Background: Opioids such as morphine are widely used for the management of pain associated with acute pancreatitis. Interestingly, opioids are also known to affect the immune system and modulate inflammatory pathways in non-pancreatic diseases. However, the impact of morphine on the progression of acute pancreatitis has never been evaluated. In the current study, we evaluated the impact of morphine on the progression and severity of acute pancreatitis.
Methods: Effect of morphine treatment on acute pancreatitis in caerulein, L-arginine and ethanol-palmitoleic acid models was evaluated after induction of the disease. The reporting of these RCTs should also be improved to allow users of the medical literature to appraise their results accurately. Large longitudinal studies are also needed to establish the risk of pancreatitis complications and adverse events related to drugs.
Abdominal pain is the main symptom and is usually accompanied by nausea, vomiting and fever. Opoids are commonly used to manage pain in acute pancreatitis but there are still some uncertainties about their clinical effectiveness and safety. There were no restrictions by language or publication status. We considered randomised clinical trials RCTs assessing the effectiveness of any opioid drug used for treating acute pancreatitis pain. Two review authors independently selected studies, assessed risks of bias and extracted data.
We performed an intention-to-treat ITT analysis. We undertook meta-analysis for some outcomes. The opioids assessed were intravenous and intramuscular buprenorphine, intramuscular pethidine, intravenous pentazocine, transdermal fentanyl and subcutaneous morphine.
One RCT, comparing subcutaneous morphine with intravenous metamizole reported non-significant reduction in the number of participants with improvements in pain intensity primary outcome RR 0.
Three studies compared analgesia using opioids with non-opioid treatments. After excluding one study that used opioids through continuous intravenous infusion, there was a decrease in the number of patients requiring supplementary analgesia RR 0. In a single study, there were no differences in the number of patients requiring supplementary analgesia between buprenorphine and pethidine RR 0.
Pancreatitis complications were not associated with a significant difference between the drugs tested. No clinically serious or life-threatening adverse events occurred related to treatment. No differences for this outcome were found between opioid and non-opioid treatments, or for type of adverse event nausea-vomiting and somnolence-sedation.
One death in the procaine group was reported across all the trials. This is because pancreatic acinar cells are able to defend themselves against cellular injury, to inhibiting further progression of the disease, in part by activating an acute phase reaction characterized by a massive but reversible changing in pancreatic gene expression 1. In fact, whereas the acute phase response genes and some stress genes are up-regulated, genes coding for secretory enzymes as well as markers of differentiation were simultaneously down-regulated 2.
Multiple cell types participate in the process of exocrine pancreas repair and regeneration which is starting almost instantaneously from the point of injury. Importantly, the cells involved in pancreas regeneration include not only the acinar cell, but also epithelial cells of the ducts, inflammatory cells such as neutrophils, macrophages and lymphocytes, and pancreatic stellate cells responsible of the transitory fibrogenesis.
The pancreatic regeneration occurs as a consequence of a coordinate activation of several signaling pathways involved in both cell growth and differentiation. The chief symptom of AP is the abdominal pain that is typically reported in the epigastric region or right upper quadrant which in the majority of the patients it is radiating into the upper back or right shoulder. AP generally causes an intense and continuous pain, and consequently, it requires an effective treatment.
Opioids, principally morphine, could be a suitable choice in the treatment of AP pain. When compared with other analgesic possibilities, morphine could decrease the necessity of additional analgesia, which could be a real clinical advantage.
However, during the last years, the utilization of opioids for the treatment of patients with AP was only partially useful because opioid, especially morphine, were from long time considered to cause dysfunction of the sphincter of Oddi when systemically administered 3 , 4.
Nonetheless, several studies, including sophisticated meta-analysis, suggest that morphine has no demonstrated significantly negative effect on the course of AP 5 - 9.
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