Detection limit of methods to assess fluid status changes in dialysis patients
2006; Elsevier BV; Volume: 69; Issue: 9 Linguagem: Inglês
10.1038/sj.ki.5000286
ISSN1523-1755
AutoresMatthias Kraemer, Christiane Rode, V. Wizemann,
Tópico(s)Body Composition Measurement Techniques
ResumoTechnical systems for an accurate and practicable fluid management of dialysis patients are urgently needed, since current clinical methods are partially subjective, imprecise, and time consuming. Such new systems should not only allow the determination of the target normohydration weight, but also must be able to detect clinically relevant changes in fluid volume (∼1 l). This study focuses on the systematic analysis of the detection limit of several candidate methods for fluid management. In a cohort of 16 new dialysis patients, several candidate methods were applied in parallel during each treatment of the initial weight reduction phase: the measurement of vena cava diameter (VCD), vena cava collapsibility index (CI), the blood volume drop during an ultrafiltration (UF) bolus (Δrelative blood volume (RBV)-), the rebound after the UF bolus (ΔRBV+), and the extracellular fluid volume determined with whole body bioimpedance spectroscopy (BIS). A clinical reference method was used to manage the fluid status of patients. All methods showed significant correlations with predialysis weight. The detection limits Wlim of candidate methods for changes in fluid status were assessed as Wlim=0.87 kg±0.64 kg (BIS), 1.74 kg±1.56 kg (VCD), 2.3 kg±1.0 kg (ΔRBV-), 7.4 kg±8.5 kg (CI), 40 kg±108 kg (ΔRBV+). Only BIS shows a satisfactorily low detection limit Wlim, whereas Wlim was rated as critical for the VCD and ΔRBV- methods, and as unacceptable for the CI and ΔRBV+ methods. Bioimpedance spectroscopy appears to be the most promising method for a practical fluid management system in dialysis. Technical systems for an accurate and practicable fluid management of dialysis patients are urgently needed, since current clinical methods are partially subjective, imprecise, and time consuming. Such new systems should not only allow the determination of the target normohydration weight, but also must be able to detect clinically relevant changes in fluid volume (∼1 l). This study focuses on the systematic analysis of the detection limit of several candidate methods for fluid management. In a cohort of 16 new dialysis patients, several candidate methods were applied in parallel during each treatment of the initial weight reduction phase: the measurement of vena cava diameter (VCD), vena cava collapsibility index (CI), the blood volume drop during an ultrafiltration (UF) bolus (Δrelative blood volume (RBV)-), the rebound after the UF bolus (ΔRBV+), and the extracellular fluid volume determined with whole body bioimpedance spectroscopy (BIS). A clinical reference method was used to manage the fluid status of patients. All methods showed significant correlations with predialysis weight. The detection limits Wlim of candidate methods for changes in fluid status were assessed as Wlim=0.87 kg±0.64 kg (BIS), 1.74 kg±1.56 kg (VCD), 2.3 kg±1.0 kg (ΔRBV-), 7.4 kg±8.5 kg (CI), 40 kg±108 kg (ΔRBV+). Only BIS shows a satisfactorily low detection limit Wlim, whereas Wlim was rated as critical for the VCD and ΔRBV- methods, and as unacceptable for the CI and ΔRBV+ methods. Bioimpedance spectroscopy appears to be the most promising method for a practical fluid management system in dialysis. Increased extracellular volume (ECV) is known to lead to edema, dyspnoea, and especially hypertension, a consequence of the increased intravascular volume. Longer-lasting hypertension causes a continuous additional workload to the heart, which typically leads to left ventricular hypertrophy and cardiovascular morbidity, including congestive heart failure. Impaired diastolic or systolic function increases the risk of onset of hypotension during dialysis, and also of sudden cardiac death. Furthermore, the presence of edema facilitates the onset of skin infections, which are frequent especially in diabetics. Skin infections may give rise to sepsis (which involves a high mortality risk) and may lead to amputations. Pulmonary congestion may give rise to bronchitis and pneumonia, gastrointestinal congestion to malabsorption of nutrients. Hypertension is regarded as an important risk factor in the end stage renal disease (ESRD) population. It is generally assumed to be caused by salt and volume overload in the majority of patients. This is supported by the experience from Tassin, France, where antihypertensive drugs could be avoided in 98% of patients by using long dialysis treatments, and a strict fluid removal and dietary salt intake reduction schedule.1Charra B. Calemard E. Laurent G. Importance of treatment time and blood pressure control in achieving long-term survival on dialysis.Am J Nephrol. 1996; 16: 35-44Crossref PubMed Scopus (187) Google Scholar, 2Charra B. Does empirical long slow dialysis result in better survival? If So, How and Why?.ASAIO J. 1993; 39: 819-822PubMed Google Scholar, 3Charra B. Laurent G. Chazot C. et al.Clinical assessment of dry weight.Nephrol Dial Transplant. 1996; 11: 16-19Crossref PubMed Scopus (154) Google Scholar Jaeger and Mehta4Jaeger J.Q. Mehta R.L. Assessment of dry weight in hemodialysis: an overview.J ASN. 1999; 10: 392-403Google Scholar claim that according to several clinical studies, at least 80% of all hypertension in dialysis patients is due to chronic volume overload.4Jaeger J.Q. Mehta R.L. Assessment of dry weight in hemodialysis: an overview.J ASN. 1999; 10: 392-403Google Scholar A still existing fluid overload was found in patients who seemed to show dialysis-resistant hypertension.5Katzarski K. Charra B. Laurent G. et al.Multifrequency bioimpedance in assessment of dry weight in haemodialysis.Nephrol Dial Transplant. 1996; 11: 20-23Google Scholar, 6Fishbane S. Natke E. Maesaka J.K. Role of volume overload in dialysis-refractory hypertension.Am J Kidney Dis. 1996; 28: 257-261Abstract Full Text PDF PubMed Scopus (102) Google Scholar Karzarski5Katzarski K. Charra B. Laurent G. et al.Multifrequency bioimpedance in assessment of dry weight in haemodialysis.Nephrol Dial Transplant. 1996; 11: 20-23Google Scholar demonstrated the relation between fluid overload and hypertension by showing that hypertensive patients have a significantly increased ECV compared to normotensive patients and controls. Again another study7Katzarski K.S. Charra B. Luik A.J. et al.Fluid state and blood pressure control in patients treated with long and short haemodialysis.Nephrol Dial Transplant. 1999; 14: 369-375Crossref PubMed Scopus (159) Google Scholar showed that lowering the post-dialysis ECV to adequately low values was essential for achieving normotension. Overhydration was found not only in hemodialysis patients, but appears to be a similar or even larger problem in peritoneal dialysis patients.8Oe B. de Fijter C.W. Geers T.B. et al.Hemodialysis (HD) versus peritoneal dialysis (PD): Latent overhydration in PD patients?.Int J Artif Organs. 2002; 25: 838-843PubMed Google Scholar, 9Enia G. Mallamaci F. Benedetto F.A. et al.Long-term CAPD patients are volume expandes and display more severe left ventricular hypertrophy than haemodialysis patients.Nephrol Dial Transplant. 2001; 16: 1464Crossref Scopus (174) Google Scholar Despite many studies support the causal relation between overhydration and hypertension, some studies investigating the short-term (e.g. intradialytic) response of blood pressure to fluid volume changes do not detect this correlation.10Luik A.J. Van Kuijk W.H.M. Spek J. et al.Effects of hypervolemia on interdialytic hemodynamics and blood pressure control in hemodialysis patients.Am J Kidney Dis. 1997; 30: 466-474Abstract Full Text PDF PubMed Scopus (38) Google Scholar, 11Leenen F.H.H. Galla S.J. Geyskes G.G. et al.Effects of hemodialysis and saline loading on body fluid compartments, plasma renin activity, and blood pressure in patients on chronic hemodialysis.Nephron. 1977; 18: 93-100Crossref PubMed Scopus (19) Google Scholar, 12Savage T. Fabbian F. Giles M. et al.Interdialytic weight gain and 48-h blood pressure in haemodialysis patients.Nephrol Dial Transplant. 1997; 12: 2308-2311Crossref PubMed Scopus (39) Google Scholar But this lack of immediate correlation may well be explained by the large number of clinical experiences indicating a lag time of several days or weeks between a volume change and a succeeding blood pressure change, as referred by Charra.13Charra B. Dry weight in dialysis: the history of a concept.Nephrol Dial Transplant. 1998; 13: 1882-1885Crossref PubMed Scopus (42) Google Scholar Antihypertensive medications today are very effective in lowering blood pressures, especially in case of normal volume state. In a state of overhydration the blood pressure-lowering effect is somewhat attenuated.14Dorhout M. Mees E.J. Cardiovascular Aspects of Dialysis Treatment. Kluwer Academic Publishers, Dordrecht, The Netherlands2000Google Scholar In many dialysis centers most patients are on antihypertensives. Nevertheless the use of such drugs has clear disadvantages compared to a normalization of blood pressure by elimination of overhydration: the intravascular volume is still overloaded, and there may be the risk of a still too high cardiac output or of insufficient perfusion due to the medication, leaving the patients on increased risk despite medication. Additionally, antihypertensive therapy is certainly more expensive than a reduction of fluid overload. The mean arterial pressure (MAP) is a predictor for survival in dialysis patients.1Charra B. Calemard E. Laurent G. Importance of treatment time and blood pressure control in achieving long-term survival on dialysis.Am J Nephrol. 1996; 16: 35-44Crossref PubMed Scopus (187) Google Scholar Avoiding long-term overhydration and in consequence hypertension therefore is a major requirement for long-term survival. Achieving a physiologically normal fluid status (normohydration) by a practical, efficient method for fluid status measurement therefore is a primary goal to avoid critical long-term consequences for the patient. A variety of concepts has been used to quantitatively assess the fluid status of a dialysis patient. Several comparisons of such methods have already been published.4Jaeger J.Q. Mehta R.L. Assessment of dry weight in hemodialysis: an overview.J ASN. 1999; 10: 392-403Google Scholar, 15Kouw P.M. Kooman J.P. Cheriex E.C. et al.Assessment of postdialysis dry weight: a comparison of techniques.J ASN. 1993; 4: 98-104Google Scholar, 16Leunissen K.M.L. Kouw P.M. Kooman J.P. et al.New techniques to determine fluid status in hemodialyzed patients.Kidney Int. 1993; 43: S-50-S-56Google Scholar, 17Franz M. Pohanka E. Tribl B. et al.Living on chronic hemodialysis between dryness and fluid overload.Kidney Int. 1997; 51: S-39-S-42Google Scholar, 18Leunissen K.M.L. Hydrationsstatus von Dialysepatienten.Dialyse-J. 1992; 40: 2-7Google Scholar In the following, only concepts used in the present study are described. Other methods for fluid status assessment and variants of the methods described are existing. In order to assess the hydration status more quantitatively, Wizemann and Schilling19Wizemann V. Schilling M. Dilemma of assessing volume state – the use and the limitations of a clinical score.Nephrol Dial Transplant. 1995; 10: 2114-2117PubMed Google Scholar developed a clinical score of volume state. Typical symptoms for hypovolemia (e.g. thirst, tiredness, hypotension, and muscle cramps) or hypervolemia (etc. dyspnoea, edema, and coughing) are observed. Also a blood pressure increase during ultrafiltration (UF), also known as 'paradoxical hypertension,'14Dorhout M. Mees E.J. Cardiovascular Aspects of Dialysis Treatment. Kluwer Academic Publishers, Dordrecht, The Netherlands2000Google Scholar is indicative of hypervolemia, despite the mechanism is not well understood. Each symptom, partially weighted according to its severity, is linked to a number, with negative numbers indicating hypovolemia, positive numbers indicating hypervolemia. By summing up numbers related to observed symptoms, a total score is obtained. Since symptoms are not always specific for fluid-related problems, they should ideally be scored only if they appear de novo after a previous symptom-free state. If such a symptom-free observation phase does not exist (e.g. in new dialysis patients), all symptoms must be assumed as fluid related. This clinical score may be combined with other usually available information, the pre- and postdialysis blood pressure and the dose of antihypertensive medication. A clinical score indicating absence of hypo- and hypervolemic symptoms, in combination with a blood pressure in the normal range and absence of antihypertensive medication may be regarded as a strong indication for a normohydrated status. This practice of fluid management requires a well-educated and dedicated staff, and is relatively time consuming and thereby expensive. The diameter of the inferior vena cava (VCD) has often been used with the intent to assess hydration status (e.g. Ando et al.20Ando Y. Yanagiba S. Asano Y. The inferior vena cava diameter as a marker of dry weight in chronic hemodialyzed patients.Artif Organs. 1995; 12: 1237-1242Crossref Scopus (62) Google Scholar, Cheriex et al.21Cheriex E.C. Leunissen K.M.L. Janssen J.H. et al.Echography of the inferior vena cava is a simple and reliable tool for estimation of 'dry weight' in haemodialysis patients.Nephrol Dial Transplant. 1989; 4: 563-568PubMed Google Scholar and Schumacher et al.22Schumacher J. Rob P. Kreft B. et al.Measurement of fluid volume shifts during hemodialysis by a mode ultrasonography.Blood Purif. 2000; 18: 103-109Crossref PubMed Scopus (8) Google Scholar). Excess extracellular fluid increases the intravascular volume, which in turn typically leads to an increased central venous pressure and VCD. VCD is typically measured by ultrasonography, as first reported by Weil and Maurat.23Weil F. Maurat P. The sign of the vena cava: echotomographic illustration of right cardiac insufficiency.J Clin Ultrasound. 1974; 2: 27-32Crossref PubMed Scopus (10) Google Scholar Since the vena cava dilates with expiration and collapses with inspiration, the minimal and maximal diameters VCDmin and VCDmax are usually measured. The collapsibility index (CI) is the fractional reduction of VCD during the breathing cycle. Collapsibility index correlates inversely with central venous pressure CVP24Tamaki S. Relationship between ventilatory change in the inferior vena cava and central venous pressure.Jpn J Soc Thorac Dis. 1981; 19: 460-469Google Scholar and has therefore been regarded another candidate indicator for fluid status measurement. A large fluid overload in the vascular system usually leads to a small collapsibility, and vice versa. Measurement of relative blood volume (RBV) is another candidate method for hydration status assessment. Relative blood volume is the percent change of blood volume from blood volume at start of hemodialysis and may be measured easily with existing devices. This method makes use of the relation between hydration and the intensity of refilling of the vascular space. The refilling which takes place during and after a short period of intense UF depends on the fluid volume in the interstitial space. Higher fluid volumes will cause an increased interstitial pressure, leading typically to increased refilling. The drop in RBV during a standardized UF bolus and the degree of refilling after the bolus should both depend on the hydration status. The relation between change in RBV and fluid status has been mentioned by several authors (e.g. Lopot and Kotyk25Lopot F. Kotyk P. Computational analysis of blood volume dynamics during hemodialysis.Int J Artif Organs. 1997; 20: 91-95PubMed Google Scholar and Steuer et al.26Steuer R.R. Leypoldt J.K. Cheung A.K. et al.Hematocrit as an indicator of blood volume and a predictor of intradialytic morbid events.ASAIO J. 1994; 40: M691-M696Crossref PubMed Scopus (89) Google Scholar). The drop in RBV from beginning to end of dialysis tends to be more pronounced in less overhydrated patients.27de Vries J.P. Kouw P.M. van der Meer N.J.M. et al.Non-invasive monitoring of blood volume during hemodialysis: its relation with post-dialytic dry weight.Kidney Int. 1993; 44: 851-854Abstract Full Text PDF PubMed Scopus (72) Google Scholar Several authors already used standardized boli for several purposes. Koomans et al.28Koomans H.A. Geers A.B. Mees E.J. Plasma volume recovery after ultrafiltration in patients with chronic renal failure.Kidney Int. 1984; 26: 848-854Abstract Full Text PDF PubMed Scopus (110) Google Scholar used a relatively long bolus, removing about UFV=2 l in 1 h, and found a clear dependence of plasma volume change from tissue hydration state. Schneditz et al.29Schneditz D. Roob J. Oswald M. et al.Nature and rate of vascular refilling during hemodialysis and ultrafiltration.Kidney Int. 1992; 42: 1425-1433Abstract Full Text PDF PubMed Scopus (113) Google Scholar used UF boli with 20 min duration and an average UF rate UFR of 2.1 l/h for investigating vascular refilling mechanisms. Wizemann used an UF bolus, removing 1% of target weight in 15 min, and a follow-up period of 45 min without UF.30Wizemann V. Leibinger A. Mueller K. Nilson A. Influence of hydration state on plasma volume changes during ultrafiltration.Artif Organs. 1995; 19: 416-419Crossref PubMed Scopus (42) Google Scholar, 31Wizemann V. Leibinger A. Mueller K. Nilson A. Einfluss des Hydrationszustandes auf ultrafiltrationsbedingte Plasmavolumenveraenderungen.Dialyse-J. 1993; 43: 8-14Google Scholar He observed that the less hydrated the patient is, the more pronounced is the fall in plasma volume during UF, and the more pronounced is the rebound after UF. Mitra et al.32Mitra S. Chamney P. Greenwood R. Farrington K. Linear decay of relative blood volume during ultrafiltration predicts hemodynamic instability.Am J Kidney Dis. 2002; 40: 556-565Abstract Full Text Full Text PDF PubMed Scopus (41) Google Scholar investigated the kinetics of the blood volume drop with kinetic models, making extensive use of UF boli (removing 40% of intradialytic weight gain with UFR=3 l/h) to determine the patient-specific response. Chamney et al.33Chamney P. Johner C. Aldridge C. et al.Fluid balance modelling in patients with kidney failure.J Med Eng Technol. 1999; 23 (45): 45Crossref PubMed Scopus (18) Google Scholar removed the total UF volume in four boli of decreasing length using an UFR=4 l/h. In a whole body bioimpedance measurement the combined electrical impedance of arm, trunk, and leg is measured at a specific frequency (mostly 50 kHz). It requires four electrodes; two attached to the wrist and two to the ankle. Via the outer electrode pair, a fixed small alternating current I is applied, and via the inner electrodes a voltage U is measured. The ratio ∣Z∣=U/I and the phase shift Φ between them depends on the amount and distribution of fluid in the body. Bioimpedance spectroscopy (BIS) utilizes the variation of the frequency of the applied current, and thereby allows to distinguish between intracellular and extracellular fluid volumes (Figure 1). Since the membranes of the cells in the current path behave as insulators, the conductivity of tissues depends much on the frequency. At low frequencies (∼5 kHz), the extracellular space is conducting almost exclusively. For high frequencies (∼1 MHz), the intracellular pathway is largely accessible additionally since the membrane shows only a low resistance. At intermediate frequencies the intracellular space is partially contributing to conductivity. The frequency variation thereby allows to determine extra- and intracellular volumes (ECV and ICV) separately (for details of method see Ackmann and Seitz34Ackmann J.J. Seitz M.A. Methods of complex impedance measurements in biologic tissue.CRC Crit Rev Biomed Eng. 1984; 11: 281-311PubMed Google Scholar, Stroud et al.35Stroud D.B. Cornish B.H. Thomas B.J. Ward L.C. The use of Cole-Cole plots to compare two multifrequency bioimpedance instruments.Clin Nutr. 1995; 14: 307-311Abstract Full Text PDF PubMed Scopus (26) Google Scholar, Ellis et al.36Ellis K.J. Bell S.J. Chertow G.M. et al.Bioelectrical impedance methods in clinicalresearch: a follow-up to the NIH technology assessment conference.Nutrition. 1999; 15: 874-880Abstract Full Text Full Text PDF PubMed Scopus (135) Google Scholar, 37Ellis K.J. Shypailo R.J. Wong W.W. Measurement of body water by multifrequency bioelectrical impedance spectroscopy in a multiethnic pediatric population.Am J Clin Nutr. 1999; 70: 847-853PubMed Google Scholar, Gudivaka et al.38Gudivaka R. Schoeller D.A. Kushner R.F. Bolt J.G. Single- and multifrequency models for bioelectrical impedance analysis of body water compartments.J Appl Physiol. 1999; 87: 1087-1096PubMed Google Scholar, Jaffrin et al.39Jaffrin M.Y. Maasrani M. Boudailliez B. le Courrier A. Extracellular and intracellular fluid volume monitoring during dialysis by multifrequency impedancecemtry.ASAIO J. 1996; 42: M533-M538Crossref PubMed Scopus (24) Google Scholar, de Lorenzo et al.40de Lorenzo A. Andreoli A. Matthie J. Withers P. Predicting body cell mass with bioimpedance by using theoretical methods: a technological review.in: Am Physiol Soc. 1997: 1542-1558Google Scholar, Patel et al.41Patel R.V. Matthie J.R. Withers P.O. et al.Estimation of total body and extracellular water using singel- and multiple-frequency bioimpedance.Ann Pharmacother. 1994; 28: 565-569PubMed Google Scholar and van Marken Lichtenbeld et al.42van Marken Lichtenbeld W.D. Westerterp K.R. Wouters L. Luijendijk S.C. Validation of bioelectrical-impedance measurements as a method to estimate body-water compartments.Am J Clin Nutr. 1994; 60: 159-166PubMed Google Scholar). Bioimpedance spectroscopy appears to be a straightforward approach to measure fluid status since it directly determines ECV, the expansion of which is assumed to cause hypertension. Fisch and Spiegel43Fisch B.J. Spiegel D.M. Assessment of excess fluid distribution in chronic hemodialysis patients using bioimpedance spectroscopy.Kidney Int. 1996; 49: 1105-1109Abstract Full Text PDF PubMed Scopus (51) Google Scholar, 44Spiegel D.M. Bashir K. Fisch B. Bioimpedance resistance ratios for the evaluation of dry weight in hemodialysis.Clin Nephrol. 2000; 53: 108-114PubMed Google Scholar used BIS to find that excess fluid in dialysis patients is confined primarily to the extracellular compartment. Katzarski et al.5Katzarski K. Charra B. Laurent G. et al.Multifrequency bioimpedance in assessment of dry weight in haemodialysis.Nephrol Dial Transplant. 1996; 11: 20-23Google Scholar demonstrated the relation between increased total body water and ECV to hypertension. They rated BIS as a highly reproducible and technically simple method, which is useful for dry weight assessment in dialysis patients. Also Oe et al.45Oe B. de Fijter W.M. de Fijter C.W. et al.Detection of hydration status by total body bioelectrical impedance analysis (BIA) in patients on hemodialysis.Int J Artif Organs. 1997; 20: 371-374PubMed Google Scholar conclude from BIS measurements that fluid removal reduces ECV and that measured volumes seem appropriate to assess hydration status in hemodialysis patients. However, a specific concept on how to derive the normohydration weight (dry weight) from BIS measurements has not yet been described. The goal of this study is to evaluate candidate methods for the assessment of fluid status in hemodialysis patients. Focus of the study is on determination of the detection limit of methods only (see Materials and Methods section and Figure 2 for a precise definition of detection limit). A sufficiently low detection limit is a basic requirement for a clinically useful method for fluid status assessment. It is not sufficient that a method just shows a correlation to fluid status changes. It is a precondition that the many undesired effects influencing measurements with each candidate method are small enough that clinically relevant changes in fluid status can still be derived from the measurement with sufficient accuracy. In this way, this study aims at a precise analysis of a specific performance characteristic (the detection limit) of candidate methods for the assessment of fluid status. The basic concept of this study is to move new dialysis patients from their initially overhydrated status to a normohydrated status, using a clinical assessment of hydration status. In parallel, the candidate methods (vena cava-, blood volume- and bioimpedance-based concepts) are applied to determine their detection limit for fluid status changes. These candidate methods are not used to determine the normohydration status. In this setting, the clinical assessment is the reference method, the candidate methods are the test methods. Using all methods in parallel in each dialysis treatment of this study allows a direct comparison of performances. In the following 'Pn' will be used as an abbreviation for 'patient no. n'. Depending on the weight reduction required to achieve the normohydrated weight according to clinical assessment, it took between 1 and about 4 weeks, in one case almost 9 weeks (P16), to move a patient into a normohydrated status (Figure 3). On average 10 treatments, or 3.3 weeks, were required in this group of patients. The postdialysis weights were always changed in moderate steps (typically 0.5–1.5 kg) to allow the patient to adapt to the reduced fluid volume. Nevertheless, in some cases a temporary increase in postdialysis weight was required to allow the patient to better adapt to the restricted fluid volume. The predialysis weight reductions between the treatments with the maximum and minimum predialysis weight are shown in Table 1. Also total weight reductions (between start of first and end of last treatment) are listed, which were between 2.2 kg (P8) and 13.8 kg (P16), on average 7.0 kg. This total weight reduction is not necessarily identical to the initial overhydration of the patient, as will be discussed later.Table 1Patient characteristics, maximum change in predialysis weight ΔWpre and total weight reductions ΔWmax for each patient (details see text)Patient no.12345678910111213141516Age (years)55728184506865734442706767246445GenderMMFMMMMFFMMMFMFMDiabetesYYYNYNNYYNYNNNYYΔWpre (kg)0.99.09.62.59.65.23.30.96.23.05.45.01.13.79.410.8ΔWmax (kg)3.510.210.53.611.77.442.28.83.57.76.22.53.912.313.8F, female; M, male; N, no; Y, yes. Open table in a new tab F, female; M, male; N, no; Y, yes. Figure 4 shows the clinical score (CS) and the equivalent dose of antihypertensive medication equivalent dose (ED), as well as MAP and heart rate HR for two selected patients (P2 and P5) with relatively large weight changes during the study. Measurements are generally plotted as function of predialysis weight Wpre, because they refer to the condition of the patient directly previous to or at the beginning of the dialysis treatment. Clinical score frequently decreased (almost steadily) with decreasing predialysis weight Wpre, starting from a level indicating significant overhydration, and finally reached 0 (P2 and P5). Equivalent dose typically followed roughly the course of CS. This means of course that a reduction of overhydration-related symptoms, indicated by a decrease in CS, usually caused the clinician to reduce antihypertensive medication in this study. Whereas in P2 MAP showed a pronounced reduction with decreasing Wpre, P5 showed only a small reduction. HR remained largely unaffected by fluid reduction in these two patients. For a more systematic analysis, changes in CS, ED, and MAP during the study in all 16 patients are summarized in Figure 5. HR remained unaffected by weight reduction in almost all patients; there was obviously no detectable correlation of HR to fluid status changes. The minimum and maximum CS for each patient during the study period is shown in Figure 5a. The maximum CS (which is identical to the initial CS except for P16) ranged from 0–8, with an average of 3.25. The minimum CS, which is identical to the final CS, was always 0 (since this is a requirement for considering a patient as normohydrated), except for P8, who refused a further weight reduction despite obvious signs of overhydration. Negative values of CS (indicative of underhydration) were never observed; underhydration could be avoided since patients were very well surveyed in this study and reduction of postdialysis weight occurred in small steps, especially at the end of the study period. In Figure 5b the maximum (initial) and minimum (final) ED during the study period is shown for each patient. One patient (P8) was noncompliant with unclear medication; data on ED are therefore not shown for this patient. The initial ED ranged between 0 and 8.75 U, with an average of 2.9 U. The final doses ranged between 0 and 2 U, with an average of 0.4 U. The initial ED always was identical to the maximum ED, the final ED identical to the minimum ED. For P1 and P14 who showed low weight reductions ΔWpre, a low level of antihypertensive medication was kept unchanged. For all other patients ED was lowered by between 80 and 100%. P16 did not receive antihypertensive medication during the study (ED=0 U). The average reduction in antihypertensive medication achieved in this study (omitting P8 and P16), as measured by ED, was 82%. The reductions ΔCS and ΔED between start end of the study period might be expected higher in patients showing a large weight reductions ΔWpre≥9 kg (P2, P3, P5, P15, and P16). In fact, only quite weak correlations of ΔCS and ΔED with ΔWpre were observed; a possible reason will be discussed below. Initial and final MAPs (Figure 5c) refer to MAPs at the beginning of the first and last treatment during the study period. These MAP data were derived from the linear regression line of the measured MAP data; this approach was used because single MAP measurements may deviate larg
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