Venous Bicarbonate Concentration Research Articles

915-P: Euglycemic Ketoacidosis in Type 1 Diabetes on an Automated Insulin Delivery System after Bariatric Surgery—A Case Series

Obesity is an increasing concern in patients with type 1 diabetes. Bariatric surgery is an effective option for weight loss and is associated with an improvement in metabolic complications. We report 2 cases of adults with type 1 diabetes using automated insulin delivery where laparoscopic sleeve gastrectomy was complicated post-operatively by euglycemic ketoacidosis. The first case was of a 28-year-old man using Control-IQ (HbA1c 7.3%, body mass index 40, and insulin requirements 0.98 Units/kg/day). His insulin requirements and carbohydrate intake decreased from 108 units and 208 grams respectively to 44 units and 8 grams during the preoperative liquid diet. His lack of carbohydrate consumption continued post-operatively. Two days after his surgery, he presented to the emergency department with nausea, where his glucose level was 12.8 mmol/L, venous pH level 7.30, venous bicarbonate concentration 20.9 mmol/L, and plasma beta-hydroxybutyrate 4.5 mmol/L. He was treated with intravenous hydration with supplementation dextrose with observation. The second case was of a 33-year-old woman using the MiniMed 770G (HbA1c 7.0%, body mass index 44, insulin requirements 0.4 units/kg/day). Post-operative day 16, she presented to the emergency department with nausea and vomiting. Her glucose level was 11.9 mmol/L venous pH was 7.31, venous bicarbonate was 17 mmol/L, and positive urinary ketones. Daily insulin requirements had reduced (from preoperatively to post-operatively) from 35.8 to 16.3 Units per day, with her carbohydrate intake from 86 to 33 grams. She was treated with intravenous insulin. Though euglycemic ketoacidosis is documented after bariatric surgery and starvation, automated insulin delivery (particularly unnoticed insulin changes) may have influenced glycemia and acidosis. Careful review of insulin administration, carbohydrate intake, and ketone monitoring is recommended in these cases. Disclosure M.Pasqua: None. M.Tsoukas: Speaker's Bureau; Novo Nordisk Canada Inc., Boehringer Ingelheim (Canada) Ltd., Eli Lilly and Company, Janssen Scientific Affairs, LLC, AstraZeneca, Sanofi. W.Hu: None.

Acetazolamide Reduces Blood Pressure and Sleep-Disordered Breathing in Patients With Hypertension and Obstructive Sleep Apnea: A Randomized Controlled Trial.

The carbonic anhydrase inhibitor acetazolamide (AZT) modulates blood pressure at high altitude and reduces sleep-disordered breathing in patients with obstructive sleep apnea (OSA). We aimed to investigate the treatment effect of AZT and in combination with continuous positive airway pressure (CPAP) on blood pressure in patients with hypertension and OSA. In a prospective, randomized, three-way crossover study, 13 male patients with hypertension and moderate to severe OSA (age 64 ± 7 years, body mass index 29 ± 4 kg/m2, and mean apnea-hypopnea index 37 ± 23 events/h) received AZT, CPAP, or AZT plus CPAP for 2-week periods. Antihypertensive medication was washed out. Office and 24-hour blood pressure, arterial stiffness, polygraphic sleep study data, and blood chemistry were compared. AZT alone and AZT plus CPAP, but not CPAP alone, reduced office mean arterial pressure compared to baseline (-7 [95% CI -11 to -4], -7 [95% CI -11 to -4] and -1 [95% CI -5 to 4] mmHg, respectively; repeated- measures analysis of variance (RM-ANOVA; P = .015). Aortic systolic pressure and augmentation index, assessed by radial artery oscillatory tonometry, were unaffected by CPAP but decreased after AZT and AZT plus CPAP (RM-ANOVA P = .030 and .031, respectively). The apnea-hypopnea index was significantly reduced in all three treatment arms, most prominently by AZT plus CPAP (RM-ANOVA P = .003). The reduction of venous bicarbonate concentration following AZT was correlated with the change of apnea-hypopnea index (r = 0.66, P = .013). AZT reduced blood pressure, vascular stiffness, and sleep-disordered breathing in patients with OSA and comorbid hypertension. Carbonic anhydrase inhibition may constitute a potential target for drug therapy in patients with sleep apnea and comorbid hypertension. Registry: ClinicalTrials.gov; Identifier: NCT02220803; Title: A Short Term Open, Randomized Cross-over Trial Exploring the Effect of Carbonic Anhydrase Inhibition by Acetazolamide on Sleep Apnea Associated Hypertension and Vascular Dysfunction; URL: https://clinicaltrials.gov/ct2/show/NCT02220803 and Registry: EU Clinical Trials Register; EudraCT Number: 2013-004866-33; Title: A short term open, randomized cross over trial exploring the effect of carbonic anhydrase inhibition by acetazolamide on sleep apnea associated hypertension; URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=2013-004866-33.

Prevalence of obesity hypoventilation syndrome in ambulatory obese patients attending pathology laboratories.

The prevalence of obesity hypoventilation syndrome (OHS) in the unselected obese is unknown. Our objectives were: (i) to determine the prevalence of OHS in ambulatory obese patients not previously referred to a pulmonologist for suspicion of sleep breathing disorders and (ii) to assess whether venous bicarbonate concentration [HCO3-v ] can be used to detect OHS. In this prospective multicentric study, we measured [HCO3-v ] in consenting obese patients attending pathology analysis laboratories. Patients with [HCO3-v ] ≥ 27 mmol/L were referred to a pulmonologist for comprehensive sleep and respiratory evaluations. Those with [HCO3-v ] < 27 mmol/L were randomized to either referral to a pulmonologist or ended the study. For the 1004 screened patients, the [HCO3-v ] was ≥27 mmol/L in 24.6% and <27 mmol/L in 45.9%. A total of 29.5% who had previously consulted a pulmonologist were excluded. A population of 241 obese patients underwent sleep and respiratory assessments. The prevalence of OHS in this population was 1.10 (95% CI = 0.51; 2.27). In multivariate analysis, PaCO2 , forced expiratory volume in 1 s (FEV1 ), apnoea-hypopnoea index (AHI), BMI, use of ≥3 anti-hypertensive drugs, anti-diabetics, proton pump inhibitors and/or paracetamol were related to raised [HCO3-v ]. The prevalence of OHS in our obese population was lower than previous estimations based on hospitalized patients or clinical cohorts with sleep breathing disorders. Apart from hypercapnia, increased [HCO3-v ] may also reflect multimorbidity and polypharmacy, which should be taken into account when using [HCO3-v ] to screen for OHS.

Chronic Kidney Disease in Cats and the Risk of Total Hypercalcemia.

BackgroundChronic kidney disease (CKD) is a common comorbidity in cats with hypercalcemia, but whether CKD is a risk factor for hypercalcemia is unclear. Hypercalcemia often is diagnosed based on total calcium concentration (tCa), which tends to underestimate the ionized calcium concentration (iCa) in cats.ObjectivesAssessment of the performance of tCa for the diagnosis of ionized hypercalcemia, and exploration of factors influencing the relationship between iCa and tCa. Determination of risk factors for incident total hypercalcemia (ie, the development of hypercalcemia based on tCa during follow‐up).AnimalsRecords of a cross‐section (n = 477) and observational cohort (n = 367) of client‐owned cats with and without azotemic CKD from first opinion practice.MethodsRetrospective cross‐sectional and retrospective cohort study. The diagnostic accuracy of tCa as an index test for ionized hypercalcemia was evaluated, and risk factors for underestimation were explored by binary logistic and linear regression in a cross‐section of cats with and without azotemic CKD. Chronic kidney disease and clinicopathological variables were assessed as predictors of incident total hypercalcemia by both time‐invariant and time‐dependent Cox regression in a cohort of cats.ResultsSpecificity of tCa for identification of ionized hypercalcemia was high (100%), but sensitivity was low. Underestimation was associated with lower venous bicarbonate concentrations. Cats with CKD had increased risk for incident total hypercalcemia (hazard ratio, 4.29; 95% confidence interval, 1.96–9.37; P < .001). Higher tCa predicted incident total hypercalcemia in both azotemic and nonazotemic cats (P < .001).Conclusions and Clinical ImportanceChronic kidney disease is a risk factor for incident total hypercalcemia, and most cats with increased tCa had concurrent ionized hypercalcemia. Higher baseline tCa predicts incident total hypercalcemia. Prospective studies assessing changes in iCa are warranted.

Venous Serum Bicarbonate Concentration Predicts Arterial pH in Adults with Diabetic Ketoacidosis

The initial assessment of metabolic acidosis in subjects with diabetic ketoacidosis (DKA) is arterial blood gas analysis. This process is expensive, painful, and technically difficult. Furthermore, blood gas analysis may not be available in some facilities, especially in developing countries where DKA-associated morbidity and mortality remain high. Therefore, we investigated the utility of venous bicarbonate concentration obtained from a basic metabolic panel in predicting arterial pH in adults with DKA. We performed a retrospective analysis of clinical and biochemical data of 396 adults admitted to 2 community teaching hospitals with DKA. We determined the correlation between arterial pH and venous serum parameters. Using multiple logistic regression, we obtained a predictive formula for arterial pH from serum venous bicarbonate level. The patient population was 59.0% male and had a mean age of 36.7 ± 13.3 years. We derived that arterial pH = 6.97 + (0.0163 x bicarbonate), and by applying this equation, we determined that serum venous bicarbonate concentration of ≤20.6 mEq/L predicted arterial pH ≤7.3 with over 95% sensitivity and 92% accuracy. Venous serum bicarbonate obtained from the basic metabolic panel is an affordable and reliable way of estimating arterial pH in adults with DKA. Validation of this formula in a prospective study would offer a more accessible means of estimating metabolic acidosis in adults with DKA, especially in developing countries where DKA incidence and mortality remain high.

Effects of Hyperventilation on Venous-Arterial Bicarbonate Concentration Difference: A Possible Pitfall in Venous Blood Gas Analysis

Objectives: Recent reports on venous blood gas analysis have shown that venous bicarbonate concentration is useful in the evaluation of the body acid-base status. Most of these reports have been based on the Bland-Altman analysis comparing arterial and venous blood gas values. We intended to elucidate any factors that decrease the agreement between venous and arterial bicarbonate concentrations, which might impair the usefulness of venous blood gas analysis. Methods: Healthy volunteers and patients with various diseases (n = 141) were evaluated by simultaneous arterial and venous blood sampling and Bland-Altman analysis. The venous-arterial bicarbonate concentration difference was compared between healthy volunteers and untreated respiratory alkalosis patients. Intentional hyperventilation (30 or 60 breaths/min, for 3 min) was also performed on 6 healthy volunteers and the venous-arterial bicarbonate concentration difference was evaluated. Results: The relative average bias in bicarbonate concentration was 2.00 mEq/l with venous bicarbonate higher than arterial bicarbonate with 95% limits of agreement of ±4.15 mEq/l. Hyperventilation challenges increased the venous-arterial bicarbonate concentration difference in an intensity-dependent manner. The venous-arterial bicarbonate concentration difference was higher in untreated respiratory alkalosis patients than in healthy volunteers (P Conclusion: Although venous bicarbonate may be useful to evaluate the body acid-base status, hyperventilation increases the venous-arterial bicarbonate concentration difference. Physicians should keep this phenomenon in mind.

Higher Venous Bicarbonate Concentration Associated with Hypoxemia, not Acute Mountain Sickness, after Ascent to Moderate Altitude

The pathophysiology underlying acute mountain sickness (AMS) and excessive hypoxemia at high altitudes is not fully understood. Previous work by our group has demonstrated a significant association between urinary measures of dehydration and bicarbonate retention in subjects developing excessive hypoxemia and AMS at high altitudes. To further characterize these findings, we returned to our original testing site to examine the hypothesis that subjects with lower levels of oxygen saturation and/or AMS would possess higher levels of venous bicarbonate. Medical history inquiry, clinical examination, Lake Louise scoring, and the collection of venous levels of bicarbonate concentration and base excess were performed on 52 lowland-dwelling persons after they completed a religious pilgrimage in the Nepal Himalayas to approximately 4,250 m. Oxygen saturation levels were strongly and inversely correlated with serum levels of venous bicarbonate and base excess, whereas AMS and Lake Louise scores were not associated with these measures of alkalosis. Our data suggest an association between measures of serum bicarbonate anion retention and decreasing oxygen saturation. Our data do not demonstrate an association between AMS or Lake Louise scores and measures of serum bicarbonate level. We propose that excessive hypoxemia at high altitudes may be associated with a compromised ability of the kidney to metabolically compensate for an altitude-induced hypocapnic alkalosis.

Hormone Replacement Therapy Causes a Respiratory Alkalosis in Normal Postmenopausal Women1

Menopause is associated with an increase in venous bicarbonate concentrations that is reversible with hormone replacement therapy (HRT). However, the mechanism underlying this effect is not known. To address this question, we studied the changes in acid-base indexes in the arterialized venous blood of normal postmenopausal women commencing conjugated equine estrogen (0.625 mg/day), medroxyprogesterone acetate (MPA; 5 mg/day), their combination, or placebo, in a double blind randomized controlled study over 3 months. Serum bicarbonate concentrations decreased significantly in the groups receiving either MPA or estrogen plus MPA (P = 0.008). This trend was apparent as early as 2 days and reached 2.7 and 2.3 mmol/L in the respective groups by 3 months. Similar changes were seen with partial pressure of carbon dioxide (P = 0.04); a change of -0.7 kPa occurred in the estrogen plus MPA group at 3 months. There were no changes in bicarbonate concentrations or partial pressure of carbon dioxide in those receiving estrogen alone or placebo. Accompanying changes in blood pH were apparent in the estrogen plus MPA group, where there was an upward trend at 1 week (P = 0.056) and a significant change from baseline (+0.013) at 3 months (P = 0.03). In the whole group, the changes in pH were inversely correlated with those in urinary excretion of hydroxyproline (r = -0.44; P = 0.01). We conclude that HRT using conjugated estrogens and MPA produces small, but sustained, changes in acid-base status. These may contribute to the effects of HRT and menopause on many tissues and disease processes, including the development of osteoporosis.

Clinical Evaluation of a Peritoneal Dialysis Solution with 33 mmol/L Bicarbonate

To evaluate the efficacy and safety of a new peritoneal dialysis solution with 33 mmol/L bicarbonate. In an acute, prospective, randomized cross-over study, 8 patients were randomized in two groups of 4. On the first study day, the first group performed two consecutive 4-hour exchanges with a dialysis solution containing 35 mmol/L lactate: the first exchange with 13.6 g/L and the second with 38.6 g/L dextrose. On the second study day, the same type of exchanges were performed with bicarbonate. The second group underwent the same treatment, but used bicarbonate solutions on the first day and control solutions on the second study day. Thirty-three patients participated in a 2-month prospective and randomized study. After a 4-week baseline period using solutions containing 40 mmol/L lactate, the patients were dialyzed with either 33 mmol/L bicarbonate solutions or 40 mmol/L lactate solutions. Peritoneal dialysis units at the University Hospital of Brescia and the Niguarda Hospital of Milan, Italy. Acute study: Control and bicarbonate solutions had similar effects on blood chemistries and peritoneal transport. Chronic study: Mean venous bicarbonate concentrations remained unchanged in the control group (26.6-27.2 mmol/L), but decreased significantly in the bicarbonate group from 28.8 mmol/L at the start of the study to 23.0 mmol/L after 2 months of bicarbonate administration. Other biochemical parameters remained unchanged. A peritoneal dialysis solution with a bicarbonate level of 33 mmol/L does not adequately correct uremic acidosis.

Necrotizing enterocolitis in horses: a retrospective study.

The clinical and clinicopathologic characteristics of fatal necrotizing enterocolitis were examined in 16 horses (age 4 months to 12 years). At initial presentation, 8 of 16 horses were pyrexic (median temperature, 38.4 degrees C; range, 33.8 to 40.6 degrees C); all 16 were tachycardic (median heart rate, 93 bpm, range, 66 to 138 bpm); 13 of 16 were tachypneic (median heart rate, 36 bpm, range, 16 to 80 bpm), dehydrated, and had discolored mucous membranes. All horses that were pyrexic were also tachycardic and tachypneic. PCV was high (> 45%) in 14 horses. Six horses were leukopenic (< 5,000 cells/microL); 12 were neutropenic (< 2,300 cells/microL), and 14 had > 100 band neutrophils/microL. Twelve horses were acidemic (pH < 7.37; range, 6.88 to 7.33) and the venous bicarbonate concentration was low (< 23 mEq/L) in 14 horses. Median anion gap in 16 horses was 31.5 mEq/L (> 15 mEq/L in 15 horses). Eleven of 16 horses were hyponatremic (< 137 mEq/L), 1 horse was hypernatremic (> 143 mEq/L), 3 were hypokalemic (< 3.2 mEq/L), 6 were hyperkalemic (> 4.5 mEq/L), and 14 were hypochloremic (< 98 mEq/L). Serum creatinine concentrations were high (> 1.4 mg/dL) in 15 horses. Abdominal fluid was examined in 12 horses 4 had total protein concentrations > 2.5 g/dL and 6 had nucleated cell counts > 5,000/ microL and < 10,000/microL; none had > 10,000/microL. Eight of 12 samples revealed a nondegenerate neutrophilia (> 50%). Abdominal fluid collected from 4 horses immediately before death was normal in 2 horses and indicative of suppurative inflammation in 2. All 8 horses tested had low or nonexistent serum immunofluorescent antibody titers to Ehrlichia risticii. Four of 16 horses had Salmonella spp isolated from feces or tissues. All 16 horses either died (5 of 16; 31%) or were euthanized because of a grave prognosis. Median time to death was 45.5 hours (range, 7 to 113 hours) from the time of admission. Death was preceded by severe abdominal pain in 14 horses. Fatal necrotizing enterocolitis of horses is characterized by a brief course, profound dehydration, electrolyte derangements, acid-base abnormalities, and terminally, severe abdominal pain. Abdominal fluid analysis was frequently not indicative of the severity of disease.

Arterial and mixed venous acid‐base status in patients with cirrhosis. Influence of liver failure

Although it has been established that liver failure is associated with arterial hypocapnia and alkalaemia (i.e., respiratory alkalosis), the influence of liver failure on mixed venous acid-base status has not yet been studied. Thus, arterial and mixed venous acid-base status were simultaneously measured in controls and in a large series of patients with cirrhosis. Grade B patients (n = 28) or Grade C patients (n = 21) had significantly lower arterial and mixed venous carbon dioxide tensions than controls (n = 29). Grade B or Grade C patients also had significantly higher arterial, mixed venous pH, and lower mixed venous bicarbonate concentrations than controls. Among Grade A patients (n = 27), those with the lowest Pugh's score (i.e., equal to five) had significantly lower mixed venous carbon dioxide tension than controls. The other arterial and mixed venous acid-base values did not differ significantly between Grade A patients with the lowest Pugh's score and controls. Grade A patients with a Pugh's score equal to six and Grade B patients had similar acid-base disorders. No significant differences were found between groups concerning the anion gap and plasma chloride concentrations. In conclusion, this study shows that in Grade B or C patients, respiratory alkalosis was responsible for mixed venous hypocapnia, alkalaemia and hypobicarbonataemia. In addition, in Grade A patients with the lowest Pugh's score (equal to five), analysis of arterial and mixed venous blood revealed that mixed venous hypocapnia was the sole anomaly of the acid-base status. This last finding suggests that mixed venous hypocapnia might be an early event preceding the onset of arterial hypocapnia.

Prediction of acute renal failure following soft-tissue injury using the venous bicarbonate concentration.

Sixty-four patients with soft-tissue injuries were studied prospectively to determine whether an initial venous bicarbonate concentration (VBC) of less than 17 mmol/L would predict the development of myoglobin-induced acute renal failure. The VBC was > 17 mmol/L in 59 patients, seven of whom had myoglobinuria. All recovered without renal complications. The remaining five patients all had VBC < 17 mmol/L and four had myoglobinuria. Acute renal failure developed in four patients (p < 0.001). The VBC on hospital arrival was the most accurate predictor of these patients' risk for the development of acute renal failure following soft-tissue injury.

Renal involvement in patients with primary Sjögren's syndrome.

Among the renal manifestations of Sjogren’s syndrome (SS), chronic tubulointerstitial nephritis (CTN) is the most common histopathological lesion. It presents clinically as renal tubular acidosis (RTA) and hyposthenuria (1-3). In contrast to the tubular changes, glomerulonephritis is a rare complication of the disease (4). Most published studies discuss the kidney involvement in primary and secondary SS together. In two studies, renal lesions were revealed in about a quarter of patients with primary SS (5, 6). We present here our observations on the renal manifestations in our primary SS patients. PATIENTS AND METHODS Sixty-five primary SS patients with extraglandular symptoms (63 women and 2 men) were followed up for a mean period of 6.2 years. All of them met the criteria for primary SS. They came from an area with I .9 million inhabitants. For the diagnosis of keratoconjunctivitis sicca and xerostomia, the Copenhagen criteria (7) were used with two modifications: parotid gland flow rate stimulated with 2% citric acid solution (abnormal if 61.5 mVlO min) was measured, and parotid gland scintigraphy or sialography was performed. Throughout the follow-up period, serum electrolytes, urea nitrogen, creatinine, urine analysis and urine cultures in the case of leukocyturia were tested in all patients. In the presence of proteinuria, with or without haematuria or systemic acidosis, further examinations were carried out. An acute oral ammonium chloride loading test with 0.1 g NH4Cl/kg body weight was carried out on 10 patients with acidaemia, and on I5 patients without evidence of renal involvement as controls (8). Urinary pH (electric pH meter), ammonia excretion (direct Berthelot method, normal range: -1 OOO md24 h) and titratable acidity (normal range: 2040 mmH+/24 h) were measured. Before and 5 h after the ingestion of the drug, blood gasometric analysis was carried out. To determine the RTA type, a bicarbonate loading test was applied and 0.125 g NaHCO,/kg body weight was given in infusion for 2 h. Venous bicarbonate concentrations were determined at the beginning and IS, 45, 75, 105 and 180 min after the beginning of the infusion. Urinary pH and bicarbonate excretion were measured at the beginning and 30, 60, 90, 120 and 180 min later (9, 10). Statistics The results were evaluated statistically by the two-tailed Student’s t-test.

Ventilatory responses to hypercapnia and hypoxia during continuous aspirin ingestion.

Hypercapnic and hypoxic ventilatory responses were serially measured in nine normal subjects given 3.9 g aspirin (ASA) per day for 9 days. Minute ventilation (VE), end-tidal carbon dioxide tension (PETCO2), venous bicarbonate concentration [HCO3-], oxygen consumption (VO2), hypercapnic ventilatory response (deltaVE/deltaPCO2), and isocapnic hypoxic ventilatory response (A) were determined before, 2 h after the first dose, and at 72-h intervals during the next 14 days. Serum salicylate levels averaged 18.6 +/- 2.0 mg/dl. VE increased (P less than 0.05, PETCO2 decreased (P less than 0.05), and [HCO3-] did not change significantly during drug ingestion. deltaVE/deltaPCO2 increased gradually to a value 37% greater than control by day 3 and remained constant (P less 0.01). A increased by 251% and VO2 by 18% within 2 h and remained constant for the remainder of the ASA period (P less than 0.01). All values returned to base line within 24 h following cessation of ASA. We conclude that during continuous ASA ingestion there is a gradual increase of hypercapnic ventilatory response. This may reflect slow entrance of ASA into the central nervous system. In contrast, there is a rapid rise in hypoxic ventilatory response which may be mechanically linked to changes in metabolic rate.