+
Approach to rational ordering of investigations
in NeonatologyDr. Kirti Naranje
Associate Professor
Neonatology
SGPGIMS, Lucknow
“We live in testing times”
+Overview
Introduction
Reasons for investigations
Inappropriate testing
General Approach
Clinical scenarios
+Introduction
Investigations are integral part of modern medicine
Single highest-volume medical activity
4-5 billion tests annually (US data)
Drives clinical decision making across all fields of medicine
Frequently overutilised
May not be always beneficial and even be harmful
+Why investigations needed?
Diagnosis- to include/exclude the disease
Establish a baseline prior to treatment initiation
Monitoring
Response to treatment
Therapeutic range of drugs
Early signs of adverse drug effect
Longterm conditions for disease control and associated complications
Targeted testing
+Inappropriate testing
Inappropriateness criteria
Objective- clearly defined and investigator-
independent
Subjective-expert review
Restrictive- „„guilty-until-proven-innocent‟‟
clear indication for ordering a test
Permissive-„„innocent-until-proven-guilty‟‟
no contraindication
Initial vs repeat testing
Overutilization/over-ordering
• tests that are ordered but not indicated
Underutilization
• tests indicated but not ordered
+Some data!!
2013
+
n=42 studies ; 1997-2012
Overutilisation rate-20.6% (95% CI 16.2–24.9%; n = 114)
Underutilsation rate-44.8%
(95% CI 33.8–55.8%; n = 18)
+
940 sample from 96 pts in adult, pediatric and neonatal ICU over 1 week
140 samples from 30 neonates in NICU
ABG samples –most common reason across all ICUs
NICUs
ABG samples - 47 % (66/140)
Capillary gas- 25% (35/140)
Full blood count- 15% (21/140)
Urea, LFT, electrolytes- 6% (9/140)
Others -27% (38/140)
Australian critical care 2016
+The Indian scenario
Rate of tests-0.5 per patient per day
+Prior considerations
What is my reason for requesting this test?
Will the test improve patient (or in some cases, family) care?
Is this the right test or combination of tests for the clinical
situation?
How will the test result be interpreted?
How will the test result influence patient management?
Are there potential harms of doing this test?
+Problematic scenarios
Incidental findings
•Screening programs
•Overdiagnosis/overtreatment
•Patient dissatisfaction of not being given treatment
Medically unexplained symptoms
•perfect storm of clinical uncertainty
•„Digging into deeper hole‟ ---more investigations
Family asks for some tests themselves
•Parent counselling
+Selecting right test, at right time, for right
patient
Often used, “shotgun approach” is inappropriate
Patient harm
misdiagnosis
Challenging
Influenced by
Emerging evidence
Changing guidelines
Clinical experience
Parents expectation
Social
+Selecting of most appropriate test
Half of the errors occur during selection process
General principles
Not to request tests that are likely to cause confusion or false reassurance
Eg fecal occult blood
An investigation is required, but there may be uncertainty as to what test to use
Eg dipstick urine for hematuria
Usefulness depend upon clinical setting
Eg INR monitoring on warfarin
+Timing of tests
Right time and right preparation, wherever necessary
Certain factors present or absent for meaningful result
TTGA in presence of gluten diet
Specific time
Therapeutic drug level
Cortisol at 8 am
According to stage of disease
AntiHbs antibody, HIV serology
+Interpreting the test results
Always interpret in clinical context
Study : 87 General practitioners, 1200 patients
66 % tests outside normal range-”normal” if performed for
patient reassurance
28% tests outside normal range-”Abnormal” if performed to
confirm suspect diagnosis
Jt Comm J Qual Patient Saf. 2005
+Interpreting the test results
How likely is it that the patient has this condition?
Pretest probability
probability that the condition being tested for is the cause of the
symptoms, before a diagnostic test result is known.
“somewhat more suggestive” or “somewhat less suggestive”
Clinical characteristics (history and examination)
Local prevalence of the diseases being considered
Clinician‟s personal experience
+Interpreting the test results
How accurate is this diagnostic test?
Sensitivity-probability of test being positive in diseased
Specificity-probability of test being negative in non-diseased
No tests is 100%sensitive and specific
The probability of an abnormal result increases when the number of tests increases
Reference range - 2 SD i.e 95% CI
5 % all tests from healthy individual outside ref range –interpreted as abnormal
+Interpreting the test results
Age appropriate reference range/nomograms
Newborn and pediatric population
False positive-patient anxiety
False negative-serious health consequences
Borderline results
Repeat
Pathologist consult
+Methods to effectively use tests
Serial rather than parallel testing
Electronic tests ordering forms
Tendency for “tickboxitis”
routinely selecting certain tests with every laboratory request
Reformatting
No standing orders for tests
Repetition of same tests even if they became normal
Consider treating without tests
Eg vit D deficiency
Consult with lab specialist (pathologist/radiologist/microbiology)
+Clinical case 1
A 1.3 kg male baby is born to a mother at 32 weeks gestation
by vaginal delivery. Mother had leaking pv 20 hrs prior to
delivery , received adequate steroid coverage. Liquor clear.
Baby cried at birth. Apgars 7,8. Baby developed respiratory
distress soon after birth, managed in NICU with CPAP
support, surfactant therapy. Currently, 18 hrs of life , on CPAP
support 5 cmH2O, with 40% FiO2, IV antibiotics, Minimal EN,
IV fluids.
Approach to investigations?
+Initial Investigations
Pretest Probability - RDS, suspect sepsis
Prematurity related issues
Chest X ray and ABG (respinvolvement)
Blood culture-most definitive
Complete blood count
HCT, TLC, DLC, ANC,
peripheral blood smear-Immature to total ratio
Micro ESR
CRP –alone shouldn‟t be used to treat
Lumbar puncture
Microscopy
CSF cultures
Cells/glucose/protein
Blood glucose
USG cranium
+TLC, Term infant
Cord : 10,000-30,000 (G 40-80%, L 20-40%, M 3-10%)
4 hrs: 16,200-31,500
24 hrs: 9400-34,000
1 mth: 5000-19,500
1-3 yr: 6000-17,500
4-7 yr: 5500-15,500
8-13 yr: 4500-13,500
+TLC, VLBW infants
N 5th cent 10th cent 50th cent 90th cent 95th cent
D 3 376 4 4.8 9.5 24.5 33.8
D 12-14 180 7.5 8.1 12.3 19.8 22.1
D 24-26 233 6.4 7.2 10.4 14.6 15.8
D 40-42 212sxs 6.1 6.8 9.1 13 14.1
Fanaroff, page 1814 (Obladen, Ped 2000; 106: 709)
+
2700
7200
+
9000
1500
+
+
>2000/cmm
<4000/cmm
+Band cells
Maximum limit (Manroe)
12-14 hrs: 1400/µL
60 hours: 600/µL
Day 5: 500/µL
5 and 28 days: unchanged
may not be applicable to VLBW infants,
+Band cells
(Novak)
+I/T ratio
Manroe :
0.16 (0 to 24 hrs)
0.13 (60 to 120 hrs)
0.12 (5 to 28 days)
Schelonka:
0.27
+C-reactive protein
Readily available
Quick
Economic
Expertise not an issue
Non specific (? perinatal factors), late marker
+C-reactive protein
Perinatal factors:
CRP peaks between 24 to 48 hours after birth,
values can exceed the cut-off of 10 mg/L
After infection: rises after 12 h and plateaues after
20–72 h
biologic half-life of CRP is 19 hours
Usually, returns to normal within 2 to 7 days of
successful treatment
+Case contd
At 48 hrs of life, baby`s condition worsen. He develops signs
of poor perfusion with delayed capillary refill time,
tachycardia, hypotension and increased work of breathing
and not maintaining saturations on CPAP 5 cmH2O and 40%
FiO2.
What next?
+
Treatment of shock
Identification of type of shock-hypovelmic, cardiogenic,
maldistributive
Investigations
Blood gas-acid/base status
Blood glucose
Lactate levels
Repeat sepsis work up
Bedside ECHO
+Case 2
A 33 weeks,1.7 kg male baby presented with history of
prolonged bleeding from finger cut injury that occurred
during trimming of nails. Despite pressure bandage, minor
bleeding continued for 2 days. Mother also noticed bluish
greenish patches over skin for last few days. The baby was
born in private hospital by LSCS in v/o PROM and prev LSCS.
The perinatal period was uneventful according to mother
and details aren`t available. On examination 3 bluish patches
over hands and legs were present. No bleeding from cut
injury at present .Systems were normal.
+Initial investigations
History of vit K admn at birth?
Platelet count
Peripheral smear
Coagulation
Prothrombin time (PT)
Activated Partial thrombin time (APTT)
Hematocrit
USG cranium
+Rationale
Platelet count
Suspected thrombocytopenia.
Hematocrit
Clues to the severity and duration of bleeding.
Peripheral blood smear
Spurious thrombocytopenia due to platelet clumping
Platelets size,volume
Coagulation screening tests
PT and APTT measures all soluble coagulation proteins.
A PT >17 sec in a neonate at any gestational age and aPTT >67sec in a term infant -abnormal
PTT in a preterm has wide range so not useful, unless a lab has nomogram of its own for different gestational age
+Index case
Prolonged PT, normal platelet counts
Suspected vitamin K deficiency bleeding disorder
PIVKA levels
+Other tests for bleeding neonate
APTT and PT mixing studies
Coagulation factor assay
Fibrinogen measurement
Thrombin time
Screening for defects in primary hemostasis
Bleeding time
PFA-100 platelet function screen
Platelet aggregation studies
+
+Case 3
A term 3.6 kg baby born to 34 years mother with blood
group O positive. No adverse perinatal events. Baby
developed jaundice at 40 hrs of birth .Systems normal
+Initial Investigations
Transcutaneous bilirubin/capillary TSB by micromethod
Total serum bilirubin with direct function
Baby blood group and DCT
HCT, retic count, peripheral smear for e/o hemolysis
For monitoring
TSB –frequency depending upon initial value and cause
+According to age of onset
+Investigations in hemolytic unconjugated
hyperbilirubinemia
+Other investigations
Cause
G6PD deficiency
Hereditary spheocyctosis -Osmotic fragility test
Sepsis w/u
Urine c/s
TORCH
Genetic
+Case4
A 36 weeks 2.4 kg male neonate presented to NICU at 39 hrs
of life with clonic seizures involving all four limbs. Baby was
born to 32 years old mother by vaginal route. There was
history of difficult labour and meconium stained liquor. Babydidn’t cry at birth and was immediately taken to local NICU
following birth. After seizure control, examination finding
revealed poor respiratory efforts requiring invasive
ventilation and shock requiring inotropes.
Investigations at this point?
+Initial work up
Blood glucose
Serum calcium with iCa, serum sodium, serum magnesium
EEG/aEEG monitoring
Hematocrit ,DLC,
USG cranium
Lumbar puncture –CSF
Cultures-blood/CSF
Cardiac: ECG ,CPK MB,ECHO
Resp: Blood gas,CXR
Nutrition: Blood glucose,electrolytes Na,K, -parenteral nutrition
Hematological:platelet count
Liver : LFTs,PT,APTT
Kidney: UO, BUN ,Creatnine, urine examination
For seizures HIE
+Investigations in neonatal seizure without apparent
etiology
+Case 5
You are called urgently to postnatal ward to see a baby. He was bornby normal vaginal delivery with no antenatal problems and goodApgars and was feeding well for the first 48 hrs of life. Since thismorning, mother noticed that he is floppy and not interested infeeding. On examination, he is pale with cold peripheries andcapillary refill time of 7 seconds, shallow respirations, weak pulsesand a heart rate of 180/ min
Approach?
Check for blood glucose/temperature
+Initial investigationsInborn errors of metabolism/duct dependent cardiac lesion/Sepsis
Blood Glucose
Urine ketones
Hct, TLC,DLC, PS, platelet count
Blood gas
Electrolytes-Na,K,Ca
Ammonia/lactate
LFT/RFT
Hct, TLC,DLC, PS, platelet count
CRP
Blood cultures
Lumbar puncture-CSF
Blood glucose
12 lead ECG,CXR
4 limb SPO2/BP
Hyperoxia test
ECHO
IEM Sepsis
Cardiac
+Specialized investigations in IEM
Driven according to predominant presentation
metabolic acidosis/hyperammonemia/hypoglycemia
Tandem mass spectrometry (TMS)- blood
Gas chromatography-mass spectrometry(GCMS)-urine
Neuroimaging MRI with MR spectroscopy
Highly specialized tests
Enzyme assays
Molecular diagnosis-whole genome exome sequencing
+Take home messages
Investigations form an integral part of clinical management
decision
Selecting the right test, at the right time, for the right patient
is a thoughtful process
Interpretation of test results should always be done in
clinical context
Methods should be employed to improve rational ordering of
investigations
+Apps
Neomate
Uptodate
+Additional References
The handbook of Neonatology_IJP publication 2018
Best Tests 2013
Cloherty manual of neonatal care 8th ed
+Acknowledgements
All newborns
Prof. Girish Gupta
Dr.Anita/Dr. Aakash