1. Incorporating the Pupillometer
into Bedside Practice
Sachin Agarwal, MD, MPH
Assistant Professor of Neurology
Neurocritical Care
Columbia University

2. Already part of protocol
to check the pupils

3. Columbia University Neuro ICU
• Largest tertiary care center in New York
• Big referral base
• SAH, ICH, trauma, acute strokes, meningitis…
• 3 full-time neurology trained neurointensivists
• 18 bed, designated Neuro ICU
• 8 neurocritical care fellows, 4 stroke fellows
• 1:2 nursing/patient ratio
• Residents and Physician assistants

4. THEN: NOW:
NPi™-100
Pupillometer

5. Why is it so hard to
assess the pupils reliably?
• Pt’s factors:
- Small pupils (patients on medications)
- Darkly pigmented iris
• Examiner’s factors:
- visual acuity
• Potential Measurement errors
- Strength of flashlight/penlight
- Distance and orientation to patient’s eye

6. Lack of objectivity
–Size
• Change of Shift: Did the pupil get bigger
or is the observer’s baseline different?
• Darkly Pigmented eyes: Where is the
iris/pupil boundary?
–Reactivity
• Fixed and Dilated: Are the pupils really
fixed, or did I see a reaction?
• Pin Point Pupils: What is a brisk pupil?

7. Implications
Very subjective measurements
• Subjective terminology applied without
standard clinical definition:
–“Brisk”
–“Sluggish”
–“Nonreactive”

8. pupils erroneously classified
as non-reactive
pupils erroneously classified
as reactive
Data from Dr. Chen’s study

9. Interexaminer Variability for Pupillary Reactivity
up to 39% for Manual Method (penlight)
Du R, Meeker M, Bacchetti P, Larson M, Holland M, Manley G,
EVALUATION OF THE PORTABLE INFRARED PUPILLOMETER,
Neurosurgery 57:198-203, 2005

10. Sedated, Intubated, Ventilated
• nearly all patients with
trauma/stroke/therapeutic
hypothermia are not fully
assessable (e.g. GCS, etc.)
BUT
A recent study did not observe a depressant effect of
high-dose adrenaline or the neuromuscular blocking
agents on the pupillary light reflex particularly during
CPR efforts.

11. Can we use something else..
• Responses such as gagging, breathing,
swallowing, and eye movements get obscured
by the use of muscle relaxants.
• Other measures used to assess the quality of
the acute resuscitation effort such as gasping,
coughing, eye movements, calorics, and the
pulse check cannot be given numerical values.

12. How is Pupillometer different
• Assesses pupil size by detecting the borders
of the iris as well as the pupil.
• It uses a flash of fixed intensity and duration.
• Objective data stored in the device for serial-
observations - immune to the change of shifts.
• Ability to detect pupillary reaction when the manual
examination cannot..
• By use of the velocity profile, it allows differentiation
between a true pupillary response and hippus.

13. Waveform of Normal Healthy
Pupillary Response
1
2
3
4
5
6
0 0.5 1 1.5 2 2.5 3
Diameter(mm)
Seconds
Latency
Constriction Velocity
First Dilation Velocity
Second Dilation Velocity
Max Diameter
Min Diameter
Stimulus Off
<Stimulus
On

15. What is NPi ?
• Each variable is compared against the mean of
a reference distribution of healthy subjects,
taking the difference and then standardizing it
by the corresponding standard deviation.
• Then the set of all the standardized
differences (or z-scores) are combined to fall
into a scale set between 0 and 5.

16. Interpretation
• NPi score ≥3: the pupil reactivity falls within
the boundaries of the normative pupil
behavior distribution (i.e."brisk" or "normal").
• An NPi value closer to 5 is considered more
"brisk" than an NPi value closer to 3.
• An NPi score <3 denotes an abnormal
pupillary light reflex
• Value of 1 being more abnormal than a value
of 3.

17. How do we use information from
the pupillary evaluation?
TRIAGE
PROGNOSIS
INDICATION FOR SURGERY

18. “Conservative therapy” or “Surgery”?
• Neurosurgeons are less likely to operate
and more likely to withdraw care on
patients who present with:
“B/L FIXED DILATED PUPIL” and GCS of 3
* Tien HC, Cunha JR, Wu SN, Chughtai T, Tremblay LN, Brenneman FD, Rizoli SB, Do trauma
patients with a Glasgow Coma Scale score of 3 and bilateral fixed and dilated pupils have
any chance of survival? J Trauma, 2006 Feb;60(2):274-8.
TRIAGE

19. • Tendency to treat less aggressively because of low
expectations for good recovery.
• A study of 189 pts with severe TBI presenting with a
GCS score of 3 were followed for their outcomes.
• There was ONLY a 50 % mortality.
• The real predictors for bad outcome were old age,
higher ICP and pupillary size and reactivity.
* ROUKOZ B. J. Neurosurg. 2009
TRIAGE

20. Better be sure about pupils

21. • Before an ICP monitor is inserted Pupillometer
provides a sensitive means to track pupillary
changes and potentially ICP problems.
• “No competent neurosurgeon would allow a pt
in this clinical scenario *GCS≤8 & a “blown
pupil”+ to be neglected when the need for
surgical decompression is so clear.”
– Guidelines for the Surgical Management of Traumatic Brain Injury, Brain
Trauma Foundation, 2006.
INDICATION FOR SURGERY

22. NPi™ and ICP
• Subjects with abnormal NPi™ had
peak ICP higher than subjects with
normal NPi™.
• Abnormal NPi™ occurred 15.9 hrs
before the first peak of ICP.
• “Blown pupils” are a late sign.
Time is Brain
0
5
10
15
20
25
30
35
40
45
50
peakofICP(mmHg)
NPi: 3 - 5 0 - 3 NR
Chen JW. Surg Neurol Int 2011;2:82.

23. Where should you obtain data
• Intensive care unit by MD/Nursing
• Emergency department by MD/Nursing
• On-site by EMS
• All of the above

24. • “Pupil reactivity to light can prognosticate outcome”
- BTF Guidelines, well established in the literature.
“…Unfavorable outcome at 12 months was …inversely
related to pupillary responsiveness...”
• “…pupil dilation may be an indicator of ischemia of the brain
stem. If cerebral blood flow and cerebral perfusion pressure
can be rapidly restored in the patient with severe head
injury who has dilated pupils, the prognosis may be good.”
* Ritter, Ann M., Muizelaar, J. Paul , Barnes Tom, Choi Sung ,Fatouros Panos Ward, John, Bullock, M.
Ross. “Brain Stem Blood Flow, Pupillary Response, and Outcome in Patients with Severe Head
Injuries.” Neurosurgery. 44(5):941-948, May 1999.
PROGNOSIS

25. Biological plausibility
• Close proximity of the pupilloconstrictor nucleus to
vital centers of the brainstem.
• PLR center lies embedded within the periaqueductal
gray matter (PAG) of the rostral mesencephalon.
• The integrity of the PAG is essential for the
maintenance of consciousness as well as pupillary
light reflex.

26. Hypothermia and Pupillometer
• UNLIKE GCS Motor score following cardiac arrest,
absent pupil response appears to exclude survival and
good outcome BUT only after 72 hrs.
• Is it possible to change that in the setting of objective
data obtained from Pupillometer ?
1Abend NS. Pediatr Crit Care Med. 2011
2Rittenberger JC. Resuscitation. 2010 Sep;81(9):1128-32.

27. • Pupillary measurements were taken when
there was a pause in chest compressions
• Pupil diameter and the amplitude of the
pupillary light reflex was measured with an
infrared pupillometer (Neuroptics, Inc.)
• Pupil measurements ended either when the
code terminated or at ROSC, and one
following ROSC.

28. • In 25 patients (83%) the pupillary light reflex
was detectable throughout or during a part of
the resuscitation.
• Median duration of the codes from arrival to
ROSC or termination of the code was 11 min
• Median interval between measurements was
1 min.
• Resuscitation. 2012 Oct;83(10):1223-8

29. CPR and pupils
• Good outcome:
Persistent light reflex +
or
absent for < 5 min
Poor outcome:
absent > 5 min
or
gradual deterioration of light reflex

30. Application in Fulminant Hepatic failure
• Cerebral complications in recipients of Liver
transplant are most likely due to:
- Intracranial HTN due to cerebral edema
- Cerebral Ischemia/ hemorrhage
FUTILE TRANSPLANTS

31. How Pupillometer can help ?
• Hepatic Encephalopathy Grade IV shows a prolonged
latency phase and reduced pupillary constrictive ratio.
• No difference with pupillary size.
• Pre-transplant all negative pupillometer response die
of complications post-transplant.
• Conclusion: risk of post-op neurological catastrophe
must be assessed pre-transplant with rapid and
effective monitoring by Pupillometer.
* Yan S. e.t al. Liver Transplanation 15:1718-1727,2009.

32. Columbia Protocol
• Get a reading at baseline and then hourly.
• 1 pupillometer for every 2 patients
• Notify Physician/NP/PA with the following:
– Unequal pupils (>1 mm diff. compared to baseline)
– Pupillary Percent change <10%
– Constriction velocity < 0.6 mm/ sec
– NPI < 3 : ICP > 20 mm Hg or potential rise within
15-30 min

33. Conclusions
• The NPi™-100 pupillometer can reliably detect
smaller changes compared to human eye.
• Allows trending of gradual changes.
• can quantify rates of change than simply
“Brisk”, “Sluggish” or “Non-reactive”.
• Could be used for Triage, surgical decision
making as well as prognostication.
• Even a Less experienced nurse/PA/NP/MD can
report similar results as of a neuro-
ophthamologist.

34. Case #1: Minor TBI
• TB, 18 year old boy, fell from skateboard
– Arrival in ED
• GCS 4-4-3
• Pupils
– Right 2.6 to 2.1, CV 1.1 mm/sec
– Left 2.5 to 2.1, CV 0.98 mm/sec
• CT negative order to repeat CT in 4 hours
– Admitted to SICU – Frequent Neuro Assess
• 3 hours later….GCS 2-4-2
• Pupils
– Right 2.1 to 2.0 with CV 0.48 mm/sec
– Left 2.1 to 1.9 with CV 0.8 mm/sec
– Neurosurgeon called…stat CT scan of brain reveals
multiple contusions

35. Case #1 Minor TBI
–CT shows contusions/shift of 8 mm
–To OR for ICP/Brain oxygen monitors
• Initial ICP 32 mm Hg opening
pressure
–Mannitol intraop
• ICP decreases to 19 mm Hg
• Right CV 0.98 mm /sec
• Left CV 0.81 mm/sec

36. Case #2: severe TBI
• 21 year old male sustains severe TBI
– ICP/Brain oxygen monitors placed
• ICP controllable first 24 hours with ICP <20
• Pupillometer
– Right Pupil 2.5 – 2.1mm CV 0.92 mm/sec
– Left Pupil 2.7 -- 2.3 mm CV 1.02 mm/sec
• Pupillometer slows 2 hours later…

37. 21 year old male sustains
severe TBI
• ICP increases to 32 mm Hg 40 minutes
later
• Treated with Hypertonic Saline
–ICP decreases
–Constriction Velocity returns to 0.95
mm/sec and 1.05 mm/sec

38. Case 3: Malignant MCA
• 45 year old male
• Ischemic stroke transfer 4.5 hours after onset

39. Application: Case 3
To OR
Post Craniectomy
Abnormal
NPI with
Normal CV

40. Case #4: SAH
• 60 year old female
– Having dinner with husband
– Complains of sudden onset of severe headache
– Asks for her BP medicine
– Husband returns to table, wife is slumped in chair
• Calls 911
• Admit as Code Stroke
– Hunt and Hess V
– Fisher IV
– To OR for ICP/PbtO2
• Post coiling CT Increase blood

41. ICU Course
• Day 11-15
–TCDs moderate spasm
–ICP d/c on Day 13
• Pupil: RCv 1.2 ms LCv 1.1 ms
–Pupillometer readings WNL
• Day 15
–PbtO2 dips
–Pupillometer slows
• R Cv 0.5ms and L Cv 0.0 ms
• Stat CT scan shows hydrocephalus
–New ICP – ventriculostomy placed

42. ICU Course
• Day 15 Post ICP
– ICP 20s decreased to 6
– Constriction velocities
• Increase to 2.55 (R) / 1.95 (L)
• Day 16 – stable