Effects of haemoglobin normalization on quality of life and cardiovascular parameters in end-stage renal failure.

BACKGROUND: The optimal haemoglobin concentration ([Hb]) for patients with end-stage renal failure is uncertain. In particular, it is unclear whether Hb normalization may be an advantage to such patients who are otherwise well. METHODS: A prospective, randomized, double-blind cross-over study was completed in 14 haemodialysis patients (12 male) aged between 23 and 65 years over a period of 18 months, using a variety of measures to examine the effect of epoetin at target [Hb] of 10 g/dl ([Hb](10)) and 14 g/dl ([Hb](14)). Patients were randomized to maintain one or other of the target levels for 6 weeks before being crossed over to the alternative [Hb]. Baseline data (mean [Hb]: 8.5+/-0.2 g/dl) were also included selectively. Six patients were known to be hypertensive. Comparisons were made between 24-h ambulatory blood pressure levels (ABP), echocardiographic findings and estimates of blood volume (BV), plasma volume (PV) and Hb mass. Quality of life estimates were obtained using the Sickness Impact Profile (SIP), and epoetin dosage requirements at target [Hb] were assessed. RESULTS: Daytime and nocturnal ABP (systolic and diastolic) were not different at the respective target [Hb], although nocturnal diastolic levels were higher compared with baseline (73+/-4 mmHg) at both [Hb](10) (83+/-3, P:<0.01) and [Hb](14) (81+/-6, P:<0.05). Significant reductions in cardiac output (5.2+/-0.3 vs 6.6+/-0.5 l/min, P:<0.01) and left ventricular end-diastolic diameter (4.8+/-0.2 vs 5.2+/-0.2 cm, P:<0. 001) were found at [Hb](14) compared with [Hb](10). Left ventricular mass index was correlated with both PV (P:<0.001) and BV (P:<0.01), but not with Hb mass. The PV decreased as the [Hb] rose (P:<0.001) but BV remained unchanged. Quality of life was significantly improved at [Hb](14) compared with [Hb](10) for both total score (6. 5+/-1.7 vs 13.4+/-3.0, P:=0.01) and psychosocial dimension score (5. 4+/-1.9 vs 15.4+/-4.0, P:<0.01). The maintenance weekly dose of epoetin required was 80% higher at [Hb](14) compared with [Hb](10) (P:<0.001). CONCLUSION: These data suggest there may be a significant haemodynamic and symptomatic advantage in maintaining a physiological [Hb] in haemodialysis patients. Although untoward effects were not identified in this study at [Hb](14), a substantially higher dose of epoetin is required to maintain this level.

Skin-prick blood samples are reliable for estimating Hb mass with the CO-dilution technique.

Investigation of the impact of environmental stimuli such as altitude exposure on hemoglobin mass currently rely on invasive techniques that require venous blood sampling. This study assessed the feasibility of lancet skin pricks as an alternative to venepuncture to estimate hemoglobin mass with the carbon monoxide (CO) dilution technique, with the intent of making the technique accessible to technicians without phlebotomy training. Sixteen healthy volunteers rebreathed CO via a small-volume rebreathing apparatus. Blood was sampled simultaneously with a glass syringe (VEN) from a superficial forearm vein and with a capillary tube from either a lanced fingertip or earlobe (CAP). As a control, VEN blood was then aliquoted into capillary tubes (CONTROL-CAP). Samples were assayed for carboxy-hemoglobin (HbCO) using a diode-array spectrophotometer. Mean %HbCO was higher in CAP than VEN (bias 0.3+/-0.2%HbCO, p < 0.01), but VEN and CONTROL-CAP were not different (p = 0.55). Compared to VEN, Hb mass derived from CAP samples was overestimated by 1.7% (15+/-22 g Hb, p = 0.01). CAP samples to estimate Hb mass demonstrated a technical error of measurement of 2.7%, which is comparable to the 1.9% reported previously with VEN samples. We conclude that using CAP samples gives a reliable measure of %HbCO, and will make the estimation of Hb mass with the CO-technique accessible to technicians without phlebotomy training.

VO2max and haemoglobin mass of trained athletes during high intensity training.

The correlation between relative haemoglobin mass (Hb mass, g x kg[-1]) and relative maximal oxygen consumption (VO2max, ml x kg(-1) x min[-1]) in 62 trained athletes (33 male runners, 12 male rowers and 17 female rowers) with national and/ or international competitive experience was examined. The correlation between Hb mass and VO2max was highest for the female rowers (n=17, r=0.92, p<0.0001), lower for the male rowers (n = 12, r=0.79, p < 0.005) and lowest for the male runners (n=33, r=0.48, p = 0.005). These results suggest that, within an athletic sample, Hb mass may be used to estimate potential aerobic power. In a second series of experiments, Hb mass was measured before and after three different training programs in sub-sets of the subjects used in the earlier study. Hb mass did not change following 12 weeks of intense rowing training, 4 weeks of heat training (32 degrees C), or 4 weeks of medium-altitude training (1740 m). The corresponding increases in VO2max were 7.8%, no change and 2.1 %, respectively. These results suggest that heat or altitude training does not increase Hb mass in trained athletes. Previous studies that demonstrate increases in total red cell volume following altitude acclimatization used subjects with only modest aerobic power, whereas the present study used trained subjects. It is concluded that trained athletes with erythrocythemic hypervolemia have limited capability to increase further either total red cell volume or Hb mass.

Influence of ingested fluid volume on physiological responses during prolonged exercise.

The effect of different rates of fluid ingestion on heart rate, rectal temperature, plasma electrolytes, hormones and performance was examined during prolonged strenuous exercise conducted at 21 degrees C. Seven well-trained males (24 +/- 1 yr; 68.6 +/- 2.9 kg; VO2 peak = 4.69 +/- 0.17 L min-1; mean +/- SEM) cycled for 2 h at 69 +/- 1% VO2 peak while receiving either no fluid replacement (NF), a volume of water estimated to prevent body weight loss (FR-100 = 2.32 +/- 0.10 L 2 h-1) or 50% of this volume (FR-60 = 1.16 +/- 0.05 L 2 h-1). The 2-h exercise bout was followed by a ride to exhaustion at a workload estimated to be 90% VO2 peak. After 2 h of exercise, NF was associated with a 3.2 +/- 0.1% weight loss, while FR-50 and FR-100 resulted in losses of 1.8 +/- 0.1 and 0.1 +/- 0.1%, respectively. Compared with FR-100, heart rate and rectal temperature were elevated (P < 0.05) during the second hour of exercise in NF, with FR-50 intermediate. Reductions in plasma volume during exercise were greater in NF and FR-50, compared with FR-100 and plasma sodium concentration was elevated in NF, decreased slightly in FR-100, with FR-50 intermediate. Plasma renin activity, aldosterone and atrial natriuretic peptide increased to similar extents in the three trials. Plasma vasopressin remained unchanged for FR-100, increased for NF, with intermediate values for FR-50. Exercise time to exhaustion at 90% VO2-peak was longer in FR-100 (328 +/- 93 s) than NF (171 +/- 75 s) with FR-50 (248 +/- 107 s) not significantly different from either FR-100 or NF. In conclusion, the responses of heart rate, rectal temperature, plasma sodium, and vasopressin during, and performance following, prolonged cycling exercise conducted at 21 degrees C are related to the amount of fluid ingested (i.e. the degree of dehydration).

Determination of hemoglobin mass and blood volume with CO: evaluation and application of a method.

An improved protocol was applied to the use of carboxyhemoglobin (HbCO) saturation for the estimation of body hemoglobin (Hb) mass, red blood cell volume, and blood volume and was appraised in normal volunteers. A body size-related dose of CO (50-90 ml), estimated to change HbCO saturation by 6.5%, was introduced into a low-volume (2.8 liters) closed-circuit rebreathing system and allowed to equilibrate over 10 min. Plots of venous HbCO were characterized by a plateau after 8 min, which remained stable for at least 40 min. No loss of CO from the vascular space was evident. Three estimations of Hb mass at weekly intervals in seven subjects produced a coefficient of variation of 0.8% such that, in the absence of physiological influences, changes as little as 1.5% in Hb mass are detectable. Venesection [498 +/- 16 (SE) ml] in seven subjects was associated with a measured decrease in Hb mass after 1 wk equal to the calculated loss. Blood volume was, however, largely restored by plasma expansion. The method is sensitive and precise. It can be used safely and repeatedly in normal volunteers and hospital patients.

Rowing performance, fluid balance, and metabolic function following dehydration and rehydration.

Eight international class lightweight rowers were examined to determine the efficacy of rehydrating with water following 24 h of dehydration on body fluid balance, metabolic function, and rowing performance. The rowers performed a maximal rowing trial on a Gjessing rowing ergometer (4200 revs, 3-kg resistance) while euhydrated (ET) and following partial rehydration (RT). Body weight was reduced using exercise together with food and fluid restriction over 24 h and was followed by consumption of 1.5 l of water over 2 h. Body weight decreased 5.16 +/- 0.14% (P < 0.05) and plasma volume decreased 12.5 +/- 1.4% (P < 0.05) after dehydration. Rehydration restored plasma volume by 6.02 +/- 0.62%. Rowing trial time increased significantly from 7.02 +/- 0.17 min for the ET to 7.38 +/- 0.21 min for the RT (P < 0.05). The net plasma lactate accumulation decreased significantly from 8.77 +/- 0.31 mmol.l-1 for the ET to 6.77 +/- 0.24 mmol.l-1 for the RT (P < 0.05). Glycogen content (glycosyl units) of the vastus lateralis decreased by 203.6 +/- 18.6 mmol.kg-1 DW during the ET compared with 139.9 +/- 13.4 mmol.kg-1 DW during the RT (P < 0.05). These results demonstrate that the dehydration/rehydration protocol reduced maximal rowing performance due to lowered plasma volume and decreased muscle glycogen utilization.