Aims
The aim of the current study was to assess the thermoregulatory responses of hemodialysis patients under four different hemodialysis (240 min) protocols: a) one typical dialysis (TD) protocol (dialysate temperature at 37 °C), b) one cold dialysis (CD) protocol (dialysate temperature at 35 °C), c) one typical dialysis protocol which included a single exercise bout (TD + E), d) one cold dialysis protocol which included a single exercise bout (CD + E).
Study Design
Ten haemodialysis patients were recruited from a single haemodialysis unit at the General Hospital of Trikala, Thessaly, Greece. All study measurements were performed at a hospital climate control room using the metabolic ward of the General Hospital of Trikala, Greece. The mean age was 57.2 ± 14.9 years (Table 1). Patients enrolled by a research assistant assigned into the study while the order that the patients assigned to the first scenario was random using a computer random number generator. Each patient was monitored during a) one protocol of typical dialysis with dialysate temperature at 37 °C (TD), b) one protocol of cold dialysis with dialysate temperature at 35 °C (CD), c) one protocol of typical dialysis which included a single exercise bout (TD + EP) and d) one protocol of cold dialysis which included a single exercise bout (CD + EP). The patient participants underwent hemodialysis therapy (Fresenius 4008B, Oberursel, Germany) three times per week with low flux, hollow fiber dialyzers and bicarbonate buffer, with the hemodialysis protocol lasting 4 hours. The dialysis protocols were performed using dialysis flow at 550 ml/min and mean average of conductivity dialysance at 137–140 mEq/L. The net ultrafiltration weight was the same in all sessions. All patients were clinically stable and they had received regular hemodialysis treatment for at least 3 months, with adequate dialysis delivery Kt/V > 1.1 and good compliance of dialysis treatment, the serum albumin was > 2.5 g/dL, hemoglobin ≥ 11 g/dL and treated with rHuEPO. Patients were not eligible for participation in the study if they had a reason to be in a catabolic state, such as hyperthyroidism, active vasculitis, malignancies, pregnant, HIV, opportunistic infections, musculoskeletal contraindication to exercise, requirement for systemic anticoagulation, participant or participated in an investigational drug or medical device study within 30 days or five half-lives or inflammations, that required intravenous antibiotics within 3 months prior to enrollment, diabetics receiving insulin therapy, New York Heart Association grade IV heart failure, and mental incapacity to consent.
Table 1
Individual characteristics of the study group
Patient (n) | Age (yr) | Dry Weight (kg) | Height (cm) | Body surface area (m2) | Cause of end-stage renal disease |
1 | 82 | 69.7 | 161 | 1.77 | Glomerulonephritis |
2 | 51 | 73.6 | 175 | 1.90 | Nephrectomy |
3 | 65 | 69.0 | 185 | 1.88 | Polycystic kidney disease |
4 | 63 | 80.0 | 175 | 1.97 | Glomerulonephritis |
5 | 61 | 80.5 | 178 | 2.00 | Glomerulonephritis |
6 | 61 | 64.2 | 158 | 1.68 | Polycystic kidney disease |
7 | 32 | 66.0 | 173 | 1.78 | IgA nephropathy |
8 | 53 | 85.3 | 174 | 2.03 | Polycystic kidney disease |
9 | 68 | 78.8 | 172 | 1.94 | Unknown causes |
10 | 36 | 48.3 | 145 | 1.39 | Glomerulosclerosis |
Note: mean ± sd; Age: 57.2 ± 14.9; Dry Weight: 71.4 ± 10.0; Height: 169.6 ± 11.6; Body Surface: 1.83 ± 0.18 |
Dialysis protocols were performed in a random order at the same time and day of the week to minimize differences in ultrafiltration volume between the four protocols. The ambient temperature in the room was 25.2–25.9 °C. Food consumption was not allowed during the dialysis procedure and all participants was wearing standardized clothing to secure the same insulating properties of clothing during the different dialysis protocols. During the different dialysis protocols, core temperature (TC) and mean skin temperature (Tsk) were recorded. The body heat storage (S) for every minute was calculated during all conditions using the thermometric method proposed by Burton (22). The data recording lasted five hours for each patient (1 hour before dialysis protocol and 4 hours during the dialysis protocol). The exercise program during TD + E and CD + E was performed between the 60th and the 120th minute of the dialysis protocol.
Core Temperature Measurements (t)
Core temperature (Tc) was measured at the gastrointestinal tract using an ingestible telemetric pill. Data recorded continuously at 1-minute intervals, throughout the course of the experimental intervention. The telemetric pill was ingested by the patients 7-hour before arriving in the hospital (23, 24).
Mean Skin Temperature Measurements (t)
Skin temperature was measured at 1-minute intervals by wireless iButtons (iButton, Maxim, USA). The iButtons were programmed before their application on the skin, as outlined by the manufacturer. The iButton resolution was set at 0.06oC and the iButton real-time clock was synchronized with a laptop computer. The iButtons were attached on the skin using water-resistant, medical-grade tape. In total four iButtons were attached on the skin, at the following anatomic locations: on the biceps, pectoralis major, rectus femoris, and gastrocnemius, and were used to calculate mean skin temperature (Tsk) using Ramanathan Eq. (22).
Body Heat Storage (s)
Body heat storage for every minute was calculated during all conditions using the thermometric method proposed by Burton: S = 3.47· mb · ΔṪb where 3.47 is the average specific heat of body tissues (in kJ·kg− 1·°C− 1), mb is the patient’s body mass (in kg), and ΔṪb is the rate of change in mean body temperature (Ṫb) at time t t from the beginning of HD (initial Ṫb at time 0) (25).
Intradialytic Exercise Program
The patients performed cycling for 60 minutes in the supine position during the TD + EP and CD + EP protocols. Patients were asked to pedal on a bedside cycle ergometer (Model 881 Monark Rehab Trainer, Monark Exercise AB, Varberg, Sweden) at 60% of their pre-assessed maximum power capacity. The exercise regime started 1 h after the commencement of the hemodialysis session. The patients’ maximum power capacity was determined by a modified version of the Åstrand Bicycle Ergometer Test protocol at bedside on a previous dialysis session during hemodialysis. Exercise was well tolerated by all patients, and no adverse reactions were reported.
Sample Size Estimation
The minimum required sample size was determined using data from a previous study (26) where 17 hemodialysis patients underwent CD aiming to reduce TC from 36.4 ± 0.4 °C at baseline to 36.1 ± 0.1 °C at the end of the dialysis protocol. Sample size calculations were conducted using G*Power 3.0 (27). The “Means: difference between two dependent means” method was used to calculate the power of the within effect. A two-tailed test selected. Statistical power and α error probability were set to 0.80 and 0.05, respectively. The minimum required sample size was determined by calculating the effect size d. Using the aforementioned published data, the resulting minimum required sample size was 10 participants.
Statistical analysis
A Multivariate Analysis of Variance (MANOVA) followed by post-hoc paired-samples t tests were used to assess the effects of time (-30, 0, 30, 60, 90, 120, 150, 180, 210, 240) and protocol (TD, CD, TD + E, CD + E) on TC, Tsk, and S. The MANOVA results demonstrated no statistically significant main or interaction effects. However, the observed power in these tests ranged between 0.17 and 0.67 (with the exception of the protocol main effect in TC which was 0.96). Given the very low power of these tests, the analysis was focused exclusively in the post-hoc paired-samples t tests. To further strengthen the analysis, Cohen’s d effect sizes (0.2–0.5: small effect; 0.5–0.8: moderate effect; >0.80: large effect) were also used to identify paired differences between protocols and times. Data are expressed in mean ± SD. A p value < 0.05 was considered statistically significant. All analyses were carried out using the Statistical Package SPSS 21.