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(-)] - [TCO (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.     

Monitoring of early postnatal glucose homeostasis and cerebral function in newborn infants of diabetic mothers. A pilot study

The aims of this pilot study were to evaluate a new technique in the monitoring of postnatal glucose homeostasis (microdialysis) and also to study possible associations between early postnatal hypoglycaemia and influences on cerebral function monitoring (CFM) in 12 newborn infants of diabetic mothers.In order to study the postnatal glucose homeostasis, frequent dialysate samples were obtained from a subcutaneous microdialysis catheter for measurements of glucose. In addition, we also received samples of dialysate lactate and glycerol. Dialysate glucose concentrations were correlated to capillary blood glucose levels, measured by a glucose oxidase method. The cerebral function monitor was applied postnatally and a registration was obtained continuously.Capillary blood glucose decreased initially, and seven newborns received intravenous glucose infusions due to glucose concentrations less than 2.2 mmol/l. Dialysate glucose concentrations were, on average, 0.4 mmol/l higher than corresponding concentrations in capillary blood. The correlation coefficient between the two measurements was 0.63 and the coefficient of variation was 19.2%. Dialysate lactate and glycerol levels increased significantly, with peak values 3-4 h postnatally. No significant overall influence of hypoglycaemia was detectable in the CFM tracing.We conclude that a relatively poor correlation was observed between glucose measurements in capillary samples and microdialysis. However, using the microdialysis technique saw indication of marked lipolysis and increased lactate production, which may be of importance for cerebral postnatal adaptation. The mild postnatal hypoglycaemia in infants of diabetic mothers does not seem to give visually detectable influences on CFM.     

Evaluation of "point of care" devices in the measurement of low blood glucose in neonatal practice

BACKGROUND: Low blood glucose in newborns is difficult to detect clinically. Hence a reliable "point of care" device (glucometer) for early detection and treatment of low glucose is needed. OBJECTIVE: To evaluate the performance of five readily available glucometers for the detection of low blood glucose in newborn infants. METHOD: Glucostix measurements were taken for newborns with risk factors using a Reflolux S (Boehringer) glucometer. If the initial reading was low (< 2.6 mmol/l), further measurements were taken with two other glucometers (phase I, Advantage and Glucotrend (Roche); phase II, Elite XL (Bayer) and Precision (Abbott)), and plasma glucose was measured in the laboratory (Aeroset; Abbott). RESULTS: Over 10 months, 101 specimens were collected from 71 newborns (57 in phase I; 44 in phase II). The Advantage glucometer usually overestimated blood glucose with a mean difference of 1.07 mmol/l (p < 0.01) at all low glucose ranges. The Glucotrend, Precision, and Elite XL glucometers performed better; the mean differences were not significantly different from the laboratory measured value (0.17 mmol/l (p = 0.37); -0.12 mmol/l (p = 0.13), and 0.24 mmol/l (p = 0.13) respectively). For detection of glucose concentrations < 2.6 mmol/l, the Precision glucometer had the highest sensitivity (96.4%) and negative predictive value (90%). For lower glucose concentrations (< 2.0 mmol/l), the Glucotrend glucometer performed even better (sensitivity 92.3%, negative predictive value 96.3%). CONCLUSION: Point of care devices should have good precision in the low glucose concentration range, sensitivity, and accuracy for early detection of neonatal hypoglycaemia. None of the five glucometers was satisfactory as the sole measuring device. The Glucotrend and Precision glucometers have the greatest sensitivity and negative predictive value. However, confirmation with laboratory measurements of plasma glucose and clinical assessment are still of the utmost importance.     

Capillary refill and core-peripheral temperature gap as indicators of haemodynamic status in paediatric intensive care patients.

OBJECTIVES: Capillary refill time is an important diagnostic adjunct in the acute resuscitation phase of the shocked child. This study assesses its relation to commonly measured haemodynamic parameters in the postresuscitation phase when the child has reached the intensive care unit, and compares this with core-peripheral temperature gap. METHODS: Ninety standardised measurements of capillary refill time were made on 55 patients, who were divided into postcardiac surgery (n = 27), and general (n = 28), most of whom had septic shock (n = 24). A normal capillary refill time was defined as < or = 2 seconds. Measured haemodynamic variables included: cardiac index, central venous pressure, systemic vascular resistance index, stroke volume index (SVI), and blood lactate. Seventy measurements were made on patients while being treated with inotropes or vasodilators. RESULTS: Capillary refill time and temperature gap both correlated poorly with all haemodynamic variables among post-cardiac surgery children. For general patients, capillary refill time was related to SVI and lactate; temperature gap correlated poorly with all variables. General patients with a prolonged capillary refill time had a lower median SVI (28 v 38 ml/m2) but not a higher lactate (1.7 v 1.1 mmol/l). A capillary refill time of > or = 6 seconds had the best predictive value for a reduced SVI. CONCLUSION: Among ventilated, general intensive care patients, capillary refill time is related weakly to blood lactate and SVI. A normal value for capillary refill time of < or = 2 seconds has little predictive value and might be too conservative for this population; septic shock.     

Clinical value of a single postnatal lactate measurement after intrapartum asphyxia

Our aim was to compare the respective values of base deficit and lactate in birth asphyxia. METHODS: Base deficit and lactate levels were measured from radial artery blood samples taken at 30 min of life in 115 term newborns suspected as having been asphyxiated during labour. Both base deficit and lactate levels were compared between patients who further developed moderate or severe encephalopathy and those who experienced no or only mild encephalopathy. Receiver operating characteristics curves and clinical values of both indicators were computed. RESULTS: The correlation between base deficit and lactate was significant (r2 = 0.51, p < 0.0001). Both indicators were significantly associated with neonatal outcome. Lactacidaemia lower than 5 mmol/l and/or base deficit level lower than 10 mEq/l were not followed by neurological complications. Plasma lactate concentration greater than 9 mmol/l was associated with moderate or severe encephalopathy with a sensitivity of 84% and a specificity of 67%. Base deficit and lactate had similar clinical values. CONCLUSIONS: Base deficit and lactate measurements in arterial blood at 30 min of life are equally valuable in assessing the severity of birth asphyxia.     

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.     

Peri-operative blood lactate concentrations in pre-term babies with necrotising enterocolitis.

AIM: Hyperlactaemia has been shown to predict mortality in preterm babies undergoing intensive care. The value of such measurement has not been evaluated in babies undergoing laparotomy for necrotising enterocolitis (NEC). The aim of this study was to determine whether peri-operative blood lactate measurements (L) can be used to predict outcome in preterm babies with necrotising enterocolitis. METHODS: Clinical and laboratory data in 24 babies who underwent laparotomy for NEC over 3 years were collected. The data were analysed to correlate blood lactate level with the clinical outcome. RESULTS: There were no statistically significant differences between babies who died and those who survived in terms of gestation, birth weight, condition at birth, etc. There was no difference in pre-operative acid-base status parameters between the groups. Median (range) of pre- and post-operative blood lactate measurements (L) are shown: Pre-op Lactate: 0.9 (0.3 to 2.4) n = 15 (Survivors); 2.7 (0.5 to 10.9) n = 5, p = 0.05 (Non-survivors). Post-op Lactate: 1.2 (0.5 to 6) n = 19 (Survivors); 4.7 (0.2 to 19.5) n = 5, p = 0.06 (Non-survivors). Babies with pre-operative hyperlactaemia ([L] > 1.6 mmol/L) were more likely to die. (Odd's Ratio 22, Confidence Interval 1.54 to 314.3, p = 0.04). Pre-operative L was not higher in babies who subsequently had bowel resection compared to those who had no bowel resection ([L] = 0.88 mmol/L [0.3 to 10.9] vs. 1.6 mmol/L [0.6 to 2.7], [p = 0.2]). Post-operative L was generally higher than pre-operative L but was a less useful predictor of death. CONCLUSION: This study suggests that elevation of L in the pre-operative period carries a poor prognosis in babies with NEC. As L was not significantly different between babies who had necrotic bowel and those who had a healthy bowel, we postulate that it reflects inadequate global tissue oxygen delivery rather than local disease process. Pre-operative optimisation of oxygen delivery has been shown to reduce mortality in high-risk adult surgical patients. Babies with NEC may also benefit from further peri-operative resuscitation.     

Serum lactate as a predictor of mortality after paediatric cardiac surgery

OBJECTIVE—To assess the value of sequential lactate measurement in predicting postoperative mortality after surgery for complex congenital heart disease in children.DESIGN—Prospective observational study.SETTING—Sixteen bedded paediatric intensive care unit (PICU).SUBJECTS—Ninety nine children ( 90 survivors, nine non-survivors).MEASUREMENTS—Serum lactate and base deficit were measured on admission and every six hours thereafter. Data were analysed by Mann-Whitney and Fisher''s exact tests.RESULTS—There was considerable overlap in initial lactate values between the survivor and non-survivor groups. Initial lactate was significantly raised in non-survivors (median 8.7, range 1.9-17.6 mmol/l) compared with survivors (median 2.4, range 0.6-13.6 mmol/l) (p = 0.0002). Twenty one patients (21.1%) with initial lactate concentrations greater than 4.5 mmol/l survived to PICU discharge. Using receiver operating characteristic analysis an initial lactate of 6 mmol/l had the optimum predictive value for mortality. Initial postoperative serum lactate >6 mmol/l predicted mortality with sensitivity 78%, specificity 83%, and positive predictive value of only 32%.CONCLUSION—Initial lactate concentrations have poor positive predictive value for mortality. The routine measurement of lactate for this purpose cannot be justified in clinical practice.     

Capillary refill and core-peripheral temperature gap as indicators of haemodynamic status in paediatric intensive care patients

OBJECTIVES—Capillary refill time is an important diagnostic adjunct in the acute resuscitation phase of the shocked child. This study assesses its relation to commonly measured haemodynamic parameters in the postresuscitation phase when the child has reached the intensive care unit, and compares this with core-peripheral temperature gap.
METHODS—Ninety standardised measurements of capillary refill time were made on 55 patients, who were divided into postcardiac surgery (n = 27), and general (n = 28), most of whom had septic shock (n = 24). A normal capillary refill time was defined as ⩽ 2 seconds. Measured haemodynamic variables included: cardiac index, central venous pressure, systemic vascular resistance index, stroke volume index (SVI), and blood lactate. Seventy measurements were made on patients while being treated with inotropes or vasodilators.
RESULTS—Capillary refill time and temperature gap both correlated poorly with all haemodynamic variables among postcardiac surgery children. For general patients, capillary refill time was related to SVI and lactate; temperature gap correlated poorly with all variables. General patients with a prolonged capillary refill time had a lower median SVI (28 v 38 ml/m²) but not a higher lactate (1.7 v 1.1 mmol/l). A capillary refill time of ⩾ 6 seconds had the best predictive value for a reduced SVI.
CONCLUSION—Among ventilated, general intensive care patients, capillary refill time is related weakly to blood lactate and SVI. A normal value for capillary refill time of ⩽ 2 seconds has little predictive value and might be too conservative for this population; septic shock

     

The inaccuracy of venous and capillary blood glucose measurement using reagent strips in the newborn period and the effect of haematocrit

The purpose of this study was to compare the accuracy of capillary and venous reagent strip tests (RST) against a reference plasma glucose method, and to assess the impact of haematocrit. One hundred and eighty infants admitted to the Neonatal Unit had blood glucose measured by reagent strip tests using capillary and venous blood samples. Venous plasma glucose was assayed by the Hexokinase method. Each infant had a venous haematocrit performed in the Neonatal Unit. Comparable inaccuracies were noted with both capillary and venous reagent strip tests at all levels. The mean difference between capillary RST and plasma glucose was 0.058 mmol/l (S.D. 1.39). The corresponding mean venous RST plasma glucose difference was 0.138 mmol/l (S.D. 0.96). The two means were statistically different from each other (P = 0.024), but this difference disappeared if the comparison was made only in babies with a PCV of 35-55%. At higher haematocrits (PCV >55%, N= 96) the mean difference between venous RST and plasma glucose was significantly more than the mean difference between capillary RST and plasma glucose (0.018 versus 0.295. P = 0.002). Hence the higher the haematocrit the more inaccurate the venous RST. This study confirms the limited value of reagent strip tests in the assessment of blood glucose in the neonatal period. It suggests that venous RST may be more inaccurate in comparison to capillary and that high haematocrits have a greater effect on venous RST than capillary RST.     

Peripheral oxygenation in hypotensive preterm babies

Monitoring oxygenation in peripheral tissues of preterm babies may be useful in understanding the redistribution of blood flow during hypotension. Hemoglobin flow and venous saturation were measured in the forearm using near infrared spectroscopy with venous occlusion and were used to calculate fractional oxygen extraction, oxygen delivery, and oxygen consumption. Thirty ventilated preterm babies (median birth weight 976 g) were studied; 15 were hypotensive and 15 normotensive. Treatment for hypotension was dopamine alone (median dose 5 microg/kg/min) in eight cases, 4.5% human albumin solution (20 mL/kg) with dopamine in five cases, and only a blood transfusion (20 mL packed cells/kg) in two cases. There was a weak correlation between hemoglobin flow and mean arterial blood pressure (r = 0.40, p = 0.03). In hypotensive compared with normotensive babies, there was a significantly lower median hemoglobin flow (10.2 versus 20.2 micromol/100 mL/min, p = 0.0006), forearm oxygen delivery (37.8 versus 75.2 micromol/100 mL/min, p = 0.0008), and oxygen consumption (11.0 versus 23.9 micromol/100 mL/min, p = 0.006), but the fractional oxygen extraction (0.327 versus 0.306, p = 0.48) and the blood lactate concentration (1.22 versus 1.20 mmol/L, p = 0.44) were similar. Following treatment of hypotension, oxygen delivery (p = 0.02) and oxygen consumption (p = 0.04) increased to 64.2 and 21.7 micromol/100 mL/min, respectively, but fractional oxygen extraction (p = 0.81) and blood lactate concentration (p = 0.94) after treatment were unchanged. VO2 was variable in the forearm of human infants. It reduced when DO2 was low, and there was no evidence of tissue injury or switch to anaerobic metabolism. Measurements of peripheral tissue oxygenation seem to be of some value in understanding the pathophysiologic changes that occur with hypotension.     

The metabolic load of stored blood. Implications for major transfusions in infants.

Plasma electrolyte, intermediary metabolite, and hormone concentrations were measured in samples of 110 units of citrate phosphate dextrose blood being used for clinical transfusions. The most important changes from the physiological range were in sodium, potassium, glucose, and lactate concentrations. Mean sodium concentrations fell from 170 mmol/l at the beginning of storage to 156 mmol/l at the end and mean potassium concentrations rose from 7 mmol/l to 25 mmol/l. Glucose had a mean concentration of 20 mmol/l at the beginning of storage and had only fallen to 15 mmol/l at the end. Mean lactate concentrations increased from 7 mmol/l at the beginning of storage to 25 mmol/l at the end. Many samples had cortisol, insulin, and growth hormone concentrations within the physiological range. Citrate phosphate dextrose blood contains a large substrate load that changes during storage and that should be taken into account when infants are transfused large volumes of blood. The strong correlation coefficients with duration of storage for sodium, potassium, and lactate (-0.71, 0.91, and 0.90, respectively) indicate that concentrations of these substrates can be predicted within a narrow range if the duration of blood storage is known.     

An inadequate glycaemic response to glucagon is linked to insulin resistance in preterm infants?

AIMS: To define clinical, metabolic, and hormonal characteristics of preterm infants relative to glucagon responsiveness. METHODS: Two phase study of 78 preterm infants (25-36 weeks gestation) on regular four hourly feeds anticipating discharge home at 36 weeks mean corrected gestation. In phase 1 infants were fasted until hypoglycaemic, or maximally for eight hours. Endocrine and metabolic profiles were obtained at completion. Phase 2 was performed the following day. A feed was omitted and replaced by a bolus dose of intravenous glucagon (100 micro g/kg). Main outcome measures were measurements of blood glucose and lactate concentrations, taken immediately pre-glucagon, and thereafter every 15 minutes for 60 minutes. A rise in glucose concentration of >1 mmol/l (55 infants) was defined as an adequate response to glucagon. An inadequate glycaemic response was <1 mmol/l (23 infants). RESULTS: Several differences in fasting blood glucose and hormone concentrations were identified in infants with an inadequate glycaemic response to glucagon compared to those with an adequate response: relative fasting hyperglycaemia (mean 3.7 v 3.3 mmol/l, p = 0.008); fasting hyperinsulinaemia (mean 4.3 v 2.6 mU/l, p = 0.014); an increased insulin:glucagon ratio (0.19 v 0.11, p = 0.014), and a lower insulin sensitivity QUICKI index (0.19 v 0.22, p = 0.04). There was no distinctive phenotype to reliably predict response to glucagon. CONCLUSION: Some preterm infants show an inadequate glycaemic response to glucagon and have features suggestive of insulin resistance. The potential long term implications of such insulin resistance may have appreciable public health consequences.     

Whole blood ionized magnesium in neonatal acidosis and preterm infants: a prospective consecutive study

The mineral magnesium is a crucial enzymatic cofactor in the cellular bioenergetic process and alternations in magnesium metabolism may be associated with neurological impairment in newborn infants. Therefore, ionized magnesium (IMg) was measured in 14 newborn infants with acidosis [umbilical arterial cord pH 7.00 +/- 0.06, Apgar score 8.3 +/- 1.6 after 5 min, gestational age (GA) 276 +/- 16 d] and 15 premature infants (umbilical arterial cord pH 7.31 +/- 0.07, GA 236 +/- 12 d). Nineteen healthy mature infants served as controls. Arterial umbilical cord samples were taken immediately after delivery and capillary blood samples were taken 2, 6, 12 and 24 h after delivery by heel stick. IMg was measured by NOVA 8. The results showed an increased umbilical cord blood IMg in infants with acidosis compared with both premature and normal infants (0.58 +/- 0.08 mmol l(-1) vs 0.51 +/- 0.03 mmol l(-1) and 0.49 +/- 0.03 mmol l(-1); p < 0.0001). In infants with acidosis IMg declined significantly 2 h after delivery to 0.49 +/- 0.05 mmol l(-1) (p < 0.0001) and did not show any further significant changes during the first day of life. In premature infants and controls IMg levels were constant during the observation period. Conclusion: These findings suggest that elevated IMg is associated with neonatal acidosis.     

Rapid whole blood lactate measurement in the fetus and mother during labour

Using a new rapid method, fetal and maternal whole blood lactate was measured before the onset of labour at elective Caesarean section in 8 patients, during labour in 34 normal patients, and in a further 28 patients whose babies showed varying degrees of clinical depression and/or acid base abnormality at birth. The mean (+/- SEM) umbilical venous and arterial and maternal venous lactate values in the 8 cases delivered by elective Caesarean section were 1.20 (+/- 0.16), 1.46 (+/- 0.22) and 1.14 (+/- 0.46) mmol/l, respectively. For the normal group the mean fetal lactates (+/- SEM) in the latent and active phases of labour, and in the umbilical vein and artery, were 1.91 (+/- 0.25), 2.42 (+/- 0.46), 2.71 (+/- 0.19) and 3.09 (+/- 0.20) mmol/l, respectively. The mean maternal venous lactate (+/- SEM) in the latent and active phases of labour and at delivery were 1.07 (+/- 0.09), 1.45 (+/- 0.12) and 2.69 (+/- 0.24) mmol/l. the rise in fetal lactate throughout labour was due in part to the rise in maternal lactate. Increasing neonatal depression was associated with increasing fetal lacticacidaemia. This associationachieved statistical significance at delivery.     

Arterial or mixed venous lactate measurement in critically ill children. Is there a difference?

Seven critically ill children had simultaneous measurement of whole blood lactate concentrations obtained from a systemic arterial and mixed venous (pulmonary artery) site. An excellent correlation was found ( r = 0.995). The mean difference between arterial and mixed venous values was 0.02 mmol/ 1 and the limits of agreement (±0.22) were —0.20 to 0.24. The differences found were clinically insignificant (two-tailed paired Student's t -test; p = 0.36) and therefore support the continued use of arterial sampling for blood lactate measurement.     

Comparison of two reflectance photometers in the assessment of neonatal hypoglycaemia.

To assess the accuracy and reliability of reflectance photometers in estimating blood glucose concentrations, two were assessed: the Ames Glucometer 3 (Bayer Diagnostics) with Glucofilm Test strips; and the Reflolux S (Boehringer Mannheim) with BM Test Glycemia 20-800 strips. These were compared with laboratory blood glucose estimations in 100 assays (50 comparisons for each machine, measuring the difference (d) between the glucose reading and the mean of the reflectance photometer and the laboratory value). The Ames Glucometer 3 (mean d = + 0.7 mmol/l, (SD 1.1) mmol/l) was less accurate than the Boehringer Reflolux S (mean d = 0.2 mmol/l, (SD (0.7) mmol/l). The range of error of both machines is wide (Ames 2 SD range + 2.9 mmol/l to -1.5 mmol/l true readings; Boehringer + 1.8 mmol/l to -1.2 mmol/l of true readings). Because of this, any reflectance photometer readings that are even slightly low should be checked with laboratory estimations. The clinical value of such machines is limited in infants with low blood glucose concentrations.     

The effect of neonatal jaundice on biotinidase activity

BACKGROUND: Jaundice is one of the most common and one of the vexing problems that can occur in newborns. A newborn screening test for biotinidase deficiency has been added to many national screening programmes. AIM: To clarify the problem of false-positive screening tests in neonates, especially in term babies, we evaluated the biotinidase activity in the serum of fullterm, premature and small-for-dates newborn infants with jaundice. METHODS: 1296 fullterms (controls N=426), 246 prematures (controls N=86) and 156 small-for-dates babies (controls N=38) aged 2-3 days with jaundice were included in the study. In jaundiced neonates and controls, 3.0 ml of blood was drawn for the evaluation of total bilirubin (t.bil), liver enzymes and biotinidase activity in the serum using a fluorimetric method. In order to test whether or not t.bil causes an artifact in the previous method, biotinidase activity was also evaluated in a number of jaundiced newborns using an HPLC method. Additionally, a preliminary in vitro experiment was carried out to test whether t.bil is an inhibitor of the enzyme. RESULTS: Biotinidase activities in the group of controls of prematures (3.30+/-1.2 mmol/min/l) and small-for-dates babies (3.34+/-0.8 mmol/min/l) were lower than those of term babies (4.99+/-1.1 mmol/min/l, p<0.001). T.bil and liver enzymes showed a statistically significant inverse correlation with biotinidase activity (p<0.001) in all the jaundiced infants of this study. Additionally, biotinidase activity, evaluated in a number of neonates with both fluorimetric and HPLC methods showed similar results. Preincubation of the serum enzyme with t.bil (>10 mg/dl) resulted in a 50% or more inhibition. CONCLUSIONS: (a) Low biotinidase activity was found in term babies, prematures and small-for-dates with jaundice. (b) The low activity of the enzyme could be due to their impaired liver function. (c) The high t.bil levels in the studied groups may play the role of an "inhibitor" of the enzyme. (d) Gestational age as well as t.bil levels should always be written on Guthrie cards for a correct evaluation of biotinidase activity.     

Physiologic and neuropathologic aspects of hypothermic circulatory arrest in newborn dogs

A model of hypothermic circulatory arrest has been developed in the newborn dog. Ten puppies were anesthetized with halothane, paralyzed, and artificially ventilated with 70% nitrous oxide 30% oxygen to arterial oxygen pressure greater than 8.0 kPa (60 mm Hg), arterial carbon dioxide pressure of 4.4-5.6 kPa (33-42 mm Hg), and arterial pH of 7.35-7.42. Animals were surface cooled to 20 degrees C, after which cardiac arrest was produced with i.v. KCl. Dogs remained asystolic without ventilation for 1.0 (n = 4), 1.5 (n = 3), or 2.0 (n = 3) h. Resuscitation was accomplished with closed-chest compression, mechanical ventilation, i.v. epinephrine and NaHCO3, and rewarming to 37 degrees C. Postarrest recovery was maintained for 3-4 h; thereafter, the puppies underwent perfusion-fixation of their brains for pathologic analysis. Plasma glucose (control = 8.3 mmol/L) increased slightly during hypothermic cardiac arrest (+36%) but was markedly elevated at 15 min postarrest (20 mmol/L). Blood lactate (control = 1.1 mmol/L) increased almost 200% during hypothermic circulatory arrest, with a further rise to 9.0 mmol/L at 15 min postarrest. Thereafter, lactate decreased in the 1-h arrested dogs but increased progressively in the other groups. Mean arterial blood pressure returned to baseline (73 mm Hg) by 15 min postarrest, remained stable in the 1-h dogs, but fell at 3 h to 62 and 34 mm Hg in the 1.5- and 2.0-h groups, respectively. No neuropathologic alterations were seen in puppies arrested for 1 h, whereas all puppies arrested for 1.5 or 2 h had varying degrees of cerebral cortical and hippocampal damage.(ABSTRACT TRUNCATED AT 250 WORDS)     

Capillary versus arterial plasma catecholamines as markers for sympatho-adrenal activity in infants.

In this study, we investigated whether capillary plasma catecholamines can be used as a suitable substitute for arterial catecholamines. Analysis was done radioenzymatically. Catecholamine concentrations were not different in arterial and simultaneously collected "arterialized" (warmed foot) capillary plasma obtained by heel-prick from 18 neonatal intensive care patients as assessed by linear regression analysis (correlation coefficient: 0.966 for noradrenaline; 0.894 for adrenaline; p less than 0.05) and by a Wilcoxon test [noradrenaline: 2.13 (0.61-10.47) versus 2.41 (1.05-10.23); adrenaline: 0.75 (0.16-1.70) versus 0.72 (0.10-1.37) nmol/L, median (range)]. However, "arterialization" of capillary blood is important; when blood was obtained in nine neonates without warming their feet, capillary concentrations of noradrenaline were higher than arterial values (p less than 0.03) and those of adrenaline were not different from arterial values. Catecholamine concentrations in arterialized capillary plasma collected in healthy full-term infants at 1 h [n = 9; noradrenaline: 6.85 (3.09-8.88) nmol/L; adrenaline: 1.34 (0.86-2.85) nmol/L] and 5 d after birth [n = 27; noradrenaline: 1.58 (0.89-3.16) nmol/L; adrenaline: 0.59 (0.25-1.64) nmol/L] reflect the well-known fall (p less than 0.01) in catecholamine levels after delivery. With a highly sensitive analytical technique, catecholamine concentrations can reliably be assessed in minute samples (100-200 microL) of arterialized capillary blood, even when concentrations have dropped to low "resting" basal levels. Moreover, the capillary sampling procedure is simple and safe, can easily be applied to healthy infants, and does not have the practical and ethical limitations of arterial blood sampling.