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A Case of Two Adverse Reactions L-A Smith, M Harkness

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A Case of Two Adverse Reactions L-A Smith, M Harkness 484 Postgrad Med J: first published as 10.1136/pgmj.2003.017020 on 5 August 2004. Downloaded from ADVERSE DRUG REACTION A case of two adverse reactions L-A Smith, M Harkness ............................................................................................................................... Postgrad Med J 2004;80:484–486. doi: 10.1136/pgmj.2003.017020 developed a bradycardia and hypotension despite the nitrate Low molecular weight heparins are now widely prescribed in infusion having been stopped. He was prescribed 1 ml of the treatment of thromboembolic disease and acute coronary 1:1000 adrenaline, given subcutaneously. The administration syndromes. Anaphylaxis is a recognised but rare potentially of adrenaline had rapid clinical effect and haemodynamic life threatening side effect of heparin. stability was regained. The angioedema had fully resolved Common clinical features of anaphylaxis are cardiovas- within two hours from onset. cular collapse, bronchospasm, cutaneous symptoms, angioe- After resolution of the angioedema, the patient developed dema, generalised oedema, or gastrointestinal symptoms. It severe chest pain, requiring large doses of intravenous is extremely rare, however, for patients to experience such nitrates and diamorphine. His ECG showed more marked dramatic and potentially life threatening consequences as widespread ST depression (fig 2). Electrocardiographic seen in the case reported here. It has been shown that changes persisted for four hours after the administration of patients may be tolerant of certain low molecular weight adrenaline. Troponin I was raised at 18.9 mg/l (.1.0 high heparins but sensitive to others. risk) at 12 hours. Adrenaline is regarded as the most important drug for any He was referred to a tertiary centre where he underwent severe anaphylactic reaction. Administration by the intra- coronary angiography, which showed triple vessel disease muscular route produces significantly higher peak plasma with an occluded right coronary artery, circumflex, left main concentrations compared with subcutaneous injection, which stem stenosis, and severe left anterior descending artery is clearly beneficial in the critically compromised patient. disease. The pattern of disease was deemed unsuitable for Current UK Resuscitation Council guidelines support the use revascularisation by percutaneous intervention or surgical of 0.5 ml of 1:1000 adrenaline to be administered grafting. The patient was optimised on medical treatment. He intramuscularly. successfully completed cardiac rehabilitation after discharge and remained well at outpatient review six months later. Unfortunately he suffered a further cardiac event and died one year after the episode of angioedema. This suspected adverse drug reaction to enoxaparin was reported to the 78 year old man with a history of ischaemic heart Committee on Safety of Medicines. disease (positive exercise test at end of stage 1 of Bruce protocol) was referred to the coronary care unit by his A http://pmj.bmj.com/ general practitioner. He had been having increasing fre- DISCUSSION quency and severity of angina for one week. His admission Low molecular weight heparins are now widely prescribed in was precipitated by an episode of severe pain unrelieved by the treatment of thromboembolic disease and acute coronary sublingual glycerine trinitrate spray. syndromes. Side effects include haemorrhage, eczematous Past medical history included treated hypertension, carci- plaque formation at the injection site,1 skin necrosis,2 throm- noma of prostate, and a femoral deep venous thrombosis. He bocytopenia, and hypersensitivity reactions (including urti- had been treated three years previously with tinzaparin caria,3 angioedema,3 and anaphylaxis4). It is extremely rare, (without any adverse effects) followed by anticoagulation however, for an individual to experience such a dramatic and with warfarin. potentially life threatening adverse reaction to heparin as on September 30, 2021 by guest. Protected copyright. His medications on admission included atenolol 100 mg seen in the case that we report. once a day, frusemide 40 mg once a day, amlodipine 10 mg Angioedema is a rare (incidence 0.1%–0.2%; with a once a day, fosfestrol tetrasodium 120 mg twice a day, threefold risk in the black population) adverse reaction to goserelin by injection every three months, isosorbide mono- angiotensin converting enzyme (ACE) inhibitors. Most nitrate 40 mg twice a day, cyclizine 50 mg three times a day, reactions occur within a few hours or in the first week after aspirin 75 mg once a day, and lisinopril 2.5 mg once a day. therapy, although delayed onset of months or years has also He was known to have had a previous sensitivity reaction to been described. Certain drugs such as ciprofloxacin, amox- pethidine, but there was no previous history of angioedema. ycillin, mefanamic acid, and injection of lignocaine as a local On admission, his pain had lessened after having anaesthetic have been postulated as co-factors in cases diamorphine already administered by his general practitioner having a delayed onset.5 It was felt that this man’s adverse and was fully relieved by 3 mg sublingual buccal suscard. The reaction was probably not due to the ACE inhibitor. It is not paramedic crew had given 300 mg aspirin. Admission 12 lead known whether he was taking an ACE inhibitor when treated electrocardiogram (ECG) showed anterolateral ischaemia with tinzaparin as his general practitioner records were (fig 1). unavailable and the deep venous thrombosis had been The patient was started on intravenous nitrate and treated elsewhere. He had no further episodes of angioedema, subcutaneous enoxaparin at treatment dose (1 mg/kg body having continued on and been discharged on lisinopril. At the weight twice daily). Thirty minutes later, the patient himself tertiary unit, he was anticoagulated with lepirudin (a noted marked tongue swelling. Following review by the recombinant hirudin). He declined any further investigation attending senior house officer he was given oxygen, 200 mg hydrocortisone and 10 mg chlorpheniramine intravenously. Abbreviations: ACE, angiotensin converting enzyme; ECG, The patient continued to develop worsening angioedema. He electrocardiogram www.postgradmedj.com Two adverse reactions 485 Postgrad Med J: first published as 10.1136/pgmj.2003.017020 on 5 August 2004. Downloaded from Figure 1 Admission ECG showing ST segment depression in the anterolateral leads. Figure 2 ECG two hours after administration of adrenaline showing increased ST segment depression in the anterolateral leads. http://pmj.bmj.com/ regarding the adverse reaction to enoxaparin and the incident possible. Prompt treatment with intramuscular adrenaline was clearly recorded in his hospital records. should follow. Supportive measures include airway support, Cross reactivity between low molecular weight heparins oxygen therapy, intravenous antihistamine, and corticoster- (dalteparin sodium and enoxaparin) has been reported, oids. Intravenous fluid and inotrope support may be required. manifesting as a skin reaction6 during prophylactic treatment Adrenaline is regarded as the most important drug for any for thromboembolism during pregnancy. Since neither severe anaphylactic reaction. There is no international con- product contains preservatives it is clearly due to the heparin sensus on the recommended dose of adrenaline.8 Current UK component alone. Enoxaparin has been used safely after Resuscitation Council guidelines support the use of 0.5 ml of on September 30, 2021 by guest. Protected copyright. adverse reaction to unfractionated heparin (rash). This is 1:1000 adrenaline to be administered intramuscularly.9 It is surprising as enoxaparin is derived from porcine unfractio- unclear as to why the attending doctor chose to prescribe the nated heparin.7 It has been shown that patients may be specified dose of adrenaline by the specified route. tolerant of certain low molecular weight heparins but sen- The prescribed dose may need to be repeated on more sitive to others.1 It is recommended to confirm the diagnosis than one occasion if clinical improvement is absent or of true hypersensitivity that a patch, prick, or intradermal test if improvement is transient. It has been shown in trials that should be performed initially for safety reasons. If these are the intramuscular route produces significantly higher negative, a subcutaneous test is necessary as it is the most peak plasma concentrations compared with subcutaneous reliable modality. injection.10 The action of adrenaline can be detrimental Anaphylaxis results from the rapid degranulation of mast by increasing myocardial oxygen consumption causing cells and basophils. The term encompasses reactions that are increased angina, myocardial ischaemia, and risk of myo- IgE mediated (anaphylaxis) and those that are non-immu- cardial infarction.11 nologically mediated (anaphylactoid). There is no clinical relevance between the two types of reaction. Reactions may ..................... be triggered by antibiotics, insect stings, foodstuffs, drugs, Authors’ affiliations blood products, and anaesthetic agents. L-A Smith, M Harkness, Friarage Hospital, Northallerton, UK Anaphylaxis may progress slowly or rapidly. Clinical expres- Correspondence to: Dr Lesley-Ann Smith, Castle Hill Hospital, Castle sion is variable. Most common features are cardiovascular Road, Cottingham, Hull HU16 5JQ, UK; [email protected] collapse, bronchospasm, cutaneous symptoms, angioedema,
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