Early metabolic effects of sepsis in the preterm infant: Lactic acidosis and increased glucose requirement

doi:10.1016/S0022-3476(05)80350-6

The Journal of Pediatrics

Volume 121, Issue 6, December 1992, Pages 951-955

https://doi.org/10.1016/S0022-3476(05)80350-6 Get rights and content

The effects of sepsis on carbohydrate metabolism were studied in preteerm newborn infants (weight>1.2 kg, appropriate for gestational age) without maternal endocrine problems, who were being examined for infection. Plasma glucose, lactate, and insulin concentrations were measured at initial evaluation and then every 8 hours for a total of 48 hours. Blood, urine, and spinal fluid were obtained for culture and countermmunoelectrophoresis. Dextrose was administered to each patient to maintain glucose levels in the normal range. Dextrose infusion rates were caiculated in milligrams per kilogram per minute. Of the 29 infants, 6 had sepsis (positive culture and counterimmunoelectrophoresis results). Infats with sepsis had significant elevations of plasma lactate concentration (p<0.003) but normal pH. The dextrose infusion rate was also significantlly elevated in the infected infants (p<0.01). No hypoglycemia or hyperglycemia was observed in either group. No significant difference in plasma insulin concentration was observed. We conclude that significant elevations in plasma lactate concentrations and dextrose infusion rate may be early clinical markers of neonatal sepsis in the first 48 hours of life.

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Tissue hypoxia remains a leading cause of morbidity and mortality in preterm infants. Current biomarkers often detect irreversible hypoxic cellular injury (i.e. lactate) and are non-specific. A new biomarker is needed which detects tissue hypoxia before irreversible damage occurs.
To investigate the relation between serum ischemia modified albumin (IMA), a marker of hypoxia; and analytic variables, patient related variables and conditions associated with hypoxia, in preterm infants.
Retrospective cohort study.
Infants with a gestational age < 30 weeks and/or birth weight < 1000 g.
We collected two remnant blood samples in the first week after birth and measured IMA. IMA/albumin ratio (IMAR) was used to adjust for albumin. We assessed correlations between IMA(R) and analytic variables (albumin, lipemia- and haemolysis index); mean-2 h SpO₂; mean-2 h variability of regional splanchnic oxygen saturation (r_sSO₂), measured using near-infrared spectroscopy; and patent ductus arteriosus (PDA).
Sixty-five infants were included. Albumin, the lipemia- and haemolysis index correlated negatively with IMA (r:-0.620, P<0.001; r:-0.458, P<0.001; and r:-0.337, P=0.002). IMAR correlated negatively with SpO₂ (rho:-0.614, P<0.001). Lower r_sSO₂ variability correlated with higher IMAR values (rho:-0.785, n=14, P=0.001 and rho:-0.773, n=11, P=0.005). Infants with a hemodynamic significant PDA (hsPDA) had higher IMAR values than infants without PDA (0.13 [0.11–0.28], n=16 vs. 0.11 [0.08–0.20], n=29, P=0.005 and 0.11 [0.09–0.18], n=13 vs. 0.09 [0.06–0.17], n=37, P=0.026).
When adjusted for albumin, the lipemia- and haemolysis index, IMAR has potential value as a marker for systemic hypoxia in preterm infants, considering the associations with SpO₂, variability of r_sSO₂, and hsPDA.
A method for lactate and pyruvate determination in filter-paper dried blood spots
2009, Journal of Chromatography A
Lactic acidemia is commonly associated with severe diseases in pediatric patients. Quantitation of blood lactate and pyruvate is important for the diagnosis and clinical management. A liquid chromatography–tandem mass spectrometry (LC–MS/MS) method using dried blood spots (DBS) was developed and could be used for simultaneous quantification of blood lactate and pyruvate. The applicability of the developed method was tested and confirmed by the regression analysis between LC–MS/MS method and enzymatic assay. Lactate and pyruvate were extracted from DBS obtained from 580 full-term, 120 pre-term infants (gestations ranging from 24 to 36 weeks), and 65 patients with suspected lactic acidemia, with methanolic internal standard (IS) solutions of sodium l-lactate-¹³C₃ and pyruvate-¹³C₃. An API-2000 LC–MS/MS system with multiple reaction monitoring (MRM) mode was applied. The within-run and between-run precisions (CV%) were determined and the results were 1.9% and 3.9% for lactate (n = 20) and 5.7% and 7.3% for pyruvate (n = 20). The linearity of lactate (r = 0.9986) and pyruvate (r = 0.9973) based on the IS was excellent. The parameter r squared (r²) of linear regression between LC–MS/MS method and enzymatic assay was 0.9405 for lactate and 0.9447 for pyruvate, respectively, and the agreement between these methods was consistent and acceptable. The stability of lactate and pyruvate on DBS was also confirmed. The LC–MS/MS method we developed is a specific, sensitive, and reproducible method for measuring blood lactate and pyruvate concentrations. The use of DBS in this method makes it particularly attractive for pediatric patients.
Evaluation and Treatment of Hypotension in the Preterm Infant
2009, Clinics in Perinatology
Citation Excerpt :
Serial lactate measurements are useful in critically ill adults as a manifestation of poor tissue oxygen delivery.26 Lactate values have been analyzed in several clinical situations in the preterm infant,27 including sepsis28 and necrotizing enterocolitis.29 Values obtained during the first day of postnatal life can predict outcome.30,31
A large proportion of very preterm infants receive treatment for hypotension. The definition of hypotension is unclear, and, currently, there is no evidence that treating it improves outcomes or, indeed, which treatment to choose among the available alternatives. Assessment of circulatory adequacy of the preterm infant requires a careful clinical assessment and may also require ancillary investigations. The most commonly used interventions, fluid boluses and dopamine, are problematic: fluid boluses are statistically associated with worse clinical outcomes and may not even increase blood pressure, whereas dopamine increases blood pressure mostly by causing vasoconstriction and may decrease perfusion. For neither intervention is there any reliable data showing clinical benefit. Prospective trials of intervention for hypotension and circulatory compromise are urgently required.
Laboratory parameters predictive of developing necrotizing enterocolitis in infants born before 33 weeks of gestation
2006, Journal of Pediatric Surgery
The aim of this study was to identify laboratory findings predictive of necrotizing enterocolitis (NEC).
Prospective follow-up of 140 infants of less than 33 weeks of gestation. Twenty-six infants developed NEC (grades I to III, criteria of Bell et al [Ann Surg 1978;187:1-7]) (NEC group). For each, 2 birth-weight, gestational age– and postnatal age–matched controls were selected (control group). Blood counts, glucose and electrolyte levels, C-reactive protein, and acid-base balance 3 days, 2 days, and 1 day before and at the onset of NEC and at corresponding ages from the controls were recorded.
Metabolic acidosis occurred, the platelet levels decreased, and the blood glucose increased on successive days in the infants with grade NEC II-III. At the onset of NEC, the infants had significantly lower platelet and higher blood glucose levels compared with controls. More than half of infants with intestinal perforation had leukocyte levels above 30 × 10⁹/L and pH less than 7.25, and their mean blood glucose levels increased to more than 1.5 mmol/L in 24 hours. The remaining parameters were not useful.
A persistent metabolic acidosis, decreasing platelet, and increasing blood glucose level on several successive days might predict a developing NEC, and leukocyte values above 30 × 10⁹/L, pH less than 7.25, and a blood glucose rise by 1.5 mmol/L or more within 24 hours predict NEC with intestinal perforation. Such findings should alert the physician to look for signs of NEC in a preterm infant.
Serial blood lactate measurements predict early outcome after neonatal repair or palliation for complex congenital heart disease
2000, Journal of Thoracic and Cardiovascular Surgery
Objectives: Neonates with congenital heart disease may appear hemodynamically stable after operation and then suddenly experience catastrophic decompensation. An improved means of predicting which infants will suddenly die in the early postoperative period may lead to lifesaving interventions. Studies indicate that blood lactate level is proportional to tissue oxygen debt, but information linking lactate levels with outcome in infants after operation is limited. We sought to determine whether a change in lactate level over time was predictive of a poor outcome defined as death within the first 72 hours or the need for extracorporeal membrane oxygenation. Methods: To test this hypothesis, we studied prospectively 46 infants who were less than 1 month old and were undergoing complex cardiac surgical palliation or repair. Postoperative arterial oxygen saturation, bicarbonate, and lactate levels were recorded on admission to the intensive care unit and every 3 to 12 hours for the first 3 days. Results: Thirty-seven patients had a good outcome, and 9 patients had a poor outcome. Mean initial lactate level was significantly greater in patients with a poor outcome (9.4 ± 3.8 mmol/L) than in patients with a good outcome (5.6 ± 2.1 mmol/L; P =.03). However, an elevated initial lactate level of more than 6 mmol/L had a low positive predictive value (38%) for poor outcome. In contrast, a change in lactate level of 0.75 mmol/L per hour or more was associated with a poor outcome (P <.0001) and predicted a poor outcome with an 89% sensitivity value, a 100% specificity value, and a 100% positive predictive value. Conclusions: Serial blood lactate level measurements may be an accurate predictor of death or the requirement for extracorporeal membrane oxygenator support for patients who undergo complex neonatal cardiac surgery. (J Thorac Cardiovasc Surg 2000;120:73-80)
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Citation Excerpt :
In adults, sepsis induces profound changes in both energy and protein metabolism. Several neonatal studies have documented glucose and lipid intolerance in neonates with sepsis,30,54,75 but the single study of protein metabolism in neonates with sepsis did not demonstrate either increased protein requirements or significant protein intolerance.70 The neonatal stress response may be different from the adult, but there is little information about how it affects protein metabolism in the infant.

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Early metabolic effects of sepsis in the preterm infant: Lactic acidosis and increased glucose requirement

J Pediatr

J Pediatr

J Pediatr

Metabolism