BACKGROUND: Topiramate (TPM) seems to have neuroprotective functions in asphyxiated newborn. TPM is reported to have multiple mechanisms of action, including inhibition of carbonic anhydrase, which may result in metabolic acidosis from decreased serum bicarbonate (HCO3). OBJECTIVE: Aim of the study was to investigate the appear of metabolic acidosis in asphixiated newborn treated whit whole body hypothermia (H) and TPM. DESIGN/METHODS: We studied 54 neonates with HIE (G.E. 274.5 ± 15.4 d, BW 3355 ± 645 g), treated with H (30-33.5°C) for 72 h. 27 newborns were treated with H and 27 with H and TPM (H-TPM). 16 newborns received 5 mg/kg/day for three days, 11 newborns received 5 mg/kg on the first day and 3 mg/kg on the second and third day. Blood gas analysis (BGA) parameters were coollected every 24 hours during hypothermia. RESULTS: BGAs, which were corrected for body temperature, were comparable in the two groups; no consistent metabolic acidosis was detected in H-TPM. Blood pH, pCO2, pO2 and lactate levels never reached statistically different values. Base excess (BE) and HCO3 were significantly lower in H in the first day of treatment (-7.4 ± 3.7 vs. -3.6 ± 3.5 mmol/L, p <0.001, and 18.8 ± 2.8 vs. 21.1 ± 3.1, p =0.004, respectively); in both groups, values have been increasing, but in H-TPM the trend showed a significant decrease compared to H. It became significantly lower in H-TPM in the third day of treatment (-0.9 ± 3.9 vs. 1.5 ± 1.7 mmol/L, p = 0.018, and 23.2 ± 3.2 vs. 25.5 ± 2.3, p = 0.013, respectively), despite pH remained normal. CONCLUSIONS: The inhibition of carbonic anhydrase may result in a hyperchloremic metabolic acidosis, most likely from a renal tubular acidosis rather than from a more central mechanism. In our study HCO3 resulted higher in H-TPM than in H before the beginning of hypothermia, but reversed to lower on the third day of treatment, possibly due to TPM induced HCO3 loss, which might have occurred even if pH was not significantly different between the two groups. The same trend was observed for BE, again on the third day of treatment. The observed effect on HCO3 and BE is hardly attributable to TPM, since in infants metabolic acidosis usually occurs after 8-26 days of treatment, with dosages as high as 8.2 to 26 mg/kg/d. Monitoring HCO3 before and during TPM therapy may be indicated, especially with conditions that predispose to acidosis.

Topiramate and metabolic acidosis during whole body hypothermia in neonatal hypoxic-ischemic encephalopathy / G. Cavallaro, L. Filippi, G. Cristofori, G. La Marca, M. Daniotti, P. Fiorini, F. Mosca. ((Intervento presentato al convegno Pediatric Academic Societies' Annual Meeting tenutosi a Vancouver nel 2010.

Topiramate and metabolic acidosis during whole body hypothermia in neonatal hypoxic-ischemic encephalopathy

F. Mosca
Ultimo
2010

Abstract

BACKGROUND: Topiramate (TPM) seems to have neuroprotective functions in asphyxiated newborn. TPM is reported to have multiple mechanisms of action, including inhibition of carbonic anhydrase, which may result in metabolic acidosis from decreased serum bicarbonate (HCO3). OBJECTIVE: Aim of the study was to investigate the appear of metabolic acidosis in asphixiated newborn treated whit whole body hypothermia (H) and TPM. DESIGN/METHODS: We studied 54 neonates with HIE (G.E. 274.5 ± 15.4 d, BW 3355 ± 645 g), treated with H (30-33.5°C) for 72 h. 27 newborns were treated with H and 27 with H and TPM (H-TPM). 16 newborns received 5 mg/kg/day for three days, 11 newborns received 5 mg/kg on the first day and 3 mg/kg on the second and third day. Blood gas analysis (BGA) parameters were coollected every 24 hours during hypothermia. RESULTS: BGAs, which were corrected for body temperature, were comparable in the two groups; no consistent metabolic acidosis was detected in H-TPM. Blood pH, pCO2, pO2 and lactate levels never reached statistically different values. Base excess (BE) and HCO3 were significantly lower in H in the first day of treatment (-7.4 ± 3.7 vs. -3.6 ± 3.5 mmol/L, p <0.001, and 18.8 ± 2.8 vs. 21.1 ± 3.1, p =0.004, respectively); in both groups, values have been increasing, but in H-TPM the trend showed a significant decrease compared to H. It became significantly lower in H-TPM in the third day of treatment (-0.9 ± 3.9 vs. 1.5 ± 1.7 mmol/L, p = 0.018, and 23.2 ± 3.2 vs. 25.5 ± 2.3, p = 0.013, respectively), despite pH remained normal. CONCLUSIONS: The inhibition of carbonic anhydrase may result in a hyperchloremic metabolic acidosis, most likely from a renal tubular acidosis rather than from a more central mechanism. In our study HCO3 resulted higher in H-TPM than in H before the beginning of hypothermia, but reversed to lower on the third day of treatment, possibly due to TPM induced HCO3 loss, which might have occurred even if pH was not significantly different between the two groups. The same trend was observed for BE, again on the third day of treatment. The observed effect on HCO3 and BE is hardly attributable to TPM, since in infants metabolic acidosis usually occurs after 8-26 days of treatment, with dosages as high as 8.2 to 26 mg/kg/d. Monitoring HCO3 before and during TPM therapy may be indicated, especially with conditions that predispose to acidosis.
2010
Settore MED/38 - Pediatria Generale e Specialistica
Topiramate and metabolic acidosis during whole body hypothermia in neonatal hypoxic-ischemic encephalopathy / G. Cavallaro, L. Filippi, G. Cristofori, G. La Marca, M. Daniotti, P. Fiorini, F. Mosca. ((Intervento presentato al convegno Pediatric Academic Societies' Annual Meeting tenutosi a Vancouver nel 2010.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/162374
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