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 Table of Contents  
Year : 2015  |  Volume : 3  |  Issue : 1  |  Page : 106-109

A rare case of ceftriaxone induced anaphylaxis in anaethesia practice

1 Department of Anaesthesiology and Intensive Care, Sri Guru Ramdas Medical College and Hospital, Amritsar, Punjab, India
2 Department of Anaesthesiology and Intensive Care, Gian Sagar Medical College and Hospital, Banur, Punjab, India

Date of Web Publication13-Apr-2015

Correspondence Address:
Dr. Sukhminder Jit Singh Bajwa
Department of Anaesthesiology and Intensive Care, Gian Sagar Medical College and Hospital, Ram Nagar, Banur - 147 001, Punjab
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/2321-4848.154958

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Medications are among the second most common cause of anaphylaxis and the primary cause of anaphylaxis in adults. The most common classes of drugs causing anaphylaxis are antibiotics especially β-lactam antibiotics and nonsteroidal anti-inflammatory drugs (NSAIDs). Diagnosis of anaphylaxis is clinically based and usually straight forward. However data on epidemiology of anaphylaxis, particularly the most profound and life threatening form such as anaphylactic shock is limited and thought to be under-reported. In spite of negative skin testing, our patient had severe reaction resulting in anaphylactic shock after antibiotic administration but was managed successfully without any residual compromise. This case reflects the limitations of screening test done preoperatively for the diagnosis of sensitization to the drugs.

Keywords: Anaphylactic shock, eftriaxone, hypersensitivity

How to cite this article:
Kumari A, Gupta R, Bajwa SS, Jagdeep. A rare case of ceftriaxone induced anaphylaxis in anaethesia practice. Arch Med Health Sci 2015;3:106-9

How to cite this URL:
Kumari A, Gupta R, Bajwa SS, Jagdeep. A rare case of ceftriaxone induced anaphylaxis in anaethesia practice. Arch Med Health Sci [serial online] 2015 [cited 2023 Feb 6];3:106-9. Available from: https://www.amhsjournal.org/text.asp?2015/3/1/106/154958

  Introduction Top

Ceftriaxone is a third generation cephalosporin antibiotic commonly used to treat infections. Incidence of ceftriaxone related hypersensitivity reaction is between 1-3% whereas incidence of anaphylaxis is rare. [1] Sign and symptoms of anaphylaxis are variable and can range from mild skin lesion to fatal reaction. It affects different organs and its most severe form results in anaphylaxis. Such patients may pose real challenges to the anesthesiologists. We report a case of antibiotic induced severe anaphylaxis resulting in anaphylactic shock in spite of negative intradermal skin testing to ceftriaxone.

  Case Report Top

A 22-years-old ASA-I male, was scheduled for correction of interlocking tibia under spinal anesthesia. Patient had no history of allergies or previous exposure to anesthesia. His preoperative blood biochemistry, chest X-ray and electrocardiogram (ECG) were normal. Patient was tested for sensitivity to ceftriaxone one day prior to surgery by intradermal skin testing which showed negative results. Patient was kept fasted overnight and premedicated with tablet alprazolam 0.5 mg night before and 1 hour prior to surgery. In the operation theatre intravenous (IV) line was secured with 18 guage (G) cannula. Intra-operative monitoring included ECG, blood pressure (BP), heart rate (HR) and oxygen saturation (SpO 2 ). Under all aseptic precautions subarachnoid block was performed at L 3 -L 4 intervertebral space with 25G Quineke's needle. Bupivacaine 0.5% (hyperbaric) 3 cc was injected after confirming clear and free flow of cerebrospinal fluid (CSF). Sensory block was checked and found to be at T 10 dermatomal level. His vitals were HR-88/min, BP-130/80 mmHg, and SpO 2 -98% on room air. After 10 minutes of spinal anesthesia, ceftriaxone 1 g was started slowly as IV infusion, prior to start of surgery. After 2-3 minutes patient started complaining of bitterness in taste, itching in the ears, face and limbs, tightness in throat, nausea, and vomiting. Pulse became feeble and BP dropped to 60/33 mmHg. An anaphylactic reaction was suspected. Antibiotic infusion was stopped immediately and 100% O 2 was given with Bain's circuit and injection Of adrenaline 0.5mg (1:10000) was administered IV. Injection phenaramine maleate 45.5 mg and hydrocortisone 200 mg were given. IV fluids were given as boluses. Injection atropine 0.6 mg and ephedrine 6 mg were also administered to rectify the symptomatology but BP and pulse became unrecordable and patient became unconscious. Immediately patient was intubated and ventilated with 100% O 2 . Adrenaline 0.5mg (1:10000) was repeated IV. HR increased to 190/min on the monitor with regular sinus rhythm. Spontaneous breathing returned but BP was still unrecordable and peripheral pulses were not palpable. Dopamine and nor-adrenaline infusions were started at the rate of 10 μg/kg/min. Patient had copious secretions and fine crepitations could be heard bilaterally on chest auscultation. Frothy fluid started coming through endotracheal tube (ETT) and mouth which was highly suggestive of pulmonary edema. Patient was sedated with butorphanol 2 mg and inj. midazolam 2 mg IV injection and was kept on assisted ventilation with 100% O 2. Resuscitation efforts with pharmacological interventions, breathing and circulation optimization continued and the patient showed two consecutive reading of blood pressure greater than 86 mmHg systolic during this period. Patient was catheterized and furosemide 20 mg injection was given in titrated doses. Patient had gradual return of spontaneous breathing with good tidal volume (TV), started moving limbs along with eye opening. Patient had bilateral vesicular breathing with no added sounds. Intraoperatively electrolytes, arterial blood gas (ABG) and chest X-ray (CXR) were normal while ECG showed sinus tachycardia. Resuscitation efforts continued till BP became 100/64 mmHg with ionotropic support, HR 176/min and SpO 2 99%. Peripheral pulses appeared with good volume and urine output was adequate. So we decided to give a trial of extubation. After extubation, patient was obeying commands, maintaining vitals as BP-120/70 mmHg, PR-146/min and SpO 2 -100% on venturi mask. Chest and cardiovascular findings were within normal limits. Methylprednisolone 125 mg injection was given slow through IV route and advised to be continued 6 hourly for next 3 days. Patient was shifted to intensive care unit (ICU) for further monitoring and discharged uneventfully after 72 hours.

  Discussion Top

Anaphylaxis is an acute life threatening reaction usually but not always mediated by immunologic mechanisms that result from sudden systemic release of mediators from mast cells and basophils. Other mediator cascade (eg. clotting and complement factor) including non mast cell-derived mediators, responsible for many symptoms occurring in anaphylactic reaction are also recruited. [2],[3] Common offenders are antimicrobials, NSAIDs, anesthetic agents, radio-contrast dyes, nutrients, and hymenoptera or latex. [4] Anaphylaxis has varied clinical presentation but cardiovascular and respiratory compromise are of greatest concern since they being the most frequent cause of fatalities. Urticaria and angiodema are most common manifestations but may be delayed or absent especially in rapidly progressive anaphylaxis. The more rapid the anaphylaxis occurs, the more likely the reaction is to be severe and potentially life threatening. [3]

Both genetic and environmental factors are involved in determining which individual in large random population will develop an allergic reaction to a given drug. Various risk factors involved are: presence of atopy, age (less frequently in children and elderly because of immaturity and involution of immune system respectively), concurrent medical diseases [Asthma, Epstein Barr Virus (EBV), HIV], previous history of drug exposure and multiple drug allergy syndromes. Genes implicated in IgE mediated allergy are E.237.G variant of FCeR16 (high affinity IgEreceptor β chain) gene, IL-4RaQ576R polymorphism, interleukin-4 (IL-4), IL-13-small nuclear polymorphism (SNP). An immediate allergic reaction to β-lactam is mediated by IL-13 (R1.30 Q and 1055C > T variants), IL-4RA (150V, 5478P, and Q551R variants). [5]

Anaphylaxis often produces signs and symptoms within minutes to an offending stimulus but some reactions may develop later (> 30 mins after exposure). Biphasic reactions which occur 1-72 hours after the initial attack have also been reported. [6] Vaso-vagal reaction is the condition most commonly confused with anaphylactic reaction.Characteristic features of this reaction include hypotension, pallor, weakness, nausea, vomiting, and diaphoresis which can be distinguished from anaphylaxis by lack of cutaneous manifestations (urticaria, angiodema, flush, and pruritis) and presence of bradycardia instead of tachycardia.So the possibility of this being the cause in this case is unlikely. Flushing episodes can also occur with several drugs and ingestants including niacin, nicotine, catecholamines, angiotensin-converting-enzyme (ACE) inhibitors and alcohol. Other conditions to consider in differential diagnosis are vocal cord dysfunction, acute anxiety, myocardial dysfunction, local anesthetic toxicity, pulmonary embolism, foreign body aspiration, acute poisoning, hypoglycemia, and seizure disorder. [3]

Increased vascular permeability is a characteristic feature of anaphylaxis, so IV fluids and epinephrine are the mainstay of management. The initial drug of choice is intramuscular (IM)/subcutaneous (SC) epinephrine [7] but since our patient had cardiovascular collapse, epinephrine injection was administered intravenously in a dose of 0.3-0.5 mg (3-5 ml of epinephrine 1:10000). Dopamine and nor-adrenaline can be administered at 2-20 μg/kg/min in refractory cases of hypotension. [3] Our patient also had refractory hypotension and responded well to inotropic support.

Glucocorticoids reduce the risk of biphasic anaphylaxis. [6] Newer markers like serial serum tryptase, is evaluated as soon as possible. Mast cell degranulation leads to markedly increased blood tryptase level which can be useful for investigation of suspected cases. Tryptase concentration in blood may not increase significantly until 30 mins or more, and peak levels occurred in 1-2 hrs after the onset of symptoms for anaphylaxis and persist up to 6 hrs. [8] Ideally serum sample should be obtained between 1-2 hrs after initiation of symptoms and 6-24 hrs later. Other markers such as serum carboxypeptidase, histamine, and their metabolites have also been evaluated to enhance the diagnostic accuracy. [3]

The diagnosis of anaphylactic drug reaction is based on clinical presentation and history of recent exposure to an offending agent. Although intradermal skin testing is highly sensitive,rapid and inexpensive but it is associated with higher false positives. [9] The test can be altered by previous ingestion of anti histaminics, steroids, β-blockers and coexisting skin disease such as eczema. Also, patency of antigen extracts needs to be maintained and rarely systemic reaction may occur. Common errors while performing intradermal skin testing which can lead to false positive and negative results are: [5]

  1. If intradermal skin testing performed without control, it make the interpretation of results more difficult,
  2. The volume of injected test dose can be varied,
  3. Both tests sites are too close together (<2 cm apart),
  4. High concentration used,
  5. if there is no bleb formation while injecting the drug,
  6. Intracutaneous bleeding sometimes misinterpreted as positive result.
The detection of specific immunoglobulin (Ig) antibodies in serum, although less sensitive than skin testing, in-vitro immunoglobulin E measurements (RAST), correlate well with the result of skin testing and clinical picture. Although these tests eliminate the need for multiple skin pricks but are more expensive and results take longer to obtain. [9] Thus, it is not possible to predict these types of reactions on the basis of history and skin testing as both false positive and negative results may occur because of faulty technique and material. Unfortunately there are not adequate skin tests for demonstrating IgE mediated potential to most drugs. Therefore, in most instances, the diagnosis of drug hypersensitivity is based on history or challenge.

Intraoperative antibiotic administration is only effective when given within 1 hr prior to skin incision. [10] Therefore we recommend that antibiotic should be given in the preoperative room or on the operation theatre (OT) table at least 30 mins before induction of anesthesia rather than its simultaneous administration with anesthetic agents to distinguish it from other entities causing anaphylaxis. Moreover we should give 1 ml of the drug initially IV as a test dose and rest of antibiotic can be given as slow IV infusion.

To conclude, prompt recognition and appropriate aggressive treatment are essential for the successful management of anaphylaxis. Constant observation and follow up of such patients is mandatory as biphasic anaphylaxis may occur after resolution of initial phase. It is strongly recommended that consultation with an allergist/immunologist be obtained. Following treatment for any episode of acute anaphylaxis, the clinician should consider an analysis of the event and the possible precipitating cause particularly with respect to those steps that could be done to prevent future episodes. Prevention of anaphylaxis is aided by the patients having medic alert identification.

  References Top

Saritas A, Erbas M, Goven I, Candar N, Ozturk O, Kandis H, et al. Asystole after the first dose of ceftriaxone. Am J Emerg Med 2012;30:1321.e3-4.  Back to cited text no. 1
Helbling A, Hurni T, Muller UR, Pichler WJ. Incidence of anaphylaxis with circulatory symptoms: A study over 3 year period comprising 940,000 inhabitants of the swisscantorn Bern. Clin Exp Allergy 2004;34:285-90.  Back to cited text no. 2
Liberman P, Nicklas RA, Oppenheimer J, Kemp SF, Lang DM, Bernstein DI, et al. The diagnosis and Management of anaphylactic practice parameter: 2010 update. J Allergy Clin Immunol 2010;126:477-80.e1-42.  Back to cited text no. 3
Kemp SF, Lockey RF. Anaphylaxis: A review of causes and mechanism. J Allergy Clin Immunol 2002;110:341-8.  Back to cited text no. 4
Thong BY, Tan TC. Epidemology and risk factors for drug allergy. Br J Clin Pharmacol 2011;71:684-700.  Back to cited text no. 5
Liberman P. Biphasic anaphylactic reactions. Ann Allergy Asthma Immunol 2005;95:217-26.  Back to cited text no. 6
Brown SG, Blackman KE, Stenlake V, Heddle RJ. Insect sting anaphylaxis; Prospective evaluation of treatment with intravenous adrenaline and volume resuscitation. Emerg Med J 2004;21:149-54.  Back to cited text no. 7
Simons FE, Frew AJ, Ansoteguil IJ, Bochner BS, Golden DB, Finkelman FD, et al. Risk assessment in anaphylaxis: Current and future approaches. J Allergy Clin Immunol 2007;120(1 Suppl):S2-24.  Back to cited text no. 8
Bhagwat AG, Saxena KN. Intraoperative anaphylaxis to inj. Ceftriaxona: Here we go again. Indian J Anaesth 2008;52:462.  Back to cited text no. 9
Mangram AJ, Horan TC, Pearson ML, Silver LC, Jarvis WR. Guideline for prevention of surgical site infection, 1999. Hospital Infection Control Practices Advisory Committee. Infect Control Hosp Epidemiol 1999;20:250-78.  Back to cited text no. 10

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