Indomethacin For Prevention Research Articles

98 Combination Rectal Indomethacin and Topical Epinephrine Is Not Superior to Rectal Indomethacin in the Prevention of Post-ERCP Pancreatitis—A Meta-Analysis

INTRODUCTION: Post Endoscopic Retrograde Cholangiopancreaticography Pancreatitis (PEP) remains one of the major complications despite the advances. Several medications have been used in an attempt to prevent PEP. The efficacy of rectal indomethacin (RI) and topical epinephrine (TE) has been proved. However, the role of combination of epinephrine and indomethacin in PEP prevention has not been extensively explored. We aimed to determine the efficacy of combined RI and TE compared to RI alone for PEP prevention in high risk patients. METHODS: We searched the databases of MEDLINE, EMBASE, and CENTRAL from inception to May 2019. The inclusion criteria were published randomized controlled trials comparing the efficacy of PEP prevention between patients receiving combined RI and TE vs. RI alone in high risk patients. The outcome of interest was the rate of PEP occurrence. Data from each study were combined using the random-effects, generic inverse variance method of DerSimonian and Laird to calculate pooled risk ratio (RR) and 95% confidence intervals (CI). I2 statistics was used to assess heterogeneity among studies, with I2 >50% indicates significant heterogeneity. RESULTS: Three randomized controlled trials met our inclusion criteria and were included in the meta-analysis and reported a total of 772 and 728 patients in RI alone and combined RI and TE group, respectively (Table 1). The occurrence of PEP in combined RI and TE group is comparable to RI group with pooled RR of 1.10 (95% CI: 0.58–2.08, I2 = 47%) (Figure 1). Studies did not stratify PEP based on the severity and hence a subgroup analysis could not be performed in this meta-analysis. CONCLUSION: Based on the results from RCTs, combination of RI and TE do not give additional benefit to RI alone for PEP prevention in high risk patients for post ERCP pancreatitis. The mechanism of action of these two medications are different but the effects are not synergistic. The single use of each medication is effective to prevent PEP. Further RCTs are required to confirm our finding in high-risk patients.

Sa2079 Efficacy and Safety of Rectal Indomethacin for Prevention of Post Endoscopic Retrograde Cholangiopancreatography Pancreatitis in a Pediatric Population

Sa2079 Efficacy and Safety of Rectal Indomethacin for Prevention of Post Endoscopic Retrograde Cholangiopancreatography Pancreatitis in a Pediatric Population

Prophylactic rectal indomethacin may be ineffective for preventing post-endoscopic retrograde cholangiopancreatography pancreatitis in general patients: A meta-analysis.

Efficacy of prophylactic indomethacin for prevention of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) in general patients remains controversial. To address this, we conducted a meta-analysis of clinical trials specifically on rectal indomethacin in prevention of PEP in consecutive patients undergoing ERCP. We searched MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials databases to identify randomized, double-blind, controlled clinical trials on rectal indomethacin in the prevention of PEP in consecutive patients undergoing ERCP. Primary outcome was the overall rate of PEP. Secondary outcomes were the overall rates of moderate to severe PEP and mild PEP. Six studies, with a total of 2473 patients, were included. Overall rate of PEP was 7% (95% CI, 6-9%). No statistical difference was observed in overall rates of PEP (OR, 0.67; 95% CI, 0.46-1.00, P = 0.050) and, additionally, rates of moderate to severe (OR, 0.66; 95% CI, 0.28-1.56, P = 0.345) or mild (OR, 0.71; 95% CI, 0.45-1.10, P = 0.127) PEP between indomethacin and placebo. In a contemporary meta-analysis of available randomized controlled trials of consecutive patients undergoing ERCP, rectal indomethacin did not show significant prevention effect of post-ERCP pancreatitis.

Linagliptin, a dipeptidylpeptidase 4 inhibitor, ameliorates indomethacin‐induced enteropathy via GLP‐2 pathway

Glucagon‐like peptide‐2 (GLP‐2) is an intestinotrophic hormone secreted from enteroendocrine L cells. We have reported that dipeptidylpeptidase 4 (DPP4) inhibition prevents formation and promotes healing of indomethacin (IND)‐induced small intestinal ulcers in rats via GLP‐2 release and GLP‐2 receptor activation. We thus further examined the effect of the clinical DPP4 inhibitor linagliptin (LNG) on IND‐induced enteropathy.Small intestinal ulcers were induced by IND treatment (10 mg/kg, sc) in rats. LNG (0.1 – 5 mg/kg) was given once before IND for prevention, and for healing, once daily for 2 days starting 1 day after IND treatment.LNG treatment dose‐dependently reduced ulcer scores, accompanied by an increase of portal venous GLP‐2 concentrations. LNG promoted ulcer healing of IND‐induced intestinal ulcers. LNG‐induced healing was reversed by a GLP‐2 receptor antagonist. Ulcer healing was further accelerated by co‐treatment with L‐alanine plus inosinate, an umami taste receptor agonist. Compared to LNG, the DPP4 inhibitor NVP‐728, metabolized in the kidney, had a little effect on the enteropathy, suggesting that a long‐acting, entero‐hepatically circulated DPP4 inhibitor may be more efficacious in the prevention of intestinal mucosal damage.These results confirm our previous study that DPP4 inhibition prevents ulceration and promotes ulcer healing of NSAID‐induced enteropathy, enhanced by the luminal umami taste receptor activation, suggesting that GLP‐2 release enhanced by DPP4 inhibition and nutrient receptor activation is useful for the treatment of NSAID‐induced enteropathy.Supported by Boehringer Ingelheim, VA Merit Review, NIH R01 DK54221

The Effect of Indomethacin in the Prevention of Post–Endoscopic Retrograde Cholangiopancreatography Pancreatitis

Acute pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP) is a severe complication with substantial morbidity and mortality. Indomethacin has been identified to prevent this complication; however, the results using indomethacin have varied. Therefore, we performed a meta-analysis on the efficacy of rectally administered indomethacin in the prevention of post-ERCP pancreatitis (PEP). A systematic search was performed in November 2012. Randomized, placebo-controlled trials (randomized controlled trials) in adult patients that compared rectally administered indomethacin versus placebo in prevention of PEP were included. Meta-analysis was performed using a fixed-effects model to assess the primary outcome (PEP) and secondary outcomes (mild or moderate to severe PEP) using Review Manager 5.1. Four randomized controlled trials met the inclusion criteria (n = 1422). The use of indomethacin near the time of ERCP demonstrated a statistically significant decrease in PEP (odds ratio [OR], 0.49; 95% confidence interval [CI], 0.34-0.71; P < 0.01), mild PEP (OR, 0.52; 95% CI, 0.32-0.86; P = 0.01), and moderate to severe PEP (OR, 0.45; 95% CI, 0.24-0.83; P = 0.01) as compared with placebo. The number needed to treat with indomethacin to prevent 1 episode of pancreatitis is 17 patients. Rectal indomethacin significantly reduced the incidence of PEP. We recommend using indomethacin before or just after the procedure in patients undergoing ERCP.

Indomethacin for prevention of post-ERCP pancreatitis and hyperamylasemia

Objective To investigate the preventive effect of Indomethacin for post-ERCP pancreatitis and hyperamylasemia. Methods A total of 600 patients, who were undergoing ERCP, were randomly divided into 3 groups to receive anal Indomethacin （ n = 200）, intravenous octreotide （ n = 200） or no special medication （ n = 200） before ERCP. The level of serum amylase before and 24h after ERCP were measured, and the rate of acute pancreatitis and hyperamylasemia after ERCP were assessed. Results Serum amylase levels before ERCP of all groups were normal. The mean serum amylase level of Indomethacin group （ 101.3 ± 77.7 U/L） after ERCP was significantly lower than those of octreotide group （ 176. 6 ± 138.3 U/L, P = 0. 040 ] and control group （227. 2 ± 264. 9 U/L, P = 0. 048 ）, while there was no difference between oc- treotide group and control group （ P 〉 0. 05 ）. The incidence of post-ERCP pancreatitis in Indomethacin group （2. 5% ） was significantly lower than that of control group （9. 5%, P =0. 003）, while there was no difference between octreotide group （9. 5 % ） and control group （ P = 0. 05 ）. The incidence of hyperamylasemia after ERCP in Indomethacin group （5. 5% ） was significantly lower than that of control group （13.5%, P =0. 006）, while there was no difference between octreotide group （10. 0% ） and control group （P 〉 0. 05）. Conclusion Anal administration of Indomethacin before ERCP can effectively reduce the incidence of acute pancreatitis and hyperamylasemia after ERCP. Key words: Indomethacin; Cholangiopancreatography, endoscopic retrograde ; Pancreatitis; Hyperamylasemia; Octreotide

Brain Injury Caused by Intraventricular Hemorrhage: Is Indomethacin the Silver Bullet for Prevention?

After a series of promising but inconclusive reports concerning the role of neonatal administration of indomethacin in prevention of IVH (see earlier discussion), the largest and most recent study (n = 431), reported by Ment et al,4 indicates that indomethacin led to a decrease in incidence and severity of the lesion. The clinically important grade 4 IVH appeared to be nearly eliminated in the indomethacin-treated group. Thus, is it now clear that indomethacin should be administered at 6 to 12 hours of life to all very low birth weight neonates? Although such a recommendation might be appropriate, I have several concerns. First, as discussed earlier, experimental studies and observations of human infants indicate that indomethacin is a cerebral vasoconstrictor, leads to a decrease in cerebral blood flow, blunts adaptive vasodilatory responses, and may cause decreases in cerebral oxygen delivery marked enough to impair oxygen utilization. The threat of cerebral ischemia after indomethacin seems real, but notably in the study of Ment et al4 the frequency of ultrasonographic evidence of cerebral ischemic injury was no different in the indomethacin versus the placebo-treated neonates. This reassuring finding must be tempered by the awareness that cranial ultrasonography is somewhat insensitive in the detection of periventricular ischemic injury in the premature infant.41,42 A second concern relates to factors associated with the study of Ment et al.4 As discussed earlier, the placebo-treated group had an unusual preponderance of grade 4 versus grade 3 IVH, and the relatively large proportion of neonates with onset of IVH before 6 to 11 hours of age were not included in the study. Would earlier administration of indomethacin benefit the neonates with early IVH, or would complications be more prominent? A third concern relates to the recent study of the neonatal complications in infants exposed antenatally to indomethacin for treatment of preterm labor.43 Thus, when compared with a matched group of untreated infants, infants exposed to indomethacin before delivery exhibited a higher incidence of IVH (28% vs 9%, P = .02) and of necrotizing enterocolitis (29% vs 8%, P = .005). However, it is quite possible that the adverse effect of antenatal indomethacin on the occurrence of IVH related to the interaction of factors associated with labor and delivery (eg, increases in cerebral venous pressure) and associated with indomethacin (eg, inhibition of platelet aggregation). Such an interaction of factors would not occur with postnatal administration of indomethacin. Nevertheless, the findings of Norton et al43 are arresting in this context. Finally, Ment et al4 are to be congratulated for a carefully designed and well-executed study. The data are very promising and indicate the importance of a multicenter study to evaluate the role of indomethacin administered at or very shortly after birth on the subsequent occurrence of IVH and periventricular hemorrhagic infarction.

Indomethacin for Prevention of IV Hemorrhage

Results of a multicenter randomized trial of low-dose indomethacin (0.1 mg/kg IV) in prevention of intraventricular hemorrhage (IVH) in very low birth weight infants are reported from Yale New Haven Hospital, CT; Brown University, Providence, RI; and Maine Medical Center, Portland, ME.

The efficacy of intravenous indomethacin in prevention of postoperative pain

Since intravenous prophylactic anti-inflammatory agents have been suggested to reduce or even replace opiates in postoperative pain therapy, we studied the demand for morphine in 45 patients recovering from abdominal surgery who had received a baseline infusion of either indomethacin, morphine or saline placebo. When extubated after inhalational anaesthesia, each patient received an i.v. bolus of either 0.5 mg.kg-1 indomethacin, 0.07 mg.kg-1 morphine or saline placebo. Thereafter a 20-h infusion of the same test analgesic was started, either 0.1 mg.kg-1.h-1 indomethacin, 0.03 mg.kg-1.h-1 morphine or saline placebo. For additional analgesia, a patient-controlled analgesia device (PCA) delivering 5-mg boluses of morphine was used. For the first 5 postoperative hours, significantly more (P less than 0.05) PCA morphine was needed in the indomethacin group (35 mg) than in the morphine group (24 mg), while the placebo group demanded mean 30 mg. For equal analgesia (measured by VAS and VRS) between 5-20 h, similar amounts (mean 23 and 19 mg) of PCA morphine were required in the indomethacin and morphine groups, in contrast to the placebo group (mean 40 mg) (P less than 0.001). Morphine infusion increased the total consumption of morphine by 25% as compared to placebo. We conclude that, following abdominal surgery, the analgesic effect of indomethacin infusion became apparent after the first 5 postoperative hours, thereafter reducing the demand for PCA morphine by about 40%. Continuous morphine infusion diminishes the postoperative demand for PCA morphine, but also increases the total morphine consumption.

I.V. indomethacin in prevention of postoperative pain

I.V. indomethacin in prevention of postoperative pain