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Am J Perinatol 2012; 29(05): 361-368
DOI: 10.1055/s-0031-1300969
Original Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Acid-Base Parameters for Predicting Magnetic Resonance Imaging Measures of Neurologic Outcome after Perinatal Hypoxia-Ischemia: Is the Strong Ion Gap Superior to Base Excess and Lactate?

Christian Mann
1   Neonatal and Pediatric Intensive Care Unit, Graubuenden Cantonal Hospital, Chur, and College for Intensive Care, Emergency and Anesthesia Nursing, University Children's Hospital Zurich, Zurich, Switzerland
,
Beatrice Latal
2   Child Development Center, University Children's Hospital Zurich, Zurich, Switzerland
,
Beth Padden
3   Rehabilitation Center, University Children's Hospital Zurich, Zurich, Switzerland
,
Ianina Scheer
4   Department of Pediatric Radiology, University Children's Hospital Zurich, Zurich, Switzerland
,
Georg Goebel
5   Department of Medical Statistics, Informatics and Health Economics, Medical University of Innsbruck, Innsbruck, Austria
,
Vera Bernet
6   Department of Neonatology, University Children's Hospital Zurich, Zurich, Switzerland
› Author Affiliations
Further Information

Publication History

10 May 2011

17 October 2011

Publication Date:
03 February 2012 (online)

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Abstract

We conducted this study to compare the strong ion gap (SIG) with base excess (BE) and lactate for predicting neurologic outcome measured by magnetic resonance imaging (MRI) in newborns with hypoxic-ischemic encephalopathy (HIE). In a retrospective cohort of 39 newborns with HIE treated with whole-body surface cooling (n = 17) and no cooling (n = 22), we measured blood SIG, BE, and lactate at 4, 24, and 48 hours after birth, and determined cerebral injury severity by T1-, T2-, and diffusion-weighted MRI scores at age 5 days. Lower SIG levels correlated with better neurologic outcome. The highest correlation coefficient (0.63) was in the “no cooling” subcohort between diffusion-weighted scores and SIG levels at 24 hours; the latter also had the highest area under the receiver operating characteristic curve (AUC), 0.90, with positive and negative predictive values of 84 and 90%. SIG outperformed lactate in the “no cooling” subcohort, and vice-versa in the “cooling” subcohort. All BE AUCs were <0.6. Overall, the SIG is similar to lactate as a prognostic parameter. BE levels at 4, 24, and 48 hours after birth do not predict neurologic outcome. While not displacing lactate the SIG is an additional prognostic parameter for newborns in the first 2 days after hypoxia-ischemia.

Keywords

acidosis - asphyxia neonatorum - cerebral palsy - hypoxia-ischemia - magnetic resonance imaging - strong ion gap
 

  • References

  • 1 Kuenzle C, Baenziger O, Martin E , et al. Prognostic value of early MR imaging in term infants with severe perinatal asphyxia. Neuropediatrics 1994; 25 (4) 191-200
    Article in Thieme ConnectPubMedGoogle Scholar
  • 2 Barkovich AJ, Hajnal BL, Vigneron D , et al. Prediction of neuromotor outcome in perinatal asphyxia: evaluation of MR scoring systems. AJNR Am J Neuroradiol 1998; 19 (1) 143-149
    PubMedGoogle Scholar
  • 3 Miller SP, Ramaswamy V, Michelson D , et al. Patterns of brain injury in term neonatal encephalopathy. J Pediatr 2005; 146 (4) 453-460
    CrossrefPubMedGoogle Scholar
  • 4 Engle WD, Laptook AR, Perlman JM. Acute changes in arterial carbon dioxide tension and acid-base status and early neurologic characteristics in term infants following perinatal asphyxia. Resuscitation 1999; 42 (1) 11-17
    CrossrefPubMedGoogle Scholar
  • 5 Toh VC. Early predictors of adverse outcome in term infants with post-asphyxial hypoxic ischaemic encephalopathy. Acta Paediatr 2000; 89 (3) 343-347
    CrossrefPubMedGoogle Scholar
  • 6 Ross MG, Gala R. Use of umbilical artery base excess: algorithm for the timing of hypoxic injury. Am J Obstet Gynecol 2002; 187 (1) 1-9
    CrossrefPubMedGoogle Scholar
  • 7 ACOG Committee on Obstetric Practice. ACOG Committee Opinion No. 348, November 2006: umbilical cord blood gas and acid-base analysis. Obstet Gynecol 2006; 108 (5) 1319-1322
    CrossrefPubMedGoogle Scholar
  • 8 Malin GL, Morris RK, Khan KS. Strength of association between umbilical cord pH and perinatal and long term outcomes: systematic review and meta-analysis. BMJ 2010; 340: c1471
    CrossrefPubMedGoogle Scholar
  • 9 Gilfix BM, Bique M, Magder S. A physical chemical approach to the analysis of acid-base balance in the clinical setting. J Crit Care 1993; 8 (4) 187-197
    CrossrefPubMedGoogle Scholar
  • 10 Fidkowski C, Helstrom J. Diagnosing metabolic acidosis in the critically ill: bridging the anion gap, Stewart, and base excess methods. Can J Anaesth 2009; 56 (3) 247-256
    PubMedGoogle Scholar
  • 11 Kellum JA, Kramer DJ, Pinsky MR. Strong ion gap: a methodology for exploring unexplained anions. J Crit Care 1995; 10 (2) 51-55
    CrossrefPubMedGoogle Scholar
  • 12 Murray D, Grant D, Murali N, Butt W. Unmeasured anions in children after cardiac surgery. J Thorac Cardiovasc Surg 2007; 133 (1) 235-240
    CrossrefPubMedGoogle Scholar
  • 13 Murray DM, Olhsson V, Fraser JI. Defining acidosis in postoperative cardiac patients using Stewart’s method of strong ion difference. Pediatr Crit Care Med 2004; 5 (3) 240-245
    CrossrefPubMedGoogle Scholar
  • 14 Forni LG, McKinnon W, Hilton PJ. Unmeasured anions in metabolic acidosis: unravelling the mystery. Crit Care 2006; 10 (4) 220
    CrossrefPubMedGoogle Scholar
  • 15 Moviat M, van Haren F, van der Hoeven H. Conventional or physicochemical approach in intensive care unit patients with metabolic acidosis. Crit Care 2003; 7 (3) R41-R45
    PubMedGoogle Scholar
  • 16 Kellum JA. Clinical review: reunification of acid-base physiology. Crit Care 2005; 9 (5) 500-507
    CrossrefPubMedGoogle Scholar
  • 17 Bruegger D, Kemming GI, Jacob M , et al. Causes of metabolic acidosis in canine hemorrhagic shock: role of unmeasured ions. Crit Care 2007; 11 (6) R130
    CrossrefPubMedGoogle Scholar
  • 18 Kaplan LJ, Kellum JA. Initial pH, base deficit, lactate, anion gap, strong ion difference, and strong ion gap predict outcome from major vascular injury. Crit Care Med 2004; 32 (5) 1120-1124
    CrossrefPubMedGoogle Scholar
  • 19 Martin M, Murray J, Berne T, Demetriades D, Belzberg H. Diagnosis of acid-base derangements and mortality prediction in the trauma intensive care unit: the physiochemical approach. J Trauma 2005; 58 (2) 238-243
    CrossrefPubMedGoogle Scholar
  • 20 Kaplan LJ, Kellum JA. Comparison of acid-base models for prediction of hospital mortality after trauma. Shock 2008; 29 (6) 662-666
    PubMedGoogle Scholar
  • 21 Funk GC, Doberer D, Sterz F , et al. The strong ion gap and outcome after cardiac arrest in patients treated with therapeutic hypothermia: a retrospective study. Intensive Care Med 2009; 35 (2) 232-239
    CrossrefPubMedGoogle Scholar
  • 22 Balasubramanyan N, Havens PL, Hoffman GM. Unmeasured anions identified by the Fencl-Stewart method predict mortality better than base excess, anion gap, and lactate in patients in the pediatric intensive care unit. Crit Care Med 1999; 27 (8) 1577-1581
    CrossrefPubMedGoogle Scholar
  • 23 Durward A, Tibby SM, Skellett S, Austin C, Anderson D, Murdoch IA. The strong ion gap predicts mortality in children following cardiopulmonary bypass surgery. Pediatr Crit Care Med 2005; 6 (3) 281-285
    CrossrefPubMedGoogle Scholar
  • 24 Gunnerson KJ, Saul M, He S, Kellum JA. Lactate versus non-lactate metabolic acidosis: a retrospective outcome evaluation of critically ill patients. Crit Care 2006; 10 (1) R22
    CrossrefPubMedGoogle Scholar
  • 25 Mann C, Held U, Herzog S, Baenziger O. Impact of normal saline infusion on postoperative metabolic acidosis. Paediatr Anaesth 2009; 19 (11) 1070-1077
    CrossrefPubMedGoogle Scholar
  • 26 Sarnat HB, Sarnat MS. Neonatal encephalopathy following fetal distress. A clinical and electroencephalographic study. Arch Neurol 1976; 33 (10) 696-705
    CrossrefPubMedGoogle Scholar
  • 27 Shankaran S, Laptook AR, Ehrenkranz RA , et al; National Institute of Child Health and Human Development Neonatal Research Network. Whole-body hypothermia for neonates with hypoxic-ischemic encephalopathy. N Engl J Med 2005; 353 (15) 1574-1584
    CrossrefPubMedGoogle Scholar
  • 28 Figge J, Mydosh T, Fencl V. Serum proteins and acid-base equilibria: a follow-up. J Lab Clin Med 1992; 120 (5) 713-719
    PubMedGoogle Scholar
  • 29 Kellum J. SIG Calculator. . Available at: http://www.nefrologiaonline.com.br/DHApoio/ABkellum_nova.xls . Accessed September 23, 2011
    PubMedGoogle Scholar
  • 30 Gunnerson KJ. Clinical review: the meaning of acid-base abnormalities in the intensive care unit part I - epidemiology. Crit Care 2005; 9 (5) 508-516
    CrossrefPubMedGoogle Scholar
  • 31 Gunnerson KJ, Srisawat N, Kellum JA. Is there a difference between strong ion gap in healthy volunteers and intensive care unit patients?. J Crit Care 2010; 25 (3) 520-524
    CrossrefPubMedGoogle Scholar
  • 32 Robertson NJ, Cowan FM, Cox IJ, Edwards AD. Brain alkaline intracellular pH after neonatal encephalopathy. Ann Neurol 2002; 52 (6) 732-742
    CrossrefPubMedGoogle Scholar
  • 33 Wayenberg JL, Vermeylen D, Bormans J, Magrez P, Müller MF, Pardou A. Diagnosis of severe birth asphyxia and early prediction of neonatal neurological outcome in term asphyxiated newborns. J Perinat Med 1994; 22 (2) 129-136
    CrossrefPubMedGoogle Scholar
  • 34 Low JA. Metabolic acidosis and fetal reserve. Baillieres Clin Obstet Gynaecol 1996; 10 (2) 211-224
    CrossrefPubMedGoogle Scholar
  • 35 Low JA, Lindsay BG, Derrick EJ. Threshold of metabolic acidosis associated with newborn complications. Am J Obstet Gynecol 1997; 177 (6) 1391-1394
    CrossrefPubMedGoogle Scholar
  • 36 Wayenberg JL, Vermeylen D, Damis E. [Definition of asphyxia neonatorum and incidence of neurologic and systemic complications in the full-term newborn]. Arch Pediatr 1998; 5 (10) 1065-1071
    CrossrefPubMedGoogle Scholar
  • 37 da Silva S, Hennebert N, Denis R, Wayenberg JL. Clinical value of a single postnatal lactate measurement after intrapartum asphyxia. Acta Paediatr 2000; 89 (3) 320-323
    CrossrefPubMedGoogle Scholar
  • 38 Zupan Simunek V. [Definition of intrapartum asphyxia and effects on outcome]. J Gynecol Obstet Biol Reprod (Paris) 2008; 37 (Suppl 1) S7-S15
    CrossrefPubMedGoogle Scholar
  • 39 Wayenberg JL. Threshold of metabolic acidosis associated with neonatal encephalopathy in the term newborn. J Matern Fetal Neonatal Med 2005; 18 (6) 381-385
    CrossrefPubMedGoogle Scholar
  • 40 Roemer VM, Beyer B. Outcome measures in perinatal medicine - pH or BE. The thresholds of these parameters in term infants. Z Geburtshilfe Neonatol 2008; 212 (4) 136-146
    Article in Thieme ConnectPubMedGoogle Scholar
  • 41 Sarkar S, Bhagat I, Dechert RE, Barks JD. Predicting death despite therapeutic hypothermia in infants with hypoxic-ischaemic encephalopathy. Arch Dis Child Fetal Neonatal Ed 2010; 95 (6) F423-F428
    CrossrefPubMedGoogle Scholar
  • 42 Shah S, Tracy M, Smyth J. Postnatal lactate as an early predictor of short-term outcome after intrapartum asphyxia. J Perinatol 2004; 24 (1) 16-20
    CrossrefPubMedGoogle Scholar
  • 43 Frey B, Pfenninger J, Bachmann D. Prognostic value of hyperlactatemia in neonates. J Pediatr 1995; 127 (2) 334-, author reply 334
    PubMedGoogle Scholar
  • 44 Murray DM, Boylan GB, Fitzgerald AP, Ryan CA, Murphy BP, Connolly S. Persistent lactic acidosis in neonatal hypoxic-ischaemic encephalopathy correlates with EEG grade and electrographic seizure burden. Arch Dis Child Fetal Neonatal Ed 2008; 93 (3) F183-F186
    CrossrefPubMedGoogle Scholar
  • 45 Nelson KB, Grether JK. Causes of cerebral palsy. Curr Opin Pediatr 1999; 11 (6) 487-491
    CrossrefPubMedGoogle Scholar
  • 46 Strijbis EM, Oudman I, van Essen P, MacLennan AH. Cerebral palsy and the application of the international criteria for acute intrapartum hypoxia. Obstet Gynecol 2006; 107 (6) 1357-1365
    CrossrefPubMedGoogle Scholar
  • 47 Graham EM, Ruis KA, Hartman AL, Northington FJ, Fox HE. A systematic review of the role of intrapartum hypoxia-ischemia in the causation of neonatal encephalopathy. Am J Obstet Gynecol 2008; 199 (6) 587-595
    CrossrefPubMedGoogle Scholar
  • 48 Shalak L, Perlman JM. Hypoxic-ischemic brain injury in the term infant-current concepts. Early Hum Dev 2004; 80 (2) 125-141
    CrossrefPubMedGoogle Scholar
  • 49 Okereafor A, Allsop J, Counsell SJ , et al. Patterns of brain injury in neonates exposed to perinatal sentinel events. Pediatrics 2008; 121 (5) 906-914
    Google Scholar
  • 50 Steinman KJ, Gorno-Tempini ML, Glidden DV , et al. Neonatal watershed brain injury on magnetic resonance imaging correlates with verbal IQ at 4 years. Pediatrics 2009; 123 (3) 1025-1030
    CrossrefPubMedGoogle Scholar
  • 51 Lloyd P. Strong ion calculator—a practical bedside application of modern quantitative acid-base physiology. Crit Care Resusc 2004; 6 (4) 285-294
    PubMedGoogle Scholar
  • 52 Lloyd P, Freebairn R. Using quantitative acid-base analysis in the ICU. Crit Care Resusc 2006; 8 (1) 19-30
    PubMedGoogle Scholar
  • 53 Elbers P. AcidBase.org. . Available at: http://www.acidbase.org/phpscripts6/start_pe.php . Accessed September 23, 2011
    PubMedGoogle Scholar
  • 54 Morgan TJ. The Stewart approach—one clinician’s perspective. Clin Biochem Rev 2009; 30 (2) 41-54
    PubMedGoogle Scholar