RESUMO
BACKGROUND: Long-acting local anaesthetics (e.g. bupivacaine hydrochloride) or sustained-release formulations of bupivacaine (e.g. liposomal bupivacaine) may be neurotoxic when applied in the setting of diabetic neuropathy. The aim of the study was to assess neurotoxicity of bupivacaine and liposome bupivacaine in streptozotocin (STZ) - induced diabetic mice after sciatic nerve block. We used the reduction in fibre density and decreased myelination assessed by G-ratio (defined as axon diameter divided by large fibre diameter) as indicators of local anaesthetic neurotoxicity. RESULTS: Diabetic mice had higher plasma levels of glucose (P < 0.001) and significant differences in the tail flick and plantar test thermal latencies compared to healthy controls (P < 0.001). In both diabetic and nondiabetic mice, sciatic nerve block with 0.25% bupivacaine HCl resulted in a significantly greater G-ratio and an axon diameter compared to nerves treated with 1.3% liposome bupivacaine or saline (0.9% sodium chloride) (P < 0.01). Moreover, sciatic nerve block with 0.25% bupivacaine HCl resulted in lower fibre density and higher large fibre and axon diameters compared to the control (untreated) sciatic nerves in both STZ-induced diabetic (P < 0.05) and nondiabetic mice (P < 0.01). No evidence of acute or chronic inflammation was observed in any of the treatment groups. CONCLUSIONS: In our exploratory study the sciatic nerve block with bupivacaine HCl (7 mg/kg), but not liposome bupivacaine (35 mg/kg) or saline, resulted in histomorphometric indices of neurotoxicity. Histologic findings were similar in diabetic and healthy control mice.
Assuntos
Anestésicos Locais/toxicidade , Bupivacaína/toxicidade , Diabetes Mellitus Experimental/complicações , Bloqueio Nervoso/efeitos adversos , Nervo Isquiático/efeitos dos fármacos , Animais , Bupivacaína/administração & dosagem , Neuropatias Diabéticas/complicações , Feminino , Injeções , Lipossomos , Camundongos Endogâmicos C57BL , Camundongos Mutantes , Nervo Isquiático/patologiaRESUMO
BACKGROUND AND OBJECTIVES: We examined whether liposome bupivacaine (Exparel) given in the interscalene brachial plexus block lowers pain in the setting of multimodal postoperative pain management for major shoulder surgery. METHODS: Fifty-two adult patients were randomized to receive either 5 mL of 0.25% bupivacaine HCl immediately followed by 10 mL of liposome bupivacaine 133 mg (n = 26) or 15 mL of 0.25% standard bupivacaine alone (n = 26) in interscalene brachial plexus block. The primary outcome (worst pain in the first postoperative week) was assessed by the Modified Brief Pain Inventory short form. Secondary outcomes were overall satisfaction with analgesia (OBAS), functionality of the surgical arm, sleep duration, time to first opioid (tramadol) request and opioid consumption (mEq), sensory-motor block characteristics, and the occurrence of adverse effects. RESULTS: Worst pain was lower in patients given liposome bupivacaine added to standard bupivacaine than in patients given standard bupivacaine alone (generalized estimating equation [GEE] estimated marginal mean values, 3.6 ± 0.3 vs 5.3 ± 0.4 points on the Numeric Rating Scale, respectively, although the effect was modest, 1.6 ± 0.5; 95% confidence interval, 0.8-2.5). Total OBAS scores indicated greater satisfaction (GEE estimated marginal mean values, 1.8 ± 0.3 vs 3.3 ± 0.4 on total OBAS, respectively, with modest effect, difference, 1.4 ± 0.5; 95% confidence interval, 0.5-2.4). There were no differences in any of the other secondary outcomes. CONCLUSIONS: Liposome bupivacaine added to standard bupivacaine may lower pain and enhance patient's satisfaction in the first postoperative week even in the setting of multimodal analgesia for major shoulder surgery.This study was registered with clinicaltrials.gov (NCT02554357) on July 11, 2015, by Principal Investigator Catherine Vandepitte, MD.
Assuntos
Anestésicos Locais/administração & dosagem , Bloqueio do Plexo Braquial/métodos , Bupivacaína/administração & dosagem , Medição da Dor/efeitos dos fármacos , Dor Pós-Operatória/prevenção & controle , Ombro/cirurgia , Idoso , Procedimentos Cirúrgicos Ambulatórios/efeitos adversos , Bupivacaína/química , Método Duplo-Cego , Feminino , Humanos , Lipossomos , Masculino , Pessoa de Meia-Idade , Medição da Dor/métodos , Dor Pós-Operatória/diagnóstico , Estudos ProspectivosRESUMO
BACKGROUND: Bradycardia and asystole can occur unexpectedly during neuraxial anesthesia. Risk factors may include low baseline heart rate, first-degree heart block, American Society of Anesthesiologists physical status 1, beta-blockers, male gender, and high sensory level. Anesthesia information management systems automatically record large numbers of physiologic variables that are combined with data input from the anesthesiologist to form the anesthesia record. Such large databases can be scanned for episodes of bradycardia. METHODS: To select spinal and epidural anesthetics that did not also involve general anesthesia, 57,240 automated anesthesia records were scanned. Obstetrical patients and patients younger than age 12 yr were excluded. The electronic records selected were then scanned for episodes of moderate (heart rate < 50 and >/= 40 beats/min) or severe (heart rate < 40 beats/min) bradycardia. RESULTS: A total of 6,663 cases (11.6%) met the inclusion criteria. Among the 677 cases of bradycardia (10.2%) were 46 cases of severe bradycardia (0.7%). In the final multivariate logistic regression analysis, baseline heart rate less than 60 beats/min (P = 0.0001) and male gender (P = 0.05) contributed significantly to risk for a severe bradycardia episode (odds ratio [OR]), 14.1 and 95% confidence interval [CI], 6.9-28.0, and OR, 2.1 and 95% CI, 1-4.3, respectively). For the 631 episodes of moderate bradycardia (9.5%), the final multivariate model included baseline heart rate less than 60 beats/min (OR, 16.2; 95% CI, 12.4-22.0), age younger than 37 yr (OR, 1.4; 95% CI, 1.1-1.7), male gender (OR, 1.4; 95% CI, 1.2-1.8), nonemergency status (OR, 1.7; 95% CI, 1.2-2.4), beta-blockers (OR, 1.6; 95% CI, 1.1-2.3), and case duration (OR, 2.0; 95% CI, 1.6-2.4) as significant risk factors. Time of occurrence of a bradycardia event was distributed widely across the entire duration of a case. CONCLUSIONS: Moderate or severe bradycardia may occur at any time during neuraxial anesthesia, regardless of the duration of anesthesia. Low baseline heart rate increases the risk for bradycardia.