Effect of 6% hydroxyethyl starch 130/0.4 on kidney and haemostatic function in cardiac surgical patients: a randomised controlled trial.

Whether third-generation hydroxyethyl starch solutions provoke kidney injury or haemostatic abnormalities in patients having cardiac surgery remains unclear. We tested the hypotheses that intra-operative administration of a third-generation starch does not worsen postoperative kidney function or haemostasis in cardiac surgical patients compared with human albumin 5%. This triple-blind, non-inferiority, clinical trial randomly allocated patients aged 40-85 who underwent elective aortic valve replacement, with or without coronary artery bypass grafting, to plasma volume replacement with 6% starch 130/0.4 vs. 5% human albumin. Our primary outcome was postoperative urinary neutrophil gelatinase-associated lipocalin concentrations, a sensitive and early marker of postoperative kidney injury. Secondarily, we evaluated urinary interleukin-18; acute kidney injury using creatinine RIFLE criteria, coagulation measures, platelet count and function. Non-inferiority (delta 15%) was assessed with correction for multiple comparisons. We enrolled 141 patients (69 starch, 72 albumin) as planned. Results of the primary analysis demonstrated that postoperative urine neutrophil gelatinase-associated lipocalin (median (IQR [range])) was slightly lower with hydroxyethyl starch (5 (1-68 [0-996]) ng.ml-1 ) vs. albumin (5 (2-74 [0-1604]) ng.ml-1 ), although not non-inferior [ratio of geometric means (95%CI) 0.91 (0.57, 1.44); p = 0.15] due to higher than expected variability. Urine interleukin-18 concentrations were reduced, but interleukin-18 and kidney injury were again not non-inferior. Of 11 individual coagulation measures, platelet count and function, nine were non-inferior to albumin. Two remaining measures, thromboelastographic R value and arachidonic acid-induced platelet aggregation, were clinically similar but with wide confidence intervals. Starch administration during cardiac surgery produced similar observed effects on postoperative kidney function, coagulation, platelet count and platelet function compared with albumin, though greater than expected variability and wide confidence intervals precluded the conclusion of non-inferiority. Long-term mortality and kidney function appeared similar between starch and albumin.

Are perioperative therapeutic doses of statins associated with postoperative pain and opioid consumption after hip surgery under spinal anaesthesia?

BACKGROUND: The anti-inflammatory effects of statins have been suggested to relieve postoperative pain. This retrospective study tested the association between the perioperative routine use of statins in therapeutic doses, and opioid requirements and pain scores, after hip replacement surgery. METHODS: With IRB approval, data was obtained for adult patients who had elective hip replacement surgery under spinal anaesthesia at Cleveland Clinic between 2005 and 2015. Patients were compared using a joint hypothesis framework. We used the inverse probability of treatment weighting method to control for observed confounding factors (a total of 26). RESULTS: We included 611 statin users and 780 non-statin users. Pain score during the initial 72 h after surgery was 0.07 higher (95% CI: -0.02, 0.17) in statin users (noninferiority test in both directions P<0.001). The estimated ratio of geometric means in the cumulative i.v. morphine equivalent opioid consumption was 1.01 (95% CI: 0.93, 1.10) for statin vs non-statin users (noninferiority test P=0.001 in the hypothesized direction and<0.001 in the other direction) during the initial 72 h after surgery. The statin and non-statin patients were deemed equivalent on postoperative opioid consumption and pain score. CONCLUSIONS: This is the first large retrospective clinical study that investigates the effects of statin use on postoperative pain and opioid consumption. We observed no difference between statin users and non-users during the initial 72 h after hip surgery. Our findings do not support the routine use of statins as part of an analgesic regimen.