Correspondence

Thiamine for the treatment of acute decompensated heart failure^B

To the Editor,

thiamine deficiency is very common in patients with heart failure [1]. Previous studies have suggested that thiamine supplementation may be an effective treatment of chronic heart failure [2,3]. It is not clear if it may also be effective in the acute setting. Two other conditions associated with thiamine deficiency, Wernicke’s encepha- lopathy and beriberi, have been known to improve within hours of thiamine supplementation [4,5].

We conducted a study that was approved by the investigational review board at Baystate Medical Center (Springfield, Mass). Consecutive emergency department (ED) patients were enrolled during times when Research staff were available. Adult patients with a primary diagnosis of acute decompensated heart failure were eligible if they had a history of heart failure and were currently on a loop diuretic. Acute decompensated heart failure was determined by the treating clinician based on worsening dyspnea within the past 24 hours, rales, and chest X-ray findings of vascular redistribution. Patients were excluded if (1) they were currently on thiamine supplementation, (2) had a diagnosis of renal failure being treated with dialysis, (3) had a history of pulmonary disease (ie, asthma, chronic obstructive pulmonary disease, or emphysema), or (4) had a concurrent ED diagnosis other than heart failure.

Patients were randomized to either the placebo or the thiamine group. Group allocation was stored in sequentially numbered opaque envelopes. The patients, health care providers, and research personnel were blinded to the group allocation.

Patients in the thiamine group received 100 mg thiamine intravenously within 30 minutes of arrival to the ED. Patients randomized to the placebo group received an equal volume of normal saline (1 mL). All other care was at the discretion of the treating clinician. In addition, at the time of enrollment, the treating attending physician was asked by the research staff if the patient would be admitted to the hospital if the dyspnea had sufficiently resolved within 4 hours regardless of the results of any diagnostic testing.

^B This study was presented at the SAEM 1999 (Boston, Mass).

The primary outcome measure was admission to the hospital. The decision to admit or discharge the patient was made by the treating attending physician 4 hours after enrollment. Our hospital does not have an observation unit. The secondary outcome measures were total in-hospital length of stay and change in dyspnea between enrollment and 4 hours postenrollment. Dyspnea was assessed by the research staff on a 6-point ordinal scale at time of arrival, enrollment, and 4 hours after enrollment.

Enrollment in this pilot study was limited to a total of 50 patients because of financial constraints. This sample size had a power of 80% to detect an absolute reduction in hospitalization of 35%. Data were analyzed using STATA software version 8 and Cytel Studio software (StatXact & LogXact) version 6 [6,7].

A total of 65 met entry criteria of which 50 gave consent. Complete data sets were available for 49 pa- tients. Baseline characteristics were similar for both groups with the possible exception for dyspnea score (Table 1). Primary and secondary outcome measures are listed in Table 2. None was statistically significant (Fisher exact test and Wilcoxon-Mann-Whitney 2-sample rank sum test).

On multivariable analysis using exact polytomous regression (adjacent category model), no statistical differ- ence was found for 4-hour change in dyspnea score controlling for dyspnea score on arrival and at enrollment

n	25	24
Age (y)	64 (54 -73)	68 (62-75)
Male sex (%)	64	71
Ethnicity/race (%)
Caucasian	64	67
African American	24	29
Hispanic	12	4
Systolic blood pressure	140 (100 -163)	138 (110 -152)
Serum
Sodium	137 (131-146)	140 (134 -149)
Creatinine	1.6 (1.4 -2.0)	1.7 (1.5-2.1)
Hemoglobin	11 (9-12)	10 (9-11)
Dyspnea score
On arrival	4 (2-5)	3 (1-5)
On enrollment	3 (2-5)	3 (1- 4)

0735-6757/$ - see front matter D 2007

Table 1 Baseline variables

Thiamine group

Control group

Data are presented as percentages or medians (interquartile range).

Correspondence 125

References

Table 2 Outcome measures

Thiamine

group

n 25

Hospitalized (%) 92

Control

group

24

96

P

N.99

Data are presented as percentages or medians (interquartile range).

In-hospital length of stay (d)	4 (2-5)	3 (1.5- 4)	.11
Dyspnea score 4 h after enrollment	2 (1-3)	2 (1-3)	.85
4-h Change in dyspnea score	1 (1-2)	1 (0 -1)	.09

( P = .052). In addition, no statistical difference was found for duration of hospitalization controlling for dyspnea score on arrival ( P = .721) using exact regression. All models controlled for dyspnea score at time of enrollment.

At time of enrollment, when asked if the patient would be admitted even if the dyspnea had sufficiently resolved within 4 hours regardless of diagnostic testing results, the treating clinician answered byesQ for 88% of the patients.

Thiamine deficiency has been shown to occur in about 40% of patients with heart failure [1-3,8-15]. Inhibition of the pyruvate dehydrogenase complex is the presumed mechanism by which thiamine deficiency exacerbates heart failure [16]. Inhibition of pyruvate dehydrogenase complex has been postulated to decrease the efficiency of adenosine triphosphate production, increase cellular acidosis, and increase free fatty acid levels [16-21].

Animal models have demonstrated that thiamine defi- ciency causes cardiac hypertrophy, depressed cardiac contractility, and dysrhythmias in the absence of beriberi [16,22-32]. Three prospective human studies with chronic congestive heart failure treated with thiamine yielded conflicting results, but all had significant methodological flaws [2,3,10].

Our pilot study had several limitations: (1) the primary outcome measure is prone to significant confounding issues; (2) the sample size was small; (3) we did not measure thiamine levels; (4) and the groups were not balanced on dyspnea score on arrival to the ED, suggesting that the thiamine group had more severe heart failure.

We did not detect a significant change in rate of hospitalization, 4-hour change in dyspnea, or length of hospitalization as a result of thiamine supplementation. However, thiamine supplementation appeared to cause a trend for improvement in 4-hour change in dyspnea when baseline dyspnea score was controlled for. For most patients with acute decompensated heart failure, the decision to admit was not based on the severity of dyspnea at time of admission.

Howard A. Smithline MD

Department of Emergency Medicine

Baystate Medical Center Tufts University School of Medicine

Springfield, MA, USA

doi: 10.1016/j.ajem.2006.05.008

1. Hanninen SA, Darling PB, Sole MJ, Barr A, Keith ME. The prevalence of thiamin deficiency in hospitalized patients with congestive heart failure. J Am Coll Cardiol 2006;47(2):354 - 61.
2. Seligmann H, Halkin H, Rauchfleisch S, et al. Thiamine deficiency in patients with congestive heart failure receiving long-term furosemide therapy: a pilot study. Am J Med 1991;91:151 - 5.
3. Shimon I, Almog S, Vered Z, et al. Improved left ventricular function after thiamine supplementation in patients with congestive heart failure receiving long-term furosemide therapy. Am J Med 1995; 98:485 - 90.
4. Brust J. Nutritional disorders of the nervous system. In: Goldman L, Bennett J, editors. Cecil textbook of medicine. 21st ed. W. B. Saunders; 2000.
5. Diltoer MW, Troubleyn J, Lauwers R, et al. Ketosis and cardiac failure: common signs of a single condition. Eur J Emerg Med 2004; 11(3):172 - 5.
6. Stata statistical software [computer program]. Version 8. College Station (TX)7 Stata Corporation; 2003.
7. Cytel studio statistical software [computer program]. Version 6. Cambridge (MA)7 CYTEL Corporation; 2004.
8. Zenuk C, Healey J, Donnelly J, Vaillancourt R, Almalki Y, Smith S. Thiamine deficiency in congestive heart failure patients receiving long term furosemide therapy. Can J Clin Pharmacol 2003;10(4):184 - 8.
9. Brady J, Rock C, Horneffer M. Thiamin status, diuretic medications, and the management of congestive heart failure. J Am Diet Assoc 1995;95:541 - 4.
10. Pfitzenmeyer P, Guilland JC, d’Athis P, Petit-Marnier C, Gaudet M. Thiamine status of elderly patients with cardiac failure including the effects of supplementation. Int J Vitam Nutr Res 1994;64(2):113 - 8.
11. Kwok T, Falconer-Smith J, Potter J, Ives D. Thiamine status of elderly patients with cardiac failure. Age Ageing 1992;21:67 - 71.
12. Hardig L, Daae C, Dellborg M, Kontny F, Bohmer T. Reduced thiamine phosphate, but not thiamine diphosphate, in erythrocytes in elderly patients with congestive heart failure treated with furosemide. J Intern Med 2000;247:597 - 600.
13. Pepersack T, Garbusinski J, Robberecht J, Beyer I, Willems D, Fuss

M. Clinical relevance of thiamine status amongst hospitalized elderly patients. Gerontology 1999;45:96 - 101.

1. O’Keeffe ST, Tormey WP, Glasgow R, Lavan JN. Thiamine deficiency in hospitalized elderly patients. Gerontology 1994;40(1): 18 - 24.
2. Levy W, Soine L, Huth M, Fishbein D. Thiamine deficiency in congestive heart failure. Am J Med 1992;93:705 - 6.
3. Sutherland DJ, Jaussi AW, Gubler CJ. The effects of thiamine deprivation, and oxythiamine- and pyrithiamine-treatment on cardiac function and metabolism in the rat. J Nutr Sci Vitaminol (Tokyo) 1974;20(1):35 - 54.
4. Singleton C, Martin P. Molecular mechanisms of thiamine utilization. Curr Mol Med 2001;1:197 - 207.
5. Haas R. Thiamin and the brain. Annu Rev Nur 1988;8:483 - 515.
6. Rathanaswami P, Pourany A, Sundaresan R. Effects of thiamine deficiency on the secretion of insulin and the metabolism of glucose in isolated rat pancreatic islets. Biochem Int 1991;25(3):577 - 83.
7. Rathanaswami P, Sundaresan R. Effects of thiamine deficiency on the biosynthesis of insulin in rats. Biochem Int 1991;24(6):1057 - 62.
8. Iwata H. Catecholamine metabolism in thiamine-deficient rats. J Nutr Sci Vitaminol (Tokyo) 1976;22(Suppl):25 - 7.
9. Boullin DJ. Pharmacological responses of thiamine-deficient rat tissues. Br J Pharmacol Chemother 1963;20:190 - 203.
10. Gubler CJ. Enzyme studies in thiamine deficiency. Int Z Vitamin- forsch 1968;38(3):287 - 303.
11. Yamashita S. Relationship between thiamine deficient cardiac lesions and myocardial and blood pyruvic acid contents. Jpn Heart J 1971; 12(5):474 - 85.

126 Correspondence

1. Yamashita S. Effect of alcohol on thiamine deficient cardiac lesions. Jpn Heart J 1971;12(4):354 - 67.
2. Yoshitoshi Y, Shibata N, Yamashita S. Experimental studies on the beriberi heart. I. Cardiac lesions in thiamine deficient rats. Jpn Heart J 1961;2:42.
3. Aldinger EE. Effect of thiamine deficiency on potential myocardial contractility. Circ Res 1965;16:238 - 43.
4. Hirota Y, Kane R, Abelmann W. Cardiovascular effects of exercise in hamsters with experimental thiamine deficiency. Jpn Circ J 1979; 43:99.
5. Cohen EM, Abelmann WH, Messer JV, Bing HL. Mechanical properties of rat cardiac muscle during experimental thiamine deficiency. Am J Physiol 1976;231(5 Pt 1):1390 - 4.
6. Cappelli V, Bottinelli R, Polla B, Reggiani C. Altered contractile properties of rat cardiac muscle during experimental thiamine deficiency and food deprivation. J Mol Cell Cardiol 1990;22(10): 1095 - 106.
7. Rindi G, Rapuzzi G. The action potential of cardiac ventricular fibre cells during thiamine deficiency. Q J Exp Physiol Cogn Med Sci 1966;51(4):249 - 55.
8. Davies MJ, Jennings RB. The ultrastructure of the myocardium in the thiamine-deficient rat. J Pathol 1970;102(2):87 - 95.

Early diagnosis of gas-forming pyometra in an aged patient can prevent mortality

To the Editor,

Pyometra is an uncommon disease, referring to the accumulation of pus in the uterine cavity [1]. It often occurs in Postmenopausal women and is associated with gyneco- logical malignancy [2]. Preoperative accurate diagnosis of pyometra is difficult, and mostly, pyometra is found until peritonitis develops [3]. We report a case with fever and lower abdominal pain, diagnosed as pyometra by ultraso- nography (US) preoperatively and treated properly without morbidity and mortality.

A 79-year-old woman visited the emergency depart- ment (ED) because of intermittent fever for 2 weeks. She

Fig. 1 Ultrasonography showed intrauterine fluid accumulation with gas component (arrow).

Fig. 2 abdominal CT scan without Contrast enhancement demonstrates an air-fluid level in the uterine cavity (arrow). Calcified spots were noted within the myometrium. Notice the distended rectosigmoid colon with stool impaction.

also complained of lower abdominal discomfort and nausea. She had been admitted to a local hospital, and urinary tract infection was impressed. However, her symptoms persisted after 5-day antibiotic therapy, and her conscious- ness became drowsy gradually. She was transferred to our hospital for further management. Her history only included diabetes mellitus under oral hypoglycemic agents.

On arrival, her consciousness was clear. Her vital signs were as follow: body temperature, 38.68C; heart rate, 96 beats per minute; respiratory rate, 20 breath per minute; and blood pressure, 116/78 mm Hg. The abdomen was soft, but mild tenderness without rebounding pain was noted over lower abdomen. Others were unremarkable. Plain abdominal radiograph showed nonspecific dilatation of small bowels and an intrauterine device (IUD) in Pelvic cavity. Laboratory results disclosed an elevated white blood cell count (37920/mm³) with left shift and an elevated C-reactive protein level of 28.43 mg/dL. Urinalysis disclosed pyuria (white blood cell N100/high- power field). Artery blood gas analysis showed metabolic acidosis. (pH 7.39, Pco₂, 24.9 mm Hg; HCO₃, 14.6 mEq/L; base excess, -9 mEq/L). Cefmetazole was prescribed.

She was referred for abdominal US for her lower abdominal pain. The US revealed intrauterine turbid fluid accumulation with gas component (Fig. 1). Gas-forming pyometra was diagnosed. Computed tomography (CT) confirmed a distended uterus with air-fluid level inside (Fig. 2), and IUD was displaced. A gynecologist was consulted, and profuse yellowish discharge was found through the cervix during pelvic examination. Cervical dilatation and curettage were performed, and IUD was removed. Blood, urine, and pus cultures all yielded Pseudomonas aeruginosa. Antibiotics with ceftazidime was prescribed, and she was discharged later and followed up at an outpatient clinic uneventfully.