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Background Both saline and lactated Ringer’s solutions are commonly given to surgical patients. However, hyperchloremic acidosis consequent to saline administration may provoke complications. The authors therefore tested the primary hypothesis that a composite of in-hospital mortality and major postoperative complications is less common in patients given lactated Ringer’s solution than normal saline. Methods The authors conducted an alternating cohort controlled trial in which adults having colorectal and orthopedic surgery were given either lactated Ringer’s solution or normal saline in 2-week blocks between September 2015 and August 2018. The primary outcome was a composite of in-hospital mortality and major postoperative renal, respiratory, infectious, and hemorrhagic complications. The secondary outcome was postoperative acute kidney injury. Results Among 8,616 qualifying patients, 4,187 (49%) were assigned to lactated Ringer’s solution, and 4,429 (51%) were assigned to saline. Each group received a median 1.9 l of fluid. The primary composite of major complications was observed in 5.8% of lactated Ringer’s versus 6.1% of normal saline patients, with estimated average relative risk across the components of the composite of 1.16 (95% CI, 0.89 to 1.52; P = 0.261). The secondary outcome, postoperative acute kidney injury, Acute Kidney Injury Network stage I–III versus 0, occurred in 6.6% of lactated Ringer’s patients versus 6.2% of normal saline patients, with an estimated relative risk of 1.18 (99.3% CI, 0.99 to 1.41; P = 0.009, significance criterion of 0.007). Absolute differences between the treatment groups for each outcome were less than 0.5%, an amount that is not clinically meaningful. Conclusions In elective orthopedic and colorectal surgery patients, there was no clinically meaningful difference in postoperative complications with lactated Ringer’s or saline volume replacement. Clinicians can reasonably use either solution intraoperatively. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

Metabolic acidosis frequently is present in surgical patients; however, different types of metabolic acidosis (hyperlactatemia, hyperchloremia, and others) may have different relationships to perioperative outcomes. We hypothesized that in postoperative surgical patients, distinctive types of metabolic acidosis would correlate differently with the outcomes of high-risk surgeries.A prospective, multicenter observational study was performed in 3 different tertiary care hospitals. Patients who required postoperative admission to the intensive care unit (ICU) were included in this study. Patients with a short life expectancy (those with untreated cancer and limited treatment), hepatic failure, renal failure, or a diagnosis of diabetes were excluded. Patients were classified at ICU admission according to the presence and type of metabolic acidosis into 4 groups: those without acidosis, those with a base excess-4 mmol/L and albumin-corrected anion gap ≤12 mmol/L (hyperchloremic), those with a base excess-4 mmol/L and increased albumin-corrected anion gap12 mmol/L, and those with a base excess-4 mmol/L and hyperlactatemia2 mmol/L. Furthermore, patients were reclassified 12 hours after admission to the ICU to verify the metabolic acidosis behavior and outcome differences among the groups.The study included 618 patients. The incidence of acidosis at ICU admission was 59.1%; 23.9% presented with hyperchloremia, 21.3% with hyperlactatemia, 13.9% with increased anion gap, and 40.9% of the patients presented without metabolic acidosis. Patients whose metabolic acidosis persisted for 12 hours had an incidence of ICU complications rates in hyperlactatemia group of 68.8%, increased anion gap of 68.6%, hyperchloremic of 65.8%, and those without acidosis over 12 hours of 59.3%. A Cox regression model for postoperative 30-day mortality showed: in hyperlactatemic acidosis, hazard ratio (HR) = 1.74, 95% confidence interval (CI) = 1.02-2.96; increased anion gap acidosis, HR = 1.68, 95% CI = 0.85-3.81; hyperchloremic acidosis, HR = 1.47, 95% CI = 0.75-2.89, and 10.3% of 30-day mortality rate in patients without acidosis. An adjusted survival curve by Cox regression found a worse 30-day survival in the hyperlactatemic group compared with the other groups (P = .03). Furthermore, in multiple comparisons among groups, patients with hyperlactatemic acidosis were more likely to develop renal dysfunction (P.001) up to the seventh day postoperatively.We found that among patients with different types of acidosis, patients who developed hyperlactatemic metabolic acidosis postoperatively showed greater rates of renal dysfunction within 7 days and hyperlactatemic acidosis represented an independent factor on 30-day mortality in high-risk surgical patients.

In the acute care setting, the type and amount of fluid administered has a significant impact on patient outcomes. In particular, 0.9% saline infusions are known to cause or exacerbate hyperchloremia. The studies presented evaluate possible complications from 0.9% saline infusions. These studies compared administration of 0.9% saline with lactated ringer or plasmalyte in the acute care setting. In each trial, the patients who were randomized to receive 0.9% saline infusions had a more severe acidosis from increased serum chloride levels. From the available data, chloride-restrictive intravenous fluid such as plasmalyte appears to reduce acid-base disturbances and improve patient outcomes.

Background:In an incidental finding, during a study of plasma chemistry after crystalloid infusion, participants reported subjective cognitive changes, particularly slower thinking, after saline but not Hartmann’s (Ringer’s lactate) solution. The authors tested the hypothesis that saline infusion would produce greater adverse cognitive changes than Plasmalyte infusion.Methods:The authors conducted a randomized, cross-over, multiple blinded study of healthy adult volunteers. On separate days, participants received 30 ml/kg over 1 h of either 0.9% saline or Plasmalyte with the order randomly allocated. Plasma chemistry was tested on venous samples. As part of a battery of cognitive tests our primary endpoint was the reaction time index after infusion.Results:The authors studied 25 participants. Plasma chloride was greater after saline than after Plasmalyte: mean difference 5.4 mM (95% CI, 4.1–6.6 mM; P < 0.001). Saline was also associated with greater metabolic acidosis: base-excess 2.5 mM more negative (95% CI, 1.9–3.0 mM more negative; P < 0.001). There was no evidence of a difference in the reaction time index between the two interventions: mean reaction time index 394 ms (SD, 72) after saline versus 385 ms (SD, 55) after Plasmalyte. Difference: saline 9 ms slower (95% CI, 30 ms slower to 12 ms faster; P = 0.39). There were minimal differences in the other cognitive and mood tests.Conclusions:Despite expected differences in plasma chemistry, the authors found that measures of cognition did not differ after infusions of Plasmalyte or saline.

BACKGROUND Normal saline (NS) and lactated Ringer's solution (LR) continue to be used interchangeably for the resuscitation of hemorrhagic shock in some institutions. We hypothesized that, aside from hyperchloremic acidosis, NS resuscitation would be similar to that of LR in a swine model of uncontrolled hemorrhage. METHODS Twenty swine weighing a mean of 37 kg underwent invasive line placement, midline celiotomy, and splenectomy. After a 15-minute stabilization period, we recorded a baseline mean arterial pressure (MAP) and created a grade V liver injury. The animals bled freely for 30 minutes after which we measured blood loss. We blindly randomized the swine to receive NS (10 animals) versus LR (10 animals) to achieve and maintain the baseline MAP for 90 minutes postinjury. Laboratory values were obtained at baseline and upon completion of the 2-hour study period. RESULTS Initial blood loss was 25 mL/kg in the NS group and 22 mL/kg in the LR group (p = 0.54). Animals required 256.3 +/- 145.4 mL/kg of fluid in the NS group as compared with 125.7 +/- 67.3 mL/kg in the LR group (p = 0.04). The urine output was higher in the NS group (46.6 +/- 39.5 mL/kg versus 18.9 +/- 12.9 mL/kg, p = 0.04). Upon study completion, the NS group had a significant hyperchloremia (119 +/- 1.9 mEq/L versus 105 +/- 2.9 mEq/L, p < 0.01) with acidosis (7.28 +/- 0.12 versus 7.45 +/- 0.06, p < 0.01) in comparison to the LR group. In addition, resuscitation with NS resulted in significantly lower fibrinogen levels (99 +/- 21 mg/dL versus 123 +/- 20 mg/dL, p = 0.02). The serum lactate was 4.7 +/- 2.2 in the LR group and 1.7 +/- 1.7 in the NS swine (p < 0.01) at the end of the study. CONCLUSIONS Resuscitation of uncontrolled hemorrhagic shock with NS requires significantly greater volume and is associated with greater urine output, hyperchloremic acidosis, and dilutional coagulopathy as compared with LR. Resuscitation with LR results in an elevation of the lactate level that is not associated with acidosis. Lactated Ringer's solution is superior to NS for the resuscitation of uncontrolled hemorrhagic shock in swine.

Disorders of acid-base and electrolytes are commonly seen in critically ill patients. The presence of these disorders typically signals the development of an underlying pathology. These disturbances can be severe and are often associated with worse outcome. Indeed, metabolic acidosis is one of the ways we quantify organ failure. Although acid-base and electrolyte disorders may be a result of the underlying pathophysiology (eg, renal failure, respiratory failure, shock), they may also result from the way in which we manage critically ill patients.The application of the physical-chemical approach to acid-base analysis has led to recent developments in the identification and quantification and understanding of mechanisms for acid-base disorders commonly found in critically ill patients. Examples include a better understanding of the role of electrolytes (especially sodium and chloride) and weak acids in the pathophysiology of acid-base disorders, the implication of acid-base derangements on the inflammatory process and organ perfusion, and the importance of resuscitation fluid composition.By adopting a physical-chemical approach to acid-base analysis we are gaining insight to the complexities of acid-base disorders and how their treatments may affect outcome.

UNLABELLED In this study, we evaluated the action of two buffer solutions on acid-base equilibrium in cases of hyperchloremic acidosis. Twenty-four patients undergoing major gynecological intraabdominal surgery received 40 mL. kg(-1). h(-1) of 0.9% saline per protocol. During surgery, in every patient, hyperchloremic acidosis occurred. At a standard base excess of -7 mmol/L, the patients were randomly assigned to receive within 20 min either a mean of 130 +/- 26 mmol of sodium bicarbonate (BIC, 1 M; n = 12) or a mean of 128 +/- 18 mmol of tris-hydroxymethyl aminomethane (THAM, 3 M; n = 12). PaCO(2), pH, serum bicarbonate concentration, standard base excess, and serum concentrations of sodium, potassium, chloride, lactate, phosphate, total protein, and albumin were determined before and 0, 10, and 20 min after buffering. The apparent strong ion difference was calculated as: serum sodium plus serum potassium minus serum chloride minus serum lactate. The effective strong ion difference and the amount of weak plasma acid were calculated by using a computer program. Immediately after buffering, standard base excess increased by 9.8 mmol/L in the BIC group and by 7.2 mmol/L in the THAM group. In both groups, PaCO(2) and the amount of weak plasma acid remained constant. Mainly because of hypernatremia, the apparent and effective strong ion difference increased in the BIC group by 8.5 and 7.9 mEq/L, respectively. In the THAM group, the apparent strong ion difference remained constant; however, the effective strong ion difference increased by 6.4 mEq/L and the anion gap decreased by 5.8 mmol/L because of the occurrence of an unmeasured cation. In conclusion, in case of buffering with BIC or THAM, the changes in pH were accompanied by, and probably caused by, an increase in strong ion difference. IMPLICATIONS By comparing two groups of patients with intraoperative hyperchloremic acidosis receiving equal doses of either sodium bicarbonate or tris-hydroxymethyl aminomethane, we assessed the action of both drugs on acid-base equilibrium. In case of "buffering," the changes in pH were accompanied by, and probably caused by, an increase in strong ion difference.

Base deficit has been established as a predictor of mortality and endpoint of resuscitation. We hypothesized that in a significant subset of surgical intensive care patients, base deficit is secondary to hyperchloremic acidosis, and that these patients experience lower mortality than those patients whose base deficits are secondary to other causes. Seventy-five consecutive surgical intensive care patients with base deficits greater than 2.0 were prospectively studied. The etiology of the patients' base deficits was determined by admission laboratory data. Patients were divided into those with hyperchloremic acidosis, and those with acidosis from other causes. Mortality within these groups was compared by Fisher's exact test. Thirty-seven patients (49.3%) had hyperchloremic acidosis. Thirty-three patients (46.7%) had lactic acidosis. Three patients (4%) had base deficits secondary to ketosis, and two patients (2.6%) had base deficits secondary to uremia. There were no significant differences in age, APACHE II scores, or volumes of resuscitation between the hyperchloremic group and the remaining patients. There were four deaths (10.8%) in the hyperchloremic group and thirteen deaths (34.2%) in the remaining patients (P = 0.03). Hyperchloremic acidosis resulted from resuscitation with lactated Ringer's solution in 18 (48.6%) of the hyperchloremic patients. Hyperchloremic acidosis is a common etiology of base deficit in the surgical intensive care unit. It is associated with lower mortality than base deficit secondary to other causes. Moreover, it is frequently induced following resuscitation with lactated Ringer's solution. Failure to properly diagnose this subset of acidotic patients may result in inappropriate clinical interventions due to the erroneous presumption of ongoing tissue hypoxia.

Purpose: We evaluated how ileal augmentation cystoplasty predisposes growing animals to hyperchloremic acidosis and abnormal skeletal development.Materials and Methods: Weanling female Wistar rats weighing 35 to 50 gm. underwent ileal augmentation cystoplasty or sham operation consisting of a similar ileal resection and closure (ileoileostomy). Both groups were stressed with 1% ammonium chloride loading. Serial bone densitometry measurements, weight and blood gas studies were performed in an 8-week growth period. Femur bone ashing and mineral analysis, arterial blood gas studies and serum bone mineral determinations (calcium, magnesium and phosphorus) were obtained at study conclusion.Results: Augmented and control animals had similar serum calcium, phosphorus and magnesium concentrations. In augmented animals metabolic acidosis developed with respiratory compensation and decreased mean serum bicarbonate plus or minus standard deviation compared to controls (18.34 +/− 3.23 versus 21.76 +/− 2.46 mE...

A prospective determination of serum electrolytes, arterial blood gases, urinalysis and urine cultures was done in 31 patients who underwent a successful continent urinary reservoir or orthotopic bladder replacement. The patients who underwent reconstruction with a long detubularized intestinal segment (group 1-50 cm. long) demonstrated the greatest tendency for metabolic hyperchloremic acidosis (35.2%). In group 2 (patients with an orthotopic bladder replacement) only 1 individual (16.7%) had hyperchloremia, which proved to be the sole metabolic derangement encountered. In group 3 (individuals with a continent gastroileac reservoir) 2 patients (25%) had a slight tendency for compensated and asymptomatic alkalosis. Urinalyses and urine cultures in groups 1 and 2 demonstrated a trend toward urine alkalinity (52.1%) and asymptomatic bacteriuria (74%), respectively. On the contrary, among the patients undergoing a gastroileac reservoir (group 3), mild urinary acidity (pH between 5 and 6) was demonstrated in 4 (50%), while asymptomatic bacteriuria was present in 3 (37.5%). In this group symptomatic urinary acidity and/or ulceration of the ileal component has not occurred to date. Metabolic hyperchloremic acidosis predominates when longer colonic segments are used for reservoir construction. This abnormality is magnified in patients in whom an accessory small bowel was resected. The majority of the gastroileac reservoir patients showed electrolytic neutrality. With our surgical technique, the gastric secretory properties predominate over those of the ileum. The differences in homeostatic findings with the use of these varieties of bowel segments suggest that we could modify the final electrolytic environment by using different combinations of bowel and bowel length.

oped rapidly, and signs suggestive of pulmonary edema were present on auscultation. Only then, approximately 30 min after the start of the hysteroscopy, was a deficit in distending fluid balance of almost 7.5 l noticed; it was unidentified before despite the presence of a systembased warning system. Because fluid overload was suspected as the most likely diagnosis, intravenous furosemide (20 mg) was given to enhance diuresis, and the hysteroscopy was discontinued. Laboratory investigations revealed a hyperchloremic metabolic acidosis enhanced by a small respiratory component (fraction of inspired oxygen, 1.0; pH, 7.12; HCO3 , 15.5 mmHg; base excess, 13.3 mM; partial pressure of carbon dioxide, 48.7 mmHg; partial pressure of oxygen, 185.2 mmHg; sodium, 141 mM; potassium, 3.2 mM; chloride, 122 mM; anion gap, 3.5 mM). There were also signs of dilutional coagulopathy (international normalized ratio, 1.4; activated partial thrombin time, 59 s). Fifty milliliters intravenous sodium bicarbonate, 8.4%, and 20 mmol potassium chloride were given as a part of corrective treatment. In the absence of signs of respiratory compromise, the laryngeal mask was removed when the patient was awake. She was agitated and somewhat confused, and her blood pressure was 150/90 mmHg. An additional dose of intravenous furosemide (20 mg) was administered. On arrival in the intermediate care unit, an oxygen saturation of 98% was achieved with 10 l oxygen via facemask. Within 4 h, the patient’s condition improved, and all hemodynamic and laboratory values were within the normal range; in particular, the laboratory indices of hyperchloremic acidosis had disappeared (chloride, 110 mM; pH, 7.42; base excess, 1m M).

Well controlled, carefully conducted blinded clinical studies are powerful tools for answering important clinical questions. Interval analysis of data is sometimes necessary as a safeguard to ensure the protection of research subjects from unnecessary risk. If the interval analysis includes end points of unknown importance, a potentially important clinical study may be stopped over a finding of questionable significance. Anesthesiologists, surgeons, and intensivists routinely administer large volume infusions to patients. Crystalloid and colloid solutions remain among the most important pharmaceuticals administered to patients, as they are used to support the circulation during periods of large fluid shifts. Clinical interest in improving practice has spawned a large number of trials over the past three decades. The state of the art has advanced from early, less than optimally controlled trials (1), to more carefully controlled, thoughtfully executed studies (2,3). Several metaanalyses have been performed and published in prominent medical journals (4,5). Strongly worded reviews and special articles remain of broad interest in these communities and have both advocated colloid solutions (5) and strongly discouraged their use (6). The enormous diversity of practice observable in the real world reflects the lack of consensus about what this vast clinical literature means. Hyperchloremic acidosis is a consequence of the infusion of large quantities of solutions containing a large concentration of chloride (0.9% normal saline in the clinical setting). Hyperchloremic acidosis was first discussed in the anesthesia literature in a randomized study of 30 patients reported by McFarlane and Lee in 1994 (7), who clearly demonstrated an association between the infusion of large quantities of normal saline and the evolution of a metabolic acidosis. Subsequent studies have confirmed their observations (8) and have generated interest in electrolyte solutions designed to avoid this problem. Hyperchloremic acidosis by itself is of no known pathologic or physiologic consequence. The greatest danger associated with it appears to be either the reaction of clinicians who may not recognize or appreciate its presence, or that it may worsen or confuse an acidosis caused by some other process. Our insight into the adverse effects of hyperchloremic acidosis is limited by the meager clinical literature and even smaller basic science literature about the subject. This lack of information reflects the minimal resources that have been allocated to understanding this problem at any level. If relevant basic science studies were to suggest greater harm associated with this syndrome, then its evolution in patients would be regarded far more seriously. In this issue of Anesthesia & Analgesia, Wilkes et al. (9) report a randomized blinded comparison of 6% hetastarch formulated in either 0.9% saline (Hespan) or a balanced salt solution very similar in composition to lactated Ringer’s solution (Hextend). Although there are other differences in the fluids compared (potassium, glucose, calcium, magnesium), the study is ultimately a careful comparison of lactate versus chloride as anions. Patients in both groups received approximately 2,500 mL of colloid solution, 1,400 mL of crystalloid solution, and comparable quantities of blood products. This represents a larger volume of 6% hetastarch than many had previously believed to be safe and also represents a different ratio of colloid to crystalloid than most clinicians use. Of course, most of the previous studies comparing crystalloid and colloid solutions involved comparisons of albumin, not hetastarch, and hence may not apply. Regardless, the study was stopped after an interim analysis revealed that patients in the saline group were developing a hyperchloremic acidosis, which should hardly have been surprising, given the prior studies by McFarlane and Lee (7) and Scheingraber et al. (8). The premature termination of the study may have prevented the authors from demonstrating an association between the different anions and perioperative incidence of nausea, vomiting, and use of antiemetics. There certainly does appear to be a qualitative difference in these variables between the two groups. The difference in Accepted for publication May 18, 2001. Address correspondence to Michael F. O’Connor, MD, Department of Anesthesia and Critical Care, Box MC 4028, University of Chicago, 5841 S. Maryland Avenue, Chicago, IL 60637.

Background Changes in acid-base balance caused by infusion of a 0.9% saline solution during anesthesia and surgery are poorly characterized. Therefore, the authors evaluated these phenomena in a dose-response study. Methods Two groups of 12 patients each who were undergoing major intraabdominal gynecologic surgery were assigned randomly to receive 0.9% saline or lactated Ringer's solution in a dosage of 30 ml x kg(-1) x h(-1). The pH, arterial carbon dioxide tension, and serum concentrations of sodium, potassium, chloride, lactate, and total protein were measured in 30-min intervals. The serum bicarbonate concentration was calculated using the Henderson-Hasselbalch equation and also using the Stewart approach from the strong ion difference and the amount of weak plasma acid. The strong ion difference was calculated as serum sodium + serum potassium - serum chloride - serum lactate. The amount of weak plasma acid was calculated as the serum total protein concentration in g/dl x 2.43. Results Infusion of 0.9% saline, but not lactated Ringer's solution, caused a metabolic acidosis with hyperchloremia and a concomitant decrease in the strong ion difference. Calculating the serum bicarbonate concentration using the Henderson-Hasselbalch equation or the Stewart approach produced equivalent results. Conclusions Infusion of approximately 30 ml x kg(-1) x h(-1) saline during anesthesia and surgery inevitably leads to metabolic acidosis, which is not observed after administration of lactated Ringer's solution. The acidosis is associated with hyperchloremia.

To the Editor. In this Editorial summarizing 3 articles on urinary reconstruction and diversion, it is clear that the results are encouraging because orthotopic bladder substitution provides an excellent quality of life. However, we should not forget the fact that the gastrointestinal tract was not designed to serve as a urinary reservoir. Its primary function is the selective absorption and secretion of different substances. When included in the urinary tract the intestine continues to function according to its initial purpose, which gives rise to metabolic consequences, such as the well-known hyperchloremic acidosis. On analysis of this process we suspected that any drug or its metabolites that are excreted by the kidney can be reabsorbed, diminishing the speed of their decrease in the serum. To avoid digoxin overdose we measured the serum levels after 2 days of administration in 22 patients with an orthotopic ileal neobladder before and after operation. Surprisingly, we found results opposite to those expected, since the digoxin loss was much faster after than before bladder substitution (see figure). The half-life of digoxin decreased from 36 to 19 hours. On this basis one should double the normal dose for ileal neobladder cases. Does this mean that for bladder substitution cases it is necessary to reestablish a new pharmacological data base? Has the author encountered similar dosage problem in his own experience?

From 1978 to 1982 bilateral ureterorectostomy and end-to-side sigmoidorectostomy were done following cystectomy for carcinoma of the bladder in 7 patients. No patient had recurrent pyelonephritis or ureterointestinal obstruction. Rectography showed the absence of rectoureteral reflux of contrast medium but rectosigmoid reflux appeared after injection of more than 150 ml. opaque solution. Adequate alkali therapy was performed in 2 patients with hyperchloremic acidosis. While there were some problems concerning the quality of urinary and fecal control achieved in our patients they were no worse than those of ordinary ureterosigmoidostomy. This operation might be recommended for patients in whom a collection appliance is unacceptable. However, before this surgical procedure can be performed the fact that the end result in terms of fecal urinary continence is unpredictable must be explained thoroughly to the patient.

A review of 129 consecutive young patients (average age 13.4 years) who underwent intestinocystoplasty or total bladder replacement during a 6 1/2-year period at our institution is presented. The most common diagnosis was myelodysplasia and the average followup was 44 months. The clinical and urodynamic aspects of 4 types of intestinocystoplasty (ileocecal, tubular sigmoid, sigmoid patch and ileal patch) are presented. All 4 operations resulted in a significant increase in bladder volume, with a decrease in filling pressure and, thus, improved vesical compliance. In combination with clean intermittent catheterization renal function was maintained or improved in 91 per cent and urinary continence was achieved in 82 per cent of the patients. Hyperchloremic acidosis requiring therapy was noted only in patients with pre-existing renal insufficiency, although mild hyperchloremia after cystoplasty was seen with all 4 types of cystoplasty. There were no operative mortalities. Significant surgical complications occurred in 36 per cent of the patients, the most common of which was vesicoureteral reflux in the ileocecal cystoplasty. Mass unit peristaltic contractions occurred in 34 per cent of the tubular-shaped bowel segments compared to only 10 per cent of the patch segments. These peristaltic contractions contributed to the greater postoperative morbidity noted in the tubular large bowel cystoplasties. The over-all success rate for intestinocystoplasty in this series was 84 per cent. Intestinocystoplasty is an effective procedure when used to increase the compliance of the lower urinary tract. In combination with clean intermittent catheterization it can be applied successfully to patients with neurogenic bladder dysfunction. Large and small bowel seem to have similar clinical and urodynamic properties. The type of intestinal segment used for intestinocystoplasty seems to be of less importance than the size and configuration. Large bowel in its native tubular configuration should be avoided.

Most conditions that affect the kidney cause a proportionate and simultaneous loss of glomerular and tubular function. The loss of glomerular function results in the retention of many products of metabolism, including the anions of various organic and inorganic acids, and urea. Loss of tubular function prevents the kidney from excreting hydrogen ions, thereby causing a metabolic acidosis. The parallel development of azotemia, anion retention, and acidosis is defined as uremic acidosis. When tubular damage develops uncoupled from glomerular damage, acidosis may occur without urea or anion retention; this is termed renal tubular acidosis. In uremic acidosis, the serum bicarbonate is replaced by phosphate. sulphate, and other anions not usually measured in standard electrolyte assays, whereas chloride replaces bicarbonate in the renal tubular acidosis, hence giving rise to the term hyperchloremic acidosis. This review centers on those fcrms of renal acidosis that occur, at least initially, with a minimum of glomerular damage. After first defining the normal mechanism by which the kidney maintains acid-base balance we define the general pathophysiologic principles that underlie the development of the different forms of renal tubular acidosis. These principles set the foundation for the subsequent discussion of the clinical manifestations. diagnosis, and therapy of these disorders.

We report an unusual association of hyperkalemia, mild hyperchloremic acidosis, and hypertension in a young woman. Pseudohyperkalemia, Addison's disease, renal insufficiency, classical hyporeninemic hypoaldosteronism, isolated hypoaldosteronism, and iatrogenic causes were excluded. The patient's findings were compatible with a rare syndrome designated as type II pseudohypoaldosteronism, Gordon's syndrome.

Studies were done on 33 cases of plastic reconstruction of the urinary tract with an isolated ileal segment. We found that electrolytes and other components in the urine can be absorbed or excreted by the isolated ileal mucosa. Although electrolyte balance was preserved in most cases the tendency for hyperchloremic acidosis and high blood urea nitrogen was observed in some patients with poor renal function. The degree and the incidence of these changes were influenced by the length of ileal segment used and the volume of urine excreted. These 2 factors were related to infection, which gave deleterious effects on renal function. Among the tests used for prognosis the excretory urogram was found to be the most simple and provided the best information.

We report 2 cases of ileal replacement of the ureters: 1 bilateral and 1 unilateral with a single kidney. Hyperchloremic acidosis developed in both patients and osteomalacia was proved by iliac bone biopsy. Patient 1 had symptomatic bone disease and control of acidosis with sodium bicarbonate was difficult because of associated hypertension. The level of alkaline phosphatase varied inversely with the level of serum bicarbonate. Pharmacological doses of 1-alpha hydroxycholecalciferol were ineffective and osteomalacia persisted in a second biopsy. Patient 2, who was asymptomatic, suffered acidosis and increased serum alkaline phosphatase levels immediately postoperatively and osteomalacia was confirmed histologically at 6 months.

The syndrome of hyperchloremic metabolic acidosis following urinary diversion through intestinal segments has posed a problem for urologists for more than 50 years. Recent work demonstrates that chlorpromazine, an intestinal cyclic-AMP inhibitor, partially corrects the metabolic derangements associated with this syndrome. Nicotinic acid has also been shown to be a potent inhibitor of intestinal cyclic-AMP. The present investigation employs nicotinic acid in a rat vesico-cecostomy model to examine its efficacy in the management of this syndrome. Rats with vesico-cecostomies treated with nicotinic acid are compared to untreated rats, rats with intestinal but not urinary diversions and non-operative controls. Nicotinic acid in a dose of 50 mg./kg./day corrects the hyperchloremia (p less than 0.02), elevated serum osmolality (p less than 0.0001), hyperammoniumemia (p less than 0.05) and acidosis (p less than 0.001). Results compare favorably to those obtained in an identical model with the use of chlorpromazine.