Intravenous Infusion Of Sodium Bicarbonate Research Articles

Mechanisms Underlying the Stimulatory Effect of Inhaled Sulfur Dioxide on Rat Vagal Bronchopulmonary Sensory Nerves

Chronic exposure to sulfur dioxide (SO2), an air pollutant, can cause airway injury and lung diseases. Acute exposure to SO2 triggers cough and reflex bronchoconstriction, indicating a stimulatory effect of SO2 on airway sensory nerves. Indeed, a recent study in our lab has demonstrated that vagal bronchopulmonary C‐fibers are the primary target of inhaled SO2. This study was carried out to investigate the underlying mechanism of this stimulatory effect of SO2 on bronchopulmonary C‐fibers. Our results showed: 1) Inhalation of SO2 (1,000–2,000 ppm, 10 breaths) evoked a pronounced and reproducible stimulatory effect on pulmonary C‐fibers in anesthetized rats. 2) Pretreatment with an intravenous infusion of sodium bicarbonate (120 μmol/kg) raised the baseline arterial pH by 0.08 units, which profoundly diminished the stimulatory effect of SO2 on pulmonary C‐fibers by 83.9%. 3) This stimulatory effect of SO2 was also significantly attenuated by a pretreatment with amiloride (a blocker of acid‐sensing ion channels, ASICs; 11 μmol/kg) alone (Δ = 70.7%); AMG9810 (an antagonist of transient receptor potential vanilloid type‐1, TRPV1; 10 μmol/kg) alone (Δ = 76.7%); and by a combination of amiloride and AMG9810 (Δ = 91.4%). 4) To further investigate if this stimulatory effect is generated by a direct action of SO2 on sensory nerves, the change in intracellular Ca2+ concentration, [Ca2+]i, was measured in isolated rat vagal pulmonary sensory neurons. Perfusion with extracellular fluid saturated with SO2 (1,000 and 2,000 ppm) evoked a significant increase in [Ca2+]i in a concentration‐dependent manner in these neurons, and these responses to SO2 were markedly suppressed by a combined pretreatment with amiloride and AMG9810. 5) In addition, inhalation of SO2 (300 and 600 ppm for 5 min) evoked cough reflex responses consistently in awake mice in a concentration‐dependent manner; the cough responses were almost completely prevented by a pretreatment with amiloride aerosol inhalation (5 mM for 4 min) in TRPV1‐knockout mice. In conclusion, this study suggested that inhalation of SO2 lowered the pH in airway/lung tissues, which exerted a stimulatory effect on vagal bronchopulmonary C‐fibers by activating both ASICs and TRPV1 channels.Support or Funding InformationNIH grants AI123832 & UL1TR001998This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Sodium bicarbonate therapy for patients with severe metabolic acidaemia in the intensive care unit (BICAR-ICU): a multicentre, open-label, randomised controlled, phase 3 trial

Acute acidaemia is frequently observed during critical illness. Sodium bicarbonate infusion for the treatment of severe metabolic acidaemia is a possible treatment option but remains controversial, as no studies to date have examined its effect on clinical outcomes. Therefore, we aimed to evaluate whether sodium bicarbonate infusion would improve these outcomes in critically ill patients. We did a multicentre, open-label, randomised controlled, phase 3 trial. Local investigators screened eligible patients from 26 intensive care units (ICUs) in France. We included adult patients (aged ≥18 years) who were admitted within 48 h to the ICU with severe acidaemia (pH ≤7·20, PaCO2 ≤45 mm Hg, and sodium bicarbonate concentration ≤20 mmol/L) and with a total Sequential Organ Failure Assessment score of 4 or more or an arterial lactate concentration of 2 mmol/L or more. We randomly assigned patients (1:1), by stratified randomisation with minimisation via a restricted web platform, to receive either no sodium bicarbonate (control group) or 4·2% of intravenous sodium bicarbonate infusion (bicarbonate group) to maintain the arterial pH above 7·30. Our protocol recommended that the volume of each infusion should be within the range of 125-250 mL in 30 min, with a maximum of 1000 mL within 24 h after inclusion. Randomisation criteria were stratified among three prespecified strata: age, sepsis status, and the Acute Kidney Injury Network (AKIN) score. The primary outcome was a composite of death from any cause by day 28 and the presence of at least one organ failure at day 7. All analyses were done on data from the intention-to-treat population, which included all patients who underwent randomisation. This study is registered with ClinicalTrials.gov, number NCT02476253. Between May 5, 2015, and May 7, 2017, we enrolled 389 patients into the intention-to-treat analysis in the overall population (194 in the control group and 195 in the bicarbonate group). The primary outcome occurred in 138 (71%) of 194 patients in the control group and 128 (66%) of 195 in the bicarbonate group (absolute difference estimate -5·5%, 95% CI -15·2 to 4·2; p=0·24). The Kaplan-Meier method estimate of the probability of survival at day 28 between the control group and bicarbonate group was not significant (46% [95% CI 40-54] vs 55% [49-63]; p=0·09. In the prespecified AKIN stratum of patients with a score of 2 or 3, the Kaplan-Meier method estimate of survival by day 28 between the control group and bicarbonate group was significant (37% [95% CI 28-48] vs 54% [45-65]; p=0·0283). [corrected] Metabolic alkalosis, hypernatraemia, and hypocalcaemia were observed more frequently in the bicarbonate group than in the control group, with no life-threatening complications reported. In patients with severe metabolic acidaemia, sodium bicarbonate had no effect on the primary composite outcome. However, sodium bicarbonate decreased the primary composite outcome and day 28 mortality in the a-priori defined stratum of patients with acute kidney injury. French Ministry of Health and the Société Française d'Anesthésie Réanimation.

Sodium Bicarbonate and Renal Function After Cardiac Surgery

BACKGROUND: The effect of urinary alkalinization in cardiac surgery patients at risk of acute kidney injury (AKI) is controversial and trial findings conflicting. Accordingly, the authors performed a prospectively planned individual patient data meta-analysis of the double-blind randomized trials in this field. METHODS: The authors studied 877 patients from three double-blind, randomized controlled trials enrolled to receive either 24 h of intravenous infusion of sodium bicarbonate or sodium chloride. The primary outcome measure was a postoperative increase in serum creatinine concentration of greater than 25% or 0.5 mg/dl (> 44 μM/L) within the first five postoperative days. Secondary outcomes included the raw change in serum creatinine, greater than 50% and greater than 100% rises in serum creatinine, developing AKI (Acute Kidney Injury Network criteria), initiation of renal replacement therapy, morbidity, and mortality. RESULTS: Patients were similar in demographics, comorbidities, and cardiac procedures. Sodium bicarbonate increased plasma bicarbonate (P < 0.001) and urine pH (P < 0.001). There were no differences in the development of the primary outcome (Bicarbonate 45% [39-51%] vs. Saline 42% [36-48%], P = 0.29). This result remained unchanged when controlling for study and covariates (odds ratio [OR], 99% confidence interval [CI]: Bicarbonate vs. Control, 1.11 [0.77-1.60], P = 0.45). There was, however, a significant study-adjusted benefit in elective coronary artery bypass surgery patients in terms of renal replacement therapy (Bicarbonate vs. Control, OR: 0.38 [99% CI: 0.25-0.58], P < 0.0001) and the development of an Acute Kidney Injury Network grade = 3 (Bicarbonate vs. Control, OR: 0.45 [99% CI: 0.43-0.48], P < 0.0001). CONCLUSIONS: Urinary alkalinization using sodium bicarbonate infusion is not associated with an overall lower incidence of AKI; however, it reduces severe AKI and need for renal replacement therapy in elective coronary artery bypass patients.

Sodium bicarbonate and renal function after cardiac surgery: a prospectively planned individual patient meta-analysis.

The effect of urinary alkalinization in cardiac surgery patients at risk of acute kidney injury (AKI) is controversial and trial findings conflicting. Accordingly, the authors performed a prospectively planned individual patient data meta-analysis of the double-blind randomized trials in this field. The authors studied 877 patients from three double-blind, randomized controlled trials enrolled to receive either 24 h of intravenous infusion of sodium bicarbonate or sodium chloride. The primary outcome measure was a postoperative increase in serum creatinine concentration of greater than 25% or 0.5 mg/dl (> 44 μM/L) within the first five postoperative days. Secondary outcomes included the raw change in serum creatinine, greater than 50% and greater than 100% rises in serum creatinine, developing AKI (Acute Kidney Injury Network criteria), initiation of renal replacement therapy, morbidity, and mortality. Patients were similar in demographics, comorbidities, and cardiac procedures. Sodium bicarbonate increased plasma bicarbonate (P < 0.001) and urine pH (P < 0.001). There were no differences in the development of the primary outcome (Bicarbonate 45% [39-51%] vs. Saline 42% [36-48%], P = 0.29). This result remained unchanged when controlling for study and covariates (odds ratio [OR], 99% confidence interval [CI]: Bicarbonate vs. Control, 1.11 [0.77-1.60], P = 0.45). There was, however, a significant study-adjusted benefit in elective coronary artery bypass surgery patients in terms of renal replacement therapy (Bicarbonate vs. Control, OR: 0.38 [99% CI: 0.25-0.58], P < 0.0001) and the development of an Acute Kidney Injury Network grade = 3 (Bicarbonate vs. Control, OR: 0.45 [99% CI: 0.43-0.48], P < 0.0001). Urinary alkalinization using sodium bicarbonate infusion is not associated with an overall lower incidence of AKI; however, it reduces severe AKI and need for renal replacement therapy in elective coronary artery bypass patients.

Prophylactic Perioperative Sodium Bicarbonate to Prevent Acute Kidney Injury Following Open Heart Surgery: A Multicenter Double-Blinded Randomized Controlled Trial

Preliminary evidence suggests a nephroprotective effect of urinary alkalinization in patients at risk of acute kidney injury. In this study, we tested whether prophylactic bicarbonate-based infusion reduces the incidence of acute kidney injury and tubular damage in patients undergoing open heart surgery. In a multicenter, double-blinded (patients, clinical and research personnel), randomized controlled trial we enrolled 350 adult patients undergoing open heart surgery with the use of cardiopulmonary bypass. At induction of anesthesia, patients received either 24 hours of intravenous infusion of sodium bicarbonate (5.1 mmol/kg) or sodium chloride (5.1 mmol/kg). The primary endpoint was the proportion of patients developing acute kidney injury. Secondary endpoints included the magnitude of acute tubular damage as measured by urinary neutrophil gelatinase-associated lipocalin (NGAL), initiation of acute renal replacement therapy, and mortality. The study was stopped early under recommendation of the Data Safety and Monitoring Committee because interim analysis suggested likely lack of efficacy and possible harm. Groups were non-significantly different at baseline except that a greater proportion of patients in the sodium bicarbonate group (66/174 [38%]) presented with preoperative chronic kidney disease compared to control (44/176 [25%]; p = 0.009). Sodium bicarbonate increased urinary pH (from 6.0 to 7.5, p<0.001). More patients receiving bicarbonate (83/174 [47.7%]) developed acute kidney injury compared with control patients (64/176 [36.4%], odds ratio [OR] 1.60 [95% CI 1.04-2.45]; unadjusted p = 0.032). After multivariable adjustment, a non-significant unfavorable group difference affecting patients receiving sodium bicarbonate was found for the primary endpoint (OR 1.45 [0.90-2.33], p = 0.120]). A greater postoperative increase in urinary NGAL in patients receiving bicarbonate infusion was observed compared to control patients (p = 0.011). The incidence of postoperative renal replacement therapy was similar but hospital mortality was increased in patients receiving sodium bicarbonate compared with control (11/174 [6.3%] versus 3/176 [1.7%], OR 3.89 [1.07-14.2], p = 0.031). Urinary alkalinization using sodium bicarbonate infusion was not found to reduce the incidence of acute kidney injury or attenuate tubular damage following open heart surgery; however, it was associated with a possible increase in mortality. On the basis of these findings we do not recommend the prophylactic use of sodium bicarbonate infusion to reduce the risk of acute kidney injury. Discontinuation of growing implementation of this therapy in this setting seems to be justified. ClinicalTrials.gov NCT00672334 Please see later in the article for the Editors' Summary.

Crack Cocaine-Induced Cardiac Conduction Abnormalities Are Reversed by Sodium Bicarbonate Infusion

We report a dramatic case of a 19-year-old man with crack cocaine overdose with important clinical complications as cardiac arrest due to ventricular fibrillation and epileptics status. During this intoxication, electrocardiographic abnormalities similar to those found in tricyclic antidepressant poisoning were observed, and they were reversed by intravenous sodium bicarbonate infusion.

Bilateral ureter stones in a 1-year-old boy

Sirs, We have read with great interest the study by Spivacow et al. regarding metabolic risk factors in children with kidney stone disease [1]. The authors found biochemical abnormalities in 84.4% of 90 children, with hypercalciuria and hypocituria being the two most common causes. This high incidence of biochemical abnormalities matched with results reported in previous studies [2, 3] that had recommended screening for metabolic abnormalities in pediatric urolithiasis even in patients with documented urinary tract anomalies. A urinary tract anomaly has long been considered a predisposing condition for the formation of calculi, with the associated urinary stasis considered to promote crystal retention and stone formation. However, several recent reports have questioned this theory and have suggested that, in patients with urinary tract anomalies, stone formation is caused by underlying metabolic abnormalities [4, 5]. We would like to present a case which demonstrates the difficulty of immediate diagnosis of stone pathogenesis in patients with urinary tract abnormalities. We describe here a case of bilateral ureter stones in a 1-year-old boy in whom tortuosities of both ureters was observed. A 1-year-old boy was referred to our hospital because of diarrhea and oliguria. The boy was delivered uneventfully at 38 weeks of gestation and had a birth weight of 3190 g. Prenatal ultrasonography during the second trimester of pregnancy did not reveal any abnormalities, and a family history of stone disease in first-degree relatives was denied. Upon referral, the boy had been lethargic and anuric for 10 h after having had watery diarrhea for the previous 7 days. The results of blood analyses were as follows: tCO2, 12 mEq/L; blood urea nitrogen, 16.3 mg/dL; creatinine, 0.7 mg/dL. Urinalysis was not performed because of the anuria, which persisted despite isotonic saline infusion. At the 12-h follow-up examination, serum creatinine had increased to 1.1 mg/dL, and the acidosis persisted (pH 7.249; tCO2 13.7 mEq/L). Renal ultrasonography revealed hydronephrosis, and nonenhanced computed tomography showed bilateral proximal ureter stones with moderate attenuation. Percutaneous nephrostomy (PCN) of both kidneys using a 6-Fr pigtail catheter was performed to relieve the ureteral obstruction, and alkalinization of urine with an intravenous sodium bicarbonate infusion was initiated on hospital day (HD) 2. After the PCN procedure, serum creatinine level dropped rapidly from 1.9 to 0.8 mg/dL, and urinary flow through a Foley catheter was observed on HD 3. Antegrade pyelography (AGP) via a PCN catheter on HD 7 confirmed that both ureters were fluent and that calculi were absent, but it also revealed tortuosities of both ureters at the ureteropelvic junction. As the ureter calculi were lysed during alkalinization, stone analysis could not be conducted. Urine drained from the renal pelvis at the time of catheter insertion was acidic (pH 5.5), and there was a high ratio of uric Pediatr Nephrol (2009) 24:2077–2078 DOI 10.1007/s00467-009-1182-1

Sodium bicarbonate to prevent increases in serum creatinine after cardiac surgery: A pilot double-blind, randomized controlled trial*

To test whether perioperative sodium bicarbonate infusion can attenuate postoperative increases in serum creatinine in cardiac surgical patients. Double-blind, randomized controlled trial. Operating rooms and intensive care unit at a tertiary hospital. Cohort of 100 cardiac surgical patients at increased risk of postoperative acute renal dysfunction. Patients were randomized to either 24 hrs of intravenous infusion of sodium bicarbonate (4 mmol/kg) or sodium chloride (4 mmol/kg). The primary outcome measure was the proportion of patients developing acute renal dysfunction defined as a postoperative increase in plasma creatinine concentration >25% of baseline within the first five postoperative days. Secondary outcomes included changes in plasma creatinine, plasma urea, urinary neutrophil gelatinase-associated lipocalin, and urinary neutrophil gelatinase-associated lipocalin/urinary creatinine ratio. Patients were well balanced for baseline characteristics. Sodium bicarbonate infusion increased plasma bicarbonate concentration (p < 0.001), base excess (p < 0.001), plasma pH (p < 0.001), and urine pH (p < 0.001). Fewer patients in the sodium bicarbonate group (16 of 50) developed a postoperative increase in serum creatinine compared with control (26 of 50) (odds ratio 0.43 [95% confidence interval 0.19-0.98]), (p = 0.043). The increase in plasma creatinine, plasma urea, urinary neutrophil gelatinase-associated lipocalin, and urinary neutrophil gelatinase-associated lipocalin/urinary creatinine ratio was less in patients receiving sodium bicarbonate, (p = 0.014; p = 0.047; p = 0.009; p = 0.004). There were no significant side effects. Sodium bicarbonate loading and continuous infusion was associated with a lower incidence of acute renal dysfunction in cardiac surgical patients undergoing cardiopulmonary bypass. The findings of this pilot study justify further investigation. (ClinicalTrials.gov, NCT00334191).

Bicarbonate infusion and pH clamp moderately reduce hyperventilation during ramp exercise in humans

To test the hypothesis that the decrease in plasma pH contributes to the hyperventilation observed in humans in response to exercise at high workloads, five healthy male subjects performed a ramp exercise [maximal workload: 352 W (SD 35)] in a control situation and when arterialized plasma pH was maintained at the resting level (pH clamp) by intravenous infusion of sodium bicarbonate [129 mmol (SD 23), beginning at 59% maximal workload (SD 5)]. Bicarbonate infusion did not modify O(2) consumption (Vo(2)) but significantly (P < 0.05) increased arterial Pco(2), plasma bicarbonate concentration, and respiratory exchange ratio (P < 0.05). At the three highest workloads, pulmonary ventilation (Ve) and Ve/Vo(2) were approximately 5-10% lower (P < 0.05) when bicarbonate was infused than in the control situation, and hyperventilation was reduced by 15-30%. These data suggest that the decrease in plasma pH is one of the factors that contribute to the hyperventilation observed at high workloads.

Sodium bicarbonate infusion during resuscitation of infants at birth

For many years, intravenous sodium bicarbonate has been used to reverse acidosis during newborn resuscitation. However, controversy surrounds its use. Most of the evidence has been derived from studies in animals, adult humans, or in uncontrolled, descriptive experiments. Despite the lack of evidence from the human neonatal population and concerns about its safety, some international resuscitation guidelines still recommend the use of sodium bicarbonate in resuscitation of the newborn. To determine whether an intravenous infusion of sodium bicarbonate, compared to placebo or no treatment, reduces mortality and morbidity (in particular regarding neurodevelopmental outcome) in infants receiving resuscitation in the delivery room at birth. We used the standard search strategy of the Cochrane Neonatal Review Group. Searches were conducted of the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 3, 2005), MEDLINE (1966 - September 2005), EMBASE (1980 - September 2005) and CINAHL (1982 - September 2005) and Pediatric Research (1987 - September 2005). Unpublished trials were sought by handsearching the conference proceedings of American Pediatric Society/Society for Pediatric Research (1990 - 2005) and European Society for Paediatric Research (1993 - 2005). Randomised or quasi-randomised controlled trials of newborn infants receiving sodium bicarbonate infusion during any resuscitation in the delivery room at birth. Two review authors independently assessed trial quality and extracted data. Study authors were contacted for additional information. We found one randomised controlled trial that fulfilled the eligibility criteria (Lokesh 2004) that compared treating asphyxiated newborn infants (infants continuing to need positive pressure ventilation at 5 minutes after birth) with sodium bicarbonate infusion (N = 27) versus 5% dextrose (N = 28). They found no evidence of an effect on mortality prior to discharge [Relative risk 1.04 (95% confidence interval 0.49 to 2.21)], abnormal neurological examination at discharge [Relative risk 0.86 (95% confidence interval 0.30 to 2.50)] or a composite outcome of death or abnormal neurological examination at discharge [Relative risk 0.97 (95% confidence interval 0.59 to 1.60)]. There was no statistically significant difference in the incidence of encephalopathy [Relative risk 1.30 (95% confidence interval 0.88 to 1.92)], intraventricular haemorrhage [Relative risk 1.04 (95% confidence interval 0.23 to 4.70)] and neonatal seizures [Relative risk 1.19 (95% confidence interval 0.50 to 2.82)]. No long term neurodevelopmental outcomes were assessed. There is insufficient evidence from randomised controlled trials to determine whether the infusion of sodium bicarbonate reduces mortality and morbidity in infants receiving resuscitation in the delivery room at birth.

Effects of intravenous infusions of sodium bicarbonate on blood oxygen binding in calves with diarrhoea

Twelve diarrhoeic calves were treated intravenously with an isotonic solution containing sodium bicarbonate, and their oxygen equilibrium curves (OECs) were calculated under standard conditions and compared with those of a...

Fluoride Reabsorption by Nonionic Diffusion in the Distal Nephron of the Dog

This study was done to test the hypothesis that fluoride reabsorption is extensive from the distal nephron, the major site for tubular fluid acidification, and to compare the distal nephron handling of fluoride and chloride. Ten stop-flow studies were done in five dogs anesthetized with pentobarbital. Urinary alkalinization was achieved by the intravenous infusion of sodium bicarbonate and acetazolamide or lithium chloride. Acidification was achieved by the infusion of sodium nitrate or sodium sulfate. The results indicate that the extent of fluoride reabsorption from the distal nephron is inversely correlated with urinary pH (P less than 0.001). When the urine was strongly acidified by the infusion of sodium sulfate, urine to plasma fluoride concentration ratios were less than 1.0, a finding not previously reported from studies of the renal handling of fluoride. The reabsorption of fluoride from the distal nephron was not correlated consistently with that of chloride. The results indicate that the distal nephron is an important site for the reabsorption of fluoride and they provide additional evidence that HF is the permeating moiety.

Extracellular pH and suppression of electrical activity during anoxia in turtle and rat brain

To evaluate the contribution of extracellular H+ activity toward depression of brain electrical activity during anoxia, extracellular pH (pHe) and field potentials were measured in turtle and rat olfactory bulbs with ion-selective microelectrodes. This study tests the hypothesis that unique regulation of pHe contributes to the remarkable tolerance of turtle brain to prolonged anoxia. Hypercapnea (20% CO2 ventilation) depressed olfactory bulb evoked potentials 25-30% in both rat and turtle. During anoxia, evoked potentials were completely abolished within 1 min in rat olfactory bulb but decreased to only 40% of control after 4 h in the turtle despite similar changes in brain pHe. Anoxia-induced acidification of turtle brain was exacerbated by hypercapnea and was attenuated by hypocapnea or by hypocapnea plus intravenous infusion of sodium bicarbonate. However, these manipulations of pHe during anoxia in turtle brain had little effect on depression of evoked potentials. We conclude that energy failure, rather than extracellular acidification, is the major contributor toward suppression of electrical activity in mammalian brain and that preservation of energy balance, rather than unique pH regulation, is responsible for protection of turtle brain during anoxia.

The effects of intravenous theophylline infusion versus intravenous Sodium Bicarbonate infusion on Lithium clearance in normal subjects

Ten normal subjects ingested lithium carbonate (600 mg p.o.b.i.d.) for three 1-week intervals. At the end of each weekly interval, subjects' lithium clearances were randomly perturbed for 12 hours with the subjects in a supine position by infusing either normal saline (308 mEq), sodium bicarbonate (350 mEq) in normal saline (308 mEq), or theophylline (mean = 14.0 μg/ml) in normal saline (308 mEq). Subjects were placed on a 200 mEq/day sodium diet during the lithium clearance perturbation stages of the study. When each patient's normal saline lithium clearance was used as a control, it was found that the theophylline produced a significantly greater % increase in lithium clearance than did the sodium bicarbonate. Theophylline infusions increased patients' individual lithium clearances by 51 ± 52%, while sodium bicarbonate infusions increased lithium clearances by 0.6 ± 33%. Theophylline infusions ought to be investigated as an alternative to hemodialysis in lithium intoxications requiring the immediate reduction of lithium concentrations.

Calculation of Sodium Bicarbonate Requirement in Metabolic Acidosis

Despite the host of complications which may be associated with intravenous sodium bicarbonate infusion, the use of this agent is a frequent necessity in patients with metabolic acidosis. No satisfactory formula for calculating bicarbonate dose has previously been described, although such an approach might be expected to reduce the incidence of these complications. The authors have devised a simple formula for bedside calculation of bicarbonate requirement in metabolic acidosis, designed to elevate the pH to the region about 7.30, and report their experience with the use of this formula in 13 instances. In all but one, the post-infusion pH was between 7.25 and 7.37, with a mean of 7.30±0.04 and no instances of serious overtitration. It is concluded that the formula is useful as a pragmatic aid in the management of patients with metabolic acidosis.

Protection of gastric mucosa against acute ulceration by intravenous infusion of sodium bicarbonate

The influence of intravenous infusion of sodium bicarbonate on gastric mucosal injury induced by topical sodium taurocholate and hemorrhagic shock was assessed in a canine ex vivo model. As expected, exposure of the gastric mucosa to sodium taurocholate and acid resulted in excessive back diffusion of hydrogen ions (H +) and mild mucosal damage. This mucosal injury was enhanced by hemorrhagic shock in the control dogs. The degree of mucosal injury was significantly less in the test dogs that received intravenous infusions of sodium bicarbonate. The protection afforded by intravenous bicarbonate was not due to a reduction in the amount of H + entering the tissue, since the net H + loss from the lumen was not significantly different between the control and the test dogs. The protective effect of intravenous infusion of sodium bicarbonate is probably secondary to an enhancement of mucosal tolerance to H +. These results support the hypothesis that the enhancement of mucosal injury during hemorrhagic shock may be a result of a decrease in the ability of the gastric mucosa to buffer the influxing H +.

Treatment of Renal Obstruction Caused by Cystine Crystals or Stones

To the Editor.— In cystinuric subjects, cystine stone formation can be prevented by high fluid intake and alkalinization. 1 Cystine stone dissolution by this treatment has also been described. 2 Dent and Senior 3 had earlier shown that in patients with cystine stones, acute diuresis may increase cystine outputs owing to cystine stone dissolution. Successful conservative treatment of acute renal obstruction due to cystine crystals or stones has not, so far as we know, been reported. In three cystinuric men (aged 26, 28, and 52 years) seen in our department over a period of 20 years, unilateral kidney obstruction was revealed by iodohippurate sodium I 131 (Hippuran I 131) renogram or intravenous pyelogram. Whether the renal obstruction was caused by cystine crystals or stones could not be verified. Treatment was by high fluid intake, and intravenous infusion of sodium bicarbonate, 1.25% in saline solution, to maintain a urinary volume of 4

Renal lithium excretion in man

Renal lithium excretion in man

Influence of Metabolic Alkalosis Induced by Intravenous Infusion of Bicarbonate Solution on Blood Pressure and Electrolytes in Hypertensive Subjects

It is a well known fact that the thiazide derivatives and their analogues produce more or less metabolic alkalosis in the subjects treated with them. Concerning the relationship of acidbase equilibrium to the regulation of blood pressure, however, we have had only a few reports. Since this prblem seems to be important to elucidate the hypotensive mechanism of the thiazide derivatives, the author attempted in the present study to determine the influence of metabolic alkalosis induced by intravenous in-fusion of sodium bicarbonate solution on blood pressure in the hypertensive subjects. Materials and Methods One hundred and fifty ml of 7 per cent sodium bicarbonate solution was infused intravenously in 10 hypertensive subjects. Blood pressure was estimated before and every 5 minutes after the infusion of bicarbonate solution, for I hour. Arterial blood pH, sodium, potassium, chloride and bicarbonate concentrations in plasrna, and sodium and potassium concentrations in the red blood cells were estimated before and 30 minutes and I hour after the infusion. Results Arterial blood pH markedly rose after the intravenous infusion of 7 per cent of sodium bicarbonate solution. Systolic and diastolic blood pressures progressively fell in all subjects. Both systolic and diastolic blood pressures showed minimum levels 30 minutes after the infusion and then gradually returned to near the pre-infusion levels. Only the decrease in diastolic pressure was significant statistically 30 and 35 minutes after the infusion. Sodium concentration in plasma slightly increased whereas potassium concentration showed a gradual decrease. These changes, however, were not significant. Bicarbonate concentration significantly increased and chloride concentration decreased but the latter change was not significant. Sodium concentration in the red blood cells slightly increased and the ratio of plasma sodium to sodium in the red blood cells decreased. But both changes were not significant. Potassium concentration in the red blood cells had no change. The ratio of potassium in the red blood cells to plasma potassium increased though its increase was not significant. Discussion DRIPPS and COMROE have reported that respiratory acidosis induced by the inhalation of C2 gas raise blood pressure in normal subjects. This finding is contrary to PAGE & OLMSTED'S observation that it lower blood pressure in normal dogs. On the other hand, WALDON and GOLDSTEIN and WELLER have noted a tendency of respiratory acidosis in the patients with essential hypertension. Because of these conflicting information, it is interesting to investigate the relationship of the alteration in acid-base equilibrium to blood pressure, especially with reference to the hypotensive mechanism of the thiazide derivatives which often disturb acid-base equilibrium to some extent. In the present study it was demonstrated that metabolic alkalosis induced by intravenous infusion of sodium bicarbonate solution lower systolic and diastolic blood pressures in the hypertensive subjects. It is, however, difficult to say whether the decrease of blood pressure following the infusion of bicarbonate solution is induced directly by metabolic alkalosis itself or indirectly through the alterations in electrolytes distribution accompanied by alkalosis. So far it would appear likely that metabolic alkalosis itself lowered blood pressure directly, since the alterations in electrolytes distribution induced by alkalosis were significant. Summary Intravenous infusion of sodium bicarbonate raised arterial blood pH and lowered gradually systolic and diastolic blood pressures in hypertensive subjects. Alterations of electrolytes distribution were not significant.

EFFECT OF MASSIVE SODIUM BICARBONATE INFUSION ON RENAL FUNCTION

The effect of both mild and severe acute alkalosis, due to intravenous sodium bicarbonate infusion, on glomerular filtration rate, renal plasma flow, and sodium and potassium clearance was investigated on 12 anesthetized dogs. The maximum load used was over 50 grams of NaHCO3administered intravenously in 4 hours, at a rate of 2.5 meq/minute. On a weight basis, in a 70-kg man, this would be equivalent to a load of 195 grams of NaHCO3given at the rate of nearly 10 meq/minute. The plasma potassium fell from 3.8 meq/l. to 2.7 meq/l. and the plasma sodium increased from 144.4 to 170.8 meq/l. with maximum NaHCO3loading. There was no apparent acute detrimental renal effect. No depression of GFR or RPF was seen in any series although the pH increased from 7.32 to 7.61. Similarly no significant effect was seen on blood pressure, hematocrit, filtration fraction, heart rate, or rectal temperature in any series. Urine flow and urine pH increased significantly with higher loading rates and concentrations.