Efficacy of postoperative analgesia with duloxetine in posthemorrhoidectomy pain: a prospective, randomized, double-blind and placebo-controlled trial.

BACKGROUND: To evaluate the effect of duloxetine when added to a multimodal analgesia regimen on posthemorrhoidectomy pain, opioid consumption, and side effects. METHODS: Prospective, randomized, double-blind placebo-controlled trial. This study included 62 patients who underwent hemorrhoidectomy. The patients were randomly assigned to receive oral duloxetine 60 mg or placebo 2 h before and 24 h after surgery. The primary outcomes were pain intensity - measured on an 11-point visual analog pain scale - and cumulative morphine consumption at 12, 24, and 48 postoperative hours. RESULTS: Fifty-two patients completed the study (25 in the duloxetine group and 27 in the placebo group). Pain scores did not differ between duloxetine and placebo: 4.5; 3.0 - 7.0 vs. 5.0; 3.5 - 7.0, p = 0.68 at 12 h, 3.0; 2.0 - 5.0 vs. 3.0; 2.0 - 5.0, p = 0.56 at 24 h, and 2.5; 1.75 - 3.75 vs. 1.5; 0.5 - 3, p = 0.08 at 48 h. Further, cumulative morphine consumption did not differ between the duloxetine and placebo groups: 4; 1.25 - 10.75 mg vs. 7; 1.0 - 12.0 mg, p = 0.68 at 12 h, 9.5; 2.0 - 17.5 mg vs. 8.0; 4.0 - 18.0 mg; p = 0.80 at 24 h, and 11.0; 2.0 - 27.0 mg vs. 10; 4.0 - 24.0 mg, p = 0.78 at 48 h. Side effects did not differ between the groups. CONCLUSIONS: Compared with placebo, duloxetine did not decrease pain intensity or morphine consumption during the first 48 h postoperatively. TRIAL REGISTRATION: The study was retrospectively registered on the Brazilian Clinical Trials Registry (identifier: RBR-9pdgms, registration date: 08/10/2020).

The effects of a short-term perioperative duloxetine treatment on post-colectomy pain: A randomized, controlled clinical trial.

STUDY OBJECTIVE: To test the hypothesis that duloxetine reduces postoperative morphine consumption and pain intensity in patients undergoing major colonic surgeries. DESIGN: Single-center, prospective, double-blinded, randomized, controlled trial. SETTING: Tertiary university hospital, from December 2019 to September 2021. PATIENTS: Sixty 18-85 years old, ASA I - III patients undergoing elective open major colonic surgeries were randomly allocated into duloxetine (duloxetine) or placebo (placebo) groups (n = 30 per group). INTERVENTIONS: Duloxetine 60 mg or placebo was administered orally 2 h before and 24 h after surgery. MEASUREMENTS: PCA morphine consumption, surgical pain at rest, and movement measured on 10-cm visual analog scales (VAS), Ramsay sedation scores, and the incidence of adverse effects potentially associated with duloxetine were assessed at patients' admission to the post-anesthesia care unit (PACU), 6, 24, and 48 h postoperatively (PO). MAIN RESULTS: After adjusting for age, BMI, ASA physical status, education level, and incision type, no differences were found between groups in PCA morphine consumption 24 PO h (duloxetine = 5.44 ± 2.06 mg; placebo = 10.33 ± 2.06 mg, p = 0.62) or 48 h PO (duloxetine = 9.18 ± 2.06 mg, placebo = 12.93 ± 2.06, p = 1). Pain at rest also did not differ between groups at 24 h PO (duloxetine = 1.76 ± 0.67 cm; placebo = 1 ± 0.67 cm, p = 1) or at 48 h PO (duloxetine = 0.84 ± 0.67 cm; placebo = 0.49 ± 0.67 cm, p = 1). Similarly, groups did not differ regarding pain on movement at 24 h PO (duloxetine = 2.09 ± 0.68 cm; placebo = 1.80 ± 0.68, p = 1) or at 48 h PO (duloxetine = 1.16 ± 0.68 cm; placebo = 0.88 ± 0.68 cm, p = 1). Sedation scores and adverse effects also did not differ between groups. CONCLUSION: Under this study's conditions, short-term duloxetine did not reduce total opioid consumption or pain intensity during the initial 48 h following major colon surgery.

Intravenous toxicity of fructose-1,6-bisphosphate in rats.

Fructose-1,6-bisphosphate (FBP) is a bisphosphorilated sugar with a protective action against events that lead to cellular damage. The toxicity of the drug was assessed when administered intravenously in Wistar rats in doses of between 250 and 4000 mg/kg. Ionic calcium, total calcium, inorganic serum phosphate and the electrocardiographic profile of these animals were assessed. The lethal dose (LD(50)) was established by means of PROBIT processing. There was no reduction in the levels of total calcium, with the administration of increased doses of FBP, although there was a significant reduction in the levels of ionic calcium in those groups that received 250 mg/kg and over. The serum phosphate showed a significant statistical increase in those groups that received 750 mg/kg and over. The LD(50) obtained in 24 h was 1068 mg/kg. Though it was not possible to elucidate the toxic mechanism of FBP, the electrocardiogram (ECG) showed that all the rats died of cardiac arrest.

Effect of fructose-1,6-bisphosphate on the nephrotoxicity induced by cisplatin in rats.

Cisplatin is one of the most active cytotoxic agents in the treatment of cancer, but its clinical use is frequently limited by nephrotoxicity. The study presented here attempted to evaluate the effect of fructose-1,6-bisphosphate in the cisplatin-induced nephrotoxicity in rats. The drugs were administered intraperitoneally as a single dose: sodium chloride 0.9%, cisplatin (6 mg/kg), fructose-1,6-bisphosphate (500 mg/kg), and cisplatin plus fructose-1,6-bisphosphate (6 and 500 mg/kg, respectively). The use of cisplatin resulted in significant elevation of serum creatinine and urea. The group that received cisplatin plus fructose-1,6-bisphosphate presented a significantly lower level of creatinine and urea compared to the cisplatin group. Acute tubular necrosis was demonstrated in the animals that received cisplatin and a less severe one in the cisplatin plus fructose-1,6-bisphosphate group. Fructose-1,6-bisphosphate has a protective effect over renal function and renal parenchyma in a rat experimental model of cisplatin-induced nephrotoxicity. The anti-inflammatory effect of fructose-1,6-bisphosphate confirms its protective effect in cases of cellular injury.

Risk factors for nosocomial infections due to Pseudomonas aeruginosa producing metallo-beta-lactamase in two tertiary-care teaching hospitals.

OBJECTIVES: To assess risk factors for nosocomial infections due to Pseudomonas aeruginosa producing metallo-beta-lactamase (MBL-PA) in two teaching hospitals where horizontal dissemination has been demonstrated. METHODS: A case-control study was performed in both hospitals (assigned as hospital 1 and 2). Cases were patients with MBL-PA infections and controls were those with non-MBL-PA infections. Multivariate analysis was performed to identify independent risk factors. RESULTS: A total of 86 cases and 212 controls were included in the study. A logistic regression model showed that exposure to beta-lactams [odds ratio (OR) 3.21; 95% confidence interval (CI) 1.74-5.93] or fluoroquinolones (OR 3.50; 95% CI 1.46-8.37) was associated with MBL-PA infections. Other independent risk factors were neurological disease (OR 3.00; 95% CI 1.61-5.58), urinary tract infection (OR 2.48; 95% CI 1.21-5.09) and renal failure (OR 2.29; 95% CI 1.13-4.65). Admission to hospital 1 (OR 5.97; 95% CI 3.45-14.09) and intensive care unit stay (OR 2.07; 95% CI 1.46-3.96) were also associated with increased risk for MBL-PA infections. CONCLUSIONS: beta-Lactam exposure is an important risk factor for MBL-PA infections even in a setting where patient-to-patient transmission plays a major role in the spread of the isolates. Other risk factors deserve further investigation, particularly exposure to fluoroquinolones.

Outbreak of carbapenem-resistant Pseudomonas aeruginosa producing SPM-1 metallo-{beta}-lactamase in a teaching hospital in southern Brazil.

OBJECTIVES: To describe the first nosocomial outbreak of Pseudomonas aeruginosa producing SPM-1 metallo-beta-lactamase (MBL) in southern Brazil. PATIENTS AND METHODS: From January to October 2004, carbapenem-resistant P. aeruginosa (CRPA) were recovered from hospitalized patients. Mortality, site of infection/colonization, patient location and susceptibility profiles were analysed. A sample of CRPA was screened for MBL production, evaluated for the presence of bla(SPM-1), bla(IMP-1) and bla(VIM-2) genes by PCR and submitted for molecular typing by DNA macrorestriction. RESULTS: A total of 135 CRPA (one isolate per patient) were recovered. Two major antibiotic susceptibility profiles comprised 63.7% of the isolates (susceptibility to polymyxin B and aztreonam, and susceptibility only to polymyxin B). Thirty-five CRPA were screened for MBL production (10 isolates from April, June and July, and 25 from September and October) and 27 (77.1%) proved to be positive for MBL production. Twenty-one of the 24 CRPA tested carried the bla(SPM-1) gene. The mortality of patients with CRPA was 48.1% and no variable was associated with death. Molecular typing revealed the presence of a clone with four related subtypes among the bla(SPM-1)-positive CRPA. CONCLUSIONS: The prevalence of MBL production by CRPA is high and horizontal transmission is a major determinant for the spread of SPM-1 CRPA among patients in this institution. As infection control measures failed to control the spread of CRPA, continuous surveillance for MBL production is warranted.

Ocurrence of blaSPM-1 and blaIMP-1 genes of metallo-beta-lactamases in clinical isolates of Pseudomonas aeruginosa from three universitary hospitals in the city of Porto Alegre, Brazil

We described the ocurrence of metallo-beta-lactamases (MBL) genes blaSPM-1 and blaIMP-1 in clinical isolates of Pseudomonas aeruginosa resistant to imipenem and/or ceftazidime obtained from three universitary hospitals in the city of Porto Alegre, Brazil. The MBL production was screened by phenotypic test and the genes were detected by PCR.

Descrevemos a ocorrência dos genes de metalo-beta-lactamases (MBL) blaSPM-1 e blaIMP-1 em isolados clínicos de Pseudomonas aeruginosa resistentes ao imipenem e/ou ceftazidima obtidos em três hospitais universitários de Porto Alegre, Brasil. A produção de MBL foi observada através de técnica fenotípica e os genes foram detectados pelo método de PCR.