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Making the Quick Diagnosis: A Case of Neonatal Shock
The Journal of Emergency Medicine, Vol. -, No. -, pp. 1–6, 2016 Ó 2016 Elsevier Inc. All rights reserved. 0736-4679/$ - see front matter
http://dx.doi.org/10.1016/j.jemermed.2016.11.003
Clinical Communications: Pediatric MAKING THE QUICK DIAGNOSIS: A CASE OF NEONATAL SHOCK Mike Gardiner, MD,* Timothy K. Ruttan, MD,† Andrew J. Kienstra, MD,* and Matthew Wilkinson, MD* *The University of Texas at Austin, Dell Medical School, Dell Children’s Medical Center of Central Texas, Austin, Texas and †Department of Emergency Medicine, University of California Davis School of Medicine, Sacramento, California Reprint Address: Mike Gardiner, MD, The University of Texas at Austin, Dell Children’s Medical Center, 4900 Mueller Boulevard, Austin, TX 78723
, Abstract—Background: The work-up and initial management of a critically ill neonate is challenging and anxiety provoking for the Emergency Physician. While sepsis and critical congenital heart disease represent a large proportion of neonates presenting to the Emergency Department (ED) in shock, there are several additional etiologies to consider. Underlying metabolic, endocrinologic, gastrointestinal, neurologic, and traumatic disorders must be considered in a critically ill infant. Several potential etiologies will present with nonspecific and overlapping signs and symptoms, and the diagnosis often is not evident at the time of ED assessment. Case Report: We present the case of a neonate in shock, with a variety of nonspecific signs and symptoms who was ultimately diagnosed with tachycardia-induced cardiomyopathy secondary to a resolved dysrhythmia. Why Should an Emergency Physician Be Aware of This?: This case highlights the diagnostic and therapeutic approach to the critically ill neonate in the ED, and expands the differential diagnosis beyond sepsis and critical congenital heart disease. Knowledge of the potential life-threatening etiologies of shock in this population allows the Emergency Physician to appropriately test for, and empirically treat, several potential etiologies simultaneously. Additionally, we discuss the diagnosis and management of supraventricular tachycardia and Wolff-Parkinson-White syndrome in the neonatal and pediatric population, which is essential knowledge for an Emergency Physician. Ó 2016 Elsevier Inc. All rights reserved.
INTRODUCTION The evaluation and treatment of a critically ill neonate presents an anxiety-provoking clinical challenge to the Emergency Physician. Although sepsis represents a significant portion of neonates presenting to the Emergency Department (ED) with shock, the differential diagnosis is broad, and common presenting signs and symptoms, such as lethargy, poor feeding, decreased tone, and irritability, are nonspecific. Adding to the challenge, several of the potential diagnoses are life-threatening, requiring emergent recognition and management to prevent significant morbidity or mortality. Due to these factors, it is important for the Emergency Physician to keep a broad differential diagnosis in mind, and to initiate early empiric treatment for several of the potential life-threatening causes, before definitive diagnosis. In this case, we present a neonate in shock with a variety of nonspecific signs and symptoms, and highlight the initial management, work-up, and ultimate diagnosis. CASE REPORT A 24-day-old male was brought into a community ED with poor feeding, lethargy, and pallor for 1 day. During the evening before presentation, the patient was reportedly feeding less vigorously, tolerating just 1 ounce of formula per feeding. He was also no longer waking
, Keywords—neonatal shock; resuscitation; cardiomyopathy; supraventricular tachycardia; Wolff-ParkinsonWhite syndrome
RECEIVED: 26 October 2016; ACCEPTED: 1 November 2016 1
2
spontaneously to feed. On the morning of presentation he became difficult to arouse, had trouble breathing, appeared pale, and was cool to touch. There was no history of vomiting, fever, cough, or nasal congestion, and no known trauma. He was born full term by spontaneous vaginal delivery at 41 weeks gestation after an uneventful pregnancy, which included routine prenatal care. Upon arrival to the community ED, the patient was found to be ill-appearing, limp, difficult to arouse, and grunting. Initial vital signs included a rectal temperature of 33.2 C, heart rate 128 beats per minute (bpm), respiratory rate of 36 breaths/min, and peripheral oxygen saturation of 100% on room air. A glucose level was found to be low at 14 mg/dL. He was externally warmed, a peripheral i.v. catheter was placed, he was given 5 mL/kg 10% dextrose solution i.v., and a 20 mL/kg normal saline bolus. After these interventions, his rectal temperature was 35 C, glucose improved to 274 mg/dL, and he was noted to be increasingly active, at which point he was emergently transferred by air to a tertiary care pediatric ED (PED). Upon arrival at the PED, the patient was found to be minimally responsive, mottled, and dusky-appearing. Rectal temperature on arrival was 29.5 C, heart rate was 120 bpm, lower-extremity blood pressure was 49/26 mm Hg, and his peripheral oxygen saturation was 87% while receiving bag-valve-mask ventilation with 100% oxygen by emergency medical services. His initial physical examination revealed a well-developed infant with an anterior fontanelle that was open, soft, and flat. His head was without signs of trauma. His pupils were equal and reactive, and the remainder of his head, eyes, ears, throat, and neck examination was unremarkable. He had poor respiratory effort, a midline trachea, and slightly coarse breath sounds. Cardiovascular examination revealed no murmur, rub, or gallop. His brachial pulses were weak and femoral pulses were not palpable. His abdomen was soft, nontender, and distended, with decreased bowel sounds noted. A firm liver edge was palpated 5 cm below the right costal margin and his spleen was not palpable. He had normal-appearing Tanner I male genitalia, and both testes were palpable in his scrotum. A normal saline bolus of 10 mL/kg was administered, and the patient’s oxygen saturation improved to 100% without improvement in his blood pressure. Rapid sequence intubation was performed with fentanyl, midazolam, rocuronium, and atropine. He was treated empirically with i.v. hydrocortisone, ampicillin, cefotaxime, and acyclovir. Initial venous blood gas was significant for a pH of 6.9, pCO2 of 37 mm Hg, a base deficit of 25 mmol/L, and an elevated lactate of 15.9 mmol/L. White blood cell count was
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27,300 cells/mm3. Initial chemistry panel was significant for a HCO3 of 6 mmol/L, anion gap of 24, an elevated blood urea nitrogen at 28 mg/dL, and normal creatinine of 0.7 mg/dL, aspartate aminotransferase and alanine aminotransferase levels of 263 U/L and 241 U/L, respectively, and a glucose level of 87 mg/dL. A chest radiograph showed mildly increased perihilar and peribronchial markings with a normal cardiothymic silhouette. Repeat blood pressure was 87/33 mm Hg in the right upper extremity, with a simultaneous right lower-extremity blood pressure of 40/23 mm Hg. Given the concern for ductal-dependent critical congenital heart disease (CHD), a prostaglandin infusion was initiated at 0.1 mg/kg/min. After initial resuscitation, the patient clinically improved with stabilization of his vital signs with a temperature of 35.5 C, a heart rate of 153 bpm, blood pressure of 94/60 mm Hg, and a peripheral oxygen saturation of 100% while mechanically ventilated. The discrepancy between upper- and lower-extremity blood pressures persisted on repeated measurements. He was admitted to the pediatric intensive care unit (PICU) for further management. On arrival in the PICU, the patient was found to have intermittent hypotension despite fluid resuscitation, and was started on milrinone and epinephrine infusions. An electrocardiogram (ECG) showed sinus tachycardia and nonspecific T wave abnormalities (Figure 1). A head computed tomography showed findings consistent with early ischemic changes, without evidence of acute trauma. An echocardiogram demonstrated normal cardiac anatomy and poor left ventricular contractility with an ejection fraction of 35%. After the echocardiogram results, the prostaglandin infusion was discontinued. The patient continued on antimicrobials and additional infectious studies were sent, all of which were ultimately negative. Overnight and into the following morning, the patient remained hemodynamically stable on inotropic support and repeat echocardiogram showed improved ventricular contractility. Approximately 12 h after admission to the PICU, the patient developed persistent tachycardia with a heart rate of 270 bpm. An ECG showed narrow QRS complexes with no discernable P-waves (Figure 2). The patient was diagnosed with supraventricular tachycardia (SVT). Adenosine 0.1 mg/kg was given with successful conversion to a normal sinus rhythm. CASE RESOLUTION After resolution of the patient’s SVT episode, a follow-up ECG was performed that showed evidence of ventricular pre-excitation with delta waves (Figure 3). The patient was diagnosed with Wolff-Parkinson-White (WPW)
Diagnosing Neonatal Shock
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Figure 1. Initial 12-lead electrocardiogram showing sinus tachycardia and nonspecific T-wave abnormalities.
syndrome and was started on a continuous i.v. esmolol infusion. He had no further episodes of SVT throughout hospitalization, and his esmolol infusion was transitioned to oral propranolol for home management. He was also started on enalapril before discharge to assist with afterload reduction in light of the poor cardiac function evident on his echocardiogram. The patient was subsequently discharged home in good condition 1 week after his initial presentation to the ED. Review of the patient’s medical record over the subsequent year after hospital discharge has revealed him to be growing well and without further medical issues. He has
received routine follow-up with cardiology and is doing well at home. The patient has had no further episodes of shock or metabolic derangements that have brought him back to the ED. DISCUSSION In our case, a 24-day-old infant presented with lethargy, poor feeding, vomiting, hypothermia, hypoglycemia, metabolic acidosis, hypoxemia, hepatomegaly, and hypotension. Although not all-inclusive, the most pertinent considerations for this patient in the ED are
Figure 2. 12-lead electrocardiogram obtained during tachycardic event.
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Figure 3. (A) 12-lead electrocardiogram obtained after termination of tachycardia and (B) Close-up view of precordial leads exhibiting pre-excitation with short PR interval, delta wave, and prolonged QRS complex.
infectious, cardiac, endocrine, metabolic, gastrointestinal, and traumatic etiologies (see Table 1). After a full evaluation for sepsis and underlying metabolic diagnoses was unremarkable, the conclusion was made that the Table 1. Differential Diagnosis for Neonatal Altered Mental Status: THE Misfits (1) T: Trauma Accidental Nonaccidental H: Heart disease Congenital heart disease Cyanotic Obstructive Aberrant coronary artery Dysrhythmia Myocarditis Pericarditis E: Endocrine Congenital adrenal hyperplasia Diabetes insipidus Thyrotoxicosis M: Metabolic Hypoglycemia Electrolyte imbalance I: Inborn errors of metabolism S: Sepsis Bacteremia Bacterial meningitis Urosepsis Pneumonia Viral sepsis Pertussis Congenital infection Infantile botulism F: Formula mishaps Underdilution Overdilution I: Intestinal catastrophes Malrotation with intestinal volvulus Necrotizing enterocolitis Intussusception T: Toxins and poisons S: Seizure
infant’s presentation was the sole result of cardiac failure as a result of resolved SVT. This conclusion is further supported by the rapid resolution of the child’s symptoms, return to a normal baseline after resolution of his dysrhythmia, and lack of further issues during routine outpatient follow-up. To our knowledge, this is the first case in the emergency medicine literature of an infant with cardiac failure leading to this particular constellation of signs, symptoms, metabolic, and hemodynamic derangements. This case adds another level of detail to the potential presentation of cardiogenic shock in a critically ill neonate. Due to the relative uncertainty of diagnosis at the time of presentation, management of a critically ill neonate presenting to the PED often involves simultaneous evaluation for and empiric treatment of several of multiple potential etiologies (1). Shock from a variety of etiologies can result in hemodynamic, thermoregulatory, and metabolic derangements that would not necessarily been seen in older children and adults. In our case of cardiogenic shock resulting from a resolved tachydysrhythmia, the patient presented with severe hypothermia and hypoglycemia in addition to the more expected findings of hypotension and end organ dysfunction. This further emphasizes the need to keep a broad differential diagnosis when evaluating critically ill neonates. The general work-up for a critically ill neonate includes blood, urine, and cerebrospinal fluid analyses with cultures. A chest x-ray study, and ECG are often helpful. Additional work-up may include 21-hydroxylase level, pH level, lactate, ammonia, liver transaminases, urine ketones, amino acids, organic acids, echocardiogram, and cranial imaging, depending on the clinical scenario. Emergency management of the critically ill neonate in shock includes ensuring a secure
Diagnosing Neonatal Shock
airway, providing respiratory support, circulatory resuscitation as necessary, and thermoregulation. Although treatment of sepsis requires rapid fluid resuscitation, the potential for underlying CHD with congestive heart failure (CHF) often necessitates smaller, more frequent fluid challenges (10 mL/kg normal saline increments) with assessment for improvement or decompensation after fluid administration. Hypoglycemia should be rapidly corrected with i.v. glucose administration. Empiric antimicrobial coverage includes broad-spectrum i.v. antibiotics with or without i.v. acyclovir, as well as consideration for hydrocortisone, and prostaglandin E1 therapy, depending on the clinical scenario (2–7). Cardiac dysrhythmias represent an underappreciated subset of the differential diagnosis of a critically ill infant, despite being relatively common in neonates (8). SVT, as seen in our patient, is the most common type of pediatric rhythm disturbance (8–11). SVT is a tachydysrhythmia originating above the level of the ventricles (10). ECG findings typically include a rapid heart rate (usually 220 280 bpm in infants), and a regular rhythm without variation throughout the respiratory cycle. While most cases are associated with a narrow QRS complex (<80 ms) and no discernable P wave before the QRS complex, a wide variety of presentations are possible, including wide QRS complexes and abnormal P waves (12). SVT is caused by re-entrant electrical activity either through an accessory atrioventricular connection (atrioventricular re-entrant tachycardia [AVRT]) or within the AV node (atrioventricular nodal re-entrant tachycardia) (13). Although dysrhythmia and SVT are more common in children with CHD, the majority of cases will present in patients with structurally normal hearts. WPW syndrome is a specific subclass of patients with AVRT, accounting for 10%–50% of all cases of SVT (10,11). Patients with WPW have antegrade conduction of impulses through an accessory pathway, leading to partial depolarization of ventricles and a ‘‘pre-excitation’’ pattern on ECG with a short PR interval, prolonged QRS interval, and a delta wave (Figure 3B). Similar to other etiologies of SVT, WPW is more common in patients with CHD, and up to 20% of WPW patients have some underlying CHD, most commonly Ebstein’s anomaly (11). While the majority of cases of WPW are spontaneous, there are genetic cases of WPW inherited in an autosomal dominant fashion (14). Thirty-eight percent of patients with WPW will have their first episode of SVT by the age of 2 months, and these patients who are diagnosed at a young age will often have resolution of symptoms by 8 months of age, although many experience relapse later in life (15).
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The clinical features of SVT are widely variable. Most episodes of SVT are paroxysmal with rapid onset and termination. Episodes may be very brief, lasting only seconds, or may persist for hours to days. Clinical features seen in infants with SVT include fatigue, lethargy, poor feeding, and irritability. Older children will experience palpitations, chest pain, fatigue, lightheadedness, and occasionally syncope. If episodes of SVT are prolonged and unrecognized, patients may progress to CHF due to a tachycardia-mediated cardiomyopathy. Infants are at a particularly high risk for this progression, as the early signs and symptoms are nonspecific and may be unrecognized for long periods of time. Studies have shown that 38%–50% of infants with SVT have signs or symptoms of CHF at the time of diagnosis, particularly those with symptoms for > 48 hours (10,12,16). As was seen in our patient’s case, tachycardia-induced myocardial dysfunction may persist beyond the resolution of SVT, and patients may present with signs of heart failure only if the dysrhythmia spontaneously resolves before presentation (17). In many cases, tachycardia-mediated cardiomyopathy is reversible after termination of the dysrhythmia, however, in other cases, there might be permanent myocardial injury and dysfunction (18). Emergent treatment of SVT begins with assessment of respiratory and hemodynamic status and standard initial resuscitation. Hemodynamically unstable patients with a tachydysrhythmia and signs of shock should receive immediate synchronized cardioversion (19). In stable patients with SVT, vagal maneuvers, such as Valsalva, and application of ice to the patient’s face have been shown to successfully terminate SVT in 20%–63% of cases (10,20,21). A recent randomized control trial in adults showed improved termination of SVT utilizing a modified Valsalva technique involving supine repositioning and passive leg raise when compared to standard semi-recumbent Valsalva, although this has not been studied in children, to our knowledge (22). If vagal maneuvers do not terminate the dysrhythmia, pharmacologic termination is the next step. Adenosine is an AV nodal blocking agent and is the initial drug of choice for conversion of SVT (19). The most common starting dose is 0.1 mg/kg delivered via rapid i.v. push, and if no response is noted, a second dose of 0.2 mg/kg is administered (19). Studies have suggested that infants do not respond as favorably as older children to these suggested doses, and some authors recommend increasing the starting dose of adenosine to 0.15–0.2 mg/kg (23). There is variation in management of patients who have SVT refractory to adenosine with amiodarone and procainamide being among the most commonly used antidysrhythmic agents in this setting (19).
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After resolution of SVT, prophylactic treatment is generally initiated with propranolol for 4 12 months, as recurrence is common in infants. Patients with WPW often require long-term or definitive therapy (10). In addition to propranolol, medications for prophylaxis of SVT include sotalol, digoxin, amiodarone, and flecanide. If electrophysiology studies are able to identify an accessory or AV nodal pathway, radiofrequency ablation is definitive therapy for patients with recurrent symptomatic SVT as an alternative to medication, especially in older children, once the procedure is more technically feasible. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS? While early evaluation and treatment of a critically ill neonate often centers around empiric management of sepsis, it is important for the Emergency Physician to keep in mind the myriad of other potential diagnoses that can lead to shock in an infant. While resuscitation and initiation of antimicrobial therapy is undertaken, broad examination and work-up aimed at identifying CHD, dysrhythmia, congenital adrenal hyperplasia, inborn errors of metabolism, gastrointestinal pathology, and trauma are critically important. In addition, understanding the emergent evaluation and treatment algorithm for SVT, depending on the patient’s hemodynamic status, is key for the Emergency Physician. REFERENCES 1. Brousseau T, Sharieff GQ. Newborn emergencies: the first 30 days of life. Pediatr Clin North Am 2006;53:69–84. 2. Greenhow TL, Hung YY, Herz AM. Changing epidemiology of bacteremia in infants aged 1 week to 3 months. Pediatrics 2012; 129:e590–6. 3. Kimberlin DW. When should you initiate acyclovir therapy in a neonate? J Pediatr 2008;153:155–6. 4. Kimberlin DW, Lin CY, Jacobs RF, et al. Natural history of neonatal herpes simplex virus infections in the acyclovir era. Pediatrics 2001; 108:223–9. 5. Freed MD, Heymann MA, Lewis AB, Roehl SL, Kensey RC. Prostaglandin E1 infants with ductus arteriosus-dependent congenital heart disease. Circulation 1981;64:899–905.
6. Guenther E, Powers A, Srivastava R, Bonkowsky JL. Abusive head trauma in children presenting with an apparent life-threatening event. J Pediatr 2010;157:821–5. 7. Dubowitz H, Bennett S. Physical abuse and neglect of children. Lancet 2007;369(9576):1891–9. 8. Badrawi N, Hegazy RA, Tokovic E, Lotfy W, Mahmoud F, Aly H. Arrhythmia in the neonatal intensive care unit. Pediatr Cardiol 2009;30:325–30. 9. Binnetoglu FK, Babaoglu K, Tu¨rker G, Altun G. Diagnosis, treatment and follow up of neonatal arrhythmias. Cardiovasc J Afr 2014;25:58–62. 10. Garson A, Gillette PC, McNamara DG. Supraventricular tachycardia in children: clinical features, response to treatment, and long-term follow-up in 217 patients. J Pediatr 1981;98:875–82. 11. Deal BJ, Keane JF, Gillette PC. Wolff-Parkinson-White syndrome and supraventricular tachycardia during infancy: management and follow-up. J Am Coll Cardiol 1985;5:130–5. 12. Perry JC. Supraventricular tachycardia. In: Garson A Jr., Bricker J, Fisher D, eds. Science and practice of pediatric cardiology. 2nd edn. Philadelphia, PA: Lippincott; 1998. 13. Ko JK, Deal BJ, Strasburger JF, Benson DW Jr. Supraventricular tachycardia mechanisms and their age distribution in pediatric patients. Am J Cardiol 1992;69:1028–32. 14. Gollob MH, Green MS, Tang ASL, et al. Identification of a gene responsible for familial Wolff Parkinson White syndrome. N Engl J Med 2001;344:1823–31. 15. Perry JC, Garson A. Supraventricular tachycardia due to Wolff-Parkinson-White syndrome in children: early disappearance and late recurrence. J Am Coll Cardiol 1990;16:1215–20. 16. Gilljam T, Jaeggi E, Gow RM. Neonatal supraventricular tachycardia: outcomes over a 27-year period at a single institution. Acta Paediatr 2008;97:1035–9. 17. McLaran CJ, Gersh BJ, Sugrue DD, Hammill SC, Seward JB, Holmes DR Jr. Tachycardia induced myocardial dysfunction. A reversible phenomenon? Br Heart J 1985;53:323–7. 18. Cruz FE, Cheriex EC, Smeets JL, et al. Reversibility of tachycardia-induced cardiomyopathy after cure of incessant supraventricular tachycardia. J Am Coll Cardiol 1990;16:739–44. 19. Kleinman ME, Chameides L, Schexnayder SM, et al. Part 14: pediatric advanced life support: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2010;122(Suppl. 3): S876–908. 20. Mu¨ller G, Deal BJ, Benson DW. ‘‘Vagal maneuvers’’ and adenosine for termination of atrioventricular reentrant tachycardia. Am J Cardiol 1994;74:500–3. 21. Wen ZC, Chen SA, Tai CT, et al. Electrophysiological mechanisms and determinants of vagal maneuvers for termination of paroxysmal supraventricular tachycardia. Circulation 1998;98:2716–23. 22. Appelboam A, Reuben A, Mann C, et al. Postural modification to the standard Valsalva manoeuvre for emergency treatment of supraventricular tachycardias (REVERT): a randomised controlled trial. Lancet 2015;386(10005):1747–53. 23. Dixon J, Foster K, Wyllie J, Wren C. Guidelines and adenosine dosing in supraventricular tachycardia. Arch Dis Child 2005;90: 1190–1.
http://dx.doi.org/10.1016/j.jemermed.2016.11.003
Clinical Communications: Pediatric MAKING THE QUICK DIAGNOSIS: A CASE OF NEONATAL SHOCK Mike Gardiner, MD,* Timothy K. Ruttan, MD,† Andrew J. Kienstra, MD,* and Matthew Wilkinson, MD* *The University of Texas at Austin, Dell Medical School, Dell Children’s Medical Center of Central Texas, Austin, Texas and †Department of Emergency Medicine, University of California Davis School of Medicine, Sacramento, California Reprint Address: Mike Gardiner, MD, The University of Texas at Austin, Dell Children’s Medical Center, 4900 Mueller Boulevard, Austin, TX 78723
, Abstract—Background: The work-up and initial management of a critically ill neonate is challenging and anxiety provoking for the Emergency Physician. While sepsis and critical congenital heart disease represent a large proportion of neonates presenting to the Emergency Department (ED) in shock, there are several additional etiologies to consider. Underlying metabolic, endocrinologic, gastrointestinal, neurologic, and traumatic disorders must be considered in a critically ill infant. Several potential etiologies will present with nonspecific and overlapping signs and symptoms, and the diagnosis often is not evident at the time of ED assessment. Case Report: We present the case of a neonate in shock, with a variety of nonspecific signs and symptoms who was ultimately diagnosed with tachycardia-induced cardiomyopathy secondary to a resolved dysrhythmia. Why Should an Emergency Physician Be Aware of This?: This case highlights the diagnostic and therapeutic approach to the critically ill neonate in the ED, and expands the differential diagnosis beyond sepsis and critical congenital heart disease. Knowledge of the potential life-threatening etiologies of shock in this population allows the Emergency Physician to appropriately test for, and empirically treat, several potential etiologies simultaneously. Additionally, we discuss the diagnosis and management of supraventricular tachycardia and Wolff-Parkinson-White syndrome in the neonatal and pediatric population, which is essential knowledge for an Emergency Physician. Ó 2016 Elsevier Inc. All rights reserved.
INTRODUCTION The evaluation and treatment of a critically ill neonate presents an anxiety-provoking clinical challenge to the Emergency Physician. Although sepsis represents a significant portion of neonates presenting to the Emergency Department (ED) with shock, the differential diagnosis is broad, and common presenting signs and symptoms, such as lethargy, poor feeding, decreased tone, and irritability, are nonspecific. Adding to the challenge, several of the potential diagnoses are life-threatening, requiring emergent recognition and management to prevent significant morbidity or mortality. Due to these factors, it is important for the Emergency Physician to keep a broad differential diagnosis in mind, and to initiate early empiric treatment for several of the potential life-threatening causes, before definitive diagnosis. In this case, we present a neonate in shock with a variety of nonspecific signs and symptoms, and highlight the initial management, work-up, and ultimate diagnosis. CASE REPORT A 24-day-old male was brought into a community ED with poor feeding, lethargy, and pallor for 1 day. During the evening before presentation, the patient was reportedly feeding less vigorously, tolerating just 1 ounce of formula per feeding. He was also no longer waking
, Keywords—neonatal shock; resuscitation; cardiomyopathy; supraventricular tachycardia; Wolff-ParkinsonWhite syndrome
RECEIVED: 26 October 2016; ACCEPTED: 1 November 2016 1
2
spontaneously to feed. On the morning of presentation he became difficult to arouse, had trouble breathing, appeared pale, and was cool to touch. There was no history of vomiting, fever, cough, or nasal congestion, and no known trauma. He was born full term by spontaneous vaginal delivery at 41 weeks gestation after an uneventful pregnancy, which included routine prenatal care. Upon arrival to the community ED, the patient was found to be ill-appearing, limp, difficult to arouse, and grunting. Initial vital signs included a rectal temperature of 33.2 C, heart rate 128 beats per minute (bpm), respiratory rate of 36 breaths/min, and peripheral oxygen saturation of 100% on room air. A glucose level was found to be low at 14 mg/dL. He was externally warmed, a peripheral i.v. catheter was placed, he was given 5 mL/kg 10% dextrose solution i.v., and a 20 mL/kg normal saline bolus. After these interventions, his rectal temperature was 35 C, glucose improved to 274 mg/dL, and he was noted to be increasingly active, at which point he was emergently transferred by air to a tertiary care pediatric ED (PED). Upon arrival at the PED, the patient was found to be minimally responsive, mottled, and dusky-appearing. Rectal temperature on arrival was 29.5 C, heart rate was 120 bpm, lower-extremity blood pressure was 49/26 mm Hg, and his peripheral oxygen saturation was 87% while receiving bag-valve-mask ventilation with 100% oxygen by emergency medical services. His initial physical examination revealed a well-developed infant with an anterior fontanelle that was open, soft, and flat. His head was without signs of trauma. His pupils were equal and reactive, and the remainder of his head, eyes, ears, throat, and neck examination was unremarkable. He had poor respiratory effort, a midline trachea, and slightly coarse breath sounds. Cardiovascular examination revealed no murmur, rub, or gallop. His brachial pulses were weak and femoral pulses were not palpable. His abdomen was soft, nontender, and distended, with decreased bowel sounds noted. A firm liver edge was palpated 5 cm below the right costal margin and his spleen was not palpable. He had normal-appearing Tanner I male genitalia, and both testes were palpable in his scrotum. A normal saline bolus of 10 mL/kg was administered, and the patient’s oxygen saturation improved to 100% without improvement in his blood pressure. Rapid sequence intubation was performed with fentanyl, midazolam, rocuronium, and atropine. He was treated empirically with i.v. hydrocortisone, ampicillin, cefotaxime, and acyclovir. Initial venous blood gas was significant for a pH of 6.9, pCO2 of 37 mm Hg, a base deficit of 25 mmol/L, and an elevated lactate of 15.9 mmol/L. White blood cell count was
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27,300 cells/mm3. Initial chemistry panel was significant for a HCO3 of 6 mmol/L, anion gap of 24, an elevated blood urea nitrogen at 28 mg/dL, and normal creatinine of 0.7 mg/dL, aspartate aminotransferase and alanine aminotransferase levels of 263 U/L and 241 U/L, respectively, and a glucose level of 87 mg/dL. A chest radiograph showed mildly increased perihilar and peribronchial markings with a normal cardiothymic silhouette. Repeat blood pressure was 87/33 mm Hg in the right upper extremity, with a simultaneous right lower-extremity blood pressure of 40/23 mm Hg. Given the concern for ductal-dependent critical congenital heart disease (CHD), a prostaglandin infusion was initiated at 0.1 mg/kg/min. After initial resuscitation, the patient clinically improved with stabilization of his vital signs with a temperature of 35.5 C, a heart rate of 153 bpm, blood pressure of 94/60 mm Hg, and a peripheral oxygen saturation of 100% while mechanically ventilated. The discrepancy between upper- and lower-extremity blood pressures persisted on repeated measurements. He was admitted to the pediatric intensive care unit (PICU) for further management. On arrival in the PICU, the patient was found to have intermittent hypotension despite fluid resuscitation, and was started on milrinone and epinephrine infusions. An electrocardiogram (ECG) showed sinus tachycardia and nonspecific T wave abnormalities (Figure 1). A head computed tomography showed findings consistent with early ischemic changes, without evidence of acute trauma. An echocardiogram demonstrated normal cardiac anatomy and poor left ventricular contractility with an ejection fraction of 35%. After the echocardiogram results, the prostaglandin infusion was discontinued. The patient continued on antimicrobials and additional infectious studies were sent, all of which were ultimately negative. Overnight and into the following morning, the patient remained hemodynamically stable on inotropic support and repeat echocardiogram showed improved ventricular contractility. Approximately 12 h after admission to the PICU, the patient developed persistent tachycardia with a heart rate of 270 bpm. An ECG showed narrow QRS complexes with no discernable P-waves (Figure 2). The patient was diagnosed with supraventricular tachycardia (SVT). Adenosine 0.1 mg/kg was given with successful conversion to a normal sinus rhythm. CASE RESOLUTION After resolution of the patient’s SVT episode, a follow-up ECG was performed that showed evidence of ventricular pre-excitation with delta waves (Figure 3). The patient was diagnosed with Wolff-Parkinson-White (WPW)
Diagnosing Neonatal Shock
3
Figure 1. Initial 12-lead electrocardiogram showing sinus tachycardia and nonspecific T-wave abnormalities.
syndrome and was started on a continuous i.v. esmolol infusion. He had no further episodes of SVT throughout hospitalization, and his esmolol infusion was transitioned to oral propranolol for home management. He was also started on enalapril before discharge to assist with afterload reduction in light of the poor cardiac function evident on his echocardiogram. The patient was subsequently discharged home in good condition 1 week after his initial presentation to the ED. Review of the patient’s medical record over the subsequent year after hospital discharge has revealed him to be growing well and without further medical issues. He has
received routine follow-up with cardiology and is doing well at home. The patient has had no further episodes of shock or metabolic derangements that have brought him back to the ED. DISCUSSION In our case, a 24-day-old infant presented with lethargy, poor feeding, vomiting, hypothermia, hypoglycemia, metabolic acidosis, hypoxemia, hepatomegaly, and hypotension. Although not all-inclusive, the most pertinent considerations for this patient in the ED are
Figure 2. 12-lead electrocardiogram obtained during tachycardic event.
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Figure 3. (A) 12-lead electrocardiogram obtained after termination of tachycardia and (B) Close-up view of precordial leads exhibiting pre-excitation with short PR interval, delta wave, and prolonged QRS complex.
infectious, cardiac, endocrine, metabolic, gastrointestinal, and traumatic etiologies (see Table 1). After a full evaluation for sepsis and underlying metabolic diagnoses was unremarkable, the conclusion was made that the Table 1. Differential Diagnosis for Neonatal Altered Mental Status: THE Misfits (1) T: Trauma Accidental Nonaccidental H: Heart disease Congenital heart disease Cyanotic Obstructive Aberrant coronary artery Dysrhythmia Myocarditis Pericarditis E: Endocrine Congenital adrenal hyperplasia Diabetes insipidus Thyrotoxicosis M: Metabolic Hypoglycemia Electrolyte imbalance I: Inborn errors of metabolism S: Sepsis Bacteremia Bacterial meningitis Urosepsis Pneumonia Viral sepsis Pertussis Congenital infection Infantile botulism F: Formula mishaps Underdilution Overdilution I: Intestinal catastrophes Malrotation with intestinal volvulus Necrotizing enterocolitis Intussusception T: Toxins and poisons S: Seizure
infant’s presentation was the sole result of cardiac failure as a result of resolved SVT. This conclusion is further supported by the rapid resolution of the child’s symptoms, return to a normal baseline after resolution of his dysrhythmia, and lack of further issues during routine outpatient follow-up. To our knowledge, this is the first case in the emergency medicine literature of an infant with cardiac failure leading to this particular constellation of signs, symptoms, metabolic, and hemodynamic derangements. This case adds another level of detail to the potential presentation of cardiogenic shock in a critically ill neonate. Due to the relative uncertainty of diagnosis at the time of presentation, management of a critically ill neonate presenting to the PED often involves simultaneous evaluation for and empiric treatment of several of multiple potential etiologies (1). Shock from a variety of etiologies can result in hemodynamic, thermoregulatory, and metabolic derangements that would not necessarily been seen in older children and adults. In our case of cardiogenic shock resulting from a resolved tachydysrhythmia, the patient presented with severe hypothermia and hypoglycemia in addition to the more expected findings of hypotension and end organ dysfunction. This further emphasizes the need to keep a broad differential diagnosis when evaluating critically ill neonates. The general work-up for a critically ill neonate includes blood, urine, and cerebrospinal fluid analyses with cultures. A chest x-ray study, and ECG are often helpful. Additional work-up may include 21-hydroxylase level, pH level, lactate, ammonia, liver transaminases, urine ketones, amino acids, organic acids, echocardiogram, and cranial imaging, depending on the clinical scenario. Emergency management of the critically ill neonate in shock includes ensuring a secure
Diagnosing Neonatal Shock
airway, providing respiratory support, circulatory resuscitation as necessary, and thermoregulation. Although treatment of sepsis requires rapid fluid resuscitation, the potential for underlying CHD with congestive heart failure (CHF) often necessitates smaller, more frequent fluid challenges (10 mL/kg normal saline increments) with assessment for improvement or decompensation after fluid administration. Hypoglycemia should be rapidly corrected with i.v. glucose administration. Empiric antimicrobial coverage includes broad-spectrum i.v. antibiotics with or without i.v. acyclovir, as well as consideration for hydrocortisone, and prostaglandin E1 therapy, depending on the clinical scenario (2–7). Cardiac dysrhythmias represent an underappreciated subset of the differential diagnosis of a critically ill infant, despite being relatively common in neonates (8). SVT, as seen in our patient, is the most common type of pediatric rhythm disturbance (8–11). SVT is a tachydysrhythmia originating above the level of the ventricles (10). ECG findings typically include a rapid heart rate (usually 220 280 bpm in infants), and a regular rhythm without variation throughout the respiratory cycle. While most cases are associated with a narrow QRS complex (<80 ms) and no discernable P wave before the QRS complex, a wide variety of presentations are possible, including wide QRS complexes and abnormal P waves (12). SVT is caused by re-entrant electrical activity either through an accessory atrioventricular connection (atrioventricular re-entrant tachycardia [AVRT]) or within the AV node (atrioventricular nodal re-entrant tachycardia) (13). Although dysrhythmia and SVT are more common in children with CHD, the majority of cases will present in patients with structurally normal hearts. WPW syndrome is a specific subclass of patients with AVRT, accounting for 10%–50% of all cases of SVT (10,11). Patients with WPW have antegrade conduction of impulses through an accessory pathway, leading to partial depolarization of ventricles and a ‘‘pre-excitation’’ pattern on ECG with a short PR interval, prolonged QRS interval, and a delta wave (Figure 3B). Similar to other etiologies of SVT, WPW is more common in patients with CHD, and up to 20% of WPW patients have some underlying CHD, most commonly Ebstein’s anomaly (11). While the majority of cases of WPW are spontaneous, there are genetic cases of WPW inherited in an autosomal dominant fashion (14). Thirty-eight percent of patients with WPW will have their first episode of SVT by the age of 2 months, and these patients who are diagnosed at a young age will often have resolution of symptoms by 8 months of age, although many experience relapse later in life (15).
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The clinical features of SVT are widely variable. Most episodes of SVT are paroxysmal with rapid onset and termination. Episodes may be very brief, lasting only seconds, or may persist for hours to days. Clinical features seen in infants with SVT include fatigue, lethargy, poor feeding, and irritability. Older children will experience palpitations, chest pain, fatigue, lightheadedness, and occasionally syncope. If episodes of SVT are prolonged and unrecognized, patients may progress to CHF due to a tachycardia-mediated cardiomyopathy. Infants are at a particularly high risk for this progression, as the early signs and symptoms are nonspecific and may be unrecognized for long periods of time. Studies have shown that 38%–50% of infants with SVT have signs or symptoms of CHF at the time of diagnosis, particularly those with symptoms for > 48 hours (10,12,16). As was seen in our patient’s case, tachycardia-induced myocardial dysfunction may persist beyond the resolution of SVT, and patients may present with signs of heart failure only if the dysrhythmia spontaneously resolves before presentation (17). In many cases, tachycardia-mediated cardiomyopathy is reversible after termination of the dysrhythmia, however, in other cases, there might be permanent myocardial injury and dysfunction (18). Emergent treatment of SVT begins with assessment of respiratory and hemodynamic status and standard initial resuscitation. Hemodynamically unstable patients with a tachydysrhythmia and signs of shock should receive immediate synchronized cardioversion (19). In stable patients with SVT, vagal maneuvers, such as Valsalva, and application of ice to the patient’s face have been shown to successfully terminate SVT in 20%–63% of cases (10,20,21). A recent randomized control trial in adults showed improved termination of SVT utilizing a modified Valsalva technique involving supine repositioning and passive leg raise when compared to standard semi-recumbent Valsalva, although this has not been studied in children, to our knowledge (22). If vagal maneuvers do not terminate the dysrhythmia, pharmacologic termination is the next step. Adenosine is an AV nodal blocking agent and is the initial drug of choice for conversion of SVT (19). The most common starting dose is 0.1 mg/kg delivered via rapid i.v. push, and if no response is noted, a second dose of 0.2 mg/kg is administered (19). Studies have suggested that infants do not respond as favorably as older children to these suggested doses, and some authors recommend increasing the starting dose of adenosine to 0.15–0.2 mg/kg (23). There is variation in management of patients who have SVT refractory to adenosine with amiodarone and procainamide being among the most commonly used antidysrhythmic agents in this setting (19).
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After resolution of SVT, prophylactic treatment is generally initiated with propranolol for 4 12 months, as recurrence is common in infants. Patients with WPW often require long-term or definitive therapy (10). In addition to propranolol, medications for prophylaxis of SVT include sotalol, digoxin, amiodarone, and flecanide. If electrophysiology studies are able to identify an accessory or AV nodal pathway, radiofrequency ablation is definitive therapy for patients with recurrent symptomatic SVT as an alternative to medication, especially in older children, once the procedure is more technically feasible. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS? While early evaluation and treatment of a critically ill neonate often centers around empiric management of sepsis, it is important for the Emergency Physician to keep in mind the myriad of other potential diagnoses that can lead to shock in an infant. While resuscitation and initiation of antimicrobial therapy is undertaken, broad examination and work-up aimed at identifying CHD, dysrhythmia, congenital adrenal hyperplasia, inborn errors of metabolism, gastrointestinal pathology, and trauma are critically important. In addition, understanding the emergent evaluation and treatment algorithm for SVT, depending on the patient’s hemodynamic status, is key for the Emergency Physician. REFERENCES 1. Brousseau T, Sharieff GQ. Newborn emergencies: the first 30 days of life. Pediatr Clin North Am 2006;53:69–84. 2. Greenhow TL, Hung YY, Herz AM. Changing epidemiology of bacteremia in infants aged 1 week to 3 months. Pediatrics 2012; 129:e590–6. 3. Kimberlin DW. When should you initiate acyclovir therapy in a neonate? J Pediatr 2008;153:155–6. 4. Kimberlin DW, Lin CY, Jacobs RF, et al. Natural history of neonatal herpes simplex virus infections in the acyclovir era. Pediatrics 2001; 108:223–9. 5. Freed MD, Heymann MA, Lewis AB, Roehl SL, Kensey RC. Prostaglandin E1 infants with ductus arteriosus-dependent congenital heart disease. Circulation 1981;64:899–905.
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