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Background and Objectives: Current guidelines recommend Na(+)-based alkali for CKD with metabolic acidosis and plasma total CO2 (PTCO2) < 22 mM. Because diets in industrialized societies are typically acid-producing, we compared base-producing fruits and vegetables with oral NaHCO3 (HCO3) regarding the primary outcome of follow-up estimated GFR (eGFR) and secondary outcomes of improved metabolic acidosis and reduced urine indices of kidney injury., Design, Setting, Participants, & Measurements: Individuals with stage 4 (eGFR, 15-29 ml/min per 1.73 m(2)) CKD due to hypertensive nephropathy, had a PTCO2 level < 22 mM, and were receiving angiotensin-converting enzyme inhibition were randomly assigned to 1 year of daily oral NaHCO3 at 1.0 mEq/kg per day (n=35) or fruits and vegetables dosed to reduce dietary acid by half (n=36)., Results: Plasma cystatin C-calculated eGFR did not differ at baseline and 1 year between groups. One-year PTCO2 was higher than baseline in the HCO3 group (21.2±1.3 versus 19.5±1.5 mM; P<0.01) and the fruits and vegetables group (19.9±1.7 versus 19.3±1.9 mM; P<0.01), consistent with improved metabolic acidosis, and was higher in the HCO3 than the fruits and vegetable group (P<0.001). One-year urine indices of kidney injury were lower than baseline in both groups. Plasma [K(+)] did not increase in either group., Conclusions: One year of fruits and vegetables or NaHCO3 in individuals with stage 4 CKD yielded eGFR that was not different, was associated with higher-than-baseline PTCO2, and was associated with lower-than-baseline urine indices of kidney injury. The data indicate that fruits and vegetables improve metabolic acidosis and reduce kidney injury in stage 4 CKD without producing hyperkalemia.

'Salivary abomasum disease' is a common syndrome in Greece affecting lambs and kids from three to 17 days of age. In this case series, we present clinical and laboratory findings from 37 affected lambs presented alive and subsequently euthanased for welfare reasons and necropsied, and also from 24 other lambs submitted dead that were also necropsied. The clinical signs in the 37 lambs presented alive included lethargy (100 per cent), absence of sucking (83.8 per cent), weakness (37.8 per cent), abdominal distension (40.5 per cent) and increased frequency of urination (24.3 per cent). Diarrhoea was not observed in any affected lambs. At necropsy of these 37 lambs, the abomasum was distended with gas (70.3 per cent), saliva (43.2 per cent) along with mixed milk clots and gastric secretions; while multiple small mucosal and serosal haemorrhages with blood clots ('coffee grains') were recorded (91.9 per cent). Eight of 37 lambs that were examined alive, had elevated blood urea nitrogen concentrations (21.6 per cent). The pH of the abomasal contents ranged from 1.0 to 2.8; Escherichia coli was cultured from six of 37 (16.2 per cent) abomasal fluid samples. A mild to moderate inflammatory cell infiltrate was present in the mucosal lamina propria of 13 of 15 abomasal samples (86.6 per cent). Kidneys were paler than normal in 13 of the total 61 lambs necropsied (21.3 per cent); while acute tubular necrosis was evident on histopathological examination of 11 of 12 examined pale kidneys (91.6 per cent). The low abomasal pH and reported successful treatment with oral sodium bicarbonate suggest that metabolic acidosis may develop during the disease; however, further studies, including blood gas analysis, and determination of D- and L-lactic acid concentrations, are necessary to confirm this hypothesis.

Unlabelled: Metabolic acidosis slowly develops during renal impairment natural evolution towards ESRD and represents an important contributing factor of CKD progression. Although, several clinical and experimental trials reported the major impact of metabolic acidosis on CKD evolution, the pathophysiology mechanism remains a matter of debate. Furthermore, international guidelines do not impose a specific treatment scheme for metabolic acidosis in CKD patients, and metabolic acidosis is not fully compensated once hemodialysis starts. Therefore, the aim of our study was to determine an adequate follow-up of metabolic acidosis therapy benefits and risks in HD patients., Patients and Methods: 164 HD patients were evaluated according to the following protocol: bioumoral laboratory tests, the measure of different important parameters (residual diuresis, UF, BP, LVMI, volemia status). The assessed data were statistic analyzed using non-paired Student's t-test for continuous variables and chi-square (χ²) test for qualitative parameters (p-value <0.05 was considered statistically significant)., Results: HD individuals were followed-up depending on their predialysis-alkaline reserve value. After therapy started, predialysis-alkaline reserve mean level increased from 19.4 mEq/L to 22.6 mEq/L (p<0.001). Furthermore, we observed a significant decrease of nitrogenous waste products values (T=10.87<1.66) and intradialytic hypotension events (p<0.001)., Conclusions: Our findings emphasize the beneficial effects of correcting metabolic acidosis using the proposed treatment scheme with direct impact on hemodynamic status improvement.

Introduction: Acute metabolic acidosis impairs cardiovascular function and increases the mortality of critically ill patients. However, the precise mechanism(s) underlying these effects remain unclear. We hypothesized that targeting pH-regulatory protein, Na(+)/H(+) exchanger (NHE1) could be a novel approach for the treatment of acute metabolic acidosis. The aim of the present study was to examine the impact of a novel NHE1 inhibitor, sabiporide, on cardiovascular function, blood oxygen transportation, and inflammatory response in an experimental model of metabolic acidosis produced by hemorrhage-induced hypovolemia followed by an infusion of lactic acid., Methods and Results: Anesthetized pigs were subjected to hypovolemia for 30 minutes. The animals then received a bolus infusion of sabiporide (3 mg/kg) or vehicle, followed by an infusion of lactic acid for 2 hours. The animals were continuously monitored for additional 3 hours. Hypovolemia followed by a lactic acid infusion resulted in a severe metabolic acidosis with blood pH falling to 6.8. In association with production of the acidemia, there was an excessive increase in pulmonary artery pressure (PAP) and pulmonary vascular resistance (PVR). Treatment with sabiporide significantly attenuated the increase in PAP by 38% and PVR by 67%, as well as significantly improved cardiac output by 51%. Sabiporide treatment also improved mixed venous blood oxygen saturation (55% in sabiporide group vs. 28% in control group), and improved systemic blood oxygen delivery by 36%. In addition, sabiporide treatment reduced plasma levels of TNF-α (by 33%), IL-6 (by 63%), troponin-I (by 54%), ALT (by 34%), AST (by 35%), and urea (by 40%)., Conclusion: These findings support the possible beneficial effects of sabiporide in the treatment of acute metabolic acidosis and could have implications for the treatment of metabolic acidosis in man.

Despite the large variety of so-called ergogenic supplements used by the sporting community, only few of them are effectively supported by scientific proof. One of the recent evidence-based supplements that entered the market is β-alanine. β-Alanine is the rate-limiting precursor for the synthesis of the dipeptide carnosine (β-alanyl-L-histidine) in human muscle. The chronic daily ingestion of β-alanine can markedly elevate muscle carnosine content, which results in improved exercise capacity, especially in sports that include high-intensity exercise episodes. The use of β-alanine is exponentially growing in recent years. This chapter aims to (1) discuss the scientific basis and physiological background of β-alanine and its synthesis product carnosine, and (2) translate these scientific findings to practical applications in sports., (Copyright © 2013 Nestec Ltd., Vevey/S. Karger AG, Basel.)

Intentional iron overdose appears to be an increasingly common form of attempted suicide. We present a case of iron overdose in a 16-year-old girl who was found unconscious in her bed and brought to our emergency department. The most remarkable diagnostic findings were the patient's comatose condition, divergent eye position and positive Babinski foot pad reflexes. Laboratory tests showed hyperglycaemia and mild metabolic acidosis. A computed tomography scan of the cerebrum showed no signs of intracerebral haemorrhage or elevated intracerebral pressure. Toxicology screening showed no use of acetaminophen, ethanol or drugs of abuse. The patient was stabilized and monitored on the intensive care ward. When she woke up, she confessed to having taken Fero-Gradumet(®). Retrospectively analysed, the serum iron concentration in the first blood sample (seven hours after ingestion) was 62 μmol/L which corresponds with moderate iron intoxication. The patient received whole bowel irrigation with 2 L polyethyleneglycol solution and de-ironing treatment with intravenous deferoxamine 20 mg/kg in eight hours. She was discharged from the hospital after three days in a good clinical condition. Retrospectively, serum hepcidin concentrations were determined and evaluated in conjunction with serum iron concentrations and the installed treatment. Before medical de-ironing interventions were started, we saw that the serum iron concentration in our patient was already declining. At the same time, we observed a sharp increase in the serum hepcidin concentration. After normalization of serum iron concentrations, hepcidin normalized as well.

The question of obtaining organs from donors who died of methanol poisoning has been discussed in the medical literature for many years. The results of such transplants published so far are very optimistic. However, the possibility of permanent and significant injury to transplanted organs caused by poisons or its metabolites raises serious concerns regarding the procedure. The long-term effects of intensive treatment of poisoning need to be considered as well. Metabolic acidosis and high blood osmolality are agents with recognized damaging potential impairing organ function at cellular level. The study traced the fate of kidney transplants from 13 donors who died of methanol poisoning and one isoned with carbon monoxide. The donors group consisted of 12 men and 2 women, of mean age 49 years (SD +/- 7.93). The kidneys were transplanted 20 men and 8 women. The mean age of recipients was 50.29 years (SD +/- 12.9). At the time of admission to the Department of Toxicology all donors presented with profound metabolic acidosis and high plasma osmolality (mean 434.71 mOsm/kg H2O (SD +/- 73.29). Metabolic acidosis was treated high doses of sodium bicarbonate (mean infusion volume of was 409 ml) before the HD procedure. Blood methanol levels were between 125 and 470 mg% (mean 317.23 SD +/- 136.83). The carboxyhaemoglobin concentration of in the donor poisoned with carbon monoxide was 47.2%. Transplantation was performed after confirmation of the brain death, the period of cold ischemia (CIT) ranged from 6 to 22 hours (mean 16.06 hours; SD +/- 3.99). Kidneys have taken function immediately after transplantation in 21 recipients. In seven cases, patients required two or three HD procedures. A total of 16 dialysis were performed post-transplants. In the group of patients, the mean glomerular filtration rate (GFR) at 3 months after transplantation was 46.71 ml/min/1.73m2 (SD +/- 10.89). During the 18 months follow-up a constant upward trend to the mean GFR 50.55 was noticed. In the group of donors, the mean blood urea concentration (BUN) 3 months after transplantation was 61.43 mg/dL, including 7 patients with BUN within the range of 80-100 mg/dL. At 18 months post transplant, the average concentration was 42.36 mg/dL, with no cases exceeding 55 mg/dL. Similarly, serum creatinine level normalized with the mean value of 3.01 mg/dL at 3 months and 1.68 mg/dL at 18 months post the procedure. There was no case exceeding 2 mg/dL. One recipient died of a heart attack after a period of more than 18 months after transplantation. However, the transplant was efficiently active at all times (GFR 56-60 ml).

Despite the widespread use, suicidal ingestion of isoniazid is a rare condition in Turkey. We reported a case of acute isoniazid intoxication associated with alcohol intake presenting with convulsion, coma and metabolic acidosis. The patient was treated successfully with intravenous pyridoxine administration. Early recognation and appropriate treatment in the intensive care unit is very important to prevent mortality in patients with acute isoniazid toxicity.

Experiments on rats showed that infusion of NO precursor L-arginine before bleeding enhanced their tolerance to hemorrhagic shock. When infused after blood loss as a component of saline solution, L-arginine improved efficiency of infusion therapy for hemorrhagic shock and increased survival rate of the animals.

Background: The aim of the present prospective study was to investigate whether a decision tree based on basic clinical signs could be used to determine the treatment of metabolic acidosis in calves successfully without expensive laboratory equipment. A total of 121 calves with a diagnosis of neonatal diarrhea admitted to a veterinary teaching hospital were included in the study. The dosages of sodium bicarbonate administered followed simple guidelines based on the results of a previous retrospective analysis. Calves that were neither dehydrated nor assumed to be acidemic received an oral electrolyte solution. In cases in which intravenous correction of acidosis and/or dehydration was deemed necessary, the provided amount of sodium bicarbonate ranged from 250 to 750 mmol (depending on alterations in posture) and infusion volumes from 1 to 6.25 liters (depending on the degree of dehydration). Individual body weights of calves were disregarded. During the 24 hour study period the investigator was blinded to all laboratory findings., Results: After being lifted, many calves were able to stand despite base excess levels below -20 mmol/l. Especially in those calves, metabolic acidosis was undercorrected with the provided amount of 500 mmol sodium bicarbonate, which was intended for calves standing insecurely. In 13 calves metabolic acidosis was not treated successfully as defined by an expected treatment failure or a measured base excess value below -5 mmol/l. By contrast, 24 hours after the initiation of therapy, a metabolic alkalosis was present in 55 calves (base excess levels above +5 mmol/l). However, the clinical status was not affected significantly by the metabolic alkalosis., Conclusions: Assuming re-evaluation of the calf after 24 hours, the tested decision tree can be recommended for the use in field practice with minor modifications. Calves that stand insecurely and are not able to correct their position if pushed require higher doses of sodium bicarbonate, if there is clinical evidence of a marked D-lactic acidosis. In those calves, determining the degree of loss of the palpebral reflex was identified as a useful decision criterion to provide an additional amount of 250 mmol sodium bicarbonate. This work demonstrates the clinical relevance of the discovery that D-lactate is responsible for most of the clinical signs expressed in neonatal diarrheic calves suffering from metabolic acidosis.

Background: Our goal was to determine the factors associated with prolonged acidosis in children with diabetic ketoacidosis., Method: The records of all children (109 admissions, 86 patients) admitted to the pediatric intensive care unit (PICU) during a 3-year period with the diagnosis of diabetic ketoacidosis were analyzed., Results: The charts were reviewed after institutional review board approval was obtained. Demographic and serial laboratory data, time to correction of acidosis, as well as the first 24-hour chloride load, total fluid administered, fluid balance, and PICU and hospital lengths of stay were recorded. The anion gap (AG = Na - Cl - HCO(3)) and the delta gap (DG = AG - 12 - [24 - HCO(3)]) were calculated. Prolonged acidosis (HCO(3) < 15 mEq/L at 24 hours) was analyzed against various independent factors on admission and during therapy. Low Na (128 vs 133 mEq/L), HCO3 (4.7 vs 9.5 mEq/L), DG (-6.3 vs -2.8 mEq/L), pH (6.97 vs 7.16), PaCO(2) (15 vs 23 mm Hg), and base excess (-26 vs -18) as well as high chloride load (17 vs 11 mEq/kg per 24 hours) were associated with prolonged acidosis (t test, P < 0.05). Stepwise logistic regression eliminated all except base excess and DG in the model. Children with prolonged acidosis had longer PICU (45 vs 34 hours) and hospital stays (5.5 vs 2.5 days) (P < 0.05). The AG was normal in all cases at 24 hours. There were no deaths., Conclusions: Nongap acidosis was present in many children with prolonged metabolic acidosis. We suggest that a continuous acetate or bicarbonate therapy via maintenance fluid might be beneficial in this subgroup of patients.

Background: Acidosis and transplantation are associated with increased risk of bone disturbances. This study aimed to assess bone morphology and metabolism in acidotic patients with a renal graft, and to ameliorate bone characteristics by restoration of acid/base homeostasis with potassium citrate., Methods: This was a 12-month controlled, randomized, interventional trial that included 30 renal transplant patients with metabolic acidosis (S-[HCO(3)(-)] <24 mmol/L) undergoing treatment with either potassium citrate to maintain S-[HCO(3)(-)] >24 mmol/L, or potassium chloride (control group). Iliac crest bone biopsies and dual-energy X-ray absorptiometry were performed at baseline and after 12 months of treatment. Bone biopsies were analyzed by in vitro micro-computed tomography and histomorphometry, including tetracycline double labeling. Serum biomarkers of bone turnover were measured at baseline and study end. Twenty-three healthy participants with normal kidney function comprised the reference group., Results: Administration of potassium citrate resulted in persisting normalization of S-[HCO(3)(-)] versus potassium chloride. At 12 months, bone surface, connectivity density, cortical thickness, and cortical porosity were better preserved with potassium citrate than with potassium chloride, respectively. Serological biomarkers and bone tetracycline labeling indicate higher bone turnover with potassium citrate versus potassium chloride. In contrast, no relevant changes in bone mineral density were detected by dual-energy X-ray absorptiometry., Conclusions: Treatment with potassium citrate in renal transplant patients is efficient and well tolerated for correction of metabolic acidosis and may be associated with improvement in bone quality. This study is limited by the heterogeneity of the investigated population with regard to age, sex, and transplant vintage.

Metabolic acidosis is a common complication associated with progressive loss of kidney function. The diminishing ability of the kidneys to maintain acid-base homeostasis results in acid accumulation, leading to various complications such as impairment in nutritional status, worsened uremic bone disease and an association with increased mortality. In addition to these adverse effects which are related to acid retention, metabolic acidosis may also cause kidney damage, possibly through the stimulation of adaptive mechanisms aimed at maintaining acid-base homeostasis in the face of decreasing kidney function. Recent clinical trials have suggested that correction or prevention of metabolic acidosis by alkali administration is able to attenuate kidney damage and to slow progression of chronic kidney disease (CKD), and may hence offer an effective, safe and affordable renoprotective strategy. We review the physiology and pathophysiology of acid-base homeostasis in CKD, the mechanisms whereby metabolic acidosis may be deleterious to kidney function, and the results of clinical trials suggesting a benefit of alkali therapy, with special attention to details related to the practical implementation of the results of these trials.

Background: We aimed to investigate the effects of active mild hyperthermia and the effects of active mild hyperthermia with propofol on mortality and inflammatory responses during endotoxin-induced shock in rats., Methods: Intravenous Escherichia coli endotoxin (15 mg/kg over 2 min) was injected in 48 rats. The animals were randomly allocated to one of the following four groups (n = 12 per group): normothermia group (group N), rectal temperature maintained between 36 °C and 38 °C; hyperthermia group (group H), rectal temperature was moderate and maintained between 39 °C and 40 °C; propofol with normothermia group (group PN), propofol (10 mg/kg/h) was administered, and temperature was between 36 °C and 38 °C; Propofol with hyperthermia group (group PH), propofol (10 mg/kg/h) administrated, and temperatures were maintained between 39 °C and 40 °C. The primary outcome was mortality 8 h after endotoxin injection. Secondary outcomes included changes in haemodynamics, arterial blood gases and plasma cytokine concentrations for the 8-h observation period., Results: Mortality rates 8 h after endotoxin injection were 92%, 100%, 68% and 50% for N, H, PN and PH groups, respectively. There was no difference in hypotension, acidosis, and increase in plasma cytokine concentrations between N and H groups, but these parameters were attenuated in group PH., Conclusion: The mortality rates in the present study were extremely high; further hypotension and elevations in plasma pro-inflammatory and anti-inflammatory cytokine concentrations after endotoxin injection were not attenuated by mild hyperthermia between 39 °C and 40 °C, but they were attenuated by propofol with mild hyperthermia., (© 2012 The Authors. Acta Anaesthesiologica Scandinavica © 2012 The Acta Anaesthesiologica Scandinavica Foundation.)

Insufficient cardiac preload and impaired contractility are frequent in early sepsis. We explored the effects of acute cardiac preload reduction and dobutamine on hepatic arterial (Qha) and portal venous (Qpv) blood flows during endotoxin infusion. We hypothesized that the hepatic arterial buffer response (HABR) is absent during preload reduction and reduced by dobutamine. In anesthetized pigs, endotoxin or vehicle (n = 12, each) was randomly infused for 18 h. HABR was tested sequentially by constricting superior mesenteric artery (SMA) or inferior vena cava (IVC). Afterward, dobutamine at 2.5, 5.0, and 10.0 μg/kg per minute or another vehicle (n = 6, each) was randomly administered in endotoxemic and control animals, and SMA was constricted during each dose. Systemic (cardiac output, thermodilution) and carotid, splanchnic, and renal blood flows (ultrasound Doppler) and blood pressures were measured before and during administration of each dobutamine dose. HABR was expressed as hepatic arterial pressure/flow ratio. Compared with controls, 18 h of endotoxin infusion was associated with decreased mean arterial blood pressure [49 ± 11 mmHg vs. 58 ± 8 mmHg (mean ± SD); P = 0.034], decreased renal blood flow, metabolic acidosis, and impaired HABR during SMA constriction [0.32 (0.18-1.32) mmHg/ml vs. 0.22 (0.08-0.60) mmHg/ml; P = 0.043]. IVC constriction resulted in decreased Qpv in both groups; whereas Qha remained unchanged in controls, it decreased after 18 h of endotoxemia (P = 0.031; constriction-time-group interaction). One control and four endotoxemic animals died during the subsequent 6 h. The maximal increase of cardiac output during dobutamine infusion was 47% (22-134%) in controls vs. 53% (37-85%) in endotoxemic animals. The maximal Qpv increase was significant only in controls [24% (12-47%) of baseline (P = 0.043) vs. 17% (-7-32%) in endotoxemia (P = 0.109)]. Dobutamine influenced neither Qha nor HABR. Our data suggest that acute cardiac preload reduction is associated with preferential hepatic arterial perfusion initially but not after established endotoxemia. Dobutamine had no effect on the HABR.

Activation of the complement system has been associated with tissue injury after hemorrhage and resuscitation in animals. We investigated whether administration of recombinant human C1-esterase inhibitor (rhC1-INH), a regulator of complement and contact activation systems, reduces tissue damage and cytokine release and improves metabolic acidosis in a porcine model of hemorrhagic shock. Male Yorkshire swine were assigned to experimental groups and subjected to controlled, isobaric hemorrhage to a target mean arterial pressure of 35 mmHg. Hypotension was maintained for 20 min followed by a bolus intravenous injection of rhC1-INH or vehicle; animals were then observed for 3 h. Blood chemistry and physiologic parameters were recorded. Lung and small intestine tissue samples were subjected to histopathologic evaluation and immunohistochemistry to determine the extent of injury and deposition of complement proteins. Cytokine levels and quantitative assessment of renal and hepatic function were measured via enzyme-linked immunosorbent assay and chemistry analyzer, respectively. Pharmacokinetics of rhC1-INH revealed dose proportionality for maximum concentration, half-life, and the time span in which the functional C1-INH level was greater than 1 IU/mL. Recombinant human C1-INH significantly reduced renal, intestinal, and lung tissue damage in a dose-dependent manner (100 and 250 IU/kg). In addition, rhC1-INH (250 IU/kg) markedly improved hemorrhage-induced metabolic acidosis and circulating tumor necrosis factor α. The tissue-protective effects of rhC1-INH appear to be related to its ability to reduce tissue complement activation and deposition. Recombinant human C1-INH decreased tissue complement activation and deposition in hemorrhaged animals, improved metabolic acidosis, reduced circulating tumor necrosis factor α, and attenuated tissue damage in this model. The observed beneficial effects of rhC1-INH treatment on tissue injury 20 min into severe hypotension present an attractive model of low-volume resuscitation, particularly in situations with a restrictive medical logistical footprint.

Background: Acute kidney injury (AKI) is a common, serious, but potentially treatable condition. Because AKI is often associated with acidosis, it has become common practice to recommend administration of sodium bicarbonate to correct acid imbalance., Objectives: To assess the benefits and harms of the use of sodium bicarbonate for people with AKI. The primary outcome measure was all-cause mortality, and secondary outcome measures were patients' need for renal replacement therapy; return to baseline kidney function; and overall survival., Search Methods: In November 2011 we searched the Cochrane Renal Group's Specialised Register using keywords relevant to this review. The register is populated using searches of Ovid MEDLINE, the Cochrane Central Register of Controlled Trials, EMBASE and handsearching records from renal-related journals and conference proceedings., Selection Criteria: All randomised controlled trials (RCTs) that investigated the use of sodium bicarbonate supplements, administered by any route, for the treatment of adults with AKI were to be included. The search strategy did not restrict inclusion based on an upper age limit or publication language. We did not consider inclusion of studies that investigated use of sodium bicarbonate for AKI prevention., Data Collection and Analysis: All authors planned to independently assess and extracted information. Information was to be collected on methods, participants, interventions and outcomes. Results were to be expressed as risk ratios (RR) for dichotomous outcomes or as mean differences (MD) for continuous data with 95% confidence intervals (CI)., Main Results: Although our literature search identified four studies, none of these met our predetermined selection criteria. Hence, no suitable studies were identified for inclusion in this review., Authors' Conclusions: We found no RCT evidence - supportive or otherwise - for the use of sodium bicarbonate for people with AKI. We concluded that there is an urgent need for well conducted RCTs in this area.

Background: A Cochrane Collaboration review (Roderick, Cochrane Data base of systemic reviews 2007, DOI 10.1002/14651858.CD0018.90.pub3) reported that there was no evidence for correction of acidosis by sodium bicarbonate in pre-end-stage renal disease (ESRD) patients, and concluded that randomized controlled trials (RCTs) are necessary to evaluate the benefits and harms of correcting metabolic acidosis in pre-ESRD patients. We wanted to evaluate if the administration of alcaly (mainly sodium bicarbonate) is able to significantly modify renal death and to reduce mortality due to cardiovascular events., Methods: This is a proposal for a multicenter, prospective, cohort, randomized and controlled study. We will randomize 600 patients with chronic kidney disease (CKD) stages 3b and 4; 300 of these patients will be included in the bicarbonate study group (Bic), in which levels of bicarbonate should be kept >24 mEq/L; the other 300 patients will be included in the usual-treatment group (no-Bic)., Results: The aim of the research protocol is to demonstrate whether the optimal correction of uremic acidosis (with administration of sodium bicarbonate or of any other alkalinizing agent - e.g., sodium citrate) reduces renal and cardiovascular mortality., Conclusions: In conclusion, the Work Group on Conservative Therapy for Chronic Renal Insufficiency proposes this prospective, multicenter, cohort, randomized, controlled study to evaluate the effects of correction of acidosis on the progression of the kidney disease evaluated as renal death in ESRD patients.

Background: The effect of sodium bicarbonate on acid-base balance in metabolic acidosis is interpreted differently by Henderson-Hasselbalch and strong ion acid-base approaches. Application of the traditional bicarbonate-centric approach indicates that bicarbonate administration corrects the metabolic acidosis by buffering hydrogen ions, whereas strong ion difference theory indicates that the co-administration of the strong cation sodium with a volatile buffer (bicarbonate) corrects the strong ion acidosis by increasing the strong ion difference (SID) in plasma., Objective: To investigate the relative importance of the effective SID of IV solutions in correcting acidemia in calves with diarrhea., Animals: Twenty-two Holstein-Friesian calves (4-21 days old) with naturally acquired diarrhea and strong ion (metabolic) acidosis., Methods: Calves were randomly assigned to IV treatment with a solution of sodium bicarbonate (1.4%) or sodium gluconate (3.26%). Fluids were administered over 4 hours and the effect on acid-base balance was determined., Results: Calves suffered from acidemia owing to moderate to strong ion acidosis arising from hyponatremia and hyper-D-lactatemia. Sodium bicarbonate infusion was effective in correcting the strong ion acidosis. In contrast, sodium gluconate infusion did not change blood pH, presumably because the strong anion gluconate was minimally metabolized., Conclusions: A solution containing a high effective SID (sodium bicarbonate) is much more effective in alkalinizing diarrheic calves with strong ion acidosis than a solution with a low effective SID (sodium gluconate). Sodium gluconate is ineffective in correcting acidemia, which can be explained using traditional acid-base theory but requires a new parameter, effective SID, to be understood using the strong ion approach., (Copyright © 2012 by the American College of Veterinary Internal Medicine.)

The term Excited Delirium Syndrome (ExDS) has traditionally been used in the forensic literature to describe findings in a subgroup of patients with delirium who suffered lethal consequences from their untreated severe agitation.(1-5) Excited delirium syndrome, also known as agitated delirium, is generally defined as altered mental status and combativeness or aggressiveness. Although the exact signs and symptoms are difficult to define precisely, clinical findings often include many of the following: tolerance to significant pain, rapid breathing, sweating, severe agitation, elevated temperature, delirium, non-compliance or poor awareness to direction from police or medical personnel, lack of fatiguing, unusual or superhuman strength, and inappropriate clothing for the current environment. It has become increasingly recognized that individuals displaying ExDS are at high risk for sudden death, and ExDS therefore represents a true medical emergency. Recently the American College of Emergency Physicians (ACEP) published the findings of a white paper on the topic of ExDS to better find consensus on the issues of definition, diagnosis, and treatment.(6) In so doing, ACEP joined the National Association of Medical Examiners (NAME) in recognizing ExDS as a medical condition. For both paramedics and physicians, the difficulty in diagnosing the underlying cause of ExDS in an individual patient is that the presenting clinical signs and symptoms of ExDS can be produced by a wide variety of clinical disease processes. For example, agitation, combativeness, and altered mental status can be produced by hypoglycemia, thyroid storm, certain kinds of seizures, and these conditions can be difficult to distinguish from those produced by cocaine or methamphetamine intoxication.(7) Prehospital personnel are generally not expected to differentiate between the multiple possible causes of the patient's presentation, but rather simply to recognize that the patient has a medical emergency and initiate appropriate stabilizing treatment. ExDS patients will generally require transfer to an emergency department (ED) for further management, evaluation, and definitive care. In this paper, we present a typical ExDS case and then review existing literature for current treatment options., (Copyright © 2011 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.)

Purpose: Continuous veno-venous hemofiltration (CVVH) and mixed acidemia often occur simultaneously in critically ill patients. In a previous study in non-acidemic pigs we found that colloids and CVVH interact specifically with respect to hemodynamic stability, with favorable effects for 6% HES 130/0.4 versus 4% gelatine (GEL) infusion. In a porcine model, we investigated whether these colloid-type associated differences are still dominant under acidemic conditions., Methods: We utilized 5 groups, a non-acidemic reference group receiving HES130 and CVVH; two acidemic groups receiving HES130 infusion (one with and one without CVVH); and two acidemic groups receiving GEL infusion (one with and one without CVVH). Mixed acidemia (pH ~7.20) was established by low tidal volume ventilation and acid infusion. Stable acidemia/CVVH application was maintained for 3 hours. Hemodynamics and blood gases were recorded., Results: Mixed acidemia led to a significant decrease in MAP and increase in MPAP in all groups. CVVH led to a further decrease in MAP but improved MPAP. During CVVH, HES130 ensured significantly higher MAP, Hb, and DO2 values than GEL infusion. In the groups without CVVH these differences between HES 130/0.4 and GEL were not observed., Conclusions: As in a previous study in non-acidemic pigs, we found a colloid-specific influence of HES130 versus GEL on hemodynamics during CVVH under acidemia. Again, HES130 infusion may lead to favorable effects. In contrast, acidemia without CVVH application was dominant over the impact of a respective colloid. The application of a CVVH seems to be an important trigger for the overall circulatory response to a particular colloid.

Background: Acute respiratory disorders may lead to sustained alveolar hypoxia with hypercapnia resulting in impaired pulmonary gas exchange. Hypoxic pulmonary vasoconstriction (HPV) optimizes gas exchange during local acute (0-30 min), as well as sustained (> 30 min) hypoxia by matching blood perfusion to alveolar ventilation. Hypercapnia with acidosis improves pulmonary gas exchange in repetitive conditions of acute hypoxia by potentiating HPV and preventing pulmonary endothelial dysfunction. This study investigated, if the beneficial effects of hypercapnia with acidosis are preserved during sustained hypoxia as it occurs, e.g in permissive hypercapnic ventilation in intensive care units. Furthermore, the effects of NO synthase inhibitors under such conditions were examined., Method: We employed isolated perfused and ventilated rabbit lungs to determine the influence of hypercapnia with or without acidosis (pH corrected with sodium bicarbonate), and inhibitors of endothelial as well as inducible NO synthase on acute or sustained HPV (180 min) and endothelial permeability., Results: In hypercapnic acidosis, HPV was intensified in sustained hypoxia, in contrast to hypercapnia without acidosis when HPV was amplified during both phases. L-NG-Nitroarginine (L-NNA), a non-selective NO synthase inhibitor, enhanced acute as well as sustained HPV under all conditions, however, the amplification of sustained HPV induced by hypercapnia with or without acidosis compared to normocapnia disappeared. In contrast 1400 W, a selective inhibitor of inducible NO synthase (iNOS), decreased HPV in normocapnia and hypercapnia without acidosis at late time points of sustained HPV and selectively reversed the amplification of sustained HPV during hypercapnia without acidosis. Hypoxic hypercapnia without acidosis increased capillary filtration coefficient (Kfc). This increase disappeared after administration of 1400 W., Conclusion: Hypercapnia with and without acidosis increased HPV during conditions of sustained hypoxia. The increase of sustained HPV and endothelial permeability in hypoxic hypercapnia without acidosis was iNOS dependent.

In a crossover study, 5 calves were made acidotic by intermittent intravenous infusion of isotonic hydrochloric acid (HCl) over approximately 24 h. This was followed by rapid (4 h) or slow (24 h) correction of blood pH with isotonic sodium bicarbonate (NaHCO(3)) to determine if rapid correction of acidemia produced paradoxical cerebrospinal fluid (CSF) acidosis. Infusion of HCl produced a marked metabolic acidosis with respiratory compensation. Venous blood pH (mean ± S(x)) was 7.362 ± 0.021 and 7.116 ± 0.032, partial pressure of carbon dioxide (Pco(2), torr) 48.8 ± 1.3 and 34.8 ± 1.4, and bicarbonate (mmol/L), 27.2 ± 1.27 and 11 ± 0.96; CSF pH was 7.344 ± 0.031 and 7.240 ± 0.039, Pco(2) 42.8 ± 2.9 and 34.5 ± 1.4, and bicarbonate 23.5 ± 0.91 and 14.2 ± 1.09 for the period before the infusion of hydrochloric acid and immediately before the start of sodium bicarbonate correction, respectively. In calves treated with rapid infusion of sodium bicarbonate, correction of venous acidemia was significantly more rapid and increases in Pco(2) and bicarbonate in CSF were also more rapid. However, there was no significant difference in CSF pH. After 4 h of correction, CSF pH was 7.238 ± 0.040 and 7.256 ± 0.050, Pco(2) 44.4 ± 2.2 and 34.2 ± 2.1, and bicarbonate 17.8 ± 1.02 and 14.6 ± 1.4 for rapid and slow correction, respectively. Under the conditions of this experiment, rapid correction of acidemia did not provoke paradoxical CSF acidosis.

Severe hyperkalemia (>7 mmol/L) is a medical emergency because of possible fatal arrhythmias. We here report the case of a 58-year-old woman surviving extreme hyperkalemia (>10 mmol/L). The patient with a history of congestive heart failure, a DDD pacemaker and mild chronic renal insufficiency was admitted with progressive weakness and sudden onset of hypotension and bradycardia in the absence of any pacemaker action. Laboratory tests revealed an extreme serum potassium level of 10.1 mmol/L, with a slightly elevated serum creatinine of 149 μmol/L. Treatment with norepinephrine, sodium bicarbonate, and insulin improved both the hemodynamic situation and the serum potassium with subsequent regaining pacemaker actions even before additional hemodialysis normalized the potassium level. A thorough investigation demonstrated that several mechanisms contributed to the extreme potassium level: urinalysis and a low transtubular potassium gradient in the presence of metabolic acidosis with normal anion gap pointed to preexisting interstitial nephritis, with renal tubular acidosis type IV as the predisposing factor, whereas several drugs and acute impairment of renal function contributed to the dangerous situation. Despite the odds for fatal outcome, the patient recovered completely, and long-term management was initiated to prevent recurrent hyperkalemia.

In the chronic kidney disease population metabolic acidosis is prevalent presenting already in the early stages of renal dysfunction. The pathogenesis associates the lack of bicarbonate production with the accumulation of organic/inorganic acids and the development of tubulointerstitial damage through ammonium retention and complement deposition. The empiric use of oral sodium bicarbonate represents an interesting therapeutic option that has been documented in a few clinical trials in human subjects. The availability of oral sodium, in its diverse forms, represents an inexpensive and simple way of treating an entity that could hasten the progression of kidney disease, as well as protein catabolism, bone disease and mortality.

Background: The effectiveness of sodium bicarbonate (SB) has recently been questioned although it is often used to correct metabolic acidosis of neonates. The aim of the present study was to examine its effect on hemodynamic changes and hydrogen peroxide (H(2)O(2)) generation in the resuscitation of hypoxic newborn animals with severe acidosis., Methods: Newborn piglets were block-randomized into a sham-operated control group without hypoxia (n = 6) and two hypoxia-reoxygenation groups (2 h normocapnic alveolar hypoxia followed by 4 h room-air reoxygenation, n = 8/group). At 10 min after reoxygenation, piglets were given either i.v. SB (2 mEq/kg), or saline (hypoxia-reoxygenation controls) in a blinded, randomized fashion. Hemodynamic data and blood gas were collected at specific time points and cerebral cortical H(2)O(2) production was continuously monitored throughout experimental period. Plasma superoxide dismutase and catalase and brain tissue glutathione, superoxide dismutase, catalase, nitrotyrosine and lactate levels were assayed., Results: Two hours of normocapnic alveolar hypoxia caused cardiogenic shock with metabolic acidosis (PH: 6.99 ± 0.07, HCO(3)(-): 8.5 ± 1.6 mmol/L). Upon resuscitation, systemic hemodynamics immediately recovered and then gradually deteriorated with normalization of acid-base imbalance over 4 h of reoxygenation. SB administration significantly enhanced the recovery of both pH and HCO(3-) recovery within the first hour of reoxygenation but did not cause any significant effect in the acid-base at 4 h of reoxygenation and the temporal hemodynamic changes. SB administration significantly suppressed the increase in H(2)O(2) accumulation in the brain with inhibition of superoxide dismutase, but not catalase, activity during hypoxia-reoxygenation as compared to those of saline-treated controls., Conclusions: Despite enhancing the normalization of acid-base imbalance, SB administration during resuscitation did not provide any beneficial effects on hemodynamic recovery in asphyxiated newborn piglets. SB treatment also reduced the H(2)O(2) accumulation in the cerebral cortex without significant effects on oxidative stress markers presumably by suppressing superoxide dismutase but not catalase activity.

We report a 54-year-old man with osteomalacia due to a bladder reconstruction performed 35 years previously. He had had slowly progressive chest and back pain for 18 months. Osteomalacia due to metabolic acidosis was suspected based on hyperalkalinephosphatasemia and a high serum chloride level, and the diagnosis was confirmed by bone scintigraphy. His symptoms and blood electrolyte levels were improved by oral medication, including sodium hydrogen carbonate. Measurement of the serum chloride level is simple and useful for evaluating acidosis, for which a regular blood test is essential in patients who have undergone bladder reconstruction.

Background: Clinical assessment of metabolic acidosis in calves with neonatal diarrhea can be difficult because increased blood concentrations of d-lactate and not acidemia per se are responsible for most of the clinical signs exhibited by these animals., Objectives: To describe the correlation between clinical and laboratory findings and d-lactate concentrations. Furthermore, the theoretical outcome of a simplified treatment protocol based on posture/ability to stand and degree of dehydration was evaluated., Animals: A total of 121 calves with diagnosis of neonatal diarrhea admitted to a veterinary teaching hospital during an 8-month study period., Methods: Prospective blinded cohort study. Physical examinations were carried out following a standardized protocol. Theoretical outcome of treatment was calculated., Results: Type and degree of metabolic acidosis were age dependent. The clinical parameters posture, behavior, and palpebral reflex were closely correlated to base excess (r = 0.74, 0.78, 0.68; P < .001) and d-lactate concentrations (r = 0.59, 0.59, 0.71; P < .001), respectively. Thus, determining the degree of loss of the palpebral reflex was identified as the best clinical tool for diagnosing increase in serum d-lactate concentrations. Theoretical outcome of treatment revealed that the tested dosages of sodium bicarbonate are more likely to overdose than to underdose calves with diarrhea and metabolic acidosis., Conclusions and Clinical Importance: The degree of metabolic acidosis in diarrheic calves can be predicted based on clinical findings. The assessed protocol provides a useful tool to determine bicarbonate requirements, but a revision is necessary for calves with ability to stand and marked metabolic acidosis., (Copyright © 2011 by the American College of Veterinary Internal Medicine.)

Clinical studies of the last 15 years have shown the benefit of pharmacological interventions on the progression of chronic kidney disease, confirming the concept of nephroprotection. Pharmacological blockade of the renin angiotensin system remains the cornerstone of the nephroprotective treatment but the benefits and limitations are now better defined. The RAS blockers are all the more efficient than the proteinuria is abundant and nephroprotection is obtained in proportion to the reduction in proteinuria. Combinations of ACEI+ARA are not validated and their use should be considered only under the supervision of a specialist when optimal monotherapy has failed. The target blood pressure has been the subject of recent controversies, particularly in type 2 diabetic patients with nephropathy. The target should be individualized based on the main risk, renal or cardiovascular. Recent maneuvers have also shown a nephroprotective effect, including the correction of metabolic acidosis with sodium bicarbonate., (Copyright © 2011. Published by Elsevier Masson SAS.)

In chronic kidney disease patients, inexorable renal function decline is reduced by renin-angiotensin system (RAS) blockers. ACE inhibitors and angiotensin receptor blockers decrease blood pressure and proteinuria. Guidelines recommend a reduction of blood pressure to less than 130/80 mmHg and urinary protein excretion below 0.5 g/d. The combined use of a diuretic increases anti-proteinuric effect and blood pressure control of RAS blockers. Drugs as mineralo-corticocoids receptor antagonist and endothelin receptor antagonists reduce further albuminuria in combination with RAS blocker, but side effects need to be precised. Both metabolic acidosis and hyperuricemia represent new therapeutic goals to slow renal function decline in CKD patients. Renal fibrosis treatment and regenerative medicine are stemming and will be important issues for kidney and other organs in the future., (Copyright © 2011 Elsevier Masson SAS. All rights reserved.)

Background: A consensus has not been established for the standard treatment of hyperkalemia in the neonatal population. Most treatment regimens include a dextrose/insulin infusion. Additional agents used include calcium, sodium bicarbonate, polystyrene sulfonate, and albuterol. This study assessed the safety and efficacy of a potassium cocktail (k-cocktail) containing dextrose, insulin, calcium gluconate, and sodium lactate for treatment of neonatal hyperkalemia., Objective: To determine whether modifications to a potassium cocktail formulation, based on a prior quality improvement project, resulted in a decrease in the incidence of hyperglycemia and acidosis associated with its use, and to evaluate the effectiveness of the k-cocktail in lowering serum potassium levels and the incidence of adverse effects., Methods: We conducted a retrospective cohort study of neonates with hyper-kalemia who received 2 k-cocktail formulations (group 1 [n = 13], original formulation, dextrose:insulin 5:1; group 2 [n = 26], modified formulation, dextrose: insulin 3.3:1). Group 2 subjects were matched 2:1 by gestational age and birth weight with those in group 1. Variables related to safety and effectiveness of therapy were assessed by medical record review. The following tests were used to assess group differences: χ(2), Fisher exact, 2-tailed t-tests, and mixed linear models., Results: The incidence of hyperglycemia during the modified k-cocktail infusion in group 2 decreased from 76.9% to 21.7% (p = 0.001). Serum blood glucose concentrations increased during the infusion, on average, for group 1 infants and were unchanged during the infusion for those in group 2. The incidence of acidosis during the infusion was similar between groups (group 1 [76.9%] vs group 2 [68.2%]; p = 0.58). No significant adverse events were observed. Serum potassium concentrations decreased similarly in both groups., Conclusions: An intravenous infusion including a dextrose:insulin ratio of 3.3:1, compared with a higher ratio, results in less hyperglycemia and appears to be as effective in decreasing potassium concentrations in newborns.

Sodium bicarbonate is used to treat metabolic acidosis or to induce metabolic alkalosis in sick neonates. The aim of this study was to quantify the decrease in serum concentration of ionized magnesium ([Mg(2+)]) when sodium bicarbonate is administered in vivo. We administered 1 mEq/kg body weight sodium bicarbonate 4.2% for correction of metabolic acidosis (n = 11) for management of persistent pulmonary hypertension (n = 3). After sodium bicarbonate treatment, serum pH increased by an average of 0.046 (P < 0.001), serum [Mg(2+)] decreased by an average of 0.07 mmol/L (P < 0.01), and serum [Ca(2+)] decreased by an average of 0.06 mmol/L (P = 0.04). There was a significant correlation between baseline [Mg(2+)] and baseline [Ca(2+)] (R(2) = 0.328, P = 0.032). Sodium bicarbonate therapy in infants causes a significant decrease in [Mg(2+)] and serum [Ca(2+)]. We suggest that infusion of sodium bicarbonate be effected while monitoring serum [Mg(2+)] and serum [Ca(2+)].

The high metabolic rate of tumours often leads to acidosis and hypoxia in poorly perfused regions. Tumour cells have thus evolved the ability to function in a more acidic environment than normal cells. Key pH regulators in tumour cells include: isoforms 2, 9 and 12 of carbonic anhydrase, isoforms of anion exchangers, Na+/HCO3- co-transporters, Na+/H+ exchangers, monocarboxylate transporters and the vacuolar ATPase. Both small molecules and antibodies targeting these pH regulators are currently at various stages of clinical development. These antitumour mechanisms are not exploited by the classical cancer drugs and therefore represent a new anticancer drug discovery strategy.

Acid-sensing ion channels (ASICs) are ligand-gated cation channels that respond to acidic stimuli. They are expressed throughout the mammalian nervous system. Complex subunit combinations and lack of specific blockers of native receptors result in the difficulty of resolving the functions of ASICs. In this study, we showed that rat pheochromocytoma cells (PC12 cells) functionally express ASICs with the activity of endogenous proton-gated conductance. PF is the principal active ingredient extracted from the root of Paeoniae alba, a Chinese herb commonly used to treat neurodegenerative disorders, especially PD. It was found that PF significantly up regulated the expression of LC3-II, which is specifically associated with autophagic vacuole membranes. PF also reduced the MPP(+) and acidosis-induced accumulation of α-synuclein, the major component of Lewy bodies. Moreover, PF was highly efficacious in modulating ASICs activity and protein expression. In addition, the data showed that PF was able to protect PC12 cells against MPP(+) and acidosis-induced cytotoxicity. In summary, these findings demonstrate for the first time that PF could enhance the autophagic degradation of α-synuclein by regulating the expression and activity of ASICs and thus produces protective effects against cytotoxicity. It also offers the experimental evidence for the potential role of ASICs in the pathogenesis of PD., (Copyright © 2011 Elsevier B.V. All rights reserved.)

The most common method of controlling acidemia during lung-protective ventilation is CO₂ removal with an extracorporeal lung assist (ECLA) system. Another possibility to prevent acidemia is based on intravenous (i.v.) application of tris-hydroxymethyl-aminomethane (3 mol/L, THAM) buffer, which can bind hydrogen protons and which can be removed from the body via renal replacement therapy (RRT). We investigated whether RRT combined with predilutional (prefilter) THAM-application provides an alternative to ECLA for a rescue situation. For this, anesthetized pigs, 40 kg of body weight, six animals per group, underwent 5 h of acidemia (pH 7.19-7.24) induced by acid infusion and permissive hypercapnia (low tidal volume ventilation, PaCO₂ 80-90 mmHg). Isovolemic, high-volume hemofiltration (HVHF) was operated with predilutional THAM-infusion for treatment. To evaluate adverse effects of this approach, we set up further groups: HVHF with postdilutional (post-filter) THAM-application; i.v.-THAM without HVHF; normal pH homeostasis with HVHF. Acid-base parameters, hemodynamics, renal function, and lung morphology were investigated. HVHF with predilutional THAM-infusion of 8 mmol/kg/h allowed fast pH normalization, significant reduction in PaCO₂ to 56 mmHg and tolerable hemodynamics. HVHF alone or lower dose i.v. THAM (2 mmol/kg/h) failed to produce a comparable result. A postdilutional THAM infusion reduced hemodynamic tolerability and increased lung edema formation. HVHF in pigs with normal acid-base status resulted in a decreased base excess and urine acidification. In conclusion, predilutional THAM-application and HVHF corrected the acid-base disorder and improved pulmonary hemodynamics. Further studies are necessary to optimize the protocol including the dosage., (© 2011, Copyright the Authors. Artificial Organs © 2011, International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.)

Introduction: Sodium acetate has been shown to cause hemodynamic instability when used as a hemodialysis buffer. The pattern of hemodynamic response to injury will be evaluated between those who received sodium acetate and those who did not.The primary purpose of the study is to analyze the effect of sodium acetate on hemodynamic parameters. Secondarily we looked at the effects on prevention and treatment of hyperchloremic metabolic acidosis., Methods: The study arm was comprised of patients who had received sodium acetate infusions in place of normal saline between March 2005 and December 2009. A control arm was created based on matching three pre-treatment variables: injury severity score (ISS), pH (+/- 0.03) and base deficit (+/- 3). A retrospective chart review was performed for patients in both arms. Blood pressure, arterial blood gas data and chemistry values were recorded for the time points of -6, -1, 0, 1, 6, 12, 24, 48, and 72 hours from start of sodium acetate infusion. Patients were excluded based on the following criteria: patients who were given sodium bicarbonate within 48 hours of starting sodium acetate, those given sodium acetate as a bolus, non-trauma patients, burn patients, patients who expired within 24 hours of arrival to the ICU, patients diagnosed with rhabdomyolysis and patients whose medical record could not be obtained., Results: A total of 78 patients were included in the study, 39 in the study arm and 39 in the control arm. There were no statistically significant drops in blood pressure within either group. The median pH between the two groups at the start of infusion was equal. Both groups trended towards normal pH with the study arm improving faster than the control arm. The median serum bicarbonate at start of sodium acetate infusion was 19 mmol/L and 20 mmol/L at time zero for the study and control arms respectively with both trending upward during the study period. Chloride trended up initially in both groups but the study arm began to correct sooner at 24 hours compared to 48 hours for the control arm., Conclusion: We analyzed the use of sodium acetate as an alternative to normal saline or lactated ringers during resuscitation of critically ill trauma patients at a single center. Our data shows that the hemodynamic profile remained favorable, without evidence of instability at any point during the study period. Normalization of hyperchloremia and metabolic acidosis occurred faster in the patients who received sodium acetate.

We have identified a novel homozygous nonsense mutation (W516X) in the kidney-type electrogenic sodium bicarbonate cotransporter 1 (NBC1) in a patient with isolated proximal renal tubular acidosis (pRTA). To specifically address the pathogenesis of this mutation, we created NBC1 W516X knock-in mice to match the patient's abnormalities. The expression of NBC1 mRNA and protein in the kidneys of NBC1(W516X/W516X) mice were virtually absent, indicating that nonsense-mediated mRNA decay (NMD) is involved in the defective transcription and translation of this mutation. These mice not only recapitulated the phenotypes of this patient with growth retardation, pRTA, and ocular abnormalities, but also showed anemia, volume depletion, prerenal azotemia, and several organ abnormalities, culminating in dehydration and renal failure with early lethality before weaning. In isolated renal proximal tubules, both NBC1 activity and the rate of bicarbonate absorption were markedly reduced. Unexpectedly, there was no compensatory increase in mRNA of distal acid/base transporters. Sodium bicarbonate but not saline administration to these mutant mice markedly prolonged their survival, decreased their protein catabolism and attenuated organ abnormalities. The prolonged survival time uncovered the development of corneal opacities due to corneal edema. Thus, NBC1(W516X/W516X) mice with pRTA represent an animal model for metabolic acidosis and may be useful for testing therapeutic inhibition of NMD in vivo.

Metabolic acidosis is a prevalent complication in moderate and late stages of chronic kidney disease (CKD). It is established that the correction of metabolic acidosis may improve metabolic bone disorders and protein degradation in the skeletal muscle, two characteristic complications of patients with advanced CKD. In the last 18 months, three randomized controlled trials have drawn the attention on a novel indication to correct metabolic acidosis in these patients, i.e., halting CKD progression. These data show that sodium bicarbonate, a cheap and easily manageable treatment, may delay the progression of CKD and the need of a renal replacement therapy such as dialysis or kidney transplantation.

Sodium bicarbonate has been standard therapy for the treatment of acidosis. In lactic acidosis and hypercapnic acidosis, however, there is no clinical data supporting its effectiveness. We reviewed the literature of the efficacy of sodium bicarbonate on lactic acidosis and hypercapnic acidosis. On both conditions, we have no solid evidence supporting its beneficial effect. Conversely, acidosis or hypercapnia might be protective in acute lung and systemic organ injury. Therefore, the unprepared use of bicarbonate might be harmful in terms of fluid and sodium overload and excess lactate concentrations. According to current literature, we cannot recommend sodium bicarbonate administration for patients with lactic acidosis and hypercapnic acidosis.