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Patient & Apparent Chief Complaint

A 65 year old female called her family doctor complaining of pain in her shoulder. Doctor called to house, and administered 40mg diclofenac (Difene) IM at 1720. Doctor left house. 30 minutes post administration, patient felt her throat beginning to swell, developed a rash, and felt dizzy and weak. Emergency call is made by patient at 1800.

Ambulance responded from base approximately 30 minutes from incident.

History

Patient developed anaphylactic reaction to IM diclofenac administered by family doctor 30 minutes prior. The patient was collapsed in an armchair, semi-conscious upon arrival of ambulance crew at 1825.

Initial Clinical Findings

• Airway – partially obstructed (laryngospasm)
• C Spine – not suspected, no MOI
• Breathing – regular, fast, shallow, audible wheeze
• Circulation – Pulse present, regular; skin colour flushed, cap refill normal (<2 sec)
• Disability – Partial LOC before ambulance arrival

Clinical Impression

Severe anaphylactic reaction

Secondary Survey

AMPLE History

• A No known allergies, had received Difene previously with no reaction
• M Not currently taking medications
• P No medical history of significance
• L Last oral intake 3 hours previous
• E NOK stated patient became dizzy, confused, c/o throat swelling, difficulty breathing, rash and itch.

Obvious urticaria, cyanosis of lips and nostrils and angioedema present

Observations – Pre-hospital

• Pulse rate 102bpm
• Pulse rhythm Regular
• ECG rate 104
• ECG rhythm Sinus Tachycardia
• Resp rate 18 per minute, shallow, audible wheeze
• Resp quality Equal air entry bilaterally
• SaO2% 99% on 100% O2 via NRB
• Cap Refill <2secs
• BP 176/68
• Pupils PEARRL, size 3
• GCS 15/15 (E4, V5, M6)
• BGL 7.6mmol/l

Pre-hospital care & management

Patient placed on 100% O2 via non-rebreather. Epinephrine 1:1,000 0.5mg IM administered. Patient commenced on Salbutamol 5mg/2.5ml nebuliser. Second dose of Epinephrine 1:1,000 0.5mg IM administered with good effect. Angioedema, urticaria, peripheral cyanosis and laryngospasm fully resolved post 2nd Epinephrine administration. Patient began to appear less confused, reported dizziness resolving. Patient began to complain of a pain in her chest post Epinephrine administration. Aspirin 300mg PO chewed and GTN 1.2mg SL administered with good effect. Transferred to ambulance. En-route patient reported easing of chest pain, and breathing effort. No audible wheeze. Angioedema and peripheral cyanosis remained resolved.

In-hospital care & management

Patient arrived to ED Resus at 1926. Triaged as Category 1 (Life-Threatening Condition) with Anaphylaxis. Brought directly to Resus room. Hartmann’s solution 1000ml commenced. Bloods taken. Admitted to high-dependency unit on medical ward for observation overnight. Patient diagnosed with anaphylactic reaction to diclofenac. Family doctor advised of same. Discharged home the following day with no long-term effects.

Identification of all interventions initiated and rationale

• Epinephrine 1,1000 IM – to reverse laryngospasm, urticaria and angioedema associated with anaphylactic reaction
• Salbutamol nebuliser – to resolve audible wheeze associated with bronchospasm due to anaphylactic reaction
• Aspirin PO – as indicated for cardiac chest pain, possibly due to Epinephrine 1:1,000 administration
• GTN SL – as indicated for cardiac chest pain, possibly due to Epinephrine 1:1,000 administration
• Pulse oximetry – to monitor oxygen saturation levels in the blood
• Supplemental oxygen – to re-oxygenate patient
• 3 Lead ECG – to identify any life-threatening arrhythmias
• 12 Lead ECG – to identify any life-threatening arrhythmias or ECG changes indicative of myocardial damage (secondary to hypoxia etc.
• CXR – to identify aspiration, pleural effusion etc. that may increase morbidity
• Blood tests – to identify any electrolyte imbalances etc.
• Hartmann’s Solution IV – as per anaphylaxis protocol

Learning Outcomes

Improving pre-hospital intervention

The recommended management of anaphylaxis follows the acronym EASIO (as per Lieberman et al., 2010 & Haskell, 2006)

• Epinephrine 1:1,000 IM
• Antihistamines IM/PO (e.g. chlorphenamine)
• Steroids IM/PO/IV (e.g. hydrocortisone)
• Inhaled β2-agonists (i.e. salbutamol) if wheeze present / IV fluids if hypotensive (NaCl)
• Oxygen @ 15lpm

The next obvious step in the management of anaphylactic reactions prehospital is to introduce antihistamines and steroids to the range of medications authorised for use. This would allow for patients post-anaphylaxis to be admitted to the ED with full anaphylaxis interventions initiated. This would ensure that the short-term effects of IM Epinephrine would not result in the patient redeveloping an anaphylactic reaction en-route to the ED post treatment. (Haskell, 2006)

Chlorphenamine IM/IV

Chlorphenamine is an antihistamine commonly used in the treatment of anaphylaxis as a secondary therapy to Epinephrine 1:1,000 IM and as a first choice therapy for allergic reactions that are not life threatening, but with symptoms that are causing the patient distress, such as urticaria. The use of an antihistamine is recommended for prehospital use, due to the release of histamine and other vasoactive chemical mediators released during anaphylaxis (Seidel & Henderson, 1996)

The use of antihistamines in a prehospital context can be useful for refractory anaphylaxis, and also as a back-up therapy to the IM administration of Epinephrine 1:1,000. Other antihistamines such as diphenhydramine may also be considered.

Hydrocortisone IM/IV

Hydrocortisone is a glucocorticoid medication (steroid) that reduces inflammation and suppresses immune response. It is used to prevent deterioration post-anaphylaxis treatment. It can also be used in the treatment of severe and life-threatening asthma and Addisonian Crisis.

The use of steroids in the treatment of anaphylaxis in a prehospital context is recommended by JRCALC Guidelines (2006) if the call to hospital time is greater than 30 minutes. Steroids can take 4-6 hours to take effect, but the quick administration of IV steroids can prevent a biphasic response from developing at a later stage.

Both Chlorphenamine and Hydrocortisone are approved medications for use by State Registered Paramedics in the UK under the JRCALC Guidelines (JRCALC, 2006)

Epinephrine 1:1,000 IM

Presentation: Vial 1mg/1ml
Administration: IM
Dosage: 0.5mg IM every 3-5 minutes if required
Effects: Alpha & beta adrenergic stimulant. Reversal of laryngospasm & bronchospasm in anaphylaxis. Antagonises the effects of histamine
Side-effects: Palpitations, tachyarrythmias, hypertension, angina-like symptoms
Additional Info: Double check concentrations on pack

Chlorphenamine IV/IM

Presentation: Vial 10mg/1ml
Administration: IV
Dosage: 10mg slow IV push
Effects: Antihistamine and anticholinergic
Side-effects: Dry mouth, headache, blurred vision, GI upset
Additional Info: Elderly more likely to suffer side effects

(JRCALC, 2006)

Although not authorised for IM use in the JRCALC Guidelines, Chlorphenamine can be safely given IM, with a recommended dose of 10-20mg for adults (NHS, 2007)

Hydrocortisone IV/IM

Presentation: Vial 100mg/1ml (as sodium succinate) or powder for reconstitution with 2ml of water for injection.
Administration: IV/IM
Dosage: 200mg
Effects: Reduces inflammation, suppresses immune response
Side-effects: Burning or itching sensation if administered too quickly
Additional Info: If thrombolysis indicated, do not administer IM

(JRCALC, 2006)

Diclofenac IM and anaphylaxis

The IM administration of diclofenac has rare, but severe, and often fatal side effects in some patients. These side effects would not be seen in the PO or PR administration of diclofenac, yet these routes provide similar absorption rates. It is recommended that where possible, medical practitioners administer diclofenac through the PO or PR route first, with IM as a last resort. These rare side effects can be experienced by patients who have previously taken diclofenac PO or PR with no adverse side effects or reaction. (Schäbitz et al., 2001)

Chest pain and its management post epinephrine administration

This patient developed crushing, central chest pain, radiating to left arm and mandible post administration of Epinephrine 1:1,000 IM . She became diaphoretic and dyspnoeic as a result. A 12-lead ECG showed no obvious changes. However, as per Chase et al. (2006) a normal or non-diagnostic ECG during chest pain does not rule out acute coronary syndrome. However, abnormal changes in anaphylaxis may be noted as per Gikas (2005) “Acute ST-elevation MI is a rare but potential complication of anaphylactic reactions, even in young adults with normal coronary arteries.”

The physiological process of anaphylaxis involves the release of many chemical mediators in the blood stream. There is evidence to suggest that histamine release and indeed the general process of anaphylaxis have the potential to cause myocardial damage through coronary vasculature spasm (Gupta et al., 2001). The administration of epinephrine in acute anaphylaxis can precipitate an acute coronary event through coronary spasm induced infarct and through vasospastic angina (Saff et al., 1993; Caballero et al., 1999)

Therefore it would be prudent for pre-hospital care providers to treat patients presenting with chest pain during anaphylaxis, (pre- or post-epinephrine administration) as per ACS treatment guidelines. If no contraindications to either are present the administration of Aspirin PO and GTN SL should be immediate therapy for chest pain in the anaphylactic patient.

References (non-Pubmed)

Haskell G (2006) Paramedic Pearls of Wisdom. Massachusetts: Jones & Bartlett

NHS (2007) Kingston Primary Care Trust: Anaphylaxis Handbook. London: NHS

Seidel J, Henderson D (1996) Prehospital Care of Pediatric Emergencies. Massachusetts: Jones & Bartlett

References

 

1.

Chase M1, Brown AM, Robey JL, Pollack CV Jr, Shofer FS, Hollander JE. Prognostic value of symptoms during a normal or nonspecific electrocardiogram in emergency department patients with potential acute coronary syndrome. Acad Emerg Med. 2006 Oct;13(10):1034-9. PMID: 16973638.

Emergency department (ED) patients with symptoms concerning for acute coronary syndrome (ACS) and a normal electrocardiogram (ECG) are at risk for adverse cardiovascular events. The authors hypothesized that patients with a normal or nonspecific ECG during symptoms have a lower risk for ACS than do […]

 

2.

Rev Esp Cardiol. 1999 Apr;52(4):273-6. PMID: 10217970.

A 41-year-old-man without previous ischemic heart disease, developed a severe anaphylactic reaction. After administration of epinephrine (0.5 mg) the patient complained of chest pain. The electrocardiogram showed an elevation of ST segment in inferior leads. Myocardial necrosis was ruled out. Corona […]

 

3.

Lieberman P1, Nicklas RA, Oppenheimer J, Kemp SF, Lang DM, Bernstein DI, Bernstein JA, Burks AW, Feldweg AM, Fink JN, Greenberger PA, Golden DB, James JM, Kemp SF, Ledford DK, Lieberman P, Sheffer AL, Bernstein DI, Blessing-Moore J, Cox L, Khan DA, Lang D, Nicklas RA, Oppenheimer J, Portnoy JM, Randolph C, Schuller DE, Spector SL, Tilles S, Wallace D. The diagnosis and management of anaphylaxis practice parameter: 2010 update. J Allergy Clin Immunol. 2010 Sep;126(3):477-80. PMID: 20692689.

These parameters were developed by the Joint Task Force on Practice Parameters, representing the American Academy of Allergy, Asthma & Immunology (AAAAI); the American College of Allergy, Asthma & Immunology (ACAAI); and the Joint Council of Allergy, Asthma and Immunology. The AAAAI and the […]

 

4.

Gikas A1, Lazaros G, Kontou-Fili K. Acute ST-segment elevation myocardial infarction after amoxycillin-induced anaphylactic shock in a young adult with normal coronary arteries: a case report. BMC Cardiovasc Disord. 2005 Feb 25;5(1):6. PMID: 15733315.

Acute myocardial infarction (MI) following anaphylaxis is rare, especially in subjects with normal coronary arteries. The exact pathogenetic mechanism of MI in anaphylaxis remains unclear. […]

 

5.

Gupta MK1, Gupta P, Rezai F. Histamine–can it cause an acute coronary event? Clin Cardiol. 2001 Mar;24(3):258-9. PMID: 11288975.

Myocardial infarction (MI) occurring during the course of an allergic urticarial reaction in the absence of systemic hypotension has been rarely reported. This paper reports the case of a 28-year-old woman with no significant risk factors for coronary artery disease who presented with generalized ur […]

 

6.

Saff R1, Nahhas A, Fink JN. Myocardial infarction induced by coronary vasospasm after self-administration of epinephrine. Ann Allergy. 1993 May;70(5):396-8. PMID: 8498731.

A case of a 30-year-old man who developed a myocardial infarction after self-administering an Epi-Pen for an episode of idiopathic anaphylaxis is reported. The patient had numerous risk factors for coronary artery disease, and it was suspected that epinephrine-induced coronary spasm caused the infar […]

 

7.

Schäbitz WR1, Berger C, Knauth M, Meinck HM, Steiner T. Hypoxic brain damage after intramuscular self-injection of diclofenac for acute back pain. Eur J Anaesthesiol. 2001 Nov;18(11):763-5. PMID: 11580784.

We present a case of hypoxic brain damage that occurred after intramuscular injection of diclofenac due to a severe anaphylactic reaction. A 38-year-old nurse treated herself for acute lower back pain with 100 mg diclofenac intramuscularly. Five minutes later, she collapsed and developed coma and re […]