Serum lactate

Normalization of laboratory measurements expected within hours to days following fluid resuscitation. Specifically, normalization of base deficit and serum lactate is recommended within 24 hours to potentially decrease mortality 48 and... 

Monitor the following serial laboratories for comparison to baseline values every 6 hours in the first 24 hours and daily thereafter until normalized sodium, serum creatinine, blood urea nitrogen, serum lactate, glucose, bilirubin, hemoglobin, hematocrit, platelets, prothrombin time, partial thromboplastin time, arterial blood gases, and pH. 

Other possible laboratory abnormalities include elevated white blood cell count, hyperglycemia, hypocalcemia, hyperbilirubinemia, elevated serum lactate dehydrogenase (LDH), and hypertriglyceridemia. 

An elevated serum lactate concentration may be an early marker for tissue hypoperfusion. 

Cardiac index and blood pressure must be sufficient to ensure adequate organ perfusion, as assessed by alert mental status, creatinine clearance sufficient to prevent metabolic azotemic complications, hepatic function adequate to maintain synthetic and excretory functions, a stable heart rate and rhythm, absence of ongoing myocardial ischemia or infarction, skeletal muscle and skin blood flow sufficient to prevent ischemic injury, and normal arterial pH (7.34 to 7.47) with a normal serum lactate concentration. These goals are most often achieved with a cardiac index greater than 2.2 L/min/m2, a mean arterial blood pressure greater than 60 mm Hg, and PAOP of 25 mm Hg or greater. 

J2. Jorgensen, C. R., Zimmerman, T. S., and Wang, Y., Serum lactate dehydrogenase elevation in ambulatory cardiac patients Evidence for chronic hemolysis. Circulation 35, 79-89 (1967). 

Banasch, M., Goetze, O., Hollborn, I., Hochdorfer, B., Bulut, K., Schlottmann, R., Hagemann, D., Brockmeyer, N.H., Schmidt, W.E. and Schmitz, F. (2005) 3C-methionine breath test detects distinct hepatic mitochondrial dysfunction in HIV-infected patients with normal serum lactate. Journal of Acquired Immune Deficiency Syndromes, 40 (2), 149-152. 

The answer is C. Pyruvate kinase deficiency is ruled out by the elevated serum lactate levels. The coma is associated with a fasting hypoglycemia, which is indicative of pyruvate carboxylase deficiency. The elevated citrulline and lysine in the serum are due to a reduction of aspartic acid levels, which are caused by the reduced levels of oxaloacetate, the product of the pymvate carboxylase reaction. 

A 67-year-old man who had taken phenformin and glibenclamide for 2 years became lethargic and confused (60). His pH was 6.91, serum lactate 25 mmol/1 and later 30 mmol/1, and blood glucose very low (0.5 mmol/1), possibly because of vomiting, anorexia, and glibenclamide. Hemodialysis was advised but not performed, since he recovered spontaneously. 

A 37-year-old woman purposely took metformin 10 g (129). She did not develop hypoglycemia, but the serum lactate increased to 3.2 mmol/1 (reference range under 2.1 mmol/1) and she became nauseated. She recovered. 

A 70-year-old man survived a suicidal attempt with metformin 63 g (132). His serum lactate concentration was 24 mmol/1 and creatinine 216 pmol/1. He received bicarbonate hemodialysis, blood pressure support, and active warming for hypothermia. After 6 hours lactate and creatinine normalized. 

A 57-year-old woman, who had taken metformin 500 mg bd for 15 years, took indometacin 50 mg qds for 2 months. She developed oliguria and acidosis (pH 6.82, serum lactate 21 mmol/1, creatinine 480 pmol/l). After stopping metformin and indometacin she improved and left hospital with stable impaired kidney function. 

A 53-year-old man taking simvastatin 40 mg/day developed rhabdomyolysis and hepatitis and had a raised serum lactate concentration (8.3 mmol/1 reference range 0.5-2.2) (8). Everything resolved 7 days after drug withdrawal. 

There was significant improvement in signs of mitochondrial toxicity in 49 patients who switched from stavudine to abacavir compared with 63 patients who continued to take stavudine in a non-randomized study for 12 months (152). Only patients who remained on their assigned treatment were included in the analysis. Lactate concentrations were assessed at baseline, week 24, and week 48, and electrical bioimpedance was performed in 22 cases and 12 controls at baseline and week 48. There were significant falls in serum lactate concentrations at weeks 24 and 48 in cases compared with controls. Patients who switched had a trend towards fat gain, while controls had significant reductions in total body fat and percentage of body fat. 

A 37-year-old HIV-infected woman receiving stavudine, lamivudine, and indinavir developed epigastric pain, anorexia, and vomiting. She had lactic acidosis (serum lactate 4.9 mmol/1), raised liver enzymes, and an increased prothrombin time. She had hepatomegaly and tachypnea and required mechanical ventilation. Her progress was complicated by pancreatitis and acute respiratory distress syndrome. Antiviral medication was stopped and she was treated with co-enzyme Q, carnitine, and vitamin C. The serum lactic acid and transaminases returned to normal over 4 weeks and she was weaned off the ventilator after 4 months. 

A 40-year-old HIV-infected woman receiving stavudine, lamivudine, nelfinavir, and co-trimoxazole developed dyspnea, dysphagia, and vomiting with lactic acidosis (serum lactate 9.4 mmol/1) and hepatomegaly. Despite ventilation for respiratory failure she died after 5 days. Autopsy showed massive hepatomegaly with steatosis. 

A 36-year-old HIV-infected woman who had been receiving stavudine, saquinavir, ritonavir, and didanosine developed lactic acidosis (serum lactate 11.4 mmol/1) and hepatomegaly. She had acute pancreatitis and, despite ventilatory support for respiratory failure, died after 8 weeks. 

Metabolic changes that protease inhibitors can cause after prolonged therapy include raised serum lactate, hypogonadism, hypertension and accelerated cardiovascular disease, reduced bone density, and avascular necrosis of the hip. Two large prospective studies in 1207 patients (972) and 3191 patients (973) have clarified the spectrum and incidence of metabolic changes in HAART and have explored the relative importance of protease inhibitors. In addition, data on fat redistribution from a postmarketing review of HIV-infected individuals taking indinavir have been published (974). 

Examination of these people revealed disruptions in bone marrow function, including cases of hypoplastic, acellular, hyperplastic, or normoblastic bone marrow. The continuing assessment further identified that ineffective erythropoiesis or increased hemolysis may have been responsible for the reticulocytosis, hyperbilirubinemia, erythroblastemia, increase in quantitative osmotic fragility, and elevated serum lactate dehydrogenase levels observed in some patients. 

There have been reports of HIV-associated neuromuscular weakness, probably associated with symptomadc lacdc acidosis (Estanislao et al., 2004). Lethal cases have been reported in associadon with stavucUne. Usually the cases have occurred after several months of use of the mecUcadon and have been associated vith sensory motor neuropathy and elevated serum lactate levels. It is tempdng to include this concUdon as another manifestadon of mitochoncUial damage induced by NRTIs. 

Drent M, Cobben NA, Van Dieijen-Visser MP, Braat SH, Wouters EF. Serum lactate dehydrogenase activity indicator of the development of pneumonitis induced by amiodarone. Eur Heart J 1998 19(6) 969-70. 

The transient and moderate rises in leukocyte alkaline phosphatase and uric acid serum concentrations that are often observed after G-CSF treatment are considered to arise from an increased neutrophil count (SEDA-17, 396). Similarly, serum lactate dehydrogenase and alkaline phosphatase activities are often increased, and this should be interpreted as the consequence of enzyme release after growth factor-induced leukocyte recovery (SED-13, 1115). 

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