Epidural analgesia (continuous infusion containing a mix of bupivacaine 0.1% and fentanyl 2 μg/ml at 6–15 ml/hour) has been demonstrated to reduce pain and improve perfusion of the pancreas compared with patients receiving controlled intravenous analgesia (fentanyl 10 μg/ml at a rate of 10–20 μg/hour) [15]. The increased pancreatic blood flow suggests that the use of epidural analgesia may decrease progression from edematous to severe necrotizing pancreatitis caused by early ischemia of the gland and thus could reduce severity of the disease. Epidural analgesia reduced the development of acute mesenteric ischemia and 30‐day mortality in critically ill patients with AP [16]. These findings support the use of epidural analgesia as a therapeutic intervention in AP.
Epidural analgesia‐related complications are rare, but may be potentially severe and include hypotension, infection, nerve damage, or epidural hematoma. Hypotension is one of the awaited side effects of the sympathetic blockade from epidural analgesia, with an incidence of 8%. It responds adequately to intravenous fluid administration and vasopressor therapy.
The pancreas sympathetic afferent innervations originate in T6–L2. The catecholamine release, one of the main factors contributing to maintenance of blood pressure, occurs by stimulation of the adrenal medulla, innervated by T5–L1. Therefore, a low thoracic block (T8–T10) should be used to minimize the block extension and lower the risk of hypotension.
Catheter dislocation can occur in 20% of patients, but the catheter can be safely replaced in patients showing no signs of local infection.
The optimal length of epidural analgesia is not well defined. Good clinical tolerance was observed with a duration of 11 days. Replacement of the catheter should be discussed if it stays in place for a longer period in order to avoid infection risks. A close follow‐up searching for local and systemic signs of untreated infection is required, and the catheter should be removed as soon as serious infectious risks are detected.
Epidural analgesia with local anesthetic can provide adequate pain relief. However, combined epidural analgesia using a major analgesic and local anesthetic resulted in better analgesia with smaller doses and a reduced hypotension rate in prospective randomized trials. Combined epidural analgesia is therefore recommended.
Epidural analgesia can be provided using a patient‐controlled epidural analgesia device, with a continuous infusion rate of 5–15 ml/hour. A bolus of 5–10 ml every 30–60 minutes could be added upon request (Table 9.2).
Use of epidural analgesia is currently limited in AP. Therefore, the clinical application and management of epidural analgesia, for example the precise thoracic level at which the epidural catheter is inserted, the duration the catheter stays in place, the type and dose of local anesthetics, and the type of opiate to be used, should be standardized. A multicenter randomized controlled trial of epidural analgesia in AP is ongoing, which will further contribute to assessing efficacy of this procedure [17]. Until then, epidural analgesia is a feasible, safe and effective procedure in patients with severe AP when managed by expert anesthesiologists in the intensive care unit and favor its clinical use in this setting. It has a promising effect on the microcirculation and organ dysfunction in AP. Epidural analgesia should be introduced as early as possible, when conventional analgesic therapy is insufficient to prevent the potential side effects of major analgesics. Furthermore, it can be supplemented by intravenous administration of NSAIDs.
Local Anesthetics
Application of local anesthetics such as procaine in patients with AP is mainly used in the German‐speaking world. Local anesthetics have a membrane‐stabilizing effect and reversibly prevent the genesis and transmission of nervous stimuli. Furthermore, they exert potent anti‐inflammatory effects on virtually every level of the inflammatory cascade, prevent overactive immune responses without impairing host defense mechanisms, and modulate gastrointestinal motor functions. In addition, they display potent neuroprotective effects and inhibit phospholipase A2. Treatment with intravenous procaine (2 g per 24 hours) improved pain severity and reduced the demand for additional pain medication compared with placebo in a randomized double‐blind study published in 2011 [18]. However, no clinical trial has been published about the effects of procaine on pancreatic pain since then. The adverse effects of procaine are weakness, dizziness, hypertension, and skin rash in patients who are sensitive to the drug.
Summary
Pain alleviation is a vital step in the management of AP. However, no guideline suggests a recommended agent due to the limitations in current evidence.
A stepped multimodal approach is recommended to be applied for pain medications in AP (Figure 9.1). Such multimodal therapy has at least two desirable effects: (i) it may decrease the use of opioids and associated side effects; and (ii) it may be a more effective pain control strategy, potentially decreasing the complications associated with suboptimal pain control.
Figure 9.1 Step‐up management of pain in acute pancreatitis. Non‐opioids such as nonsteroidal anti‐inflammatory drugs (NSAIDs) or paracetamol (PCM) are recommended to be initiated at first step. Weak opioids (e.g. tramadol) with or without non‐opioids should be considered if the pain is constant and/or not controlled with non‐opioid analgesics. If pain still persists or increases, strong opioids with or without non‐opioids can be initiated. If pain is not relieved within a given time by conventional analgesic therapy, epidural analgesia is indicated.
NSAIDs are the first choice of analgesics. Opioid medications should be considered in a patient who has constant and/or severe pain not controlled with non‐opioid analgesics. The initial choice of opioid should be a weaker, mixed agonist/antagonist or partial agonist (e.g. tramadol) before using stronger opioids (e.g. morphine, meperidine, sufentanil). Sufentanil can be recommended because it is a potent opioid with high therapeutic index. If pain is not relieved within a given time by conventional analgesic therapy, epidural analgesia is indicated. Epidural analgesia is an efficient approach to pain management and may reduce the proinflammatory state and improve the outcome of AP.
References
1 1 Meng W, Yuan J, Zhang C, et al. Parenteral analgesics for pain relief in acute pancreatitis: a systematic review. Pancreatology 2013; 13(3):201–206.
2 2 Martinez J, Pérez‐Mateo M. Guidelines for the treatment of pain in acute pancreatitis. In: Domínguez‐Muñoz JE (ed.) Clinical Pancreatology for Practising Gastroenterologists and Surgeons. Oxford: Blackwell Publishing, 2005:87–94.
3 3 Peiró AM, Martínez J, Martínez E, et al. Efficacy and tolerance of metamizole versus morphine for acute pancreatitis pain. Pancreatology 2008; 8(1):25–29.
4 4 Pezzilli R, Morselli‐Labate AM, Corinaldesi R. NSAIDs and acute pancreatitis: a systematic review. Pharmaceuticals (Basel) 2010; 3(3):558–571.
5 5 Gülen B, Dur A, Serinken M, et al. Pain treatment in patients with acute pancreatitis: a randomized controlled trial. Turk J Gastroenterol 2016; 27(2):192–196.
6 6 Sorensen HT, Jacobsen J, Norgaard M, et al. Newer cyclo‐oxygenase‐2 selective inhibitors, other non‐steroidal anti‐inflammatory drugs and the risk of acute pancreatitis. Aliment Pharmacol Ther 2006; 24:111–116.
7 7 Thompson DR. Narcotic analgesic effects on the sphincter of Oddi: a review of the data and therapeutic implications in treating pancreatitis. Am J Gastroenterol 2001; 96(4):1266–1272.
8 8 Ona XB, Comas DR, Urrútia G. Opioids for acute pancreatitis pain.