| Abstract|| |
Achieving dry weight after hemodialysis (HD) is critical as chronic fluid over-load can result in left ventricular hypertrophy, while small fluid shifts may result in intra-dialytic morbid events (IME). In the pediatric population, estimating dry weight can be difficult due to growth while on dialysis. Continuous non-invasive monitoring of the hematocrit (NIVM) has been proposed as a more accurate method of estimating dry weight. Fifteen pediatric patients on chronic HD (6 males and 9 females; mean age 11.4 ± 2.28 years) were included in an uncontrolled prospective study involving three phases. In phase 1, patients were observed for one month for their dry weight and frequency of IME. Phase 2 consisted of using NIVM-guided ultrafiltration algorithm for rate of blood volume (BV) reduction and post-dialysis refill, recommending an intra-dialytic reduction in BV of 8% in the first hour and <4% per hour thereafter and without significant post-dialytic vascular refill. Phase 3 comprised a one month period for comparing the results. IME decreased from 33 episodes per 180 sessions in phase 1 to 4 per 180 sessions during phase 3 (P = 0.04), without a significant difference in pre-systolic or post-systolic or mean BP before and after the intervention (all P >0.1). In phase 1, 40% of patients experienced no IME, 33% experienced one or two IME while 27% experienced more than two IME; during phase 3, 80% experienced no IME, 20% experienced one or two IME while no one experienced more than two IME. NIVM can serve as an objective method for determining dry weight as well as predicting and preventing IME in the pediatric population on maintenance HD.
|How to cite this article:|
Fadel FI, Makar SH, Eskander AE, Aon AH. Decreasing intra-dialytic morbid events and assessment of dry weight in children on chronic hemodialysis using non-invasive changes in hematocrit. Saudi J Kidney Dis Transpl 2014;25:1030-7
|How to cite this URL:|
Fadel FI, Makar SH, Eskander AE, Aon AH. Decreasing intra-dialytic morbid events and assessment of dry weight in children on chronic hemodialysis using non-invasive changes in hematocrit. Saudi J Kidney Dis Transpl [serial online] 2014 [cited 2018 Apr 23];25:1030-7. Available from: http://www.sjkdt.org/text.asp?2014/25/5/1030/139916
| Introduction|| |
A patient's dry weight is defined as the weight at the termination of a regular dialysis session, below which the patient will become symptomatically hypotensive. Incorrect estimation of dry weight will lead either to chronic fluid overload or to chronic dehydration. Unfortunately, there is no standard measure of dry weight, as a consequence of which it is difficult to ascertain the adequacy of fluid removal for an individual patient. Intra-dialytic morbid events (IME) faced while trying to achieve a proper dry weight, and often characterized by a drop in blood pressure (BP), are still the most frequent complications during HD treatment.  This causes discomfort, reduces treatment efficacy and thus increases morbidity of the patients.
Moreover, in the pediatric population, estimating and achieving dry weight can be more difficult for a number of reasons, not the least of which is growth of the patients while on dialysis. A technique that may help attain better control of volume status is continuous non-invasive monitoring of the hematocrit (NIVM).  We aimed in this work to study the benefit of using such a method in better assessment of dry weight and check its possible favorable effect on IME.
| Materials and Methods|| |
Fifteen chronic HD patients (9 females and 6 males) with a mean age of 11.4 ± 2.28 years were included in the study. Inclusion criteria were age below 16 years and patients on maintenance HD therapy for at least three months and expected to continue attending HD sessions regularly (not yet scheduled for transplantation during the period of the study). Exclusion criteria were non-compliance to medical orders and factors affecting hematocrit values, including blood loss through hemorrhage or clotted HD lines.
The original renal disease among the study group included hereditary nephropathies including cystinosis and oxalosis (n = 3); cystic kidney diseases (n = 1); urological problems including vesico ureteric reflux, posterior ure-theral valve and neurogenic bladder (n = 3); chronic interstitial nephritis (n = 3); mem-branoproliferative glomerulonephritis (n = 1) and unknown etiology (n = 4).
The patients included were on regular maintenance HD, three times/week, 4 h per session, on Fresenius 4008B HD machines using Fresenius low-flux membrane dialyzers chosen based on patient's surface area. The study was conducted at the HD unit, Children Hospital, Cairo University. The dialysate solution was bicarbonate based, flow rate was constant at 500 mL/min and the dialysate temperature was constant for all patients at 36°C.
Non-invasive hematocrit monitoring
NIVM was performed using the CRIT-LINE III TQA monitor™ device, which calculates the hematocrit using a photometric technique that is based on the absorption and scattering of light by erythrocytes. Under the assumption that the total red cell volume remains constant during the HD session, changes in the hematocrit will be inversely proportional to changes in the blood volume (BV).
The study was performed in three sequential phases:
- Phase 1: Collection of the following parameters for one month as baseline data:
- Clinically estimated dry weight, patient's weight pre- and post-HD.
- Pre- and post-HD systolic and diastolic BP (SBP and DBP, respectively).
- IME (hypotension, light headedness, nausea, vomiting or cramps) necessitating intervention (saline bolus, stopping ultrafiltration, Trendlenberg posi-ion) were recorded carefully in the patients' files. A period of 15 min without symptoms, after successfully treating an IME, was to elapse before considering a newly developing symptom as another IME.
- HD machine data such as blood flow rate, ultrafiltration rate and volume were collected.
- Patient's laboratory data: Hemoglobin, hematocrit, serum albumin, blood urea, serum creatinine, serum sodium, potassium, calcium, phosphorus and alkaline phosphatase, beside Kt/V.
- Phase 2:
Based on the analysis of the shape of curve obtained during the non-interventional part of this phase, an interventional part was started during which upward and downward modification of the UF goal using the technique of NIVM by a Critline III TQA monitor™ and NIVM-guided UF protocol was made. This was aimed to achieve an intra-dialytic reduction in BV of approximately 8% in the first hour and <4% per hour thereafter, up to a total BV reduction between 12% and 16% with negative post-dialytic vascular refill (magnitude of modification: 50 mL at a time; frequency of modification not more frequent than every 15 min if needed). Once fitted, the weight of the patient at that moment was considered the dry weight and the data were reanalyzed. 
- Non-interventional observational period: In this phase, the dialysis prescription was prepared based on clinical evaluation and only observational (non-interventional) records of BV changes using a CRIT-LINE III TQA monitor™ instrument, both during and after stopping ultrafiltration (UF).
Based on data retrieved from previous studies,  observational records took into consideration the following:
- The percentage of intra-dialytic reduction in BV, where
- Type A curve: Those with almost no or insignificant change in BV during the HD session
- Type B curve: Those with intra-dialytic reduction in BV of approximately 8% in the first hour and <4% per hour thereafter, up to a total BV reduction between 12% and 16%.
- Type C curve: Those with excessive reduction in BV during HD session exceeding 16%.
- The extent of post-dialytic vascular compartment refill in the selected patients for 10 min following termination of session, during which UF and dialysis were stopped (only the HD machine blood flow pump was functioning),
- Positive refill: A decrease in hematocrit >0.5% within 10 min after stopping UF (the period at which the majority of vascular refilling takes place, if any) was considered to reflect a significant vascular refill,
- Negative refill: A decrease in hematocrit <0.5% within 10 min after stopping UF or no decrease at all was considered to reflect a non-significant vascular refill. 
Each patient was determined to have either A, B or C curves and also either positive or negative refill for three sessions,
- Interventional period
- Phase 3:
This was followed by another observational follow-up period of one month after having estimated and modified the dry weight using the Crit-line III TQA monitor™. During phase 3, we collected the same relevant data previously collected during phase 1 of the study for the sake of comparison. The Crit-line III TQA monitor™ was still used in this phase just to observe the curves pattern without intervention. Data were compared between the different phases.
The data collected were analyzed using SPSS win statistical package version 17 (SPSS Inc., Chicago, IL, USA). Quantitative data were presented as mean ± standard deviation (SD). Qualitative data were presented by number and percentage (frequency distribution). Comparison between data of phase 1 and 3 was done using Student's t test. Probability value (P) less than 0.05 was considered significant. Written informed consent was obtained from the patients' care providers before the study. The current work was approved by the Ethics Committee on Human Experimentation, first in the Center of Pediatric Nephrology and Transplantation (CPNT), Cairo University Children Hospital, and then by the general pediatric department, Cairo University, and was in agreement with the Declaration of elsinki and its revisions.
| Results|| |
Basic descriptive data of the 15 patients are summarized in [Table 1].
IME and hypotension: A total of 33 IME occurred during a total of 180 treatment sessions during phase 1 of the study. Forty percent of the patients experienced no IME, 33% experienced one or two IME while 27% experienced more than two IME. During phase 3 of the study, a total of four IME during 180 treatment sessions occurred compared with 33 during phase 1 (P = 0.04). Eighty percent experienced no IME, 20% experienced one or two IME while none experienced more than two IME. Of the 33 IME during phase 1, 25 were associated with hypotension compared with two episodes of hypotension associated with the four IME during phase 3 of the study (P = 0.01).
Blood pressure readings
[Table 2] summarizes the comparison between BP measurements during the study, including the pre-dialysis SBP and DBP, post-dialysis SBP and DBP, pre- and post-dialysis mean blood pressure indices (MBPI) and % change in MBPI before and after the treatment session. Comparison between similar BP indices pre- and post-intervention proved to be nonsignificant (all P >0.1).
Dry weight (type of curve and post-dialytic vascular refill)
[Table 3] summarizes the type of curves and refill during the study.
|Table 3: Types of curves and refill of study group during phase 1 and on starting phase 3.|
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- In patients with flat curve (type A), downward adjustment of dry weight was needed to reach an ideal curve (curve B, negative refill) [Figure 1].
- In patients with curve B, downward adjustment of dry weight to some extent was needed if there was positive refill in order to reach an ideal curve [Figure 2].
|Figure 2: Downward adjustment of dry weight in a patient with curve B and positive post-dialytic vascular refill.|
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- In patients with curve B and negative refill, no change in the dry weight was made [Figure 3].
|Figure 3: Confirmation and approval of clinically estimated dry weight using the CRIT-LINE monitor.|
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- In patients with curve C, an upward adjustment of dry weight was needed to reach an ideal curve (curve B, negative refill) [Figure 4].
It is noteworthy that, regarding some variables that may affect hemodynamic stability, we found no significant difference in hemoglobin or hematocrit levels during phases 1 and 3 of the study (hemoglobin 9.3 ± 1.23 g/dL during phase 1 and 9.2 ± 1.17 g/dL during phase 3 (P = 0.74); hematocrit 28.5 ± 3.9% during phase 1 and 28.16 ± 3.7% during phase 3 (P = 0.79).
| Discussion|| |
In this study, we found that assessment of the dry weight based on NIVM led to significant reduction in the frequency of IME and associated hypotension. Although the frequency of both IME and hypotension were significantly lower in phase 3 than in phase 1, not all IME were associated with hypotension, confirming that BP measurement alone during HD is not sufficient to detect hypovolemia.
As in the current study, Jain et al found in a retrospective study of the pediatric age group that there was a significant reduction of IME, especially among those below 35 kg (P = 0.01) (all our study population were below 35 kg).  They also found that IME was more liable to occur if BV changed >8% per hour during the first 90 min and if BV changed >4% per hour at 90-240 min, and that is what was adopted in our study.
In adults as well, Steuer and co-workers found that there was a significant percentage of chronic HD population who could tolerate additional fluid removal without hypovolemic symptoms even though they were considered to be at dry weight by routine physical examination and that the identification of these patients could be facilitated by intra-dialytic BV monitoring. 
Some studies have reported that hypotensive episodes during HD were all characterized by a lower BV at that moment and a greater reduction in BV during the 10 min preceding the event when compared with the data of non-hypotensive controls at comparable moments of time.  These results suggest that continuous monitoring of changes in BV would assist in the early detection of hypovolemia, especially in dehydrated patients. During the interven-tional period of phase 2 of our study, we took this into consideration and, when the BV changed rapidly, we considered decreasing the UF rate to guard against the occurrence of hypotension.
Moreover, in addition to the rapid decline in BV during dialysis to predict and prevent IME, a critical level for each patient, "crash-crit," was suggested by Barth et al below which IME would possibly occur during each treatment session as long as the patients' hemoglobin level is not changed. Therefore, the patient-specific hematocrit threshold or "crash-crit" adds additional predictive value to the change in BV curve in anticipation of hypovolemic morbidity.  This tool seems to be valuable but it was not tested during our current study.
In the current study, NIVM was found to be helpful in the assessment of dry weight based on two criteria: The type of curve and the type of vascular refill. We assume that reaching type B curve and negative vascular refill is an indicator to reaching the dry weight.  This is supported by the fact that reaching B curve with negative refill in all 15 patients after intervention showed significantly lower IME and hypotension. Moreover, each group was compared separately before and after the intervention. We found that in the group with clinical under-estimation of the dry weight (change in relative BV exceeding 15% during treatment session), , increasing the dry weight to reach curve B, and negative refill showed no statistical difference in the BP indices while there was a statistically significant lower frequency of IME and hypotension after the intervention. On the other hand, while decreasing dry weight in those with initial flat curve, positive refill or both, to reach curve B and negative refill, caused no increase in IME or hypotension.
We recommend that the dry weight obtained by experienced interpretation of the data retrieved from the CRIT-LINE monitor should be strictly abided by, which is also Patel et al's conclusion.  In a systematic review, Goldstein et al found that the application of NIVM-guided UF algorithm significantly decreased hospitalization for fluid overload/hypertension (64 total days in 1999, four total days in 2000 and 2001 combined) while maintaining acceptable patient BP control and minimizing requirement of anti-hypertensive medication. 
There are some limitations to our study. First, the small number of patients sometimes limits the power of the study and its conclusions. Second, this study was a short-term study, and it remains to be seen whether the beneficial effects of NIVM that were observed during the study period would persist on a long-term basis and whether this would later affect other complications caused by over- or under-hydration.
In this study, we demonstrated the value of dry weight assessment using NIVM over conventional physical methods, which led to reduction in the frequency of IME among those who were previously hypotension-prone and without a significant increase in their BP readings. Additionally, correcting the clinically over-estimated dry weight and enhancing more fluid removal from this group did not cause significant increase in the frequency of IME.
Conflict of Interests
No conflict of interests are present in our work and no grants were provided for this study.
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Dr. Samuel H Makar
Nephrology Department, Cairo University Pediatric Hospital, Cairo
[Figure 1], [Figure 2], [Figure 3], [Figure 4]
[Table 1], [Table 2], [Table 3]