Full text of DOI:10.1093/ndt/gfg136

Nephrol Dial Transplant (2003) 18: 1406–1409
DOI: 10.1093/ndt/gfg136
Nephroquiz
(Section Editor: M. G. Zeier)
Supported by an educational grant from
Dialysis-resistant pulmonary oedema
irregular, and respirations 19umin. She had distended
neck veins, a loud first heart sound, gallop rhythm, and
grade 2 systolic ejection murmurs best heard over the
aortic area. Carotid and femoral pulses were strong,
but extremities were cold. Rales were present in the
right lung field. She had 2q pitting oedema on her
legs. There was a thrill over the arteriovenous fistula
on her left wrist. Her pulse rate remained rapid during
fistula occlusion by finger pressure (a negative
Branham’s sign).
A chest radiograph revealed an increase in heart size
when compared with a film taken 2 months earlier.
There were increased infiltrates over the right lung,
suggesting an inflammatory process or localized
oedema (Figure 1). ECG showed atrial fibrillation at
120umin with non-specific ST and T wave changes. Her
white blood cell count was 9100umm3 and haemoglobin
was 7.5 gudl. Her blood urea nitrogen was 77 mgudl,
creatinine 6.6 mgudl, albumin 2.2 gudl and plasma
Case
A 61-year-old woman with hypertension and kidney
failure due to type 2 diabetes mellitus presented with
fatigue, stinging pain in her legs, and nausea and
vomiting. A radial-cephalic arteriovenous fistula had
been created 6 weeks earlier, but she was unwilling to
initiate haemodialysis therapy. One week later, she was
admitted because of shortness of breath. She had fever
and symptoms of upper respiratory infection, but
denied having chest pain and use of alcohol. The
patient had a poor dietary intake, but had gained 3 kg
of body weight in the preceding month. She was taking
valsartan, labetalol, simvastatin and furosemide.
On physical examination, her blood pressure was
208u96 mmHg, temperature 38.78C, pulse 120umin and
Fig. 1. A chest radiograph shows cardiac enlargement and alveolar
infiltrates located predominantly in the right perihilar region.
Fig. 2. Persisted pulmonary oedema resistant to haemodialysis.
#
2003 European Renal Association–European Dialysis and Transplant Association

Dialysis-resistant pulmonary oedema
1407
glucose 154 mgudl. Her thyroid function test was moderate biatrial enlargement, mild pericardial effu-
normal. She was treated with empirical antibiotics, sion, and a hyperdynamic left ventricle. The estimated
diuretics, vasodilator, digitalis, diltiazem and packed pulmonary-artery systolic pressure was 65 mmHg.
RBC transfusions. Her rapid heart rate was controlled There were no segmental wall-motion abnormalities.
and her anaemia was corrected, but repeated chest Doppler sonography of the patient’s left wrist showed
radiograph revealed progressive haziness of bilateral
a patent arteriovenous fistula with a flow of
lungs. Microbiology studies were negative. Arterial 600 mlumin. She was placed on a bi-PAP ventilator
blood gas analysis showed pH 7.27, PaO2 67 mmHg, because her dyspnea became exacerbated.
PaCO2 31.5 mmHg and bicarbonate 14.6 mmolul.
Haemodialysis was started.
She lost 7 kg by aggressive ultrafiltration in 10 days.
Her skin turgor became poor, but dyspnea remained.
Pulmonary oedema persisted shown by a follow-up
Questions
chest radiograph (Figure 2). An echocardiogram . What is your diagnosis?
revealed concentric left ventricular hypertrophy, . What consequences of therapy should be expected
mild-to-moderate mitral and tricuspid regurgitation,
and treated?

1408
S.-C. Hung et al.
dialysate. Routine thiamine supplementation is there-
fore recommended in malnourished dialysis patients
[3]. High-output heart failure associated with thiamine
deficiency results from a decrease in systemic vascular
resistance and a compensatory increase of cardiac
output. The response to thiamine is often dramatic,
with an increase in systemic vascular resistance,
decrease in cardiac output, diuresis, and clearing of
pulmonary congestion in 48 h [4]. Nevertheless, in this
diabetic patient with a high probability of cardio-
vascular comorbidity due to her multiple risk factors,
the sudden return of vascular tone after thiamine
supplementation will pose a haemodynamic load to her
already diseased myocardium. Moreover, diuresis may
be only marginal because of her advanced kidney
failure. Thus, both increased afterload and preload
may unmask her coexistent cardiovascular diseases,
paradoxically leading to a low-output heart failure [5].
Accordingly, treatment with thiamine alone may
actually worsen her pulmonary oedema. Medical
therapy for congestive heart failure and further ultra-
filtration should be continued in addition to intrave-
nous thiamine 100 mg daily. Her dyspnea gradually
improved in 2 weeks. A follow-up chest radiograph
showed a complete resolution of pulmonary oedema
and return of heart size to normal (Figure 3).
Answers to the quiz on the preceding page
Congestive heart failure should be suspected in this
patient with ‘unusual’ pulmonary oedema refractory to
aggressive ultrafiltration. Many potential causes lead
to the development of congestive heart failure in
haemodialysis patients, and each cause is often multi-
factorial. Echocardiogram rules out left ventricular
systolic dysfunction due to valvular heart disease,
pericardial disease, ischaemic heart disease and cardio-
myopathy. Furthermore, her biventricular congestive
heart failure, an enlarged heart size, and worsening
symptoms with a reduction in her heart rate make
diastolic dysfunction seem unlikely. The patient has a
long history of hypertension, diabetes mellitus, dys-
lipidaemia and kidney failure. Intermittent ischaemia
associated with extensive coronary disease stays a
possibility, but should be carefully ruled out by
thallium stress test or cardiac catheterization if her
symptom persists in despite of appropriate therapy.
However, her characteristic physical findings of a
hyperdynamic circulation imply the cause of her
congestive heart failure is primarily high-output heart
failure [1].
The differential diagnosis of high-output heart
failure is shown in Table 1. Hyperthyroidism and over-
flow of arteriovenous fistula are excluded by labora-
tory and sonographic examinations. The failure of her
symptoms to be improved after correction of anaemia
suggests anaemia itself is a minor contributor rather
than the sole cause of her congestive heart failure.
Although the patient is not an alcoholic, she is at risk
of chronic thiamine deficiency due to restricted diet
and use of diuretics [2]. Her vomiting and fever at
presentation is likely to precipitate acute thiamine
depletion, which is further aggravated owing to
removal during aggressive dialysis. The presence of
peripheral neuritis (dry beriberi), as evidenced by her
stinging leg pain, also raised the possibility of wet
beriberi. The diagnosis of thiamine deficiency was
confirmed on the basis of a low serum thiamine level at
25 nmolul (normal 50–125 nmolul).
Conflict of interest statement. None declared.
Clinical manifestations of thiamine deficiency
include congestive heart failure, peripheral neuropathy
and encephalopathy, which may mimic many uraemic
complications and make the diagnosis easily missed in
patients with end-stage kidney failure. Thiamine is a
small molecular water-soluble vitamin with a low
affinity to plasma proteins and can be lost into the
Table 1. Differential diagnosis of high-output heart failure
1. Hyperthyroidism
2. Severe anaemia
3. Pregnancy
4. Arteriovenous fistulas
5. Thiamine deficiency (wet beriberi)
6. Paget’s disease
Fig. 3. Clearing of pulmonary oedema and return of heart size to
normal after thiamine administration.

Dialysis-resistant pulmonary oedema
1409
References
Szu-Chun Hung
Sze-Hung Hung
Wu-Chang Yang
1. Lurie JD, Sox HC. High on the differential. N Engl J Med 1997;
337: 1377–1381
2. 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: 485–490
3. Hung SC, Hung SH, Tarng DC, Yang WC, Chen TW,
Huang TP. Thiamine deficiency and unexplained encephalo-
pathy in hemodialysis and peritoneal dialysis patients. Am J
Kidney Dis 2001; 38: 941–947
4. Colucci WS, Price DT. Cardiac manifestations of systemic
diseases. In: Braunwald E, ed. Harrisons’s Principles of Internal
Medicine. McGraw-Hill, New York, NY: 2001; 1374–1376
5. Robin E, Goldschlager N. Persistence of low cardiac output after
relief of high output by thiamine in a case of alcoholic beriberi
and cardiomyopathy. Am Heart J 1970; 80: 103–108
Der-Cherng Tarng
Division of Nephrology
Department of Medicine
Taipei Veterans General Hospital and
National Yang-Ming University School of Medicine
Taiwan
Email: dctarng@vghtpe.gov.tw