Acute Non-cardiogenic Pulmonary Edema Associated with the Radiographic Contrast Medium Ioversol

Acute Non-cardiogenic Pulmonary Edema Associated with the Radiographic Contrast Medium Ioversol

Contrast medium induced pulmonary edema
CASE REPORT
Acute Non-cardiogenic Pulmonary Edema Associated with the
Radiographic Contrast Medium Ioversol
1
1
1
2
Honda Hsu , Chih-Ming Lin , Chung-Yen Tsai , Shau-Bin Chou , Tzong-Bor Sun
1
1,3
2
Division of Plastic Surgery and Center for Hyperbaric Oxygen Therapy , Department of Radiology , Buddhist Tzu Chi General
Hospital, Hualien, Taiwan; Institute of Medical Sciences3, Tzu Chi University, Hualien, Taiwan
ABSTRACT
Ioversol is an iodinated, low-osmolality, nonionic contrast agent used in angiography. Life threatening non-cardiogenic pulmonary
edema after intravenous administration of radiographic contrast medium is a rare event. We could find no report of ioversol-related
pulmonary edema. We present a case of 65-year-old woman with diabetes mellitus and peripheral arterial occlusive disease who
underwent angiography for evaluation of both lower limbs. Cold sweating, dyspnea, and lost of consciousness were noticed soon
after 125 mL of ioversol injection. She was intubated immediately and chest radiograph showed severe pulmonary edema. After
intensive mechanical ventilatory support, she recovered and was extubated 72 hours after the anaphylactic episode. Reports in the
English literatures show that severe, life-threatening, adverse effects associated with radiographic contrast medium are rare. Our
presenting case may be the first associated with the specific radiocontrast ioversol. Prompt differential diagnosis, aggressive ventilatory support, and avoid dehydration are essential to prevent a fatal outcome. (Tzu Chi Med J 2005; 17:273-277)
Key words: contrast medium, pulmonary edema, ioversol, angiography, adverse effect
INTRODUCTION
Angiography is a common routine investigation in
the diagnosis of peripheral arterial occlusive disease
(PAOD). Most common adverse reactions include
nausea, palpitations and heat sensation. Severe reactions
such as dyspnea, hypotension and cardiac arrest are reported in 0.04% of all cases [1]. Life threatening noncardiogenic pulmonary edema after intravenous administration of radiographic contrast is a rare event. We
present a 65-year-old diabetic woman who presented
with a painful gangrene in the right foot for several
months. She sustained acute pulmonary edema during
the angiography for evaluation of both lower limbs. The
initial symptoms/signs, resuscitation procedures, and
physiological responses were collected and analyzed.
Our experience in managing this rare case provides information for future management of this idiosyncratic
life threatening situation.
CASE REPORT
A 65-year-old woman presented with right foot pain
for several months. She had visited many clinics, but
only intravenous analgesics were administered. Recently
necrotic skin changes were noticed over the medial and
lateral malleolar area. She was referred from a local clinic
for further treatment. She reported persistent continuous leg pain, which was partially relieved by dangling
her legs over the side of the bed. There was no history
of claudication as she was wheelchair bound due to left
Received: October 19, 2004, Revised: November 10, 2004, Accepted: November 26, 2004
Address reprint requests and correspondence to: Dr. Tzong-Bor Sun, Division of Plastic Surgery and Center for Hyperbaric
Oxygen Therapy, Buddhist Tzu Chi General Hospital, 707, Section 3, Chung Yang Road, Hualien, Taiwan
Tzu Chi Med J 2005 17 No. 4
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H. Hsu, C. M. Lin, C. Y. Tsai, et al
hemiparesis from a cerebral vascular accident 15 years
previously. She also had a history of diabetes mellitus
and hypertension with irregular medical treatment. She
had no known allergies. Physical examination showed
necrotic skin changes over the medial and lateral malleolar area measuring 7 cm × 8 cm and 5 cm × 5 cm
respectively. Pulse was absent in both legs, and the femoral pulses were also very difficult to palpate. A diagnosis of diabetic foot and peripheral arterial occlusive disease was made. Routine chest radiograph on admission
was normal (Fig. 1A). The electrocardiogram on admission demonstrated possible left ventricular hypertrophy
by voltage criteria and ST-T depression which suggested
possible chronic myocardial ischemia. The patient recalled several episodes of palpitation and chest tightness.
Laboratory data revealed white blood cells 10100/µL,
hemoglobin 6.8 g/dL, platelets 532000/µL, erythrocyte
sedimentation rate (ESR) 70 mm/hr, blood urea nitrogen (BUN) 15 mg/dL, creatinine 1.4 mg/dL, glutamic
oxaloacetic transaminase (GOT) 15 IU/L, and glutamic
pyruvic transaminase (GPT) 6 IU/L.
Angiography was done to evaluate the circulatory
status of both lower limbs. In the Department of
Radiology, 125 mL of ioversol (Optiray 320, Mallinckrodt Pharmaceuticals, St. Louis, MO, USA), an
iodinated, low osmolality, non-ionic contrast medium,
was injected intra-arterially. While the angiography was
being performed, the patient complained of sudden
dizziness, nausea and chillness. Cold sweating and lost
of consciousness was noticed. Oxygen saturation was
80% on 10 L/min of oxygen by face mask. She was intubated immediately. After intubation, profuse pink,
foamy sputum was secreted from the endotracheal tube.
A chest radiograph was taken and she was then transferred to the surgical intensive care unit (SICU)
immediately. Her blood pressure was 130-150/70-90
mmHg and did not decrease throughout the period of
emergent management while she was in the radiological department.
Chest radiograph showed interstitial changes with
acinar shadows in both lung fields (Fig. 1B). An electrocardiogram showed sinus tachycardia with ischemic
changes in the inferolateral area, although there was no
chest pain. Arterial blood gases after intubation on 100%
oxygen were pH 7.322, pCO2 42.5 mmHg, pO2 485
mmHg, HCO3 22.3 mmol/L, BE -3.1 mmol/L. Total creatine kinase (CK 451 IU/L) and MB isoform (CK-MB
17 IU/L), as well as troponin I (0.04 ng/dL) suggested a
low possibility of acute myocardial infarction. Her central venous pressure was 1 mmHg. She was placed on
mechanical ventilation with positive end expiratory pressure (PEEP). Fluid replacement was given, as well as
OTQ
coricosteroids (Solucortef 200 mg initially, and then 100
mg/day). Blood pressure was maintained at 130-150/7090 mmHg without infusion of inotropic agents. The cardiologists were consulted. Cardiac echography revealed
a left ventricle ejection fraction of 50%, moderate mitral valve incompetence and normal wall motion. The
skin turgor was dry with continuous clear urine output
from the indwelling Foley catheter. In considering the
underling myocardial ischemia from the routine ECG, a
dopamine infusion 3 µg/kg/hr was given alone with fluid
resuscitation. After mechanical ventilation with PEEP
and fluid replacement, she gradually improved over the
next 72 hours as confirmed by serial chest radiographs
(Fig. 1C, D). Serial daily input/output amounts recorded
from the first day were 2213/2345, 3165/1635, and 3886/
3155 mL. Serum BUN and creatinine levels on the third
day were 16 mg/dL and 1.5 mg/dL respectively.
Angiograms of the legs showed diffuse segmental obstruction of the femoral artery with formation of collateral vessels.
DISCUSSION
We presented a patient with PAOD and underlining
myocardial ischemia who developed pulmonary edema
after injection of ioversol for lower limb angiography.
The key to successful management of this challenging
situation was to decide whether the pulmonary edema
was cardiogenic or non-cardiogenic, because these two
conditions had different principles of treatment, in regard to fluid restriction or supplement. Thinking
retrospectively, the etiology of pulmonary edema for this
case was not likely to be cardiogenic for the following
reasons. First, a central venous pressure measurement
of 1 mmHg suggested there was no right side heart
failure. Second, the systemic blood pressure remained
in the normal range without the aid of inotropic agents,
so the possibility of left side heart failure was low. Third,
the serum cardiac enzyme studies did not suggest acute
myocardial infarction. Fourth, more than 1000 mL of
crystalloid or colloid solution was infused every 8 hours
over the first 3 days after the episode. Together with
mechanical ventilatory support, this fluid resuscitation
resolved the pulmonary edema despite cardiac size enlargement and the central venous pressure increased from
1 to 8 mmHg. Fortunately, the patient survived after
proper treatment following initial recognition of ioversol
induced non-cardiogenic pulmonary edema.
Non-ionic radiographic contrasts are used worldwide. Ioversol, N,N'-Bis (2,3-Dihydroxypropyl)-5-[N(2-Hydroxyethyl)-Glycolamido]-2,4,6-Triiodoisoph-
Tzu Chi Med J 2005 17 No. 4
Contrast medium induced pulmonary edema
A
B
C
D
Fig. 1. Serial changes of the chest radiograph. (A) Chest radiograph of the patient on admission displays normal lung fields. (B)
Chest radiograph immediately after angiography shows a butterflypattern, characterized by the central predominance
of shadows with a clear zone at the peripheral lobes. (C) Chest radiograph shows improved lung fields after assisted
mechanical ventilatory support for 24 hours. (D) Chest radiograph shows clear lung fields after assisted mechanical ventilatory support for 48 hours.
Tzu Chi Med J 2005 17 No. 4
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H. Hsu, C. M. Lin, C. Y. Tsai, et al
thalamide (molecular weight = 807.13), is an iodinated,
low-osmolality, nonionic contrast agent, with an elimination half-life of 2 hours. It distributes rapidly throughout extracellular fluid following injection. There is no
significant deposit in tissue. It does not cross the bloodbrain barrier, but accumulates within interstitial tissues
of malignant tumors. Ioversol reaches a peak serum concentration immediately and the concentration falls rapidly within 5 to 10 minutes. It is excreted unchanged in
the urine [2]. Adverse effects have been described as
minimal. The most frequent adverse effect seen is nausea in less then 1% of patients [1]. It is particularly useful for painful examinations such as peripheral
angiography, for patients with hemodynamic instability
or for patients with limited cardiac reserve [3].
Adverse effects that have been described with
ioversol include transient bradycardia in 1 patient [3],
angina in 1 patient [4], and transient prolonged QT intervals and small increases in the left ventricular end
diastolic pressure in patients undergoing left ventriculography [5]. Isolated dizziness, lightheadedness, vertigo and disorientation have also been observed. Headache associated with Ioversol has been reported in 0.5%
of patients [6]. Nausea is the most common adverse
effect, occurring in 0.8% of patients [3, 6]. Ioversol can
also cause a slight elevation in the serum creatinine, but
clinically significant changes in renal function have not
been detected. There are also sporadic reports of blurred
vision, hypoxia, pruritus and urticaria [6].
Pulmonary edema as a result of ioversol administration is a rare event. Two types of pulmonary edema
are described: cardiogenic and non-cardiogenic. In the
non-cardiogenic type there is a rise in microvascular permeability with fluid lost from the circulation. This leads
to alveolar edema. The pathogenesis of contrast-induced,
non-cardiogenic pulmonary edema is unclear. Edema
could be caused by mediator release and complement
activation resulting in endothelial damage or as the result of a direct irritant effect of the drug on the lungs [1].
Treatment of contrast medium related non-cardiogenic pulmonary edema is different from that of the cardiogenic type. Administration of furosemide and vasodilators may lead to fatal deterioration as described in previous case reports. Treatment as anaphylaxis is also not
beneficial. Primary emergent treatment such as maintenance of the airway and ventilation with positive end
expiratory pressure together with fluid resuscitation to
increase the left ventricular preload is important [1].
The pathophysiology of radiographic contrast medium induced pulmonary edema is still unknown. Sendo
et al demonstrated that contrast medium in high doses
produces pulmonary edema by inhibiting endothelial
OTS
nitric oxide (NO) production, and nitrovasodilators protect against this adverse effect in rats [7]. Based on the
experimental findings in rats, Hayshi et al suggested that
the adverse phenomenon is induced by non-osmolality
related toxicity of the contrast medium [8]. Carbazochrome sodium sulfonate (AC-17), a capillary stabilizer,
was used to block radiographic contrast medium-induced
pulmonary dysfunction by maintaining the endothelial
barrier function in a rodent model [9]. The tryptase liberated from mast cells may also play a crucial role in the
contrast medium-induced pulmonary dysfunction in rats
[10].
Severe non-cardiogenic pulmonary edema as a result of ioversol injection is a rare event. Recent randomized, double-blind clinical trials have reported no cases
of this disorder [11]. We found only 20 reports of noncardiogenic pulmonary edema associated with radiographic contrast [1,12-19] and none of these cases involved ioversol. Our presenting case maybe the first noncardiogenic pulmonary edema associated with ioversol.
In conclusion, this case serves to remind us that although
severe life-threatening adverse effects associated with
radiographic contrast medium are rare, we still should
remain vigilant. Non-cardiogenic pulmonary edema associated with radiographic contrast is life-threatening
or fatal if not treated correctly. Prompt adequate management is essential if the patient’s life is to be saved.
REFERENCES
1. Paul RE, George G: Fatal non-cardiogenic pulmonary
oedema after intravenous non-ionic radiographic
contrast. Lancet 2002; 359:1037-1038.
2. Sirken G, Raja R, Garces J, Bloom E: Contrast-induced
translocational hyponatremia and hyperkalemia in advanced kidney disease. Am J Kidney Dis 2004; 43:e31e35.
3. Grassi CJ, Bettmann MA, Finkelstein J, Reagan K:
Ioversol. Double-blind study of a new low osmolar contrast agent for peripheral and visceral arteriography.
Invest Radiol 1989; 24:133-137.
4. Hirshfeld JW Jr, Wieland J, Davis CA, et al: Hemodynamic and electrocardiographic effects of ioversol during cardiac angiography. Comparison with iopamidol and
diatrizoate. Invest Radiol 1989; 24:138-144.
5. Reagan K, Bettman MA, Finkelstein J, Ganz P, Grassi
CJ: Double-blind study of a new nonionic contrast agent
for cardiac angiography. Radiology 1988; 167:409-413.
6. Benamor M, Aten EM, McElvany KD, et al: Ioversol clinical safety summary. Invest Radiol 1989; 24(Suppl 1):
S67-S72.
7. Sendo T, Kataoka Y, Takeda Y, Furuta W, Oishi R: Nitric oxide protects against contrast media-increased pulmonary vascular permeability in rats. Invest Radiol 2000;
35:472-478.
Tzu Chi Med J 2005 17 No. 4
Contrast medium induced pulmonary edema
8. Hayashi H, Kumazaki T, Asano G: Pulmonary edema
induced by intravenous administration of contrast media:
Experimental study in rats. Radiat Med 1994; 12:47-52.
9. Sendo T, Goromaru T, Aki K, Sakai N, Itoh Y, Oishi R:
Carbazochrome attenuates pulmonary dysfunction induced by a radiographic contrast medium in rats. Eur J
Pharmacol 2002; 450:203-208.
10. Sendo T, Itoh Y, Goromaru T, et al: A potent tryptase
inhibitor nafamostat mesilate dramatically suppressed
pulmonary dysfunction induced in rats by a radiographic
contrast medium. Br J Pharmacol 2003; 138:959-967.
11. Floriani I, Ciceri M, Torri V, Tinazzi A, Jahn H, Noseda
A: Clinical profile of ioversol. A metaanalysis of 57
randomized, double-blind clinical trials. Invest Radiol
1996; 31:479-491.
12. Tajima T, Honda H, Kuroiwa T, et al: Pulmonary complications after hepatic artery chemoembolization or infusion via the inferior phrenic artery for primary liver
cancer. J Vasc Interv Radiol 2002; 13:893-900.
13. Bristedt P, Tylen U: Pulmonary edema following intravenous injection of nonionic low-osmolar contrast medium--appearance on HRCT. A case report. Acta Radiol
1998; 39:81-83.
Tzu Chi Med J 2005 17 No. 4
14. Delacour JL, Floriot C, Wagschal G, Daoudal P, Chambers R, Xuan PB: Non-cardiac pulmonary edema following intravenous contrast injection. Intensive Care
Med 1988; 15:49-50.
15. Goldsmith SR, Steinberg P: Noncardiogenic pulmonary
edema induced by nonionic low-osmolality radiographic
contrast media. J Allergy Clin Immunol 1995; 96:698699.
16. Hauggaard A: Non-cardiogenic pulmonary oedema after intravenous administration of non-ionic contrast
media. Acta Radiol 1996; 37:823-825.
17. Kussmaul WG 3rd, Mishra JP, Matthai WH, Hirshfeld
JW Jr: Complications of cardiac angiography using lowor high-osmolality contrast agents in patients with left
main coronary stenosis. Cathet Cardiovasc Diagn 1997;
42:376-379.
18. Miller SH: Anaphylactoid reaction after oral administration of diatrizoate meglumine and diatrizoate sodium
solution. Am J Roentgenol 1997; 168:959-961.
19. Ramesh S, Reisman RE: Noncardiogenic pulmonary
edema due to radiocontrast media. Ann Allergy Asthma
Immunol 1995; 75:308-310.
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