Dialysability of sugammadex and its complex with rocuronium in intensive care patients with severe renal impairment.

BACKGROUND Renal excretion is the primary route for the elimination of sugammadex. We evaluated the dialysability of sugammadex and the sugammadex-rocuronium complex in patients with severe renal impairment in the intensive care unit (ICU). METHODS Six patients in the ICU with acute severe renal impairment received general anaesthesia for transoesophageal echocardiography, to replace their tracheal tubes, or for bronchoscopy. Five of the six patients were in the ICU after cardiac/vascular surgery and one for pneumonia-induced respiratory failure. They all received rocuronium 0.6 mg kg(-1), followed 15 min later by sugammadex 4.0 mg kg(-1). Two patients were studied for two dialysis episodes and four patients for four episodes. Rocuronium and sugammadex concentrations were measured in plasma and dialysate at several time points before, during, and after high-flux dialysis. Dialysis clearance in plasma and dialysate, and reduction ratio (RR) (the extent of the plasma concentration reduction at the end of a dialysis episode when compared with before dialysis) were calculated for each dialysis episode. RESULTS Dialysis episodes lasted on average 6 h. Observed RRs indicated mean reductions of 69% and 75% in the plasma concentrations of sugammadex and rocuronium, respectively, during the first dialysis episode. Reductions were around 50% during sequential dialysis episodes. On average, dialysis clearance of sugammadex and rocuronium in blood was 78 and 89 ml min(-1), respectively. CONCLUSIONS Haemodialysis using a high-flux dialysis method is effective in removing sugammadex and the sugammadex-rocuronium complex in patients with severe renal impairment.

[1]  T. Suzuki,et al.  Correlation between cardiac output and reversibility of rocuronium‐induced moderate neuromuscular block with sugammadex , 2012, Acta anaesthesiologica Scandinavica.

[2]  G. Cammu,et al.  Dialysability of sugammadex and its complex with rocuronium in subjects with severe renal impairment: 9AP3-4 , 2011 .

[3]  H. Frasa,et al.  Determination of sugammadex in human plasma, urine, and dialysate using a high-performance liquid chromatography/tandem mass spectrometry assay. , 2011, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[4]  J. Smeets,et al.  Sugammadex is cleared rapidly and primarily unchanged via renal excretion , 2011, Biopharmaceutics & drug disposition.

[5]  W. van Biesen,et al.  Pro/con debate: Continuous versus intermittent dialysis for acute kidney injury: a never-ending story yet approaching the finish? , 2011, Critical care.

[6]  J. Smeets,et al.  Safety, Tolerability and Pharmacokinetics of Sugammadex Using Single High Doses (Up to 96 mg/kg) in Healthy Adult Subjects , 2010, Clinical drug investigation.

[7]  J. Scholz,et al.  Reversal of rocuronium-induced neuromuscular blockade with sugammadex compared with neostigmine during sevoflurane anaesthesia: results of a randomised, controlled trial , 2010, European journal of anaesthesiology.

[8]  H. Lemmens,et al.  Reversal of profound vecuronium-induced neuromuscular block under sevoflurane anesthesia: sugammadex versus neostigmine. , 2010, BMC anesthesiology.

[9]  K. Khuenl-Brady,et al.  Sugammadex Provides Faster Reversal of Vecuronium-Induced Neuromuscular Blockade Compared with Neostigmine: A Multicenter, Randomized, Controlled Trial , 2010, Anesthesia and analgesia.

[10]  J. Driessen,et al.  Reduced clearance of rocuronium and sugammadex in patients with severe to end-stage renal failure: a pharmacokinetic study. , 2010, British journal of anaesthesia.

[11]  M. W. van den Heuvel,et al.  Safety, tolerability and pharmacokinetics of sugammadex using single high doses (up to 96 mg/kg) in healthy adult subjects: a randomized, double-blind, crossover, placebo-controlled, single-centre study. , 2010, Clinical drug investigation.

[12]  T. Heier,et al.  Safety and efficacy of sugammadex for the reversal of rocuronium-induced neuromuscular blockade in cardiac patients undergoing noncardiac surgery , 2009, European journal of anaesthesiology.

[13]  A. Bom,et al.  Preclinical pharmacology of sugammadex. , 2009, Journal of critical care.

[14]  R. G. Craig,et al.  Neuromuscular blocking drugs and their antagonists in patients with organ disease , 2009, Anaesthesia.

[15]  R. Soto,et al.  Reversal of Profound Rocuronium-induced Blockade with Sugammadex: A Randomized Comparison with Neostigmine , 2008, Anesthesiology.

[16]  J. Driessen,et al.  Multicentre, parallel-group, comparative trial evaluating the efficacy and safety of sugammadex in patients with end-stage renal failure or normal renal function. , 2008, British journal of anaesthesia.

[17]  C. Meistelman,et al.  Reversal of rocuronium-induced neuromuscular block with sugammadex is faster than reversal of cisatracurium-induced block with neostigmine. , 2008, British journal of anaesthesia.

[18]  J. Proost,et al.  Early Reversal of Profound Rocuronium-induced Neuromuscular Blockade by Sugammadex in a Randomized Multicenter Study: Efficacy, Safety, and Pharmacokinetics , 2007, Anesthesiology.

[19]  P. White,et al.  Sugammadex Reversal of Rocuronium-Induced Neuromuscular Blockade: A Comparison with Neostigmine–Glycopyrrolate and Edrophonium–Atropine , 2007, Anesthesia and analgesia.

[20]  P. Hans,et al.  Effective Reversal of Moderate Rocuronium- or Vecuronium-induced Neuromuscular Block with Sugammadex, a Selective Relaxant Binding Agent , 2007, Anesthesiology.

[21]  M. Giovannelli,et al.  Org 25969 (sugammadex), a selective relaxant binding agent for antagonism of prolonged rocuronium-induced neuromuscular block. , 2006, British journal of anaesthesia.

[22]  J. Driessen,et al.  Pharmacokinetics and pharmacodynamics of rocuronium in patients with and without renal failure , 2005, European journal of anaesthesiology.

[23]  M. Marshall,et al.  Sustained low-efficiency daily diafiltration (SLEDD-f) for critically ill patients requiring renal replacement therapy: towards an adequate therapy. , 2004, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[24]  P. Desmond,et al.  Liquid chromatography/mass spectrometric bioanalysis of a modified gamma-cyclodextrin (Org 25969) and Rocuronium bromide (Org 9426) in guinea pig plasma and urine: its application to determine the plasma pharmacokinetics of Org 25969. , 2002, Rapid communications in mass spectrometry : RCM.

[25]  C. Keller,et al.  Pharmacodynamics and pharmacokinetics of rocuronium in intensive care patients. , 1997, British journal of anaesthesia.

[26]  V. Slavov,et al.  Neostigmine Reversal of Vecuronium Neuromuscular Block and the Influence of Renal Failure , 1996, Anesthesia and analgesia.

[27]  L. Lindgren,et al.  Pharmacokinetics of glycopyrronium in uraemic patients. , 1993, British journal of anaesthesia.

[28]  J. Wierda,et al.  Time course of neuromuscular effects and pharmacokinetics of rocuronium bromide (Org 9426) during isoflurane anaesthesia in patients with and without renal failure. , 1993, British journal of anaesthesia.

[29]  E. O'sullivan,et al.  Clearance of atracurium and laudanosine in the urine and by continuous venovenous haemofiltration. , 1991, British Journal of Anaesthesia.

[30]  L. Sheiner,et al.  Renal function and the pharmacokinetics of neostigmine in anesthetized man. , 1979 .