Determination of total body water in uraemic patients by bioelectrical impedance

The measurement of total body water by bioeiectrical impedancein a group of renal patients was evaluated against the tritiumdilution method. The effect of haemodialysis and the presenceof peritoneal dialysate on the impedance were also investigated.The correlation between the two methods is r = 0.90 with a residualstandard deviation of 3.7. The standard devi ation of the differencesbetween the two methods against the means was 3.66 which meansthat total body water (TBW) estimated by the bioelectrical impedance(BEI) method may be 6.181 (X ± 2 SD) above or 8.381 belowthe ³H₂O method. The BEI method overestimated the actual weightloss after haemodialysis (3.87±1.71 versus 2.43±1.81)but underestimated the volume of peritoneal dialysate in situThe BEI method would not be appropriate for use in assessingtotal body water and monitoring acute volume changes in patientswith renal failure who are on strict fluid restriction.     

PHARMACOKINETICS OF SINGLE-DOSE I.V.MORPHINE IN NORMAL VOLUNTEERS AND PATIENTS WITH END-STAGE RENAL FAILURE

Morphine 0.125 mgkg^–1 was administered i.v. to 11 normalsubjects and nine patients with chronic renal failure requiringregular haemodialysis. Plasma morphine concentrations were measuredusing high pressure liquid chromatography (HPLC). Although therewas considerable individual variation in both groups, mean plasmaconcentrations of morphine were significantly higher in thepatients with renal failure for 15 min after administration.The decay of plasma concentration fitted a three-compartmentmamillary pharmacokinetic model in all subjects. Derived values(mean $ SEM) of T^x, volume of distribution of the second compartment(V₂), total volume of distribution at steady state ( V^ss1) andtransfer rate constant from the first to the second compartment(k₁₂) were significantly different between groups. Mean valuesof terminal elimination half-life (T⁷) and total body clearancewere similar in the two groups. It was concluded that eliminationof unchanged morphine is not impaired significantly in patientswith chronic renal failure, although accumulation of morphine-3-glucuronideprobably occurs. Although the pharmacological effect of morphineis not related temporally to plasma morphine concentrations,the higher values in patients with renal failure may be implicatedin their increased sensitivity to the drug     

Continuous Ambulatory Peritoneal Dialysis vs Haemodialysis: A Lesser Risk of Amyloidosis?

We compared plasma beta-2-microglobulin ß₂M at a 1-yearinterval in 25 CAPD patients and 25 patients haemodialysed withcuprophane membranes and matched for residual renal functionand duration of renal replacement therapy. Plasma ß₂Mremained lower in CAPD patients throughout the study, and increasedsignificantly with time both in CAPD and haemodialysis patients,as renal function decreased. In both groups, plasma ß₂Mwas negatively correlated with residual creatinine clearance,the influence of the latter being much greater in haemodialysis,as demonstrated by comparison of the regression lines. In haemodialysis,but not in CAPD. plasma ß₂M also correlated with timeon dialysis. In CAPD patients. the daily peritoneal output averaged 38 mg(range 16–59 mg), and was directly correlated with plasmaß₂M CAPD thus allows a significant peritoneal removal of ß₂Mwhich progressively takes over from the declining renal function,resulting in lower plasma ß₂M than in matched haemodialysispatients. However, the peritoneal removal of ß₂M remainsinsufficient and values increase with time as renal functiondeclines. Thus, if ß₂M amyloidosis is related to raisedplasma levels, the risk of ß₂M amyloidosis in CAPDshould simply be delayed as compared to haemodialysis.     

Tissue Uptake of 125I-{beta}2-Microglobulin({beta}2-M) in Anephric Animals in the Presence or Absence of Aluminium Intoxication

In long-term haemodialysis patients a new type of amyloidosiscomposed of ß₂-microglobulin (ß₂-M) hasrecently been described. The amyloid deposition has a particularpredilection for articular structures. In the pathogenesis ofthis complication markedly elevated plasma ß₂-M concentrations,such as those observed in anuric patients, have a role. However,other as yet ill-defined factors must also be implicated, possiblecandidates being aluminium intoxication and the widely usedregenerated cellulose (cuprophan) membrane. In the present experimentalstudy, we examined tissue distribution of exogenous ß₂-Mafter i.v. injection of ¹²⁵I-ß₂-M to bilaterally nephrectomisedrats. One hundred and twenty minutes after injection, most radioactivityremained in the vascular compartment. The accumulation in tissueswas weak, and no predilection for a particular tissue becameapparent. Interestingly, chronically aluminium-overloaded, acutelyanephric rats accumulated a significantly greater amount of¹²⁵I-ß₂-M in their spleens than anephric rats withoutprior aluminium intoxication. We then attempted to induce ß₂-M amyloid depositionin rats and mice, some of whom had undergone chronic aluminiumintoxication and subcutaneous implantation of regenerated cellulosefragments for various periods of time. They were subsequentlymade anephric to obtain high plasma ß₂-M concentrations.None of the animals developed ß₂-M amyloidosis inspleen, liver, skin and mechanically altered joint synovium. In conclusion, chronic aluminium intoxication enhances splenicaccumulation of exogenous ¹²⁵I-ß₂-M in anephric rats.The factors required to form ß₂-M-amyloidosis in vivohave still to be defined.     

Determination of the Acid-base Status in Blood of Patients on Chronic Haemodialysis and of Bicarbonate in Dialysate: Comparison of Three Techniques and Their Mathematically Derived Values

The study deals with the comparison of acid-base parametersin blood of patients on chronic haemodialysis and of bicarbonatedialysate determined by Gas-Check AVL 945, equilibration technique(ET) , and a titrimetric method. The results show that an acceptableagreement exists between AVL and ET with respect to measurementsof pH, pCO₂ HC0₃^– and base excess. However, the valuesobtained for total buffer base related to the actual haemoglobinconcentration are significantly lower (P <0.001) when determinedby AVL. A titrimetric method is proposed for routine measurement ofHCO₃^– in bicarbonate dialysate. Values obtained usingthis method are 3–4 mmol/l higher than those determinedby AVL and ET. However, when the values for pK₁' and for thesolubility coefficient used in the Henderson-Hasselbaich equationare replaced by those for saline-bicarbonate solutions, resultsobtained using the titrimetric determined values agree wellwith those obtained by AVL and ET.     

Time course of inulin and creatinine clearance in the interval between two haemodialysis treatments

BACKGROUND: Urinary volume of haemodialysis patients with residual renalfunction increases during the interdialytic interval. The contributionof GFR to this change in water and solute excretion has notbeen quantified in detail. The creatinine clearance (Cl^c) asa determinant of the GFR may overestimate GFR caused by thetubular secretion of creatinine. Cimetidine has been used toinhibit the secretion of creatinine in non-dialysed patients.No data are available on its usefulness in haemodialysis patients. METHODS: Two identical interdialytic intervals (DI) of 3 days (DI-1,DI-2) were investigated in 11 patients. The interval betweenDI-1 and DI-2 was 1 week. During DI-2 cimetidine 800 mg dailywas administered. Each DI was divided in four urine-collectionperiods. RESULTS: The water and solute excretion in DI-1 and DI-2 were similar.Urinary production increased from 0.37 ±0.30 ml/min to0.66 ±0.33 ml/min (P<0.05), inulin clearance (C1¹)increased from 1.8±1.1 ml/min to 2.7 ± 1.2 ml/min(P<0.05), fractional sodium excretion from 9.0 ± 5.7%to 14.5 ± 9.0% (P<0.05). In contrast to Cl_i;; theCl_c showed no increase during the interdialytic interval bothin DI-1 and DI-2. The overestimation of GFR by creatinine (Cl_i– Clⁱ) decreased during DI-1 from 1.35 ±1.69 ml/minto 0.26 ± 0.60 (P<0.05) and during DI-2 from 1.01±1.33 ml/min to 0.10 ± 0.67 (P<0.01). The ratioCl^c/Clⁱ decreased during DI-1 from 1.78 ± 0.53 to 1.09± 0.19 (P< 0.01) and during DI-2 from 2.02 ±1.13to 1.05 ± 0.30 (P<0.01). All parameters were not differentbetween the comparable days of DI-1 and DI-2. CONCLUSION: We conclude that the urinary volume in the interdialytic intervalis directly related to changes in GFR. During the interdialyticinterval GFR increased and tubular secretion of creatinine decreased.The administration of cimetidine did not improve the accuracyof Cl_c as a measurement of GFR in end-stage renal failure.     

DEADSPACE AND THE SINGLE BREATH TEST FOR CARBON DIOXIDE DURING ANAESTHESIA AND ARTIFICIAL VENTILATION: Effects of tidal volume and frequency of respiration

Using the single breath test for carbon dioxide (SBT-CO₂) thecomponent of physiological deadspace were investigated duringanaesthesia with IPPV in 58 patients. A square-wave inspiratoryflow and an end-inspiratory pause (25% and 10% of cycle time,respectively) were used. At tidal volumes of 0.45 litre (f =17 b.p.m.),and 0.75 litre (f = 9 b.p.m.), median values forVD_phys/VT were 0.44 and 0.31. Increasing VT and decreasing fdid not change airway deadspace (VD^RW) so that the fractionVD^RW/VT was decreased (P<0.001). The alveolar deadspace fraction,VD^alv/VT^alv, was decreased in 93% of patients (P<0.001).These improvements with increasing VT can be attributed to beneficialeffects on gas distribution and diffusion time. Patients withlarge alveolar deadspaces had steeply sloping SBT-CO₂ phaseIII, and increased expiratory time constants of the respiratorysystem. The median arterial—end-tidal PCO₂ difference,(PaCO₂ – PE'CO₂), was 0.6 kPa at small and 0.3 kPa atlarge tidal volumes (P<0.001). Three patients had zero andfour had negative (PaCO₂ - PE'CO₂) values at large tidal volumes.When phase III slopes steeply, negative (PaCO₂ – PE'CO₂)values may be observed in the presence of alveolar deadspace.     

TIME COURSE OF NEUROMUSCULAR EFFECTS AND PHARMACOKINETICS OF ROCURONIUM BROMIDE (ORG 9426) DURING ISOFLURANE ANAESTHESIA IN PATIENTS WITH AND WITHOUT RENAL FAILURE

We have studied the onset and duration of action and pharmacokineticsof rocuronium bromide (Org 9426) during anaesthesia with nitrousoxide, fentanyl and isoflurane after a single bolus dose ofrocuronium 0.6 mg kg^–1 in nine patients with chronic renalfailure requiring regular haemodialysis, and in nine healthycontrol patients. Blood samples were collected over 390 minand concentrations of rocuronium and its putative metabolitesmeasured using HPL C. Onset time for maximum block, durationof clinical relaxation (T1₂₅) and recovery index, were 61 (SD25.0) s and 65 (16.4) s, 55 (26.9) min and 42 (9.3) min and28 (12.3) min and 19 (8.8) min, respectively, for patients withand without renal failure. The time for TOF ratio to returnspontaneously to 0.7 was 99 (41.1) min and 73 (24.2) min, respectively,in the two groups. None of these differences was significant.The pharmacokinetic data were best described by a three-exponentialequation. There were significant differences between patientswith and without renal failure in the rates of clearance (2.5(1.1) ml kg^–1 min^–1 and 3.7(1.4) ml kg^–1 min^–1respectively) and the mean residence times (97.1 (48.7) minand 58.3(9.6) min) (P<0.05). The differences in other kineticparameters were not significant. We conclude that the effectsof rocuronium may be prolonged in patients with renal disease,because of a decreased clearance of the drug.     

Cerebral haemodynamics in patients with chronic renal failure: effects of haemodialysis

Background. We measured middle cerebral artery (MCA) flow velocity(FV), dynamic pressure autoregulation, and carbon dioxide reactivity(CRCO₂) in patients with chronic renal failure before and afterhaemodialysis using transcranial Doppler ultrasonography. Methods. Twelve patients on long-term haemodialysis were recruited.MCA FV was measured continuously. The transient hyperaemic responsetest was used to assess cerebral autoregulation, and per centchange in FV per kPa change in end-tidal carbon dioxide wascalculated to assess CRCO₂. All measurements were recorded beforeand after haemodialysis. Results. MCA FV (mean [SD]) decreased from 57 (10) cm s^–1before to 46 (13) cm s^–1 after haemodialysis (P<0.01).The transient hyperaemic response ratio (THRR) was (mean [SD])1.29 (0.13) before haemodialysis and did not change significantlyfollowing haemodialysis (1.36 [0.10]). CRCO₂ was 21.7 (8.3)%kPa^–1 before haemodialysis and remained unchanged afterwards(20.9 [3.8]% kPa^–1). Values in normal subjects for MCAFV, THRR and CRCO₂ are 56 (12) cm s^–1, 1.26 (0.13) and22 (6)% kPa^–1, respectively. Conclusions. MCA FV decreases significantly after haemodialysis.Dynamic pressure autoregulation and CRCO₂ remain normal in patientswith chronic renal failure, and are not altered significantlyby haemodialysis. Presented at the European Society of Anaesthesiologists AnnualCongress Amsterdam, May 1999.