the ill-appearing neonates

1. The Ill-Appearing Neonates Atima Delaney, MD Division of Emergency Medicine Children�s Hospital Boston

2. Case 10-day-old infant presents with poor feeding for 3 days, today noted to be lethargic PE: Limp, cyanotic, mottledV/S T 37, HR 80, RR 12, BP 52/38, O2 Sat 80% RAHEENT: open, soft AF, pupils 3->2 mmHeart: RRR, no murmurLungs: no retractions, clear BSAbdomen: soft, nontender, no HSMExt: cap refills > 5 secondsNeuro: decreased tone throughout

3. Case What is initial management? What history should be taken? What are the differential diagnoses?

4. Unique Features of the Neonates

5. Ill-appearing Infants Clinical FeaturesDepressed or altered mental statusLethargyGrunting respirationHead bobbingIncreased work of breathingBradypnea, apneaPoor muscle tone or floppySkin changes: pallor, cyanosis, poor cap refills,

6. Differential Diagnoses Most common causes for catastrophic illness in the neonates

7. Differential Diagnoses �NEO SECRETS�

8. Inborn Error of Metabolism Presentation 2-7 days of age Several categories of IEM (amino acid disorders, organic acidemias, urea cycle disorders, disorders of carbohydrate metabolism, fatty acid oxidation defects, and mitochondrial disorders) GI: Poor feeding, poor suck, vomiting, FTT, hepatosplenomegaly, jaundice CNS: Irritability, lethargy, coma, death Hyperammonemia, profound acidosis Consult metabolism presentation after taking certain protein or carb, infection Although IEM may be included in newborn screening tests, infants can present before the results are available.presentation after taking certain protein or carb, infection Although IEM may be included in newborn screening tests, infants can present before the results are available.

9. Electrolytes Abnormality Hyponatremia: Water intoxication, SIADH, CAH Hypernatremia:Breastfeeding difficulty (dehydration), DI Hypoglycemia Hypocalcemia Hypocal - often seen first few days of life, high phosphate level in cow�s milk formula, maternal or congenital hypoparathyroidism, maternal vit D deficiency, hypomagnesemiaHypocal - often seen first few days of life, high phosphate level in cow�s milk formula, maternal or congenital hypoparathyroidism, maternal vit D deficiency, hypomagnesemia

10. Overdose/Toxic Exposure Methhemoglobinemia-Newborns are at risk -Reports of association with Prilocaine and occasionally EMLA use Carbon monoxide poisoning

11. Seizures May not present as tonic-clonic activity Hypoxic-ischemia injuryIntracranial hemorrhageCNS infectionsElectrolyte abnormalitiesInborn error of metabolismCongenital abnormality of brainDrug withdrawal Lip smacking, bicycling movements of the legs, tongue thrusting, apnea, and staring spellsElectrolytes: hypoglycemia, hypo/hypernatremia, hypocalcemia, hypomagnesemiaDrug withdrawal: methadone, barbituratesCNS infection: including STORCH Lip smacking, bicycling movements of the legs, tongue thrusting, apnea, and staring spellsElectrolytes: hypoglycemia, hypo/hypernatremia, hypocalcemia, hypomagnesemiaDrug withdrawal: methadone, barbituratesCNS infection: including STORCH

12. Seizures Lorazepam Phenobarbital or phynetoin/fosphynetoin Consider giving 10% Calcium gluconate if seizure persists after standard therapy Consider giving MgSO4 Pyridoxine (Vit B6) if seizure persists after above

13. Enteric Emergencies True surgical emergency Volvulus - twisting around mesenteric artery Bilious emesis (>90%), maybe well-appearing Shock if bowel is ischemic or necrotic Arrest in embryogenic gut rotation resulting in narrow mesenteric base Risk of bowel ischemia Ladd�s band procedureArrest in embryogenic gut rotation resulting in narrow mesenteric base Risk of bowel ischemia Ladd�s band procedure

14. Enteric Emergencies UGI series-Dilated duodenum-Abnormal duodeno-jejunal junction * The DJJ is low and to the right of the normal location In the image on the left, the duodenal bulb is to left of the spine. In the image on the right, with malrotation, the duodenal bulb is overlying spine. * The proximal small bowel (jejunum) is in the right upper quadrant. * The cecum is in the upper and/or left abdomen. * The large bowel is in the left abdomen. * The DJJ is low and to the right of the normal location In the image on the left, the duodenal bulb is to left of the spine. In the image on the right, with malrotation, the duodenal bulb is overlying spine. * The proximal small bowel (jejunum) is in the right upper quadrant. * The cecum is in the upper and/or left abdomen. * The large bowel is in the left abdomen.

15. Enteric Emergencies Necrotizing enterocolitis-More common in preemies-Term infants with risk factors -Ill-appearing, distended abdomen, bloody stools anoxic or stress event at birthanoxic or stress event at birth

16. Cardiac CHD often presents during first month of life Presentations1) cyanosis2) mottle or gray appearance3) CHF cyanosis due to R to L shunting Mottle or gray due to outflow obstruction CHF due to L to R intracardiac shuntingcyanosis due to R to L shunting Mottle or gray due to outflow obstruction CHF due to L to R intracardiac shunting

17. Cardiac DUCTAL DEPENDENT LESIONS Right-to-Left ShuntCyanosis, metabolic acidosis, decreased perfusion or CHF on CXRTransposition of great arteriesTetralogy of FallotTruncus arteriosusTotal anomalous venous return Left-sided Obstructive LesionsSevere systemic hypoperfusion, decreased or absent pulses, metabolic acidosis, cardiomegaly with pulmonary congestion on CXRHypoplastic left heart, Coarctation of aorta, interrupted aortic arch, AS -cyanotic lesions & obstructive lesions = ductal dependent -The ductal dependent lesions are usually of 2 types: left-sided and right-sided obstructive lesions. -Left-sided obstructive lesions (aortic stenosis, coarctation of the aorta, interrupted aortic arch, hypoplastic left heart syndrome) present with signs of severe systemic hypoperfusion with pallor, mottling, decreased or absent pulses, severe metabolic acidosis, and cardiomegaly with pulmonary congestion on chest radiograph (CXR). -R-sided obstructive lesions (pulmonary atresia, severe pulmonary stenosis, tetralogy of Fallot, tricuspid atresia) present with severe cyanosis, metabolic acidosis, and decreased perfusion of the lung fields on CXR. -cyanotic lesions & obstructive lesions = ductal dependent -The ductal dependent lesions are usually of 2 types: left-sided and right-sided obstructive lesions. -Left-sided obstructive lesions (aortic stenosis, coarctation of the aorta, interrupted aortic arch, hypoplastic left heart syndrome) present with signs of severe systemic hypoperfusion with pallor, mottling, decreased or absent pulses, severe metabolic acidosis, and cardiomegaly with pulmonary congestion on chest radiograph (CXR). -R-sided obstructive lesions (pulmonary atresia, severe pulmonary stenosis, tetralogy of Fallot, tricuspid atresia) present with severe cyanosis, metabolic acidosis, and decreased perfusion of the lung fields on CXR.

18. Cardiac Presents with CHF Left-to-Right Shunt-Large VSD-Complete AV canal defect-Large PDA SVT -Lesions with pulmonary overcirculation (atrial or ventricular septal defects, atrioventricular canal, truncus arteriosus, and partial anomalous pulmonary venous return) can present with evidence of congestive heart failure and respiratory distress; however, the deterioration in these infants is not as dramatic as with ductal dependent lesions. Congestive heart failure may also be due to supraventricular tachycardia-Lesions with pulmonary overcirculation (atrial or ventricular septal defects, atrioventricular canal, truncus arteriosus, and partial anomalous pulmonary venous return) can present with evidence of congestive heart failure and respiratory distress; however, the deterioration in these infants is not as dramatic as with ductal dependent lesions. Congestive heart failure may also be due to supraventricular tachycardia

19. Cardiac Ill-appearing neonates not responding to initial resuscitation, consider ductal- dependent CHD Hyperoxia Test100% O2 for 10 minutes Symptoms similar to septic shock!!!!! In septic appearing infants, if there is no clinical improvement after resuscitation and treatment of septic shock�..think of congenital heart disease!!!!!!!!!!!!!!!!! Diagnosis will be delayed: transferring to another facility for echoSymptoms similar to septic shock!!!!! In septic appearing infants, if there is no clinical improvement after resuscitation and treatment of septic shock�..think of congenital heart disease!!!!!!!!!!!!!!!!! Diagnosis will be delayed: transferring to another facility for echo

20. Recipe Incorrect formula preparation Home remedies Botulism-Infant botulism-Peak 2-4 mo.-Hypotonia, constipation, descending flaccid paralysis, autonomic instability, CN deficits home remedies: baking soda for colic, herbal tea for constipation or colichome remedies: baking soda for colic, herbal tea for constipation or colic

21. Endocrine 21-hydroxylase deficiencySalt-losing or Non-salt losing formsGirls: ambiguous genitaliaBoys: salt-losing adrenal crisis (vomiting, hyptension, hyponatremia, hyperkalemia, metabolic acidosis, hypoglycemia) -The most common is 21-hydroxylase deficiency resulting in the inability to convert progesterone to aldosterone or cortisol and causing an accumulation of testosterone. -Adrenal hyperplasia develops as a result of overstimulation by ACTH (which has no negative feedback from cortisol) -Deficiency of aldosterone with urinary salt wasting: classic electrolyte findings and cardiovascular collapse -Female infants classically present with ambiguous genitalia with varying degrees of virilization. Typically recognized in nursery -However, a male infant may only have a hyperpigmented scrotum and no other physical abnormalities and can only be recognized by appropriate laboratory evaluation and results of the newborn screen if available. -The most common is 21-hydroxylase deficiency resulting in the inability to convert progesterone to aldosterone or cortisol and causing an accumulation of testosterone. -Adrenal hyperplasia develops as a result of overstimulation by ACTH (which has no negative feedback from cortisol) -Deficiency of aldosterone with urinary salt wasting: classic electrolyte findings and cardiovascular collapse -Female infants classically present with ambiguous genitalia with varying degrees of virilization. Typically recognized in nursery -However, a male infant may only have a hyperpigmented scrotum and no other physical abnormalities and can only be recognized by appropriate laboratory evaluation and results of the newborn screen if available.

22. Trauma Inflicted head injury

23. Sepsis & Meningitis All ill-appearing infants should be considered sepsis until proven otherwise Irritability, lethargy, poor feeding, � fever, hypothermia, apnea, cyanosis, poor perfusion Early onset: First few days - 6 days Associated with perinatal risk factors Late onset: = 7 days Common organisms: GBS, E.coli, Gram neg rods, Listeria monocytogenes, Strep pneumoniae Early onset: 85% presents within 24 hours. Early-onset sepsis syndrome is associated with acquisition of microorganisms from the mother Maternal risk factors: PROM, maternal fever Meningitis: GBS 50%, E. Coli 25%, Rest < 10% each Late-onset sepsis syndrome occurs at 7-90 days of life and is acquired from the caregiving environment Pneumonia is more common in early-onset sepsis, whereas meningitis and bacteremia are more common in late-onset sepsis. Absence of fever or hypothermia doesn�t rule out Bulging fontanelle and nuchal rigidity are present in small number of patientsEarly onset: 85% presents within 24 hours. Early-onset sepsis syndrome is associated with acquisition of microorganisms from the mother Maternal risk factors: PROM, maternal fever Meningitis: GBS 50%, E. Coli 25%, Rest < 10% each Late-onset sepsis syndrome occurs at 7-90 days of life and is acquired from the caregiving environment Pneumonia is more common in early-onset sepsis, whereas meningitis and bacteremia are more common in late-onset sepsis. Absence of fever or hypothermia doesn�t rule out Bulging fontanelle and nuchal rigidity are present in small number of patients

24. HSV Birth- 1 month (peak 10-17 days) 1. Localized skin, eye, mouth (SEM)2. CNS � SEM3. Disseminated HSV cultures of vesicles, oropharynx, conjunctiva, urine, blood, stool or rectum, and CSF HSV PCR and LFTs - Mucocutaneous vesicles- Seizure- CSF pleocytosis with negative gram stain- Mother known to have HSV enterovirus (coxsackievirus, ECHO virus)enterovirus (coxsackievirus, ECHO virus)

25. Other Overwhelming Viral Infections Enterovirus-Myocarditis-Hepatitis Bronchiolitis with apneaRisk factors: age < 6 weeks, preemie, low O2 Sat

26. Sepsis CBC, UA, blood & urine culture, CRP LP Start Ampicillin + Gentamicin (early onset) or Ampicillin + Cefotaxime/Ceftazidime Start Acyclovir IV-CSF pleocytosis & negative gram stain-CSF pleocytosis & vesicular rash, focal neurologic signs, pneumonitis, hepatitis, maternal hx-CSF elevated RBC (cover gram neg bacilli or late onset) (cover gram neg bacilli or late onset)

27. History Maternal Hx: GBS Birth Hx: delivery, complications, birth weight Neonatal course Symptoms Feeding, UOP and stooling, emesis - bilious? Inflicted injury: no clear hx or hx inconsistent with findings -weight: lost 10% - level off by day 5-7, back to BW day 10-14, gain 20-30 g/day -Poor feeding, improper formula mixing, sweating during the feed (equivalent to stress test - if sweaty, poor suck, stops feeding after few minutes - consider CHF) -fever - although overwhelming infection can present with high, normal or low temperature-weight: lost 10% - level off by day 5-7, back to BW day 10-14, gain 20-30 g/day -Poor feeding, improper formula mixing, sweating during the feed (equivalent to stress test - if sweaty, poor suck, stops feeding after few minutes - consider CHF) -fever - although overwhelming infection can present with high, normal or low temperature

28. Physical Exam General Appearance Vital signs, pulse oxBP: neonates - SBP 60 mmHg, infants - SBP 70 mmHgHR: >220/min consider SVTRR: tachypnea, apnea, periodic breathingT: lack of fever does not exclude serious infection 4-Ext BPDiminished pulse and BP -> left-ventricular outflow obstruction GA: tone, color, perfusion, work of breathing - V/S BP, HR < 220, RR < 60, periodic breathing temp = rectal temp Broslow tapeGA: tone, color, perfusion, work of breathing - V/S BP, HR < 220, RR < 60, periodic breathing temp = rectal temp Broslow tape

29. Physical Exam Head: fontanelle, scalp HEENT: pupils, neck Chest: nasal flaring, grunting, retractions, breath sounds, murmur Abdomen: distention, rigidity, hepatomegalyNormal exam doesn�t exclude abdominal pathology Skin: cap refills, petechiae Neuro: mental status, muscle tone, abnormal movement -most murmurs in neonates are pathologic: VSD, PDA, PS, Aortic stenosis -Abdominal distention nonspecific, tenderness may be difficult to evaluate, rigidity is worrisome, hepatomegaly - CHF-most murmurs in neonates are pathologic: VSD, PDA, PS, Aortic stenosis -Abdominal distention nonspecific, tenderness may be difficult to evaluate, rigidity is worrisome, hepatomegaly - CHF

30. Management ABCD Obtain V/S, pulse oxymetry, glucose Monitoring Treat hypovolemia and electrolyte abnormality Treat hypothermia & maintain body temperature Give O2Give O2

31. Airway Intubation Preemie: 2.5 mmFull-term: 3 - 4 mm1 yo- toddler: 4-4.5 mm Broselow tape Cuffed or uncuffed tubesCuffed tube: high inspiratory pressure RSI: atropine recommended

32. Circulation IV, umbilical vein, IO IO access early if failed IV attempts Give 20 ml/kg NSS bolus (unless CHF) Septic shock:- Requires several fluid boluses- Children who received > 40 ml/kg in the first hour do better than those receiving < 20 ml/kg (Carcillo, JAMA 1991) Maintenance fluid D5 1/4NSS @ 4 ml/kg/hr

33. Circulation Anemia or trauma: 10 ml/kg PRBC If no improvement in BP, mental status, skin perfusion after 60-80 ml/kg of NSS -> Dopamine starting 6-10 mcg/kg/min-> Consider central line

34. Hypoglycemia Presumed hypoglycemia in all critically ill infants until proven otherwise Treat if blood glucose < 50 mg/dL Give D10 W 5-10 ml/kg -poor feeding, small glycogen storage, high metabolic demands in critically ill infants-poor feeding, small glycogen storage, high metabolic demands in critically ill infants

35. Antibiotics & Acyclovir Presumed septic until proven otherwise Early antibiotic (within 30-40 min) in most ill-appearing infants = 28 days: Ampicillin + gentamicin or Ampicillin + Cefotaxime Older infants: Ceftriaxone Acyclovir: infants = 28 daysMucocutaneous vesiclesSeizureCSF pleocytosis with negative gram stainCSF RBC from atraumatic LP Ampicillin treats gram positive, listeria and enterococcus. Gentamin treats gram negative and synergistic effect. Ceftriaxone in younger infants can cause biliary sludging. S. pneumo meningitis - add vanco to cover resistant strain Ampicillin treats gram positive, listeria and enterococcus. Gentamin treats gram negative and synergistic effect. Ceftriaxone in younger infants can cause biliary sludging. S. pneumo meningitis - add vanco to cover resistant strain

36. Other Specific Treatment Prostaglandin E1- Cyanotic or obstructive heart disease with hemodynamic instability- Temporarily restore pulmonary and systemic blood flow- Consult cardiologist & neonatologist- 0.05 mcg/kg IV infusion, titrate to lowest dose Side effects: apnea, tachycardia, hypotension Hydrocortisone-Usually male patient with adrenal crisis-Draw blood work before if possible stress dose hydrocortisonestress dose hydrocortisone

37. Diagnostic studies Bedside:glucose, urine dipstick, EKG LabsCBC, blood cultureElectrolytes, Ca, Mg, PhosBlood gasAmmonia, lactate, pyruvate, blood & urine ketoneUA, urine cultureLP for CSF, CSF culture (if stable) CSF HSV PCR or enterovirus (if indicated)Bilirubin level infants may not demonstrate pyuria when UTI is present, always obtain urine cultureinfants may not demonstrate pyuria when UTI is present, always obtain urine culture

38. Radiology Tests CXR Abdominal plain film Head CT Upper GI series

39. Summary Treat sepsis in all ill-appearing neonates Check bedside glucose in all ill-appearing neonates DDx: NEO SECRETS Neonates with bilious emesis needs work-up to rule out volvulus which is true surgical emergency Monitor glucose and temperature throughout ED stay