To Test or Not to Test – that is the question …

Kevin Chan, MD, MPH, FRCPC, FAAPClinical Chief, Children’s Health

Division Head, Pediatric Emergency, Janeway Children’s Hospital

To indicate when should investigations be conducted for fever: bloodwork, urine, chest X-rays, and LP

To look at what the value of clinical and ultrasound is on predicting acute appendicitis

Identify current risk factors for the need for CT in head injury

Identify the various rules for ankles and knees and their requirements for X-rays

Objectives

A 6 week old baby comes in with a 1 day history of fever. Besides the temperature, his vitals signs are stable and his examination is normal?

How many of you would:a. Do a full septic workup including LP?b. Do a partial septic workup without a LP?c. Do a urine test?d. Do no testing?

Case #1

A 6 week old baby comes in with a 1 day history of fever. Besides the temperature, his vitals signs are stable and his examination is normal?

How many of you would:a. Do a full septic workup including LP?b. Do a partial septic workup without a LP?c. Do a urine test?d. Do no testing?

* All of the answers may be right …

Case #1

In the Pre-Hib and Pre-Prevenar eras

Prior to Hib and Prevenar vaccines: 20% of children had a fever with no identifiable

source of infection, or a self-limited viral infection 10% of all children with fever without focus had

occult bacteremia or serious bacterial illness 3% of well appearing children had bacteremia

Source: Baraff LJ. “Management of fever without source in infants and children.” Annals of Emergency Medicine. 2000; 36: 602-614.

In the 1980s, pre-Hib and pre-Prevenar vaccines

Risk of bacteremia

5%

1%

15,000 30,000 WBC

Why Are We Interested?

After Hib: 1.5-2% rate of occult bacteremia 90% of bacteremia was Streptococcus pneumoniae

Source: Lee GM, Harper MB. “Risk of bacteremia for febrile young children in the post-Haemophilus influenzae type b era.” Archives of Pediatrics and Adolescent Medicine. 1998; 152: 624-628.

Traditional Work-up

Toxic children: Septic work-up with iv antibiotics < 28 days: Full septic-workup until culture results are

obtained, or source of fever is identified 28-90 days: Screening blood work, and Ceftriaxone

given (50 mg/kg) 3-36 months, non-toxic, < 39°C: Observation unless

other diagnoses considered 3-36 months, non-toxic, > 39°C, and WBC > 15,000:

Treat with antibiotics until culture results obtainedSource: Baraff LJ, Bass JW, Fleisher GR, et al. “Practice guideline for the management of infants and children 0 to 36 months of age with fever without source. Agency for Health Care Policy and Research.” Annals of Emergency Medicine. 1993 July; 22 (7): 1198-1210.

Diagnostic CriteriaCriteria Boston Philadelphia Rochester

Age 28-90 days 28-90 days < 60 days

Appearance Well-looking Well-looking Well-looking

CSF WBC < 10 / mm3 < 8 / mm3

Urinalysis < 10 WBC/hpf < 10 WBC/hpf < 10 WBC/hpf

WBC count < 20 x 109 < 15 x 109 5-15 x 109

Band:Neutrophil Ratio

< 0.2

Band count < 1.5 x 109

CXR (if obtained) Normal Normal

Stool Negative for blood; Few or no WBC

< 5 WBC/hpf

Prior history Previously healthy

Stoll and Rubin (2004)

Retrospective Chart Review over 15 months 2-36 months of age Occult Bacteremia: 0.91% (0-1.9%) PPV of WBC Count > 15,000 = 3.2% PPV of WBC Count > 20,000 = 7.1% Caveat: only 28% of infants < 6 months had 3

vaccinations; only 66% of infants < 12 months had received 3 vaccinations

Stoll ML, Rubin LG. “Incidence of Occult Bacteremia Among Highly Febrile Young Children in the Era of the Pneumococcal Conjugate Vaccine.” Archive of Pediatrics and Adolescent Medicine. July 2004; 158: 671-675.

Herz et al. (2006)

Retrospective case series, 1998-2003 3 months to 3 years Prevenar introduced: April 2000 84% reduction in S. pneumoniae bactermia (1.3 to 0.2%) 56% reduction in overall bacteremia (1.6 to 0.7%) E.coli dominating < 1 year (2.5 time more frequent than

S. pneumoniae), all 27 patient had UTIs as well

Source: Herz AM, Greenhow TL, Alcantara J, et al. “Changing Epidemiology of Outpatient Bacteremia in 3- to 36- Month-Old Children After the Introduction of Heptavalent-Conjugated Pneumococcal Vaccine.” Pediatric Infectious Disease Journal. April 2006; 25 (4): 293-300.

Blood Cultures Obtained

1998-1999 1999-2000 2000-2001 2001-2002 2002-20030

1000

2000

3000

4000

5000

6000

Pediatric Clinics Emergency Departments

Important Change

WBC count > 15,000: 74% sensitivity, 54.5% specificity in predicting

bacteremia Positive Predictive Value: 1.5% Negative Predictive Value: 99.5%

Treating a child with WBC > 15,000 has little value in the post-Prevenar era

Sard et al. (2006)

Retrospective chart review, community setting US 1-36 months January 1997 – January 2005 Significant decline of S. pneumoniae from 1% to

0.2% in patients with blood cultures drawn If WBC < 15 x 109, time to positive culture > 24

hours, and Gram stain negative predictive of contaminant

Source: Sard B, Bailey MC, Vinci R. “An Analysis of Pediatric Blood Cultures in the Postpneumococcal Conjugate Vaccine Era in a Community Hospital Emergency Department.” Pediatric Emergency Care. May 2006; 22 (5): 295-300.

Carstairs et al. (2007)

Noncurrent prospective observational cohort study

< 36 months Compared vaccinated vs. unvaccinated

children for pneumococcal bacteremia 0% vs. 2.4% positive pneumococcal blood

cultures (vac. vs. unvac)Carstairs KL, et al. “Pneumococcal Bacteremia in Febrile Infants Presenting to the Emergency Department Before and After the Introduction of the Heptavalent Pneumococcal Vaccine.” Annals of Emergency Medicine. June 2007; 49 (6): 772-777.

Waddle and Jhaveri (2009)

Retrospective review: microbiology laboratory database and chart review

3-36 months Significant drop in occult bacteremia from 6.8%

(3.6-12.1%) to 0.4% (0 – 2.2%) between the pre- and post- PCV7 era, fever with no focus

No change in UTI rates (6.8% vs. 7.6%) However, antibiotic usage did not change

Source: Waddle E, Jhaveri R. “Outcomes of febrile children without localising signs after pneumococcal conjugate vaccine.” Archives of Disease in Childhood. 2009; 94: 144-147.

Wilkinson et al. (2009)

Retrospective chart review over 4 years 8408 children, 3-36 months Not all children got blood cultures with fever

(results are therefore underreported) Occult bacteremia: 0.25% (0.16-0.37%) Streptococcal bacteremia: 0.17% (0.09-0.27%) 7.6 contaminants for every true positive blood

cultureSource: Wilkinson M, Bulloch B, Smith M. “Prevalence of Occult Bacteremia in Children Aged 3 to 36 Months Presenting to the Emergency Department with Fever in the Postpneumococcal Conjugate Vaccine Era.” Academic Emergency Medicine. 2000; 16: 220-225.

Implications

Need 588 cultures to detect 1 case Need 14,700 cultures to detect one S. Pneumoniae

meningitis, 49,000 cultures to prevent one neurologic sequelae and 184,000 cultures to prevent 1 S. pneumoniae death

Large costs associated with contaminated blood cultures

Summary of Articles

3 to 36 months, well-appearing children: 0.17 - 0.91% have pneumococcal bacteremia 0.65 - 0.91% have occult bacteremia UTI rates have not declined (consideration for

during urinalysis) Time to get rid of the blood culture and relying on

the WBC count if the child is immunized There is something that is useful, but expensive:

pro-Calcitonin … (Enguix et al. Intensive Care Medicine, 2001: 27: 211-215)

The evidence for doing bloodwork

Risk of bacteremia

0.2%

.025%

15,000 30,000 WBC

Caveats

Evidence of serotype replacement occurring (with non-vaccine specific serotypes) *

Immunization accuracy is questionable when taken from parents, an ED registry, and a state immunization registry†

Sources: * Singleton RJ, Hennessy TW, Bulkow LR. “Invasive Pneumococcal Disease Caused by Nonvaccine Serotypes Among Alaska Native Children With High Levels of 7-Valent Pneumococcal Conjugate Vaccine Coverage.” JAMA. April 25, 2007; 297 (16): 1784-1792.† Williams ER, Meza Ye, Salazar S, Dominici P, Fasano CJ. “Immunization Histories Given by Adult Caregivers Accompanying Children 3-36 Months to the Emergency Department: Are Their Histories Valid for the Haemophilus influenza B and Pneumococcal Vaccines?” Pediatric Emergency Care. May 2007; 23 (5): 285-288.

For Children, 28-90 days old

Evidence of a decline in Invasive Pneumococcal Disease (bacteremia or meningitis) secondary to herd effects 43% reduction of population rates in the US Studies from Ontario show 30% reduction At this time, no studies on initial ED presentation and

correlation with outcomes Time to revisit the Boston/Rochester/ Philadelphia criteria?

Source: Poehling KA, Talbot TR, Griffin MR et al. “Invasive Pneumococcal Disease Among infants Before and After Introduction of Pneumococcal Conjugate Vaccine.” JAMA. 2006; 295 (14): 1668-1674.

Rates of UTI generally hover about 7% (Levine et al. Pediatrics; 2004: 113: 1728-1734) Even in RSV+ bronchiolitis patients, the UTI risk is

5.4% (3.0-8.8%) In RSV- bronchiolitis, the UTI risk is 10.1% (8.3-12.2%)

However, urine bag specimens are not useful (Al-Orifi F, J Peds, 2000: 137: 221-226) 63% false positivity rate leading to significant call

backs, and too many children being placed on antibiotics inappropriately

The need for urine

If there’s no symptoms, there’s no value in doing a CXR (Bramson, Pediatrics: 1993: 92 (4): 524-526)

Clinical findings Tachypnea Rales/rhonchi Retractions, wheezing, coryza Grunting, stridor, nasal flaring Cough

Do I need to do a CXR?

1 in about 12 children with fever and cough past 48 hours would have a lobar pneumonia (irrespective of the severity)

In the post-Prevenar era, this is about 1 in 20-25 (Nelson et al. Vaccine. 2008; 26 : 4947-4954)

Previously

Infectious Disease Society of North America (Bradley et al. Clinical Infectious Disease; 2011 53(7): e25-e76) Treat if looks like pneumonia Don’t treat if it doesn’t look like pneumonia Do CXR if you’re not sure, but not useful if

done too early (at least 24 hours) There is another argument, do CXR to

prevent overprescribing antibiotics

What to do?

<28 days, full septic work-up 28-60 days is controversial

Full septic Partial septic are generally agreed upon (from

PAS conference 2013)

Investigations for fever

For children > 60 days Sick or not sick?

If sick, investigate Vaccinated or unvaccinated?

If unvaccinated, consider investigating Then, take a urine CXR if unsure about respiratory diagnosis

Investigations for fever

There’s no clear statement in the literature Generally, accepted at 14 days, you should test

Essentially to r/o leukemia But investigate chronic infections/rheumatologic

conditions 5-14 days is a gray zone

Definitely, if Kawasaki’s suspected Otherwise, no clear literature

<5 days, looking well: no need for bloodwork

When do I investigate when fever persists?

A 14 year-old girl comes in with RLQ pain for 12 hours, she has a fever, anorexia, but has not vomited. The pain did not migrate, but she does have cough and percussion tenderness. She comes back and has a normal WBC and no left shift. What is the likelihood that she has appendicitis?

Case #2

Cough/percussion tenderness = 2 Anorexia = 1 Pyrexia (fever) = 1 Nausea/emesis = 1 Tenderness in the RLQ = 2 Leukocytosis (> 10,000 WBC) = 1 PMN = 1 Migration of pain = 1

Pediatric Appendicitis Score

Score 8 and above, indicates a likely appendicitis

Score 3 and below, indicates unlikely appendicitis

Pediatric Appendicitis Score

A 14 year-old girl comes in with RLQ pain for 12 hours, she has a fever, anorexia, but has not vomited. The pain did not migrate, but she does have cough and percussion tenderness. She comes back and has a normal WBC and no left shift. What is the likelihood that she has appendicitis?

Her PAS is 6. We’re not sure … she’s equivocal.

Case #2

Established by Barbara Garcia-Pena (at Children’s Hospital, Boston) was to do US then CT for suspected pediatric appendicitis (AJR, 2000; 175 (1): 71-74)

Currently, the recommendation by the American Society of Radiology

Recognition of CT abdomen and its potential cancer risks (Brenner, AJR, 2001; 176: 289-296, and Pearce, Lancet, 2012, 380: 499-505.)

The American Algorithm

Initial U/S, with a repeat U/S for equivocal examinations

Grant Thompson did a survey across the PERC sites and showed that this was the most common algorithm

The Canadian Algorithm

Combined Use of Ultrasound and Interval Pediatric Appendicitis

Score in Suspected Appendicitis

Suzanne Schuh, Andrea Doria, Marcela Preto-Zampreski, Jacob Langer, Carina Man, and Kevin

Chan

Looked at a 4 hour PAS scores, in combination with an U/S to determine if repeated clinical examination could eliminate the need for further testing

Primary objective: To compare the proportion of children who are candidates for early disposition from the ED US-PAS approach versus a strict (1 or 2) Ultrasound

approach Secondary objectives:

Clinical outcomes, resource use and economic costs

Our Research

Candidates for Early Disposition

The U/S approach = 72/294 (24.5%) could be discharged early

The U/S – PAS approach = 179/294 (60.9%) could be discharge early (p<0.0001)

What does this mean for early discharge?

Test characteristics of 2 pathways

US approach

93.2% diagnostically accurate

97.2% of appendicitis cases detected

90.7% of non-appendicitis cases detected

Sens: 97.3%, Spec: 90.7%, PPV: 86.4%, NPV: 98.2%

US – PAS Approach

95.2% diagnostically accurate

97.2% of appendicitis cases detected

94% of non-appendicitis cases detected

Sens: 97.3%, Spec: 94%, PPV: 90.8%, NPV: 98.2%

Resource Usage of 2 pathways

US approach

43 second ultrasounds 4 CTs 120 surgeries, 14

negative operations 136 hospitalizations Mean LOS in ED = 597

minutes

US – PAS approach

38 second ultrasounds 4 CTs 115 operations, 9

negative operations 128 hospitalizations Mean LOS = 530 minutes

The US-PAS approach saves approximately $110 million ($82-146 million) to the health care system and $115 million ($86-156 million) to society in the US

It saves $1.8 million ($1.4-2.3 million) to the health care system and $2.4 million ($1.8-3.0 million) to society in Canada

Compared to the US-CT approach, the savings are approximately $170 million ($126-$245 million) in the US.

Cost Savings

First study to look at the interval PAS score to help disposition decisions in suspected appendicitis

Doing this, reduces the number of CTs, and provides an indication of who can be discharged sooner in the Emergency department

This approach saves resources and costs, and represents a small but sizable savings in appendicitis care.

Discussion

A recent study by Mittal et al. (Academic Emergency Medicine. 2013; 20: 697-702) showed that U/S have suboptimal sensitivity, and highlights the value of ultrasound with clinical re-assessment.

The initial PAS by itself was not helpful in identifying appendicitis.

Discussion

Just because an ultrasound is reported at positive, 1/3 of them with low PAS scores (2-5) did NOT have appendicitis Suggest surgical consultation with this group Remember that negative appendectomies do

have a complication risk of about 4.6%, and cannot be ignored.

Note

In the US, still about 35% of children (Bachur et al., J Peds; 2012; 160: 1034-1038) undergo a CT, yet only 3% of these cases required CT.

How do we avoid the CT? Re-evaluation of the criteria of appendicitis at 6 mm

may be warranted New work on focused MRI examination of the RLQ

being conducted Longer duration of abdominal pain, increases U/S

sensitivity

Discussion

A 12 year-old boy is playing soccer and is pushed into the goal post. He comes in with a headache and is dizzy. He has a severe headache and a large hematoma on his frontal-temporal region. He has a GCS of 14. His examination right now is otherwise normal (including normal vital signs, no neck stiffness and a normal neurological exam.) What do you do?

a. Get a CT of the headb. Get a skull X-rayc. Observe for 6 hours in the ERd. Admit to hospital for observation

Case #3

A 12 year-old boy is playing soccer and is pushed into the goal post. He comes in with a headache and is dizzy. He has a severe headache and a large hematoma on his frontal-temporal region. He has a GCS of 14. His examination right now is otherwise normal (including normal vital signs, no neck stiffness and a normal neurological exam) What do you do?

a. Get a CT of the headb. Get a skull X-rayc. Observe for 4-6 hours in the ERd. Admit to hospital for observation

Case #3

CATCH rules (3866 patients (Osmond et al. CMAJ, 2010: 182 (4): 341-348) (for patients with GCS of 13-15) 4 high risk factors (sensitivity of 100% (86.2-100%))

Failure to reach GCS within 2 hours Suspicion of open skull fracture Worsening headache Irritability

3 medium risks factors (sensitivity of 98.1%) (94.6-99.4%)) Large, boggy hematoma Signs of basilar skull fracture Dangerous mechanism of injury

Any of them should necessitate a CT

How important is mechanism?

PECARN has tracked out 42,412 patients (Kuperman et al., Lancet 2009; 374: 1160-1170)

Severe injury mechanisms: High-speed MVA (either occupant or pedestrian struck) Bicycle-related injury (or similar vehicle) High-speed projectile Fall from a height or down stairs

Isolated severe injury mechanisms (PECARN Head Injury Predictor Rules)

No significant signs or symptoms of TBI Altered mental status (GCS < 15, agitation, sleepiness, slow

responses or repetitive questioning) Nonfrontal scalp hematoma LOC > 5 seconds Palpable skull fracture Not acting normally according to parents

How important is mechanism?

(Nigrovic et al. Arch Pediatr Adolescent Medicine, 2012 (4): 356-361) 42,099 had injury mechanisms

5869 (14%) had severe injury mechanisms 3302 (8%) had isolated severe injury mechanisms

367 children had clinically important Traumatic Brain Injuries (TBIs) (0.9%)

4/1327 children < 2 had clinically important TBIs with isolated severe injury mechanisms

12/1975 children > 2 had clinically important TBIs with isolated severe injury mechanisms

The Results

Isolated severe injury mechanisms No significant signs or symptoms of TBI

Altered mental status (GCS < 15, agitation, sleepiness, slow responses or repetitive questioning)

Nonfrontal scalp hematoma LOC > 5 seconds Palpable skull fracture Not acting normally according to parents

If we add no Seizures Neurologic deficits on examination Scalp hematoma Skull fracture LOC at any time Vomiting Headache (> 2 years) Amnesia (> 2 years)

If we add a few other criteria

< 2 years: 1 out of 756 (0.1%) had a significant TBI 4 month-old who fallen > 3 feet with evidence of facial

trauma, who had a subarachnoid and subdural hemorrhage

> 2 years: 2 out of 730 (0.3%) had significant TBI 10 year-old ejected during a motor vehicle collision with

multisystem trauma and traumatic hyphema with a cerebral hemorrhage

12 year-old struck by a motor vehicle who sustained multisystem trauma and facial trauma with a subarachnoid hemorrhage and subdural hematoma

None of them required neurosurgery

The Results

If they look well, and the mechanism doesn’t appear significant, you can send the child home

The bottom line

It is safe to d/c home In the PECARN study, 100% (99.97%-100) had

no need for neurosurgical intervention with a normal CT and GCS of 14-15 (Holmes et al., Academic Emergency Medicine, Oct 2011, 58 (4): 315-322).

If you do a CT, with a GCS of 14-15 …

Hamilton et al. (Pediatrics, 2010: 126 (1): e33) 17,962 children in Calgary

Missed 2 with delayed deterioration of LOC 1 case was an intracranial mass Other case was a 7 year-old who ran into a wall and had an

epidural bleed. Required neurosurgery, but no complications Had seizure, headache and skull #

Missed 8 without deterioration of LOC None of these required neurosurgery

Can safely send kids home at 6 hours, as long as none of the worrisome features are present

But if I send the child home … will he be okay?

If any worrisome features, should conduct a CT Most well looking kids with minor head injuries,

can be quickly discharged If concerned, monitor out up to 6 hours

If features are worsening, do CT If features are getting better, can safely discharge

Do not tell parents to wake their child up at night (Carroll et al., Journal of Rehabilitation Medicine, 2004: 43 (Suppl): 84-105)

CT Head or not to CT Head?

A 10 year-old boy trips and falls while playing spotlight (a highly Newfoundland game, I suspect). It is an eversion injury. He complains that his ankle hurts and his lateral

malleolus is tender and sore . The rest of the ankle, including the medial malleolus is not tender. He could wait bear initially, but now cannot walk. Does he need an X-ray?a. Yesb. No

Case #4

A 10 year-old boy trips and falls while playing spotlight (a highly Newfoundland game, I suspect). It is an eversion injury. He complains that his ankle hurts and his lateral

malleolus is tender and sore . The rest of the ankle, including the medial malleolus is not tender. He could wait bear initially, but now cannot walk. Does he need an X-ray?a. Yesb. No

Case #4

Ottawa Ankle Rules

Plint et al (Academic Emergency Medicine, 1999: 6(10): 1005-1009) showed that: OAR was 100% (95-100%) sensitive for

significant ankle fractures with 24% specificity (20-28%)

OAR was 100% sensitive (82-100%) for the midfoot, with 36% specificity (29-43%)

Ottawa Ankle Rules in Children

Low Risk Ankle Rules

These patients should be excluded

Boutis et al. (Lancet, 2001: 358: 2118-2121) Showed 100% sensitivity (93.3-100%) and

100% NPV (99.2-100%) Reduced X-rays by 62.8%

Follow-up study at 6 sites showed 100% sensitivity (85.4-100%) and 53.1 specificity (48.1-58.1%) (CMAJ 2013: e-print, DOI: 10.1503/cmaj122050) Reduced X-rays by 22%

Low Risk Ankle Rules

Gravel et al (2009; Annals of Emergency Medicine, 54 (4): 534-540) Showed that the sensitivity was higher in the

OAR, 100% compared to LRAR: 87%) LRAR missed some deemed significant

fractures Argument made that the application of LRAR in

the study was not done correctly

Comparison study

Application of the OAR + application of the fibular swelling question

(LRAR) Reduces X-rays

Majority of these children with fibular swelling can be managed by ankle splints (Boutis et al., Pediatrics, 2007: 119: e1256) Removable splints lead to faster recovery, better

physical function, patients prefer, and saves money.

Either way …

A 12 year-old girl twists her knee? She can weight bear, but it hurts to extend her knee fully?

Does she need an X-ray?a. Yesb. No

Case #5

A 12 year-old girl twists her knee? She can weight bear, but it hurts to extend her knee fully?

Does she need an X-ray?a. Yesb. No

Case #5

Isolated Patella tenderness Tenderness at the head of the fibula Inability to flex knee to 90 degrees Inability to take 4 steps initially and in the

emergency department

Ottawa Knee Rules

Bullock et al (2003, Annals of Emergency Medicine, 42 (1): 48-55) 100% sensitive (94.9-100%) and 42.8%

specific (39.1-46.5%) Saves 31% of x-rays

Results

If < 28 days: full septic work-up 28-60 days: no clear decision

Full-septic, partial septic or nothing (significant research being done on this group)

>60 days: urine + CXR if respiratory symptoms

WBC and left shift, not as useful Prolonged fever > 14 days: bloodwork

should be done

Conclusions

Appendicitis testing Clinical re-evaluation at 4 hours is useful Positive appendicitis ultrasounds should be correlated with

clinical findings to reduce the number of children taken to the OR

CTs only with significant mechanisms or clinical findings. If a child looks normal post head-injury, generally safe to send home. Observation period: 6 hours is all that is required to be pretty sure the child is fine.

We can reduce the number of x-rays by following ankle and knee rules

Conclusions

Any questions?Kevin.chan@easternhealth.ca