D-Lactic acidosis 25 years after bariatric surgery due to Salmonella enteritidis

Nutrition 28 (2012) 108–111

Contents lists available at ScienceDirect

Nutrition journal homepage: www.nutritionjrnl.com

International ward rounds

D-Lactic acidosis 25 years after bariatric surgery due to Salmonella enteritidis Antonietta Gigante M.D. a, *, Liborio Sardo M.D. a, Maria Ludovica Gasperini M.D. a, Antonio Molinaro M.D. b, Oliviero Riggio M.D. (Professor) b, Alessandro Laviano (Professor) a, Antonio Amoroso M.D. (Professor) a a b

Department of Clinical Medicine, “Sapienza” University of Rome, Rome, Italy Division of Gastroenterology, “Sapienza” University of Rome, Rome, Italy

a r t i c l e i n f o

a b s t r a c t

Article history: Received 5 July 2011 Accepted 5 July 2011

D-lactic acidosis is a rare complication that occurs in patients with short bowel syndrome due to surgical intestine resection for treatment of obesity. The clinical presentation is characterized by neurologic symptoms and high anion gap metabolic acidosis. The incidence of this syndrome is unknown, probably because of misdiagnosis and sometimes symptoms may be incorrectly attributed to other causes. Therapy is based on low carbohydrate diet, sodium bicarbonate intravenous, rehydratation, antiobiotics, and probiotics that only produce L-lactate. In the case we describe, D-lactic acidosis encephalopathy occurred 25 y after bypass jejunoileal, due to Salmonella enteriditis infection. Ó 2012 Elsevier Inc. All rights reserved.

Keywords: D-lactic acidosis Short-bowel syndrome Bypass jejuno-ileal Bariatric surgery Encephalopathy

Introduction D-lactic acidosis (DLA) is an uncommon neurologic syndrome that occurs in patients with jejunoileal bypass, small bowel resections, and other forms of short bowel syndrome. The clinical manifestations of DLA are episodes of encephalopathy and metabolic acidosis with an increased anion gap. Most of the cases described in the literature have occurred within a few months to 10 y after surgical resection of the bowel, especially after ingestion of high-grade carbohydrates. We present a case of DLA that occurred 25 y after bypass jejunoileal caused by Salmonella enteritidis, which was able to change intestinal mucosa, raising load D-lactate-producing bacteria. The important decrease in urine and plasma D-lactate levels and clinical resolution after antibiotic therapy suggest that selective bacterial overgrowth by Salmonella was the determining factor in the development of the recurrent syndrome. Case report A 51-y-old Caucasian woman was admitted to the emergency department in an acute confusional state characterized by disorientation, weakness, nausea, dehydration, blurred vision, and slurred speech, appearing drunk. Her medical history was significant * Corresponding author. Tel./Fax: 0039.0649972074. E-mail address: [email protected] (A. Gigante). 0899-9007/$ - see front matter Ó 2012 Elsevier Inc. All rights reserved. doi:10.1016/j.nut.2011.07.005

for a jejunoileal bypass procedure in 1985 for obesity with residual intestinal absorption of 80-90 cm; 9 y later, she was hospitalized for neurologic syndrome, probably due to bacterial overgrowth. Since then, she had begun therapy with rifaximine, 2 weeks every month, until hospitalization. The patient has been free of symptoms and any complications related to short bowel syndrome for 15 years. On admission, her temperature was 37.6 C, blood pressure 120/80 mmHg, pulse 79 bpm. Physical examination was negative except for mild and diffuse abdominal pain with no organomegaly or ascites. Arterial blood gas analysis showed normocloremic metabolic acidosis with increased anion gap; laboratory tests are summarized in Table 1. No drugs, alcohols, lactate, ketones, or salicylates were detected in her blood. Neurologic testing, including computed tomography, was unrevealing. Thus, the treatment with intravenous administration of 150 mEq sodium bicarbonate was started and acid-base imbalance was normalized with improvement of neurologic symptoms within a few hours. The patient was transferred to our department of internal medicine to evaluate the etiology of metabolic acidosis and neurologic symptoms. Because of her previous bypass jejunoileal, DLA was suspected, and we proposed a carbohydrate load that the patient refused. Three days later, after a meal, the patient showed the same neurologic disturbances and physical weakness as presented on admission. During this acute episode, arterial blood gas analysis showed high anion gap normocloremic metabolic acidosis, and sera and urine were collected to measure the level of D-lactic acid (colorimetric assay kit, EnzyChrom D-Lactate Assay Kit; BioAssay

A. Gigante et al. / Nutrition 28 (2012) 108–111

109

Table 1 Summary of daily serum and urine chemistries Laboratory data

Sodium (mmol/L) Potassium (mmol/L) Chloride (mmol/L) BUN (mg/dL) Creatinine (mg/dL) Glucose (mg/dL) Ammonium Urine ketones Bicarbonate (mmol/L) Anion gap (mmol/L) Plasma L-lactate (mmol/L) Plasma D-lactate (mmol/L) Urine D-lactate (mmol/L) pH Pco2 (mmHg) Po2 (mmHg) BE (B) (mmol/L)

Second episode

Third episode

Day 1

First episode Day 2

Day 1

Day 2

Day 1

Day2

Day 1

Day 5

Day 30

140 4.6 104 29 1.4 90 31 Negative 10 26 0.6 d d 7.17 28 103 17

141 4.2 106 28 1.2 88 32 Negative 16 19 1.3 d d 7.43 24 93 6

143 3.5 105 21 1.5 94 28 Negative 11 27 1.1 27.2 38.5 7.28 25 123 13

141 3.1 104 22 1.1 85 d Negative 23.8 12 0.8 26.6 7.45 7.44 35 94 0

142 3.6 105 26 1.2 77 d Negative 16.8 20 0.7 27 23 7.33 31 91 8.5

140 3.7 103 32 1 102 d Negative 23.7 13 0.9 24 5.45 7.43 35 94 0.7

142 4.1 104 30 1.4 96 d Negative 22.8 15 1.1 9.51 1.06 7.41 36 92 1.2

138 3.8 106 28 1.2 81 d Negative 21.4 11 0.7 4.2 1.04 7.42 33 99 2.5

140 4.2 105 31 1.3 75 d Negative 23 12 1.1 2.9 1.01 7.4 37 98 1.5

Systems, Hayward, CA, USA) (Fig.1, Table 1). The levels of serum and urinary D-lactic acid were high at 27.2 and 32.4 mmol/L, respectively (normal range, 0-3 mmol/L). Treatment was started with intravenous administration of sodium bicarbonate and, over the next 12 h, the patient gradually recovered from neurologic impairment and the acid-base imbalance was normalized (Table 1). After this second episode, we decided to reduce carbohydrate intake. A surgical consultant suggested bypassing the conversion, which the patient refused. However, 2 d later, the patient presented a third episode of metabolic acidosis with confusion, slurred speech, anxiety, and weakness, appearing drunk. Sera and urine collected of D-lactic acid levels were high (Fig. 1). Because of increased numbers of evacuations from three to seven daily, a rise in temperature to 38.5 C, and diffuse abdominal pain, stool cultures were performed showing positivity for S. enteritidis responsive to ciprofloxacin. Therefore, the patient started ciprofloxacin 500 mg twice daily for a week. She also received medical nutrition therapy planning with 1485 Kcal in divided meals with 49.5% carbohydrates, 22.6% proteins, and 27.9% fats. Over the next 7 d, no episodes of encephalopathy or metabolic acidosis occurred; stool cultures, Widal reaction, D-lactic acid in serum and urine were negative, and the patient was discharged with antibiotics and

Fig. 1. Correlation between serum and urine D-lactate and blood pH.

Start treatment

probiotics (rifaximine and Lactobacillus GG). No more attacks happened in 6 mo of follow-up. Discussion DLA is an uncommon and often misdiagnosed neurologic syndrome that occurs in patients with jejunoileal bypass, small bowel resections, and other forms of short bowel syndrome. The clinical manifestations of DLA are episodes of encephalopathy and metabolic acidosis with an increased anion gap. Headache, weakness, delirium, visual disturbances, slurred speech, ataxia, cranial nerve palsies, and aggressive and abusive behavior are hallmarks of DLA encephalopathy, with the patients often appearing drunk [1]. The incidence of DLA is unknown, probably due to misdiagnosis; sometimes symptoms may be incorrectly attributed to other causes. DLA is well documented in veterinary medicine; however, encephalopathy after jejunoileal bypass was first described in humans by De Wind in1976 and, to date, there are approximately 40 cases reported in literature [2]. DLA can occur within a few months to 10 y after surgical resection of bowel and most cases occur after ingestion of high-grade carbohydrates [3]. However, Narula et al. reported an unusual case that occurred 23 y after jejunoileal bypass [2]. The diagnosis was performed on the basis of neurologic manifestations and high level of D-lactate. No universal reference values for Dlactate are available and normally are undetectable, but usually, when the measured concentration results in an excess of 3 mmol/L, it contributes to the acidosis [4]. Blood gas analysis reveals a metabolic acidosis usually with an increased anion gap [1]; L- and D-lactate are found at low concentrations in the stool of healthy subjects as a result of conversion of both isomers of lactate to short-chain fatty acid by the intestinal bacteria. The development of DLA is promoted by an alteration of the normal intestinal flora [5], often secondary to surgical procedures. In these patients, malabsorption in the proximal bowel causes a large amount of carbohydrate available to colonic bacteria. Subsequently, carbohydrates are fermented, producing lactic acid and short-chain fatty acids able to reduce the luminal pH of the colon favoring overgrowth of lactate-generating bacteria (Land D-lactate). Progressive increase of lactic-acid-producing bacteria and further decrease of pH promote growth and survival of gram-positive organisms producing D-lactate,

110

A. Gigante et al. / Nutrition 28 (2012) 108–111

predominantly Lactobacillus acidophilus and fermenti, Streptococcus bovis, Clostridium perfrigens, Eubacterium, and Bifidobacterium [1,6]. D-lactate is absorbed by the intestinal epithelial cells, resulting in its plasma accumulation [2]. It is well known that lactate dehydrogenase can effectively metabolize only L-lactate, while D-lactate is only slowly metabolized [7] through D-2-hydroxy acid dehydrogenase (D-2-HDH). This enzyme is present in the kidney cortex and liver that often are damaged in patients with short bowel syndrome, lowering D-2-HDH concentration. Moreover, transient renal injury due to dehydration could impair urinary excretion of D-lactate episodically [1]. Regarding neurologic symptoms, is possible that D-lactate itself is toxic to the brain, causing altered intraneuronal pH that interferes with ATP. Other possible causes are the production of false neurotransmitters (mercaptans, aldehydes, alcohols, and amines), especially in the cerebellum, altered brain oxygen consumption, and the absence of D-2-HDH [2,4,8]. Deficiencies of thiamin might further contribute to the onset of D-lactate encephalopathy, interfering with pyruvate metabolism by inhibiting activity of pyruvate dehydrogenase. Increased pyruvate may then inhibit D-2-HDH and lactic acid dehydrogenase, resulting in an accumulation of D-lactate and L-lactate [9]. Oh et al. observed that normal subjects are able to metabolize D-lactate at a rate of 1.5 mmol/kg/h when intravenously infused with DL-lactate at a rate of 1.92 mmol/kg/h [10]. We reported an unusual case of D-lactic encephalopathy that occurred 25 y after jejunoileal bypass. Usually DLA occurs from several months to years after development of bowel surgery because a prolonged period of time is necessary to generate intestinal flora with D-lactate-producing bacteria [11]. Through the years, these patients received different antibiotics and probiotics, contributing to increased Lactobacillus population, and D-lactate production exceeded the renal excretory capacity [6]. It has been reported that trimethoprim-sulfamethoxazole and doxycycline antibiotic therapy promote selective survival of D-lactate-producing bacteria and subsequently accumulation at the concentrations observed in the DLA syndrome [6]. On the other hand, although D-lactate-producing bacteria is typically sensitive to vancomycin, metronidazole, and tetracycline, DLA has been unexpectedly observed after administration of these antibiotics [12]. Our patient received rifaximine, because the first episode of encephalopathy until admission ensured long-term protective effects. Even if probiotics may be useful in promoting recolonization of nonpathogenic flora in patients with short bowel syndrome, the literature has reported two cases of DLA with lactobacillus tablets therapy [1,13]. Additional exogenous sources as propylene glycol, lactated Ringer’s, and peritoneal dialysis solutions contribute to D-lactate accumulation, adding to the amount produced by colonic bacteria [14]. Treatment of DLA consists of reducing the amount of substrates for bowel fermentation by restricting enteral intake of carbohydrates or fasting, correction of metabolic acidosis with bicarbonate, rehydration to improve renal excretion of D-lactate, and non-absorbable antibiotics to modified intestinal flora, reducing D-lactate-producing bacteria. A diet containing less than 10% of normal carbohydrates intake [8] limits substrate for bacterial production of D-lactate and antibiotic therapy, promoting an intestinal flora by bacteria not producing D-lactate. Antibiotics most active against acid-resistant bacteria are clindamycin, tetracycline, metronidazole, neomycin, vancomycin, and kanamycin. Although there are no clear guidelines regarding duration of therapy because of the small number of patients reported in the literature, antibiotic therapy is necessary for long-term prevention of recurrences [1,15]. Finally, Uchida et al. reported

that probiotics in a patient added to kanamicin to recolonizate intestine with non-pathogenic floras to prevent DLA considered probiotics in the long-term treatment [15]. However, because bile acid-deconjugating activity in both lactobacilli and probiotic yeast is not known, the final recommendation is not yet possible [16]. Fermented carbohydrate restriction with more frequent smaller meals is important in the management of DLA to avoid D-lactate-producing bacteria and not favor D-lactate encephalopathy [1]. During hospitalization, our patient presented fever and increased daily evacuations; stool cultures were performed showing positivity for S. enteritidis. Salmonellae are facultative anaerobic gram-negative bacilli with the highest incidence during the summer. Several factors, related both to the pathogen and to the host influence, are important in the development of Salmonella infection including antimicrobial therapy [17–19]. In fact, prolonged use of antibiotics can reduce the infectious dose necessary to cause disease by diminishing the normally protective resident flora [18]. Furthermore, in patients submitted to gastrointestinal surgery, the infectious dose is lower to developing typhoid or non-typhoid fever [18]. Salmonella infection in our patient was encouraged in both these factors and reduced bile salts concentration due to jejunoileal bypass [20]. In the course of this infection, degradation and release of toxic substances by neutrophils cause damage of the intestinal mucosa [18]. Changes in intestinal mucosa and reduced pH due to carbohydrate fermentation by Salmonella are able to raise the load of D-lactate-producing bacteria. In our clinical case, we gave the patient rifaximine in an attempt to eradicate D-lactate-producing Lactobacilli and lactobacillus GG to recolonize the bowel with flora that do not produce D-lactic acid. In fact, Lactobacillus casei, subspecies rhamnosus (lactobacillus GG), produces only L-lactate [15]. Conclusion In conclusion, in patients with DLA, we suggest a management based on limiting dietary carbohydrate intake, less than 10% of daily requirement, alternating antibiotic and probiotics that only produce L-lactate. Moreover, carbohydrates should be avoided during the last evening feeding because of the highest concentration of serum D-lactate level. We also recommend stool examinations in patients with fever and increased daily evacuations, especially if it occurs many years after gastrointestinal resection. In the case we reported, the decrease in urine and plasma D-lactate levels and the absence of symptoms after antibiotics therapy suggest that selective bacterial overgrowth by Salmonella has been the determining factor in the development of the recurrence syndrome. After antibiotic therapy for intestinal infection and 9 mo follow-up, the patient is still symptom-free. References [1] Petersen C. D-lactic acidosis. Nutr Clin Pract 2005;20:634–45. [2] Narula RK, El Shafei A, Ramaiah D, Schmitz PG. D-lactic acidosis 23 years after jejuno-ileal bypass. Am J Kidney Dis 2000;36:E9. [3] Thurn JR, Pierpont GL, Ludvigsen CW, Eckfeldt JH. D-lactate encephalopathy. Am J Med 1985;79:717–21. [4] Zhang DL, Jiang ZW, Jiang J, Cao B, Li JS. D-lactic acidosis secondary to short bowel syndrome. Postgrad Med J 2003;79:110–2. [5] Halperin ML, Kamel KS. D-lactic acidosis: turning sugar into acids in the gastrointestinal tract. Kidney Int 1996;49:1–8. [6] Coronado BE, Opal SM, Yoburn DC. Antibiotic-induced D-lactic acidosis. Ann Intern Med 1995;122:839–42. [7] Luft F. Lactic acidosis update for critical care clinicians. J Am Soc Nephrol 2001;12:S15–9. [8] Kamar M, Raziel A, Susmallian S, Kyzer S, Charuzi I. D-lactic acidosis in a patient after subtotal colectomy. Isr Med Assoc J 2003;5:891–2.

A. Gigante et al. / Nutrition 28 (2012) 108–111 [9] Vella A, Farrugia G. D-lactic acidosis: pathologic consequence of saprophytism. Mayo Clin Proc 1998;73:451–6. [10] Oh MS, Uribarri J, Alveranga D, Lazar I, Bazilinski N, Carroll HJ. Metabolic utilization and renal handling of D-lactate in men. Metabolism 1985; 34:621–5. [11] Bongaerts GP, Tolboom JJ, Naber AH, Sperl WJ, Severijnen RS, Bakkeren JA, et al. Role of bacteria in the pathogenesis of short bowel syndromeassociated D-lactic acidemia. Microb Pathol 1997;22:285–93. [12] Gavazzi C, Stacchiotti S, Cavalletti R, Lodi R. Confusion after antibiotics. Lancet 2001;357:1410. [13] Munakata S, Arakawa C, Kohira R, Fujita Y, Fuchigami T, Mugishima H. A case of D-lactic acid encephalopathy associated with use of probiotics. Brain Dev 2010;32:691–4. [14] Jorens PG, Demey HE, Schepens PJ, Coucke V, Verpooten GA, Couttenye MM, et al. Unusual D-lactic acid acidosis from propylene glycol metabolism in overdose. J Toxicol Clin Toxicol 2004;42:163–9.

111

[15] Uchida H, Yamamoto H, Kisaki Y, Fujino J, Ishimaru Y, Ikeda H. D-lactic acidosis in short-bowel syndrome managed with antibiotics and probiotics. J Pediatr Surg 2004;39:634–6. [16] Bongaerts G, Severijnen R, Skladal D, Bakkeren J, Sperl W. Yeast mediates lactic acidosis suppression after antibiotic cocktail treatment in short small bowel? Scand J Gastroenterol 2005;40:1246–50. [17] Mentzing LO, Ringertz O. Salmonella infection in tourists. Prophylaxis against salmonellosis. Acta Pathol Microbiol Scand 1968;74:405–13. [18] Kasper DL, et al. Harrison’s Principles of Internal Medicine. 16th ed. McGraw-Hill, New York. [19] Que JU, Casey SW, Hentges DJ. Factors responsible for increased susceptibility of mice to intestinal colonization after treatment with streptomycin. Infect Immun 1986;53:116–23. [20] Selsted ME, Miller SI, Henschen AH, Ouellette AJ. Enteric defensins: antibiotic peptide components of intestinal host defense. J Cell Biol 1992; 118:929–36.