Renal dysfunction after total knee replacement is not aggravated by bone cement

Background : Total knee replacement (TKR) has been associated with postoperative renal dysfunction. The use of monomeric methylmethacrylate (MMA) bone cement causes hypotension by several mechanisms.
Methods : In 30 patients undergoing TKR with (n=16), or without (n = 14) bone cement , serum levels of creatinine, cystatin C and creatine kinase (CK) and urinary levels of creatinine and markers for glomerular (albumin, IgG) and tubular (protein HC) function were recorded preoperatively and on days 1, 2, 4 and 8 postoperatively.
Results : There were no changes in serum creatinine. Both groups had a transient, 5-fold rise in CK and a continuous increase in cystatin C. The urinary concentration of proteins increased postoperatively with a peak in the glomerular markers on day 1 and in the tubular marker on day 2. There were no significant differences in proteinuria between the groups. The 95% CIs for the difference in the means of the AUCs of the logarithmically transformed values for the proteins were never more than 19%. On day 8 all proteins had returned to their preoperative levels.
Conclusion : Postoperatively, there was a transient increased leakage of proteins, indicating glomerular and tubular dysfunction. This was not influenced by the use of MMA bone cement.     

No Effect of Diclofenac on the Pharmacokinetics of Cloxacillin

Abstract: We studied the influence of diclofenac on the pharmacokinetics of cloxacillin in healthy volunteers, 60 years or older, as well as the possible effect of cloxacillin and diclofenac on urinary protein excretion. In a randomized, double-blind, cross-over study 15 subjects were given 1 g cloxacillin, and placebo or 75 mg diclofenac, as single intravenous doses. Plasma concentrations of cloxacillin were followed over 10.5 hr, and urine excretion of cloxacillin over 24 hr. The effect of the drugs on urinary excretion of protein indicators of glomerular (albumin, IgG) and tubular (protein HC) function was also studied. Total plasma clearance of cloxacillin was with placebo 219+51 (mean + S.D), and with diclofenac 212+39 ml/min./1.73 m² (ns); renal clearance was 97+21 and 96+24 ml/min./1.73 m², respectively (ns). The terminal t_1/2 of cloxacillin was 1.03+0.42 hr with placebo, and 1.12+0.37 with diclofenac (ns). The mean ratio of AUC_0-∞'s (cloxacillin plus diclofenac/cloxacillin plus placebo) was 1.03 (90% CI: 0.99, 1.08). Urinary excretion of the proteins was low and was not increased by cloxacillin or diclofenac. In healthy volunteers, 60 years or older, diclofenac does not alter cloxacillin pharmacokinetics, and neither cloxacillin nor diclofenac in single intravenous doses cause renal dysfunction.     

Extra- and intracellular pH in the brain during seizures and in the recovery period following the arrest of seizure activity

The objective of the study was to estimate changes in extracellular pH (pHe) and intracellular pH (pHi) during seizures and in the recovery period following the arrest of seizure activity. Seizures of 5- and 20-min duration were induced in rats by fluorothyl added to the insufflated gas mixture, and recovery for 5, 15, and 45 min was instituted by withdrawal of the fluorothyl supply following 20 min of continuous seizures. Changes in pHe were measured by double-barreled, liquid ion-exchange pH microelectrodes, and in pHi by the CO2 method, following estimation of tissue PCO2 and extracellular fluid (ECF) volume. The animals were either normoxic or rendered moderately hypoxic (arterial PO2 40-50 mm Hg). Upon induction of seizures in normoxic animals, pHe decreased by a mean of 0.36 unit, the values being identical at 5 and 20 min. In moderate hypoxia, seizures sustained for 20 min were accompanied by a further fall in pHe (mean decrease 0.51 unit). The changes in pHe seemed mainly to reflect the nonionic diffusion of lactic acid from cells to the ECF (tissue lactate levels approximately 10 and 15 mumol g-1 during seizures in normoxic and hypoxic animals, respectively). However, the gradual fall in pHe attributable able to lactic acid production was preceded by rapid acidification, sometimes exceeding the steady-state values subsequently attained. This acidification was interpreted to reflect spreading depression and fast transcellular Na+/H+ exchange. Following cessation of seizure discharge, pHe normalized at a surprisingly slow rate, with some acidosis persisting even after 45 min. The difference between cerebrovenous and arterial PCO2 was reduced during seizures and increased in the recovery period, probably reflecting alterations in the blood flow/metabolic rate coupling. Impedance changes were slight, indicating only minor changes in ECF volume. Changes in pHi after 5 min of seizures ranged from 0.20 (normoxic animals) to 0.32 (hypoxic animals) unit, the pHi values after 20 min being 0.07-0.08 unit higher. The results suggest the regulation of pHi during ongoing seizures. Upon arrest of seizure activity, pHi rapidly increased to normal and subsequently to supranormal values. Postepileptic intracellular alkalosis occurred at a time when pHe was still reduced and in spite of the fact that tissue lactate values had not normalized. It is concluded that the rapid normalization of pHi and overt alkalosis were caused by the simultaneously occurring oxidation of lactate, with the removal of a stoichiometrical amount of H+, and the extrusion of H+ from cells, possibly via a Na+/H+ exchanger, the latter probably delaying normalization of pHe.     

Pharmacokinetics of cloxacillin in patients undergoing hip or knee replacement

Objective: The pharmacokinetics of cloxacillin was investigated in 14 men and 24 women undergoing cemented hip (n = 19; age range 56–90) or knee replacement surgery (n = 19; age range 51–84) for osteoarthritis. Cloxacillin 1 g was given intravenously as a bolus dose at the induction of anesthesia, and plasma samples and urine were collected for 6 h. Drug levels were determined using HPLC. Results: Preoperative serum creatinine levels were 84 μmol · l⁻¹ in hip patients and 72 μmol · l⁻¹ in knee patients. The calculated values for creatinine clearance were 63 and 85 ml · min⁻¹ · 1.73 m⁻², respectively. Total clearance of cloxacillin was 134 ml · min⁻¹ · 1.73 m⁻² in eighteen evaluated patients undergoing hip replacement, and 162 ml · min⁻¹ · 1.73 m⁻² in eighteen patients undergoing knee surgery. Renal clearance was 72 and 79 ml · min⁻¹ · 1.73 m⁻², respectively. Non-renal clearance was 57 ml · min⁻¹ · 1.73 m⁻² in hip patients and 77 ml · min⁻¹ · 1.73 m⁻² in knee patients. Renal clearance of cloxacillin correlated with the estimated creatinine clearance (r = 0.652). Although women received higher doses than men (median 2.02 vs 2.32 mmol · 1.73 m⁻²), there were no sex differences in clearance corrected for body surface area. Conclusion: Total clearance of cloxacillin was lower in patients undergoing hip replacement than in patients undergoing replacement of the knee, but there was no difference between men and women. Received: 7 May 1996 / Accepted in revised form: 15 October 1996     

Renal impairment after hip or knee arthroplasty: Urinary excretion of protein markers studied in 59 patients

We studied renal function during and after surgery in 38 patients undergoing total hip replacement (THR) and 21 patients undergoing total knee replacement (TKR). Serum creatinine and renal excretion of albumin, IgG, protein HC and creatinine were recorded preoperatively and on days 1, 2, 4, and 8. THR patients were randomized to treatment with (n 17) or without (n 21) prophylactic isoxazolyl penicillins, which all TKR patients had. In all 3 groups, the urinary concentration of proteins increased postoperatively with a peak in the glomerular markers (albumin, IgG) on days 1 and 2, and in the tubular marker (protein HC) on days 2 and 4. There were no statistically significant differences between the groups. On day 8, all urinary protein concentrations had essentially returned to their preoperative levels. Serum creatinine decreased by 10% in THR patients on day 1 and then returned to baseline levels, but there was a gradual increase up to 13% in TKR patients.