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A Case of Lactation “Bovine” Ketoacidosis
The Journal of Emergency Medicine, Vol. 35, No. 4, pp. 385–387, 2008 Copyright © 2008 Elsevier Inc. Printed in the USA. All rights reserved 0736-4679/08 $–see front matter
doi:10.1016/j.jemermed.2007.04.013
Clinical Communications: Adults A CASE OF LACTATION “BOVINE” KETOACIDOSIS Alan C. Heffner,
MDⴱ
and David P. Johnson,
DO†
ⴱDepartment of Critical Care Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, and †Department of Emergency Medicine, Naval Medical Center Portsmouth, Portsmouth, Virginia Reprint Address: Alan C. Heffner, MD, Department of Internal Medicine/Division of Critical Care, Department of Emergency Medicine, Carolinas Medical Center, PO Box 32861, Charlotte, NC 28232
e Abstract—A 35-year-old postpartum lactating woman presented with dyspnea and was found to be in non-diabetic ketoacidosis (pH 7.24, HCO3 10 mmol/L, urine ketones >80 mg/dL). Rapid clinical and laboratory resolution occurred after intravenous dextrose and enteral feeding along with discontinuation of lactation. This represents a rarely reported case of lactation “bovine” ketoacidosis in humans. We review the historical precedence for the diagnosis and detail the underlying physiology. © 2008 Elsevier Inc.
partment with a chief complaint of shortness of breath. The patient reported a 2-day history of progressive fatigue and dyspnea followed by palpitations and lightheadedness with light exertion. She denied syncope, chest pain, cough, orthopnea, fever, vomiting, diarrhea, weight loss, abdominal pain, dysuria, vaginal discharge, and lower extremity swelling or pain. The patient reported attention to diet selection but denied fasting, carbohydrate avoidance, ketogenic diet, attempted weight loss, or meal intolerance. Antepartum care was remarkable for borderline gestational diabetes by glucose tolerance testing with normal fasting blood sugar. Uncomplicated spontaneous vaginal delivery of her full-term twin gestation occurred 12 weeks prior. The patient reported uneventful breast-feeding and formula supplementation of her thriving twin infants. The patient had a history of paroxysmal atrial fibrillation diagnosed 1 year prior. Pharmacologic cardioversion was required for a single recurrence of atrial fibrillation during the second trimester. Past surgical history included gastric bypass and cholecystectomy 5 years prior, and remote appendectomy. Daily medications consisted of prenatal vitamins and norethindrone 0.35 mg. The patient denied alcohol, tobacco, recreational drugs, and over-the-counter medications. Triage vital signs were: temperature 36.17°C (97.1°F), blood pressure 117/65 mm Hg, heart rate 94 beats/min, respiratory rate 32 breaths/min, and 99% SaO2 on room air. The patient appeared well nourished and alert but apprehensive. Head and neck examination was nor-
e Keywords— ketosis; bovine; pregnancy; postpartum; starvation
INTRODUCTION Ketoanions play an important physiologic role as metabolic substrate during fasting. Mild ketosis is common during acute illness but rarely contributes to significant acidosis (1). In contrast, pathologic ketosis leading to metabolic acidosis is well recognized in the syndromes of diabetic and alcoholic ketoacidosis. We recently cared for a nondiabetic, nonalcoholic postpartum female who developed clinically significant ketoacidosis precipitated by breast-feeding twin infants. The case, historical precedence, and underlying pathophysiology of lactation “bovine” ketoacidosis are described herein. CASE REPORT A 35-year-old gravida 3, para 2, 12 weeks postpartum lactating white woman presented to our Emergency De-
RECEIVED: 27 June 2005; FINAL ACCEPTED: 17 February 2007
SUBMISSION RECEIVED:
20 October 2006; 385
386
A. C. Heffner and D. P. Johnson
Table 1. Initial Laboratory Data Venous blood gas Arterial blood gas Glucose BUN Cr Na K Cl HCO3 Ca Mg Total protein Albumin Alkaline phosphatase AST ALT Bilirubin Lactic acid Ethanol Serum osms Serum ketones Salicylates WBC Hgb Platelets Urinalysis: Specific gravity Glucose Bilirubin Ketones PH Blood Nitrite Leukocyte esterase Qualitative HCG
7.22, pCO2 24, pO2 32, HCO3 10, Base excess ⫺18 7.24, pCO2 16, pO2 124, HCO3 7, Base excess ⫺21 68 mg/dL 20 mg/dL 0.7 mg/dL 139 mmol/L 4.3 mmol/L 107 mmol/L 10 mmol/L 9.0 mg/dL 2.0 mg/dL 8.1 g/dL 4.9 g/dL 135 IU/L 22 IU/L 31 IU/L 0.4 mg/dL 0.80 mmol/L ⬍10.0 mg/dL 286 mOsm/L Moderate ⬍0.1 mg/dL 7.9 ⫻ 1000/mm3 15.8 gm/dL 363 ⫻ 1000/mm3 1.029 Negative Negative ⬎80 mg/dL 6.0 Negative Negative Negative Negative
mal, without evidence of pallor, icterus, adenopathy, thyromegaly, meningismus, or jugular venous distention. Chest auscultation revealed resting tachypnea with clear lungs, and heart examination was regular without murmur or gallop. The abdomen had a wellhealed midline scar, normal bowel sounds, and no tenderness to palpation or organomegaly. The extremities were well perfused with normal pulses and no edema or tenderness to palpation. Neurologic examination was normal. Emergency Department laboratory results are shown in Table 1. An electrocardiogram showed sinus tachycardia, normal axis and intervals, and non-specific ST-segment and T-wave changes. Electrocardiographic monitoring showed sinus tachycardia without ectopy. Chest radiography was normal. The patient was presumptively diagnosed with mild dehydration and non-diabetic ketoacidosis. Initial intervention included intravenous isotonic saline, thiamine 100 mg, magnesium sulfate 2 gm, and 5% dextrose in normal saline infusion, followed by a meal. Marked
symptomatic improvement occurred within 6 h and intravenous supplementation was discontinued. The patient tolerated a normal diet during hospitalization with serum bicarbonate and anion gap normalization within 24 h of presentation. Insulin was not administered. Limited lactation was continued via breast pump on hospital day 1. Nutritional consultation calculated caloric requirements of lactation and discovered mild carbohydrate and protein dietary deficiency. The patient was discharged home on a normal diet and multi-vitamin supplements.
DISCUSSION Ketogenesis represents a physiologic response to metabolic substrate availability. Fatty acid metabolism is subject to hormonal control by insulin and counter-insulin stress hormones (catecholamines, glucagon, cortisol, and growth hormone). Fasting ketosis develops within hours and occurs nightly in most individuals. Starvation ketosis resulting from prolonged caloric deprivation leads to maximal ketogenesis at 2– 4 days (1). However, the relative insulinopenia of starvation produces mild ketogenesis that rarely leads to clinically significant acidemia in the absence of other physiologic stressors (2– 4). Exaggerated ketosis occurring with gestational starvation and hyperemesis gravidarum likely represents an altered threshold for ketogenesis during pregnancy (5). Sequelae of gastric bypass, including diet intolerance and micronutrient deficiency, do not seem contributory in this case (6). Our patient described attention to diet selection but denied deliberate weight loss, early satiety, or meal intolerance. She exhibited no signs of macro- or micronutrient deficiency, and tolerated a general diet with calorie count during hospitalization. Under alternative circumstances our patient’s mild caloric deficit would be insignificant. We believe the metabolic demands and hormonal milieu of lactation were major pathophysiologic factors leading to clinically significant ketoacidosis as described in dairy cattle (7). The syndrome of “bovine ketosis” is a well-characterized disorder of lactating cattle. After calving, the metabolic and glucose demands of milk secretion exceed the sum of ingested carbohydrate and glycogen stores (8,9). Early ketosis and inhibition of gluconeogenesis represent glucose- and protein-sparing mechanisms that enable lactation with preservation of lean body mass during this catabolic state (8). These events occur in the absence of concomitant or precipitating illness. Bovine ketosis in humans is rare, but has been previously reported. Chernow et al. describe a 19-year-old, 7 weeks postpartum, non-diabetic, non-alcoholic nursing mother who presented after a 2-week history of nausea, emesis, and abdominal pain (7). She had undertaken a
Lactation Ketoacidosis Table 2. Syndromes of Ketosis Diabetic ketoacidosis (DKA) Alcoholic ketoacidosis (AKA) Starvation ketosis Ketogenic diet Hypoglycemic ketosis Stress hormone influenced Exercise Pregnancy Lactation “bovine” ketosis Drug associated Salicylate Isopropyl alcohol
hypocaloric weight reduction program with significant weight loss before admission. Initial laboratory evaluation revealed ketonuria, arterial pH of 7.25, serum bicarbonate of 10 mEq/L, and serum glucose of 200 mg/dL (during 5% dextrose infusion). Treatment with antibiotics and insulin were initiated under the presumed diagnosis of urinary tract infection and diabetic ketoacidosis. Normal pre-treatment blood glucose levels were later recognized and insulin was discontinued. A 2500-kcal/day diet was initiated and ketoacidosis resolved within 24 h. Altus and Hickman describe the case of a 30-year-old, 14 weeks postpartum, non-diabetic, non-alcoholic nursing mother who presented with vomiting, nausea, rapid breathing and dehydration (10). She admitted to a high protein, carbohydrate-free diet. Laboratory evaluation revealed normal blood glucose, arterial pH of 7.07, serum bicarbonate ⬍5 mEq/L, and positive serum and urinary ketones screens. Treatment with intravenous fluids, low-dose insulin, and electrolyte replacement led to clinical resolution within 24 h. Our patient differs from the aforementioned cases by the breastfeeding of twin infants and the absence of severe
387
carbohydrate restriction or concomitant illness. We surmise that the metabolic demands of breast-feeding twin infants coupled with mild carbohydrate deficiency exaggerated an otherwise physiologic conservation mechanism to produce clinically significant ketoacidosis as described in dairy cattle. This case of lactation “bovine” ketoacidosis serves to increase our awareness of pathologic ketosis (Table 2) and underscores the importance of patient education and nutrition during pregnancy and lactation. Acknowledgment—This work was supported by National Institutes of Health training grant #5 T32 HL007820-09. The views expressed in this article are those of the author or authors and do not necessarily reflect the official policy or position of the Department of the Navy, Department of Defense, or United States Government.
REFERENCES 1. Oster JR, Epstein M. Acid-base aspects of Ketoacidosis. Am J Nephrol 1984;137–51. 2. Owen OE, Caprio S, Reichard GA, et al. Ketosis of starvation: a revisit and new perspectives. Clin Endocrinol Metab 1983;12:359 –79. 3. Toth HL, Greenbaum LA, Severe acidosis caused by starvation and stress. Am J Kidney Dis 2003;42:16 –9. 4. Miaskiewicz S, Levey GS, Owen O. Severe metabolic ketoacidosis induced by starvation and exercise. Am J Med Sci 1989;297:178 – 80. 5. Mahoney CA. Extreme gestational starvation ketoacidosis: case report and review of the pathophysiology. Am J Kidney Dis 1992;20:276 – 80. 6. Woodard CB. Pregnancy following bariatric surgery. J Perinat Neonat Nurs 2004;18:329 – 40. 7. Chernow B, Finton C, Rainey TG, O’Brian TG. “Bovine ketosis” in a nondiabetic postpartum woman. Diab Care 1982;5:47–9. 8. Holtenius P, Holtenius K. New aspects of ketone bodies in energy metabolism of dairy cows: a review. J Vet Med 1996;43:579 – 87. 9. Stinson O. So-called postparturient dyspepsia of bovines and its specific treatment. Vet Rec 1929;9:1115–9. 10. Altus P, Hickman JW. Severe spontaneous ‘bovine’ ketoacidosis in a lactating woman. J Indiana State Med Assoc 1983;76:392–3.
doi:10.1016/j.jemermed.2007.04.013
Clinical Communications: Adults A CASE OF LACTATION “BOVINE” KETOACIDOSIS Alan C. Heffner,
MDⴱ
and David P. Johnson,
DO†
ⴱDepartment of Critical Care Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, and †Department of Emergency Medicine, Naval Medical Center Portsmouth, Portsmouth, Virginia Reprint Address: Alan C. Heffner, MD, Department of Internal Medicine/Division of Critical Care, Department of Emergency Medicine, Carolinas Medical Center, PO Box 32861, Charlotte, NC 28232
e Abstract—A 35-year-old postpartum lactating woman presented with dyspnea and was found to be in non-diabetic ketoacidosis (pH 7.24, HCO3 10 mmol/L, urine ketones >80 mg/dL). Rapid clinical and laboratory resolution occurred after intravenous dextrose and enteral feeding along with discontinuation of lactation. This represents a rarely reported case of lactation “bovine” ketoacidosis in humans. We review the historical precedence for the diagnosis and detail the underlying physiology. © 2008 Elsevier Inc.
partment with a chief complaint of shortness of breath. The patient reported a 2-day history of progressive fatigue and dyspnea followed by palpitations and lightheadedness with light exertion. She denied syncope, chest pain, cough, orthopnea, fever, vomiting, diarrhea, weight loss, abdominal pain, dysuria, vaginal discharge, and lower extremity swelling or pain. The patient reported attention to diet selection but denied fasting, carbohydrate avoidance, ketogenic diet, attempted weight loss, or meal intolerance. Antepartum care was remarkable for borderline gestational diabetes by glucose tolerance testing with normal fasting blood sugar. Uncomplicated spontaneous vaginal delivery of her full-term twin gestation occurred 12 weeks prior. The patient reported uneventful breast-feeding and formula supplementation of her thriving twin infants. The patient had a history of paroxysmal atrial fibrillation diagnosed 1 year prior. Pharmacologic cardioversion was required for a single recurrence of atrial fibrillation during the second trimester. Past surgical history included gastric bypass and cholecystectomy 5 years prior, and remote appendectomy. Daily medications consisted of prenatal vitamins and norethindrone 0.35 mg. The patient denied alcohol, tobacco, recreational drugs, and over-the-counter medications. Triage vital signs were: temperature 36.17°C (97.1°F), blood pressure 117/65 mm Hg, heart rate 94 beats/min, respiratory rate 32 breaths/min, and 99% SaO2 on room air. The patient appeared well nourished and alert but apprehensive. Head and neck examination was nor-
e Keywords— ketosis; bovine; pregnancy; postpartum; starvation
INTRODUCTION Ketoanions play an important physiologic role as metabolic substrate during fasting. Mild ketosis is common during acute illness but rarely contributes to significant acidosis (1). In contrast, pathologic ketosis leading to metabolic acidosis is well recognized in the syndromes of diabetic and alcoholic ketoacidosis. We recently cared for a nondiabetic, nonalcoholic postpartum female who developed clinically significant ketoacidosis precipitated by breast-feeding twin infants. The case, historical precedence, and underlying pathophysiology of lactation “bovine” ketoacidosis are described herein. CASE REPORT A 35-year-old gravida 3, para 2, 12 weeks postpartum lactating white woman presented to our Emergency De-
RECEIVED: 27 June 2005; FINAL ACCEPTED: 17 February 2007
SUBMISSION RECEIVED:
20 October 2006; 385
386
A. C. Heffner and D. P. Johnson
Table 1. Initial Laboratory Data Venous blood gas Arterial blood gas Glucose BUN Cr Na K Cl HCO3 Ca Mg Total protein Albumin Alkaline phosphatase AST ALT Bilirubin Lactic acid Ethanol Serum osms Serum ketones Salicylates WBC Hgb Platelets Urinalysis: Specific gravity Glucose Bilirubin Ketones PH Blood Nitrite Leukocyte esterase Qualitative HCG
7.22, pCO2 24, pO2 32, HCO3 10, Base excess ⫺18 7.24, pCO2 16, pO2 124, HCO3 7, Base excess ⫺21 68 mg/dL 20 mg/dL 0.7 mg/dL 139 mmol/L 4.3 mmol/L 107 mmol/L 10 mmol/L 9.0 mg/dL 2.0 mg/dL 8.1 g/dL 4.9 g/dL 135 IU/L 22 IU/L 31 IU/L 0.4 mg/dL 0.80 mmol/L ⬍10.0 mg/dL 286 mOsm/L Moderate ⬍0.1 mg/dL 7.9 ⫻ 1000/mm3 15.8 gm/dL 363 ⫻ 1000/mm3 1.029 Negative Negative ⬎80 mg/dL 6.0 Negative Negative Negative Negative
mal, without evidence of pallor, icterus, adenopathy, thyromegaly, meningismus, or jugular venous distention. Chest auscultation revealed resting tachypnea with clear lungs, and heart examination was regular without murmur or gallop. The abdomen had a wellhealed midline scar, normal bowel sounds, and no tenderness to palpation or organomegaly. The extremities were well perfused with normal pulses and no edema or tenderness to palpation. Neurologic examination was normal. Emergency Department laboratory results are shown in Table 1. An electrocardiogram showed sinus tachycardia, normal axis and intervals, and non-specific ST-segment and T-wave changes. Electrocardiographic monitoring showed sinus tachycardia without ectopy. Chest radiography was normal. The patient was presumptively diagnosed with mild dehydration and non-diabetic ketoacidosis. Initial intervention included intravenous isotonic saline, thiamine 100 mg, magnesium sulfate 2 gm, and 5% dextrose in normal saline infusion, followed by a meal. Marked
symptomatic improvement occurred within 6 h and intravenous supplementation was discontinued. The patient tolerated a normal diet during hospitalization with serum bicarbonate and anion gap normalization within 24 h of presentation. Insulin was not administered. Limited lactation was continued via breast pump on hospital day 1. Nutritional consultation calculated caloric requirements of lactation and discovered mild carbohydrate and protein dietary deficiency. The patient was discharged home on a normal diet and multi-vitamin supplements.
DISCUSSION Ketogenesis represents a physiologic response to metabolic substrate availability. Fatty acid metabolism is subject to hormonal control by insulin and counter-insulin stress hormones (catecholamines, glucagon, cortisol, and growth hormone). Fasting ketosis develops within hours and occurs nightly in most individuals. Starvation ketosis resulting from prolonged caloric deprivation leads to maximal ketogenesis at 2– 4 days (1). However, the relative insulinopenia of starvation produces mild ketogenesis that rarely leads to clinically significant acidemia in the absence of other physiologic stressors (2– 4). Exaggerated ketosis occurring with gestational starvation and hyperemesis gravidarum likely represents an altered threshold for ketogenesis during pregnancy (5). Sequelae of gastric bypass, including diet intolerance and micronutrient deficiency, do not seem contributory in this case (6). Our patient described attention to diet selection but denied deliberate weight loss, early satiety, or meal intolerance. She exhibited no signs of macro- or micronutrient deficiency, and tolerated a general diet with calorie count during hospitalization. Under alternative circumstances our patient’s mild caloric deficit would be insignificant. We believe the metabolic demands and hormonal milieu of lactation were major pathophysiologic factors leading to clinically significant ketoacidosis as described in dairy cattle (7). The syndrome of “bovine ketosis” is a well-characterized disorder of lactating cattle. After calving, the metabolic and glucose demands of milk secretion exceed the sum of ingested carbohydrate and glycogen stores (8,9). Early ketosis and inhibition of gluconeogenesis represent glucose- and protein-sparing mechanisms that enable lactation with preservation of lean body mass during this catabolic state (8). These events occur in the absence of concomitant or precipitating illness. Bovine ketosis in humans is rare, but has been previously reported. Chernow et al. describe a 19-year-old, 7 weeks postpartum, non-diabetic, non-alcoholic nursing mother who presented after a 2-week history of nausea, emesis, and abdominal pain (7). She had undertaken a
Lactation Ketoacidosis Table 2. Syndromes of Ketosis Diabetic ketoacidosis (DKA) Alcoholic ketoacidosis (AKA) Starvation ketosis Ketogenic diet Hypoglycemic ketosis Stress hormone influenced Exercise Pregnancy Lactation “bovine” ketosis Drug associated Salicylate Isopropyl alcohol
hypocaloric weight reduction program with significant weight loss before admission. Initial laboratory evaluation revealed ketonuria, arterial pH of 7.25, serum bicarbonate of 10 mEq/L, and serum glucose of 200 mg/dL (during 5% dextrose infusion). Treatment with antibiotics and insulin were initiated under the presumed diagnosis of urinary tract infection and diabetic ketoacidosis. Normal pre-treatment blood glucose levels were later recognized and insulin was discontinued. A 2500-kcal/day diet was initiated and ketoacidosis resolved within 24 h. Altus and Hickman describe the case of a 30-year-old, 14 weeks postpartum, non-diabetic, non-alcoholic nursing mother who presented with vomiting, nausea, rapid breathing and dehydration (10). She admitted to a high protein, carbohydrate-free diet. Laboratory evaluation revealed normal blood glucose, arterial pH of 7.07, serum bicarbonate ⬍5 mEq/L, and positive serum and urinary ketones screens. Treatment with intravenous fluids, low-dose insulin, and electrolyte replacement led to clinical resolution within 24 h. Our patient differs from the aforementioned cases by the breastfeeding of twin infants and the absence of severe
387
carbohydrate restriction or concomitant illness. We surmise that the metabolic demands of breast-feeding twin infants coupled with mild carbohydrate deficiency exaggerated an otherwise physiologic conservation mechanism to produce clinically significant ketoacidosis as described in dairy cattle. This case of lactation “bovine” ketoacidosis serves to increase our awareness of pathologic ketosis (Table 2) and underscores the importance of patient education and nutrition during pregnancy and lactation. Acknowledgment—This work was supported by National Institutes of Health training grant #5 T32 HL007820-09. The views expressed in this article are those of the author or authors and do not necessarily reflect the official policy or position of the Department of the Navy, Department of Defense, or United States Government.
REFERENCES 1. Oster JR, Epstein M. Acid-base aspects of Ketoacidosis. Am J Nephrol 1984;137–51. 2. Owen OE, Caprio S, Reichard GA, et al. Ketosis of starvation: a revisit and new perspectives. Clin Endocrinol Metab 1983;12:359 –79. 3. Toth HL, Greenbaum LA, Severe acidosis caused by starvation and stress. Am J Kidney Dis 2003;42:16 –9. 4. Miaskiewicz S, Levey GS, Owen O. Severe metabolic ketoacidosis induced by starvation and exercise. Am J Med Sci 1989;297:178 – 80. 5. Mahoney CA. Extreme gestational starvation ketoacidosis: case report and review of the pathophysiology. Am J Kidney Dis 1992;20:276 – 80. 6. Woodard CB. Pregnancy following bariatric surgery. J Perinat Neonat Nurs 2004;18:329 – 40. 7. Chernow B, Finton C, Rainey TG, O’Brian TG. “Bovine ketosis” in a nondiabetic postpartum woman. Diab Care 1982;5:47–9. 8. Holtenius P, Holtenius K. New aspects of ketone bodies in energy metabolism of dairy cows: a review. J Vet Med 1996;43:579 – 87. 9. Stinson O. So-called postparturient dyspepsia of bovines and its specific treatment. Vet Rec 1929;9:1115–9. 10. Altus P, Hickman JW. Severe spontaneous ‘bovine’ ketoacidosis in a lactating woman. J Indiana State Med Assoc 1983;76:392–3.