Sieberth, HG, Mann H, Stummvoll HK (eds): Continuous Hemofiltration. Contrib Nephrol. Basel, Karger, 1991, vol 93, pp 152-155
Lactate or Bicarbonate for Intermittent Hemofiltration? M. Clasen, R. B6hm, J. Riehl, U. Gladziwa, K. V. Dakshinamurty, B. Schacht, H. Mann, H.G. Sieberth Department of Internal Medicine II, Technical University of Aachen, FRG
Continuous hemofiltration (HF) has been widely accepted as a therapy for acute renal failure specially in critically ill patients with multiple organ failure. Continuous HF has 3 aims: (1) detoxification of blood; (2) removal of fluid overload; and (3) compensation of metabolic acidosis. For the latter aim, commercial substitution fluids for intermittent HF contain 30-45 mmol/l lactate. However, lactate is thought to have negative effects on metabolic and hemodynamic parameters. In our clinic we observed several times lactic acidosis during lactate-buffered HF (LBHF) in some patients, which gave the reason for the present study. Bicarbonate-buffered substitution fluids are commercially not available because readily mixed fluids containing bicarbonate are not stable for days. As an alternative we used buffer-free solutions which were mixed with bicarbonate immediately before use. The aim of our study was to compare the effects of bicarbonate- and lactate-buffered HF substitution fluids in patients with chronic renal insufficiency undergoing intermittent HF.
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Patients and Methods
The intraindividual changes in metabolic and hemodynamic parameters in II patients undergoing chronic intermittent HF were evaluated in a 9-week crossover trial comparing bicarbonate-buffered HF (BBHF) with LBHF (fig. I). The patients underwent intermittent HF at regular intervals 3 times a week. The demographic data are given in table I. The following parameters were controlled at the beginning, during and at the end of each HF: pH; standard bicarbonate; base excess; blood glucose; plasma lactate (Enzymatic test, DuPont; sodium-fluoride-containing test tubes); potassium; heart rate, and systolic, diastolic and mean arterial blood pressure. The 2 different lactate-buffered solution fluids used in the trial contained: sodium, 138 or 142 mmol/I; potassium, 0 or 2 mmol/I; calcium, 2 mmol/I; magnesium, 0.75 mmol/I; chloride, 103 or 111.5 mmol/I; lactate, 34 or 44.5 mmol/I, and glucose, ommol/1. The bicarbonate solution fluids contained: sodium, 105 mmol/I; potassium, 0 or 2 mmol/I; calcium, 1.75 mmol/I; magnesium, 0.5 mmol/I; chloride, 109.5 mmol/I; lactate, 3 mmol/I; glucose, I gl/I, and bicarbonate, 34.4 mmol/1. LBHF and BBHF periods were identical as concerns the duration of treatment. amounts of substituate and net ultrafiltration. Statistical analysis was performed by analysis of variance and paired Student's t test.
Lactate or Bicarbonate for Intermittent Hemofiltration?
LBHF
o
BBHF
3
Weeks
153
LBHF
6
9
Fig. 1. Study protocol of the 9-week crossover trial. Solution fluids contained in LBHF 44.5 mmol/I lactate and in BBHF 34.4 mmol/I bicarbonate and 3 mmol/I lactate.
Table 1. Patient data
4/7 61.6 51-76 35 1-98
7 4 3
Results LBHF increased mean plasma lactate levels in all patients from basal 1.37 ± 0.9 to 6.4 ± 2.1 mmol/l at the end of HF (normal range 10 mmol/l. In contrast, BBHF led to significantly (p < 0.001) lower basal lactate levels (0.95 ± 0.4 mmol/l) followed by a slight increase to 1.1 ± 0.4 mmol/l. Surprisingly, all parameters of acid-base balance (mean pH levels, standard bicarbonate, base excess) showed a better control of metabolic acidosis by LBHF than by BBHF (table 2). Standard bicarbonate levels raised more slowly during LBHF than during BBHF with no change during the first part of the treatment. Nevertheless, at the end of HF, mean standard bicarbonate levels were significantly higher (p < 0.001) during LBHF. Blood glucose and potassium levels were similar during both treatments. Mean arterial blood pressure, heart rate and the number of hy-
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Female/male ratio Age, years Mean Range Duration of HF treatment, months Mean Range Diagnoses Hypertension Chronic pyelonephritis Diabetes mellitus Chronic glomerulonephritis Goodpasture's syndrome Malignant hypertension Multiple myeloma
Clasen et al.
154
Table 2. Mean values of pH and standard bicarbonate (mmoljl)
Time of HF Before During End
LBHF
BBHF
LBHF
pH
bicarbonate
pH
bicarbonate
pH
bicarbonate
7.34 7.39 7.42
19.4 19.5 21.6
7.30* 7.35* 7.37*
16.6* 18.2* 18.7*
7.36 7.40 7.43
19.7 20.2 22.3
* P < 0.005.
potensive periods were comparable during LBHF and BBHF, showing no statistically significant difference. A questionnaire about subjective feelings given to the patients showed that 3 out of 11 patients felt subjectively better during the bicarbonate treatment. Especially, scores for pruritus tended to be lower under this treatment, whereas complaints of headache and nausea were unchanged. Lactate as a buffer precursor must be metabolized to bicarbonate to achieve compensation of metabolic acidosis. The high values of plasma lactate found are well known from patients with severe lactic acidosis. In case of impaired liver function, sepsis or hypoxemia, lactate can accumulate in critically ill patients and metabolic acidosis will be additionally intensified [1]. A renal replacement therapy for patients with multi organ failure must consider this undesired side effect. Nevertheless, no lactic acidosis was found during this chronic intermittent therapy. Bicarbonate as the physiological buffer has been widely established for acute hemodialysis [2]. For reasons like chemical instability, the readily mixed bicarbonate-containing substitution fluids are not available for HF. We could demonstrate in the present study that a buffer-free solution which is mixed with bicarbonate immediately before use is a practical and safe alternative. Buffering effects of bicarbonate could be proven directly after the start of HF, whereas LBHF increases standard bicarbonate not before 2 h of treatment. The overall better buffering effect of LBHF in our study is not related to the presence of lactate or bicarbonate in the substitution fluid, but to the higher quantity of buffer. In contrast to other authors [3], we suggest that bicarbonate concentrations should contain about 40 mmol/I to produce a sufficient buffering effect. In general, buffer concentrations should be adapted to the individual requirement of the patients which can be estimated by the daily urea generation rate [4].
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Discussion
Lactate or Bicarbonate for Intermittent Hemofiltration?
155
It is clear that bicarbonate is the buffer of choice for acute renal replacement therapy even if its applicability for chronic and intermittent HF seems to be more difficult. In conclusion: (1) lactate as a buffer equivalent in intermittent HF increases plasma lactate levels far above the normal range; (2) but lactate for intermittent HF produces better control of metabolic acidosis compared to bicarbonate buffer (34.4 mmol/l); (3) BBHF is a safe and practical alternative to LBHF, especially for continuous treatment in critically ill patients prone to lactic acidosis, and (4) for intermittent HF, the bicarbonate concentration of substitution fluids should be higher than 35 mmol/l.
3 4
References Mizock BA: Controversies in lactic acidosis. JAM A 1987;258:497-501. Leunissen KML, van Hoof JP: Acetate or bicarbonate for hemodialysis? Nephrol Dial Transplant 1988;3: 1-7. Vlaho M: Bikarbonat-Hlimofiltration versus Laktat-Hlimofiltration. Nieren- Hochdruckkrankheiten 1990;7:285-290. Stiller S, Mann H: Comparison of different methods of blood detoxification; in Sieberth HO, Mann H: Continuous Arteriovenous Hemofiltration (CAVH). Basel, Karger, 1985, pp 143-151.
Dr. Wolfgang Clasen, Krankenhaus der Missionsschwestern Hiltrup, Westfalenstrasse 109, D-W-4400 Munster (FRO)
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2 2
Lactate or Bicarbonate for Intermittent Hemofiltration? M. Clasen, R. B6hm, J. Riehl, U. Gladziwa, K. V. Dakshinamurty, B. Schacht, H. Mann, H.G. Sieberth Department of Internal Medicine II, Technical University of Aachen, FRG
Continuous hemofiltration (HF) has been widely accepted as a therapy for acute renal failure specially in critically ill patients with multiple organ failure. Continuous HF has 3 aims: (1) detoxification of blood; (2) removal of fluid overload; and (3) compensation of metabolic acidosis. For the latter aim, commercial substitution fluids for intermittent HF contain 30-45 mmol/l lactate. However, lactate is thought to have negative effects on metabolic and hemodynamic parameters. In our clinic we observed several times lactic acidosis during lactate-buffered HF (LBHF) in some patients, which gave the reason for the present study. Bicarbonate-buffered substitution fluids are commercially not available because readily mixed fluids containing bicarbonate are not stable for days. As an alternative we used buffer-free solutions which were mixed with bicarbonate immediately before use. The aim of our study was to compare the effects of bicarbonate- and lactate-buffered HF substitution fluids in patients with chronic renal insufficiency undergoing intermittent HF.
Downloaded by: Université de Paris 193.51.85.197 - 1/27/2020 4:46:42 AM
Patients and Methods
The intraindividual changes in metabolic and hemodynamic parameters in II patients undergoing chronic intermittent HF were evaluated in a 9-week crossover trial comparing bicarbonate-buffered HF (BBHF) with LBHF (fig. I). The patients underwent intermittent HF at regular intervals 3 times a week. The demographic data are given in table I. The following parameters were controlled at the beginning, during and at the end of each HF: pH; standard bicarbonate; base excess; blood glucose; plasma lactate (Enzymatic test, DuPont; sodium-fluoride-containing test tubes); potassium; heart rate, and systolic, diastolic and mean arterial blood pressure. The 2 different lactate-buffered solution fluids used in the trial contained: sodium, 138 or 142 mmol/I; potassium, 0 or 2 mmol/I; calcium, 2 mmol/I; magnesium, 0.75 mmol/I; chloride, 103 or 111.5 mmol/I; lactate, 34 or 44.5 mmol/I, and glucose, ommol/1. The bicarbonate solution fluids contained: sodium, 105 mmol/I; potassium, 0 or 2 mmol/I; calcium, 1.75 mmol/I; magnesium, 0.5 mmol/I; chloride, 109.5 mmol/I; lactate, 3 mmol/I; glucose, I gl/I, and bicarbonate, 34.4 mmol/1. LBHF and BBHF periods were identical as concerns the duration of treatment. amounts of substituate and net ultrafiltration. Statistical analysis was performed by analysis of variance and paired Student's t test.
Lactate or Bicarbonate for Intermittent Hemofiltration?
LBHF
o
BBHF
3
Weeks
153
LBHF
6
9
Fig. 1. Study protocol of the 9-week crossover trial. Solution fluids contained in LBHF 44.5 mmol/I lactate and in BBHF 34.4 mmol/I bicarbonate and 3 mmol/I lactate.
Table 1. Patient data
4/7 61.6 51-76 35 1-98
7 4 3
Results LBHF increased mean plasma lactate levels in all patients from basal 1.37 ± 0.9 to 6.4 ± 2.1 mmol/l at the end of HF (normal range 10 mmol/l. In contrast, BBHF led to significantly (p < 0.001) lower basal lactate levels (0.95 ± 0.4 mmol/l) followed by a slight increase to 1.1 ± 0.4 mmol/l. Surprisingly, all parameters of acid-base balance (mean pH levels, standard bicarbonate, base excess) showed a better control of metabolic acidosis by LBHF than by BBHF (table 2). Standard bicarbonate levels raised more slowly during LBHF than during BBHF with no change during the first part of the treatment. Nevertheless, at the end of HF, mean standard bicarbonate levels were significantly higher (p < 0.001) during LBHF. Blood glucose and potassium levels were similar during both treatments. Mean arterial blood pressure, heart rate and the number of hy-
Downloaded by: Université de Paris 193.51.85.197 - 1/27/2020 4:46:42 AM
Female/male ratio Age, years Mean Range Duration of HF treatment, months Mean Range Diagnoses Hypertension Chronic pyelonephritis Diabetes mellitus Chronic glomerulonephritis Goodpasture's syndrome Malignant hypertension Multiple myeloma
Clasen et al.
154
Table 2. Mean values of pH and standard bicarbonate (mmoljl)
Time of HF Before During End
LBHF
BBHF
LBHF
pH
bicarbonate
pH
bicarbonate
pH
bicarbonate
7.34 7.39 7.42
19.4 19.5 21.6
7.30* 7.35* 7.37*
16.6* 18.2* 18.7*
7.36 7.40 7.43
19.7 20.2 22.3
* P < 0.005.
potensive periods were comparable during LBHF and BBHF, showing no statistically significant difference. A questionnaire about subjective feelings given to the patients showed that 3 out of 11 patients felt subjectively better during the bicarbonate treatment. Especially, scores for pruritus tended to be lower under this treatment, whereas complaints of headache and nausea were unchanged. Lactate as a buffer precursor must be metabolized to bicarbonate to achieve compensation of metabolic acidosis. The high values of plasma lactate found are well known from patients with severe lactic acidosis. In case of impaired liver function, sepsis or hypoxemia, lactate can accumulate in critically ill patients and metabolic acidosis will be additionally intensified [1]. A renal replacement therapy for patients with multi organ failure must consider this undesired side effect. Nevertheless, no lactic acidosis was found during this chronic intermittent therapy. Bicarbonate as the physiological buffer has been widely established for acute hemodialysis [2]. For reasons like chemical instability, the readily mixed bicarbonate-containing substitution fluids are not available for HF. We could demonstrate in the present study that a buffer-free solution which is mixed with bicarbonate immediately before use is a practical and safe alternative. Buffering effects of bicarbonate could be proven directly after the start of HF, whereas LBHF increases standard bicarbonate not before 2 h of treatment. The overall better buffering effect of LBHF in our study is not related to the presence of lactate or bicarbonate in the substitution fluid, but to the higher quantity of buffer. In contrast to other authors [3], we suggest that bicarbonate concentrations should contain about 40 mmol/I to produce a sufficient buffering effect. In general, buffer concentrations should be adapted to the individual requirement of the patients which can be estimated by the daily urea generation rate [4].
Downloaded by: Université de Paris 193.51.85.197 - 1/27/2020 4:46:42 AM
Discussion
Lactate or Bicarbonate for Intermittent Hemofiltration?
155
It is clear that bicarbonate is the buffer of choice for acute renal replacement therapy even if its applicability for chronic and intermittent HF seems to be more difficult. In conclusion: (1) lactate as a buffer equivalent in intermittent HF increases plasma lactate levels far above the normal range; (2) but lactate for intermittent HF produces better control of metabolic acidosis compared to bicarbonate buffer (34.4 mmol/l); (3) BBHF is a safe and practical alternative to LBHF, especially for continuous treatment in critically ill patients prone to lactic acidosis, and (4) for intermittent HF, the bicarbonate concentration of substitution fluids should be higher than 35 mmol/l.
3 4
References Mizock BA: Controversies in lactic acidosis. JAM A 1987;258:497-501. Leunissen KML, van Hoof JP: Acetate or bicarbonate for hemodialysis? Nephrol Dial Transplant 1988;3: 1-7. Vlaho M: Bikarbonat-Hlimofiltration versus Laktat-Hlimofiltration. Nieren- Hochdruckkrankheiten 1990;7:285-290. Stiller S, Mann H: Comparison of different methods of blood detoxification; in Sieberth HO, Mann H: Continuous Arteriovenous Hemofiltration (CAVH). Basel, Karger, 1985, pp 143-151.
Dr. Wolfgang Clasen, Krankenhaus der Missionsschwestern Hiltrup, Westfalenstrasse 109, D-W-4400 Munster (FRO)
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2 2
