Case Report
A 78 yr-old obese man (usual body weight 110 Kg, BMI 35 kg/m2) was admitted to the Renal Intensive Care Unit (ICU) for oliguric AKI on stage 3b CKD (usual serum creatinine [Scr] concentration, 2 mg/dL, CKD-EPI eGFR 32.6 mL/min/1.73 m2) associated with septic shock due to newly diagnosed infective endocarditis. His drug treatment included pregabalin, 50 mg twice daily, for severe neuropathic pain secondary to diabetic neuropathy. On admission, he complained of severe dyspnea and fatigue. Physical examination revealed a pyretic 118-Kg oliguric patient with severe peripheral edema and diffuse basal pulmonary rales. Blood pressure was 105/70 mmHg while on norepinephrine 16 mcg/min, with pulse rate 100 beats/min. Breaths were 28/min, with peripheral oxygen saturation at 97% while on non-invasive mechanical ventilation (BPAP modality, PSV 12 cmH2O, PEEP 8 cmH2O, FiO2 50%). APACHE II score was 30. Laboratory findings showed a stage 3 AKI with mild metabolic acidosis. Given the persistent oliguria associated with severe fluid overload unresponsive to the high-dose loop diuretic therapy and hemodynamic instability, KRT was started as Continuous Venovenous Hemodiafiltration (CVVHDF) with regional citrate anticoagulation (RCA), using the Prismax system (Baxter Renal Care, USA) and a polyacrylonitrile AN69 hemofilter (ST 150, 1.5 m2, Baxter Renal Care, USA). A low concentration citrate solution (18 mmol/L; Regiocit, Baxter) was combined with a phosphate-containing solution, used as both dialysis and post-dilution replacement fluid (Biphozyl, Baxter) for a prescribed dialysis dose of 30 ml/Kg/h. Three days after, given the slow but progressive improvement of fluid overload, KRT modality was shifted to Sustained Low-Efficiency Dialysis (SLED) by using the same system and the same dialysis solutions, with a prescribed effluent volume of 100 ml/min. On the fourth ICU day, patient’s hemodynamic status definitely improved, and KRT was thereafter continued as every other day conventional Intermittent Hemodialysis (IHD).
Given the reported neuropathic pain and aiming at reducing opioids consumption, chronic therapy with pregabalin was confirmed. Moreover, given the expected extracorporeal clearance, the prescribed pregabalin dose was increased at KRT start to 75 mg every 12 hours.
The evaluation of TDM of pregabalin in course of different KRT modalities was performed by Liquid Chromatography coupled with tandem mass spectrometry (LC-MS/MS system) (Shimadzu Italia, Milano) (Supplemental Material 1 ) [11]. At the same dose administered (75 mg every 12 hours) a progressive reduction of pregabalin serum levels in course of prolonged KRT modalities (CKRT and SLED) was observed, while a rapid decrease was observed during IHD with a negligible post treatment rebound (Figure 1 ).