Tuberculin skin test reaction depends on type of purified protein derivative: implications for cut-off values.

SETTING: Due to purified protein derivative (PPD) RT23 stock-outs in 2014, PPD-Tubersol and PPD-Bulbio have been used for latent tuberculosis infection (LTBI) testing in the Netherlands.OBJECTIVE: To determine whether PPD-RT23, PPD-Tubersol and PPD-Bulbio were associated with differential indurations and confirmation using interferon-gamma release assays (IGRAs).DESIGN: LTBI surveillance data from 2013 to 2016 were extracted. Regression analyses were used to determine whether IGRA confirmation of TST-positive indurations depended on PPD, controlling for sex, age, incidence in country of origin, and bacille Calmette-Guérin (BCG) status.RESULTS: A total of 20 956 individuals were tested with PPD-RT23: 10 382 with PPD-Tubersol and 18 562 with PPD-Bulbio. Overall, 21% with PPD-Bulbio had an induration of ≥5 mm compared to 12% of those tested with PPD-RT23 and PPD-Tubersol. Compared to PPD-RT23, PPD-Bulbio indurations ≥5 mm were significantly less often IGRA-confirmed among contacts (aOR 1.3, 95% CI 1.1-1.6) and BCG-vaccinated immigrants (PPD-RT23, aOR 2.4, 95% CI 1.4-4.1). Increasing the PPD-Bulbio cut-off from ≥5 to ≥10 mm would save respectively 26%, 42%, and 35% of IGRAs among contacts, health care workers (HCWs) and BCG-vaccinated immigrants, with small absolute numbers of positive IGRAs missed (range 0-55 annually).CONCLUSION: PPD-Bulbio shows larger TST indurations than other PPDs, but is less often IGRA-confirmed. Increasing the TST cut-off from 5 to 10 mm prior to testing with an IGRA in HCWs and immigrants is recommended.

[Tuberculosis screening coverage of immigrants: marked attrition in follow-up screenings]. / Dekkingsgraad van tuberculosescreening bij immigranten: sterke afname bij vervolgscreening.

OBJECTIVE: To estimate the coverage of bi-annual follow-up screening for tuberculosis amongst immigrants, excluding asylum seekers. DESIGN: Retrospective cohort study. METHODS: Participation in bi-annual chest X-ray screening during the first 18 months was recorded for immigrants who underwent entry screening in 1996 in the following Dutch municipal health services (MHS's): Zuid-Kennemerland (Haarlem), Flevoland (Lelystad), Midden-Brabant (Tilburg) en West-Friesland (Hoorn). The number of immigrants that had left the country before the subsequent screening was taken into account in the Zuid-Kennemerland MHS data on screening coverage. RESULTS: Of the 2147 immigrants who underwent entry screening in 1996 (48% men and 52% women; 68% aged 15-34 years), 1075 (50%; range: 29-76) returned for the first follow-up screening and 620 (29%; 21-61) returned for the second. In MHS Zuid-Kennemerland, 113 of the 777 immigrants who had a chest X-ray at entry had left the country before the first follow-up screening, and another 89 had left before the second. Of the remaining persons, who were probably still in the Netherlands, 454 (68%; 454/777 = 58%) returned for the first follow-up screening, and 166 (29%; 166/777 = 21%) returned for the second. CONCLUSION: The coverage of screening for tuberculosis in immigrants decreased after the obligatory entry screening, even when corrected for those who left the country.

Interstitial fluid volume during cardiac surgery measured by means of a non-invasive conductivity technique.

Fluid accumulation in the interstitium is frequently found after cardiac surgery. In extreme this can lead to pulmonary and myocardial oedema. The origin of this accumulation is not exactly known and may be twofold. It is probably a combination of the noninfectious whole body inflammatory response and a change in Starling forces due to a decrease in colloid osmotic pressure (COP) which is caused by the primed extracorporeal circuit. To study the changes in interstitial fluid volume (ISFV) a non-invasive conductivity technique was used. The relationship between temperature and conductivity was first investigated in vitro. A linear relationship was found between conductivity and different saline solutions and temperature. From the in vitro experiments it can be concluded that temperature corrected conductivity does not depend on haematocrit. After the in vitro experiments eleven patients undergoing cardiac surgery were studied. During the first minutes of cardiopulmonary bypass (CPB) a steep significant decrease in COP to 61.4 +/- 6.9% (from 19.6 +/- 1.1 to 12.0 +/- 1.2 mmHg), and a rise in ISFV to 105.5 +/- 2.8% (from 12.3 +/- 1.4 mS to 14.0 +/- 1.3 mS) was noticed. After this decrease COP increased significantly, till the end of the operation, but did not reach the pre-operative level. An increase in ISFV was noticed till the rewarming point. After this point no significant change in ISFV was noticed. Furthermore, a significant correlation was found between the fluid balance and the ISFV increase at the start, at the end of CPB, and at the end of the operation.(ABSTRACT TRUNCATED AT 250 WORDS)

The influence of alternating current frequency on flow related admittance changes of blood: a concept for improvement of impedance cardiography.

Impedance cardiography is based on admittance changes induced by volume changes of the intrathoracic blood vessels, but also by the longitudinal orientation of red blood cells induced by flow. An experiment was set up to separate these two phenomena and to study their frequency dependence. Admittance changes of flowing blood with variable haematocrit, of a saline solution and of plasma were measured in an in vitro set-up. Four different alternating current frequencies were used: 100 kHz, 5 MHz, 15 MHz and 20 MHz. The measured admittance appeared to be dependent on blood flow: when blood flow increased, admittance in the longitudinal direction increased. This increase was stronger for higher haematocrits, probably due to the longitudinal orientation of the blood cells. At higher frequencies, the orientation effect of the red cells became negligibly small. No frequency or flow dependent admittance change was detected when saline or plasma was used as the perfusate. It is concluded that the orientation effect can be neglected at high frequencies. Impedance cardiography in this range will give more reliable information about volume changes.

Non-invasive conductivity technique to detect changes in haematocrit: in vitro validation.

An on-line haematocrit measurement in extracorporeal circuits might be useful under some clinical circumstances (e.g. haemodialysis or cardiac surgery). As no such measurement exists, a device has been developed that makes it possible to detect haematocrit (Ht) continuously without a loss of blood. It is a multi-frequency system for the detection of electrical conductivities. The aim of this study was to investigate whether this device can measure Ht alterations properly. Ht alterations were induced by adding pure mannitol and 20% mannitol to fresh human blood. Furthermore, the effect of both mannitol substances on the intracellular ion content, intracellular conductivity and Ht were investigated. Alternations in Ht were established by the addition of 1000, 800, 600, 400, 200 and 0 mg of pure mannitol to 10 ml of fresh human blood, and 3.0, 2.5, 2.0, 2.0, 1.5, 1.0, 0.5 and 0 ml of 20% mannitol to fresh human blood until a total volume of 10 ml was achieved. Although their effects were significantly different, pure mannitol and 20% mannitol both caused a reduction in mean cellular volume, and thus in Ht. A highly significant correlation was found between Ht and intracellular conductivity (r = 0.90, p < 0.001). In addition to these effects, addition of pure mannitol and 20% mannitol had different effects on the intracellular ion content. Pure mannitol caused an increase in intracellular ion content due to a transcellular ion shift, whereas 20% mannitol induced a decrease. From this study, it can be concluded that the multi-frequency conductivity method observes changes in Ht (and intracellular fluid volume) in an accurate manner.(ABSTRACT TRUNCATED AT 250 WORDS)

The influence of Ringer's lactate and gelatin infusion on the internal fluid balance of healthy volunteers measured by a non-invasive conductivity technique.

Eight healthy male volunteers received in random order at an interval of 1 week 2 litres of Ringer's lactate or 0.8 litre of gelatin (Gelofusine) over half an hour, after overnight fasting. At the end of the infusion period, blood volume and mean arterial pressure had increased significantly in both groups but the increase in blood volume was more pronounced with the colloid. Extracellular fluid volume increased significantly after Ringer's lactate, while a significant decrease was noticed after gelatin. A small decrease in intracellular fluid volume was noted after infusion of Gelofusine, whereas it did not change after infusion of Ringer's lactate. During the 30 min after infusion, blood volume decreased significantly after both treatments but after the colloid it remained higher than the initial value. During the post-infusion period, no significant changes in either intra- or extracellular volume were seen after either treatments. At the end of the study, urine production was significantly more after the Ringer's lactate. It can be concluded that infusion of 0.8 litre of gelatin results in a larger and longer lasting increase in blood volume than 2 litres of Ringer's lactate, probably due to mobilization of extracellular fluid volume. It also leads to extracellular fluid accumulation. The decrease in blood volume after infusion is caused by increased urine production, since no changes were seen in intra- and extracellular fluid volume during this period.

Non-invasive monitoring of blood volume during hemodialysis: its relation with post-dialytic dry weight.

Hemodialysis has a profound effect on fluid balance. Since fluid is initially withdrawn from the intravascular compartment, blood volume will decrease rapidly. A fluid shift (refill) from the overhydrated interstitium towards the intravascular compartment counteracts hypovolemia. Underestimation of postdialytic dry weight will cause interstitial dehydration and consequently a low refill capacity. This can cause hypovolemia-induced hypotension, a serious problem in the daily practice of hemodialysis: during one out of three sessions a hypotensive episode occurs. Clinical criteria to estimate post-dialytic dry weight are insensitive. We have developed non-invasive methods to estimate dry weight and changes in blood volume (BV) more accurately. The aim of this study was to investigate the relation between hydration state of the patient and changes in BV during treatment. Therefore, 37 hemodialysis patients were divided into three groups according to their post-dialytic extracellular fluid volume (EFV), which was measured by means of the non-invasive conductivity method: de- (N = 11), normo- (N = 18), and overhydrated (N = 8). Using an on-line optical reflection method, changes in BV were measured continuously during hemodialysis. BV decrease, corrected for ultrafiltration, was stronger in the dehydrated (4.4 +/- 1.5%/liter) than in the normohydrated (3.3 +/- 1.5%/liter) and overhydrated (2.7 +/- 1.9%/liter) groups. In the dehydrated group, the frequency of hypotensive episodes (48.5 +/- 20.2%) was significantly greater compared to the normohydrated (20.5 +/- 23.5%) or overhydrated (6.5 +/- 6.5%) group, P < 0.005.(ABSTRACT TRUNCATED AT 250 WORDS)

Implications of the dielectrical behaviour of human blood for continuous online measurement of haematocrit.

A study was designed to explore the possibility of detecting the haematocrit of blood by means of admittance measurements. The admittance and phase angle of blood kept in a measuring cell were determined at various frequencies between 60 kHz and 24 MHz. A reliable and accurate estimation of haematocrit was obtained in two ways. First, low-frequency admittance, high-frequency admittance and a factor x, which was the conductive percentage of cell content, were used. Secondly, the maximum phase angle was used. Both methods can be applied to obtain continuous on-line information about haematocrit for blood volume control during haemodialysis.

The adjustment of post dialytic dry weight based on non-invasive measurement of extracellular fluid and blood volumes.

One of the major problems in the clinical practice of hemodialysis is an incorrect estimation of post dialytic (PD) dry weight. Underestimation of dry weight leads to hypovolemia induced hypotension, and overestimation to hypertension, pulmonary edema, and left ventricular hypertrophy. Because of the insensitivity of clinical variables to estimate dry weight, a more accurate technique is warranted. For this purpose and for the continuous surveillance of changes in blood volume (BV) during hemodialysis, two non-invasive techniques were applied. Based on post dialytically obtained extracellular fluid volume (EFV) values, measured by means of a conductivity method, 30 stable hemodialysis patients were divided into three groups for further analysis: de- (n = 9), normo- (n = 15), and overhydrated (n = 6). Using an on-line optical reflection method, changes in BV were measured continuously during therapy. Mean BV decrease, corrected for UF, differed slightly between the three groups (0 = 1.84 +/- 2.06, N = 3.20 +/- 1.80, D = 4.20 +/- 1.60 %/L). However, eight hypotensive episodes occurred in group D versus none in groups N and O. These hypotensive episodes were characterized by a greater reduction of BV--corrected for ultrafiltration--from the start of treatment until the moment of hypotension (6.96 +/- 2.21 %/L), compared with the 22 non hypotensive controls (2.16 +/- 2.01 %/L, p < 0.001). Based on the PD EFV dry weight of the overhydrated and dehydrated patients was decreased and increased, respectively, by 500 g after each session, until PD EFV was within normal bounds.(ABSTRACT TRUNCATED AT 250 WORDS)

Assessment of postdialysis dry weight: a comparison of techniques.

Because clinical indices of hydration state are insensitive, the estimation of correct postdialysis dry weight is still major problem. Recently, some new techniques have been introduced to assess postdialysis dry weight more accurately. The plasma concentrations of the biochemical markers atrial natriuretic peptide (ANP) and cGMP are related to intravascular hydration state. The echographically measured inferior caval vein diameter (VCD) is linked to right atrial pressure and blood volume (BV). Regional noninvasive conductivity measurements provide information about regional extracellular fluid volume (EFV). In this study of postdialysis ANP and cGMP concentrations, VCD and EFV yielded postdialysis diagnoses of hydration state in 18 patients on maintenance dialysis. In order to verify the established diagnosis, hemodynamic and BV changes during dialysis were studied. In postdialysis underhydrated patients, differentiated according to VCD and EFV standards, a pronounced decrease in BV, stroke volume, and left ventricular end-diastolic diameter compared with postdialysis normohydrated patients was observed. Hemodynamic and BV changes during dialysis were identical in the groups selected according to postdialysis ANP level. Only a difference in BV decrease was demonstrated between the groups selected according to postdialysis cGMP. Predialysis and postdialysis VCD correlated well with the corresponding EFV (r = 0.7 and r = 0.8, respectively). Because VCD and EFV were related and interpretation yielded diagnoses of postdialysis hydration state that were substantiated by the finding of classical hemodynamic features of underhydration, both are an asset in the diagnosis of postdialysis dry weight. cGMP values are less informative, and ANP does not provide any information at all.

New techniques to determine fluid status in hemodialyzed patients.

In this paper, several newly developed techniques for the estimation of the fluid status in hemodialysis patients were reviewed. Whereas echography of the inferior caval vein and the measurement of ANP and cGMP levels merely provide information about the intravascular volume, conductivity measurements are able to detect changes in the extracellular and intracellular compartments without being able to differentiate between the intravascular and interstitial fluid spaces. Echography of the inferior caval vein as a tool to assess over- and underhydration has been successfully validated against objective standards as right atrial pressure, total blood volume and the change in hemodynamic parameters during dialysis. Conductivity measurements were significantly related to vena cava measurements before and after dialysis. Whereas ANP levels were significantly related to the vena cava diameter before dialysis, in another group of patients, only a significant relation between the vena cava diameter and cGMP was observed in patients with normal left atrial hemodynamics, whereas they were not in patients with a dilated left atrium. Furthermore, in normovolemic patients with mitral insufficiency, ANP levels after dialysis remained increased compared to patients without mitral insufficiency, suggesting that, in addition to volume expansion, also altered left atrial hemodynamics influence the release of cGMP and ANP. Conductivity measurements and ANP before and after dialysis were not related, whereas only cGMP after dialysis was significantly related to conductivity measurements. ANP and cGMP were not related to the change in hemodynamic parameters during dialysis, questioning their reliability in the assessment of underhydration.

Non-invasive conductivity method for detection of dynamic body fluid changes: in vitro and in vivo validation.

Since intracellular and extracellular fluid volume (ICV, ECV) cannot be measured under dynamic circumstances, a non-invasive conductivity technique was developed for this purpose. To validate the technique, experiments in vitro and in vivo were performed. In vitro, dilution of blood led to a variation in haematocrit, which could be calculated accurately by means of the low-frequency conductivity value combined with the plasma conductivity value. Combination of high- and low-frequency conductivity values made calculation of haematocrit possible without measuring plasma conductivity. Changes in mean cellular volume, caused by addition of osmotically active substances, were detectable in the same way. Haemolysis of blood cells was performed to validate the intracellular conductivity. For in vivo validation the effects of position change (erect to supine) and of 40 mg frusemide i.v. were investigated. Position change caused a significant decrease in ECV and tended to increase blood volume (BV). Frusemide caused a mean iso-osmotic urine production of 1.8 +/- 0.2 litres. ECV decreased 12.3 +/- 2.0% (P < 0.05), while ICV increased 5.0 +/- 3.0% (P < 0.05). BV decreased by 7.0 +/- 5.4% (P < 0.05), while mean blood pressure increased (P < 0.05). Changes in both ECV and in ICV were correlated with diuresis (r = 0.88 and r = 0.85 respectively; P < 0.01). The ICV increase was unexpected and might be caused by an aldosterone-induced transcellular sodium influx. From both studies it can be concluded that non-invasive conductivity measurements are reliable for detecting changes in ECV and ICV under dynamic circumstances.

Continuous measurement of blood volume during hemodialysis by an optical method.

A new method is described to noninvasively and continuously measure changes in blood volume (BV) during hemodialysis by means of an optical reflection method with an optical monitor (950 nm) clipped onto the arterial blood line. The amount of reflected light (L) appeared to be linearly proportional to the erythrocyte concentration (r = 0.91). Changes in L correlated well with changes in erythrocyte concentration during hemodialysis (r = 0.94). A study in 10 patients on regular dialysis was done. The BV decrease after 3 hr of treatment was 17.0 +/- 5.2%, and it correlated with the amount of fluid withdrawn by ultrafiltration (mean, 2,519 +/- 589 ml). Five hypotensive episodes were seen that were characterized by a higher rate of BV fall during the preceding 15 min (9.9 +/- 1.9 versus 3.6 +/- 4.3%/hrp; p < 0.05) and by a lower BV value at that moment (78.2 +/- 3.4 versus 84.5 +/- 4.5%; p < 0.025) than in the other five patients at comparable times. It was concluded that this optical method was a means to detect hypovolemia at an early stage and to prevent ultrafiltration induced hypotension.

The recovery of the fluid balance after hemodialysis and hemofiltration.

Dialysis dysequilibrium syndrome is a frequent complication of renal replacement therapy and seems to be related to changes in fluid balance. From previous studies it is known that these changes are less pronounced during hemofiltration (HF), leading to a lower incidence of complaints compared to hemodialysis (HD). To assess the severity and duration of the dysequilibrium syndrome, intracellular (ICV) and extracellular fluid volumes (ECV) were measured during and after HD and HF by means of a non-invasive conductivity method. Blood volume changes were calculated from pre- and post-treatment erythrocyte counts. Seven HD and eight HF patients were studied. Ultrafiltration volume did not differ between both groups. Blood volume decrease was less during HF due to a significant decrease in ICV, the latter being in contrast to an ICV increment during HD. The significant decrease in ICV led to a less severe decrease in ECV (90 versus 85%). Overall, this resulted in a better vascular refill during HF. At the end of treatment ICV and ECV were not in equilibrium yet. During the recovery period ICV increased roughly 3% in the HF group. In the HD group some patients showed an increase while others showed a decrease in ICV. Overall, no change in ICV was noticed. During recovery ECV decreased further in both groups. The measured recovery period was significantly shorter after HF (245 +/- 68 min) than after HD (299 +/- 37), supporting the hypothesis that HF is a more physiological way of treatment compared to HD.

Effects of zinc supplementation on zinc status and immunity in haemodialysis patients.

The depression of immunity to various antigens in chronic uremia is a frequently encountered phenomenon. Zinc deficiency might well be an important factor in its genesis. The aim of this study was to investigate the role of zinc deficiency in this reduced immune response. Two groups of 7 patients on haemodialysis who had failed to respond with seroconversion to an earlier vaccination against hepatitis B were revaccinated. One group received zinc by the addition of zinc chloride to the dialysate. Before initiation of the study zinc in plasma and leucocytes was measured. No difference in plasma and leucocyte zinc was observed between the two groups. Zinc in leucocytes was lower in patients than in a group of healthy volunteers (61.5 pmol/10E6 cells +/- 4.6 versus 73.8 +/- 5.6, p less than 0.005). Plasma zinc showed no difference between patients and healthy volunteers. During zinc supplementation zinc in plasma rose in the patient group receiving zinc (10.4 mmol/L +/- 1.5 to 14.2 +/- 1.9, p less than 0.005). However, no rise in leucocyte zinc was seen. At the end of the trial seroconversion had occurred in 2 patients in each group. It is concluded that zinc supplementation in haemodialysis patients does not lead to the restoration of leucocyte zinc to normal levels. Neither did it lead to an enhanced antibody response in our population after revaccination of haemodialysis patients against hepatitis B.

Influence of high and low sodium dialysis on blood volume preservation.

Haemodialysis has a profound effect on fluid balance. Since fluid is initially withdrawn from the intravascular compartment, hypovolaemia is a frequent complication. A fluid shift from the overhydrated interstitium towards the intravascular compartment can counteract hypovolaemia. However, a fast decline in extracellular osmolality may cause an increase in the intracellular volume, reducing the available amount of fluid to compensate for the hypovolaemia. To overcome this problem, the use of alternating high and low sodium dialysate is advocated. In this study six patients were studied during standard haemodialysis (HD) and during dialysis with alternating high and low sodium dialysate (HLSD). Changes in intracellular fluid volume (IFV) and extracellular fluid volume (EFV) of tissue and blood were measured by means of a non-invasive electrical conductivity method. Changes in blood volume (BV) were studied by serial erythrocyte counts. Plasma sodium concentration was determined at regular intervals. The distribution volume of sodium during the high and low sodium episodes of HLSD was calculated according to a mathematical model. HLSD led to fluctations in plasma sodium concentration that induced changes in red cell volume, but not in IFV. Distribution of sodium was largely confined to blood. BV was better preserved during HLSD than during HD, probably due to a higher mean plasma sodium concentration. Postdialysis sodium concentration however, was not significantly different between HLSD and HD. These data suggest that the better BV preservation during HLSD results from an induced osmotic gradient across the capillary wall, rather than from an osmotic gradient across the cell membrane.

The influence of dialysate sodium and variable ultrafiltration on fluid balance during hemodialysis.

An important factor in the development of hypotension during hemodialysis (HD) is a decrease in blood volume, due to ultrafiltration (UF) and an insufficient refill of the intravascular compartment. This insufficient refill might be caused by a transcellular fluid shift from the extracellular to the intracellular compartment. We studied the influence of dialysate sodium concentration and UF rate on the refill rate, blood volume, intracellular (ICV) and extracellular fluid volume (ECV). Three different HD strategies were studied in 15 patients: (A) conventional HD (dialysate sodium 140 mmol/L); (B) HD with a sodium profile (140-148 mmol/L); and (C) HD with a sodium profile and a variable UF rate (high-low UF rate). ICV and ECV were measured by non-invasive conductivity measurements, blood volume was calculated from erythrocyte counts before and after treatment. Blood volume decrease was most pronounced during conventional HD, due to insufficient refilling without a detectable transcellular fluid shift. The sum of the decrease in ICV and EVC was less than during (B) and (C). The insufficient refill led to a higher prevalence of hypotension and cramps. The strategies (B) and (C) led to an significant and comparable transcellular fluid shift to the extracellular compartment. Thus, the use of a sodium profile led to a better intravascular refill and clinical tolerance of HD. Addition of a UF profile did not improve this any further.