Anaphylaxis is a rare hypersensitivity reaction that can rapidly progress to circulatory collapse and cardiac arrest. Causes of the circulatory collapse include the heart itself—such as reduced contractility, myocardial ischemia, arrhythmias, or dynamic left ventricular outflow obstruction—or the peripheral circulation, due to hypovolemia from vasodilation or third-spacing of intravascular volume.1–6
While epinephrine administration is recommended as first-line therapy, management of anaphylaxis refractory to initial epinephrine treatment is less clear.2,6 On occasion, excessive epinephrine administration may exacerbate underlying pathology.3,5 Transesophageal echocardiography (TEE) can distinguish between causes of shock and inform management when anaphylaxis has responded poorly to epinephrine therapy.3–5,7
We present a case where TEE examination performed during cardiopulmonary resuscitation (CPR) following severe anaphylaxis, enabled rapid identification of the cause of circulatory collapse. This guided subsequent management that deviated from traditional resuscitation. Our patient has provided written consent, in compliance with local research ethics committee requirements, and the report adheres to the relevant Enhancing the Quality and Transparency of Health Research (EQUATOR) case report (Consensus-Based Clinical Case Reporting Guideline Development [CARE]) guidelines.
A 26-year-old woman was booked for urgent endovascular stenting of a large 30 mm right renal artery saccular aneurysm. Her weight was 93 kg (body mass index [BMI] was 32.9 kg/m2), and medical history consisted of childhood asthma, gastroesophageal reflux, and hypertension. Transthoracic echocardiography during investigation of her hypertension reported a “small ventricle” but otherwise no abnormalities. On the day of surgery, she was given 2 mg of intravenous (IV) midazolam in the anesthetic bay. Standard monitoring was applied and radial artery invasive blood pressure monitoring attempted, but without success.
Anesthesia was induced with IV propofol 200 mg, remifentanil 100 µg, and rocuronium 70 mg. Immediately following induction, she became tachycardic, her heart rate rising from 76 to 170 beats per minute. She developed an erythematous rash, and bag-mask ventilation became difficult. She was urgently intubated with edematous vocal cords seen at laryngoscopy. A diagnosis of anaphylaxis was declared, and she was administered three 100 µg boluses of IV epinephrine, 1000 mg sugammadex, and 1 L of crystalloid. Her initial hemodynamic response was appropriate, with a blood pressure of 135/60 mm Hg, although bronchospasm persisted.
Despite a further 1 L of crystalloid, two 100 µg boluses of IV epinephrine, and commencement of an epinephrine infusion, she progressed to circulatory collapse, with no palpable pulses and an unrecordable blood pressure. A cardiac anesthesiologist was consulted for TEE. Manual chest compressions were commenced, and a TEE probe advanced into the stomach. Echocardiographic examination continued during CPR. At the 2-minute rhythm check, she was observed to be in sinus tachycardia with impalpable central pulses, unrecordable pulse oximetry or blood pressure, and end-tidal carbon dioxide <20 mm Hg.
Initial midpapillary transgastric short-axis (TG-SAX) echocardiography demonstrated a hyperdynamic, empty left ventricle (LV) with no regional wall motion abnormalities (Figure 1; Supplemental Digital Content, Video, http://links.lww.com/AACR/A300). TEE suggested hypovolemia as the likely cause of circulatory collapse with pulseless electrical activity (PEA). Based on these findings, despite absent pulses, chest compressions were discontinued and IV fluid resuscitation prioritized. Following rapid infusion of a third liter of crystalloid, femoral pulses became palpable and a femoral arterial line was inserted. TEE-guided resuscitation continued to prioritize IV fluid administration, with ongoing assessment of LV filling. Her epinephrine infusion was rapidly weaned from 35 to 8 µg/min with further volume expansion. Serial examinations are displayed in Figure 2 and the Supplemental Digital Content (Video, http://links.lww.com/AACR/A300), demonstrating improved ventricular filling and systolic function. Additional medications given were promethazine 25 mg, ketamine 100 mg for bronchospasm, ranitidine 25 mg, and hydrocortisone 200 mg. Following 5 L crystalloid over 30 minutes, both vascular surgery and anesthetic teams concluded urgent angiography should proceed over concerns of potential aneurysm rupture given aggressive resuscitation with chest compressions, IV epinephrine, and rapid fluid load. During subsequent endovascular stenting, she remained stable with decreasing epinephrine requirements. She was extubated in the intensive care department the following morning without neurological sequelae. Serial tryptases were elevated: 84.5, 56.6, and 46.6 µg/mL at 15 minutes, 3 hours, and 6 hours, respectively (normal range: 0–11.4 µg/mL), suggestive of an anaphylactic reaction. She later tested positive for allergy to rocuronium, vecuronium, and pancuronium, with a negative reaction to cisatracurium challenge.
While there have been previous case reports of the use of TEE in anaphylaxis, none of these patients were undergoing CPR.3–5 Our case report illustrates how utilization of TEE during CPR facilitated targeted resuscitation in the setting of circulatory collapse where fluid loading, not chest compressions, was the immediate requirement.
Current Advanced Cardiac Life Support (ACLS) guidelines in PEA arrest recommend early commencement and minimal interruption of chest compressions, treatment of reversible causes of arrest, 2-minute rhythm and pulse checks, and in the absence of detectable pulse, administration of 1 mg boluses of IV epinephrine. ACLS guidelines on CPR were originally developed for treatment of out-of-hospital cardiac arrests, typically caused by thrombotic phenomena or arrhythmia, and were later extrapolated into the hospital setting.8,9 Intraoperative cardiac arrest may warrant a more targeted approach, accounting for differences in etiology, clinical context, and availability of specialized treatment.8
For example, the utility of chest compressions in hypovolemic shock has been questioned. External compression of the heart in the absence of adequate preload may not improve outcomes, and animal models have demonstrated no advantage of compressions over fluid resuscitation alone in the management of hemorrhagic shock.8–10 Furthermore, chest compressions can be associated with morbidity, and pulse checks that prompt continuation of compressions are unreliable.11,12 In our case, TEE examination caused no interruption to active CPR and allowed us to deviate from traditional ACLS by ceasing demonstrably ineffective compressions to focus on treating the primary cause of shock—hypovolemia. Performing TEE during CPR may itself not be without risk; however, there is a low overall complication rate of 0.2% for TEE in the intraoperative setting (bleeding, endotracheal tube malplacement, dental injury, perforation).13
The apparent hypovolemia in anaphylaxis is a combination of vasodilation and increased vascular permeability and can require up to 50 mL/kg of fluid replacement.1,6 The United Kingdom 6th National Audit Project reported inadequate fluid administration in 20% of cases of severe anaphylaxis.14 In our patient, this was quickly recognized during TEE assessment (Figure 1) and a total of 53 mL/kg crystalloid was infused, demonstrating the large fluid shifts that can occur.
Several abbreviated protocols for hemodynamic assessment by TEE emphasize rapid qualitative assessment with minimal echographic windows.7,13 The TG-SAX view was the principal window used here, as it allows rapid evaluation of volume status, systolic function, and regional wall motion abnormalities. In this view, the myocardium supplied by all 3 coronary arteries can be simultaneously observed.13 Hypovolemia can be identified in the TG-SAX view by measuring LV end-diastolic area (LVEDA) as an index for preload.7 While LVEDA varies between patients, Royse7 has suggested a working normal range of 8 to 14 cm2, with an LVEDA <8 cm2 suggestive of hypovolemia. Serial examination can monitor response to fluid therapy, even in the presence of wall motion abnormalities.7,13
Additional measurements, such as fractional shortening (FS), fractional area of change (FAC), and Simpson biplane method, may also be helpful in estimating ventricular systolic function. The FAC is calculated as the percentage difference in LVEDA and LV end-systolic area (LVESA), measured by tracing the blood-pool area at the midpapillary TG-SAX window. Normal values for FAC are described as 50%–65% with a FAC >65% indicating increased systolic function suggestive of vasodilation.7 FAC offers practical advantages over Simpson biplane method, which has a higher risk of foreshortening in TEE, and requires withdrawal of the probe to the midesophageal window and additional measurement of LVEDA and LVESA in both apical 4-chamber and 2-chamber views.7,13 However, both methods involve tracing the blood-pool area on recorded images, which may not be practical in the resuscitation setting. FS offers a further method using M-mode of the LV base at the level of the mitral valve chordae to measure the percentage change between LV end-diastolic and end-systolic diameter (normal range FS: 28%–44%).7 Qualitative assessment is often adequate to characterize significantly abnormal echocardiographic findings commonly seen in profound circulatory collapse, as was the case in our patient where the LV was observed to be empty at end systole suggesting FS and FAC approaching 100% (Figure 1; Supplemental Digital Content, Video, http://links.lww.com/AACR/A300).
Finally, we proceeded with endovascular angioplasty despite a presumed severe hypersensitivity reaction due to concerns for potential aneurysmal rupture and the minimally invasive nature of the procedure. A recent case series did not identify increased hypersensitivity complications in patients who proceeded with planned surgery following severe anaphylactic reactions; however, there is currently limited evidence to guide decision-making and an individualized approach is recommended.15
In conclusion, our patient experienced a severe enough anaphylactic reaction to warrant CPR but recovered with good neurological outcome. Early TEE assessment allowed us to target the cause of her circulatory collapse, rather than use a standardized approach that might have prolonged potentially ineffective chest compressions in an empty ventricle. TEE can rapidly identify the likely mechanism and guide treatment of circulatory collapse in anaphylaxis without interrupting concurrent resuscitative efforts.
We would like to thank the St George Hospital theatre staff—including nurses, orderlies, physicians, and especially our anesthetic nurse Yvette Page—whose professionalism and assistance in the resuscitation was central to attaining a good outcome for this patient.
Name: Christopher S. Long, MD.
Contribution: This author helped by performing a literature review, drafting and editing the manuscript, formatting the media, consenting the patient for participation in this report, and submitting the final manuscript.
Name: Matthew R. Miller, MSc.
Contribution: This author helped by performing a literature review, drafting and editing the manuscript, and coordinating the input from various authors. He is a supervising consultant anesthetist during the described clinical case.
Name: Gabrielle M. McMullin, MCh.
Contribution: This author helped draft and edit the manuscript and advised on subject matter as a subject expert in vascular surgery. She is a consultant vascular surgeon for described case.
Name: Sharon L. Tivey, MBBS.
Contribution: This author helped draft and edit the manuscript, gave advice as a subject expert on echocardiography, and performed the original transesophageal echocardiography examination during the described clinical case.
This manuscript was handled by: Kent H. Rehfeldt, MD.
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