Effect of volume expansion on renal citrate and ammonia metabolism in KCl-deficient rats.

When rats with desoxycorticosterone acetate (DOCA)-induced potassium chloride deficiency are given sodium chloride there is simultaneously a partial correction of metabolic alkalosis and a marked reduction in urinary citrate excretion and renal citrate content. To examine DOCA's role in this phenomenon and to determine how sodium chloride alters renal metabolism, rats were made KC1 deficient using furosemide and a KC1-deficient diet. Renal citrate and ammonia metabolism were then studied after chronic oral sodium chloride administration or acute volume expansion with isotonic mannitol. Although both maneuvers partially corrected metabolic alkalosis, sodium chloride raised serum chloride concentration while mannitol significantly decreased it. Urinary citrate excretion decreased to 10% of control in rats given NaCl and to 50% of control in rats infused with mannitol. The filtered load of citrate was constant or increased indicating increased tubular citrate reabsorption. Renal cortical citrate content also decreased approximately 50%. Renal cortical slices from KCl-deficient rats incubated in low or normal chloride media produced equal amounts of 14CO2 from (1, 5-14C) citrate. In addition, urinary ammonia excretion increased by over 300% in both groups. This occurred in the mannitol group despite increased urinary pH and flow rate indicating a rise in renal ammonia production. It seems that neither DOCA nor an increase in serum chloride concentration explains the experimental results. Rather, it appears that volume expansion is responsible for increased renal tubular citrate reabsorption and renal ammonia production. As these renal metabolic responses ordinarily occur in response to acidosis, the data are consistent with the hypothesis that volume expansion reduces renal cell pH in 3KCl-deficient rats.     

Metabolic alkalosis

Metabolic alkalosis is a primary pathophysiologic event characterized by the gain of bicarbonate or the loss of nonvolatile acid from extracellular fluid. The kidney preserves normal acid-base balance by two mechanisms: bicarbonate reclamation, mainly in the proximal tubule, and bicarbonate generation, predominantly in the distal nephron. Bicarbonate reclamation is mediated mainly by a Na(+)-H(+) antiporter and to a smaller extent by the H(+)-ATPase (adenosine triphosphate-ase). The principal factors affecting HCO3(-) reabsorption include effective arterial blood volume, glomerular filtration rate, chloride, and potassium. Bicarbonate regeneration is primarily affected by distal Na(+) delivery and reabsorption, aldosterone, arterial pH, and arterial partial pressure of carbon dioxide. To generate metabolic alkalosis, either a gain of base or a loss of acid must occur. The loss of acid may be via the gastrointestinal tract or via the kidney. Excess base may be gained by oral or parenteral HCO3(-) administration or by lactate, acetate, or citrate administration. Factors that help maintain metabolic alkalosis include decreased glomerular filtration rate, volume contraction, hypokalemia, hypochloremia, and aldosterone excess. Clinical states associated with metabolic alkalosis are vomiting, mineralocorticoid excess, the adrenogenital syndrome, licorice ingestion, diuretic administration, and Bartter's and Gitelman's syndromes. The effects of metabolic alkalosis on the body are variable and include effects on the central nervous system, myocardium, skeletal muscle, and liver. Treatment of this disorder is simple, once the pathophysiology of the cause is delineated. Therapy consists of reversing the contributory factors that are promoting the alkalosis and, in severe cases, administration of carbonic anhydrase inhibitors, acid infusion, and low bicarbonate dialysis.     

Acetazolamide: a second wind for a respiratory stimulant in the intensive care unit?

ABSTRACT: Patients with chronic obstructive pulmonary disease (COPD) are affected by episodes of respiratory exacerbations, some of which can be severe and may necessitate respiratory support. Prolonged invasive mechanical ventilation is associated with increased mortality rates. Persistent failure to discontinue invasive mechanical ventilation is a major issue in patients with COPD. Pure or mixed metabolic alkalosis is a common finding in the intensive care unit (ICU) and is associated with a worse outcome. In patients with COPD, the condition is called post-hypercapnic alkalosis and is a complication of mechanical ventilation. Reversal of metabolic alkalosis may facilitate weaning from mechanical ventilation of patients with COPD. Acetazolamide, a non-specific carbonic anhydrase inhibitor, is one of the drugs employed in the ICU to reverse metabolic alkalosis. The drug is relatively safe, undesirable effects being rare. The compartmentalization of the different isoforms of the carbonic anhydrase enzyme may, in part, explain the lack of evidence of the efficacy of acetazolamide as a respiratory stimulant. Recent findings suggest that the usually employed doses of acetazolamide in the ICU may be insufficient to significantly improve respiratory parameters in mechanically ventilated patients with COPD. Randomized controlled trials using adequate doses of acetazolamide are required to address this issue.     

Metabolic alkalosis in the critically ill

Metabolic alkalosis is the commonest form of acid-base disorder seen in critically ill patients. Although the effects of acidosis have long been known, those of severe metabolic alkalosis are only slowly being recognized. Metabolic alkalosis is itself associated with an increased mortality and a knowledge of the causative factors and treatment options is important. In one study, around 50% of general surgical patients developed postoperative metabolic alkalosis, whereas other acid-base disturbances were uncommon. Metabolic alkalosis results from an accumulation of alkali or a loss of acid. Clinical signs are nonspecific but dehydration may be prominent because of a contraction of the extracellular fluid volume due to loss of chloride. Metabolic alkalosis leads to hypoventilation in patients both with and without lung disease, although in the latter, the effect is relatively transient. In patients with chronic obstructive lung disease, however, the development of metabolic alkalosis leads to prolonged hypoventilation and the establishment of a mixed acid-base disorder that may cause difficulty in weaning in the ventilated patient. This is an often forgotten cause of prolonged stay in the intensive care unit with consequent cost and morbidity implications.     

Acid-base disturbances in surgical operation]

Metabolic acidosis immediately after surgical operation is followed by metabolic alkalosis. Hormonal change by surgical stress and anaerobic glucolysis due to tissue ischemia cause initial lactic acidosis. Later alkalosis may be caused by secondary aldosteronism and bicarbonate production from lactate and citrate supplied by massive infusion and transfusion. Postoperative complications, such as respiratory insufficiency, renal failure and hypovolemic or septic shock, cause acidosis. In the gastrointestinal surgery, acidosis can be caused by starvation and loss of bicarbonate contained in bile, pancreatic juice or intestinal fluid, and alkalosis can be caused by loss of HCl in gastric juice. Severe acidosis can be caused by extracorporeal circulation, hypothermia, low output syndrome or declamping shock in cardioaortic surgery.     

Effets stimulants respiratoires de l’acétazolamide en réanimation

Patients suffering from chronic obstructive pulmonary disease (COPD) present episodes of respiratory exacerbation, which may be severe and necessitate ventilatory support. Persistent failure to discontinue invasive mechanical ventilation is a major issue in patients suffering from COPD. Metabolic alkalosis is a common finding in the intensive care unit, associated with a worse outcome. In COPD patients, this condition is called post-hypercapnic alkalosis and represents a complication of mechanical ventilation. Reversal of metabolic alkalosis may facilitate weaning from mechanical ventilation of COPD patients. Acetazolamide, a non-specific carbonic anhydrase inhibitor, is one of the drugs used in the intensive care unit to reverse metabolic alkalosis. Acetazolamide is relatively safe. Its pharmacodynamics and compartmentalization of the different isoforms of carbonic anhydrase enzyme may in part explain the lack of evidence of acetazolamide’s efficacy as respiratory stimulant. Recent findings have suggested that acetazolamide doses routinely used in the intensive care unit may be insufficient to significantly improve respiratory parameters in mechanically ventilated COPD patients, especially in the presence of high serum chloride levels or co-administration of systemic corticosteroids or furosemide. Randomized controlled trials using adequate doses of acetazolamide are required to address this issue.     

简化局部枸橼酸抗凝在连续性静-静脉血液滤过中的应用

目的 探讨简化局部枸橼酸抗凝(RCA)在连续性静-静脉血液滤过(CVVH)中应用的安全性与有效性.方法 14例患者用简化RCA方法行CVVH治疗,将枸橼酸钠置换液以2 000 ml/h或3 000 ml/h的速度前稀释输入,10%葡萄糖酸钙和25%硫酸镁从外周静脉泵入或滤器静脉端输入;分别于治疗前及治疗后4、8、12 h测定患者血清电解质、血气分析、凝血功能,并观察患者病情变化,测定治疗后滤器容积.结果 14例患者共进行CVVH治疗34例次,治疗时间4～36 h,平均(16.0±7.5)h;30例次未更换滤器完成治疗,治疗后滤器容积(97.19±2.75)ml,均大于原有容积的80%;滤器使用寿命平均(14.79±5.98)h.治疗12 h时患者滤器动脉端采血检测凝血酶原时间(PT)较治疗前明显缩短[(12.2±1.2)s比(14.0±3.3)s],且滤器动脉端血浆总钙明显升高[(2.46±0.30)mmol/L比(2.07±0.36)mmol/L,均P<0.05];而滤器动脉端采血检测活化部分凝血活酶时间(APTT)、凝血酶时间(TT)及Ca2+、Mg2+浓度和pH值、剩余碱(BE)均无明显变化.1例低氧血症患者因严重并发症停止治疗;均未出现高钠血症、碱中毒、出血并发症.结论 将拘橼酸钠加人置换液中的简化RCA方法可以安全用于置换液速度>2 000 ml/h的CVVH;并可避免RCA导致的高钠血症、碱中毒等并发症.     

Glucose-induced alkalosis in fasting subjects: Relationship to renal bicarbonate reabsorption during fasting and refeeding

This study documents the development of alkalosis in patients returning to caloric intake after a period of starvation and investigates the mechanisms responsible for this metabolic alteration. We studied the acid-base status, bicarbonate reabsorption, acid excretion, and sodium metabolism during fasting and glucose refeeding in 19 patients receiving sodium supplements.Metabolic alkalosis developed promptly in all of the subjects who terminated an 18 day fast with 300 g of glucose daily for 4 days. Tubular maximum reabsorptive capacity for bicarbonate and renal bicarbonate threshold determinations were performed at varying intervals in six and seven subjects, respectively, who had fasted for 3-18 days. The results demonstrated that bicarbonate reabsorptive capacity was normal or low during early fasting, markedly elevated during the 2nd wk; and moderately elevated during the 3rd wk of fasting. Glucose administration at all stages of fasting caused a further increase in bicarbonate threshold.Sodium balance during fasting with sodium supplements was found to follow a triphasic pattern, with the occurrence of a natriuresis during the 1st wk followed by a period of sodium retention after which neutral daily sodium balance was reestablished. Correlation of bicarbonate reabsorption with sodium homeostasis indicated a slight decrease in renal bicarbonate threshold during the natriuretic phase, a marked increase in bicarbonate reabsorption during the period of sodium retention, and a continued moderate elevation of threshold after sodium balance was reestablished. This relationship was interpreted to indicate that changes in bicarbonate reabsorption during fasting and refeeding may be secondary to alterations in the renal reabsorption of sodium.     

The meaning of acid-base abnormalities in the intensive care unit: part III -- effects of fluid administration

Stewart's quantitative physical chemical approach enables us to understand the acid-base properties of intravenous fluids. In Stewart's analysis, the three independent acid-base variables are partial CO2 tension, the total concentration of nonvolatile weak acid (ATOT), and the strong ion difference (SID). Raising and lowering ATOT while holding SID constant cause metabolic acidosis and alkalosis, respectively. Lowering and raising plasma SID while clamping ATOT cause metabolic acidosis and alkalosis, respectively. Fluid infusion causes acid-base effects by forcing extracellular SID and ATOT toward the SID and ATOT of the administered fluid. Thus, fluids with vastly differing pH can have the same acid-base effects. The stimulus is strongest when large volumes are administered, as in correction of hypovolaemia, acute normovolaemic haemodilution, and cardiopulmonary bypass. Zero SID crystalloids such as saline cause a 'dilutional' acidosis by lowering extracellular SID enough to overwhelm the metabolic alkalosis of ATOT dilution. A balanced crystalloid must reduce extracellular SID at a rate that precisely counteracts the ATOT dilutional alkalosis. Experimentally, the crystalloid SID required is 24 mEq/l. When organic anions such as L-lactate are added to fluids they can be regarded as weak ions that do not contribute to fluid SID, provided they are metabolized on infusion. With colloids the presence of ATOT is an additional consideration. Albumin and gelatin preparations contain ATOT, whereas starch preparations do not. Hextend is a hetastarch preparation balanced with L-lactate. It reduces or eliminates infusion related metabolic acidosis, may improve gastric mucosal blood flow, and increases survival in experimental endotoxaemia. Stored whole blood has a very high effective SID because of the added preservative. Large volume transfusion thus causes metabolic alkalosis after metabolism of contained citrate, a tendency that is reduced but not eliminated with packed red cells. Thus, Stewart's approach not only explains fluid induced acid-base phenomena but also provides a framework for the design of fluids for specific acid-base effects.     

Bartter syndrome: an overview

The term Bartter syndrome denotes a group of renal diseases which share a common denominator of hypokalaemia and metabolic alkalosis. The patch-clamp technique has made possible the analysis of single ion channels, improving our understanding of the molecular physiopathology of all the 'Bartter-like' syndromes. Genetic mapping of each defect has further clarified the mutations involved and the possible modes of inheritance. This improved understanding has opened new avenues for therapy, improving mortality and morbidity in these patients. Another group of illnesses, the 'pseudo-Bartter syndrome', may produce a hypokalaemic metabolic alkalosis without primary renal disease. The underlying illness needs to be identified and treated.     

Severe metabolic alkalosis due to baking soda ingestion: case reports of two patients with unsuspected antacid overdose

Oral ingestion of baking soda (sodium bicarbonate) has been used for decades as a home remedy for acid indigestion. Excessive bicarbonate ingestion places patients at risk for a variety of metabolic derangements including metabolic alkalosis, hypokalemia, hypernatremia, and even hypoxia. The clinical presentation is highly variable but can include seizures, dysrhythmias, and cardiopulmonary arrest. We present two cases of severe metabolic alkalosis in patients with unsuspected antacid overdose. The presentation and pathophysiology of antacid-related metabolic alkalosis is reviewed.     

肺心病病人438例刚入院时动脉血气结果的分析

对438例肺心病病人刚入院时的动脉血气进行分析.结果显示,慢性呼吸性酸中毒特别是失代偿性呼酸最为常见,共235例,占53.65%,其余依次为慢性呼酸并代酸、慢性呼喊并代碱、慢性呼碱及代酸.慢性呼酸并代酸最为严重,及时行动脉血气分析有助于临床诊治.     

急性危重病人并发碱中毒769例分析

目的提高对急性危重病人并发碱中毒的认识和救治水平.方法分析了769例急性危重病人的动脉血气、血清电解质参数及临床资料.结果急性危重病人碱中毒的类型依次为呼吸性碱中毒(呼碱)并代谢性碱中毒(代碱)216例(28.1%),单纯呼碱159例(20.7%),呼碱并代谢性酸中毒(代酸)105例(13.6%),单纯代碱93例(12.1%),三重酸碱失衡90例(11.7%),呼吸性酸中毒(呼酸)并代碱64例(8.3%)和代碱并代酸42例(5.5%).769例中PaO2＜8.0kPa(1kPa=7.5mmHg)者386例(50.2%).全组中死亡者316例(41.1%).结论急性危重病人碱中毒是常见的,其中以呼碱并代碱和单纯性呼碱为最常见,通常原发疾病因素引起呼碱或伴有低氧血症.救治原则为积极治疗原发疾病,从纠正原发失衡着手,维持水电解质平衡,对于合并多脏器功能损害的重度碱中毒患者,可行血液透析或血液超滤法快速纠正严重的碱血症和过多的体液负荷.尽快使pH恢复正常至关重要.     

Regulation of glutamine metabolism in vitro by bicarbonate ion and pH

The effect of variations of medium pH and bicarbonate concentration on glutamine oxidation was studied in slices and mitochondria from dog renal cortex. Decreasing pH and bicarbonate concentration increased the rate of oxidation of glutamine-U-(14)C to (14)CO(2) in both slices and mitochondria, an effect comparable to the acute stimulation of glutamine utilization produced by metabolic acidosis. Decreases in the concentration of glutamate and alpha-ketoglutarate, which accompany metabolic acidosis in the intact animal, also occurred in tissue slices when pH and [HCO(3) (-)] were lowered; decrease in alpha-ketoglutarate but not in glutamate content occurred in mitochondria under these conditions. Study of independent variations of medium pH and [HCO(3) (-)] showed that simultaneous changes in both pH and [HCO(3) (-)] produced a greater effect on glutamine metabolism than did change in either of these parameters alone.The rate of glutamine oxidation was also compared in tissue preparations from pairs of litter-mate dogs with chronic metabolic acidosis and alkalosis. No significant difference in the rate of glutamine oxidation was present in mitochondria from the two sets of animals. Slices from animals with chronic metabolic acidosis consistently oxidized glutamine at a more rapid rate than slices from alkalotic dogs both at high and at low concentrations of bicarbonate in the medium. We believe this difference is a result of the same mechanism which leads to the delayed increase in ammonium excretion during induction of metabolic acidosis.The close parallel between the effects demonstrated here and the changes in ammonium production and glutamine utilization in the intact animal with metabolic acidosis suggest that the observed in vitro changes accurately represent the operation of the physiologic mechanism by which acid-base changes regulate ammonium excretion. The similarity between the changes in glutamine oxidation observed in this study and those described previously for citrate suggests that one control mechanism affects the metabolism of both citrate and glutamine. Thus, we believe that the increase in citrate clearance in metabolic alkalosis and the increase in glutamine utilization and ammonium production in metabolic acidosis reflect the operation of the same underlying biochemical mechanism. This mechanism permits changes in pH and [HCO(3) (-)] in the cellular environment to regulate the rate of mitochondrial uptake and oxidation of several physiologically important substrates.     

Citrate vs. heparin for anticoagulation in continuous venovenous hemofiltration: a prospective randomized study

Objective To compare the efficacy and safety of adjusted-dose unfractionated heparin with that of regional citrate anticoagulation in intensive care patients treated by continuous venovenous hemofiltration (CVVH).Design and setting Prospective, randomized, clinical trial in a 32-bed medical and surgical ICU in a university teaching hospital.Patients ICU patients with acute renal failure requiring continuous renal replacement therapy, without cirrhosis, severe coagulopathy, or known sensitivity to heparin.Interventions Before the first CVVH run patients were randomized to receive anticoagulation with heparin or trisodium citrate. Patients eligible for another CVVH run received the other study medication in a cross-over fashion until the fourth circuit.Measurements and results Forty-nine circuits (hemofilters) were analyzed: 23 with heparin and 26 with citrate. The median lifetime of hemofilters was 70 h (interquartile range 44–140) with citrate anticoagulation and 40 h (17–48) with heparin (p=0.0007). One major bleeding occurred during heparin anticoagulation and one metabolic alkalosis (pH=7.60) was noted with citrate after a protocol violation. Transfusion rates (units of red cells per day of CVVH) were, respectively, 0.2 (0.0–0.4) with citrate and 1.0 (0.0–2.0) with heparin (p=0.0008).Conclusions Regional citrate anticoagulation seems superior to heparin for the filter lifetime and transfusion requirements in ICU patients treated by continuous renal replacement therapy.     

慢性肺原性心脏病与三重型酸碱失衡

分析２９１例慢性肺原性心脏病患者，发现有三重型酸碱失衡２１例（占７．２％），其中呼吸性酸中毒（呼酸）＋代谢性酸中毒（代酸）＋代谢性碱中毒（代碱）１７例，呼碱＋代酸＋代碱４例，绝大部分患者为老年人及多器官损害患者，１６例有肾功能不全。本组资料提示三重型酸碱失衡时血气表现非常复杂，ＡＧ值明显增加（本组最低值为１６．８ｍｍｏｌ／Ｌ，最高值为３１．４ｍｍｏｌ／Ｌ，平均值为２４．１ｍｍｏｌ／Ｌ），呼酸型三重型酸碱失衡者的ｐＨ值偏低，呼碱型三重型酸碱失衡者的ｐＨ多偏高。作者提出：三重型酸碱失衡的治疗原则是维持ｐＨ值正常，兼顾三种原发失衡，对每一种失衡的治疗不能操之过急，治疗的关键在于治疗原发性疾病，避免医源性因素，尤其注意利尿剂、激素等的合理使用。     

Bench-to-bedside review: treating acid-base abnormalities in the intensive care unit--the role of renal replacement therapy

Acid–base disorders are common in critically ill patients. Metabolic acid–base disorders are particularly common in patients who require acute renal replacement therapy. In these patients, metabolic acidosis is common and multifactorial in origin. Analysis of acid–base status using the Stewart–Figge methodology shows that these patients have greater acidemia despite the presence of hypoalbuminemic alkalosis. This acidemia is mostly secondary to hyperphosphatemia, hyperlactatemia, and the accumulation of unmeasured anions. Once continuous hemofiltration is started, profound changes in acid–base status are rapidly achieved. They result in the progressive resolution of acidemia and acidosis, with a lowering of concentrations of phosphate and unmeasured anions. However, if lactate-based dialysate or replacement fluid are used, then in some patients hyperlactatemia results, which decreases the strong ion difference and induces an iatrogenic metabolic acidosis. Such hyperlactatemic acidosis is particularly marked in lactate-intolerant patients (shock with lactic acidosis and/or liver disease) and is particularly strong if high-volume hemofiltration is performed with the associated high lactate load, which overcomes the patient's metabolic capacity for lactate. In such patients, bicarbonate dialysis seems desirable. In all patients, once hemofiltration is established, it becomes the dominant force in controlling metabolic acid–base status and, in stable patients, it typically results in a degree of metabolic alkalosis. The nature and extent of these acid–base changes is governed by the intensity of plasma water exchange/dialysis and by the 'buffer' content of the replacement fluid/dialysate, with different effects depending on whether lactate, acetate, citrate, or bicarbonate is used. These effects can be achieved in any patient irrespective of whether they have acute renal failure, because of the overwhelming effect of plasma water exchange on nonvolatile acid balance. Critical care physicians must understand the nature, origin, and magnitude of alterations in acid–base status seen with acute renal failure and during continuous hemofiltration if they wish to provide their patients with safe and effective care.     

Statistics review 9: One-way analysis of variance

Acid–base disorders are common in critically ill patients. Metabolic acid–base disorders are particularly common in patients who require acute renal replacement therapy. In these patients, metabolic acidosis is common and multifactorial in origin. Analysis of acid–base status using the Stewart–Figge methodology shows that these patients have greater acidemia despite the presence of hypoalbuminemic alkalosis. This acidemia is mostly secondary to hyperphosphatemia, hyperlactatemia, and the accumulation of unmeasured anions. Once continuous hemofiltration is started, profound changes in acid–base status are rapidly achieved. They result in the progressive resolution of acidemia and acidosis, with a lowering of concentrations of phosphate and unmeasured anions. However, if lactate-based dialysate or replacement fluid are used, then in some patients hyperlactatemia results, which decreases the strong ion difference and induces an iatrogenic metabolic acidosis. Such hyperlactatemic acidosis is particularly marked in lactate-intolerant patients (shock with lactic acidosis and/or liver disease) and is particularly strong if high-volume hemofiltration is performed with the associated high lactate load, which overcomes the patient's metabolic capacity for lactate. In such patients, bicarbonate dialysis seems desirable. In all patients, once hemofiltration is established, it becomes the dominant force in controlling metabolic acid–base status and, in stable patients, it typically results in a degree of metabolic alkalosis. The nature and extent of these acid–base changes is governed by the intensity of plasma water exchange/dialysis and by the 'buffer' content of the replacement fluid/dialysate, with different effects depending on whether lactate, acetate, citrate, or bicarbonate is used. These effects can be achieved in any patient irrespective of whether they have acute renal failure, because of the overwhelming effect of plasma water exchange on nonvolatile acid balance. Critical care physicians must understand the nature, origin, and magnitude of alterations in acid–base status seen with acute renal failure and during continuous hemofiltration if they wish to provide their patients with safe and effective care.     

Bench-to-bedside review: Treating acid–base abnormalities in the intensive care unit – the role of renal replacement therapy

Acid–base disorders are common in critically ill patients. Metabolic acid–base disorders are particularly common in patients who require acute renal replacement therapy. In these patients, metabolic acidosis is common and multifactorial in origin. Analysis of acid–base status using the Stewart–Figge methodology shows that these patients have greater acidemia despite the presence of hypoalbuminemic alkalosis. This acidemia is mostly secondary to hyperphosphatemia, hyperlactatemia, and the accumulation of unmeasured anions. Once continuous hemofiltration is started, profound changes in acid–base status are rapidly achieved. They result in the progressive resolution of acidemia and acidosis, with a lowering of concentrations of phosphate and unmeasured anions. However, if lactate-based dialysate or replacement fluid are used, then in some patients hyperlactatemia results, which decreases the strong ion difference and induces an iatrogenic metabolic acidosis. Such hyperlactatemic acidosis is particularly marked in lactate-intolerant patients (shock with lactic acidosis and/or liver disease) and is particularly strong if high-volume hemofiltration is performed with the associated high lactate load, which overcomes the patient's metabolic capacity for lactate. In such patients, bicarbonate dialysis seems desirable. In all patients, once hemofiltration is established, it becomes the dominant force in controlling metabolic acid–base status and, in stable patients, it typically results in a degree of metabolic alkalosis. The nature and extent of these acid–base changes is governed by the intensity of plasma water exchange/dialysis and by the 'buffer' content of the replacement fluid/dialysate, with different effects depending on whether lactate, acetate, citrate, or bicarbonate is used. These effects can be achieved in any patient irrespective of whether they have acute renal failure, because of the overwhelming effect of plasma water exchange on nonvolatile acid balance. Critical care physicians must understand the nature, origin, and magnitude of alterations in acid–base status seen with acute renal failure and during continuous hemofiltration if they wish to provide their patients with safe and effective care.     

Intensive-care unit experience in the Mayo liver transplantation program: the first 100 cases

The first 100 liver transplantations at the Mayo Clinic were performed in 83 patients, who required a total of 917 patient days in the intensive-care unit (ICU). The mean duration of stay in the ICU was 5.91 days after liver transplantation and 6.15 days for patients who subsequently required readmission to the ICU. During the immediate postoperative period, hypothermia and hyperglycemia invariably occurred. Later during the initial admission or on readmission to the ICU, there arose the possibility of infections and renal insufficiency. Prompt diagnosis and treatment are necessary for hypertension, hypokalemia, severe metabolic alkalosis, fever, altered mental status, oliguria, and signs of graft failure in liver transplant patients. In our patient series, selective bowel decontamination minimized the occurrence of gram-negative and fungal sepsis, and use of antihypertensive agents and correction of coagulopathies may have decreased the risk of intracranial bleeding in patients with hypertension and clotting defects. Anticipation of potential conditions postoperatively and early implementation of treatment are key factors in the successful ICU management of patients who have undergone liver transplantation.