Mean Serum Lactate Research Articles

Oxidative effects of long-term onion (Allium cepa) feeding on goat erythrocytes

Toxic compounds such as disulfides of onions cause oxidative-induced haemolysis in several animal species. In order to study the outcomes of long-term onion consumption on some oxidative haemolysis markers, 12 adult female goats were allocated to three groups, receiving 0% (served as control), 30% (dry matter basis) and 60% spring-grown onion for 60 days. Blood samples were obtained before feeding the onion and every 10 days up to 80 days for measuring malonyldialdehyde (MDA), methaemoglobin (MetHb), mean corpuscular fragility (MCF), serum-free haemoglobin and serum lactate dehydrogenase (LDH) and for evaluating their relation to packed cell volume (PCV) and haemoglobin (Hb) concentrations. PCV and Hb concentrations reduced, however, remained within reference ranges in onion-fed goats. MetHb showed a significant negative correlation with both PCV and Hb (P < 0.05) in onion-fed goats and a significant positive correlation with MCF and serum-free haemoglobin in goats receiving 30% onion. MetHb showed a significant positive correlation with MCF in goats fed with 60% onion. MDA showed a positive correlation with LDH and serum-free haemoglobin concentrations. These results suggest a role for oxidative damage in destructing red cells in goats feeding onions. However, it seems that up to 60% onions in diet can be consumed by goats without noticeable clinical anaemia.

Azaperone and sudden death of drive net-captured southern chamois

The use of tranquilizers in the capture of southern chamois (Rupicapra pyrenaica) for scientific and/or management purposes (collection of samples, marking, translocations) was studied to improve animal welfare during capture operations. We used clinical findings and a statistical approach to analyze the causes of six incidences of mortality during captures using drive nets and tranquilizers in this species. Hematology and serum biochemistry, pathology, the use of tranquilizers and their dosages, the number of people involved in the capture of the chamois, and the location were all taken into account. The selection of candidate models to explain mortality was conducted using the theoretic information approach. Both observational findings and the models selected suggested that high doses of azaperone and to a lesser extent haloperidol had an effect on mortality rates. The higher mean serum lactate concentrations found in the chamois that died suggests that fatigue levels increased drug sensitivity and provoked the appearance of adverse effects, thereby increasing the probability of death. We conclude that butyrophenones—and especially azaperone—have a low safety margin in the southern chamois, contrary to what has been described for other species.

New aspects in the diagnosis and management of acute mesenteric infarction

A retrospective analysis of 121 patients (45 men; 76 women) suffering from mesenteric ischemia was done to compare current diagnostic and therapeutic modalities. The average age was 72.9 years and the overall mortality was 76%. In 45 patients (37%) only explorative laparotomy was performed with none surviving, and 11 patients (9%) died before any form of therapy could be undertaken. Twenty-six patients (21%) had bowel resection alone (mortality: 62%): 8 also had preoperative thrombolytic therapy (38% mortality): 21 (17%) had bowel resection combined with a revascularization procedure with a mortality of 48%; and 10 (8%) had revascularization alone (70% mortality). Significant findings for mortality were duration of symptoms more than twelve hours, central mesenteric occlusion with extensive intestinal infarction, stage of hypovolemic shock, and age. Mean serum lactate concentration was 8.6 ± 2.8 mmol/L (normal 1.5 ± 1.0 mmol/L) at onset, and level normalization following surgery was significant for an uncomplicated recovery (p<0.001). Patients treated with primary anastomosis (63% mortality) did poorer than those with a delayed anastomosis (47% mortality), but this was not significant (p<0.1).

Femoral-Based Central Venous Oxygen Saturation Is Not a Reliable Substitute for Subclavian/Internal Jugular-Based Central Venous Oxygen Saturation in Patients Who Are Critically Ill

Central venous oxygen saturation (Scv(O(2))) has been used as a surrogate marker for mixed venous oxygen saturation (Sv(O(2))). Femoral venous oxygen saturation (Sfv(O(2))) is sometimes used as a substitute for Scv(O(2)). The purpose of this study is to test the hypothesis that these values can be used interchangeably in a population of patients who are critically ill. We conducted a survey to assess the frequency of femoral line insertion during the initial treatment of patients who are critically ill. Scv(O(2)) vs Sfv(O(2)) STUDY: Patients with femoral and nonfemoral central venous catheters (CVCs) were included in this prospective study. Two sets of paired blood samples were drawn simultaneously from the femoral and nonfemoral CVCs. Blood samples were analyzed for oxygen saturation and lactate. One hundred and fifty physicians responded to the survey. More than one-third of the physicians insert a femoral line at least 10% of the time during the initial treatment of patients who were critically ill. Scv(O(2)) vs Sfv(O(2)) STUDY: Thirty-nine patients were enrolled. The mean Scv(O(2)) and Sfv(O(2)) were 73.1% +/- 11.6% and 69.1% +/- 12.9%, respectively (P = .002), with a mean bias of 4.0% +/- 11.2% (95% limits of agreement: -18.4% to 26.4%). The mean serum lactate from the nonfemoral and femoral CVCs was 2.84 +/- 4.0 and 2.72 +/- 3.2, respectively (P = .15). This study revealed a significant difference between paired samples of Scv(O(2)) and Sfv(O(2)). More than 50% of Scv(O(2)) and Sfv(O(2)) values diverged by > 5%. Sfv(O(2)) is not always a reliable substitute for Scv(O(2)) and should not routinely be used in protocols to help guide resuscitation.

Comparison of different criteria for the diagnosis of primary myelofibrosis reveals limited clinical utility for measurement of serum lactate dehydrogenase

Primary myelofibrosis shows histological and pathogenetic overlap with essential thrombocythemia and polycythemia vera. Several diagnostic classifications have been proposed for primary myelofibrosis, although little is known about their clinical utility. In a comparison of three recent classifications, overall concordance was 79%. Inclusion of raised serum lactate dehydrogenase categorized 9% of patients as primary myelofibrosis when other criteria were not met. Although mean serum lactate dehydrogenase levels were higher in patients with primary myelofibrosis, levels were also increased in the majority of patients with essential thrombocythemia or polycythemia vera, and significant overlap was observed. A positive correlation with higher leukocyte and platelet count, and disease duration in primary myelofibrosis, suggests that serum lactate dehydrogenase is a biomarker for disease bulk and/or cellular proliferation. In conclusion, raised lactate dehydrogenase lacks specificity for primary myelofibrosis, consistent with the concept of a phenotypic continuum between essential thrombocythemia, polycythemia vera and primary myelofibrosis.

Outcome of severe lactic acidosis associated with metformin accumulation

IntroductionMetformin associated lactic acidosis (MALA) may complicate metformin therapy, particularly if metformin accumulates due to renal dysfunction. Profound lactic acidosis (LA) generally predicts poor outcome. We aimed to determine if MALA differs in outcome from LA of other origin (LAOO).MethodsWe conducted a retrospective analysis of all patients admitted with LA to our medical ICU of a tertiary referral center during a 5-year period. MALA patients and LAOO patients were compared with respect to parameters of acid-base balance, serum creatinine, hospital outcome, Simplified Acute Physiology Score II (SAPS II) and Sequential Organ Failure Assessment (SOFA) score, using Pearson's Chi-square or the Mann-Whitney U-test.ResultsOf 197 patients admitted with LA, 10 had been diagnosed with MALA. With MALA, median arterial blood pH was significantly lower (6.78 [range 6.5 to 6.94]) and serum lactate significantly higher (18.7 ± 5.3 mmol/L) than with LAOO (pH 7.20 [range 6.46 to 7.35], mean serum lactate 11.2 ± 6.1 mmol/L). Overall mortality, however, was comparable (MALA 50%, LAOO 74%). Furthermore, survival of patients with arterial blood pH < 7.00 (N = 41) was significantly better (50% vs. 0%) if MALA (N = 10) was the underlying condition compared to LAOO (N = 31).ConclusionsCompared to similarly severe lactic acidosis of other origin, the prognosis of MALA is significantly better. MALA should be considered in metformin-treated patients presenting with lactic acidosis.

Bedside detection of low systemic flow in the very low birth weight infant on day 1 of life

We aimed to assess the relationship between the clinical and biochemical parameters of perfusion and superior vena cava (SVC) flow in a prospective observational cohort study of very low birth weight (VLBW) infants. Newborns with congenital heart disease were excluded. Echocardiographic evaluation of SVC flow was performed in the first 24 h of life. Capillary refill time (forehead, sternum and toe), mean blood pressure, urine output and serum lactate concentration were also measured simultaneously. Thirty-eight VLBW infants were examined. Eight patients (21%) had SVC flow less than 40 ml/kg/min. There was a poor correlation between the capillary refill time (in all sites), mean blood pressure, urine output and SVC flow. The correlation coefficient for the serum lactate concentration was r = -0.28, p = 0.15. The median serum lactate concentration was 3.5 (range 2.8-8.5) vs. 2.7 (range 1.2-6.9) mmol/l (p = 0.01) in low flow versus normal flow states. A serum lactate concentration of >2.8 was 100% sensitive and 60% specific for detecting a low flow state. Combining a capillary refill time of >4 s with a serum lactate concentration of >4 mmol/l had a specificity of 97% for detecting a low SVC flow state. Serum lactate concentrations are higher in low SVC flow states. A capillary refill time of >4 s combined with serum lactate concentrations >4 mmol/l increased the specificity and positive and negative predictive values of detecting a low SVC flow state.

Cardiovascular Magnetic Resonance Imaging for Intensive Care Infants: Safe and Effective?

Cardiac magnetic resonance imaging (MRI) is an important diagnostic tool for congenital heart disease (CHD), as reflected by class 1 recommendations for the use of cardiac MRI by various consensus panels. However, little is known about the safety and clinical utility of cardiac MRI for these critically ill infants with CHD, whose further management cannot be directed by echocardiography. This study aimed to assess the safety, the potential hemodynamic side effects, and the clinical benefits of cardiac MRI for infants with complex CHD during their intensive care unit stay. Infants referred from the pediatric cardiac intensive care unit (PCICU) to the authors' cardiac MRI program in the past 2 years were retrospectively analyzed using the electronic chart system available at their institution. Data collected included age, diagnosis, inotropic support, urine output, diuretic medication, body temperature and lactate levels, length of MRI examination, adverse effects during and after the procedure, clinical implications of MRI, length of stay in the PCICU, and mean blood pressure and heart rate before, during, and after MRI. Among 592 patients in the past 2 years, 20 (3.4%) were referred for MRI testing during their stay in the PCICU. The mean age of the infants was 4.8+/-3.2 months. Four of the patients were neonates, and eight were postoperative patients. Intracardiac malformations were present in 16 of the infants, vascular rings causing tracheal stenosis in 3 patients, and cardiomyopathy in 1 patient. The mean stay in the PCICU was 28+/-43 days. Eight of the infants were ventilated, with a mean fraction of inspired oxygen (FiO2) of 0.30+/-0.15. Four were receiving inotropic support. All the nonventilated children were intubated for the MRI and extubated in the MRI laboratory. The mean duration of the MRI (door-to-door time) was 110+/-27 min. All except one patient were hemodynamically stable, and no increase in catecholamine support was necessary during or after the scans. A 10-month-old girl receiving inotropic support needed a single dose of epinephrine due to a short episode of bradycardia after a breathhold for a contrast agent MRI angiography. Mean body core temperature at arrival to the PCICU was 36.8+/-0.7 degrees C. The mean serum lactate level after the MRI was 1.2+/-0.4 mmol/l. The mean blood pressure and heart rate before, during, and after MRI were unchanged. The mean diuresis on examination day was insignificantly lower (2.4%) than the day before with unchanged medication (5.09+/-1.58 vs 5.53+/-1.77 ml/kg/h). For 14 (70%) of the 20 patients, surgical or catheter interventional procedures were initiated based on novel MRI information. Cardiac MRI can be performed safely with low risk and limited hemodynamic changes for infants during their stay in the PCICU. Cardiac MRI provides key information for invasive management decisions in this subset of patients.

Relationship between serum lactate level and periventricular leukomalacia

In a case control study, we evaluated the serum lactate levels during the early days of life in preterm infants with periventricular leukomalacia (PVL), who were presumed to have suffered injury around birth. Thirteen infants diagnosed by ultrasonography as suffering from cystic PVL during the neonatal period and 26 normally developed infants matched by gestational age were enrolled in the study. The serum lactate level was measured repeatedly during the 72 h after birth. The mean serum lactate levels on admission were 2.95 ± 0.43 and 3.21 ± 0.29 mmol/L in the PVL and control groups, respectively. There was no statistically significant difference in the serum lactate level between the groups at any point during the first 72 h after birth. In conclusion, the serum lactate level was not elevated in preterm infants with PVL suggesting that the serum lactate level is not a useful predictor for the development of PVL in infants.

The Relationship of Serum Lactate and Base Deficit in Burn Patients to Mortality

Serum lactate and base deficit in trauma patients have been shown to correlate with mortality. This study examines the relationship of these parameters to mortality among burn patients. We evaluated patients with >or=20% TBSA burn injury who had a serum lactate or base deficit recorded during the initial 48 hours of admission over a 5-year period. The primary study outcome was mortality. The mean (+/-SD) age of study patients (N = 128) was 35.2 +/- 21.1 years, the mean burn size was 41.7 +/- 17.9% TBSA, and the mortality rate was 17.1%. Mean serum lactate values of patients who died were significantly higher than those of survivors at admission and at 12, 18, and 24 hours after admission. The highest serum lactate value in the first 48 hours after admission was higher for nonsurvivors than survivors. Mean base deficit at admission and 6 hours after admission was significantly lower in patients who died than in survivors; in addition, the worst base deficit during the first 48 hours of care was significantly lower in patients who died than in those who survived. Early serum lactate and base deficit values are often worse for burn patients who die than for survivors. Elevation of serum lactate values during the first 48 hours after a burn is an independent risk factor for death, but no threshold value for serum lactate is demonstrable. Resuscitation should not be withheld from burn patients on the basis of any lactate or base deficit value.

Serum Lactate Level Has Prognostic Significance After Pediatric Cardiac Surgery

The determination of postoperative course after cardiac surgery has always been a challenging issue. It is more sophisticated in the pediatric age group. The aim of this investigation was to identify whether increased concentrations of lactate in arterial blood has a predictive value for postoperative morbidity and mortality after heart surgery. From May 2002 to June 2003, 60 infants operated on at the authors' institution were included in this prospective study. The patients were divided into 2 groups according to their respective postoperative serum lactate values. After the stabilization period in the intensive care unit (first 3 hours postoperatively), samples for serum lactate were obtained from arterial blood at 3 (t1), 6 (t2), and 12 hours (t3) postoperatively. The patients were subdivided into 2 groups according to their respective mean serum lactate values. A value of 4.8 mmol/L (3 times the normal upper limit) was chosen as a threshold for serum lactate. The patients with a mean value of greater than 4.8 mmol/L (group 1) were compared with the remaining group of patients (group 2). The relationship between serum mean lactate level and intraoperative and postoperative clinical variables was evaluated. Among the patients in this study, 26 (43.3%) had a serum mean lactate level more than 4.8 mmol/L and 34 (56.7%) had a level of 4.8 mmol/L or less. Age, aortic cross-clamping time, cardiopulmonary bypass time, and the lowest hematocrit during cardiopulmonary bypass were significant variables that influenced the postoperative serum mean lactate level. Six patients died in the postoperative period and 54 infants survived. The hospital mortality was significantly higher in group 1 than in group 2 (19.0% v 2.9%; p = 0.037, kappa = 0.179). Multivariate analysis revealed that serum mean lactate level correlated significantly with inotrope score, intubation time, and intensive care unit stay. Blood lactate concentration of 4.8 mmol/L or higher during the early postoperative hours identifies a group of patients with increased risk of postoperative morbidity and mortality.

Effects of Oral Administration of a Commercial Activated Charcoal Suspension on Serum Osmolality and Lactate Concentration in the Dog

The purpose of this investigation was to determine the effects of an activated charcoal (AC) suspension containing propylene glycol and glycerol on serum osmolality, osmolal gap, and lactate concentration in dogs. Six healthy adult dogs were administered 4 g/kg AC in a commercially available suspension that contained propylene glycol and glycerol as vehicles. Blood samples were taken before and 1, 4, 6, 8, 12, and 24 hours after the administration of the test suspension. Samples were analyzed for osmolality, blood gases, and concentrations of lactate, sodium, potassium, serum urea nitrogen, and glucose. Osmolal gaps were calculated for each time point. Mean serum osmolality, osmolal gap, and lactate concentration were significantly increased after suspension administration compared to baseline. Serum osmolality increased from 311 mOsm/kg at baseline to 353 mOsm/kg, osmolal gap increased from 5 to 52 mOsm/kg, and lactate concentration increased from 1.9 to 4.5 mmol/L after suspension administration (all P < .01). Three of the 6 dogs vomited between 1 and 3 hours after the administration of the test suspension, and 4 of 6 dogs were lethargic. All dogs drank frequently after AC administration. Commercial AC suspension administered at a clinically relevant dose increases serum osmolality, osmolal gap, and lactate concentration in dogs. These laboratory measures and the clinical signs of vomiting, lethargy, and increased frequency of drinking might complicate the diagnosis or monitoring of some intoxications (such as ethylene glycol) in dogs that have previously received AC suspension containing propylene glycol, glycerol, or both as vehicles.

Effects of Oral Administration of a Commercial Activated Charcoal Suspension on Serum Osmolality and Lactate Concentration in the Dog

The purpose of this investigation was to determine the effects of an activated charcoal (AC) suspension containing propylene glycol and glycerol on serum osmolality, osmolal gap, and lactate concentration in dogs. Six healthy adult dogs were administered 4 g/kg AC in a commercially available suspension that contained propylene glycol and glycerol as vehicles. Blood samples were taken before and 1, 4, 6, 8, 12, and 24 hours after the administration of the test suspension. Samples were analyzed for osmolality, blood gases, and concentrations of lactate, sodium, potassium, serum urea nitrogen, and glucose. Osmolal gaps were calculated for each time point. Mean serum osmolality, osmolal gap, and lactate concentration were significantly increased after suspension administration compared to baseline. Serum osmolality increased from 311 mOsm/kg at baseline to 353 mOsm/kg, osmolal gap increased from 5 to 52 mOsm/kg, and lactate concentration increased from 1.9 to 4.5 mmol/L after suspension administration (all P < .01). Three of the 6 dogs vomited between 1 and 3 hours after the administration of the test suspension, and 4 of 6 dogs were lethargic. All dogs drank frequently after AC administration. Commercial AC suspension administered at a clinically relevant dose increases serum osmolality, osmolal gap, and lactate concentration in dogs. These laboratory measures and the clinical signs of vomiting, lethargy, and increased frequency of drinking might complicate the diagnosis or monitoring of some intoxications (such as ethylene glycol) in dogs that have previously received AC suspension containing propylene glycol, glycerol, or both as vehicles.

First-Line Therapy and Mitochondrial Damage: Different Nucleosides, Different Findings

Background: Antiretroviral therapy has been associated with the development of morphologic body-shape changes and metabolic abnormalities, including dislipemia, insulin resistance, and hyperlactatemia. Mitochondrial damage secondary to the use of nucleoside analogue reverse transcriptase inhibitors (NRTIs) has been related to some of these complications, although the role of different NRTIs in their development is not well established. Objectives: To assess the incidence of hyperlactatemia and lipodystrophy body-shape changes in drug-na ve HIV-infected patients who began highly active antiretroviral therapy (HAART) based on a backbone of two different NRTI combinations. Method: Prospective, longitudinal, observational study of all consecutive drug-naïve HIV-infected individuals who started HAART with zidovudine (AZT) plus lamivudine (3TC) or didanosine (ddI) plus stavudine (d4T) between June 2000 and June 2003 at one single institution. Serum lactate levels and lipodystrophy body-shape changes were monitored periodically during 12 months. Results: At 1 year, mean lactate values remained <2 mmol/L in all 26 patients who received AZT+3TC, but they significantly increased (mean, 2.6 mmol/L) in 50 patients treated with ddI+d4T. The percentage of patients with hyperlactatemia (lactate ≥2 mmol/L) steadily increased in those on ddI+d4T (from 30% at 3 months to 71% at 12 months), whereas it remained below 10% in patients treated with AZT+3TC. Two patients on ddI+d4T developed lactic acidosis. Mean serum lactate dehydrogenase (LDH), gamma-glutamyltransferase (GGT), and amylase significantly increased in patients treated with ddI+d4T, whereas they remained unaltered in patients under AZT+3TC. Significant correlations were found between lactate and LDH, alkaline phosphatase (AP), and GGT. In the multivariate analysis, treatment with ddI+d4T, LDH, and AP was significantly associated with lactate levels. At 12 months, subcutaneous lipoatrophy was significantly more frequent in patients treated with ddI+d4T than in those on AZT+3TC (35% vs. 8%; p = .01). Conclusion: In drug-naïve HIV-infected patients who start antiretroviral therapy, ddI+d4T-based combinations produce a greater increase in serum lactate and lipoatrophy than therapies based on AZT+3TC within the first year of therapy. An increase in LDH, amylase, GGT, and AP levels may signal an increase in lactate, which may be harmful.

First-Line Therapy and Mitochondrial Damage: Different Nucleosides, Different Findings

Background: Antiretroviral therapy has been associated with the development of morphologic body-shape changes and metabolic abnormalities, including dislipemia, insulin resistance, and hyperlactatemia. Mitochondrial damage secondary to the use of nucleoside analogue reverse transcriptase inhibitors (NRTIs) has been related to some of these complications, although the role of different NRTIs in their development is not well established. Objectives: To assess the incidence of hyperlactatemia and lipodystrophy body-shape changes in drug-na ve HIV-infected patients who began highly active antiretroviral therapy (HAART) based on a backbone of two different NRTI combinations. Method: Prospective, longitudinal, observational study of all consecutive drug-naïve HIV-infected individuals who started HAART with zidovudine (AZT) plus lamivudine (3TC) or didanosine (ddI) plus stavudine (d4T) between June 2000 and June 2003 at one single institution. Serum lactate levels and lipodystrophy body-shape changes were monitored periodically during 12 months. Results: At 1 year, mean lactate values remained <2 mmol/L in all 26 patients who received AZT+3TC, but they significantly increased (mean, 2.6 mmol/L) in 50 patients treated with ddI+d4T. The percentage of patients with hyperlactatemia (lactate ≥2 mmol/L) steadily increased in those on ddI+d4T (from 30% at 3 months to 71% at 12 months), whereas it remained below 10% in patients treated with AZT+3TC. Two patients on ddI+d4T developed lactic acidosis. Mean serum lactate dehydrogenase (LDH), gamma-glutamyltransferase (GGT), and amylase significantly increased in patients treated with ddI+d4T, whereas they remained unaltered in patients under AZT+3TC. Significant correlations were found between lactate and LDH, alkaline phosphatase (AP), and GGT. In the multivariate analysis, treatment with ddI+d4T, LDH, and AP was significantly associated with lactate levels. At 12 months, subcutaneous lipoatrophy was significantly more frequent in patients treated with ddI+d4T than in those on AZT+3TC (35% vs. 8%; p = .01). Conclusion: In drug-naïve HIV-infected patients who start antiretroviral therapy, ddI+d4T-based combinations produce a greater increase in serum lactate and lipoatrophy than therapies based on AZT+3TC within the first year of therapy. An increase in LDH, amylase, GGT, and AP levels may signal an increase in lactate, which may be harmful.

Extracorporeal membrane oxygenation in piglets using a polymerized bovine hemoglobin-based oxygen-carrying solution (HBOC-201)

Purpose: The purpose of this study was to determine if the polymerized bovine hemoglobin-based oxygen-carrying solution HBOC-201 is an acceptable substitute for blood in a healthy porcine, extracorporeal membrane oxygenation (ECMO) model. Methods: Ten piglets (15 to 25 kg) were placed on venoarterial ECMO. Four animals received blood-primed ECMO, and 6 animals received HBOC-201–primed ECMO. Hemodynamic variables, urine output, blood gas analyses, complete blood counts, and lactate levels were followed for 6 hours. Data were analyzed using a nonparametric sign test and repeated measures analysis of variance (ANOVA). Results: All animals survived the 6-hour ECMO procedure. Heart rate, mean arterial pressure, urine output, and serum lactate levels were not significantly different between groups. Postpriming volume was 176 ± 156 mL in the blood group. None of the animals in the HBOC-201 group required additional volume to maintain target flow during ECMO (P <.05). Arterial pH, pO2, and oxygen content between groups were not significantly different. Hematocrit for the HBOC-201 group was significantly (P <.05) lower than the blood group. Conclusions: HBOC-201–primed ECMO in a healthy porcine model showed similar hemodynamics and equivalent oxygen carrying capacity to blood-primed ECMO. Postpriming volume requirement was decreased significantly in the HBOC group. ECMO using HBOC-201 instead of blood appears promising and warrants further investigation. J Pediatr Surg 37:1387-1392. Copyright 2002, Elsevier Science (USA). All rights reserved.

Reduced postnatal cerebral glucose metabolism measured by PET after asphyxia in near term fetal lambs.

The effects of fetal asphyxia on cerebral function and development, involve the transition from fetal to neonatal life. Changes in cerebral glucose metabolism may be an early postnatal indicator of fetal asphyxia. The objective is to develop an experimental lamb model involving the transition from fetal to neonatal life and to examine the effect of fetal asphyxia with cerebral hypoxic ischemia on early postnatal cerebral glucose metabolism. Fetal asphyxia was induced by total umbilical cord occlusion in eight near-term fetal lambs (134-138 days) with the ewe under isoflurane-opiate anesthesia. The mean occlusion time until cardiac arrest was 14.5 (4.2) min (SD). Lambs were immediately delivered and standardized resuscitation was instituted after 2 min asystole. At 4 hr postnatal age, [18-F]Fluoro-2-deoxy-glucose (18-FDG) was injected intravenously in eight asphyxiated lambs and in eight controls. Cerebral glucose metabolism was examined by positron emission tomography (PET). As a result the mean arterial blood pressure, acid-base values, blood glucose and serum lactate at 4 hr postnatal age did not differ significantly between lambs subjected to umbilical cord occlusion and controls. EEG was abnormal in all lambs subjected to cord occlusion and normal in the controls at 4 hr postnatal age. Global cerebral metabolic rate (CMRgl) as determined by PET was significantly lower in lambs subjected to cord occlusion mean/median (SD) 22.2/19.6 (8.4) micromol/min/100 g) than in controls mean/median (SD) 37.8/35.9 (6.1); P < 0.01). Global CMRgl is significantly reduced in newborn lambs 4 hr after fetal asphyxia induced by umbilical cord occlusion. A reduction in CMRgl is an early indicator of global hypoxic cerebral ischemia.

Endothelin-1 impairs neutrophil respiratory burst and elimination of Escherichia coli in rabbits.

During systemic inflammation, elevated levels of endothelin (ET)-1 have been reported. The aim of this study was to investigate the effects of ET-1 on neutrophil (PMN) respiratory burst, phagocytosis, and elimination of Escherichia coli from blood and tissues. Prospective, randomized, controlled trial. Experimental laboratory in a university hospital. A total of 18 female chinchilla rabbits. To quantify the clearance process, defined numbers (10(8) colony-forming units) of E. coli were injected intravenously into anesthetized rabbits, 60 mins after onset of continuous 0.2 microg/kg/min ET-1 administration (n = 9) and after saline infusion (control group, n = 9), respectively. To evaluate potential effects of ET-1 on bacterial elimination and killing, blood clearance of E. coli and colonization of different organs were investigated. Variables monitored were neutrophil respiratory burst and phagocytosis activity, rates of bacterial elimination from the blood, arterial blood pressure, blood gases, serum lactate concentrations, and nitrite and nitrate levels. The animals were killed 3 hrs after bacterial injection and tissue samples of liver, kidney, spleen, and lung were collected for bacterial counts. Compared with the control group, ET-1 significantly impaired PMN respiratory burst (p < .05) and prolonged elimination of injected E. coli from the blood (p < .01), whereas phagocytosis functions remained unaltered. The reduced PMN burst activity after ET-1 was associated with a higher bacterial colonization of all organs (lung, p < .01; spleen, p < .05). Endothelin-1 induced increases in mean arterial pressure (p < .01) and serum lactate concentrations, whereas nitrite and nitrate levels remained unaltered. Endothelin-1 impairs respiratory burst and bacterial clearance from the blood and tissue. Thus, elevated levels of ET-1 during sepsis could induce organ hypoperfusion and cause disturbances in immune functions, increasing the risk of bacterial infections.

Serum anion gap in the differential diagnosis of metabolic acidosis in critically ill newborns

Objectives: To determine in critically ill newborn infants (1) the range of the serum anion gap without metabolic acidosis and (2) whether the serum anion gap can be used to distinguish newborns with lactic acidosis from those with hyperchloremic metabolic acidosis. Study design: Umbilical arterial blood gases and serum electrolyte and lactate concentrations were measured simultaneously in 210 samples from 63 infants over the first week of life. Metabolic acidosis was defined as a blood base deficit (BD) >4 mmol/L. The anion gap was calculated as [Na +] – [C1 –] – [T CO 2]. Lactic acidosis was defined as a serum lactate concentration >2 SD above the mean serum lactate concentration in samples without metabolic acidosis. Results: In 89 blood samples with BD <4 mmol/L, serum lactate concentration decreased with postnatal age ( r = 0.51). The upper limit of serum lactate concentration was 3.8 mmol/L at less than 48 hours, 2.4 mmol/L between 48 and 96 hours, and 1.5 mmol/L for infants greater than 96 hours of age. The mean serum anion gap ± 2 SD in 174 samples without lactic acidosis was 8 ± 4 mmol/L; in 36 samples with lactic acidosis it was 16 ± 9 mmol/L ( P < .0001). Serum anion gap and lactate concentration were poorly correlated for samples without lactic acidosis ( r = 0.04) but highly correlated in those with lactic acidosis ( r = 0.81, P < .0001). None of the 85 samples with metabolic acidosis but without lactic acidosis had an anion gap >16 mmol/L; only 4 of 36 samples with lactic acidosis had an anion gap <8 meq/L. However, 25 of 36 samples with lactic acidosis had serum anion gaps of 8 to 16 mmol/L. Conclusion: In the presence of metabolic acidosis, a serum anion gap >16 mmol/L is highly predictive of lactic acidosis; a serum anion gap <8 is highly predictive of the absence of lactic acidosis; an anion gap = 8 - 16 mmol/L has no use in the differential diagnosis of metabolic acidosis in the critically ill newborn. (J Pediatr 1999;135:751-5)

Regression of left ventricular hypertrophy with losartan potassium therapy in patients with hypertension

The aim of this study was to assess the effects of losartan potassium, an angiotensin II receptor antagonist, on systolic blood pressure; diastolic blood pressure; and left ventricular dimensions, functions, and mass index (LVMI) in patients with mild-to-moderate essential hypertension. Twenty patients aged 40 to 65 years with either uncontrolled or previously untreated hypertension and echocardio-graphically documented left ventricular hyptertrophy (LVH) defined by LVMI >130 g/m 2 for men and >110 g/m 2 for women were included in the study. Blood pressure measurements were taken at 2-week intervals. Blood samples were taken before treatment and after 3 months of treatment for determination of lipid concentrations and other laboratory variables used to monitor safety, and two-dimensional M-mode and Doppler echocardiographic measurements were obtained. Losartan was associated with a statistically significant reduction of mean systolic blood pressure from 173 ± 6 mm Hg to 135 ± 10 mm Hg and diastolic blood pressure from 100 ± 4 mm Hg to 82 ± 7 mm Hg without a change in heart rate. Significant decreases were identified in interventricular septal and left ventricular posterior wall thicknesses (from 12.5 ± 0.8 mm to 11.5 ± 0.8 mm and 12.1 ± 1.0 mm to 11.1 ± 0.8 mm, respectively). LVMI decreased from 138.8 ± 18.7 g/m 2 to 126.0 ± 21.8 g/m 2 after 3 months of treatment. Left ventricular dimensions and ejection fraction did not change significantly compared with baseline values. The Doppler echocardiographic assessment of mitral E/A ratio, which is a marker of diastolic function, increased significantly from baseline. Except for a significant increase in mean serum lactate dehydrogenase activity, laboratory findings (including serum lipid concentrations) remained constant. No clinical adverse effects attributable to losartan were observed. Results of this study suggest that losartan is an effective, well-tolerated drug that reduces LVH, improves left ventricular diastolic functions, and controls systolic and diastolic blood pressures in patients with mild-to-moderate essential hypertension.