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CASE REPORT
Year : 2020  |  Volume : 6  |  Issue : 1  |  Page : 60-62

Anaphylactic shock with intravenous furosemide: a rare undesired effect


1 Department of Anaesthesia, Maulana Azad Medical College, New Delhi, India
2 PGIMS, Rohtak, Haryana, India

Date of Submission17-Feb-2020
Date of Decision04-Mar-2020
Date of Acceptance17-Mar-2020
Date of Web Publication30-Apr-2020

Correspondence Address:
Dr. Manisha Manohar
PGIMS Rohtak, Haryana-124001
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/mamcjms.mamcjms_13_20

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  Abstract 


Furosemide is a potent diuretic, with structural similarity to sulphonamide antibiotics. Its relative safety profile is one of the reasons to account for its widespread use. We report a rare case of fatal anaphylaxis with intravenous furosemide administered in our critical care settings for pulmonary edema. Chemical similarity of furosemide with sulphonamide antibiotics shares the possibility of similar allergic side effects. Thus, a more careful clinical use of furosemide, especially if administered intravenous should be kept in mind to avoid such catastrophic events.

Keywords: Anaphylaxis, fatal outcome, furosemide, sulphonamides


How to cite this article:
Gahlot D, Talukdar R, Seth V, Manohar M. Anaphylactic shock with intravenous furosemide: a rare undesired effect. MAMC J Med Sci 2020;6:60-2

How to cite this URL:
Gahlot D, Talukdar R, Seth V, Manohar M. Anaphylactic shock with intravenous furosemide: a rare undesired effect. MAMC J Med Sci [serial online] 2020 [cited 2020 Aug 3];6:60-2. Available from: http://www.mamcjms.in/text.asp?2020/6/1/60/283501



Key Messages: Furosemide should be administered with more vigilance than the usual current practices and preferably after a prior test dose especially in patients with prior history of positive allergic reaction to sulphonamides.


  Introduction Top


Furosemide is a potent and commonly used loop diuretic, structurally related to thiazide diuretics and sulphonamide antibiotics. It is a sulpha drug with chemical formulation of 4-chioro-N-furfuryl-5-sulphamoylanthranilic acid [Figure 1] and [Figure 2].[1]
Figure 1 Sulphonamide nucleus

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Figure 2 Furosemide chemical structure

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Only few case reports with mild allergic reactions to the drug have been reported in the literature.[1],[2] Machtey has reported two patients suffering from sudden death within one minute of single intramuscular dose of furosemide, but reason being anaphylaxis to the drug is not clear as both patients had severe congestive heart failure with high risk of underlying life-threatening events.[3] Severe anaphylaxis with angioedema due to injection of furosemide has not been reported in the literature till date. We report a rare case of severe anaphylaxis with intravenous furosemide.


  Case History Top


A 40-year-old male patient with uncontrolled diabetes presented to the emergency department with history of respiratory distress and altered sensorium for past few hours. On examination, patient was disoriented with RR = 35–40 per min, BP = 90/60 mm hg, PR = 130–140/min and SPO2 = 90%–91%, RBS = 350 mg%. On auscultation of chest, bilateral crepitations were present. Kidney function test was deranged (blood urea = 110 mg/dl and creatinine = 2.5 mg/dl) with decreased urine output.

A provisional diagnosis of diabetes with acute kidney injury and lower respiratory tract infection with respiratory failure was made. Patient was intubated in the emergency department in view of respiratory failure and transferred to The Intensive Care Unit (ICU) for further management. Although, patient’s vitals improved, tachycardia persisted with nil urine output. An intravenous dose of 10 mg furosemide was administered in view of decreased urine output. During hospital stay, patient’s clinical condition and biochemical investigations improved. On eight ICU day, patient developed pink frothy sputum with bilateral crepitations and decreased urine output. A diagnosis of pulmonary edema was made, and patient was administered furosemide 40 mg intravenously. Within few minutes of furosemide administration patient developed severe airway edema, chest edema, facial edema with severe bronchospasm followed by cardiovascular collapse. A diagnosis of anaphylaxis to injection furosemide was made and Injection adrenaline 1 mg intravenous in 10 ml saline was administered along with injection hydrocortisone 200 mg, injection dexamethasone 8mg and injection pheniramine maleate 20 mg, however, there was no improvement in patient’s clinical condition. Patient was administered 100% oxygen. The bronchospasm was so severe that patient could not be ventilated adequately and became hemodynamically unstable. Cardiopulmonary resuscitation (CPR) was started soon with repeated doses of intravenous adrenaline. Unfortunately, patient could not be revived after 30–40 min of CPR.


  Discussion Top


Furosemide is a potent diuretic agent that inhibits reabsorption of sodium and chloride in the medullary portions of ascending limb of loop of Henle. It is a very commonly used drug in critical care settings indicated for mobilization of edema fluid, treatment of raised intracranial pressure, hypercalcemia treatment and differential diagnosis of acute oliguria.[4]

Commonly known side effects of furosemide are hypotension, electrolyte imbalance and metabolic alkalosis. Some of the rare side effects of the drug are bone marrow suppression, immune thrombocytopenia, acute pancreatitis, dermatologic abnormalities, and interstitial nephritis.[1]

Chemically, furosemide contains a sulphonamide nucleus. Thus, theoretically cross sensitivity of this drug may occur in patients with sulphonamide allergies. However, limited case reports question its practical application. Hence administration of furosemide test dose or intradermal skin testing is not a part of routine protocol. Strom et al.[5] have reported in a retrospective cohort study an association between hypersensitivity after the receipt of sulphonamide antibiotics and a subsequent allergic reaction after the receipt of a sulphonamide nonantibiotic drugs, however they reported this association to be due to a predisposition to allergic reactions rather than to cross-reactivity with sulphonamide based drugs. On the other hand, Wang et al have reported only mild allergic reaction to furosemide in patients undergoing nuclear renograms with sulphonamide allergies.[6]

Anaphylaxis is a type 1 hypersensitivity reaction (Ig E mediated) with four grades as per the severity. Grade 1 is mild reaction with cutaneous symptoms, grade 2 is moderate reaction with tachycardia, hypertension and mild dyspnoea, grade 3 is severe reaction with hypotension, laryngeal edema and bronchospasm, grade 4 is anaphylactic shock with respiratory and cardiac arrest.[7] The present patient had cardiovascular collapse with difficult ventilation immediately after administration of furosemide injection indicating a grade 4 anaphylactic reaction to intravenous furosemide. In the present case, patient had no elicited history of any drug allergy, lack of prior exposure to sulphonamide drugs can be one explanation to this. The patient received first low dose of furosemide on 1st day of hospital admission which acted as a sensitizing dose, administration of second larger dose resulted in severe anaphylactic reaction to the drug. A larger dose of furosemide and intravenous route of administration possibly resulted in fatal reaction to the drug. The diagnosis of anaphylaxis to furosemide in the present case is based on clinical signs and symptoms, we could not perform a subcutaneous test dose. Although, a reliable biomarker to confirm the diagnosis is not available, Ig E antibodies may have supplemented the diagnosis.[2]

Furosemide is one of the commonly used drugs in operating room settings in surgeries with major fluid shifts and in ICU settings. Its relative safety profile is one of the reasons to account for its widespread use. Apart from few mild allergic reactions reported in the literature, severe anaphylaxis resulting in fatal outcome that occurred in our case is very rare. However, chemical similarity of furosemide with sulphonamide antibiotics and the possibility of sharing the similar side effects cannot be ignored1. Therefore, a more careful clinical use of furosemide especially if administered intravenous should be kept in mind and prior test dose should be used in patients with positive history to sulphonamide allergy for an improved patient outcome. We report this rare side effect of intravenous furosemide to prevent any similar catastrophic but preventable outcome from use of a relatively common drug. Other examples of non-antibiotics containing sulphonamide nucleus are Acetazolamide, dapsone, thiazides, metolazone, indapamide, sulfonylureas, and probenecid. Therefore, they all pose theoretical risk of similar allergic reactions and need to be administered cautiously. A more detailed knowledge of chemical structure of drugs being used routinely can help intensivists and anaesthesiologists to be on the higher safeguard and avoid rare but similar fatal outcomes. Therefore, we should use intravenous preparations of drugs with sulphonamide nucleus such as furosemide more cautiously and preferably after a prior test dose for a safer patient outcome.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Hansbrough JR, Wedner H. Anaphylaxis to intravenous furosemide. J Allergy Clin Immunol 1987;80:538-41.  Back to cited text no. 1
    
2.
Domínguez-Ortega J, Martínez-Alonso JC. Anaphylaxis to oral furosemide. Allergologia et Immunopathologia 2003;31:345-7.  Back to cited text no. 2
    
3.
Machtey I. Sudden death after intramuscular furosemide. Lancet 1968;2:1301.  Back to cited text no. 3
    
4.
Stoelting RK. Pharmacology and physiology in anesthetic practice. 4th edition. Netherlands: Wolters Kluwer; 2005. 488-90.  Back to cited text no. 4
    
5.
Strom BL. Absence of cross-reactivity between sulfonamide antibiotics and sulfonamide nonantibiotics. N Engl J Med 2003; 349:17.  Back to cited text no. 5
    
6.
Wang Y. Safety of administering furosemide during nuclear diuretic renography in patients with sulfonamide allergies. AJR 2018;210:866-8.  Back to cited text no. 6
    
7.
Ring J, Beyer K, Biedermann T, Bircher A, Duda D, Fischer J et al. Guideline for acute therapy and management of anaphylaxis. S2 guideline of DGAKI, AeDA, GPA, DAAU, BVKJ, ÖGAI, SGAI, DGAI, DGP, DGPM, AGATE and DAAB. Allergo J Int 2014;23:96-112.  Back to cited text no. 7
    


    Figures

  [Figure 1], [Figure 2]



 

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