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Concept: Metabolic acidosis


Lactic acidosis is a frequent cause of poor outcome in the intensive care settings. We set up an experimental model of lactic acid infusion in normoxic and normotensive rats to investigate the systemic effects of lactic acidemia per se without the confounding factor of an underlying organic cause of acidosis.

Concepts: Acid, PH, Sepsis, Metabolic acidosis, Bicarbonate, Acidosis, Sodium bicarbonate, Lactic acidosis


Bixalomer (BXL) was developed to improve gastrointestinal symptoms and reduce constipation, relative to sevelamer hydrochloride, in hemodialysis patients. We prospectively evaluated the safety and effectiveness of switching maintenance dialysis patients from sevelamer hydrochloride to BXL.

Concepts: Nephrology, Dialysis, Effectiveness, Cellular respiration, Hemodialysis, Metabolic acidosis, Renal dialysis, Sevelamer


Background. The Extracorporeal Treatments in Poisoning (EXTRIP) workgroup was created to provide evidence-based recommendations on the use of extracorporeal treatments (ECTR) in poisoning and the results are presented here for acetaminophen (APAP). Methods. After a systematic review of the literature, a subgroup selected and reviewed the articles and summarized clinical and toxicokinetic data in order to propose structured voting statements following a pre-determined format. A two-round modified Delphi method was chosen to reach a consensus on voting statements, and the RAND/UCLA Appropriateness Method was used to quantify disagreement. Following discussion, a second vote determined the final recommendations. Results. Twenty-four articles (1 randomized controlled trial, 1 observational study, 2 pharmacokinetic studies, and 20 case reports or case series) were identified, yielding an overall very low quality of evidence for all recommendations. Clinical data on 135 patients and toxicokinetic data on 54 patients were analyzed. Twenty-three fatalities were reviewed. The workgroup agreed that N-acetylcysteine (NAC) is the mainstay of treatment, and that ECTR is not warranted in most cases of APAP poisoning. However, given that APAP is dialyzable, the workgroup agreed that ECTR is suggested in patients with excessively large overdoses who display features of mitochondrial dysfunction. This is reflected by early development of altered mental status and severe metabolic acidosis prior to the onset of hepatic failure. Specific recommendations for ECTR include an APAP concentration over 1000 mg/L if NAC is not administered (1D), signs of mitochondrial dysfunction and an APAP concentration over 700 mg/L (4630 mmol/L) if NAC is not administered (1D) and signs of mitochondrial dysfunction and an APAP concentration over 900 mg/L (5960 mmol/L) if NAC is administered (1D). Intermittent hemodialysis (HD) is the preferred ECTR modality in APAP poisoning (1D). Conclusion. APAP is amenable to extracorporeal removal. Due to the efficacy of NAC, ECTR is reserved for rare situations when the efficacy of NAC has not been definitively demonstrated.

Concepts: Dialysis, Evidence-based medicine, Systematic review, Randomized controlled trial, Liver, Hemodialysis, Hemofiltration, Metabolic acidosis


Abstract Context. Haemodialysis is sometimes used for patients with massive acetaminophen overdose when signs of “mitochondrial paralysis” (lactic acidosis, altered mental status, hypothermia and hyperglycaemia) are present. The role of haemodialysis is debated, in part because the evidence base is weak and the endogenous clearance of acetaminophen is high. There is also concern because the antidote acetylcysteine is also dialyzable. We prospectively measured serum acetylcysteine concentrations during haemodialysis in three such cases. Case details. Three adults each presented comatose and acidemic 10 to ˜ 18 h after ingesting > 1000mg/kg of acetaminophen. Two were hypothermic and hyperglycaemic. Serum lactate concentrations ranged from 7 mM to 12.5 mM. All three were intubated, and initial acetaminophen concentrations were as high as 5980 μM (900 μg/mL). An intravenous loading dose of 150 mg/kg acetylcysteine was initiated between 10.8 and ˜ 18 h post ingestion, and additional doses were empirically administered during haemodialysis to compensate for possible antidote removal. A single run of 3-4 h of haemodialysis removed 10-20 g of acetaminophen (48-80% of remaining body burden), reduced serum acetaminophen concentrations by 56-84% (total clearance 3.4-7.8 mL/kg/min), accelerated native acetaminophen clearance (mean elimination half-life 580 min pre-dialysis, 120 min during and 340 min post-dialysis) and corrected acidemia. Extraction ratios of acetylcysteine across the dialysis circuit ranged from 73% to 87% (dialysance 3.0 to 5.3 mL/kg/min). All three patients recovered fully, and none developed coagulopathy or other signs of liver failure. Discussion. When massive acetaminophen ingestion is accompanied by coma and lactic acidosis, emergency haemodialysis can result in rapid biochemical improvement. As expected, haemodialysis more than doubles the clearance of both acetaminophen and acetylcysteine. Because acetylcysteine dosing is largely empirical, we recommend doubling the dose during haemodialysis, with an additional half-load when dialysis exceeds 6 h.

Concepts: Dialysis, Liver, Hemodialysis, Dose, Paracetamol, Metabolic acidosis, Half-life, Acetylcysteine


Acute metabolic acidosis is associated with increased morbidity and mortality because of its depressive effects on cardiovascular function, facilitation of cardiac arrhythmias, stimulation of inflammation, suppression of the immune response, and other adverse effects. Appropriate evaluation of acute metabolic acidosis includes assessment of acid-base parameters, including pH, partial pressure of CO(2) and HCO(3)(-) concentration in arterial blood in stable patients, and also in central venous blood in patients with impaired tissue perfusion. Calculation of the serum anion gap and the change from baseline enables the physician to detect organic acidoses, a common cause of severe metabolic acidosis, and aids therapeutic decisions. A fall in extracellular and intracellular pH can affect cellular function via different mechanisms and treatment should be directed at improving both parameters. In addition to supportive measures, treatment has included administration of base, primarily in the form of sodium bicarbonate. However, in clinical studies of lactic acidosis and ketoacidosis, bicarbonate administration has not reduced morbidity or mortality, or improved cellular function. Potential explanations for this failure include exacerbation of intracellular acidosis, reduction in ionized Ca(2+), and production of hyperosmolality. Administration of tris(hydroxymethyl)aminomethane (THAM) improves acidosis without producing intracellular acidosis and its value as a form of base is worth further investigation. Selective sodium-hydrogen exchanger 1 (NHE1) inhibitors have been shown to improve haemodynamics and reduce mortality in animal studies of acute lactic acidosis and should also be examined further. Given the important effects of acute metabolic acidosis on clinical outcomes, more intensive study of the pathogenesis of the associated cellular dysfunction and novel methods of treatment is indicated.

Concepts: Immune system, Better, Blood, PH, Acid-base homeostasis, Metabolic acidosis, Anion gap, Acidosis


Variable ionized calcium measurements in post filter blood samples during continuous renal replacement therapy (renal dialysis) using regional citrate anticoagulation (RCA) have been reported using commercial blood gas analyzers, resulting in analyzer-dependent differences in decisions regarding adjustment of citrate dose.

Concepts: Renal failure, Chronic kidney disease, Nephrology, Dialysis, Hemodialysis, Renal replacement therapy, Electrolyte, Metabolic acidosis


Lactic acidosis is a common cause of high anion gap metabolic acidosis. Sodium bicarbonate may be considered for an arterial pH <7.15 but paradoxically depresses cardiac performance and exacerbates acidosis by enhancing lactate production. This study aimed to evaluate the cause and mortality rate of lactic acidosis and to investigate the effect of factors, including sodium bicarbonate use, on death.

Concepts: Blood, PH, Lactic acid, Metabolic acidosis, Anion gap, Acidosis, Sodium bicarbonate, Lactic acidosis


In children, the most common cause of an elevated anion gap (AG) with ketonemia, ketonuria, hyperglycemia, and glycosuria is diabetic ketoacidosis. However, when the clinical history is not clear, other causes must be considered. A 9-month-old girl was transferred to our pediatric intensive care unit (PICU) because of severe metabolic acidosis. On admission, she presented with Kussmaul breathing, tachycardia, irritability, and fever. Blood gasses revealed metabolic acidosis with superimposed respiratory alkalosis and elevated AG. Fluid replacement and bicarbonate for urine alkalinization were started. Ketonemia, acidic urine with glycosuria, ketonuria, and high blood glucose prompted an insulin infusion. Measurement of plasma salicylate confirmed toxic levels. When confronted, the parents admitted to accidentally preparing the child’s bottle with water containing salicylic acid 1000 mg. Although the incidence of salicylate intoxication has declined, it remains an important cause of pediatric morbidity and mortality.

Concepts: Ammonia, Diabetes mellitus, PH, Metabolic acidosis, Anion gap, Acid-base disturbances, Acidosis, Kussmaul breathing


Strokelike episodes are a cardinal feature of several mitochondrial syndromes, including mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes (MELAS). Recent advances in the understanding of the pathophysiologic mechanisms of strokelike episodes in MELAS have led to improved treatment options.

Concepts: Metabolic acidosis, Lactic acidosis


To investigate the decreased response to hypothermia in neonates with hypoxic-ischemic encephalopathy (HIE) and infection, we sought to determine the association of fetal inflammation/infection with perinatal metabolic acidosis.

Concepts: Pregnancy, Infant, Fetus, The Association, Metabolic acidosis