Haptoglobin 2-2 Phenotype Is Associated With Increased Acute Kidney Injury After Elective Cardiac Surgery in Patients With Diabetes Mellitus.

BACKGROUND: Recent studies reported an association between the 2-2 phenotype of haptoglobin (Hp 2-2) and increased cardiorenal morbidity in nonsurgical diabetic patients. Our goal was to determine whether the Hp 2-2 phenotype was associated with acute kidney injury (AKI) after elective cardiac surgery in patients with diabetes mellitus. METHODS AND RESULTS: We prospectively enrolled 99 diabetic patients requiring elective cardiac surgery with cardiopulmonary bypass. Haptoglobin phenotypes were determined by gel electrophoresis. Cell-free hemoglobin, haptoglobin, and total serum bilirubin were quantified as hemolysis markers. The primary outcome was postoperative AKI, as defined by the Acute Kidney Injury Network classification. The incidence of AKI was significantly higher in Hp 2-2 patients compared with patients without this phenotype (non-Hp-2-2; 55.6% versus 27%, P<0.01). The need for renal replacement therapy was also significantly higher in the Hp 2-2 group (5 patients versus 1 patient, P=0.02). Thirty-day mortality (3 versus 0 patients, P=0.04) and 1-year mortality (5 versus 0 patients, P<0.01) were also significantly higher in patients with the Hp 2-2 phenotype. In multivariable analysis, Hp 2-2 was an independent predictor of postoperative AKI (P=0.01; odds ratio: 4.17; 95% confidence interval, 1.35-12.48). CONCLUSIONS: Hp 2-2 phenotype is an independent predictor of postoperative AKI and is associated with decreased short and long-term survival after cardiac surgery in patients with diabetes mellitus.

Perioperative lidocaine infusion reduces the incidence of post-mastectomy chronic pain: a double-blind, placebo-controlled randomized trial.

BACKGROUND: Chronic post-surgical pain (CPSP) is a not uncommon complication after mastectomy, with a reported incidence between 20% and 68%. Careful dissection, the use of minimally invasive surgical techniques, and attempts to reduce the associated inflammatory and hyperalgesic responses are suggested methods to prevent CPSP. OBJECTIVE: To determine if the use of perioperative lidocaine infusion is associated with decreased incidence of CPSP after mastectomy. STUDY DESIGN: Double-blind, placebo-controlled randomized trial. METHODS: This is a secondary analysis of data from 61 out of 71 patients who underwent mastectomy for breast cancer. Patients were randomized to either placebo (Group P; n = 27) or intravenous lidocaine (Group L; n = 34, bolus 1.5 mg/kg at induction, then infusion at 2 mg/kg/hr, up to 2 hours after the end of surgery) in a prospective double-blind design. CPSP was assessed at 6 months after surgery. Stepwise logistic regression analysis was performed to assess the efficacy of lidocaine. RESULTS: Overall 12 (20%) patients developed CPSP, 8 (30%) in the placebo group and 4 (12%) in the lidocaine group. Predictive factors for CPSP that remained significant after multivariate analysis included lidocaine (associated with a 20-fold decrease in CPSP, P = 0.013), breast implant placement (associated with a 16-fold increase in CPSP, P = 0.034), and radiotherapy (associated with a 29-fold increase in CPSP, P = 0.008). LIMITATIONS: Small sample size. CONCLUSION: Perioperative lidocaine administration was associated with a decreased incidence of CPSP, while breast implant placement and radiotherapy were associated with an increased incidence. These findings suggest a protective effect of lidocaine on CPSP development in mastectomy patients.

The pharmacokinetics of methadone in adolescents undergoing posterior spinal fusion.

BACKGROUND: The optimal methadone dosing regimen for children undergoing spinal surgery is uncertain because of sparse pediatric pharmacokinetic data and a paucity of analgesic effect data. The minimum effective analgesic concentration of methadone in opioid naïve adults is 58 mcg · L(-1). METHODS: Adolescents aged 12-19 years undergoing idiopathic scoliosis correction were administered 0.25 mg · kg(-1) racemic methadone IV prior to surgical incision. Arterial blood samples for methadone assay were obtained at 0 min, 5 min, 10 min, 15 min, 20 min, 40 min, 1 h, 2 h, 4 h, 5 h, 6 h, 8 h, 10 h, 12 h, 24 h, and 48 h. Compartment analysis was undertaken using nonlinear mixed effects models. Parameter estimates were standardized to a 70-kg person using allometric models. RESULTS: A three-compartment linear disposition model best described observed time-concentration profiles. Population parameter estimates (between-subjects variability) were central volume (V1) 19.1 (126%) L 70 kg(-1), peripheral volumes of distribution V2 65.5 (60%) L 70 kg(-1), V3 485 (23%) L 70 kg(-1), clearance (CL) 9.3 (11%) L · h(-1) · 70 kg(-1), and inter-compartment clearances Q2 282 (95%) L · h(-1) 70 kg(-1), Q3 139 (42%) L · h(-1) 70 kg(-1). The terminal elimination half-life was 44.4 h. The mean observed methadone concentration was <58 mcg · L(-1) by the first hour after administration. CONCLUSIONS: Current pharmacokinetic parameter estimates in adolescents are similar to those reported in adults. Methadone undergoes rapid redistribution after bolus administration. This may result in plasma concentrations that provide inadequate analgesia postoperatively. We would suggest following the bolus (0.25 mg.kg(-1)) with an infusion (0.1-0.15 mg · kg(-1) · h(-1) for 4 h) during spinal surgery to ensure adequate plasma concentrations for 24 h.