Electroencephalographic consequences of alkalinization therapy during lactic acidosis: Different effects of sodium bicarbonate and carbicarb

To explore the differences between sodium bicarbonate and an experimental buffer, Carbicarb in the therapy of lactic acidosis, we performed the following studies. Rats were subjected to a combined respiratory and metabolic acidosis designed to simulate clinical lactic acidosis following cardiac arrest and resuscitation. The electroencephalogram (EEG) was monitored during induction and therapy of acidosis. The acidosis model was associated in a 22% fall in the amplitude of the EEG along with marked decreases in mean blood pressure, arterial PO₂, and pH, as well as increases in arterial PCO₂. Bicarbonate infusion was associated with a marked fall in mean blood pressure along with transient increases in arterial PCO₂, which were accompanied by significant and sustained decreases in the amplitude of the EEG. In contrast, Carbicarb did not lower blood pressure and had only transient effects on the amplitude of the EEG. These data suggested that bicarbonate therapy had deleterious effects on cerebral electric activity in this model of acidosis that were not shared by Carbicarb. if these data are confirmed in humans, Carbicarb may have advantages over bicarbonate in the clinical therapy of acute acidosis.     

Adverse haemodynamic effects of sodium bicarbonate in metabolic acidosis

In a patient with viral pneumonia, acute respiratory and renal failure and metabolic acidosis, a reduction in left ventricular stroke work was observed on the three occasions that 100 ml of 8.4% sodium bicarbonate was infused. Blood pressure and cardiac output decreased on two of the occassions. Since intravenous sodium bicarbonate may produce adverse cardiovascular effects, a right heart catheter should be inserted to monitor these effects when alkali therapy is administered to an acutely ill patient with metabolic acidosis.     

Effectiveness of sodium bicarbonate infusion on mortality in septic patients with metabolic acidosis

Objective

Although sodium bicarbonate (SB) solution has been widely used in clinical practice, its effect on mortality when administered to a large population of patients with acidosis is not known. The study aimed to investigate the effectiveness of SB infusion in septic patients with metabolic acidosis.

Methods

Septic patients with metabolic acidosis were identified from the Medical Information Mart for Intensive Care (MIMIC)-III database. Propensity score (PS) was used to account for the baseline differences in the probability to receive SB or not. The marginal structural Cox model (MSCM) was employed to adjust for both baseline and time-varying confounding factors.

Main results

A total of 1718 septic patients with metabolic acidosis were enrolled in the study, including 500 in the SB group and 1218 in the non-SB group. Both pH [7.16 (standard deviation (SD): 0.10) vs. 7.22 (SD: 0.07); p?<?0.001] and bicarbonate concentration (BC) [11.84 (SD: 3.63) vs. 14.88 (SD: 3.36) mmol/l; p?<?0.001] were significantly lower in the SB than that in the non-SB group. While there was no significant mortality effect in the overall population [hazard ratio (HR): 1.04; 95% CI 0.86–1.26; p?=?0.67], SB was observed to be beneficial in patients with acute kidney injury (AKI) stage 2 or 3 and pH?<?7.2 (HR 0.74; 95% CI 0.51–0.86; p?=?0.021). Similar results were replicated with the MSCM.

Conclusion

Our study observed that SB infusion was not associated with improved outcome in septic patients with metabolic acidosis, but it was associated with improved survival in septic patients with AKI stage 2 or 3 and severe acidosis. The results need to be verified in randomized controlled trials.

     

The effect of sodium bicarbonate on cytokine secretion in CKD patients with metabolic acidosis

The incidence of acidosis increases with the progression of chronic kidney disease (CKD). Correction of acidosis by sodium bicarbonate may slow CKD deterioration. Inflammation, which is common in CKD, may be related to acidosis. Whether the slower rate of GFR decline following the correction of acidosis is related to changes in inflammatory markers is unknown. The current study examined whether correcting CKD-acidosis affected inflammatory cytokines secretion. Thirteen patients with CKD 4–5 and acidosis were tested for cytokines secretion from peripheral-blood mononuclear cells at baseline and after one month of oral sodium bicarbonate. Following treatment with sodium bicarbonate there was no change in weight, blood pressure, serum creatinine, albumin, sodium, calcium, phosphate, PTH, hemoglobin and CRP. Serum urea decreased (134 ± 10–116 ± 8 mg/dl, P = 0.002), potassium decreased (5.1 ± 0.4–4.8 ± 0.1 mequiv./l, P = 0.064), pH increased (7.29 ± 0.01–7.33 ± 0.01, P = 0.008), and serum bicarbonate increased (18.6 ± 0.4 mequiv./l to 21.3 ± 0.3 mequiv./l, P = 0.001). The secretion of the anti-inflammatory cytokine IL-10 decreased (2.75 ± 0.25 ng/ml to 2.29 ± 0.21 ng/ml, P = 0.041). There was no significant change in the secretion of the other pro-inflammatory and anti-inflammatory cytokines, including IL-1β, IL-2, IL-6, TNFα, IFNγ, IL-1ra. Thus, correcting acidosis in CKD with bicarbonate decreases IL-10 secretion. Its significance needs to be further investigated.     

Parallel adaptation of the rabbit renal cortical sodium/proton antiporter and sodium/bicarbonate cotransporter in metabolic acidosis and alkalosis.

Recent studies have shown that the bicarbonate reabsorptive capacity of the proximal tubule is increased in metabolic acidosis. For net bicarbonate reabsorption to be regulated, there may be changes in the rate of apical H+ secretion as well as in the basolateral base exit step. The present studies examined the rate of Na+/H+ exchange (acridine orange method) and Na+/HCO3 cotransport (22Na uptake) in apical and basolateral membranes prepared from the rabbit renal cortex by sucrose density gradient centrifugation. NH4Cl loading was used to produce acidosis (arterial pH, 7.27 +/- 0.03), and Cl-deficient diet with furosemide was used to produce alkalosis (arterial pH, 7.51 +/- 0.02). Maximal transport rate (Vmax) of Na+/H+ antiporter and Na+/HCO3 cotransporter were inversely related with plasma bicarbonate concentration from 6 to 39 mM. Furthermore, the maximal transport rates of both systems varied in parallel; when Vmax for the Na+/HCO3 cotransporter was plotted against Vmax for the Na+/H+ antiporter for each of the 24 groups of rabbits, the regression coefficient (r) was 0.648 (P less than 0.001). There was no effect of acidosis or alkalosis on affinity for Na+ of either transporter. We conclude that both apical and basolateral H+/HCO3 transporters adapt during acid-base disturbances, and that the maximal transport rates of both systems vary in parallel during such acid-base perturbations.     

Comparison of sodium bicarbonate with dichloroacetate treatment of hyperlactatemia and lactic acidosis in the ischemic rat

Serum lactic acidosis is characterized by a pH less than 7.25 and lactate greater than 5 mEq. Although sodium bicarbonate (NaHCO3) is standard treatment for this condition, clinical and experimental studies suggest that high doses of NaHCO3 may be ineffectual or even detrimental to brain, cardiovascular, and respiratory function, as well as survival. For this reason, low dose therapy with NaHCO3 has been recommended. Sodium dichloroacetate (NaDCA) has been used successfully to treat clinical and experimentally-induced lactic acidosis. The present study was designed to compare the effects of low dose NaHCO3 with NaDCA on blood pressure, blood chemistries and brain metabolites in rats with a low flow-induced (Type A, the most common type) lactic acidosis. Fasted male Wistar rats were subjected to cerebral ischemia and systemic hypotension for 30 min at which time, if the pH or HCO-3 fell to 7.2 or 10, respectively, the rat was treated with NaHCO3, NaDCA, or an equal volume of sterile water. Over the 30 min of recirculation that followed ischemia, treatment had no effect on blood pressure or glucose or on brain glucose or glycogen. NaHCO3 had no effect on lactate but appeared to stabilize pH and increase HCO3- more than in sham- or NaDCA-treated rats. Although NaDCA caused a greater increase in HCO3- than sham treatment, pH continued to decline. However, lactate decreased more in NaDCA- than in sham- or NaHCO3- treated rats. These results suggest that low dose NaHCO3 is not detrimental in this model; however, although NaHCO3 stabilized pH, it did not rapidly correct the acidosis. NaDCA at this dose had no effect on the acidosis but was effective in decreasing lactate. Since serum lactate has previously correlated with survival and since higher doses of NaDCA have corrected lactic acidosis in other studies, future evaluation of postischemic treatment with higher doses of NaDCA is warranted.     

A nomogram for the emergency treatment of metabolic acidosis

Results obtained using a new standardized method of correction of acidotic states are reported in this paper. The treatment consists in giving the patient a mixture of buffers including sodium bicarbonate, sodium lactate and Tham. The formula needed for a particular patient can be calculated by the use of a nomogram that takes into account all the parameters that define the acidotic state. Sixty-seven patients with different degrees of severe acidosis have been treated by this method. Optimum correction has been obtained in all the cases. The efficiency of the correction has been evaluated by the method proposed in the preceding paper (Bondoli, Magalini &; Proietti, 1973).     

碳酸氢钠治疗开放性胫骨骨折伴感染的临床研究

目的探讨碳酸氢钠在治疗胫骨开放性骨折伴感染中的作用。方法胫骨开放性骨折伴感染患者根据骨折开放程度随机分为常规治疗组与碳酸氢钠治疗组。常规治疗组患者给予骨折复位,感染创口局部冲洗,静脉滴注抗生素抗感染治疗;碳酸氢钠治疗组在常规治疗的基础上给予碳酸氢钠静脉滴注与感染创口局部冲洗。治疗前创口感染伤口渗出液行涂片找细菌与测定pH值,并在治疗前、后检测血pH值及电解质的变化。结果感染伤口感染菌主要为铜绿假单胞菌,其次为大肠埃希菌。铜绿假单胞菌感染伤口pH值7.2±0.013,大肠埃希菌感染伤口pH值7.3±0.011。血液pH值及电解质在治疗前后均无显著变化。碳酸氢钠治疗组住院治疗时间及创口愈合时间明显短于普通治疗组(P<0.05)。结论碳酸氢钠可以促进骨折感染伤口与骨折的愈合,缩短住院时间,有一定应用价值。     

Changes in bone sodium and carbonate in metabolic acidosis and alkalosis in the dog

Metabolic acidosis and alkalosis were produced in adult dogs over 5- to 10-day periods. Midtibial cortical bone was analyzed for calcium, sodium, phosphorus, and carbonate. In acidosis bone CO(3)/Ca decreased 9.5% and bone Na/Ca decreased 6.3%. In alkalosis bone CO(3)/Ca increased 3.1% and bone Na/Ca increased 3.0%.Previous attempts to account for changes in net acid balance by summation of extra- and intracellular acid-base changes have uniformly resulted in about 40-60% of acid gained or lost being "unaccounted for." If it is assumed that changes in tibial cortex reflect changes in the entire skeletal system, changes in bone CO(3) (=) are sufficiently large to account for the "unaccounted for" acid change without postulating changes in cellular metabolic acid production.     

Severe metabolic acidosis induced in a patient during fasting by KCl administration

The purpose of this study was to determine the cause of an acute metabolic acidosis of the normal anion gap type which developed during a 3 day period when 64 mmol of KCl was administered daily to an obese but otherwise healthy subject fasted for 2 weeks (called the index case). She had typical ketoacidosis of fasting for the first 13 days of fasting; since the plasma [K] was 3.6 mmol/l, she was given 64 mmol of KCl daily for 3 days. On day 3 of KCl treatment, the plasma [HCO3] was 13 mmol/l with no change in the plasma anion gap or 3-hydroxybutyrate concentration; the plasma [K] had risen to 4.3 mmol/l. The cause of the acidosis was a reduction of urine ammonium excretion by 42 mmol/day without a parallel fall in the rate of 3-hydroxybutyrate excretion. Since renal ammonium production can be inhibited by K administration, 5 other obese subjects were studied in a similar fashion to gain insight into the problem. They had a similar reduction in the daily rate of ammonium excretion (41 mmol) after KCl; however, their daily 3-hydroxybutyrate excretions declined by a similar amount (47 mmol) and thus metabolic acidosis did not develop.     

瑞白混合液联合2％碳酸氢钠溶液治疗恶性肿瘤化疗患者口腔霉菌感染

化疗是治疗肿瘤的主要方法,虽然化疗可以杀伤肿瘤细胞,但也在不同程度上损伤了正常组织、细胞,其中口腔霉菌感染就是其常见的并发症之一。许多恶性肿瘤患者在使用化疗药物时,如5-氟尿嘧啶,可引起局部的炎症反应及血管扩张,造成口腔等黏膜的感染。     

Severe metabolic acidosis and disturbances of calcium metabolism induced by acetazolamide in patients on haemodialysis

1. To investigate mechanisms of extrarenal buffering in uraemic acidosis, we studied the effects of the carbonic anhydrase inhibitor, acetazolamide, in normal subjects and in patients with end-stage kidney disease on maintenance haemodialysis with virtually no urine output. 2. Acetazolamide (500 mg) was administered daily for 7 days, after pretreatment for 1 month with 1,25-dihydroxyvitamin D (n = 12) or placebo (n = 12); only placebo was administered to a third group (n = 12) of haemodialysis patients. In addition, acetazolamide was administered to normal control subjects (n = 12). 3. Treatment with acetazolamide resulted in a more marked metabolic acidosis in haemodialysis patients than in normal control subjects and the effect in haemodialysis patients was attenuated by prior treatment with 1,25-dihydroxyvitamin D. 4. The administration of acetazolamide to haemodialysis patients led to an increase in serum inorganic phosphorus, bone isoenzyme of alkaline phosphatase and parathyroid hormone, and a reduction in serum calcium, whereas acetazolamide had no effect on these variables in normal subjects. In contrast, in the haemodialysis patients previously treated with 1,25-dihydroxyvitamin D, acetazolamide increased serum inorganic phosphorus, bone isoenzyme of alkaline phosphatase, parathyroid hormone and serum calcium. 5. We hypothesize that the metabolic acidosis induced by acetazolamide in haemodialysis patients may result from interference with the mechanisms of extrarenal buffering. 6. As parathyroid hormone, 1,25-dihydroxyvitamin D and carbonic anhydrase are thought to be involved in bone buffering, we suggest that the marked acidosis seen in haemodialysis patients treated with acetazolamide may be due to impaired parathyroid hormone-mediated bone buffering.     

Dimethyl sulfoxide and sodium bicarbonate in the treatment of refractory cancer pain

Pain is a major concern of cancer patients and a significant problem for therapy. Pain can become a predominant symptom in advanced cancers. In this open-label clinical study, the authors have treated 26 cancer patients who have been declared as terminal without the option of conventional treatment. These patients suffered from high levels of pain that was poorly managed by all available interventional approaches recommended by World Health Organization (WHO) guideline. The results indicate that intravenous infusion of dimethyl sulfoxide (DMSO) and sodium bicarbonate (SB) solution can be a viable, effective, and safe treatment for refractory pain in cancer patients. These patients had pain due to the disease progression and complication of chemotherapy and radiation. Moreover, the preliminary clinical outcome of 96-day follow-up suggests that the application of DMSO and SB solution intravenously could lead to better quality of life for patients with nontreatable terminal cancers. The data of this clinical observation indicates that further research and application of the DMSO and SB combination may help the development of an effective, safe, and inexpensive therapy to manage cancer pain.     

The value of the chloride:sodium ratio in differentiating the aetiology of metabolic acidosis

OBJECTIVE: Stewart's physicochemical approach to acid-base balance defines the aetiology of a metabolic acidosis by quantifying anions of tissue acids (TA), which consist of unmeasured anions (UMA) and/or lactate. We hypothesised that an increase in TA during metabolic acidosis would lead to a compensatory fall in the plasma chloride (Cl) relative to sodium (Cl:Na ratio) in order to preserve electro-neutrality. Thus, the Cl:Na ratio could be used as a simple alternative to the anion gap in identifying raised TA. PATIENTS: Two hundred and eighty two consecutive patients who were admitted to our Paediatric Intensive Care were enrolled in the study. INTERVENTIONS: We obtained 540 samples (admission n = 282, 24 h n = 258) for analysis of blood chemistry, lactate and quantification of TA and UMA. Samples were subgrouped into those with metabolic acidosis (standard bicarbonate < 22 mmol/l) either with or without increased UMA (> 3 mEq/l). MEASUREMENTS AND RESULTS: Metabolic acidosis occurred in 46% of samples, of which 52.3% (120/230) had increased UMA. The dominant component of TA was UMA rather than lactate, and these two components did not always rise in tandem. Our hypothesis of relative hypochloraemia was supported by a lower Cl:Na ratio (P < 0.0001) but not a lower absolute Cl (P = 0.5) in the acidotic subgroup with raised UMA, and by the inverse relationship between TA and the Cl:Na ratio. (coefficient of determination (r2) = 0.37, P < 0.0001). The best discriminator for the presence of raised TA was the albumin-corrected anion gap (AGcorr), however, this could not track changes in TA with clinical accuracy. The Cl:Na ratio discriminated reasonably well, a ratio of < 0.75 identified TA (positive predictive value (PPV) 88%) with a likelihood ratio (LR) similar to the AG (7.8 vs7.4). Conversely, a high ratio (> 0.79) excluded TA (PPV 81%, LR 4.5). Base deficit (BD) and lactate performed poorly. CONCLUSION: In metabolic acidosis due to TA, plasma Cl concentration decreases relative to sodium. The Cl:Na ratio is a simple alternative to the AG for detecting TA in this setting.     

低嘌呤饮食联合碳酸氢钠、非布司他治疗肥胖合并高尿酸血症的临床研究

目的 探究低嘌呤饮食联合碳酸氢钠、非布司他治疗肥胖合并高尿酸血症的临床疗效.方法 前瞻性选取2018年1月至2019年3月保定市第一中心医院收治的肥胖合并高尿酸血症患者124例,采用随机数字表法分为观察组与对照组,对照组采用低嘌呤饮食治疗,观察组在对照组基础上联合碳酸氢钠、非布司他治疗.对比2组患者治疗前和治疗后3个月...     

双胍类药物引起乳酸酸中毒21例分析

目的提高对双胍类药物引起的乳酸酸中毒的认识,探讨降低糖尿病乳酸酸中毒病死率的方法。方法回顾性分析2006年至2010年河南宏力医院收治的21例糖尿病乳酸酸中毒患者的临床资料。结果老年患者服药依从性不高,双胍类药物使用不当,肝、肾功能损害是服用双胍类药物的糖尿病患者出现乳酸酸中毒的易发因素,严重乳酸酸中毒可引起多器官功能衰竭及死亡。本组21例中9例死亡,死亡组pH值、HCO3-、阴离子间隙较存活组明显下降（P〈0.05）。结论严格掌握双胍类降糖药的禁忌证,提高患者的依从性,可减少糖尿病乳酸酸中毒的发病,早期给氧、充分补液、应用葡萄糖加小剂量胰岛素、尽早血液透析是治疗糖尿病乳酸酸中毒成功的关键。     

非典型抗精神病药物治疗精神分裂症所致代谢综合征对照研究

目的探讨非典型抗精神病药物治疗精神神分裂症患者导致代谢综合征的发生状况。方法将同期住院的128例精神分裂症患者随机分为A组、B组、C组、D组,每组32例,分别口服氯氮平、奥氮平、喹硫平、阿立哌唑治疗,观察12周。于治疗前及治疗4周、8周、12周末测量身高、体质量及腰围,计算体质量指数,检测血糖、血脂、胰岛素等。结果4组患者治疗12周末均出现不同程度的代谢异常,A组代谢综合征发生率为37．5％、B组为28．12％、C组为34．37％,D组为3．12％,以A组、B组、C组尤为明显（P〈0．05或0．01）。治疗8周末起,A组、B组、C组体质量、体质量指数、腰围、空腹血糖、胰岛素、胰岛素抵抗指数各项指标检测结果均较治疗前显著升高（P〈0．05或0．01）,D组各项指标与治疗前比较差异均无显著性（P〉0．05）。结论不同类型的非典型抗精神病药物导致代谢综合征的发生率有较大差异性,以氯氮平、喹硫平、奥氮平治疗导致代谢综合征的发生更为显著。