Osmolal and anion gaps in dogs with acute endotoxic shock

Serum osmolalities, biochemical concentrations, osmolal and anion gaps, blood lactate concentrations, and acid base status were evaluated in anesthetized, healthy control dogs and in dogs with endotoxic shock. The osmolal gap was not affected by endotoxemia. Compared with control dogs, dogs with endotoxic shock had mildly, though insignificantly, increased anion gaps and significantly increased blood lactate concentrations. The anion gap in dogs with endotoxic shock was positively (r = 0.77) and significantly correlated with the blood lactate concentration. Therefore, the blood lactate concentration of a dog in endotoxic shock may be estimated by use of the equation: lactate = 0.27 (anion gap) - 1.46. Confidence limits for this estimation were calculated. Dogs with endotoxic shock developed a lactic acidosis and hyperchloremic metabolic acidosis, with hyperventilation.     

Arterial lactate concentration, hospital survival, sepsis and SIRS in critically ill neonatal foals

REASONS FOR PERFORMING STUDY: Blood lactate concentration has been shown to be a useful clinical indicator in human patients, but has not been formally investigated in critically ill foals. OBJECTIVE: To investigate the association of blood lactate with hospital survival, markers of cardiovascular status, metabolic acid base status, sepsis and systemic inflammatory response syndrome (SIRS). METHODS: A database containing clinical, haematological, plasma biochemical and hospital outcome data on neonatal foals referred to an intensive care unit in 2000-2001 was analysed. Seventy-two foals for which arterial lactate was measured at admission were included in the study. RESULTS: Sixty-one foals had an admission lactate concentration > 2.5 mmol/l. Admission lactate was statistically associated with hospital survival, mean arterial pressure, blood creatinine concentration, bacteraemia, anion gap, lactate concentration at 18-36 h after admission and evidence of SIRS, but not with packed cell volume or heart rate. Lactate at 18-36 h was also associated with survival and evidence of SIRS. Anion gap, base excess, base excess due to unidentified anions (BEua), simplified strong ion gap or bicarbonate correctly classified foals for presence of hyperlactaemia (> 5 mmol/l) in < or = 80% of animals. CONCLUSIONS: Admission blood lactate gives important prognostic information. Lactate should be measured rather than assumed from the anion gap, base excess, BEua, simplified strong ion gap or bicarbonate. POTENTIAL RELEVANCE: Blood lactate concentrations at admission are clinically relevant in neonatal foals and warrant further investigation. This should include the clinical value of measuring changes in lactate in response to treatment.     

Clinical evaluation of blood lactate levels in equine colic.

Blood lactate levels were evaluated in 36 horses (43 cases) presented with colic. A correlation between increasing blood lactate levels and decreasing percentage survival has been shown. An appreciable anion gap was found in 7 of 10 cases analyzed in detail but in each case the entire gap could not be accounted for by lactate alone. Proposals are offered to account for the unmeasured anions. Blood lactate determination is suggested as a prognostic rather than a diagnostic aid for the equine practitioner and should be used to augment other clinical findings in the horse exhibiting colic.     

Retrospective evaluation of the prognostic utility of plasma lactate concentration,base deficit,pH, and anion gap in canine and feline emergency patients

Objective

To determine the association of plasma lactate concentration, pH, base deficit (BD), and anion gap (AG) in dogs and cats on presentation to an emergency room with outcome, and to compare the prognostic significance of hyperlactatemia with a concurrent metabolic acidosis with that of hyperlactatemia and a normal metabolic acid–base balance.

Design

Retrospective study.

Setting

University teaching hospital.

Animals

Five hundred sixty‐six dogs and 185 cats that had venous blood gas analysis performed.

Interventions

None.

Measurements and Main Results

Medical records were reviewed for plasma lactate concentrations, electrolyte concentrations, and acid–base parameters obtained on emergency room admission, clinical diagnosis, and in‐hospital mortality. The primary outcome measure was all‐cause mortality for the hospitalized visit. Median plasma lactate concentration and AG were higher, BD was more negative, and pH was lower, in non‐survivor dogs and cats. The prevalence of hyperlactatemia was 53% in dogs and 30% in cats. Lactic acidosis was present in 42% and 80% of hyperlactatemic dogs and cats, respectively. Multivariate regression analyses revealed that plasma lactate concentration, BD, and pH, but not AG, were independent predictors of mortality in dogs, and that only plasma lactate concentration was an independent predictor of mortality in cats. Mortality was highest for animals with lactic acidosis, at 59.8% in dogs and 49% in cats. Mortality in dogs with lactic acidosis was significantly higher than dogs with hyperlactatemia and a normal acid–base status (P < 0.0001).

Conclusions

The presence and magnitude of hyperlactatemia on presentation to the emergency room may help identify dogs and cats with high likelihood of in‐hospital mortality, and the presence of lactic acidosis specifically may help identify dogs with yet higher risk of in‐hospital mortality.     

Acid-base disorders in milk-fed calves with chronic indigestion.

Acid-base disorders were investigated in 50 calves with chronic indigestion and metabolic acidosis. In the calves that were unable to stand up, the acidosis was significantly more severe than in the calves that could stand up. The anion gap and four different components of the base excess were calculated by the method described by Fencl. The anion gap was high in more than half of the calves, and it was significantly associated with the base excess due to unidentified anions. However, in seven of the calves, the excess of unidentified anions would not have been detected without the calculations, which made it possible to measure the effect of sodium, chloride, plasma protein and unidentified anions on the acid-base balance. Twenty-four of the calves had a combination of hyperchloraemic and high anion gap metabolic acidosis. Changes in sodium and plasma protein concentrations had a minor impact on the calves' acid-base status.     

Electrolyte abnormalities associated with diarrhea in rhesus monkeys: 100 cases (1986-1987)

Serum electrolyte values from 100 rhesus monkeys with diarrhea were reviewed. The most frequent finding was hyponatremia (88%), with hypochloremia next most frequently detected (80%). Metabolic acidosis was less common (59%) and usually associated with high anion gap values. Associations between electrolyte abnormalities and age, housing, or case outcome were not found. Bacteriologic culturing was performed on fecal specimens from 90 monkeys. Campylobacter coli or C jejuni alone was isolated from 42 (46.7%) specimens, C coli and Shigella flexneri were isolated from 25 (27.8%) specimens, and S flexneri alone was isolated from 6 (6.7%) specimens. A pathogen was not isolated from 17 (18.9%) specimens. Hyponatremia, hypochloremia, acidosis, and high anion gap values were most severe in monkeys infected with Campylobacter sp, either alone or with concurrent S flexneri infection. Serum sodium concentrations less than 132 mEq/L and serum Cl concentrations less than 93 mEq/L were consistently associated with Campylobacter sp infection.     

Effect of acute acidemia on blood biochemical variables in healthy ponies

L-Lactic acid and D,L-lactic acid infusion in ponies resulted in metabolic acidosis with high anion gap (AG). Increased AG was explained entirely by increased blood L- and D-lactate concentrations. Hydrochloric acid infusion caused metabolic acidosis with decreased AG. Saline (NaCl) infusion caused mild metabolic acidosis, with no significant change in AG. Plasma K+ concentration was decreased by all types of infusions, with a maximum of 0.50, 0.25, 0.40, 0.50 mmol/L below baseline at the end of infusion in the L-lactic acid-, D,L-lactic acid-, HCl-, and NaCl-infused ponies, respectively. Only hydrochloric acid had a tendency to increase plasma K+ concentration. Hypophosphatemia developed in NaCl- and HCl-infused ponies, but not in the D,L-lactic acid-infused ponies. Serum inorganic phosphate concentration in L-lactic acid-infused ponies increased initially, but was significantly (P less than 0.05) lower than values in the other ponies at 4 hours after onset of infusion. In ponies, the effect of acidemia on plasma K+ and serum inorganic phosphate concentrations was similar to that reported for other species. Changes were small in magnitude and depended on the nature of the acid anion. Results indicate that large changes in plasma K+ and serum inorganic phosphate concentrations during acidosis are probably not a direct result of acidemia.     

Relationship between urine ammonium ion excretion and urine anion gap in dogs.

Acidemia stimulates renal ammonia production and excretion. This adaptive response allows increased H+ secretion and generation of new bicarbonate. To determine whether a relationship existed between urine ammonium (NH4+) concentration and excretion and urine anion gap (Na+ + K(+)- Cl-), ammonium chloride (NH4Cl) was administered per OS for 5 days to induce systemic acidemia in 12 healthy Beagles. During NH4Cl administration, a strong, statistically significant (P less than 0.0001) relationship was apparent between urine NH4+ concentration measured in millimoles per liter and urine anion gap. Regression equation: urine [NH4+] = 8.2 - 0.416 x urine anion gap; r = -0.897. A statistically significant (P = 0.0001) relationship existed between urine NH4+ excretion measured in millimoles per kilogram of body weight per day and urine anion gap. Regression equation: urine NH4+ excretion = 0.74 - 0.38 x urine anion gap; r = -0.768. As urine NH4+ concentration or excretion increased, urine anion gap became more negative. Before NH4Cl administration (no systemic acidemia), a weak, but statistically significant (P = 0.015) relationship was observed between urine NH4+ concentration and urine anion gap. Regression equation: urine [NH4+] = 65.2 - 0.141 x urine anion gap; r = -0.41. However, a relationship was not evident between urine NH4+ excretion and urine anion gap before NH4Cl administration. Hence, urine anion gap is a reliable index of urine NH4+ concentration and excretion only in dogs with metabolic acidosis. In human beings with distal renal tubular acidosis, NH4+ excretion is inappropriately low and results in a positive urine anion gap.(ABSTRACT TRUNCATED AT 250 WORDS)     

Experimental model of hypochloremic metabolic alkalosis caused by diversion of abomasal outflow in sheep

Hypochloremic metabolic alkalosis accompanied by hypokalemia and hyponatremia was induced experimentally in 7 adult sheep by diversion (loss) of gastric contents through an Ivan and Johnston cannula placed in the cranial part of the duodenum just distal to the pylorus. Cannula placement was easily accomplished, and cannulae were tolerated well by the sheep. Volume of effluent produced during the 60- to 120-hour period of diversion ranged from 7.7 to 14.9 L and tended to be greatest during the first 24 hours. All sheep became dehydrated, with mean PCV and plasma total protein concentration increases of 94.2 and 61.7%, respectively. Plasma chloride concentration decreased in linear fashion from a prediversion mean of 113 mEq/L (range, 111 to 117 mEq/L) to an end-point mean of 54 mEq/L (range, 45 to 65 mEq/L). Plasma sodium and potassium concentrations also decreased, though potassium concentration increased terminally. There were rapid increases in arterial blood pH and bicarbonate and base excess concentrations during the first 48 hours after diversion. However, during the final stages of diversion, sheep developed superimposed metabolic acidosis with increased plasma lactate concentration and high anion gap.     

Mixed acid-base disorders

Mixed acid-base disturbances are combinations of two or more primary acid-base disturbances. Mixed acid-base disturbances may be suspected on the basis of findings obtained from the medical history, physical examination, serum electrolytes and chemistries, and anion gap. The history, physical examination, and serum biochemical profile may reveal disease processes commonly associated with acid-base disturbances. Changes in serum total CO2, serum potassium and chloride concentrations, or increased anion gap may provide clues to the existence of acid-base disorders. Blood gas analysis is usually required to confirm mixed acid-base disorders. To identify mixed acid-base disorders, blood gas analysis is used to identify primary acid-base disturbance and determine if an appropriate compensatory response has developed. Inappropriate compensatory responses (inadequate or excessive) are evidence of a mixed respiratory and metabolic disorder. The anion gap is also of value in detecting mixed acid-base disturbances. In high anion gap metabolic acidosis, the change in the anion gap should approximate the change in serum bicarbonate. Absence of this relationship should prompt consideration of a mixed metabolic acid-base disorder. Finding an elevated anion gap, regardless of serum bicarbonate concentration, suggests metabolic acidosis. In some instances, elevated anion gap is the only evidence of metabolic acidosis. In patients with hyperchloremic metabolic acidosis, increases in the serum chloride concentration should approximate the reduction in the serum bicarbonate concentration. Significant alterations from this relationship also indicate that a mixed metabolic disorder may be present. In treatment of mixed acid-base disorders, careful consideration should be given to the potential impact of therapeutically altering one acid-base disorder without correcting others.     

Use of clinical pathology in evaluation of horses with colic

Clinical pathology is a valuable adjunct to physical examination of cases of colic. The present review considers evaluation of cases of colic for three main purposes: (1) making a prognosis, (2) deciding whether to operate, and (3) making a diagnosis. Blood tests noted to be useful for prognostication were hematocrit, lactate and urea nitrogen concentrations, pH, anion gap, fibrin/fibrinogen degradation products, antithrombin III activity, prothrombin time, and thrombin time. Horses with a poor prognosis often have relative polycythemia, marked lactic acidosis, high anion gap, azotemia, and coagulation abnormalities evidenced by increased fibrin/fibrinogen degradation products, decreased antithrombin III activity, and prolonged prothrombin and thrombin times. The decision to operate is usually a clinical one, supported by relative polycythemia, hyperglycemia, and, possibly, abnormal peritoneal fluid analysis. Diagnosis of the primary problem (causing the colicky signs) is also often based largely on physical examination. However, peritoneal fluid analysis provides worthwhile data, especially in cases of peritonitis or intestinal ischemia and infarction.     

Physicochemical Interpretation of Acid‐Base Abnormalities in 54 Adult Horses with Acute Severe Colitis and Diarrhea

Background

The quantitative effect of strong electrolytes, pCO₂, and plasma protein concentration in determining plasma pH and bicarbonate concentrations can be demonstrated with the physicochemical approach. Plasma anion gap (AG) and strong ion gap (SIG) are used to assess the presence or absence of unmeasured anions.

Hypotheses

The physicochemical approach is useful for detection and explanation of acid‐base disorders in horses with colitis. AG and SIG accurately predict hyperlactatemia in horses with colitis.

Animals

Fifty‐four horses with acute colitis and diarrhea.

Methods

Retrospective study . Physicochemical variables were calculated for each patient. ROC curves were generated to analyze sensitivity and specificity of AG and SIG for predicting hyperlactatemia.

Results

Physicochemical interpretation of acid‐base events indicated that strong ion metabolic acidosis was present in 39 (72%) horses. Mixed strong ion acidosis and decreased weak acid (hypoproteinemia) alkalosis was concomitantly present in 17 (30%) patients. The sensitivity and specificity of AG and SIG to predict hyperlactatemia (L‐lactate > 5 mEq/L) were 100% (95% CI, 66.4–100; P < .0001) and 84.4% (95% CI, 70.5–93.5 P < .0001). Area under the ROC curve for AG and SIG for predicting hyperlactatemia was 0.95 (95% CI, 0.86–0.99) and 0.93 (95% CI, 0.83–0.99), respectively.

Conclusion and Clinical relevance

These results emphasize the importance of strong ions and proteins in the maintenance of the acid‐base equilibria. AG and SIG were considered good predictors of clinically relevant hyperlactatemia.     

Influence of D-lactate on metabolic acidosis and on prognosis in neonatal calves with diarrhoea

Three hundred bucket-fed diarrhoeic calves up to the age of 21 days were used to investigate the degree in which D-lactic acid contributes to metabolic acidosis in bucket-fed calves with naturally acquired neonatal diarrhoea. Fifty-five percent of all diarrhoeic calves had serum D-lactate concentrations higher than 3 mmol/l. Mean (+/-SD) D-lactate values were 5.7 mmol/l (+/-5.3, median: 4.1 mmol/l). D-lactate values were distributed over the entire range of detected values from 0 to 17.8 mmol/l in calves with base excess of -10 to -25 mmol/l. Serum D-lactate concentration was higher in patients with ruminal acidosis (6.6 +/- 5.2 mmol/l; median: 5.9 mmol/l) than in those with physiological rumen pH (5.3 +/- 5.4 mmol/l; median: 3.7 mmol/l). There was no evidence of a correlation (r = 0.051) between the serum levels of D-lactate and creatinine (as an indicator of dehydration). D-lactate was correlated significantly with both base excess (r = -0.685) and anion gap (r = 0.647). The proportion of cured patients was not significantly different between the groups with elevated (>3 mmol/l) and normal serum D-lactate concentrations. This study shows that hyper-D-lactataemia occurs frequently in diarrhoeic calves, has no impact on prognosis but may contribute to the clinical picture associated with metabolic acidosis in these animals.     

Measuring statistical agreement between four point of care (POC) lactate meters and a laboratory blood analyzer in cats

The use of blood lactate concentrations as a prognostic indicator and therapeutic gauge in feline medicine has been hindered by the inability to obtain values in a timely manner with minimal quantities of blood. Recently, hand-held point-of-care (POC) lactate meters have become commercially available. The objective of this prospective study was to determine if lactate values produced by three commercially available and one medical grade POC meter were in agreement with a laboratory blood analyzer. Blood samples from 47 cats were collected on presentation to an emergency service and processed on four POC meters and a Stat Profile Critical Care Xpress blood analyzer. The results were analyzed using the Bland-Altman method. The blood lactate values produced by the hospital grade POC meter and one of the commercially POC meters were in good agreement with the Critical Care Xpress blood analyzer. Other commercially available POC meters produced acceptable agreement.     

Severity and nature of acidosis in diarrheic calves over and under one week of age

A prospective study of the severity of dehydration and acidosis was carried out in 42 calves under 35 days of age presented for treatment of neonatal diarrhea. Clinically the mean level of dehydration was 8 to 10%. The plasma volume was 65% of that in the hydrated calf but the calves only gained 6.5% in weight during therapy.

Calves under eight days of age often had a lactic acidosis. Blood pH was 7.118±0.026 (mean ± 1 standard error), bicarbonate concentration 18.8±1.3 mmol/L, base deficit 11.4±1.7 mmol/L and lactate of 3.6± 0.06 mmol/L. Calves over eight days usually had a nonlactic acidosis. Blood pH was 7.042±0.021, bicarbonate 10.8±1.0 mmol/L, base deficit 19.5±1.2 mmol/L and lactate 1.2±0.3 mmol/L. These values were all significantly different from those in younger calves.

Over all calves there was a poor correlation between the severity of acidosis and dehydration(r=0.05). The severity of lactic acidosis was related to the severity of dehydration. Mean bicarbonate requirements to correct acidosis were calculated to be 200 mmol(17 g of sodium bicarbonate)and 450 mmol(37 g of sodium bicarbonate)in calves under and over eight days of age respectively. Both groups of calves required a mean volume of 4L of fluid to correct dehydration.

     

Lactate: physiology and clinical utility

Objective: To review the physiology of lactate production and metabolism, the causes of lactic acidosis, and the current applications of lactate monitoring in humans and animals. Data sources: Human and veterinary studies. Summary: Lactate production is the result of anaerobic metabolism. Tissue hypoxia due to hypoperfusion is the most common cause of lactic acidosis. Studies in critically ill humans have shown that serial lactate monitoring can be used to assess the severity of illness and response to therapy. Several veterinary studies have also shown lactate as a useful tool to assess severity of illness. Conclusions: Lactate measurement in critically ill veterinary patients is practical and can provide information to assess severity of illness. Further veterinary studies are needed to establish the value of serial lactate measurements for prognostic and therapeutic purposes. Information regarding lactate measurement in cats is limited, and further studies are warranted.     

Effect of dietary lactic acid on rumen lactate metabolism and blood acid-base status of lambs switched from low to high concentrate diets.

Two experiments were conducted with ruminally fistulated wether lambs to determine the effect of lactic acid addition to a hay diet on rumen lactate metabolism, blood acid-base status and subsequent adaptation to a high concentrate diet. In Exp. 1, lambs were fed mature brome hay (H), H plus 5% (w/w) D,L lactic acid (H5L) or H plus 10% lactic acid (H10L) (three lambs per treatment) for 14 days (phase I) then switched to a 90% concentrate diet for 2 days (phase II). In Exp. 2, lambs were fed alfalfa-brome hay (H) (six lambs), H plus 2.5% lactic acid (H2.5L) (six lambs) or H plus 5% lactic acid (H5L) (four lambs) during phase I, then switched to a 70% concentrate diet (3 days) followed by a 90% concentrate diet (10 days) (phase II). During both experiments rumen fluid samples were taken periodically for pH and lactate analyses and in vitro L- or D-lactate disappearance (IVLD) studies. Blood samples were taken to measure acid-base status, serum lactate, and serum calcium, magnesium and phosphorus. Dietary lactic acid enhanced IVLD during phase I of both experiments. L and D isomer IVLD rates were similar and followed zero-order kinetics. In Exp. 2, IVLD increased rapidly during phase II in response to increased concentrate level in the diet; the enhanced rates of H2.5L and H5L lambs were sustained for the first 3 days of phase II. Blood data from both experiments indicated a deleterious effect of dietary lactic acid on blood acid-base balance; however, this treatment effect was not manifested in any symptoms of acute acidosis. There was a decrease (P less than .05) in serum calcium during phase II of both experiments. In Experiment 1, serum calcium increased linearly (P less than .05) in response to dietary lactic acid level. In Exp. 1, rumen fluid total lactate and L-lactate were lower (P less than .05) for H5L vs H lambs during phase II. However, all lambs in Exp. 1 experienced acute acidosis; four of the nine lambs subsequently died. There was evidence of acidosis in Exp. 2, but there were no clear treatment effects during phase II on rumen fluid pH or lactate, or feed intake. All lambs adapted to the high concentrate diets as evidenced by rumen lactate levels and feed intakes. In both experiments, the proportion of L-lactate in rumen fluid decreased from almost 100 to about 50% of total lactate by the end of phase II.     

Risk factors and prognostic variables for survival of foals with radiographic evidence of pulmonary disease

The medical records of 163 neonatal foals that had thoracic radiographs taken within 48 hours of admission to a referral hospital were reviewed. The objectives of this study were (1) to identify risk factors for the development of thoracic radiographic changes and (2) to identify prognostic indicators for survival in foals with radiographic evidence of pulmonary disease. Failure of transfer of passive immunity (IgG concentration < or = 400 mg/dL) was the only risk factor for radiographic evidence of respiratory disease identified by multivariate analysis. Hypoxemic patients (PaO2 < or = 60 mm Hg) were 4.9 times more likely to reveal radiographic abnormalities in a subset of foals for which arterial blood gas results were available. Foals with a serum creatinine concentration > 1.7 mg/dL upon presentation, dyspnea, and a history of dystocia were significantly more likely to die based on the multivariate statistical outcome analysis. An anion gap > or = 20 mEq/dL was strongly associated with nonsurvival in a subset of foals with arterial blood gas results. These hematologic and biochemical variables can be readily obtained during the initial evaluation of sick foals. The presence of a high anion gap appeared to have the greatest clinical impact and may be a useful prognostic indicator in foals with radiographic evidence of respiratory disease. In contrast, the majority of physical examination variables, including evaluation of tachypnea, abnormal respiratory sounds, fever, weakness, and milk reflux from the nares, which are usually obtained during the general respiratory evaluation of foals, were unrelated to outcome.     

Evaluation of initial plasma lactate values as a predictor of gastric necrosis and initial and subsequent plasma lactate values as a predictor of survival in dogs with gastric dilatation‐volvulus: 84 dogs (2003–2007)

Objective – To test whether an initial plasma lactate≥6.0 mmol/L is associated with the presence of macroscopic gastric wall necrosis and overall survival in dogs presenting with gastric dilatation‐volvulus (GDV). Additionally, if no association was identified we sought to identify a different predictive initial plasma lactate concentration and to examine whether serial plasma lactate concentrations provide better prediction of survival. Design – Retrospective study over a 5‐year period (2003–2007). Setting – Urban private referral small animal teaching hospital. Animals – Eighty‐four client‐owned dogs with a diagnosis of GDV and plasma lactate measurements. Interventions – None. Measurements and Main Results – There was no statistically significant relationship found between survival and the presence of macroscopic gastric wall necrosis with the initial plasma lactate≥6 mmol/L. There was a significant relationship between the initial plasma lactate >2.9 mmol/L for predicting necrosis and <4.1 mmol/L for predicting survival to discharge. Forty dogs that had an increased initial plasma lactate (>2.5 mmol/L) also had a subsequent plasma lactate measured within 12 hours of presentation, with 37/40 dogs surviving and 70% of these surviving dogs having the subsequent lactate decrease by≥50% within 12 hours. The 3/40 that died failed to decrease their plasma lactate by≥50% from the initial blood lactate. Conclusion – The results of this study indicate that an initial presenting plasma lactate concentration≥6.0 mmol/L is not predictive of macroscopic gastric wall necrosis or survival in dogs presenting with GDV. A decrease in plasma lactate concentrations≥50% within 12 hours may be a good indicator for survival. Limitations to the study include its retrospective nature, the small number of patients, and the number of dogs that were euthanized rather than allowed to progress to a natural outcome.