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Mimi Lu, MD, FAAEM Clinical Assistant Professor

Assistant Residency Program Director

Director, Pediatric Emergency Medicine Education

University of Maryland School of Medicine

Baltimore, Maryland

No relevant financial disclosures

Outline Recent literature pertaining to

Fever

Bronchiolitis

Sedation

Questions? mlu@umaryland.edu

For a PDF copy of all slides, go to:

lectures.umem.org/AAEM [will be posted after AAEM for 1 month]

FEVER

Case: the febrile infant

18 day boy felt “warm” at home

◦ ROS negative

◦ T = 38.4 ºC rectal

◦Well-appearing

◦ unremarkable physical exam

9 week 9 month girl

39.4

Infant Fever

Work-up:

Infant Fever Work-up: ABC’s

• Full sepsis evaluation:

– Analysis of urine (UA, UCx)

– Blood (CBCD, BCx)

– CSF (cell count, protein, glucose, GS/Cx)

– ± CXR

– ± Antibiotics

Rochester

Philadelphia

Boston

Boston Philadelphia Rochester

Age (days) 28-89 29-56 0-60

Temp (0C) > 38.0 > 38.0 > 38.0

Infant Obs. Score Yes Yes No

Peripheral WBC < 20,000 < 15,000 5-15,000

CSF obtained Yes Yes No

Antibiotic given Yes No No

SBI in low risk pts (%) 5.4 0 1.1

NPV (%) 94.6 100 98.9

Sensitivity (%) Not stated 100 92.4

Component of fever protocols

Avner, Emerg Med Clin North Am, 2002

UCx

UA

BCx

CBC

CSF

admit

UCx

UA

BCx

CBC

CSF

UCx

UA

BCx

CBC

UCx

UA

BCx

UCx

UA

UCx

UA

BCx

CBC

CSF

admit

UCx

UA

BCx

CBC

CSF

UCx

UA

Future….

Viral tests?

Inflam markers?

OUT with the

and IN with the

Changing epidemiology

Greenhow, Pediatr Infect Dis J, 2014

Population study

◦ Impact of prenatal screen and immunizations

SBI < 90 days

◦ 13% overall incidience

◦ 92% SBI are UTI

No Listeria or meningococcus

Greenhow, 2014

Clinical appearance, WBC: poor predictors

Greenhow, 2014

Table 3: Bacterial Pathogens Detected in 129 Blood, 823 Urine and 16 CSF cultures

Greenhow et al, Pediatr Infect Dis J, 2014

Listeria in neonates

Hassoun et al, Pediatr Emerg Care, 2014

Epidemiology and ampicillin sensitivity of

listeria and enterococcal infections

2 center retrospective review, 2006-2010

1192 neonates

Listeria in neonates

Results

6% SBI

◦ 1/1192 (0.08%) enterococcal bacteremia

◦ 1/1192 (0.08%) listeria bacteremia

◦ 15/1192 (1.4%) enterococcal UTI

◦ UA less helpful for enterococcal UTI vs E coli

◦ Increasing resistance to ampicillin

Listeria in neonates

Conclusion:

Listeria is uncommon cause of neonatal

SBI in febrile neonates presenting to ED

Empiric use of ampicillin may need to be

reconsidered

Occult bacteremia

Hernandez-Bou, Acta Paediatr, 2015

Rate of bacteremia after 13-valent

pneumococcal conjugated vaccine

591 pts, 3 mo to 36 mo

1% bacteremia, 2.7% contamination

Occult bacteremia

Conclusion

Occult bacteraemia is an uncommon

event in well-appearing febrile children

aged three to 36 months

Close follow-up should replace blood

analysis

The $$ is in the pee!!!

AAP Clinical Practice Guideline, 2011

UTI

Frumkin, J Emerg Med, 2014

Retrospective observational 5 year study

4403 urine cultures

Age 0-36 months

Boys: cultured less but higher positive culture rate; more gram-positive organisms

TMX/SMP and amoxicillin/clavulanic acid effective against all isolates

UTI and Bacteremia

Schnadower et al, Pediatrics, 2010

PECARN retrospective review

29-60 day infants with UTI

Conclusion

Low risk: adverse events and bacteremia

Consider brief hospitalization or

outpatient management

UTI and Bacteremia

Averbuch, Pediatr Infect Dis J, 2014

Hernandez-Bou, Pediatr Infect Dis J, 2014

Conclusion

Afebrile young infant with UTI still at risk

for bacteremia

Well-appearing infants with UTI with PCT

< 0.7 ng/ml at very low risk bacteremia

UTI and Meningitis

Paquette, Pediatr Emer Care, 2011

Tebruegge, PLoS One, 2011

Greenhow, Pediatr Infect Dis, 2014

Risk of co-existing UTI and meningitis is

small (except neonates!). More selective

approach warranted.

New stimulation technique to obtain midstream urine in newborns.

María Luisa Herreros Fernández et al. Arch Dis Child 2013;98:27-29

Copyright © BMJ Publishing Group Ltd & Royal College of Paediatrics and Child Health. All rights reserved.

UCx

UA

BCx

CBC

CSF

admit

UCx

UA

BCx

CBC

CSF

UCx

UA

Future….

Viral tests?

Inflam markers?

Inflammatory markers

White Blood Cell (WBC)

Absolute Neutrophil Count (ANC)

C Reactive Protein (CRP)

Procalcitonin (PCT)

© 2007 Lippincott Williams & Wilkins, Inc. Published by Lippincott Williams & Wilkins, Inc. 5

FIGURE 2 . ROC for PCT, CRP, WBC count, and ANC for prediction of SBI.

Andreola, Pediatr Infect Dis J, 2007

WBC and height of fever inaccurate

predictors of SBI in infants 3-24 months.

Fever and White Count

Rudinsky, Acad Emerg Med, 2009

De et al, Arch Dis Child, 2014

Greenhow, Pediatr Infect Dis J, 2014

CRP and PCT

CRP and PCT strong predictors of SBI

Nijman, Pediatr Infect Dis J, 2014

Segal et al, Arch Dis Child, 2014

Procalcitonin

Pierce, Curr Opin Pediatr, 2014

Review of diagnostic and prognostic utility

of PCT in children

England, J Emerg Med, 2014

Meta-analysis of febrile infants <90 days

Procalcitonin and SBI

Mahajan et al, Acad Emerg Med, 2014

Prospective multicenter study

226 febrile children < 36 months

13.3% SBI

Conclusion

Procalcitonin more accurate biomarker for identifying young febrile infants and children with SBIs

RSV and SBI risk

RSV positive RSV negative

Any SBI 17/244 7% (4.1%-10.9%)

116/925 12.5% (10.5%-14.8%)

UTI 14/261 5.4% (3.0%-8.8%)

98/966 10.1% (8.3%-12.2%)

Bacteremia 3/267 1.1% (0.2%-3.2%)

22/968 2.3% (1.4%-3.4%)

Meningitis 0/251 0% (0%-1.2%)

8/938 0.9% (0.4%-1.7%)

Levine, Pediatrics, 2004

Conclusion: Febrile infants with bronchiolitis

have lower risk of SBI … but check for UTI

Bronchiolitis and SBI risk

Melendez and Harper, 2003

Levine, 2004

Titus and Wright, 2003

Ralston, 2011

Influenza and SBI risk

Influenza + (N = 123) Influenza - (N = 721)

Any SBI 3/119 2.5% (0.5%-7.2%)

92/690 13.3% (10.9%-16.1%)

UTI 3/123 2.4% (0.5%-6.9%)

77/712 10.8% (8.6%-13.3%)

Bacteremia 0/123 0% (0%-2.4%)

16/715 2.2% (1.3%-3.6%)

Meningitis 0/119 0% (0%-2.5%)

6/698 0.9% (0.3%-1.9%)

Enteritis 0/3 0% (0%-56.2%)

1/60 1.7% (0.3-8.9%)

Krief, Pediatrics, 2009

Fever: sources decreasing SBI risk

Focal bacterial infection

◦ AOM, cellulitis

Named viral infection

◦ Bronchiolitis, croup

◦ Infant < 3 months: still consider UTI

◦ Infant > 3 months: SBI/UTI unlikely

Summary

OUT with the

and IN with the

UCx

UA

BCx

CBC

CSF

admit

UCx

UA

BCx

CBC

CSF

UCx

UA

Future….

Viral tests?

Inflam markers?

BRONCHIOLITIS

Clinical Practice Guideline

Diagnosis

Based on H&P

No routine labs or radiographs

Risk factors:

◦ age < 12 weeks, prematurity, underlying CP

disease, immunodeficiency

Ralston et al, Pediatrics, 2014

Clinical Practice Guideline

Treatment

Albuterol?

Epinephrine?

Steroids?

Hypertonic saline?

Ralston et al, Pediatrics, 2014

Clinical Practice Guideline

Treatment

Supplemental oxygen?

Continuous pulse oximetry?

Antibiotics?

Fluids?

Ralston et al, Pediatrics, 2014

Oximetry in bronchiolitis

Schuh et al, JAMA, 2014

Randomized, double-blind, parallel group

2008 to 2013

213 healthy infants 4 wks to 12 mo

Mild to moderate bronchiolitis

Oximetry in bronchiolitis

Results

Hospitalization rates using true saturation vs altered display (41% vs 25%)

No difference: use of supplemental oxygen, LOS ED, unscheduled visits within 72 hrs

Conclusion

Oxygen saturation should not be only factor in decision, to admit; may need to re-evaluate its use

HFNC on Wards?

Mayfield et al, J Paediatr Child Health, 2014

Prospective pilot study

Safety and impact on ward

Responders identified within 60 minutes

HFNC 4 times less likely to need PICU

No adverse events

Conclusion:

HFNC treatment on the paediatric ward is safe

HFNC vs nCPAP

Metge et al, Eur J Pediatr, 2014 Jul

Retrospective review

French PICU

2 consecutive bronchiolitis seasons

Conclusion

No difference between RR, HR, FiO2, CO2 in management of severe bronchiolitis in PICU

Summary so far…

Out with the “L”, in with the “P”

Continued supportive care with

bronchiolitis

Early intervention with HFNC or NIPPV

Sedation

Ideal sedative agent(s)

Safe

Easy to administer

Effective and predictable

Rapid onset of action

Rapid recovery

Minimal adverse effects

Sedative agents

Ketamine

Midazolam

Morphine

Fentanyl

Meperidine

Methohexital

Clonidine

Propofol

Etomidate

Dexmedetomidine

Diphenhydramine

Chloral hydrate

Pentobarbital

Ketamine

Reliable

Dissociative agent

Amnesia

Analgesic properties

Favorable safety profile

Ketamine

Hypertension

Tachycardia

Prolonged recovery period

Emergence reaction

Laryngospasm

Emesis

Ketamine

Kinder et al, Pediatr Emerg Care, 2012

◦ Higher BMI associated with higher risk of

vomiting

Street,and Gerard, J Pediatr, 2014

◦ Fixed dose ketamine

Chinta et al, Ann Emerg Med, 2015

◦ Rapid administration

Sedative-hypnotic agent

Rapid onset

Rapid recovery

Short duration of action

Amnestic properties

Antiemetic

Propofol

Propofol

No analgesia

Transient hypotension

Dose-dependent respiratory depression

Bradycardia

Hypoxia

Ketamine-Propofol

Analgesic/ anesthetic synergy

◦ Reduced total dose required of each agent

◦ Less toxicity

Complementary effects

◦ Sympathomimetic effects counter

hemodynamic depression

◦ Analgesic effects of ketamine

◦ Antiemetic effects of propofol

Sharieff, Peds Emerg Care, 2007

Shah, Ann Emerg Med, 2011

Alletag, Pediatr Emerg Care, 2012

“Newer” agents

Dexmedetomidine

Highly selective alpha agonist

Adjunctive agent for sedation and sedation

Rapid recovery

Safe

Effective

Phan and Nahata, Paediatr Drugs, 2008

Teshome et al, Hosp Pediatr, 2014

Sheta et al, Paediatr Anesth, 2014

Yuen et al, Anesth Analg, 2014

Pasin et al, Paediatri Anesth, 2015

Nitrous oxide

Pasaron et al, Pediatr Surg Int, 2015

Provides safe sedation and amnesia

Decreased pain and anxiety

No fasting or postoperative monitoring

Inhaled nitrous oxide vs IV ketamine

Lee, Pediatr Emeg Care, 2012

Prospective randomized study

Results for nitrous oxide:

◦ Less total sedation time

◦ Less recovery time

◦ Longer induction times

◦ Lower sedation level

◦ Comparable pain scales and satisfaction

iNO vs ketamine

Conclusion:

Nitrous oxide inhalation was preferable

to injectable ketamine

Safe, faster recovery, maintains sufficient

sedation time, and does not induce

unnecessarily deep sedation.

Del Pizzo and Callahan, Pediatr Emerg Care, 2014

Intranasal ketamine

Tsze et al, Pediatr Emerg Care, 2012

Andolfatto et al, Acad Emerg Med, 2013

Nielsen et al, Paediatr Anesth, 2014

Graudins et al, Ann Emerg Med, 2015

PICHFORK Trial

Comparison?

Surendar, J Clin Pediatr Dent, 2014

◦ Triple blind randomized study

◦ Intranasal dexmedetomidine, midazolam and

ketamine for their sedative and analgesic

properties: a triple blind randomized study.

Conclusion:

◦ All study drugs can be used safely and

effectively through IN route

Bonus!

Withdrawl of OTC CCM

Alternatives:

◦ Fluids

◦ Humidified air?

◦ NSAIDS?

◦ Anti-histamines?

◦ Echinacea

◦ Zinc

◦ Honey

◦ Vitamin C?

2.5 mL qhs (>1 year of age)

Summary

Fever

◦ Decrease: Listeria and LPs

◦ Increase: Urine cultures, Procalcitonin

Bronchiolitis

◦ Continued supportive care

◦ High flow nasal cannula

Sedation

◦ Dexmedetomidine

◦ Intranasal meds

Questions?

mlu@umaryland.edu

For a PDF copy of all slides, go to:

lectures.umem.org/AAEM [will be posted after AAEM for 1 month]