The objective of this study was to investigate regional organ perfusion acutely following uncontrolled hemorrhage in an animal model that simulates a penetrating vascular injury and accounts for prehospital times in urban trauma. We set forth to determine if hypotensive resuscitation (permissive hypotension) would result in equivalent organ perfusion compared to normotensive resuscitation.Twenty four (n=24) male rats randomized to 4 groups: Sham, No Fluid (NF), Permissive Hypotension (PH) (60% of baseline mean arterial pressure - MAP), Normotensive Resuscitation (NBP). Uncontrolled hemorrhage caused by a standardised injury to the abdominal aorta; MAP was monitored continuously and lactated Ringer's was infused. Fluorimeter readings of regional blood flow of the brain, heart, lung, kidney, liver, and bowel were obtained at baseline and 85 minutes after hemorrhage, as well as, cardiac output, lactic acid, and laboratory tests; intra-abdominal blood loss was assessed. Analysis of variance was used for comparison.Intra-abdominal blood loss was higher in NBP group, as well as, lower hematocrit and hemoglobin levels. No statistical differences in perfusion of any organ between PH and NBP groups. No statistical difference in cardiac output between PH and NBP groups, as well as, in lactic acid levels between PH and NBP. NF group had significantly higher lactic acidosis and had significantly lower organ perfusion.Hypotensive resuscitation causes less intra-abdominal bleeding than normotensive resuscitation and concurrently maintains equivalent organ perfusion. No fluid resuscitation reduces intra-abdominal bleeding but also significantly reduces organ perfusion.

To delineate the characteristics of the clinical manifestation, pathology of skeletal muscle and gene mutations of mitochondrial encephalomyopathy with lactic acidosis and stroke-like episode (MELAS) in children.The clinical manifestation, laboratorial data, brain images, muscle pathology and mitochondrial gene mutations were analyzed in 24 patients with MELAS who were diagnosed in Department of Pediatrics, Peking University First Hospital. Their prognosis was evaluated by following up.Symptoms of central nervous system such as stroke-like episodes, vomiting, convulsion and headache were present in all the 24 cases. Nine cases had the symptoms of myopathy. Twenty cases had developmental delay. Short stature, being thin and hairy was very common in these cases. Serum lactate level increased in all the cases, pyruvate increased in 17 cases. Elevated CSF lactate was found in 2 cases. Magnetic resonance imaging (MRI) was performed on 24 cases, out of them 23 were abnormal. The lesions mainly involved cerebral lobes. Occipital lobe was the most common site of lesions. Computed tomography (CT) was performed on 13 cases, low density lesions were present in 10 cases, basal ganglia calcifications in 5 cases. Muscle biopsy was performed on 8 cases, ragged-red fibers (RRF) were found in 4/8 cases, and abnormal accumulation of mitochondria were found in 3/8 cases. The mtDNA gene mutational analysis showed A3243G mutation in these patients. The mutation rates varied from 11.6% to 75.0%. The same mutation were found in 4/5 mothers who had the genetic tests, and the mutation rates of the mothers varied from 15.0% to 23.6%. The clinical information of 11 cases was available through recent following up. Three cases died, the others had some degrees of mental retardation.Children with MELAS had various clinical manifestations. Central nervous system and skeletal muscle were usually involved. Short stature and hypertrichosis were common signs. The prognosis of this disease was disappointing. mtDNA A3243G was the most common mutation in MELAS. Fully understanding the characteristics of its clinical manifestation, laboratory tests, brain image, muscle pathology and molecular features can be helpful to the early diagnosis and treatment.

Lactic acidosis in the absence of hypoxia or tissue hypoperfusion (type B) is very rare and is associated with the use of some drugs or malignancy. We report a 79-year-old woman, with a marginal non-Hodgkin's lymphoma of the spleen that was subjected to a splenectomy one year ago. She presented with unexplained tachypnea associated with pancytopenia and elevation of IgM to 10 times over the higher normal limit. Laboratory tests showed the presence of metabolic acidosis and high lactic acid levels in the absence of infection, tissue hypoxia or hypoperfusion. She was treated with sodium bicarbonate and steroids without obtaining a reduction in lactate levels. Twelve days after admission, a single dose of Rituximab quickly normalized lactate concentrations and platelet count. After the fourth dose of Rituximab, pancytopenia disappeared and IgM fell to 25% of its baseline concentration.

We describe the case of a patient with severe lactic acidosis, as well as presenting some data on its incidence, diagnosis, prognostic factors, and the most appropriate treatment. A 76 year-old male patient with diabetes on treatment with metformin, hypertension, dyslipaemia, and with mild cognitive impairment, was admitted to the Intensive Care Unit in a state of circulatory shock, requiring aggressive treatment with vasopressors and volume. The patient had acute kidney injury with an anuria of 3 days, probably secondary to dehydration to vomiting and to NSAIDs. As a result of the acute renal damage, the patient suffered a severe metformin-associated lactic acidosis. The rest of the causes of metabolic acidosis with an increased anion gap were ruled out, as well as a possible sepsis or rhabdomyolysis. Metformin-associated lactic acidosis is an uncommon metabolic condition, but with a high mortality. To reduce the mortality of these patients, it is important to make an early diagnosis using the clinical records, physical examination, and laboratory tests, with an early resuscitation with volume, vasopressors, bicarbonate, and renal replacement therapy.

To describe the natural history of clinical and laboratory features associated with the m.3243A>G mitochondrial DNA point mutation. Natural history data are needed to obtain prognostic information and for clinical trial planning.We included 85 matrilineal relatives from 35 families with at least 2 visits in this prospective cohort study. Thirty-one were fully symptomatic with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS), and 54 were carrier relatives. Evaluations included standardized questionnaires (medical history and daily living functioning), physical examination, neuropsychological testing, and a battery of imaging and laboratory tests. We evaluated changes in clinical and laboratory features over time and survival. Outcomes are reported over a follow-up period of up to 10.6 years (mean 3.8 ± 2.2 years for patients and 5.5 ± 3.0 for carrier relatives).Neurologic examination, neuropsychological testing, and daily living scores significantly declined in all patients with MELAS, whereas no significant deterioration occurred in carrier relatives. Cerebral MRI scores declined significantly in patients with MELAS. Magnetic resonance spectroscopy estimates of lactate in the lateral ventricles increased over time, and high lactate was associated with increased mortality. Symptom onset in childhood often was associated with worse outcome. Patients with MELAS had a greater death rate than carrier relatives.Patients with MELAS carrying the m.3243A>G mutation show a measurable decline in clinical and imaging outcomes. It is hoped that these data will be helpful in anticipating the disease course and in planning clinical trials for MELAS.

The aim of this paper is to present a case of a 61-year-old male transferred to the Regional Center of Clinical Toxicology from the Department of Endocrinology with suspected methanol poisoning. The patient presented symptoms of diabetes with extreme hyperglycemia >1600 mg/dl and nonketotic hyperosmolar coma. Laboratory tests showed metabolic/respiratory acidosis, methanol 80 mg/dl, ethanol 0.47 g/l, creatinine 3.5 mg/dl, urea 140 mg/dl, lactic acid 4.11 mmol/l, myoglobin >1000 ng/ml, HbA1C >14.5%. During a few days prior to the hospitalization the patient was drinking a great amount of fruit juices and milk (a dozen or so litres per twenty four hours). The eventuality of metabolizing glucose and aspartame into methanol is known from professional literature. The possibility of excessive consumption of aspartame and its metabolites causing methanol poisoning in the presented patient was considered.

Nine rhesus macaques were implanted with multisensor telemetry devices and internal jugular vein catheters before being infected with Zaire ebolavirus. All animals developed viremia, fever, a hemorrhagic rash, and typical changes of Ebola hemorrhagic fever in clinical laboratory tests. Three macaques unexpectedly survived this usually lethal disease, making it possible to compare physiological parameters in lethally challenged animals and survivors. After the onset of fever, lethal illness was characterized by a decline in mean arterial blood pressure, an increase in pulse and respiratory rate, lactic acidosis, and renal failure. Survivors showed less pronounced change in these parameters. Four macaques were randomized to receive supplemental volumes of intravenous normal saline when they became hypotensive. Although those animals had less severe renal compromise, no apparent survival benefit was observed. This is the first report of continuous physiologic monitoring in filovirus-infected nonhuman primates and the first to attempt cardiovascular support with intravenous fluids.

We present an uncommon case of lactic acidosis after concomitant administration of Metformin and Tenofovir. This is a 74-year-old man with a history of diabetes mellitus receiving treatment with metformin. He had coronary artery disease and HIV infection treated with emtricitabine, tenofovir and recently started on efavirenz. He presented with zoster-like abdominal pain, tachypnoea, nausea and vomiting. On clinical examination, the patient was afebrile, hypotensive and tachycardic, he was markedly dehydrated and oliguric. The abdomen was soft, tender on palpation, not distended without rebound tenderness. The arterial blood gases revealed marked lactic acidosis and the laboratory tests on admission showed acute renal failure. The patient received nine treatments of slow continuous veno-venous hemofiltration (CVVHF). Despite the prolonged period of anuria, urine output progressively improved after 25 days and serum biochemical parameters of renal function returned to normal within 40 days. Health professionals must be aware of this uncommon effect in patients on antiretroviral treatment. Prompt initiation of CVVHF resulted in resolution of both lactic acidosis and renal failure.

A 36-year-old African American man with end-stage renal disease on chronic maintenance hemodialysis was transferred first from a hospital to a long-term acute care facility for advanced care then to the intensive care unit of our university hospital with unexplained abdominal pain, nausea, hypotension, altered mental status and anion gap metabolic acidosis. Subsequent review of the patient's medication list revealed that the he had been on linezolid for 6 weeks for the treatment of vancomycin-resistant Enterococcus fecalis bacteremia.Medical history, physical examination, laboratory tests, CT imaging of the thorax, abdomen and pelvis and PCR-based tests to determine the presence of polymorphisms in the 16S ribosomal RNA gene.Lactic acidosis associated with prolonged exposure to linezolid.Discontinuation of linezolid.

To decide whether the use of blood lactate monitoring in critical care practice is appropriate. We performed a systematic health technology assessment as blood lactate monitoring has been implemented widely but its clinical value in critically ill patients has never been evaluated properly.PubMed, other databases, and citation review.We searched for lactate combined with critically ill patients as the target patient population. Two reviewers independently selected studies based on relevance for the following questions: Does lactate measurement: 1) perform well in a laboratory setting? 2) provide information in a number of clinical situations? 3) relate to metabolic acidosis? 4) increase workers' confidence? 5) alter therapeutic decisions? 6) result in benefit to patients? 7) result in similar benefits in your own setting? 8) result in benefits which are worth the extra costs?We concluded that blood lactate measurement in critically ill patients: 1) is accurate in terms of measurement technique but adequate understanding of the (an)aerobic etiology is required for its correct interpretation; 2) provides not only diagnostic but also important prognostic information; 3) should be measured directly instead of estimated from other acid-base variables; 4) has an unknown effect on healthcare workers' confidence; 5) can alter therapeutic decisions; 6) could potentially improve patient outcome when combined with a treatment algorithm to optimize oxygen delivery, but this has only been shown indirectly; 7) is likely to have similar benefits in critical care settings worldwide; and 8) has an unknown cost-effectiveness.The use of blood lactate monitoring has a place in risk-stratification in critically ill patients, but it is unknown whether the routine use of lactate as a resuscitation end point improves outcome. This warrants randomized controlled studies on the efficacy of lactate-directed therapy.