1 Department of Anaesthesia and Intensive Care, Middelheim General Hospital, Antwerp, Belgium. 2 Clinical Laboratory, Stuyvenberg Hospital, Antwerp, Belgium. 3 Department of Anaesthesia, University of Antwerp, Belgium. 4 Department of Cardiovascular Surgery, Middelheim General Hospital, Antwerp, Belgium
Corresponding author: Department of Anaesthesia and Intensive Care, Middelheim General Hospital, Lindendreef 1, B-2020 Antwerp, Belgium. E-mail: dirk.himpe@pi.be
Accepted for publication: November 19, 2002
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Abstract |
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Methods. Twenty patients scheduled for coronary surgery were studied prospectively. All patients were treated identically, except for the prime, which either contained lactate or was lactate free. Just before bypass and before coming off bypass, haemoglobin, glucose, plasma osmolality and colloid osmotic pressure were determined; albumin, lactate, sodium, potassium, ionized calcium, magnesium, phosphate, arterial pH, PCO2, bicarbonate, and base excess were measured for use in Stewarts analysis.
Results. Metabolic acidosis had resolved by the end of bypass with the lactated prime. Although the strong ion gap (apparent minus effective strong ion difference) increased significantly in both groups, its composition differed significantly between the groups. The Stewart technique detected polyanionic gelatin as a weak acid component contributing to the unidentified anion fraction. Colloid osmotic pressure was maintained in both groups.
Conclusion. Exogenous lactate attenuates acidosis related to CPB. The oncotic and weak acid deficits produced by hypoalbuminaemia may be compensated for temporarily during CPB by polyanionic synthetic colloids such as succinylated gelatin.
Br J Anaesth 2003; 90: 4405
Keywords: acidbase equilibrium, metabolic acidosis; protein, albumin; metabolism, lactate; blood, replacement
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Introduction |
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Liskaser and colleagues3 further concluded that CPB-related acidbase disorders are largely iatrogenic, and are derived from pump prime effects. However, metabolic acidosis during CPB is also inversely related to the colloid osmotic pressure (COP)8 and the blood-buffering capacity, which may vary with the degree of haemodilution.9 10
We hypothesized that during CPB using an iso-oncotic prime, acidosis is reduced by the addition of lactate, a bicarbonate precursor, to the prime. Applying Stewarts biophysical approach,5 we tested this hypothesis by means of a randomized double-blind study comparing succinylated gelatin dispersed in either a lactated solution, or saline with sodium hydroxide (NaOH).
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Methods |
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A volume of 1700 ml was necessary to prime the extracorporeal circuit. Patients were randomly allocated to receive one of two solutions (data on composition provided by the respective manufacturers): Group I, succinylated gelatin 30 g Geloplasma® (Fresenius) in 150 milliequivalents (mEq) Na+, 5 mEq K+, 100 mEq Cl, 3 mEq Mg2+, 30 mEq lactate; Group II, succinylated gelatin 40 g Gelofusin® (B. Braun) in 154 mEq Na+, 120 mEq Cl, 34 mEq OH per litre.
Just after CPB (T1), haemoglobin, glucose, plasma osmolality, COP, albumin, lactate, sodium, potassium, ionized calcium, magnesium, phosphate and bicarbonate concentrations, arterial pH, PCO2, and base excess were measured.
Use of cardioplegic solutions was avoided by using an intermittent technique of cross-clamping the aorta,11 as these solutions can interfere with the biochemical measurements. Total cross-clamp times for each patient were noted.
All measurements were repeated after rewarming to normothermia at the end of CPB just before separation (T3). While the patients blood was cooled to 30°C, the -stat acidbase management strategy was followed.12 13 Arterial carbon dioxide tensions were kept rigorously in the normal 37°C ranges using exhaust capnometry,14 with intermittent arterial blood sampling to control arterial partial pressures of carbon dioxide and oxygen.
Arterial lactate was also sampled immediately after going on bypass (Ts) to take account of the exogenous lactate levels (Ts) in the two groups. COP, and lactate and haemoglobin levels were measured again after 40 min of hypothermic CPB (T2).
Quantitative analysis of the results at T1 and T3 was performed using Stewarts biophysical approach as modified by Figge and colleagues.15 As described by Liskaser and colleagues,3 this method starts with calculation of the apparent strong ion difference (SIDa), which decreases with acidosis:
SIDa = Na+ + K+ + Mg2+ + Ca2+ Cl(1)
(all concentrations in mEq litre1).
Then, applying the mathematical model of Figge and colleagues,15 the contribution to the electrical balance of measured weak acids such as carbon dioxide, phosphate and albumin can be expressed by calculating the effective strong ion difference (SIDe):
SIDe = [1000x2.46x1011xPCO2/(10pH)] + [albumin (0.123xpH0.631)] + [phosphatex(0.309xpH0.469)](2)
(PCO2 in mm Hg, albumin in g litre1, and phosphate in mol litre1).
This formula takes into account the role of known weak acids in the electrical equilibrium. When lactate is also included as a strong ion, the difference between SIDa and SIDe must tend to zero in order to guarantee charge neutrality. If not, unmeasured charges must be present in the plasma to explain the difference, known as the strong ion gap (SIG):
SIG = SIDa SIDe lactate(3)
With a positive value for SIG, unidentified anions in the blood contribute to the measured pH, and strong and weak ions preserve electroneutrality. Since electroneutrality implies an equal number of mEq of cations and anions in the blood, the variable mEq litre1 is used throughout for clarity.
Statistical analysis
With a power of 80%, a sample size of 10 subjects in each treatment group was estimated to be appropriate. This calculation was based on an estimated between-group difference of 40% in the number of subjects having changes in SIDa over time of more than 1.5 mEq, which can be considered clinically relevant.3 4 A Wilcoxon matched-pairs ranked sign test was used on each group to test whether changes over time from T1 to T3 were significant. Adjusting for multiple comparisons, changes with time in haemoglobin, COP and lactate values were measured at Ts (lactate only), T2 and T3, and compared with T1 (baseline). Once all these changes over time were calculated for each group, a MannWhitney U-test was performed to compare the two groups at the different time points, to test the hypothesis that the lactated prime affected acidbase variables differently over the time span of CPB. Sample size estimation and statistical analysis were performed using the Statistica package for Windows (StatSoft Inc., Tulsa, OK, USA). P-values <0.05 were considered significant.
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Results |
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Even though unbuffered hyperchloraemic solutions generally decrease SIDa, it remained unchanged in Group II. This is related to the effects of the 34 mEq per litre OH in the buffer, which also reduced the chloride content from the start of CPB. In contrast, in Group I, SIDa increased, reflecting the alkalization.
The initial peak of lactate in Group I was overcome by its conversion to bicarbonate, with significantly higher concentrations of the latter at the end of CPB compared with Group II. Lactate concentrations in both groups were comparable by the end of CPB at T3 (Fig. 2).
A similar SIG occurred in both groups. Lactate could not be the cause of this increase since the SIG remained almost unchanged once lactate was removed from the calculation (SIG minus lactate). This suggests the presence of a massive amount of unmeasured and unidentified weak anions, equal in both groups. The importance of these findings is presented in Gamble diagrams (Fig. 3), demonstrating the sums of the relative serum concentrations of, respectively, cations and anions by the use of two proportional bars, both of equal height, to demonstrate electroneutrality.
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Discussion |
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Even though SIDa was expected to decline in Group II as a result of the high chloride content of the prime,16 it remained virtually unchanged and the acidosis was reduced by the presence of NaOH. By contrast, in Group I, the SIDa increased, confirming how exogenous proton-free lactate vitiated the acidosis without causing a higher plasma lactate at the end of CPB. Lactate contributed to the reduction in acidosis both by its conversion to bicarbonate and by reducing consistently the initial chloride load.17
On theoretical grounds, bicarbonate precursors such as acetate and gluconate (Plasmalyte®, Baxter) could also be used. With these substances in the prime, and performing Stewarts acidbase analysis immediately after the start of CPB, Liskaser and colleagues3 and Prough4 highlighted unique information on the initial effects of prime delivery. However, only the values obtained at the completion of surgery were given; no data relating to the effects just before separation from CPB were given.3 In contrast, our study design allowed comparison of the interaction between patient, prime and pump during the strictly defined period of CPB. Although we found lower end-pump glucose concentrations with the non-lactated prime, this difference was not statistically significant. Whether the greater increase in post-pump hyperglycaemia caused by the lactate could be avoided by using gluconate and/or acetate needs further study.17
In experimental animal sepsis, the combination of lactate and hetastarch as a colloid (Hextend) was associated with less metabolic acidosis and longer survival compared with normal saline.18 According to Kellum,18 Stewarts calculations in his study were not influenced by the starch, which is uncharged. In contrast, polyanionic colloids such as gelatin are likely to have complex effects on these calculations.19 With similar amounts of gelatin in both primes used in the present study, it can be assumed that these molecules are the unidentified weak acids20 responsible for the similar and pronounced increases in the SIG observed in each group.
Loss of weak acid (e.g. decreased albumin concentration) reduces the anion gap and masks acidosis.21 Such changes suggest another (false) argument for the use of albumin in CPB besides increasing oncotic pressure, drug-carrying capacity and free-radical scavenging.22
As well as its oncotic properties, gelatin as a polyanion has been shown to compensate for the weak acid loss secondary to hypoalbuminaemia in the present study. However, a mathematical correction of the Stewart equations, similar to the approach used by Figge and colleagues15 for albumin, is not available.23 For this reason, the known synthetic colloidal weak acid component could not be added into the equation appropriately. It contributes to a more positive SIG, together with unmeasured endogenous metabolites like ketoacids, citrate and pyruvate, all known to be present at the end of CPB.3 Explanations, based on Stewarts analysis, of the effects of using large amounts of anionic colloids in CPB therefore require further experimental confirmation.
In conclusion, exogenous lactate attenuates CPB-related acidosis. Other bicarbonate precursors may also have such an effect. Hypoalbuminaemia, with its oncotic and weak acid deficits, may temporarily be compensated for during CPB by polyanionic synthetic colloids such as succinylated gelatin.
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References |
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