Title:Plasma Exchange Successfully Treats Central Pontine Myelinolysis after Acute Hypernatremia from Intravenous Sodium Bicarbonate Therapy

Transcription

1 Author's response to reviews Title:Plasma Exchange Successfully Treats Central Pontine Myelinolysis after Acute Hypernatremia from Intravenous Sodium Bicarbonate Therapy Authors: Kyung Yoon Chang In-Hee Lee Gi Jun Kim Kangwon Cho Hoon Suk Park Hyung Wook Kim Version:2Date:11 March 2014 Author's response to reviews: see over

2 March 11th, 2014 Dear Editor-in-Chief, BMC Nephrology; Thank you very much for the evaluation of our manuscript. We are returning a revised manuscript which incorporates many of the suggestions made by reviewers. A response to the reviewers suggestions has been listed one by one. All authors revised our manuscript before resubmission, responding to editor and reviewers comments. We highlighted the changes made to the manuscript by using underlined text. We hope that the comments of the reviewers are adequately addressed in the revised manuscript. Manuscript ID: Title: Plasma Exchange Successfully Treats Central Pontine Myelinolysis after Acute Hypernatremia from Intravenous Sodium Bicarbonate Therapy Sincerely, Hyung Wook Kim, MD Department of Internal Medicine, St. Vincent s Hospital, The Catholic University of Korea. 93, Jungbu-Daero (Ji-Dong), Paldal-Gu, Suwon, Gyeonggi-Do, , Korea. Tel: , Fax: , khw@catholic.ac.kr 1

3 Answer to the reviewers Reviewer 1: 1. A short discussion of the studies investigating the benefits of re-inducing hyponatremia in case of rapid overcorrection in order to avoid osmotic demyelination should be included. During recent years some studies, mainly animal studies, have investigated this. Thank you for nice comment. There have been some animal studies investigating the benefits of re-inducing hyponatremia in the case of rapid overcorrection of hyponatremia in order to avoid osmotic demyelination [17, 18]. As the reviewer suggested, we revised discussion section as follows; There have been some animal studies investigating the benefits of re-inducing hyponatremia in the case of rapid overcorrection of hyponatremia in order to avoid osmotic demyelination. Gankam Kengne et al. demonstrated that re-induction of hyponatremia by an intraperitoneal administration of water 12 hours after rapid overcorrection of hyponatremia effectively prevented the opening of the BBB, reduced neurological manifestations, decreased microglial activation, and resulted in a significant decrease in mortality in rats [17]. The rat experiment by Soupart et al. showed that after exposure to an excessive correction of chronic hyponatremia, even when rats have developed myelinolysis-related neurologic symptoms, hypotonic fluids administration could improve survival and could prevent the subsequent development of brain myelinolysis [18]. 2

4 17. Gankam Kengne F, Soupart A, Pochet R, Brion JP, Decaux G: Re-induction of hyponatremia after rapid overcorrection of hyponatremia reduces mortality in rats. Kidney Int 2009, 76: Soupart A, Penninckx R, Stenuit A, Perier O, Decaux G: Reinduction of hyponatremia improves survival in rats with myelinolysis-related neurologic symptoms. J Neuropathol Exp Neurol 1996, 55: Reviewer 2: 1. The authors need to stress that a causal relationship hasn't been found; just an association. Thank you for the reviewer s comment and appropriate point. As the reviewer suggested, we revised abstract section as follows; We diagnosed her with CPM associated with the rapid development of hypernatremia after intravenous sodium bicarbonate therapy We should keep in mind that acute hypernatremia and CPM can be associated with intravenous sodium bicarbonate therapy, and that CPM due to acute hypernatremia may be effectively treated with plasma exchange. As the reviewer suggested, we revised discussion section and conclusion as follows; 3

5 Our patient s course supports the concept that intravenous sodium bicarbonate therapy for the treatment of metabolic acidosis can be associated with acute hypernatremia and CPM. In the setting of acute hypernatremia, CPM may be successfully treated with plasma exchange, likely due to the rapid correction of the hyponatremia. We should keep in mind that acute hypernatremia and CPM can be associated with intravenous sodium bicarbonate therapy, and CPM due to acute hypernatremia may be effectively treated with plasma exchange. 2. It is not clear the fractional excretion of bicarbonate and the U-B PCO 2 were technically measured correctly. The fractional excretion to diagnose proximal RTA needs to be measured when the blood bicarbonate is 25 mm and the U-B PCO 2 for distal RTA needs to be assessed when the urine bicarbonate concentration is high and the urine ph is ~ 7.8. The authors need to clarify how they measured this. As the reviewer suggested, we added the details of method and results of sodium bicarbonate (NaHCO 3 ) loading test in case presentation section as follows; We performed a sodium bicarbonate (NaHCO 3 ) loading test to confirm distal RTA [7]. In NaHCO 3 loading test, 8.4% NaHCO 3 solution was infused intravenously at a rate of 57 meq/hour (1 meq/kg/hour). Urine and blood samples were taken at 1-hour intervals and urine and blood PCO 2 were measured using a blood gas analyzer. When the urine ph was raised to 7.6, Urine PCO 2, blood PCO 2, urine HCO 3, blood HCO 3, urine creatinine and serum 4

6 creatinine were 44.5 mmhg, 34.8 mmhg, 40.1 meq/l, 25.8 meq/l, 64.5 mg/dl, and 0.7 mg/dl, respectively. The results of NaHCO 3 loading test revealed a fractionated excretion of HCO 3 of 1.68% and the urine-to-blood carbon dioxide tension gradient (U-B PCO 2 ) of 9.7, suggesting distal RTA. 7. Kim S, Lee JW, Park J, Na KY, Joo KW, Ahn C, Kim S, Lee JS, Kim GH, Kim J, Han JS: The urine-blood PCO gradient as a diagnostic index of H(+)-ATPase defect distal renal tubular acidosis. Kidney Int 2004, 66: Thanks again for reviewer s comments. Editorial Request 1. Acknowlegements We added an Acknowlegements section as follows; The authors would like to thank Young-Soo Kim, MD (Uijeongbu St. Mary's Hospital, The Catholic University of Korea) for critical comments on the manuscript. This work was not granted or funded by any third party. 2. Please include the address of all the authors in the title page. 5

7 We added the address of all the authors in the title page. 6