RESUMEN
PURPOSE: Acute kidney injury (AKI) is a potentially serious complication of cardiac surgery. Anemia and red blood cell (RBC) transfusion have individually been identified as potentially modifiable risk factors, but their interrelationship with AKI has not been clearly defined. The purpose of this study was to explore the interrelationship of preoperative anemia, intraoperative anemia, and RBC transfusion on the day of surgery with AKI in cardiac surgery. METHODS: This historical cohort study included 16 hospitals, each contributing data on approximately 100 consecutive patients who underwent cardiac surgery with cardiopulmonary bypass. Acute kidney injury was defined as a > 50% increase in creatinine levels during the first postoperative week. Multivariable regression was used to identify the interrelationship between preoperative anemia (hemoglobin < 130 g·L(-1) in males and < 120 g·L(-1) in females), intraoperative anemia (hemoglobin < 80 g·L(-1) during cardiopulmonary bypass), RBC transfusion on the day of surgery, and their interaction terms, after adjusting for site and baseline AKI risk. RESULTS: Of the 1,444 patients included in the study, 541 (37%) had preoperative anemia, 501 (35%) developed intraoperative anemia, 619 (43%) received RBC transfusions, and 238 (16%) developed AKI. After risk-adjustment, an individual with the combination of these three risk factors had a 2.6-fold (95% confidence interval 2.0 to 3.3) increase in the relative risk of AKI over an individual with none of these risk factors. CONCLUSIONS: Preoperative anemia, intraoperative anemia, and RBC transfusion on the day of surgery are interrelated risk factors for AKI after cardiac surgery. Targeting these risk factors may reduce the burden of AKI.
Asunto(s)
Lesión Renal Aguda/etiología , Anemia/complicaciones , Puente Cardiopulmonar/métodos , Transfusión de Eritrocitos/métodos , Lesión Renal Aguda/epidemiología , Lesión Renal Aguda/prevención & control , Anciano , Anemia/epidemiología , Puente Cardiopulmonar/efectos adversos , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Análisis de Regresión , Estudios Retrospectivos , Factores de RiesgoRESUMEN
BACKGROUND: Transversus abdominis plane (TAP) infiltration has been increasingly used for postsurgical analgesia in abdominal/pelvic procedures; however, duration/extent of analgesia with standard local anesthetics is limited. This pilot study assessed the preliminary efficacy and safety of two volumes of liposome bupivacaine administered via TAP infiltration in patients undergoing robotic laparoscopic prostatectomy. METHODS: In this single-center, open-label, prospective study, patients older than 18 years received TAP infiltration with liposome bupivacaine immediately after surgery. The first 12 patients received a total volume of 20 mL liposome bupivacaine (266 mg); the next 12 received 40 mL liposome bupivacaine (266 mg). The liposome bupivacaine was diluted with 0.9% normal saline. The primary efficacy measure was duration of analgesia, measured by time to first opioid administration. Secondary outcome measures included patient-assessed pain scores, opioid use, and opioid-related adverse events (AEs). RESULTS: Twenty-four patients received liposome bupivacaine (20 mL, n=12; 40 mL, n=12) and were included in the primary analysis. Three refused participation in a 10-day follow-up visit and did not complete the study. Median time to first opioid administration after surgery was 23 and 26 minutes for the 20 and 40 mL groups, respectively. Mean total amount of postsurgical opioids ranged from 25.4 to 27.3 mg; after hospital discharge to day 10, both groups required a mean of 0.7 oxycodone/acetaminophen tablets/day. Mean pain scores of 4.4 and 5.3 were reported at 1 hour and 3.1 and 3.9 at 2 hours postsurgery, with 20 and 40 mL doses, respectively. Neither group had mean scores higher than 3.0 at any further assessments. No opioid-related or treatment-related serious AEs were reported. CONCLUSION: Median time to first opioid administration did not differ between the two groups. No differences in secondary outcomes were observed on the basis of volume administered. These initial findings suggest further study of liposome bupivacaine administered via TAP infiltration as part of a multimodal analgesic regimen in laparoscopic robotic prostatectomy may be warranted.
RESUMEN
Rifalazil is a benzoxazinorifamycin which inhibits bacterial DNA-dependent RNA polymerase. The benzoxazine ring endows benzoxazinorifamycins with unique physical and chemical characteristics which favor the use of rifalazil and derivatives in treating diseases caused by the obligate intracellular pathogens of the genus chlamydia. Minimal inhibitory concentrations of benzoxazinorifamycins against chlamydia are in the pg/mL range. These compounds have potential as monotherapeutic agents to treat chlamydia-associated disease because they retain activity against chlamydia strains resistant to currently approved rifamycins such as rifampin. A pivotal clinical trial with rifalazil has been initiated for the treatment of peripheral arterial disease. The rationale for this innovative use of rifalazil, including the association of C. pneumoniae in atherosclerotic plaque formation, as well as rifalazil's potency and efficacy against chlamydia in both preclinical and clinical studies, is discussed. Other benzoxazino derivatives may have utility as stand-alone topical antibacterials or combination antibacterials to treat serious Gram-positive infections. None of the benzoxazinorifamycins examined to date induce the cytochrome P450 3A4 enzyme. This is in contrast to currently approved rifamycins which are strong inducers of P450 enzymes, resulting in drug-drug interactions that limit the clinical utility of this drug class.
Asunto(s)
Antibacterianos/uso terapéutico , Infecciones por Chlamydia/tratamiento farmacológico , Rifampin/uso terapéutico , Rifamicinas/uso terapéutico , Animales , Antibacterianos/metabolismo , Antibacterianos/farmacocinética , Aterosclerosis/tratamiento farmacológico , Aterosclerosis/microbiología , Infecciones por Chlamydia/microbiología , Chlamydophila pneumoniae/efectos de los fármacos , Chlamydophila pneumoniae/aislamiento & purificación , Humanos , Enfermedades Vasculares Periféricas/tratamiento farmacológico , Enfermedades Vasculares Periféricas/microbiología , Rifampin/metabolismo , Rifampin/farmacocinética , Rifamicinas/metabolismo , Rifamicinas/farmacocinéticaRESUMEN
OBJECTIVES: To determine the safety and effectiveness of single-dose rifalazil, a new rifamycin, for the treatment of nongonococcal urethritis (NGU). STUDY DESIGN: Randomized, double-blind trial comparing rifalazil, 2.5, 12.5 or 25 mg, with 1.0 g azithromycin for the treatment of NGU. One hundred and seventy men were evaluated for Chlamydia trachomatis, Ureaplasma urealyticum, and Mycoplasma genitalium infection before therapy and 2- and 5-weeks posttreatment. RESULTS: C. trachomatis, M. genitalium, and U. urealyticum were present in 42%, 24%, and 28% of subjects, respectively. Microbiologic eradication of C. trachomatis with rifalazil 25 mg at 2- and 5- weeks was 85% and 83%, respectively. Rifalazil was ineffective in eradicating M. genitalium and U. urealyticum. Overall clinical cure rates at 2- and 5-weeks were 86% (95% CI 67-96) and 59% (39-78) in the rifalazil-treated 25 mg group, and 77% (56-91) and 63% (41-81) in the azithromycin-treated group. CONCLUSIONS: Rifalazil was well tolerated and eradicates C. trachomatis but not M. genitalium and U. ureaplasma in men with NGU.
Asunto(s)
Antibacterianos/uso terapéutico , Azitromicina/uso terapéutico , Rifamicinas/uso terapéutico , Enfermedades Bacterianas de Transmisión Sexual/tratamiento farmacológico , Uretritis/tratamiento farmacológico , Adulto , Antibacterianos/administración & dosificación , Azitromicina/administración & dosificación , Infecciones por Chlamydia/tratamiento farmacológico , Infecciones por Chlamydia/patología , Chlamydia trachomatis , Método Doble Ciego , Esquema de Medicación , Humanos , Masculino , Infecciones por Mycoplasma/tratamiento farmacológico , Infecciones por Mycoplasma/patología , Mycoplasma genitalium , Rifamicinas/administración & dosificación , Enfermedades Bacterianas de Transmisión Sexual/microbiología , Enfermedades Bacterianas de Transmisión Sexual/patología , Resultado del Tratamiento , Infecciones por Ureaplasma/tratamiento farmacológico , Infecciones por Ureaplasma/patología , Ureaplasma urealyticum , Uretritis/patologíaRESUMEN
Rifalazil and other benzoxazinorifamycins (new chemical entities [NCEs]) are rifamycins that contain a distinct planar benzoxazine ring. Rifalazil has excellent antibacterial activity, high intracellular levels and high tissue penetration, which are attributes that favour its use in treating diseases caused by the obligate intracellular pathogens of the genus Chlamydia. Recent studies have shown that rifalazil has efficacy in the treatment of human sexually transmitted disease caused by Chlamydia trachomatis. The extraordinary potency of rifalazil and other NCEs, such as ABI-0043, extends to the related microorganism, C. pneumoniae, a respiratory pathogen that can disseminate and persist chronically in the vasculature, resulting in increased plaque formation in animal studies. A pivotal clinical trial with rifalazil has been initiated for the treatment of peripheral arterial disease. Other opportunities include gastric ulcer disease caused by Helicobacter pylori and antibiotic-associated colitis caused by infection with Clostridium difficile in the colon. The NCEs could prove to be valuable as follow-on compounds in these indications, as rifampin replacements in antibacterial combination therapy or as stand-alone topical antibacterials (e.g., to treat acne). Neither rifalazil nor NCEs appear to induce the cytochrome P450 3A4, an attribute of rifampin that can result in adverse events due to drug-drug interactions.
Asunto(s)
Antibacterianos/uso terapéutico , Aterosclerosis/tratamiento farmacológico , Infecciones por Chlamydia/tratamiento farmacológico , Enfermedad de la Arteria Coronaria/tratamiento farmacológico , Rifamicinas/uso terapéutico , Animales , Antibacterianos/administración & dosificación , Antibacterianos/farmacocinética , Aterosclerosis/microbiología , Infecciones por Chlamydia/microbiología , Chlamydia trachomatis/efectos de los fármacos , Chlamydia trachomatis/aislamiento & purificación , Chlamydophila pneumoniae/efectos de los fármacos , Chlamydophila pneumoniae/aislamiento & purificación , Chlamydophila psittaci/efectos de los fármacos , Chlamydophila psittaci/aislamiento & purificación , Enfermedad de la Arteria Coronaria/microbiología , Modelos Animales de Enfermedad , Esquema de Medicación , Evaluación Preclínica de Medicamentos , Farmacorresistencia Bacteriana , Humanos , Pruebas de Sensibilidad Microbiana , Ensayos Clínicos Controlados Aleatorios como Asunto , Rifamicinas/administración & dosificación , Rifamicinas/farmacocinéticaRESUMEN
UNLABELLED: We performed a randomized, prospective, parallel-group, open-label, multicenter trial to compare the effects of pre- versus postoperative interscalene block using levobupivacaine on postoperative pain and analgesic requirements. One-hundred-two outpatients scheduled for elective shoulder surgery were randomized to receive 30 mL of 0.5% levobupivacaine either preoperatively (PRE group) or postoperatively (POST group). Analgesic outcome measures during the postoperative period were: (a). time to first request for analgesic medication after surgery, (b). pain intensity using the visual analog scale at rest and during arm movement, and (c). total analgesic consumption of nonsteroidal antiinflammatory drugs and opioids. The time to first analgesic request did not differ between treatment groups. However, mean maximum pain intensity scores during the day of surgery were significantly less for the PRE group than the POST group, both at rest (P = 0.001) and after movement (P = 0.004). The mean opioid administered during surgery was lower in the PRE than the POST group (P < 0.001). Levobupivacaine was well tolerated in both treatment groups, and no adverse reactions were related to this local anesthetic. In conclusion, preoperative interscalene block with levobupivacaine provided superior pain control for the first 12 h after surgery, but this benefit was not maintained during the week after discharge because the subjects assumed control of their own pain relief as outpatients. IMPLICATIONS: Preoperative interscalene block with levobupivacaine provides safe and effective analgesia for same-day elective shoulder surgery, but the benefit of this one-time intervention does not persist.