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Techniques of opioid administration.

Burwaiss M,et al.

Journal: Anaesthesia and Intensive Care Medicine. 2013; 14 (11): 491-495. 8 references
Reprint: Moutaz Burwaiss, MBChB, FRCA, Consultant Anaesthetist and Pain Specialist, Glasgow Royal Infirmary, Glasgow, UK.
Faculty Disclosure: Abstracted by N Walea, who has nothing to disclose

Editor's Note:
This is a useful review of the routes of administration possible for opioids in patients in whom the oral route will not suffice or is unavailable. Those not familiar with all these routes would note morphine equivalents and unique properties of each route to avoid adverse effects.
Pharmacology of opioids
Technique: types of delivery

The main pharmacological treatment for severe acute pain continues to be opioids. Traditional methods of opioid administration are oral, intramuscular, subcutaneous and intravenous. Acute pain management has improved with the introduction of advanced techniques for administration of opioids (patientcontrolled analgesia [PCA] and epidural analgesia) and, more recently, innovative non-invasive modalities. Morphine is the gold standard to which all other opioids are compared. Oral opioids are available asimmediate-release (IR) and slow-release (SR) and can be used as step-down analgesia from epidurals or PCAs. Oral morphine has a bioavailability of about 30%--10 mg of IV morphine is roughly equivalent to 30mg of oral morphine—the ratio is only a guide since inter-patient variability requires each patient be
carefully titrated to an appropriate dose. In patients unable to take oral medications and when other methods are unsuitable, rectal opioid suppositories may be useful. Absorption of the drug varies with the site of placement in the rectum, contents of the rectum and its blood supply. Drugs absorbed from the lower half of the rectum drain into the inferior vena cava and avoid first pass metabolism. Contraindications to the use of this route include previous colorectal surgery and a rectal lesion.
For the treatment of moderate to severe acute pain, intramuscular and subcutaneous injections of opioids are commonly used. Absorption depends on the perfusion of the chosen site for injection with absorption being minimal during periods of low perfusion (hypovolaemia, shock, hypothermia) but, when profusion improves, a large dose of opioid may be dumped into the patient’s systemic circulation. Subcutaneous injection via an indwelling cannula in the subcutaneous tissue of the upper outer aspect of the arm or thigh is less invasive, has a high patient acceptability, and reduced risk of nerve injury. A superlative means of establishing rapid analgesia is an intravenous bolus which may be used for hypotensive or hypovolaemic patients, when absorption of the drug after intramuscular or subcutaneous administration is less predictable, to achieve initial pain relief and to deal with episodes of inadequate analgesia. To obtain stable analgesic levels and avoid the peaks and trough of intermittent bolus doses, intravenous infusion of opioids is used. Slow onset time and inter-patient variability of response to opioids may result in inadequate treatment of pain or delay the onset of side-effects such as respiratory depression. Bolus doses should be used to obtain analgesia before beginning infusion and if breakthrough pain occurs. The patient is allowed to self administer a predetermined dose of opioid within the controls of a lockout period by means of intravenous patient-controlled analgesia (IV PCA). This results in less variability in blood levels of the drug but does require establishing analgesia prior to PCA commencing like a continuous IV infusion. Epidural and intrathecal routes provide the most rapid analgesia of all available modalities because of the direct application within the central nervous system. Patient-controlled epidural analgesia (PCEA) allows patients to self-titrate the amount of drug required on the basis of individual analgesic need and may reduce the number of dosing adjustments required. Doses of drug for intrathecal analgesia are much smaller than those for epidural analgesia. Only opioid solutions formulated for spinal administration should be used because other formulations may contain potentially neurotoxic preservatives. Due to their high potency, lipophilicity and low molecular weight, fentanyl and buprenorphine are the most commonly used opioids for transmucosal and transdermal administration. Intranasal opioids must be given in small volumes and at high concentration to avoid run-off into the pharynx. Using both nostrils doubles the absorptive capacity and use of atomized particles enhances absorption. Pulmonary absorption is unpredictable and variable and is unlikely to be used for pain relief. Transdermal drug delivery relies on passive diffusion into the skin with slow onset time and stale plasma levels but body temperature of greater than 40degrees C and external heating devices can increase absorption rates by
one-third. At least 4 days are required for steady state plasma levels so transdermal routes are unsuitable for the management of acute pain. 
Important Points:
To make opioid administration more effective, it is necessary to individualize treatment regimens by titrating the drug dose and frequency to suite the patient; that is, to titrate the dose against the effect and minimize adverse effects. 

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