Lactic Acidosis in Diabetes

Lactic acidosis is occasionally responsible for metabolic acidosis in diabetics. It may occur in the presence of normal blood levels of the ketone bodies, and such cases are often described as having “non-ketotic diabetic acidosis.” Lactic acid may contribute to the metabolic acidosis in patients with true diabetic ketoacidosis, but the blood lactate concentrations in these patients are not usually very high. In some patients the ketoacidosis is replaced by a lactic acidosis during treatment. This usually occurs in association with a serious underlying disorder and is associated with a poor prognosis. A transient increase in blood lactate concentration was in fact observed in most patients after the beginning of treatment, but the significance of this finding is uncertain.     

血乳酸水平动态监测在危重症患者的应用的临床价值分析

目的:探讨动态监测动脉乳酸水平对危重患者的应用的临床价值分析。方法:对2010年2月~2011年6月间收治的危重病患者的血乳酸水平进行动态监测,通过比较死亡组患者和存活组患者乳酸水平及其它临床指标,比较不同乳酸水平组患者的临床资料来分析乳酸在危重症患者的应用价值。结果:死亡组和存活组患者在性别、年龄差异无明显的统计学意义(P>0.05);病死组乳酸水平、APACHEⅡ评分、住ICU时间(天)、机械通气时间明显高于生存组,差异有显著的统计学意义(P<0.01);严重乳酸酸中毒组患者在APACHEⅡ评分、休克发生率、MODS发生率、死亡发生率均明显高于乳酸酸中毒组和高乳酸血症组,差异有明显的统计学意义(P<0.05),乳酸酸中毒组休克发生率、MODS发生率、死亡发生率均明显高于高乳酸血症组,差异有明显的统计学意义(P<0.05)。结论:动态监测动脉乳酸水平是判断危重患者预后的一个良好指标,动脉乳酸越高,预后差。     

The Clinical Significance of Elevated Blood Lactate

Three patients with elevated blood lactate values are described. The first, despite moderate hyperlactatemia of 5.3 mEq./1. and severe acidosis with an arterial blood pH of 6.98, had no “excess lactate”. In a second patient, moderate acidosis with a pH of 7.27 and blood lactate of 7.5 mEq./1., of which 33% was excess lactate, was found to be secondary to tissue hypoxia on an ischemic basis and preceded the onset of clinical shock by four hours. A third patient, diabetic and under treatment with phenformin hydrochloride, presented with many features suggestive of pulmonary embolism, including marked pulmonary hypertension. A diagnosis of idiopathic lactic acidosis was established when the arterial blood pH was found to be 6.77 and a blood lactate value of 14.2 mEq./1., 60% as excess lactate, was discovered in the absence of a demonstrable cause of tissue hypoxia. Exploration of the pulmonary vascular bed showed no sign of mechanical blockage. The diagnostic, therapeutic and prognostic value of measuring blood lactic acid, and of quantitating the proportion circulating as “excess lactate”, is emphasized.     

Effect of Sodium Bicarbonate Administration on Mortality in Patients with Lactic Acidosis: A Retrospective Analysis

Background

Lactic acidosis is a common cause of high anion gap metabolic acidosis. Sodium bicarbonate may be considered for an arterial pH <7.15 but paradoxically depresses cardiac performance and exacerbates acidosis by enhancing lactate production. This study aimed to evaluate the cause and mortality rate of lactic acidosis and to investigate the effect of factors, including sodium bicarbonate use, on death.

Methods

We conducted a single center analysis from May 2011 through April 2012. We retrospectively analyzed 103 patients with lactic acidosis among 207 patients with metabolic acidosis. We used SOFA and APACHE II as severity scores to estimate illness severity. Multivariate logistic regression analysis and Cox regression analysis models were used to identify factors that affect mortality.

Results

Of the 103 patients with a mean age of 66.1±11.4 years, eighty-three patients (80.6%) died from sepsis (61.4%), hepatic failure, cardiogenic shock and other causes. The percentage of sodium bicarbonate administration (p = 0.006), catecholamine use, ventilator care and male gender were higher in the non-survival group than the survival group. The non-survival group had significantly higher initial and follow-up lactic acid levels, lower initial albumin, higher SOFA scores and APACHE II scores than the survival group. The mortality rate was significantly higher in patients who received sodium bicarbonate. Sodium bicarbonate administration (p = 0.016) was associated with higher mortality. Independent factors that affected mortality were SOFA score (Exp (B) = 1.72, 95% CI = 1.12–2.63, p = 0.013) and sodium bicarbonate administration (Exp (B) = 6.27, 95% CI = 1.10–35.78, p = 0.039).

Conclusions

Lactic acidosis, which has a high mortality rate, should be evaluated in patients with metabolic acidosis. In addition, sodium bicarbonate should be prescribed with caution in the case of lactic acidosis because sodium bicarbonate administration may affect mortality.     

Effect of Hypotensive Resuscitation with a Novel Combination of Fluids in a Rabbit Model of Uncontrolled Hemorrhagic Shock

Objective

The aim of this study was to compare the effects of hypotensive and normotensive resuscitation with a novel combination of fluids via lactate Ringer’s solution (LRS), 6% hydroxyethyl starch 130/0.4 solution (HES), and 7.5% hypertonic saline solution (HSS) at early stage of uncontrolled hemorrhagic shock (UHS) before hemostasis.

Methods

New Zealand white rabbits (n = 32) underwent UHS by transecting the splenic parenchyma, followed by blood withdrawal via the femoral artery to target mean arterial pressure (MAP) of 40–45 mmHg. Animals were distributed randomly into 4 groups (n = 8): in group Sham, sham operation was performed; in group HS, UHS was untreated; in group HS-HR, UHS was treated by hypotensive resuscitation with HSS and LRS+HES (ratio of 2∶1) to MAP of 50–55 mmHg; in group HS-NR, UHS was treated by normotensive resuscitation with HSS and LRS+HES (ratio of 2∶1) to MAP of 75–80 mmHg. Outcomes of hemodynamics, inflammatory and oxidative response, and other metabolic variables were measured and the histopathological studies of heart, lung and kidney were performed at the end of resusucitation.

Results

Hypotensive resuscitation with the novel combination of fluids for UHS rabbits decreased blood loss, maintained better stabilization of hemodynamics, and resulted in relatively higher hematocrit and platelet count, superior outcomes of blood gas, and lower plasma lactate concentration. Besides, hypotensive resuscitation attenuated the inflammatory and oxidative response significantly in UHS rabbits.

Conclusion

Hypotensive resuscitation with the novel combination of fluids via HSS and LRS+HES (ratio of 2∶1) has an effective treatment at early stage of UHS before hemostasis.     

Heart Rate Variability Analysis in an Experimental Model of Hemorrhagic Shock and Resuscitation in Pigs

Background

The analysis of heart rate variability (HRV) has been shown as a promising non-invasive technique for assessing the cardiac autonomic modulation in trauma. The aim of this study was to evaluate HRV during hemorrhagic shock and fluid resuscitation, comparing to traditional hemodynamic and metabolic parameters.

Methods

Twenty anesthetized and mechanically ventilated pigs were submitted to hemorrhagic shock (60% of estimated blood volume) and evaluated for 60 minutes without fluid replacement. Surviving animals were treated with Ringer solution and evaluated for an additional period of 180 minutes. HRV metrics (time and frequency domain) as well as hemodynamic and metabolic parameters were evaluated in survivors and non-survivors animals.

Results

Seven of the 20 animals died during hemorrhage and initial fluid resuscitation. All animals presented an increase in time-domain HRV measures during haemorrhage and fluid resuscitation restored baseline values. Although not significantly, normalized low-frequency and LF/HF ratio decreased during early stages of haemorrhage, recovering baseline values later during hemorrhagic shock, and increased after fluid resuscitation. Non-surviving animals presented significantly lower mean arterial pressure (43±7vs57±9 mmHg, P<0.05) and cardiac index (1.7±0.2vs2.6±0.5 L/min/m², P<0.05), and higher levels of plasma lactate (7.2±2.4vs3.7±1.4 mmol/L, P<0.05), base excess (-6.8±3.3vs-2.3±2.8 mmol/L, P<0.05) and potassium (5.3±0.6vs4.2±0.3 mmol/L, P<0.05) at 30 minutes after hemorrhagic shock compared with surviving animals.

Conclusions

The HRV increased early during hemorrhage but none of the evaluated HRV metrics was able to discriminate survivors from non-survivors during hemorrhagic shock. Moreover, metabolic and hemodynamic variables were more reliable to reflect hemorrhagic shock severity than HRV metrics.     

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Clinical observations have indicated that patients who are in shock and who have coexisting acidosis respond relatively poorly to sympathomimetic amines. In experiments with dogs, it was found that, in the presence of acidosis, the pressor action of epinephrine, norepinephrine and metaraminol was considerably reduced. The effect on cardiac rhythm was also considerably lessened after the pH value of the blood had been lowered. In view of these observations in animals, six human patients with profound shock and acidosis were studied. All had a considerably lessened pressor response to vasopressor agents; then, after elevation of the blood pH by intravenous infusion of a 1-molar solution of sodium lactate, responsiveness was restored. These observations emphasize the desirability of close observation of the acid-base status, and early treatment of acidosis, as an important aspect in the management of patients with shock.     

VASOPRESSOR AGENTS—Influence of Acidosis on Cardiac and Vascular Responsiveness

Clinical observations have indicated that patients who are in shock and who have coexisting acidosis respond relatively poorly to sympathomimetic amines. In experiments with dogs, it was found that, in the presence of acidosis, the pressor action of epinephrine, norepinephrine and metaraminol was considerably reduced. The effect on cardiac rhythm was also considerably lessened after the pH value of the blood had been lowered.In view of these observations in animals, six human patients with profound shock and acidosis were studied. All had a considerably lessened pressor response to vasopressor agents; then, after elevation of the blood pH by intravenous infusion of a 1-molar solution of sodium lactate, responsiveness was restored.These observations emphasize the desirability of close observation of the acid-base status, and early treatment of acidosis, as an important aspect in the management of patients with shock.     

Sodium Bicarbonate Treatment during Transient or Sustained Lactic Acidemia in Normoxic and Normotensive Rats

Introduction

Lactic acidosis is a frequent cause of poor outcome in the intensive care settings. We set up an experimental model of lactic acid infusion in normoxic and normotensive rats to investigate the systemic effects of lactic acidemia per se without the confounding factor of an underlying organic cause of acidosis.

Methodology

Sprague Dawley rats underwent a primed endovenous infusion of L(+) lactic acid during general anesthesia. Normoxic and normotensive animals were then randomized to the following study groups (n = 8 per group): S) sustained infusion of lactic acid, S+B) sustained infusion+sodium bicarbonate, T) transient infusion, T+B transient infusion+sodium bicarbonate. Hemodynamic, respiratory and acid-base parameters were measured over time. Lactate pharmacokinetics and muscle phosphofructokinase enzyme''s activity were also measured.

Principal Findings

Following lactic acid infusion blood lactate rose (P<0.05), pH (P<0.05) and strong ion difference (P<0.05) drop. Some rats developed hemodynamic instability during the primed infusion of lactic acid. In the normoxic and normotensive animals bicarbonate treatment normalized pH during sustained infusion of lactic acid (from 7.22±0.02 to 7.36±0.04, P<0.05) while overshoot to alkalemic values when the infusion was transient (from 7.24±0.01 to 7.53±0.03, P<0.05). When acid load was interrupted bicarbonate infusion affected lactate wash-out kinetics (P<0.05) so that blood lactate was higher (2.9±1 mmol/l vs. 1.0±0.2, P<0.05, group T vs. T+B respectively). The activity of phosphofructokinase enzyme was correlated with blood pH (R2 = 0.475, P<0.05).

Conclusions

pH decreased with acid infusion and rose with bicarbonate administration but the effects of bicarbonate infusion on pH differed under a persistent or transient acid load. Alkalization affected the rate of lactate disposal during the transient acid load.     

Metabolic Adaptations May Counteract Ventilatory Adaptations of Intermittent Hypoxic Exposure during Submaximal Exercise at Altitudes up to 4000 m

Intermittent hypoxic exposure (IHE) has been shown to induce aspects of altitude acclimatization which affect ventilatory, cardiovascular and metabolic responses during exercise in normoxia and hypoxia. However, knowledge on altitude-dependent effects and possible interactions remains scarce. Therefore, we determined the effects of IHE on cardiorespiratory and metabolic responses at different simulated altitudes in the same healthy subjects. Eight healthy male volunteers participated in the study and were tested before and 1 to 2 days after IHE (7×1 hour at 4500 m). The participants cycled at 2 submaximal workloads (corresponding to 40% and 60% of peak oxygen uptake at low altitude) at simulated altitudes of 2000 m, 3000 m, and 4000 m in a randomized order. Gas analysis was performed and arterial oxygen saturation, blood lactate concentrations, and blood gases were determined during exercise. Additionally baroreflex sensitivity, hypoxic and hypercapnic ventilatory response were determined before and after IHE. Hypoxic ventilatory response was increased after IHE (p<0.05). There were no altitude-dependent changes by IHE in any of the determined parameters. However, blood lactate concentrations and carbon dioxide output were reduced; minute ventilation and arterial oxygen saturation were unchanged, and ventilatory equivalent for carbon dioxide was increased after IHE irrespective of altitude. Changes in hypoxic ventilatory response were associated with changes in blood lactate (r = −0.72, p<0.05). Changes in blood lactate correlated with changes in carbon dioxide output (r = 0.61, p<0.01) and minute ventilation (r = 0.54, p<0.01). Based on the present results it seems that the reductions in blood lactate and carbon dioxide output have counteracted the increased hypoxic ventilatory response. As a result minute ventilation and arterial oxygen saturation did not increase during submaximal exercise at simulated altitudes between 2000 m and 4000 m.     

Prognostic Value of Lactate and Central Venous Oxygen Saturation after Early Resuscitation in Sepsis Patients

The objective of this study was to evaluate the prognostic value of static and dynamic variables of central venous oxygen saturation (ScvO₂) and lactate in patients with severe sepsis or septic shock who underwent early quantitative resuscitation. We also investigated whether ScvO₂ measured after initial resuscitation could provide additive prognostic value to that of lactate. We analyzed the sepsis registry for patients presenting to the emergency department and included patients with simultaneous measurements of lactate and ScvO₂ at the time of presentation (H0) and 6 hours (H6) after resuscitation. The primary outcome was 28-day mortality and multivariable logistic analysis was used to adjust for confounders. A total of 363 patients were included, and the overall 28-day mortality was 18%. The area under the receiver operator characteristic curve for predicting 28-day mortality was as follows: lactate (H6), 0.81; lactate (H0), 0.73; relative lactate change, 0.67; ScvO₂ (H6), 0.65; relative ScvO₂ change 0.59; ScvO₂ (H0), 0.58. Patients with lactate normalization showed significantly lower 28-day mortality compared to patients without lactate normalization (3% vs. 28%, P<0.01). However, in those who achieved ScvO₂ (H6) ≥70%, there was a significant difference in 28-mortality only in patients without lactate normalization (21% vs. 39%, P<0.01) but no difference in those with lactate normalization (4% vs. 3%, P = 0.71). In multivariable analysis, lactate normalization was significantly associated with 28-day mortality (adjusted odds ratio [OR] for 28-day mortality, 0.20; 95% confidence interval [CI], 0.07–0.54; P <0.01), but ScvO₂ (H6) ≥70% showed only a marginal association (the adjusted OR for 28-day mortality, 0.51; 95% CI, 0.26–1.01; P = 0.05). ScvO₂ (H6) ≥70% was associated with 28-day mortality only in cases without lactate normalization in subgroup analysis (adjusted OR 0.37, 95% CI, 0.18–0.79; P = 0.01). Six-hour lactate was the strongest predictor of 28-day mortality in patients with severe sepsis or septic shock. Six-hour ScvO₂ provided additional prognostic value only in cases where lactate values were not normalized after resuscitation.     

Epinephrine induces tissue perfusion deficit in porcine endotoxin shock: evaluation by regional CO(2) content gradients and lactate-to-pyruvate ratios

Epinephrine is widely used as a vasoconstrictor or inotrope in shock, although it may typically induce or augment lactic acidosis. Ongoing debate addresses the question of whether hyperlactatemia per se is a sign of tissue perfusion deficit or aerobic glycolysis. We wanted to test the hypothesis that epinephrine has selective detrimental effects on visceral perfusion and metabolism. We performed rigorous regional venous blood gas analyses as well as intraperitoneal microdialysis. We used a mathematical model to calculate regional arteriovenous CO(2) content gradients and estimated the magnitude of the Haldane effect in a porcine model of prolonged hypotensive shock induced by endotoxin infusion (mean arterial blood pressure < 60 mmHg). Subsequently, vasopressors (epinephrine or norepinephrine) were administered and adjusted to maintain systemic mean arterial pressure > 70 mmHg for 4 h. Epinephrine caused systemic hyperlactatemia and acidosis. Importantly, both systemic and regional venous lactate-to-pyruvate ratios increased. Epinephrine was associated with decreasing portal blood flow despite apparently maintained total splanchnic blood flow. Epinephrine increased gastric venous-to-arterial Pco(2) gradients and CO(2) content gradients with decreasing magnitude of the Haldane effect, and the regional gastric respiratory quotient remained higher after epinephrine as opposed to norepinephrine infusion. In addition, epinephrine induced intraperitoneal lactate and glycerol release. We did not observe these adverse hemodynamic or metabolic changes related to norepinephrine with the same arterial pressure goal. We conclude that high CO(2) content gradients with decreasing magnitude of the Haldane effect pinpoint the most pronounced perfusion deficiency to the gastric wall when epinephrine, as opposed to norepinephrine, is used in experimental endotoxin shock.     

Inhaled Carbon Monoxide Protects against the Development of Shock and Mitochondrial Injury following Hemorrhage and Resuscitation

Aims

Currently, there is no effective resuscitative adjunct to fluid and blood products to limit tissue injury for traumatic hemorrhagic shock. The objective of this study was to investigate the role of inhaled carbon monoxide (CO) to limit inflammation and tissue injury, and specifically mitochondrial damage, in experimental models of hemorrhage and resuscitation.

Results

Inhaled CO (250 ppm for 30 minutes) protected against mortality in severe murine hemorrhagic shock and resuscitation (HS/R) (20% vs. 80%; P<0.01). Additionally, CO limited the development of shock as determined by arterial blood pH (7.25±0.06 vs. 7.05±0.05; P<0.05), lactate levels (7.2±5.1 vs 13.3±6.0; P<0.05), and base deficit (13±3.0 vs 24±3.1; P<0.05). A dose response of CO (25–500 ppm) demonstrated protection against HS/R lung and liver injury as determined by MPO activity and serum ALT, respectively. CO limited HS/R-induced increases in serum tumor necrosis factor-α and interleukin-6 levels as determined by ELISA (P<0.05 for doses of 100–500ppm). Furthermore, inhaled CO limited HS/R induced oxidative stress as determined by hepatic oxidized glutathione:reduced glutathione levels and lipid peroxidation. In porcine HS/R, CO did not influence hemodynamics. However, CO limited HS/R-induced skeletal muscle and platelet mitochondrial injury as determined by respiratory control ratio (muscle) and ATP-linked respiration and mitochondrial reserve capacity (platelets).

Conclusion

These preclinical studies suggest that inhaled CO can be a protective therapy in HS/R; however, further clinical studies are warranted.     

Determination of pH or lactate in fetal scalp blood in management of intrapartum fetal distress: randomised controlled multicentre trial

Objective To examine the effectiveness of pH analysis of fetal scalp blood compared with lactate analysis in identifying hypoxia in labour to prevent acidaemia at birth.Design Randomised controlled multicentre trial.Setting Labour wards.Participants Women with a singleton pregnancy, cephalic presentation, gestational age ≥34 weeks, and clinical indication for fetal scalp blood sampling. Interventions Standard pH analysis (n=1496) or lactate analysis (n=1496) with an electrochemical microvolume (5 μl) test strip device. The cut-off levels for intervention were pH <7.21 and lactate >4.8 mmol/l, respectively.Main outcome measure Metabolic acidaemia (pH <7.05 and base deficit >12 mmol/l) or pH <7.00 in cord artery blood.Results Metabolic acidaemia occurred in 3.2% in the lactate group and in 3.6% in the pH group (relative risk 0.91, 95% confidence interval 0.61 to 1.36). pH <7.00 occurred in 1.5% in the lactate group and in 1.8% in the pH group (0.84, 0.47 to 1.50). There was no significant difference in Apgar scores <7 at 5 minutes (1.15, 0.76 to 1.75) or operative deliveries for fetal distress (1.02, 0.93 to 1.11).Conclusion There were no significant differences in rate of acidaemia at birth after use of lactate analysis or pH analysis of fetal scalp blood samples to determine hypoxia during labour. Trial registration ISRCT No 1606064.     

Pre-Existing Hypoxia Is Associated with Greater EEG Suppression and Early Onset of Evolving Seizure Activity during Brief Repeated Asphyxia in Near-Term Fetal Sheep

Spontaneous antenatal hypoxia is associated with high risk of adverse outcomes, however, there is little information on neural adaptation to labor-like insults. Chronically instrumented near-term sheep fetuses (125 ± 3 days, mean ± SEM) with baseline PaO₂ < 17 mmHg (hypoxic group: n = 8) or > 17 mmHg (normoxic group: n = 8) received 1-minute umbilical cord occlusions repeated every 5 minutes for a total of 4 hours, or until mean arterial blood pressure (MAP) fell below 20 mmHg for two successive occlusions. 5/8 fetuses with pre-existing hypoxia were unable to complete the full series of occlusions (vs. 0/8 normoxic fetuses). Pre-existing hypoxia was associated with progressive metabolic acidosis (nadir: pH 7.08 ± 0.04 vs. 7.33 ± 0.02, p<0.01), hypotension during occlusions (nadir: 24.7 ± 1.8 vs. 51.4 ± 3.2 mmHg, p<0.01), lower carotid blood flow during occlusions (23.6 ± 6.1 vs. 63.0 ± 4.8 mL/min, p<0.01), greater suppression of EEG activity during, between, and after occlusions (p<0.01) and slower resolution of cortical impedance, an index of cytotoxic edema. No normoxic fetuses, but 4/8 hypoxic fetuses developed seizures 148 ± 45 minutes after the start of occlusions, with a seizure burden of 26 ± 6 sec during the inter-occlusion period, and 15.1 ± 3.4 min/h in the first 6 hours of recovery. In conclusion, in fetuses with pre-existing hypoxia, repeated brief asphyxia at a rate consistent with early labor is associated with hypotension, cephalic hypoperfusion, greater EEG suppression, inter-occlusion seizures, and more sustained cytotoxic edema, consistent with early onset of neural injury.     

Hemodynamic and therapeutic effects of intravenous dopamine

The effects of intravenous dopamine were evaluated in 10 patients with severe but stable coronary artery disease, 17 consecutive patients with primary cardiogenic shock and 3 with severe congestive heart failure and oliguria. Dopamine infusion at 10 μg/kg·min in the 10 patients increased cardiac output by 35%, left ventricular peak dP/dt by 38%, left ventricular minute work index by 44% and mean systolic ejection rate by 7% (P < 0.01); heart rate, aortic pressure, left ventricular end-diastolic pressure and tension-time index were unchanged. For oxygen, potassium and lactate, arterial and coronary sinus values, coronary arteriovenous oxygen differences and myocardial extraction were unchanged. Hemodynamically 13 of the 17 patients in shock responded favourably to dopamine infusion (0.5 to 15 μg/kg·min), with decrease in heart rate, increase in systolic arterial pressure from 75 to 100 mm Hg (P <0.001), decrease in ventricular filling pressure from 20 to 16 mm Hg (P < 0.01) and increase in urine output from 10 to 100 ml/h (P < 0.01). Eleven of those patients survived the shock episode. A close relation was observed between the hemodynamic response to dopamine, survival from the shock episode and the time between onset of shock and initiation of therapy. Low rates of dopamine infusion induced diuresis in the three patients with severe cardiac failure.Dopamine thus seems to improve the mechanical efficiency of the heart in coronary artery disease. Cardiac output is selectively increased and myocardial ischemia does not appear to be induced; those beneficial effects as well as presumably specific action on renal flow and natriuresis, improve immediate survival from cardiogenic shock and severe heart failure.     

Effect of respiratory alkalosis during exercise on blood lactate

A biofeedback model of hyperventilation during exercise was used to assess the independent effects of pH, arterial CO2 partial pressure (PaCO2), and minute ventilation on blood lactate during exercise. Eight normal subjects were studied with progressive upright bicycle exercise (2-min intervals, 25-W increments) under three experimental conditions in random order. Arterialized venous blood was drawn at each work load for measurement of blood lactate, pH, and PaCO2. Results were compared with those from reproducible control tests. Experimental conditions were 1) biofeedback hyperventilation (to increase pH by 0.08-0.10 at each work load); 2) hyperventilation following acetazolamide (which returned pH to control values despite ventilation and PaCO2 identical to condition 1); and 3) metabolic acidosis induced by acetazolamide (with spontaneous ventilation). The results showed an increase in blood lactate during hyperventilation. Blood lactate was similar to control with hyperventilation after acetazolamide, suggesting that the change was due to pH and not to PaCO2 or total ventilation. Exercise during metabolic acidosis (acetazolamide alone) was associated with blood lactate lower than control values. Respiratory alkalosis during exercise increases blood lactate. This is due to the increase in pH and not to the increase in ventilation or the decrease in PaCO2.     

Mixed acid-base disorders, hydroelectrolyte imbalance and lactate production in hypercapnic respiratory failure: the role of noninvasive ventilation

Background

Hypercapnic Chronic Obstructive Pulmonary Disease (COPD) exacerbation in patients with comorbidities and multidrug therapy is complicated by mixed acid-base, hydro-electrolyte and lactate disorders. Aim of this study was to determine the relationships of these disorders with the requirement for and duration of noninvasive ventilation (NIV) when treating hypercapnic respiratory failure.

Methods

Sixty-seven consecutive patients who were hospitalized for hypercapnic COPD exacerbation had their clinical condition, respiratory function, blood chemistry, arterial blood gases, blood lactate and volemic state assessed. Heart and respiratory rates, pH, PaO₂ and PaCO₂ and blood lactate were checked at the 1st, 2nd, 6th and 24th hours after starting NIV.

Results

Nine patients were transferred to the intensive care unit. NIV was performed in 11/17 (64.7%) mixed respiratory acidosis–metabolic alkalosis, 10/36 (27.8%) respiratory acidosis and 3/5 (60%) mixed respiratory-metabolic acidosis patients (p = 0.026), with durations of 45.1±9.8, 36.2±8.9 and 53.3±4.1 hours, respectively (p = 0.016). The duration of ventilation was associated with higher blood lactate (p<0.001), lower pH (p = 0.016), lower serum sodium (p = 0.014) and lower chloride (p = 0.038). Hyponatremia without hypervolemic hypochloremia occurred in 11 respiratory acidosis patients. Hypovolemic hyponatremia with hypochloremia and hypokalemia occurred in 10 mixed respiratory acidosis–metabolic alkalosis patients, and euvolemic hypochloremia occurred in the other 7 patients with this mixed acid-base disorder.

Conclusions

Mixed acid-base and lactate disorders during hypercapnic COPD exacerbations predict the need for and longer duration of NIV. The combination of mixed acid-base disorders and hydro-electrolyte disturbances should be further investigated.     

Diabetic ketoacidosis in a community of suburban Osaka. Analysis of 39 episodes of ketoacidosis and related conditions

Thirty-nine episodes of hyperglycemia and disturbance of acid-base equilibrium were classified according to the result of nitroprusside test for serum (or urine) ketones, serum electrolytes, glucose, lactate, beta-hydroxybutyrate and arterial blood pH and gas analysis into the following 6 groups; (1) diabetic ketoacidosis (DKA), (2) mild DKA, (3) DKA with mixed acid-base disturbance, (4) DKA with lactic acidosis, (5) lactic acidosis with mild ketonemia, (6) lactic acidosis. Their clinical manifestations, laboratory findings, insulin and i.v. fluid requirement in the early phase of therapy were surveyed and compared with those reported from Western countries. The fundamental problems of groups (1) to (4) were hyperglycemia and acid-base disturbance. Groups (5) and (6) were characterized by underlying serious medical illness, accompanied by lactic acidosis and hyperglycemia. All patients in groups (1) to (4) recovered but 7 of 10 patients in groups (5) and (6) died within the first 7 days. DKA with or without lactic acidosis and lactic acidosis with or without mild ketonemia appeared as two separate conditions from the standpoint of management and prognosis and were differentiated only by nitroprusside test for serum ketones. DKA with lactic acidosis and DKA without it could not be differentiated by routine blood chemistries and therapy for the two did not differ so that they were thought to be in the same spectrum of metabolic alteration.     

Metabolic and hemodynamic responses of lower limb during exercise in patients with COPD

Premature lacticacidosis during exercise in patients with chronic obstructive pulmonarydisease (COPD) may play a role in exercise intolerance. In this study,we evaluated whether the early exercise-induced lactic acidosis inthese individuals can be explained by changes in peripheralO₂ delivery(O₂).Measurements of leg blood flow by thermodilution and of arterial andfemoral venous blood gases, pH, and lactate were obtained during astandard incremental exercise test to capacity in eight patients withsevere COPD and in eight age-matched controls. No significantdifference was found between the two groups in leg blood flow at restor during exercise at the same power outputs. Blood lactateconcentrations and lactate release from the lower limb were greater inCOPD patients at all submaximal exercise levels (allP < 0.05). LegO₂at a given power output was not significantly different between the twogroups, and no significant correlation was found between this parameterand blood lactate concentrations. COPD patients had lower arterial andvenous pH at submaximal exercise, and there was a significant positivecorrelation between venous pH at 40 W and the peakO₂ uptake(r = 0.91, P < 0.0001). The correlation betweenvenous pH and peak O₂ uptakesuggests that early muscle acidosis may be involved in early exercisetermination in COPD patients. The early lactate release from the lowerlimb during exercise could not be accounted for by changes inperipheralO₂. The present results point to skeletal muscle dysfunction as being responsible for the early onset of lactic acidosis inCOPD.