Clinical Pancreatology for Practising Gastroenterologists and Surgeons. Группа авторов
World J Gastroenterol 2006; 12(31):5068–5070.
9 Guidelines for the Treatment of Pain in Acute Pancreatitis
László Czakó
First Department of Medicine, University of Szeged, Szeged, Hungary
Introduction
Abdominal pain is the most common symptom as well as the most serious complaint from patients with acute pancreatitis (AP). Management of AP is limited to supportive care and the treatment of complications when they develop. Pain management is one of the main clinical objectives in these patients and this does not hamper diagnosis or modify the course of the disease. However, the treatment of pain improves comfort and patient‐reported outcomes.
Analgesics for AP can be divided into three categories: nonsteroidal anti‐inflammatory drugs (NSAIDs), opioid analgesics, and local anesthetics. The choice of analgesics is currently not straightforward. There is very limited evidence and the overall quality of evidence is very low regarding the degree of efficacy of the various pharmacological substances used to treat pain in AP [1].
Nonsteroidal Anti‐inflammatory Drugs
NSAIDs are the first‐line therapy for pain and they are generally administered to AP patients upon admission to the hospital. NSAIDs provide analgesia but are also associated with anti‐inflammatory and antipyretic effects, and also work to prevent blood clots. NSAIDs work by inhibiting the activity of cyclooxygenase enzymes (COX‐1 and/or COX‐2). These enzymes are involved in the synthesis of key biological mediators, namely prostaglandins, which are involved in inflammation, and thromboxanes, which are involved in blood clotting [2]. There are two types of NSAID available: nonselective and COX‐2 selective. Most NSAIDs are nonselective, and inhibit the activity of both COX‐1 and COX‐2. These NSAIDs, while reducing inflammation, inhibit platelet aggregation (especially aspirin) and increase the risk of gastrointestinal ulcers/bleeding. COX‐2 selective inhibitors have less gastrointestinal side effects, but promote thrombosis and substantially increase the risk of heart attack. As a result, COX‐2 selective inhibitors are generally contraindicated due to the high risk of undiagnosed vascular disease. By inhibiting physiological COX activity, all NSAIDs increase the risk of kidney disease and, through a related mechanism, heart attack.
Intravenous metamizole (2 g per 8 hours i.v. with slow perfusion) demonstrated similar efficacy to that of morphine (10 mg per 4 hours s.c.) in acute pancreatitis [3]. Most importantly, this drug seems to have the same efficacy as opiates in controlling AP pain. Therefore, it was suggested that metamizole may be used as a first‐line analgesic drug in AP, reserving opioids as a second choice and which may be used in the case of metamizole failure [4].
Paracetamol (acetaminophen) is generally not considered an NSAID because it has only minor anti‐inflammatory activity. It treats pain mainly by blocking COX‐2, mainly in the central nervous system. Intravenous administration of paracetamol 1 g was as effective as dexketoprofen 50 mg or tramadol 1 mg/kg in reducing pain in AP in a randomized trial [5]. The primary side effect of acetaminophen administration is potential liver toxicity, and therefore caution is advised in patients with preexisting liver dysfunction.
There are numerous case reports on the association of NSAID use with AP. Large population‐based case–control studies demonstrated that there is a risk for AP in patients taking NSAIDs, with an adjusted odds ratio (OR) of 2.7. The highest risk is for diclofenac (OR 5.0) and the lowest for naproxen (OR 1.1). Therefore, naproxen should be the preferred analgesic for limiting the risk of development of AP. COX‐2 selective inhibitors are associated with a lower risk (OR 1.4) of AP than most other NSAIDs [6].
Patient‐controlled analgesia (PCA) is a delivery system with which patients self‐administer predetermined doses of analgesic medication to relieve their pain. PCA provides small on‐demand analgesic doses that allow patients to safely titrate to their own therapeutic plasma level of analgesic. PCA improves pain relief and results in greater patient satisfaction. Continuous perfusion of analgesic may be administered in addition to the on‐demand dose. It may provide more effective pain relief during sleep and decreases the number of loading doses administered by the patient (Table 9.1).
Table 9.1 Intravenous administration of analgesics.
| Drug | Concentration | Infusion rate | Bolus (i.v.) |
|---|---|---|---|
| Metamizol | 500 mg/ml | — | 3× 1000 mg i.v. daily |
| Acetaminophen | — | — | 2–4× 1000 mg i.v. daily |
| Diclofenac | 25 mg/ml | — | 2× 75 mg i.v. daily |
| Ibuprofen | 4 mg/ml 6 mg/ml | — | 3× 400 mg i.v. daily 2× 600 mg i.v. daily |
| Tramadol | 50 mg/ml | 10–15 mg/h | 4× 50–100 mg i.v. daily |
| Nalbuphine | 10 mg/ml | — | 4× 20 mg i.v. daily |
| Meperidine (pethidine) | 50 mg/ml | — | 4× 15–50 mg i.v. daily |
| Morphine | 10 mg/ml 20 mg/ml | 1–2 mg/h | 2 mg i.v. 6× 5–10 mg i.m. daily |
| Fentanyl | 50 μg/ml | 25–100 μg/h | 50–100 μg i.v. |
| Sufentanil | 5 μg/ml | 5–10 μg/h | 5–10 μg i.v. |
Opioid Analgesics
Opioids represent the next stage in the treatment of pancreatic pain. Opioids can be classified by their actions: agonist (e.g. morphine, hydromorphone, fentanyl), partial agonist (e.g. buprenorphine), agonist/antagonist (e.g. pentazocine), and antagonist (e.g. naloxone). Pure opioid agonists are the most potent analgesics, and they are stronger pain relievers than non‐opioids.
Opioids acts by binding to opioid receptors (μ1 and μ2, κ and δ) found in the central, peripheral, and autonomic nervous system. They induce analgesia by inhibiting neurotransmitter release on presynaptic neuronal terminals in the spinal cord and inhibition of postsynaptic neurons preventing the ascending transmission of the pain signal. Tramadol possesses both weak opioid agonist activity and inhibition of serotonin and norepinephrine uptake. This dual mechanism of action is considered to underlie its effectiveness in some pain patterns that are poorly responsive to other treatments. Tramadol has been shown to be superior to morphine, with fewer gastrointestinal side effects for the same level of analgesia.
Traditionally,