Metabolic Acidosis Group Research Articles

SIGNIFICANCE OF ACID BASE STATUS AT ADMISSION IN ACUTE ORGANOPHOSPHORUS POISONING AND ITS IMPACT ON OUTCOMEHOSPITAL BASED OBSERVATIONAL STUDY FROM NORTH EAST INDIA

BACKGROUND: Organophosphorus compounds (OPCs) are being used worldwide as an insecticide, herbicide, fungicide in agriculture field and household garden. Acute respiratory failure has been found to be the most common cause of death in OPC poisoning due to increased secretions and decreased ventilation leading to acid base disturbances. This study was undertaken to assess acid base status in patients with acute OPCs poisoning and to determine its association with the clinical outcome in patients with acute OPCs poisoning. MATERIALS AND METHODS This was a prospective observational study conducted in Dept of General Medicine, Silchar Medical College and Hospital from 1st June 2021 to 31st May 2022 for a period of one year. It was a hospital based observational study. A total of 100 patients were evaluated, with history of ingestion of OP compound and clinical features suggestive of acute OPCs poisoning after fulfillment of inclusion and exclusion criteria. RESULTS Total 100 patients were studied and majority were in the age group of 21-30 years. On Arterial Blood Gas Study,88% had acid base imbalance and 12% had normal acid base balance. Majority of the patient had respiratory alkalosis (49%), followed by respiratory acidosis (16%),metabolic acidosis (15%),metabolic alkalosis (8%).The overall mortality in our study was 19%.The mortality rate in metabolic acidosis group was 46.66%, respiratory acidosis group was 37.5%, metabolic alkalosis group was 12.5 % and respiratory alkalosis group was 10.2 %. CONCLUSION Acid -base imbalances are present in majority of the patients presenting with acute OPC poisoning. The assessment of the initial acid base status can help in determining the prognosis of the patients, help to intensify management and reduce the overall mortality in patients with acute OPC poisoning.

Metabolic Acidosis and Adverse Outcomes and Costs in CKD: An Observational Cohort Study

Metabolic acidosis is a risk factor for progression of chronic kidney disease (CKD), but little is known about its effect on health care costs and resource utilization. We describe the associations between metabolic acidosis, adverse kidney outcomes, and health care costs inpatients with CKD stages G3-G5 and not receiving dialysis. Retrospective cohort study. An integrated claims-clinical data set of US patients with CKD stages G3-G5, with serum bicarbonate values of 12 to<22 mEq/L (metabolic acidosis group) or 22 to 29 mEq/L (normal serum bicarbonate level group). The primary exposure variable was the baseline serum bicarbonate level. The primary clinical outcome was the composite of all-cause mortality, maintenance dialysis, kidney transplant, or a decline in the estimated glomerular filtration rate of≥40% (DD40). The primary cost outcome was all-cause predicted per-patient per-year cost, assessed over a 2-year outcome period. Logistic and generalized linear regression models, adjusted for key covariates such as age, sex, race, kidney function, comorbidities, and pharmacy insurance coverage, were used to assess serum bicarbonate levels as a predictor of DD40 and health care costs, respectively. 51,558 patients qualified. The metabolic acidosis group experienced higher rates of DD40 (48.3% vs. 16.7%, P<0.001) and higher all-cause yearly costs ($65,172 vs. $24,681, P<0.001). Two-year adjusted odds ratio of DD40 per 1-mEq/L increase in serum bicarbonate levels was 0.873 (95% CI, 0.866-0.879); the parameter estimate (±SE) for costs was-0.070±0.0075 (P<0.001). Possible residual confounding. Patients with CKD and metabolic acidosis had higher costs and rates of adverse kidney outcomes compared with patients with normal serum bicarbonate levels. Each 1-mEq/L increase in serum bicarbonate levels was associated with a 13% decrease in 2-year DD40 events and a 7% decrease in per-patient per-year cost.

Metabolic acidosis is associated with increased risk of adverse kidney outcomes and mortality in patients with non-dialysis dependent chronic kidney disease: an observational cohort study

BackgroundManagement of chronic kidney disease (CKD) requires the management of risk factors, such as hypertension and albuminuria, that affect CKD progression. Identification of additional modifiable risk factors is necessary to develop new treatment strategies for CKD. We sought to quantify the association of metabolic acidosis with CKD progression and mortality in a large U.S. community-based cohort.MethodsIn this longitudinal, retrospective cohort study we identified non-dialysis-dependent patients with stage 3‒5 CKD from Optum’s de-identified integrated electronic health records. We selected cohorts of patients with confirmed metabolic acidosis or normal serum bicarbonate levels based on 2 consecutive serum bicarbonate values: 12 to < 22 mEq/L or 22-29 mEq/L, respectively, 28‒365 days apart. The primary composite outcome was ≥ 40 % decline in estimated glomerular filtration rate (eGFR), renal replacement therapy (chronic dialysis or kidney transplant), or all-cause mortality (DD40). Secondary outcomes included each component of the composite outcome. Cox proportional hazards models were used for the DD40 outcome and secondary outcomes, while logistic regression models were used for the DD40 outcome at 2 years.ResultsA total of 51,558 patients qualified for the study. The unadjusted 2-year incidence of adverse renal and fatal outcomes was significantly worse among patients in the metabolic acidosis group vs. those who had normal serum bicarbonate levels: 48 % vs. 17 % for DD40, 10 % vs. 4 % for ≥ 40 % decline in eGFR, 20 % vs. 6 % for renal replacement therapy, and 31 % vs. 10 % for all-cause mortality (all P < 0.001). Over a ≤ 10-year period, for each 1-mEq/L increase in serum bicarbonate, the adjusted hazard ratio for DD40 was 0.926 (95 % confidence interval [CI], 0.922–0.930; P < 0.001); over a ≤ 2-year period, the adjusted odds ratio for DD40 was 0.873 (95 % CI, 0.866–0.879; P < 0.001).ConclusionsIn this large community cohort of patients with stage 3‒5 CKD, the presence of metabolic acidosis was a significant, independent risk factor for the composite adverse outcome of CKD progression, renal replacement therapy, and all-cause mortality (DD40).

Study on Acid-Base Balance Disorders and the Relationship Between Its Parameters and Creatinine Clearance in Patients with Chronic Renal Failure

Objectives: We aimed to determine the parameters of acid-base balance in patients with chronic renal failure (CRF) and the relationship between the parameters evaluating acid-base balance and creatinine clearance. Methods: The current cross-sectional study was conducted on 300 patients with CRF (180 males and 120 females). Clinical examination and blood tests by taking an arterial blood sample for blood gas measurement as well as venous blood for biochemical tests to select study participants were performed. Results: Patients with CRF in the metabolic acidosis group accounted for 74%, other types of disorders were less common. The average pH, PCO₂, HCO₃, tCO₂ and BE of the patient group were 7.35 ± 0.09, 34.28 ± 6.92 mmHg, 20.18 ± 6.06 mmol/L, 21.47 ± 6.48 mmHg and -4.72 ± 6.61 mmol/L respectively. These parameters are lower than normal values and decrease by progressing chronic kidney disease (CKD) stage. These parameters correlated moderately with creatinine clearance. Conclusions: In patients with CRF, metabolic acidosis is predominant, and acid-base balance parameters are positively correlated with creatinine clearance.

Is Metabolic Acidosis a Novel Risk Factor for a Long-Term Graft Survival in Patients after Kidney Transplantation?

Background: Results of both experimental and clinical studies suggest that metabolic acidosis (MA) contributes to the progression of chronic kidney disease (CKD) and mortality in CKD patients. It is unknown whether the same relationship exists in kidney transplantation (KTx) patients. The aim of this observational study was to examine this relationship between MA and both mortality and renal outcomes in patients after KTx. Methods: Four hundred eighty-six (290 male; 196 female) patients aged 48 ± 12 years, at least 1 year after KTx, were analyzed. Blood HCO₃^– was measured, and patients were then observed over 3 years. MA was defined as the blood HCO₃^– concentration <22 mmol/L. The end points of survival analysis were death and initiation of dialysis therapy. In patients who did not reach the above-mentioned end points, the difference between final (after 3 years of follow-up) and initial estimated glomerular filtration rate (eGFR) was calculated. Results: MA was initially diagnosed in 57 (12%) patients after KTx. Three-year patient survival was 89.5% in the MA group and 97.4% in the non-MA group (p = 0.001). Three-year graft survival was 73.7% for patients with MA and 93.0% for patients without MA (p < 0.001). In patients with MA who did not reach study end points, blood bicarbonate concentration at baseline correlated positively with a change in eGFR (R = 0.48, p = 0.002, n = 36). Such a correlation was not found in patients without MA (n = 388). Conclusions: (1) MA significantly increases the risk of mortality in patients after KTx. (2) The intensity of MA may be associated with progression of transplanted kidney dysfunction in KTx patients.

Possible mechanisms of cardiac contractile dysfunction and electrical changes in ammonium chloride induced chronic metabolic acidosis in Wistar rats.

Metabolic acidosis could occur due to either endogenous acids accumulation or bicarbonate loss from the gastrointestinal tract or commonly from the kidney. This study aimed to investigate the possible underlying mechanism(s) of chronic acidosis-induced cardiac contractile and electrical changes in rats. Twenty four adult Wistar rats, of both sexes, were randomly divided into control group and chronic metabolic acidosis group, which received orally 0.28 M NH(4)Cl in the drinking water for 2 weeks. At the end of experimental period, systolic and diastolic blood pressure values were measured. On the day of sacrifice, rats were anesthetized by i.p. pentobarbitone (40 mg/kg b.w.), transthoracic echocardiography and ECG were performed. Blood samples were obtained from abdominal aorta for complete blood count and determination of pH, bicarbonate, chloride, sodium, potassium, troponin I, CK-MB, IL-6, renin and aldosterone levels. Hearts from both groups were studied for cardiac tissue IL-6 and aldosterone in addition to histopathological examination. Compared to control group, chronic metabolic acidosis group showed anemia, significant systolic and diastolic hypotension accompanied by significant reduction of ejection fraction and fraction of shortening, significant bradycardia, prolonged QTc interval and higher widened T wave as well as significantly elevated plasma levels of renin, aldosterone, troponin I, CK-MB and IL-6, and cardiac tissue aldosterone and IL-6. The left ventricular wall of the acidosis group showed degenerated myocytes with fibrosis and apoptosis. Thus, chronic metabolic acidosis induced negative inotropic and chronotropic effects and cardiomyopathy, possibly by elevated aldosterone and IL-6 levels released from the cardiac tissue.

Effects of Acute Respiratory and Metabolic Acidosis on Diaphragm Muscle Obtained from Rats

Acute respiratory acidosis is associated with alterations in diaphragm performance. The authors compared the effects of respiratory acidosis and metabolic acidosis in the rat diaphragm in vitro. Diaphragmatic strips were stimulated in vitro, and mechanical and energetic variables were measured, cross-bridge kinetics calculated, and the effects of fatigue evaluated. An extracellular pH of 7.00 was obtained by increasing carbon dioxide tension (from 25 to 104 mmHg) in the respiratory acidosis group (n = 12) or lowering bicarbonate concentration (from 24.5 to 5.5 mM) in the metabolic acidosis group (n = 12) and the results compared with a control group (n = 12, pH = 7.40) after 20-min exposure. Respiratory acidosis induced a significant decrease in maximum shortening velocity (-33%, P < 0.001), active isometric force (-36%, P < 0.001), and peak power output (-59%, P < 0.001), slowed relaxation, and decreased the number of cross-bridges (-35%, P < 0.001) but not the force per cross-bridge, and impaired recovery from fatigue. Respiratory acidosis impaired more relaxation than contraction, as shown by impairment in contraction-relaxation coupling under isotonic (-26%, P < 0.001) or isometric (-44%, P < 0.001) conditions. In contrast, no significant differences in diaphragmatic contraction, relaxation, or contraction-relaxation coupling were observed in the metabolic acidosis group. In rat diaphragm, acute (20 min) respiratory acidosis induced a marked decrease in the diaphragm contractility, which was not observed in metabolic acidosis.

Effect of Dietary Induced Metabolic Acidosis on Bone Mineral Acquisition in 2-8 Month Old Lambs

Dietary induced metabolic acidosis (MA) results in a negative calcium balance in normal animals. In order to maintain acid-base homeostasis the body's primary base buffer source calcium is mobilized from bone. This study examined the impact of dietary induced MA on bone in an adolescent ovine model. We hypothesized that a MA diet would reduce bone mineral density (BMD) in growing sheep. Twelve 2 month old lambs of mixed sex were divided into 2 groups. The MA group consumed a ration that was relatively acidogenic compared to the control diet (CD) for 6 months. DXA was performed on days 0 and 180. Arterial blood samples were evaluated on days 0, 30, 120, 150 and 180 for pH, pCO2, pO2, HCT, Na, K, ionized Ca, HCO3–, TCO2, base excess (BE), and O2 saturation. Histomorphometry of the femoral diaphysis was performed from samples harvested at 180 days. Statistical analysis consisted of a 2-way ANOVA for sex and diet with repeated measures for bone mineral content (BMC) and blood parameters, a 2-way ANOVA for one time measurements at 180 d including BMD of the whole body, radii, femora and lumbar vertebrae, and 1-way ANOVA to compare histomorphometric measurements. Percent increase from baseline for BMD of the whole body was 1.8x greater in the CD group than the MA group. BMC of the whole body and lumbar vertebrae was significantly less in the MA group. Lumbar BMD on day 180 was 30% less in the MA group. Cortical bone was less affected. Radii and femora BMD was 18% and 21% less, respectively, in the MA group than in the CD group. MA treatment significantly decreased pH, HCT, iCa, HCO3–, TCO2 and BE. However, no blood parameters were outside the normal range for this species. Histomorphometry revealed significantly decreased cortical area and thickness and increased mineral apposition rate and endosteal active surface length in the femoral cortex of the MA group compared to the CD group. This study demonstrated a well compensated dietary induced MA that resulted in a significant decrease in bone mineral acquisition in juvenile sheep. Diets that induce MA may have a profound impact on lowering peak BMD in adolescents and therefore predispose individuals to osteoporosis later in life.

Acute haemodynamic effects of sodium bicarbonate administration in respiratory and metabolic acidosis in anaesthetized dogs.

Twenty-seven halothane-anaesthetized, mechanically ventilated adult mongrel dogs were randomly assigned to either respiratory acidosis group [pHa 7.22 (0.03, SD), PaCO2 9.6 (1.1) kPa, base excess -0.5 (1.4) mmol.l-1, n = 9], metabolic acidosis group [pHa 7.20 (0.05), PaCO2 5.5 (0.4) kPa, base excess -11.1 (2.1) mmol.l-1, n = 9], or nonacidosis group [pHa 7.37 (0.07), PaCO2 5.2 (0.4) kPa, base excess -1.1 (1.5) mmol.l-1, n = 9]. Respiratory acidosis and metabolic acidosis were induced by decreasing respiratory rate and continuous infusion of 2 mmol.l-1 hydrochloric acid, respectively. Sodium bicarbonate solution 1 mmol.kg-1 was injected into the right atrium over five seconds when haemodynamic stability was obtained. In all three groups, acute administration of sodium bicarbonate produced transient decreases in mean arterial pressure and RV dP/dtmax, and transient increase in right atrial pressure 30 seconds after injections, but these variables returned to the pre-injection values by the end of the three minutes observation period. Although no significant differences were seen in haemodynamic variables among the three groups at 30 seconds, one and three minutes, maximum reductions in both RV dP/dtmax and PBF in the metabolic acidosis group (260 (143) mmHg.s-1 and 0.38 (0.26) l.min-1) were significantly greater than those in the non-acidosis group (127 (34) mmHg.s-1 and 0.08 (0.09) l.min-1; P < 0.05).

Temporary acidosis during reperfusion limits myocardial infarct size in dogs.

We tested the hypothesis that myocardial extracellular acidosis during early reperfusion limits infarct size. The left anterior descending coronary artery was perfused with blood through a bypass tube in dogs. We occluded the bypass tube for 40 (protocol I; n = 24 hearts) and 90 min (protocol II; n = 36 hearts). In protocols I and II, we infused one group of hearts with HCl (60 micrograms.kg-1.min-1) for 60 min after the onset of reperfusion (the metabolic acidosis group), and another group of hearts were ventilated with 3 liters of 70% O2-30% CO2 mixed with room air 10 min before the onset of reperfusion for 70 min (the respiratory acidosis group). pH in the coronary venous blood and myocardial pH during reperfusion in the metabolic and respiratory acidosis groups were lower than those in the control groups. Infarct sizes in the metabolic (16.4 +/- 2.5 and 22.3 +/- 2.5%) and respiratory (16.7 +/- 2.6 and 22.3 +/- 2.5%) acidosis groups in protocols I and II, respectively, were smaller than those in the control groups (33.1 +/- 3.0 and 40.6 +/- 4.1%, respectively). Thus we conclude that temporary acidosis during reperfusion limits infarct size.

Effect of vanadate in acute metabolic acidosis

Summary: The effect of vanadate on urinary excretion of acid and electrolyte in dogs with hydrochloric acid (HCI)‐induced acute metabolic acidosis was studied. Vanadate caused no changes in systemic and renal haemodynamics, blood parameters and net acid excretion (NAE) in the control group. In the acute metabolic acidosis group, metabolic acidosis per se also had no effect on haemodymic parameters. Fractional excretion of bicarbonate was decreased, while NAE was markedly increased. Following vanadate treatment, acute acid‐loaded animals showed an increase in mean arterial pressure (MAP), but a decreased glomerular filtration rate and effective renal plasma flow. These animals had reduced NAE compared to that seen with HCI alone. Thus, vanadate impaired the renal adaptive responses to acute metabolic acidosis. the decreased NAE induced by vanadate might be caused by its known inhibitory effect on hydrogen‐potassium‐adenosine triphosphatase (H‐K‐ATPase) and sodium‐potassium‐adenosine triphosphatase (Na‐K‐ATPase), and by renal vasoconstriction.

Normovolaemic haemodilution attenuates cardiac depression induced by sodium bicarbonate in canine metabolic acidosis

This study was designed to determine if coexisting metabolic acidosis or normovolaemic haemodilution, or both, modifies the acute cardiodepressant effect of i.v. sodium bicarbonate. Thirty-one mongrel dogs were anaesthetized with halothane, and the lungs ventilated mechanically; dogs were allocated randomly to one of four groups: control group (pHa 7.39 (SD 0.03), base excess -1.0 (1.6) mmol litre-1, haemoglobin 13.9 (2.5) g dl-1 (n = 8)), metabolic acidosis group (pHa 7.21 (0.05), base excess -11.2 (2.1) mmol litre1, haemoglobin 13.4 (2.6) g dl-1 (n = 8)), anaemia group (pHa 7.40 (0.04), base excess 0.1 (2.0) mmol litre-1, haemoglobin 7.2 (1.1) g dl-1 (n = 8)) or anaemia acidosis group (pHa 7.22 (0.04), base excess -11.0 (2.2) mmol litre-1, haemoglobin 7.4 (0.3) g dl-1 (n = 7)). Metabolic acidosis was induced by continuous i.v. infusion of hydrochloric acid 2 mol litre-1. Normovolaemic haemodilution was undertaken by phlebotomy and simultaneous exchange with lactated Ringer's solution at 37 degrees C. Mean arterial pressure (MAP), pulmonary artery pressure, right atrial pressure (RAP), maximum rate of change of pressure in the right ventricle (RV dP/dtmax) and pulmonary blood flow (PBF) were measured at 30 s, 1 and 3 min after administration of 7% sodium bicarbonate solution 1 mmol kg-1 given into the right atrium over 5 s. Sodium bicarbonate produced significant decreases in MAP and RV dP/dtmax at 30 s in all groups except for the anaemia acidosis group (P < 0.05). There was a significant decrease in right ventricular stroke volume in the metabolic acidosis group from baseline values (P < 0.05), and compared with the three other groups (P < 0.05). These results indicate that the cardiodepressant effect of sodium bicarbonate 1 mmol kg-1 i.v. during metabolic acidosis was more pronounced than without acidosis, but was attenuated in the presence of normovolaemic haemodilution.

Newborn complications after intrapartum asphyxia with metabolic acidosis in the term fetus

OBJECTIVES: Our purpose was to determine the newborn complications after respiratory or metabolic acidosis at delivery and to demonstrate the characteristics of an asphyxial insult predictive of these complications. STUDY DESIGN: Fifty-nine term fetuses with metabolic acidosis were matched with 59 fetuses with normal blood gas measures at delivery. Fifty-one fetuses with respiratory acidosis were also examined. A complication score expressed the magnitude of newborn complications during the 10 days after delivery. RESULTS: Newborn complications were not increased after respiratory acidosis. Newborn complications after metabolic acidosis increase in frequency and severity with the increasing severity and duration of the metabolic acidosis. Thirty-two of the 59 newborns in the metabolic acidosis group had a high complication score. The index values predictive of high scores were the duration of the metabolic acidosis and the Apgar score at 1 minute. CONCLUSIONS: Intrapartum fetal asphyxia with a severe metabolic acidosis accounts for complications in all newborn systems. The probability of a high complication score increases from 14% with favorable index values to 85% with unfavorable index values. (AM J OBSTET GYNECOL 1994; 170:1081-7.)

Myocardial Uptake and Pharmacodynamics of Quinidine and Propafenone in Isolated Rabbit Hearts

The influence of metabolic and respiratory acidosis on the myocardial accumulation and pharmacodynamics of quinidine and propafenone was studied in isolated perfused rabbit hearts. Three pH groups were evaluated: physiologic buffer, pH 7.4; metabolic acidosis, pH 7.0; and respiratory acidosis, pH 7.0. Myocardial accumulation of quinidine and propafenone was significantly reduced during acidosis. Although myocardial quinidine concentrations were similar in the metabolic acidosis group (14.4 +/- 1.2 micrograms/g) and the respiratory acidosis group (14.5 +/- 1.3 micrograms/g), the myocardial propafenone concentration was significantly less during metabolic acidosis (8.9 +/- 2.0 micrograms/g) as compared with respiratory acidosis (12.7 +/- 2.4 micrograms/g, p less than 0.05). The myocardial concentration-effect relationships were linear over the observed myocardial concentration ranges. The slopes of the linear concentration-effect relationships describing QRS duration were increased twofold by both types of acidosis as compared with normal pH (p less than 0.05). In contrast, the slopes of the concentration-effect relationships describing changes in ventricular repolarization and refractoriness were increased only during metabolic acidosis as compared with pH 7.4 (p less than 0.05). Thus, for any given concentration of drugs, the effects of quinidine and propafenone on ventricular conduction time are dependent on the pH of the perfusate, whereas these drug effects on ventricular repolarization and refractoriness are dependent on the buffer composition.