

Pethidine is a synthetic opioid which is structurally different from morphine but which has similar actions. It has a short half life and similar bioavailability and clearance to morphine. Pethidine has a short duration of action and may need to be given hourly. Pethidine has a toxic metabolite (norpethidine) which is cleared by the kidney, but which accumulates in renal failure or following frequent and prolonged doses and may lead to muscle twitching and convulsions. Extreme caution is advised if pethidine is used over a prolonged period or in patients with renal failure.

Parenteral doses range from 25mg to a maximum of 150mg. Frequency of administration 1 to 4 hourly.

Methadone is different from morphine and pethidine but has the same actions. It differs from the other agents in that it is well absorbed by mouth and undergoes little metabolism. It is slowly metabolised in the liver and has a very long half life. The resultant prolonged duration of action makes it more suitable for use in chronic pain rather than acute postoperative pain although it has been used successfully for this purpose.

Oral doses range from 2.5mg to 25mg given 6 to 12 hourly.

Fentanyl is used chiefly for intraoperative analgesia because of its relatively short duration of action. It has similar actions and side effects to morphine and is metabolised in the liver. Postoperatively it has been used intrathecally or epidurally as described earlier.

Buprenorphine is described as a partial agonist, which, in practical terms, means that it has different properties from drugs which work mainly at the mu receptor. Buprenorphine appears to have some action at all the major opioid receptors. Its most useful attribute is that it can be delivered by the sublingual route. It is rapdly absorbed and has a prolonged duratiuon of action (6 h) but is associated with a high incidence of nausea, vomiting and sedation. Of the opioids, buprenorphine poses the least risk to patients with renal failure as the metabolites are virtually inactive and if accumulation does occur it is of no significance. Sublingual doses range from 200-400mcg 8 hourly.

Nalbuphine and Butorphanol are known as agonist/antagonists as unlike conventional opioids, they act at the kappa receptor rather than the mu receptor. Both have been used to provide postoperative analgesia by intermittent, continuous and PCA techniques. They exhibit a ceiling effect for analgesic activity (which has limited their popularity) and also for respiratory depression which should make clinical use safer. They are alleged to have a lower abuse potential than conventional opioid agents.

Side effects and toxicity

Opioid analgesics share many side effects though the degree may vary between agents. The most common include nausea, vomiting, constipation and drowsiness. Larger doses produce respiratory depression and hypotension. The specific antidote naloxone is indicated if there is coma or very slow respiration. Because of its short action, repeated injections of 200 - 400mcg intravenously may be necessary. Alternatively, it may be given by continuous intravenous infusion, the rate of administration being adjusted according to response.

(Continued...)

---

©World Federation of Societies of Anaesthesiologists WWW implementation by the NDA Web Team, Oxford

---