A Randomized Controlled Trial of Topical Analgesia Post-Hemorrhoidectomy (TAPH Trial).

BACKGROUND: Postoperative pain remains the greatest problem after hemorrhoidectomy. Pain is hypothesized to arise from bacterial infection, sphincter spasm, and local inflammation. OBJECTIVE: A randomized controlled factorial trial was conducted to assess the effects of metronidazole, diltiazem, and lidocaine on post-hemorrhoidectomy pain. DESIGN: A double blinded randomized controlled factorial trial. SETTINGS: A multicenter trial was conducted in Auckland, New Zealand. PATIENTS: 192 Participants were randomized (1:1:1:1) into four parallel arms. INTERVENTIONS: Participants were randomized into one of four groups receiving topical treatment with 10% metronidazole (M), 10% metronidazole + 2% diltiazem (MD), 10% metronidazole + 4% lidocaine (ML), or 10% metronidazole + 2% diltiazem + 4% lidocaine (MDL). Participants were instructed to apply to the anal verge 3 times daily for 7 days. MAIN OUTCOME MEASURES: The primary outcome was pain on the visual analogue scale on day 4. The secondary outcomes included analgesia usage, pain on bowel motion, and functional recovery index. RESULTS: There was no significant difference in the pain and recovery scores when diltiazem or lidocaine was added to metronidazole (score difference between presence and absence of D in the formulation: -3.69, 95% CI: -13.3, 5.94, p = 0.46; between presence and absence of L: -5.67, 95% CI: -15.5, 3.80, p = 0.24). The combination of MDL did not further reduce pain. Secondary analysis revealed a significant difference between the best (ML) and worst (MDL) groups in both pain and functional recovery scores. There were no significant differences in analgesic usage, complications, or return to work between the groups. No clinically important adverse events were reported. The adverse event rate did not change in the intervention groups. LIMITATIONS: Topical metronidazole was utilized in the control group, rather than a pure placebo. CONCLUSION: There was no significant difference in pain when topical diltiazem or lidocaine, or both, was added to topical metronidazole. CLINICAL TRIAL REGISTRATION IDENTIFIER: NCT04276298.

A systematic review and meta-analysis of the efficacy of topical sphincterotomy treatments for anal fissure.

BACKGROUND: Anal fissure is a common condition that can be treated medically or surgically. Chemical sphincterotomy is often used before surgical intervention. This study aims to evaluate the effectiveness of topical agents for chemical sphincterotomy on healing of anal fissures and side-effects. METHODS: A Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) compliant systematic review was performed using MEDLINE, EMBASE, Scopus, and CENTRAL databases. Eligible studies included randomized controlled trials which compared topical sphincterotomy agents with topical placebo agents or each other. Studies that included surgical treatments were excluded. Overall evidence was synthesized according to the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. RESULTS: Thirty-seven studies met the study selection criteria. Seventeen studies show that glyceryl trinitrate (GTN) was significantly more likely to heal anal fissure than placebo (relative risk (RR) = 1.96, 95% confidence interval (95%CI) = 1.35-2.84, I2 = 80%). Eleven studies showed a marginally significant difference between healing rates for diltiazem vs GTN, RR = 1.16, (1.01-1.33) I2 = 48%. There was no significant difference in healing between diltiazem and placebo, RR = 1.65, (0.64-4.23), I2 = 92%. GTN significantly reduced pain on the visual analog scale compared to the placebo group, MD-0.97 (-1.64 to -0.29) I2 = 92%. There was high certainty of evidence that GTN was significantly more likely to cause headache than placebo (RR = 2.73 (1.82-4.10) I2 = 58%) and diltiazem RR = 6.88 (2.19-21.63) I2 = 17%. CONCLUSION: There is low certainty evidence topical nitrates are an effective treatment for anal fissure healing and pain reduction compared to placebo. Despite widespread use of topical diltiazem, more evidence is required to establish the effectiveness of calcium channel blockers compared to placebo.

Does investigating an elevated C-reactive protein detect infectious complications earlier after major colorectal surgery? A prospective clinical trial.

BACKGROUND: C-reactive protein (CRP) is a useful negative predictor of infectious complications following colorectal surgery. Whilst a CRP level below reported cut-offs on postoperative day (POD) 3 to 5 can be reassuring, it can be difficult to interpret an elevated CRP above these cut-offs. This study evaluated whether investigating an elevated CRP on POD 3-5 allows earlier detection of infectious complications. METHODS: Adult patients undergoing elective colonic or rectal resection were prospectively evaluated over two consecutive time periods. Group 1 had CRP levels measured on POD 3-5 with routine clinical care while Group 2 followed an algorithm where CRP levels above certain cut-offs (170 mg/L on POD3, 125 mg/L on POD4, or increase of 50 units from POD 3-4 or POD 4-5) led to an abdominopelvic CT scan and septic screen. Complications were graded as per the Clavien-Dindo classification and Comprehensive Complication Index (CCI). RESULTS: 120 patients were included in Group 1 and 60 patients were included in Group 2. There were no significant differences between the two groups with regards to patient, operation or disease characteristics. Whilst the overall complication burden was significantly greater in Group 2 (CCI 29.6 versus 12.2, P < 0.001), there were no significant differences between the groups in the day of diagnosis of infectious complication, the overall incidence, or type of complications. CONCLUSION: Early investigation of an elevated or increasing CRP on POD 3-5 following elective major colorectal surgery did not allow earlier detection of infectious complications.