Acid-base and bio-energetics during balanced versus unbalanced normovolaemic haemodilution.
Fluids balanced to avoid acid-base disturbances may be preferable to saline which causes metabolic acidosis in high volume. We evaluated add-base and bio-energetic effects of haemodilution with a crystalloid balanced on physical chemical principles, versus crystalloids causing metabolic acidosis or metabolic alkalosis
Anaesthetised, mechanically ventilated Sprague-Dawley rats (n = 32, allocated to four groups) underwent six exchanges of 9 ml crystalloid for 3 ml blood. Exchange was with one of three crystalloids with strong ion difference (SID) values of 0, 24 (balanced) and 40 mEq/l. Controls did not undergo haemodilution.
Mean haemoglobin concentration fell to approximately 50 g/l after haemodilution. With SID 24 mEq/l fluid, metabolic add-base remained unchanged. Dilution with SID 0 mEq/l and 40 mEq/l fluids caused a progressive metabolic acidosis and alkalosis restively. Standard base excess (SBE) and haemoglobin concentration were directly correlated in the S1 D 0 mEq/l group ([R.sub.2] = 0.61), indirectly correlated in the SBE 40 mEq/l group ([R.sub.2] = 0.48) and showed no correlation in the SID 24 mEq/l group ([R.sub.2] = 0.003). There were no significant differences between final ileal values of C[O.sub.2] gap, nucleotides concentration, energy charge or luminal lactate concentration. SID 40 mEq/l crystalloid dilution caused a significant rise in subcutaneous lactate In this group mean kidney ATP concentration was significantly less than controls and renal energy charge significantly lower than SID 0 mEq/l and control groups.
We conclude that a crystalloid S1 D of 24 mEq/l provides balanced haemodilution. Bio-energetic perturbations with higher SID haemodilution maybe more severe and need further investigation.
Key Words: acid-base, balanced crystalloid, bio-energetics, haemodilution, strong ion difference
Metabolic acidosis is a consequence of large volume saline administration (1), most commonly seen during repletion of extracellular fluid deficits (2-7). Other causes include acute normovolaemic haemodilution (8,9) and cardiopulmonary bypass (10-12).
There is evidence that this can be harmful. Saline infusions have been linked to mental changes, abdominal discomfort, oliguria (13), an increased gastric carbon dioxide gap (14) and postoperative bleeding (15). Hydrochloric acid exposure is pro-inflammatory, both in vitro (16) and in vivo (17). Experimental hyperchloraemia reduces renal blood flow and glomerular filtration rate (18) and causes inducible nitric oxide synthase (iNOS) activation, acute lung injury and intestinal dysfunction (19-21). In animal models of haemorrhagic and septic shock, fluids designed to prevent metabolic acidosis enhance survival (22-24).
The mechanism of so-called 'dilutional acidosis' is one of simple physical chemistry (9,25,26), the principles of which were first set out by Stewart (27-29). In the Stewart paradigm, metabolic acid-base status is a function of extracellular strong ion difference (SID) and the concentration of non-volatile weak acid ([A.sub.TOT]). SID is the net charge in mEq/l of all fully dissociated plasma anions and cations (i.e. strong ions). [A.sub.TOT] in plasma consists primarily of albumin and phosphate. An increase in [A.sub.TOT] and/or a decrease in SID can cause a metabolic acidosis. The converse applies in metabolic alkalosis.
Saline infusion causes a metabolic acidosis because its SID is zero (equal concentrations of the strong cation [Na.sup.+] and the strong anion [Cl.sup.-]). Consequently, extracellular SID falls on rapid administration, causing a metabolic acidosis which outstrips the metabolic alkalosis of [A.sub.TOT] dilution. To balance saline, some [Cl.sup.-] must be replaced with HC03, or alternatively with strong anions which undergo metabolic 'disappearance', such as lactate, gluconate, acetate or citratezb. Enough chloride must be replaced to balance the fall in extracellular SID against the [A.sub.TOT] dilution effect.
We calculated previously, by linear regression of in vitro and in vivo haemodilution data (9,21) that 24 mEq/l of [Cl.sup.-] must be replaced to create a balanced crystalloid (an effective SID of 24 mEq/l). Accordingly, in the current study we prepared and tested a crystalloid with a SID of 24 mEq/l. We compared the acid-base effects of haemodilution using this theoretically balanced fluid with those of two other fluids, with SID values of 40 mEq/l and 0 mEq/l respectively. We collected various bio-energetic data during this process.
MATERIALS AND METHODS
The protocol was approved by the Animal Experimentation Committee of the University of Queensland. The principles of laboratory animal care met the standards of the National Health and Medical Research Council of Australia.
Progressive normovolaemic haemodilution of anaesthetised, mechanically ventilated rats was performed using three solutions with SID values of 0, 24 and 40 mEq/l (Table 1). These normotonic crystalloids were prepared on the day of experiment by admixture of 0.9% saline, 0.45% saline (Baxter Healthcare, Sydney, N.S.W, Australia) and 8.4% sodium bicarbonate (Astra Pharmaceuticals, Sydney, N.S.W, Australia).
Metabolic acid-base status was quantified by standard base excess (SBE) (30). Other data collected were:
1. Plasma [lactate].
2. Ileal luminal C[O.sub.2] gap.
3. Subcutaneous [lactate].
4. Ileal luminal [lactate].
5. Ileal [nucleotides].
6. Renal [nucleotides].
After a water-only overnight fast, male Sprague-Dawley rats (368-442g) from the Central Animal Breeding House of the University of Queensland were anaesthetised with sodium pentobarbitone 60 mg/kg IP and ventilated via a tracheostomy with air/oxygen and isoflurane using a Harvard Rodent Ventilator (Model 683, Southnatick, MA, U.S.A.). Heat loss was reduced by placing the anaesthetised animals on a warming pad under reflecting metal foil.
A 20 gauge cannula was placed in the carotid artery for fluid administration, monitoring of arterial blood pressure and intermittent blood withdrawal. A polycarbonate microdialysis catheter (CMA/20 Microdialysis AB, Sweden) was advanced into a subcutaneous tunnel between the inguinal area and axilla.
At laparotomy a length of silastic tubing was inserted into the proximal ileum via an anti-mesenteric incision. The air was expelled, the incision closed with 3/0 silk and a multiparameter tissue gas sensor (Paratrend 7, Diametrics Medical, Bucks, U.K.) passed into the tubing. A second microdialysis catheter was advanced into a separate section of ileal lumen through another incision. Both microdialysis catheters were infused at 2 [micro]l/min with fluid (CMA Microdialysis, AB, Sweden), having the following electrolyte composition: [[Na.sup.+]] 147 mEq/l, [[K.sup.+]] 4 mEq/l, [[Ca.sup.++]] 4.6 mEq/l, [[Cl.sup.-]] 156 mEq/l.
PC[O.sub.2] measurements from ileal lumen, corrected to 37[degrees]C and updated every second, were displayed continuously. Minute ventilation was adjusted to achieve an arterial PC[O.sub.2] at 37[degrees]C of 30-50 mm Hg, as determined by blood gas analysis (ABL 620, Radiometer, Copenhagen, Denmark). The inspired isoflurane concentration was set to maintain surgical anaesthaesia, the target mean arterial pressure being 100 mmHg. The ileal temperature monitored via the Paratrend 7 sensor was kept within the range 3538[degrees]C.
There were eight rats in each of the three SID groups and eight controls, allocated to groups in a simple ABCD sequence. Throughout each experiment the allotted crystalloid (or saline in controls) was infused at 3 ml/h. All but the control animals underwent six episodes of haemodilution, at the rate of one dilution every 10 minutes. Each dilution episode began with a 3 ml blood withdrawal, followed by immediate infusion of 9 ml of allocated crystalloid. If the mean arterial pressure fell below 90 mmHg between withdrawals, further 0.5 ml aliquots of crystalloid were infused.
A microdialysis specimen was collected immediately prior to the first haemodilution. Ten minutes after the final haemodilution a second microdialysis specimen was collected, whereupon a segment of ileum and one kidney were snap-frozen using clamps pre-cooled in liquid nitrogen and stored at -70[degrees]C for later assay. All animals were sacrificed under anaesthesia by cardiotomy.
Measurements and data collection
Ileal PC[O.sub.2] values were recorded immediately prior to the first haemodilution and 10 minutes after the final dilution. Arterial specimens timed to coincide with ileal PC[O.sub.2] measurements were subjected to blood gas analysis at 37[degrees]C, along with measurements of haemoglobin and plasma lactate concentrations. In haemodiluted animals and in the first three controls, further arterial blood gas measurements (from one to five per subject) were performed. However, for the final five controls blood collection was restricted to initial and final specimens, to minimise the need for saline replacement and associated acid-base perturbations.
ATP, ADP and AMP concentrations in kidney and gut, expressed per gram of tissue protein, were measured using a previously described method (31).
Dialysate samples were collected over 10 minutes and stored at 4[degrees]C (CMA Microdialysis AB, Sweden). Perfusion fluid was used as reference blanks. Lactate was assayed according to the instructions of the Bio Merieux PAP kit (Cat#61192, Baulkham Hills, N.S.W. Australia), but volumes were modified for a 96 well plate and measured at 492-550 nm on a 96 well plate reader. Hence the volume of the samples and standards were 10 [micro]l instead of 100 [micro]l, diluted with 100 [micro]l of working solution instead of 1 ml. The standard curve was a mean average single point curve of a stock solution of 0.3 mM/1. From the curve, sample solution lactate concentration was calculated, the dilution factor being 1 in 10.
Standard base excess (SBE) was calculated by substituting plasma pH and blood PC[O.sub.2] in the Van Slyke equation (30), using a haemoglobin concentration of 50 g/1. Gut and subcutaneous C[O.sub.2] gaps were calculated as regional PC[O.sub.2]-arterial PC[O.sub.2]. Energy charge (dimensionless) was calculated using the formula, energy charge=
([ATP] + 0.5 [ADP])/([ATP] + [ADP + [AMP]) (32).
Within-group comparisons pre- and post-treatment were by two way analysis of variance. For between-group comparisons of traits, analyses of variance were calculated. Where appropriate, an analysis of covariance on final measurements was undertaken using the corresponding initial measurement as covariate. Means were compared using Tukey's method, which controls the family error rate for comparisons among all means. In each case residuals were examined graphically and subjected to an Anderson-Darling test of normality. If the Anderson-Darling statistic was statistically significant for non-normality of distribution (P:50.05), a Kruskal-Wallis analysis was also performed.
Unless specified, data are reported as mean[+ or -]SD. Linear regression was performed using Excel 2003, Microsoft, Redmond, WA. All other analyses were performed using Minitab statistical software, release 13.
These are summarised in Figure 1 and Tables 2 to 4. Initial SBE values in the SID 40 mEq/l group, measured during baseline infusion of allocated fluid, were significantly greater than those of the SID 0 mEq/l group (Table 2). Otherwise pre-dilution measured and derived indices were similar in all four groups (Table 2). After dilution there were large, highly significant falls in haemoglobin concentration to approximately 50 g/1 (Table 3). There was also a slight but significant haemoglobin fall in controls (Table 3).
[FIGURE 1 OMITTED]
After haemodilution, all groups were in their expected SBE categories, with a metabolic acidosis in the SID 0 mEq/l group, no metabolic acid-base disturbance in SID 24 mEq/l and control groups and a metabolic alkalosis in the SID 40 mEq/l group (Table 3, Figure 1). During haemodilution, SBE was directly correlated with haemoglobin concentration in the SID 0 mEq/l group ([R.sub.2]=0.61), indirectly correlated with haemoglobin in the SID 40 mEq/l group ([R.sub.2]=0.48) and showed no correlation with haemoglobin in the SID 24 mEq/l group ([R.sub.2]=0.003) (Figure 1). The final SBE reduction in the SID 0 mEq/l group (mean SBE -7.8 mEq/l, mean pH 7.33, Table 3) was of similar magnitude to the SBE increase in the SID 40 mEq/l group (mean SBE 6.7 mEq/l, mean pH 7.51, Table 3).
Although there were no differences in final plasma lactate concentration between groups (Table 3), values had fallen significantly in the SID 0 mEq/l and SID 24 mEq/l groups, whereas there was a non-significant increase in the SID 40 mEq/l group. Final ileal COZ gap values had increased significantly in all treatment groups and to a similar extent in controls (Table 3). No mean gut nucleotide concentration or energy charge value reached statistical significance relative to the other group means (Table 4).
SID 40 mEq/l dilution produced other significant findings. Final subcutaneous lactate concentration significantly exceeded pre-dilution levels and also exceeded final values in both other treatment groups and controls (Table 3). Mean kidney ATP concentration for the SID 40 mEq/l group was significantly less than in controls, whereas mean kidney AMP was higher (Table 4). Mean renal energy charge in the SID 40 mEq/l group was low compared with both SID 0 mEq/l and control subjects (Table 4).
These data provide direct confirmation that a crystalloid SID of 24 mEq/l maintains normal metabolic acid-base balance during normovolaemic haemodilution to very low haematocrits (Figure 1, Table 3). Both other fluids behaved as predicted, with SID 0 mEq/l and 40 mEq/l haemodilution causing a progressive metabolic acidosis and alkalosis respectively. The severity of metabolic acidosis in the SID 0 mEq/l group was similar to clinical reports of saline associated acidosis (2-4,7,14,15).
We found that the metabolic alkalosis of the SID 40 mEq/l group was associated with a more prominent deterioration in renal energy charge (Table 4), and a marked increase in skin lactate concentration (Table 3). The non-significant increase in plasma lactate in this group contrasted with significant dilutional lactate reductions in the other two treatment groups (Table 3).
There are a number of possible explanations for the more severe bio-energetic perturbations in the SID 40 mEq/l group. Increased lactate concentration is an anaplerotic effect of alkalaemia (33,34), operating as a feedback loop which buffers pH swings (35,36). Anaerobic stress may have been greater in this alkalaemic group. Potential alkalaemic stressors include conformational changes in Cytochrome C (38) and reduced oxygen availability from vasoconstriction and increased haemoglobin-oxygen affinity (39). The protocol produced haematocrit values known to critically limit splanchnic oxygenation (37). Superimposed metabolic alkalosis may have stressed this precarious bioenergetic state, albeit with renal and cutaneous manifestations rather than gastrointestinal.
By contrast, acidaemia, as produced by the SID 0 mEq/l fluid, can protect against bio-energetic stress (40-43), despite pro-inflammatory effects and iNOS promotion (16,17). This may have contributed to the less severe bio-energetic perturbations of the SID 0 mEq/l group.
We studied both individual nucleotide concentrations and overall energy charge in kidney and small gut. Control energy charge values were >0.8, consistent with previous reports (44,45). Post-dilution renal energy charge was low across the board, especially in the SID 24 mEq/l and SID 40 mEq/l groups (Table 4). A reduced energy charge indicates that consumption is outstripping regeneration of ATP and ADP by oxidative phosphorylation (32). In other studies, reduced renal oxygen delivery of varying severity and aetiology produced similar energy charge reductions, to values ranging from 0.34 to 0.6 (44,45). The fact that only the SID 40 mEq/l group renal energy charge (0.46, Table 4) was significantly lower than controls probably reflects lack of statistical power. An unresolved question is whether the low renal energy charge reflected a primary slowdown in ATP/ADP regeneration, or increased consumption, or perhaps a combination of both. To answer this question, specific data on ATP turnover were needed.
In contrast, gut nucleotides and energy charge in all groups showed little evidence of bio-energetic compromise, despite extreme haemodilution (Table 4). Data from experimental shock induced by sepsis, haemorrhage and pulmonary embolism also point to a greater bio-energetic robustness in gut compared to kidney (45). All treatment groups developed significant ileal C[O.sub.2] gap elevations not exceeding those of controls (Table 3). The unchanged ileal luminal lactate (Table 3) and preservation of ileal nucleotides and energy charge (Table 4) favoured C[O.sub.2] accumulation from flow stagnation, rather than bicarbonate titration from tissue metabolic acidosis (46-49).
What are the clinical implications of these findings? First and foremost, the data confirm that a crystalloid balanced for large volume infusion requires an effective SID of 24 mEq/l, as inferred from previous experimentation (9,25). Hartmann's solution is the commercial fluid closest to this ideal, but suffers several design drawbacks, such as hypotonicity, presence of divalent cations and the need for efficient lactate metabolism, as discussed elsewhere (26).
Second, the possibility that high SID fluid causes additional bio-energetic stress requires clarification, since there are several commercial fluids with effective SID values even higher than 40 mEq/l (26). All are likely to cause metabolic alkalosis in large volumes, although rarely coupled with the extreme acute anaemia of this experiment. Perhaps best known is Plasma-Lyte 148 (Baxter Healthcare, Toongabbie, Sydney, N.S.W Australia), used in cardiopulmonary bypass (11) and for intravascular volume expansion (2).
Currently there is little information on the effects of such high SID fluids on tissue well-being (2,11). A limitation of our own data from this perspective is that they lack statistical power, represent a relatively narrow spectrum of flow and bio-energetic end-points and do not quantify ATP turnover. More importantly they give no information on organ function or survival. Nevertheless, it is worth noting that even without haemodilution, mortality in critical illness escalates as the pH rises above 7.55 (12), although how much is causation versus association is unclear.
In conclusion, we confirm in this animal model of crystalloid haemodilution that a fluid with a SID of 24 mEq/l preserves normal metabolic acid-base status, whereas fluid SID values of 0 mEq/l and 40 mEq/l cause a progressive metabolic acidosis and alkalosis respectively. We suggest that the relative safety of higher SID fluids needs further study. These findings have application in designing fluids for volume expansion, normovolaemic haemodilution and cardiopulmonary bypass.
Financial support was provided by a research gtant from the Australian and New Zealand College of Anaesthetists.
(1.) Gunnerson KJ, Kellum JA. Acid-base and electrolyte analysis in critically ill patients: are we ready for the new millenium? Curr Opin Crit Care 2003; 9:468-473.
(2.) McFarlane C, Lee A. A comparison of Plasmalyte 148 and 0.9% saline for intra-operative fluid replacement. Anaesthesia 1994; 49:779-781.
(3.) Scheingraber S, Rehm M, Sehmisch C, Finsterer U. Rapid saline infusion produces hyperchloremic acidosis in patients undergoing gynecologic surgery. Anesthesiology 1999; 90:12651270.
(4.) Waters JH, Miller LR, Clack S, Kim JV Cause of metabolic acidosis in prolonged surgery. Crit Care Med 1999; 27:21422146.
(5.) Prough DS, Bidani A. Hyperchloremic metabolic acidosis is a predictable consequence of intraoperative infusion of 0.9% saline. Anesthesiology 1999; 90:1247-1249.
(6.) Mustafa I, Leverve XM. Metabolic and hemodynamic effects of hypertonic solutions: sodium-lactate versus sodium chloride infusion in postoperative patients. Shock 2002; 18:306-310.
(7.) Takil A, Eti Z, Irmak P, Gogus FY. Early postoperative respiratory acidosis after large intravascular volume infusion of lactated Ringer's solution during major spine surgery. Anesth Analg 2002; 95:294-298.
(8.) Rehm M, Orth V, Scheingraber S, Kreimeier U, Brechtelsbauer H, Finsterer U. Acid-base changes caused by 5% albumin versus 6% hydroxyethyl starch solution in patients undergoing acute normovolemic haemodilution: a randomized prospective study. Anesthesiology 2000; 93:1174-1183.
(9.) Morgan TJ, Venkatesh B, Hall J. Crystalloid strong ion difference determines metabolic acid-base change during acute normovolemic haemodilution. Intensive Care Med 2004; 30:1432-1437.
(10.) Hayhoe M, Bellomo R, Lin G, McNicol L, Buxton B. The aetiology and pathogenesis of cardiopulmonary bypass-associated metabolic acidosis using polygeline pump prime. Intensive Care Med 1999; 25:680-685.
(11.) Liskaser FJ, Bellomo R, Hayhoe M, Story D, Poustie S, Smith B et al. Role of pump prime in the etiology and pathogenesis of cardiopulmonary bypass-associated acidosis. Anesthesiology 2000; 93:1170-1173.
(12.) Himpe D, Neels H, De Hert S, Van Cauwelaert P Adding lactate to the prime solution during hypothermic cardiopulmonary bypass: a quantitative acid-base analysis. Br J Anaesth 2003; 90:440-445.
(13.) Williams EL, Hildebrand KL, McCormick SA, Bedel MJ. The effect of intravenous lactated Ringer's solution versus 0.9% sodium chloride solution on serum osmolality in human volunteers. Anesth Analg 1999; 88:999-1003.
(14.) Wilkes NJ, Woolf R, Mutch M, Mallett SV, Peachey T, Stephens R et al. The effects of balanced versus saline-based Hetastarch and crystalloid solutions on acid-base and electrolyte status and gastric mucosal perfusion in elderly surgical patients. Anesth Analg 2001; 93:811-816.
(15.) Waters JH, Gottleib A, Schoenwald P, Popovich MJ, Sprung J, Nelson DR. Normal saline versus lactated Ringer's solution for intraoperative fluid management in patients undergoing abdominal aortic aneurism repair: an outcome study. Anesth Analg 2001; 93:817-822.
(16.) Kellum JA, Song M, Li J. Lactic and hydrochloric acids induce different patterns of inflammatory response in LPS-stimulated RAW 264.7 cells. Am J Physiol Regul Integr Comp Physiol 2004; 286:R686-692.
(17.) Kellum JA, Song M, Venkataraman R. Effects of hyperchloremic acidosis on arterial pressure and circulating inflammatory molecules in experimental sepsis. Chest 2004; 125:243-248.
(18.) Wilcox CS. Regulation of renal blood flow by plasma chloride. J Clin Invest 1983; 71:726-735.
(19.) Pedoto A, Caruso JE, Nandi J, Oler A, Hoffmann SP, Tassiopoulos AK et al. Acidosis stimulates nitric oxide production and lung damage in rats. Am J Respir Crit Care Med 1999; 159:397-402.
(20.) Pedoto A, Nandl J, Oler A, Camporesi EM, Hakim TS, Levine RA. Role of nitric oxide in acidosis-induced intestinal injury in anesthetised rats. J Lab Clin Med 2001; 138:270-272.
(21.) Haque IU, Huang CJ, Scumpia PO, Nasiroglu O, Skimming JW Intravascular infusion of acid promotes intrapulmonary inducible nitric oxide synthase activity and impairs blood oxygenation in rats. Crit Care Med 2003; 31:1454-1460.
(22.) Healey MA, Davis RE, Liu FC, Loomis WH, Hoyt DB. Lactated Ringer's is superior to normal saline in a model of massive hemorrhage and resuscitation. J Trauma 1998; 45:894-899.
(23.) Traverso LW, Lee WP, Langford MJ. Fluid resuscitation after an otherwise fatal hemorrhage: 1.Crystalloids solutions. J Trauma 1986; 26:168-175.
(24.) Kellum JA. Fluid resuscitation and hyperchloremic acidosis in experimental sepsis: Improved short-term survival and acid-base balance with Hextend compared with saline. Crit Care Med 2002; 30:300-305.
(25.) Morgan TJ, Venkatesh B, Hall J. Crystalloid strong ion difference determines metabolic acid-base change during in vitro haemodilution. Crit Care Med 2002; 30:157-160.
(26.) Morgan TJ. The meaning of acid-base abnormalities in ICU Part III: Effects of fluid administration. Crit Care 2005; 9:204211.
(27.) Stewart PA. How to understand acid-base. In: Stewart PA (ed). A quantitative acid-base primer for biology and medicine. Elsevier, New York, 1981; 1-286.
(28.) Stewart PA. Modern quantitative acid-base chemistry. Can J Physiol Pharmacol 1983; 61:1444-1461.
(29.) Story DA. Intravenous fluid administration and controversies in acid-base. Crit Care Resusc 1999; 1:156.
(30.) Siggaard-Andersen O, Fogh-Andersen N. Base excess or buffer base (strong ion difference) as measure of a non-respiratory acid-base disturbance. Acta Anaesthesiol Scand 1995; 39 (Suppl 107):123-128.
(31.) Morgan TJ, Venkatesh B, Crerar-Gilbert A, Willgoss D, Endre ZH. Intravenous sodium crocetinate does not alter gut hypercapnic responses or renal energy stores during transient ischemia. Intensive Care Med 2003; 29:652-654.
(32.) Atkinson DE. The energy charge of the adenylate pool as a regulatory parameter. Interaction with feedback modifiers. Biochemistry 1968; 7:4030-4034.
(33.) Ui M. A role of phosphofructokinase in pH-dependent regulation of glycolysis. Biochim Biophys Acta 1966; 124:310-322.
(34.) Eldridge F, Salzer J. Effect of respiratory alkalosis on blood lactate and pyruvate in humans. J Appl Physiol 1967; 22:461-468.
(35.) Hood VL, Tannen RL. Protection of acid-base balance by pH regulation of acid production. N Engl J Med 1998; 339:819-826.
(36.) Madias NE, Cohen JJ, Adrogue HJ. Influence of acute and chronic respiratory alkalosis on pre-existing chronic metabolic alkalosis. Am J Physiol 1990; 258:F479-F485.
(37.) Van Bommel J, Siegemund M, Henny P, Trouwborst A, Ince C. Critical hematocrit in intestinal oxygenation during severe normovolemic haemodilution. Anesthesiology 2001; 94:152-160.
(38.) Gupta RK, Koenig SH. Some aspects of pH and temperature dependence of the NMR spectra of cytochrome c. Biochem Biophys Res Commun 1971; 45:1134-1143.
(39.) Korosi A, Kahn T, Kalb T, Uribarri J. Marked hyperlactatemia associated with severe alkalemia in a patient with thrombotic thrombocytopenic purpura. Am J Kidney Dis 2000; 36:E6.
(40.) Bonventre JV, Cheung JY. Effects of metabolic acidosis on viability of cells exposed to anoxia. Am L Physiol 1985; 249:C149-C159.
(41.) Heijnen BH, Elkhaloufi Y, Straatsburg III, van Gulik TM. Influence of acidosis on liver ischemia and reperfusion injury in an in vivo rat model. J Appl Physiol 2002; 93:319-323.
(42.) Leverve XM. Lactic acidosis. A new insight? Minerva Anestesiol 1999;65:205-209.
(43.) Laffey JG, Kavanagh BE Hypothesis. Carbon dioxide and the critically ill--too little of a good thing? Lancet 1999; 354:1283-1286.
(44.) Cross M, Endre ZH, Stewart-Richardson P, Cowin GJ, Westhuyzen J, Duggleby RG et al. 23Na-NMR detects hypoxic injury in intact kidney: increases in sodium inhibited by DMSO and DMTU. Magn Reson Med 1993; 30:465-475.
(45.) Zager RA. Adenine nucleotide changes in kidney, liver, and small intestine during different forms of ischemic injury. Circulation Research 1991; 68:185-196.
(46.) Vincent J-L, Creteur J. Gastric mucosal pH is definitely obsolete--please tell us more about gastric mucosal PC[O.sub.2]. Crit Care Med 1998; 26:1479-1481.
(47.) Schlichrig R, Mehta N, Gayoski TJP Tissue-arterial PC[O.sub.2] difference is a better marker of ischemia than intramural pH (pHi) or arterial pH-pHi difference. J Crit Care 1996; 11:51-56.
(48.) Heino A, Hartikainen J, Merasto ME, Alhava E, Takala J. Systemic and regional PC[O.sub.2] gradients as markers of intestinal ischemia. Intensive Care Med 1998; 24:599-604.
(49.) Neviere R, Chagnon J-L, Teboul J-L, Vallet B, Wattle E Small intestine intramucosal PC[O.sub.2] hypoxia. Crit Care Med 2002; 30:379-384.
(50.) Wilson RF, Gibson D, Percinel AK, Ali MA, Baker G, LeBlanc LP et al. Severe alkalosis in critically ill surgical patients. Arch Surg 1972;105:197-203.
T. J. MORGAN *, B. VENKATESH [dagger], A. BEINDORF [double dagger], I. ANDREW [section], J. HALL ** University of Queensland Intensive Care Laboratories, Royal Brisbane Hospital, Brisbane, Queensland, Australia
* M.B., B.S., F.J.F.I.C.M., Senior Specialist, Adult Intensive Care Units, Mater Health Services.
[dagger] F.R.C.A., F.J.F.I.C.M., M.D., Associate Professor of Intensive Care, Intensive Care Unit, The Princess Alexandra and Wesley Hospitals.
[double dagger] M.D., Senior Registrar in Intensive Care, Division of Anesthesiology and Intensive Care.
[section] B.Soc. Sc., M.Sc., Research Officer, School of Population Health, University of Queensland, Princess Alexandra Hospital.
** M.Sc., Biomedical Scientist, Division of Anesthesiology and Intensive Care.
Address for reprints: Dr T. J. Morgan, Adult Intensive Care, Mater Misericordiae Health Services, Raymond Terrace, South Brisbane, Qld. 4101.
TABLE 1 Three test fluids--electrolyte concentrations and SID values in mEg/l SID 0 SID 24 SID 40 [[Na.sup.+]] 140 140 140 [[Cl.sup.-]] 140 116 100 [[HCO.sub.3]] 0 24 40 TABLE 2 Initial values (pre-haemodilution) Control SID 0 Hb (g/l) 154[+ or -]15 151[+ or -]10 pH 7.37[+ or -]0.05 7.37[+ or -]0.05 SBE (mEq/l) -1.4[+ or -]2.9 -2.5[+ or -]3.3 [PCO.sub.2] (mmHg) 42[+ or -]7 42[+ or -]9 Plasma lactate (mmol/l) 1.6[+ or -]0.3 2.1[+ or -]0.7 Ileal [CO.sub.2] gap (mmHg) 16[+ or -]4 17[+ or -]6 Subcutaneous lactate (mmol/l) 0.79[+ or -]0.50 0.64[+ or -]0.56 Ileal luminal lactate (mmol/l) 0.32[+ or -]0.69 0.80[+ or -]0.97 SID 24 SID 40 Hb (g/l) 152[+ or -]14 158[+ or -]17 pH 7.4[+ or -]0.02 7.38[+ or -]0.02 SBE (mEq/l) 0.6[+ or -]1.2 1.1 * [+ or -]2.9 [PCO.sub.2] (mmHg) 41[+ or -]2 45[+ or -]6 Plasma lactate (mmol/l) 1.8[+ or -]0.4 2.0[+ or -]0.9 Ileal [CO.sub.2] gap (mmHg) 16[+ or -]2 14[+ or -]5 Subcutaneous lactate (mmol/l) 1.29[+ or -]0.91 1.12[+ or -]0.81 Ileal luminal lactate (mmol/l) 0.98[+ or -]1.47 0.27[+ or -]0.24 * Differs from SID 0 group SBE value (P<0.05). TABLE 3 Final values (post-haemodilution) Control Hb (g/l) 145 (a) * [+ or -] 13 pH 7.40 (a) (b) [+ or -] 0.06 SBE (mEq/l) -2.0 (a) [+ or -] 3.3 [PCO.sub.2] (mmHg) 37 (a) [+ or -] 3 Plasma lactate (mmol/l) 1.5 (a) [+ or -] 0.3 Ileal [CO.sub.2] gap (mmHg) 24 (a) * [+ or -] 10 Subcutaneous lactate (mmol/l) 0.93 (a) [+ or -] 0.30 Ileal luminal lactate (mmol/l) 0.26 (a) [+ or -] 0.28 SID 0 Hb (g/l) 53 (b) ([pi])[+ or -] 13 pH 7.33 (a) [+ or -] 0.04 SBE (mEq/l) -7.7 (b) ([pi]) [+ or -] 1.9 [PCO.sub.2] (mmHg) 341 (a) * [+ or -] 6 Plasma lactate (mmol/l) 1.1 (a) * [+ or -] 0.2 Ileal [CO.sub.2] gap (mmHg) 25 (a) ([pi]) [+ or -] 6 Subcutaneous lactate (mmol/l) 0.61 (a) [+ or -] 0.46 Ileal luminal lactate (mmol/l) 0.84 (a) [+ or -] 0.83 SID 24 Hb (g/l) 56 (b) ([pi]) [+ or -] 13 pH 7.46 (b) (c) ([pi]) [+ or -] 0.03 SBE (mEq/l) 1.5 (a) [+ or -] 1.5 [PCO.sub.2] (mmHg) 36 (a) ([section]) [+ or -] 4 Plasma lactate (mmol/l) 1.2 (a) * [+ or -] 0.4 Ileal [CO.sub.2] gap (mmHg) 22 (a) * [+ or -] 6 Subcutaneous lactate (mmol/l) 0.84 (a) [+ or -] 0.63 Ileal luminal lactate (mmol/l) 0.36 (a) [+ or -] 0.61 SID 40 Hb (g/l) 48 (b) ([pi]) [+ or -] 12 pH 7.51 (c) * [+ or -] 0.10 SBE (mEq/l) 6.7 (c) ([section]) [+ or -] 2.5 [PCO.sub.2] (mmHg) 40 (a) [+ or -] 9 Plasma lactate (mmol/l) 2.4 (a) [+ or -] 2.0 Ileal [CO.sub.2] gap (mmHg) 28 (a) ([section]) [+ or -] 8 Subcutaneous lactate (mmol/l) 2.30 (b) * [+ or -] 0.33 Ileal luminal lactate (mmol/l) 0.81 (a) [+ or -] 0.81 (a) (a,b,c) For each row, mean values followed by a letter in common do not differ at the 5% level. * Differs from initial mean in Table 2 (P<0.05). ([section]) Differs from initial mean in Table 2 (P<0.01). TABLE 4 Gut and renal nucleotide concentrations and energy charge Control Gut ATP (mol/g protein) 21.3 (a) [+ or -] 3.7 Gut ADP (mol/g protein) 3.3 (a) [+ or -] 0.9 Gut AMP (mol/g protein) 0.4 (a) [+ or -] 0.6 Renal ATP (mol/g protein) 13.1 (a) [+ or -] 5.6 Renal ADP (mol/g protein) 3.7 (a) [+ or -] 2.0 Renal AMP (mol/g protein) 0.8 (a) [+ or -] 1.0 Gut energy charge 0.92 (a) [+ or -] 0.02 Renal energy charge 0.86 (a) [+ or -] 0.08 SID 0 Gut ATP (mol/g protein) 17.0 (a) [+ or -] 9.4 Gut ADP (mol/g protein) 6.3 (a) [+ or -] 8.1 Gut AMP (mol/g protein) 2.6 (a) [+ or -] 5.3 Renal ATP (mol/g protein) 8.4 (a) (b) [+ or -] 3.4 Renal ADP (mol/g protein) 4.6 (a) [+ or -] 1.8 Renal AMP (mol/g protein) 2.6 (a) (b) [+ or -] 2.1 Gut energy charge 0.77 (a) [+ or -] 0.28 Renal energy charge 0.70 (a) [+ or -] 0.16 SID 24 Gut ATP (mol/g protein) 17.4 (a) [+ or -] 3.5 Gut ADP (mol/g protein) 3.3 (a) [+ or -] 1.3 Gut AMP (mol/g protein) 1.2 (a) [+ or -] 1.6 Renal ATP (mol/g protein) 9.4 (a) (b) [+ or -] 7.1 Renal ADP (mol/g protein) 4.7 (a) [+ or -] 2.0 Renal AMP (mol/g protein) 2.8 (a) (b) [+ or -] 1.3 Gut energy charge 0.87 (a) [+ or -] 0.08 Renal energy charge 0.64 (a) (b) [+ or -] 0.18 SID 40 Gut ATP (mol/g protein) 16.2 (a) [+ or -] 5.1 Gut ADP (mol/g protein) 3.9 (a) [+ or -] 1.1 Gut AMP (mol/g protein) 0.7 (a) [+ or -] 1.0 Renal ATP (mol/g protein) 4.0 (b) [+ or -] 4.1 Renal ADP (mol/g protein) 3.1 (a) [+ or -] 2.4 Renal AMP (mol/g protein) 2.9 (b) [+ or -] 1.4 Gut energy charge 0.87 (a) [+ or -] 0.07 Renal energy charge 0.46 (b) [+ or -] 0.24 (a,b) For each row, means followed by a letter in common do not differ at the 5% level.
|Printer friendly Cite/link Email Feedback|
|Title Annotation:||Original Papers|
|Author:||Morgan, T.J.; Venkatesh, B.; Beindorf, A.; Andrew, I.; Hall, J.|
|Publication:||Anaesthesia and Intensive Care|
|Article Type:||Clinical report|
|Date:||Apr 1, 2007|
|Previous Article:||Pneumothorax in association with spontaneous ventilation general anaesthesia--an unusual cause of hypoxaemia.|
|Next Article:||Treatment of multilevel degenerative disc disease with intradiscal electrothermal therapy.|