scholarly journals Acid-base balance in acute ethylene glycol poisoning in rats treated with fomepizole

2014 ◽  
Vol 83 (1) ◽  
pp. 29-36
Author(s):  
Jędrzej Przystanowicz ◽  
Barbara Zielińska-Psuja ◽  
Joanna Kowalówka-Zawieja ◽  
Karina Sommerfeld

Introduction. Ethylene glycol (EG) is relatively nontoxic but undergoes a multi-step oxidation to toxic metabolites, aldehydes and acids. The accumulation of organic acids, mainly glycolates, leads to the development of profound, life-threatening metabolic acidosis. A key therapy is an antidotal treatment with fomepizole (4-MP), the inhibitor of the first step of EG biotransformation enzyme, alcohol dehydrogenase.Aim. The aim of the study was to demonstrate the efficacy of fomepizole in the prevention of acid-base balance disorders in acute ethylene glycol poisonings in rats.Material and methods. Adult male Wistar rats were given EG (p.o.) with single (i.p.) or multiple (p.o.) doses of 4-MP (EG 3830 and 5745 mg/kg, respectively, 4-MP in single dose of 10 mg/kg or 15 mg/kg followed by 10 mg/kg every 12 hours). Blood gas analysis was performed and blood pH, bicarbonate concentration and base excess were evaluated.Results and conclusions. The single dose of 4-MP was effective in preventing a decrease in blood pH, bicarbonate concentration and base excess during the entire experimental period (pH 7.35 vs 7.21 at hour 12, bicarbonate concentration 27.2 vs 18.3 mmol/dm3 at hour 8, base excess 1.8 vs -8.2 mmol/dm3 at hour 18). The multiple administration of 4-MP started 2 hours after EG poisoning resulted in rapid restoration of proper values of acid- -base balance parameters. Fomepizole is highly efficacious in restraining the acid-base balance disorders which are concomitant with acute ethylene glycol poisonings.

2007 ◽  
Vol 292 (3) ◽  
pp. G899-G904 ◽  
Author(s):  
Markus Sjöblom ◽  
Olof Nylander

When running in vivo experiments, it is imperative to keep arterial blood pressure and acid-base parameters within the normal physiological range. The aim of this investigation was to explore the consequences of anesthesia-induced acidosis on basal and PGE2-stimulated duodenal bicarbonate secretion. Mice (strain C57bl/6J) were kept anesthetized by a spontaneous inhalation of isoflurane. Mean arterial blood pressure (MAP), arterial acid-base balance, and duodenal mucosal bicarbonate secretion (DMBS) were studied. Two intra-arterial fluid support strategies were used: a standard Ringer solution and an isotonic Na2CO3 solution. Duodenal single perfusion was used, and DMBS was assessed by back titration of the effluent. PGE2 was used to stimulate DMBS. In Ringer solution-infused mice, isoflurane-induced acidosis became worse with time. The blood pH was 7.15–7.21 and the base excess was about −8 mM at the end of experiments. The continuous infusion of Na2CO3 solution completely compensated for the acidosis. The blood pH was 7.36–7.37 and base excess was about 1 mM at the end of the experiment. Basal and PGE2-stimulated DMBS were markedly greater in animals treated with Na2CO3 solution than in those treated with Ringer solution. MAP was slightly higher after Na2CO3 solution infusion than after Ringer solution infusion. We concluded that isoflurane-induced acidosis markedly depresses basal and PGE2-stimulated DMBS as well as the responsiveness to PGE2, effects prevented by a continuous infusion of Na2CO3. When performing in vivo experiments in isoflurane-anesthetized mice, it is recommended to supplement with a Na2CO3 infusion to maintain a normal acid-base balance.


2020 ◽  
Author(s):  
Joost Janssen ◽  
Joris M.K. van Fessem ◽  
Tijmen Ris ◽  
Robert Jan Stolker ◽  
Markus Klimek

Abstract Background: The superiority of either the traditional or Stewart based approach to acid-base balance has focused primarily on analyzing metabolic acidemia, with little attention given to patients with neutral pH. In this study, we evaluate metabolic disturbances in patients in the immediate postoperative period focusing on patients with neutral pH, while comparing the Stewart and traditional approach. Methods: We conducted a single center retrospective observational cohort study. Over a 17 month period, data on arterial blood gas analysis, electrolytes and albumin on the morning after surgery were retrieved from patients admitted to the postsurgical high dependency unit (HDU). Albumin corrected anion gap (AG), apparent (SIDa) and effective strong ion difference (SIDe) and strong ion gap (SIG) were calculated.Results: Out of 1207 HDU admissions, 400 cases had a complete set of laboratory-data including albumin of which 281 presented with neutral pH (7.35 ≤ pH ≤ 7.45), 64 with acidemia (pH < 7.35) and 55 with alkalemia (pH > 7.45). In pH neutral patients the following acidifying disturbances were found: SIDa was lowered in 101 (36%), SIG was raised in 60 (21%). Base excess (BE) was decreased in 16 (6%) and corrected AG raised in 107 (38%). The alkalizing effect of hypoalbuminemia was present in 137 (49%). Out of 134 cases with normal BE and corrected AG, SIDa was lowered in 58 (43%). Out of 136 cases with normal SIDa and SIG, none had lowered BE and 28 increased AG (21%). Length of stay was significantly longer in patients with hypoalbuminemia, lowered SIDa and increased corrected AG, but not decreased BE (Hypoalbuminemia: 16 days vs. 10 days, P < 0.001. Low SIDa: 15 days vs. 12 days, P = 0.015. Increased AG: 16 days vs. 11 days, P < 0.001. Low BE: 14 days vs. 13 days, P = 0.736).Conclusions: Metabolic disturbances, characterized mainly by the presence of lowered SIDa, increased AG and hypoalbuminemia, are frequent in our population with apparent neutral acid-base balance based on pH and base excess. These changes on the morning after surgery are associated with increased length of stay.


2020 ◽  
Author(s):  
Joost Janssen ◽  
Joris M.K. van Fessem ◽  
Tijmen Ris ◽  
Robert Jan Stolker ◽  
Markus Klimek

Abstract Background The superiority of either the traditional or Stewart based approach to acid-base balance has focused primarily on analyzing metabolic acidemia, with little attention given to patients with neutral pH. In this study, we evaluate metabolic disturbances in patients in the immediate postoperative period focusing on patients with neutral pH, while comparing the Stewart and traditional approach. Methods We conducted a single center retrospective observational cohort study. Over a 17 month period, data on arterial blood gas analysis, electrolytes and albumin on the morning after surgery were retrieved from patients admitted to the postsurgical high dependency unit (HDU). Albumin corrected anion gap (AG), apparent (SIDa) and effective strong ion difference (SIDe) and strong ion gap (SIG) were calculated. Results Out of 1207 HDU admissions, 400 cases had a complete set of laboratory-data including albumin of which 281 presented with neutral pH (7.35 ≤ pH ≤ 7.45), 64 with acidemia (pH < 7.35) and 55 with alkalemia (pH > 7.45). In pH neutral patients the following acidifying disturbances were found: SIDa was lowered in 101 (36%), SIG was raised in 60 (21%). Base excess (BE) was decreased in 16 (6%) and corrected AG raised in 107 (38%). The alkalizing effect of hypoalbuminemia was present in 137 (49%). Out of 134 cases with normal BE and corrected AG, SIDa was lowered in 58 (43%). Out of 136 cases with normal SIDa and SIG, none had lowered BE and 28 increased AG (21%). Length of stay was significantly longer in patients with hypoalbuminemia, lowered SIDa and increased corrected AG, but not decreased BE (Hypoalbuminemia: 16 days vs. 10 days, P < 0.001. Low SIDa: 15 days vs. 12 days, P = 0.015. Increased AG: 16 days vs. 11 days, P < 0.001. Low BE: 14 days vs. 13 days, P = 0.736). Conclusions Metabolic disturbances, characterized mainly by the presence of lowered SIDa, increased AG and hypoalbuminemia, are frequent in our population with apparent neutral acid-base balance based on pH and base excess. These changes on the morning after surgery are associated with increased length of stay.


2017 ◽  
Vol 69 (3) ◽  
pp. 637-643 ◽  
Author(s):  
A.F. Sabes ◽  
A.M. Girardi ◽  
D. Zangirolami Filho ◽  
G.M. Bueno ◽  
J.A. Oliveira ◽  
...  

ABSTRACT This study aimed to investigate the changes in the acid-base balance of sheep with experimentally induced acute ruminal lactic acidosis (ARA). Ten ewes orally received 15 grams of sucrose per kilogram of body mass. Arterial blood samples for blood gas analysis were obtained at the following intervals: before the induction of ARA (control), and 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 48, 72, 96, 120 and 144 hours after sucrose administration. Urine samples for pH measurement were obtained at the following times: -15 days, -7 days, and immediately before sucrose administration, then at 24, 48, 72, 96, 120 and 144 hours. Thereafter, both blood and urine samples were obtained on the 2nd, 3rd, and 4th following weeks. From 4 hours after the induction, elevation of the pH, bicarbonate and base excess on the arterial blood was observed. After 12 hours, the animals showed a decrease of these parameters, as well as urine acidification, which are symptomatic of metabolic acidosis. Within 28 hours, all parameters were normalized except the base excess, which only returned to normal after 72 hours. Despite the occurrence of acidemia, there was no need for medication and no animals died.


2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Joost W. Janssen ◽  
Joris M. K. van Fessem ◽  
Tijmen Ris ◽  
Robert Jan Stolker ◽  
Markus Klimek

Abstract Background The superiority of either the traditional or Stewart based approach to acid-base balance has focused primarily on analyzing metabolic acidemia, with little attention given to patients with neutral pH. In this study, we evaluate metabolic disturbances in patients in the immediate postoperative period focusing on patients with neutral pH, while comparing the Stewart and traditional approach. Methods We conducted a single center retrospective observational cohort study. Over a 17-month period, data on arterial blood gas analysis, electrolytes, and albumin on the morning after surgery were retrieved from patients admitted to the postsurgical high dependency unit (HDU). Albumin-corrected anion gap (AG), apparent (SIDa) and effective strong ion difference (SIDe), and strong ion gap (SIG) were calculated. Results Out of 1207 HDU admissions, 400 cases had a complete set of laboratory-data including albumin of which 281 presented with neutral pH (7.35 ≤ pH ≤ 7.45), 64 with acidemia (pH < 7.35) and 55 with alkalemia (pH > 7.45). In pH neutral patients, the following acidifying disturbances were found: SIDa was lowered in 101 (36%), and SIG was raised in 60 (21%). Base excess (BE) was decreased in 16 (6%) and corrected AG raised in 107 (38%). The alkalizing effect of hypoalbuminemia was present in 137 (49%). Out of 134 cases with normal BE and corrected AG, SIDa was lowered in 58 (43%). Out of 136 cases with normal SIDa and SIG, none had lowered BE and 28 increased AG (21%). Length of stay was significantly longer in patients with hypoalbuminemia, lowered SIDa, and increased corrected AG, but not decreased BE (hypoalbuminemia: 16 days vs. 10 days, P < 0.001; low SIDa: 15 days vs. 12 days, P = 0.015; increased AG: 16 days vs. 11 days, P < 0.001; low BE: 14 days vs. 13 days, P = 0.736). Conclusions Metabolic disturbances, characterized mainly by the presence of lowered SIDa, increased AG, and hypoalbuminemia, are frequent in our population with apparent neutral acid-base balance based on pH and base excess. These changes on the morning after surgery are associated with increased length of stay.


1994 ◽  
Vol 77 (5) ◽  
pp. 2318-2324 ◽  
Author(s):  
S. M. Torrance ◽  
C. Wittnich

This study examines the neonatal response to graded hypoxia and determines the arterial PO2 (PaO2) threshold for oxygen-restricted metabolism as confirmed by the development of lactic acidosis and altered oxygen handling. Anesthetized, intubated, and ventilated 3-day-old pigs (n = 56) were randomly assigned to one of five predetermined acute (120 min) graded hypoxia groups: normoxia (PaO2 = 80 Torr) or mild (60 Torr), moderate (40 Torr), moderately severe (30 Torr), or severe (20 Torr) hypoxia. In moderate hypoxia, lactate and acid-base homeostasis were unaltered due to a significant increase in oxygen extraction (P < 0.05) that was sufficient to maintain the arteriovenous oxygen content difference (oxygen uptake). In moderately severe hypoxia, increased arterial lactate and decreased HCO3- and base excess were evidence of anaerobic metabolism, yet pH was unaltered, indicating adequate buffering. In this group, despite the increase in oxygen extraction, oxygen uptake was reduced, indicating the onset of oxygen-restricted metabolism. The severe hypoxia group had significantly increased lactate (21.7 +/- 3.9 mmol/l), decreased pH (7.01 +/- 0.07) and base excess (-21.5 +/- 3.0 mmol/l), and depletion of HCO3- (9.7 +/- 1.6 mmol/l) (P < 0.0001). Here, increases in oxygen extraction were severely limited by availability, resulting in significantly reduced oxygen uptake, anaerobic metabolism, and profound lactic acidosis.


2017 ◽  
Vol 30 (1) ◽  
pp. 68-72
Author(s):  
Naonori Kumagai ◽  
Hiroki Kudo ◽  
Takeshi Rikiishi ◽  
Makiko Nakayama ◽  
Toshinari Takahashi ◽  
...  

1996 ◽  
Vol 16 (1_suppl) ◽  
pp. 126-129 ◽  
Author(s):  
Mariano Feriani ◽  
Claudio Ronco ◽  
Giuseppe La Greca

Our objective is to investigate transperitoneal buffer fluxes with solution containing lactate and bicarbonate, and to compare the final effect on body base balance of the two solutions. One hundred and four exchanges, using different dwell times, were performed in 52 stable continuous ambulatory peritoneal dialysis (CAPD) patients. Dialysate effluent lactate and bicarbonate and volumes were measured. Net dialytic base gain was calculated. Patients’ acid-base status and plasma lactate were determined. In lactate-buffered CAPD solution, lactate concentration in dialysate effluent inversely correlated with length of dwell time, but did not correlate with plasma lactate concentration and net ultrafiltration. Bicarbonate concentration in dialysate effluent correlated with plasma bicarbonate and dwell time but not with ultrafiltration. The arithmetic sum of the lactate gain and bicarbonate loss yielded the net dialytic base gain. Ultrafiltration was the most important factor affecting net dialytic base gain. A previous study demonstrated that in patients using a bicarbonate-buffered solution the net bicarbonate gain is a function of dwell time, ultrafiltration, and plasma bicarbonate. By combining the predicted data of the dialytic base gain with the calculated metabolic acid production, an approximate body base balance could be obtained with both lactate and bicarbonate-buffered CAPD solutions. The body base balance in CAPD patients is self-regulated by the feedback between plasma bicarbonate concentration and dialytic base gain. The level of plasma bicarbonate is determined by the dialytic base gain and the metabolic acid production. This can explain the large interpatient variability in acid-base correction. Bicarbonate-buffered CAPD solution is equal to lactate solution in correcting acid-base disorders of CAPD patients.


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