Circulatory system, Management of shock, selection of vasoactive agents

5/25/20
1
Circulatory Insufficiency and Shock
Dr Lokesh Tiwari
Additional Professor and Head of Pediatrics; In-charge PICU
All India Institute of Medical Sciences Patna
PICU Sensitization and Observership Program AIIMS Patna
Steps in structured assessment
EVALUATE
IDENTIFY
INTERVENE
At any point life-threatening problem life saving interventions
• Initial impression (PAT)
• Primary assessment
(ABCDE)
• Secondary assessment
• Diagnostic tests

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2
Initial Impression: Evaluation A-B-C
Appearance TICLS: Tone, Interactiveness,
Consolability, Look / Gaze,
Speech / Cry
Breathing Work of breathing – Increased,
decreased or absent, Abnormal
sounds
Circulation
(Color)
Pale, cyanosis, mottled,
bleeding
Approach to a sick Child
Unresponsive, No
breathing, No Pulse
Unresponsive, No breathing or only
gasping, Pulse +
Pulse <60/ minute with poor perfusion despite
adequate oxygenation and ventilation.
PAT
Start CPR and follow CPR algorithm
Responsive, Breathing + Pulse +
Airway stablization and rescue breathing
Proceed with primary assessment

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3
Approach to A Sick Child
Intervene
Respiratory insufficiency Circulatory insufficiency Neurological impairment
Severity
• Respiratory distress
• Respiratory Failure
• Compensated shock
• Hypotensive Shock
• Cortical
• Brainstem
Cardiopulmonary failure / Cardiac arrest
Type
1. Upper airway obstruction
2. Lower airway obstruction
3. Lung parenchymal disease
4. Disordered control of
breathing
1. Hypovolemic shock
2. Distributive shock
3. Cardiogenic Shock
4. Obstructive shock
1. Primary brain
dysfunction
2. Secondary brain
dysfunction
Oxygen, CPAP or invasive
ventilation as appropriate.
Oxygen, IV / intraosseous
access, saline bolus,
inotrops, elective
intubation & ventilation,
needle thoracotomy etc.
Elective intubation,
dextrose bolus, seizure
control, care of raised ICT
etc.
SECONDARY
ASSESSMENT
SAMPLE History
Signs and symptoms, Allergies
Medication received, Past medical
History, Last meal taken, Event
FOCUSED EXAMINATION of the areas not
covered in the primary assessment (head to
toe)
Identify the specific aetiology to the physiological problem identified during primary
assessment
Specific targeted therapies to identified problem
Approach to A Sick Child
Intervene
Respiratory insufficiency Circulatory insufficiency Neurological impairment
Severity
• Respiratory distress
• Respiratory Failure
• Compensated shock
• Hypotensive Shock
• Cortical
• Brainstem
Cardiopulmonary failure / Cardiac arrest
Type
1. Upper airway obstruction
2. Lower airway obstruction
3. Lung parenchymal disease
4. Disordered control of
breathing
1. Hypovolemic shock
2. Distributive shock
3. Cardiogenic Shock
4. Obstructive shock
1. Primary brain
dysfunction
2. Secondary brain
dysfunction
Oxygen, CPAP or invasive
ventilation as appropriate.
Oxygen, IV / intraosseous
access, saline bolus,
inotrops, elective
intubation & ventilation,
needle thoracotomy etc.
Elective intubation,
dextrose bolus, seizure
control, care of raised ICT
etc.
SECONDARY
ASSESSMENT
SAMPLE History
Signs and symptoms, Allergies
Medication received, Past medical
History, Last meal taken, Event
FOCUSED EXAMINATION of the areas not
covered in the primary assessment (head to
toe)
Identify the specific aetiology to the physiological problem identified during primary
assessment
Specific targeted therapies to identified problem

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4
Circulation - Assessment
1. Heart rate and rhythm
2. Peripheral and central pulses
3. Capillary refill time
4. Skin color and temperature
5. Blood pressure
• Additional information about efficacy of circulation:
–Sensorium & Urine output
Circulation: HR
Age Heart rate (HR) at different ages
Awake HR Sleeping HR
Neonate (<1 month) 100-205 90-160
Infant (1 month – 1 year) 100-180 90-160
Toddler (1-3 years) 98-140 80-120
Pre-schooler (4-5 years) 80-120 65-100
School age (6-12 years) 75-118 58-90
Adolescent (13-18 years) 60-100 50-90

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5
Heart Rates in Children
85 220 300
60 180 200
Normal
SVT
Normal
SVT
Child
Infant
Sinus Tachycardia
Sinus Tachycardia
Bradycardia and
tachyarrhythmia cut off
Heart rate Clinical correlate
<60 bpm Bradycardia
Upto 220 in
infant
Sinus Tachycardia
>220 bpm in
infant
Tachyarrhythmia
>180 bpm in
a child
Tachyarrhythmia
Upto 180 in
a child
Sinus Tachycardia
Palpation of Central and
Distal Pulses

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6
Capillary Refill Time
Prolonged capillary refill
Skin perfusion: Color & Temperature
• Decreased cardiac output results in decreased perfusion and
oxygenation of extremities
• Look for
• Cold extremities
• Pallor
• Mottling
• Cyanosis
Consider ambient environmental conditions & Monitor line of demarcation of
temperature difference over extremities with treatment

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Definition of Hypotension
Age Systolic BP (mm Hg)
Term Neonates (0-28 days) < 60
Infants (1-12 months) < 70
Children 1-10 yrs 70 + (age x 2)
Children > 10 yrs < 90
Hypotension with hemorrhage: > 20-25% acute blood loss
Blood pressure
Urine output
• Indirect indicator of adequate circulation
• Indicates kidney perfusion and function
• Helps to monitor response to treatment
• An indwelling catheter is important to monitor ongoing perfusion of
the kidneys

5/25/20
8
Circulatory Insufficiency - Categorization
By Severity
Compensated
• Tachycardia
• Cool pale diaphoretic skin
• Delayed CRT
• Weak peripheral pulses
• Narrow pulse pressure
• Oliguria
Hypotensive
• Above all plus
• BP below 5th percentile
• Change in mental status
Disability
• Quick evaluation of neurological function
• Assesses the third vital organ the brain
• Brain injury may be direct (primary) or secondary to hypoxia and
shock (secondary)
• Two step evaluation : cortical and brainstem assessment
• Severity and duration of hypoxia will give rise to different signs
• Bedside glucose estimation must be a part of disability assessment

5/25/20
9
Disability
• Cortical functions
• AVPU response scale / GCS score
• Brain stem function
• Pupillary equality, size, and
response to light
• Sudden / severe hypoxia
• Decreased level of consciousness
• Loss of muscle tone
• Generalized seizures
• Pupillary dilatation
• Gradual hypoxia
• Decreased level of consciousness,
• Irritability, lethargy, agitation
These signs may be
deranged due to
primary CNS insults too!
AVPU Scale and GCS
AVPU Response GCS Score
Alert 15
Verbal 13
Pain stimulation 8
Unresponsive to
noxious
stimulation
6
Disability
Abnormal Pupil Responses and Possible Causes
Pinpoint pupil Narcotic ingestion
Dilated pupil Sympathetic autonomic activity
Sympathomimetic ingestion (cocaine)
Anticholinergic ingestion (local/systemic
atropine)
Raised ICP
Unilaterally dilated pupils Inadvertent topical absorption of drugs
like ipratropium
Dilating eye drops
Unilaterally dilated pupils with
altered mental status
Ipsilateral uncal herniation

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Exposure
• Undress as appropriate, avoid exposure to cold environment
• Look for deformities / bruises / bleeds
• Take care of cervical spine in case of injuries
• Record core temperature and take corrective measures for both hypo
and hyperthermia
• Remember skin and core temperature are not same especially in
children with shock
Secondary Assessment
Aim: to gain information
that helps reach the specific
etiology that caused
impaired respiratory,
cardiovascular or neurologic
function
Focused
History
Focused
Examination
S igns & symptoms
A llergies (food, milk,
environmental)
M edication received (chronic
anticonvulsants)
P ast medical history (associated
co-morbidities)
L ast meal taken (for planning
sedation & procedures)
E vents that brought child to ER
Examination of areas and
systems not covered in
primary assessment
• Head to toe
• Lymph nodes
• Detailed cardiac exam
(murmur, gallop etc)
• Abdominal exam for
organomegaly
• Throat examination
• Neck stiffnessPICU Sensitization and Observership Program AIIMS Patna

5/25/20
11
Diagnostic Tests
Investigations to identify & label severity of respiratory &
circulatory insufficiency
•ABG, Electrolytes, Calcium
•X-Ray Chest, ECG, ECHO
•Hb, Arterial lactate
•Invasive B.P., CVP
•Central venous SO2
Severity Respiratory distress
Respiratory failure
Compensated shock
Hypotensive Shock
Cortical
Brainstem
Type UA Obstruction
LA Obstruction
Lung Parenchymal disease
Disordered control of breathing
Hypovolemic shock
Distributive shock
Cardiogenic Shock
Obstructive shock
Primary brain dysfunction
Secondary brain
dysfunction
Severity
Cardiopulmonary failure
Cardiac arrest
Respiratory Circulatory Neurological
Evaluate - IDENTIFY - Intervene

5/25/20
12
Septic Shock
Dr Lokesh Tiwari
Additional Professor of Pediatrics; In-charge PICU
All India Institute of Medical Sciences Patna

5/25/20
13
Organ dysfunction
Final common pathway of death
Septic Shock
• Sepsis: life-threatening organ dysfunction caused by a
dysregulated host response to infection.
• Shock: Inability of circulation to meet the metabolic
demands of the body.
• Septic shock is a subset of sepsis with circulatory and
cellular/ metabolic dysfunction associated with a higher risk
of mortality
Final common pathway of death

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14
Management of shock
3 phases of rapid recognition, stabilization / resuscitation and further critical care
management in ICU
1. Early detection of signs of septic shock: crucial and based on quick primary
assessment. Low blood pressure (systolic or diastolic) is not essential to level it as
septic shock.
2. Initial stabilization and resuscitation:
• First 10-15 minutes of detection of sign of shock, airway, oxygenation, ventilation and monitoring
of heart rate / rhythm and pulse oximetry should be taken care of and vascular access should be
established.
• Within first hour: first dose of broad-spectrum antibiotic and fluid resuscitation, appropriate
vasoactive drug infusion if there is no response to fluid therapy.
3. Further critical care management and ongoing care: hemodynamic monitoring,
continue and titrate vasoactive drugs and add newer agent, stress dose
hydrocortisone if there is no response to fluid therapy and vasoactive agents or there
is risk for adrenal insufficiency.
Early detection of signs of septic shock
Five components of circulatory assessment.
1.Heart rate and rhythm High HR
2.Central and peripheral pulses Poor
3.Capillary re-fill time flush or prolong
4.Skin color and temperature warm or cool
5.Blood pressure Low, normal or high

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• Urine output: an important tool of ongoing assessment.
• Infants is 1.5-2 ml/kg/hour
• Older children is 1 ml/kg/hour.
• Altered mental status: Due to hypoxemia and poor brain
perfusion
• Anxiety, restlessness, seizure or loss of consciousness
Type of Shock
Severity Compensated shock
Hypotensive Shock
Type 1.Hypovolemic shock
2.Distributive shock
3.Cardiogenic Shock
4.Obstructive shock

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16
Management of shock
3 phases of rapid recognition, stabilization / resuscitation and further critical care
management in ICU
1. Early detection of signs of septic shock: crucial and based on quick primary
assessment. Low blood pressure (systolic or diastolic) is not essential to level it as
septic shock.
2. Initial stabilization and resuscitation:
• First 10-15 minutes of detection of sign of shock, airway, oxygenation, ventilation and monitoring
of heart rate / rhythm and pulse oximetry should be taken care of and vascular access should be
established.
• Within first hour: first dose of broad-spectrum antibiotic and fluid resuscitation, appropriate
vasoactive drug infusion if there is no response to fluid therapy.
3. Further critical care management and ongoing care: hemodynamic monitoring,
continue and titrate vasoactive drugs and add newer agent, stress dose
hydrocortisone if there is no response to fluid therapy and vasoactive agents or there
is risk for adrenal insufficiency.
Initial stabilization and resuscitation
• Positioning:
• supine position or most comfortable position for responsive child.
• Support airway and breathing:
• Ensure effective oxygenation and ventilation.
• Start high concentration of oxygen preferably by high flow device (NRM).
• Respiratory Failure: non-invasive or invasive ventilation (CPAP or mechanical
ventilation)
• SpO2 monitoring, ABG and ScVO2
• Vascular access:
• Large bore, preferably 2
• Interosseous needle if IV cannulation is not possible.
• Start fluid therapy with in first five minutes of identification of shock
• Central venous access is desirable but not mandatory for fluid therapy and inotropic
support in emergency.

5/25/20
17
Initial stabilization and resuscitation:
Fluid Bolus
• Rapid administration of isotonic crystalloid solution as 20 ml/kg bolus
over 5-10 min
• Reassessment after every bolus
• Repeat fluid boluses if needed to restore BP and perfusion.
• In septic shock, children may need 60 ml/kg or more during first hour
and up to 200 ml/kg in first 8 hours of management.
• Rapid push technique
• Standard infusion pumps or syringe pumps cannot deliver rapid bolus
at desired rate
Fluid Bolus
• If cardiogenic shock is suspected or history of ingestion of calcium
channel blockers or beta adrenergic blockers, consider small fluid
bolus (5-10 ml/kg) over 10-20 minutes.
• Caution for pulmonary edema specially in case of anemia and severe
febrile illness, especially in settings where further inotropic support,
mechanical ventilation and ongoing assessment in PICU is not
possible.

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18
Fluid Bolus
• Standard resuscitation fluid is Isotonic crystalloids (0.9 % saline or RL)
• Consider albumin and other colloids only in case of albumin
deficiency or large third spacing
• Blood products in case of visible or occult blood loss
• Hydroxyethyl starches should NOT be used.
Ongoing Assessment of Shock
Warm shock Warm shock Cold shock
Airway Usually open unless there is altered sensorium
Breathing Quite tachypnoea unless there is associated pneumonia or cardiogenic pulmonary edema
Circulation Tachycardia, bradycardia (sometime)
Bounding peripheral pulses
Flash capillary refill time
Warm peripheries
Hypotension or normo tension
Wide pulse pressure
Altered sensorium or restlessness
Oliguria
Tachycardia, sometime bradycardia
Poor peripheral pulses
Prolong capillary refill time
Cold peripheries
Hypotension or normo tension
Narrow pulse pressure
Altered sensorium or restlessness
Oliguria
Disability Altered GCS or AVPU scale
Exposure Fever or warm extremities
Normal, Petechial or purpuric rash
Pale or ashen grey skin, Fever, Increased
difference between core and peripheral
temperature > 2°C

5/25/20
19
Within first hour:
• First dose of broad-spectrum antibiotic
• Vasoactive agent if there is no response to fluid therapy
• Epinephrine for shock with cold extremities
• Nor epinephrine for shock with warm extremities;
• Dopamine as alternative in both conditions) infusion.

5/25/20
20
New Predictive Score for PICU: Pediatric
quick SOFA Score - AIIMS Patna Model
Age <1 year 1-5 year >5 year Score
Respiratory Rate >53 >37 >25 1
Systolic BP <70 <80 <90 1
Altered Mentation
(Modified GCS)
<15 <15 <15 1
SIRS qSOFA P AIIMS Patna
1. Sensitivity %(95 %CI) 72.7 ( 49.8- 89.3) 90.9 (70.8, 98.9)
2 Specificity %(95 %CI) 36.7 ( 29.0 - 44.9) 76.7 (69.1, 83.2)
3 Positive predictive value 14.4 ( 85.0 - 22.4) 36.4 (23.8, 50.4)
4 Negative predictive value 90.2 (79.8 – 96.3) 98.3 (94, 99.8 )
5 Positive likelihood ratio 1.148 (0.865 - 1.525) 3.896 (2.833, 5.359)
6 Negative likelihood ratio 0.744 (0.364 - 1.519) 0.119 (0.032, 0.446)
7 Odds Ratio 1.544 (0.571 - 4.177) 32.857 (7.317, 147.548)
8 Diagnostic accuracy 41.3% 78.4%
Aims & Objectives: Quick Sequential Organ Failure Assessment (qSOFA) score (respiratory
rate ≥22 breaths/min, systolic blood pressure ≤100 mm Hg, and altered mental status) may
predict complications in adult patients with infection.1 There is no such score for children.
We propose a new score named “Pediatric quick SOFA score- AIIMS Patna Model” to
predict poor outcome in children at the time of admission.
Methods
In this single center observational cohort study, proposed Pediatric quick SOFA Score was
calculated during first hour of PICU admission based on age specific respiratory rate2
,
systolic blood pressure and modified Glasgow coma scale cut offs for children as described
in table 1. All patients were also screened for SIRS, sepsis and septic shock during first 24
hours of admission. Sensitivity, specificity and ROC to predict mortality were calculated for
SIRS and PqSOFA score ≥ 2.
Table 1. Pediatric quick SOFA Score
Results
consecutive 172 patients were analyzed. Mean age of patients admitted was 5.30 years
(range 2 months to 17 years) and male: Female ratio was 1.23: 1. Total 150 children
survived and 22 died in this cohort with all cause mortality rate of 12.79%.
Sensitivity of PqSOFA Score ≥ 2 to predict death was 90.91% (95% CI 70.8-98.8) as
compared to 72.73 % (95% CI 49.78-89.27) that of SIRS. Specificity was 76.0% (95% CI 68.3-
82.6) vs 36.67 (95% CI 28.9-44.9) respectively. Odds Ratio was 31.66 (95% CI 7.05-142; P<
0.001) for PqSOFA as compared to 1.544 (95% CI 0.57-4.17; p = 0.39) for SIRS. Diagnostic
accuracy of PqSOFA Score was 78.4%as compared to 41.3%for SIRS.
The AUC of PqSOFA score for hospital mortality was significantly higher than SIRS (AUC 0.87 vs
0.55 P = 0.001).
0
20
40
60
80
100
0 20 40 60 80 100
100-Specificity
Sensitivity
SIRS
QSOFA__2
AUC 0.87
P 0.001
AUC 0.54
Variable AUC SE a 95% CI b
SIRS 0.55 0.052 0.47 to 0.62
qSOFA_2 0.87 0.038 0.81 to 0.92
SIRS vs PqSOFA ≥ 2
Difference between areas 0.323
SE 0.0716
95% CI 0.182 to 0.463
z statistic 4.506
Significance level P < 0.0001
Conclusions
1. We proposed “Pediatric quick SOFA score- AIIMS Patna Model” for prediction of
survival outcome in children within first hour of PICUadmission.
2. Proposed score has significantly better predictive value and diagnostic accuracy than
conventional SIRS criteria.
L. Tiwari1, C. Anand1, G. Kumar1, J. Chaturvedi2, N.R. Mishra3
1All India Institute of Medical Sciences Patna, Pediatrics, Patna, India, 2Mahavir Cancer Hospital and Research Institute Patna, Anaesthesiology,
Patna, India; 3Veer Surendra Sai Institute of Medical Sciences and Research, Pediatrics, Burla, India
Choice of Vasoactive drugs in Fluid
Refractory Septic Shock
Dr Lokesh Tiwari
Additional Professor of Pediatrics; In-charge PICU, All India Institute of Medical Sciences Patna

5/25/20
21
Case
• 8 Year old boy, 32 kg
• Fever and cough x 3 days • Sick Child that needs immediate
attention
• Attached to monitors (SPO2 in
room air 88%)
• O2 by NRM: SPO2 94%
Anxious/ stressed
Increased
WoB
Off color/
not pink
Case
• Airway clear
• In respiratory distress
• RR 46/min, subcostal and intercostal
retractions ++, B/L crepts, SPO2 on
O2 by NRM: 94%
• HR 140/min, cold peripheries, weak
peripheral pulses, CRT 4 sec, BP
76/50
• Pupils Normal; RBS 82
• Skin is cool
Respiratory distress with hypotensive shock (likely septic shock)

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22
Treatment
• O2 by NRM; SpO2- 94%
• IV Access, blood gas, CBC, electrolytes and blood culture sent
• NS bolus 20 ml/ kg (640 ml each bolus) over 15 min;
repeated once
• Inj Ceftriaxone and Paracetamol
What next?

5/25/20
23
Heart rate (increased or decreased); Peripheral perfusion: cool or warm extremities, CRT >2 sec or flash, Altered skin color &
Temperature; fever or hypothermia; Blood pressure: Normal or hypotension; Altered GCS /AVPU:
Airway, breathing & circulation, oxygen, Attach monitors to record HR, BP and SPO2, Vascular access (IV or IO) and sampling
if possible (Ca, glucose, electrolytes, Blood gas, Bl culture)
Fluid bolus: 20 ml/kg isotonic crystalloid over 5-10 minutes, reassess, repeat as needed
Medication: Antimicrobials with in 1 hour, Antipyretics if needed
Reassessment for Signs of Septic Shock
HR, Peripheral pulses, CRT, Skin color & Temp, BP,
GCS /AVPU
5
Min
15
Min
Reassessment
retractions +, B/L crepts, SPO2 on O2 by
NRM: 94%
peripheral pulses, CRT 3 sec, BP 74/50
• ABG: pH- 7.18; PaCO2- 20; HCO3- 12;
PaO2- 74; Lactate- 2.8, RBS- 88
GCS /AVPU
Resolving signs of Shock
Improved GCS/AVPU, normal HR
and temp, CRT <2 sec, adequate
systolic and diastolic BP
Ongoing Care, treat infection,
organ support
Signs of Shock persist
Fluid Refractory Septic Shock
Critical care consultation and vasoactive drugs
• Shock with cold extremities: Epinephrine 0.05-0.3 mcg/kg/min
• Shock with warm extremities: Norepinephrine 0.05-0.3 mcg/kg/min
• Alternative dopamine 5-10 mcg/kg/min
5
Min
15
Min
30
to
40
mIn
Variables Warm shock Cold shock
HR Tachycardia / bradycardia Tachycardia / bradycardia
Pulses Bounding peripheral pulses Poor peripheral pulses
CFT Flush capillary refill time Prolong capillary refill time
Peripheries Warm Cold
BP Hypotension or normotension Hypotension or normo tension
Pulse pressure Wide Narrow
Sensorium Altered or restlessness Altered or restlessness
Urine Output Oliguria Oliguria
Skin Warm / Normal / Petechial or
purpuric rash
Pale or ashen grey skin,
core and periph temp gradient >
2°C

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24
GCS /AVPU
5
Min
15
Min
30
to
40
mIn
Reassessment
retractions +, B/L crepts, SPO2 on O2 by
NRM: 94%
peripheral pulses, CRT 3 sec, BP 74/50
• ABG: pH- 7.18; PaCO2- 20; HCO3- 12;
PaO2- 74; Lactate- 2.8, RBS- 88
Shock with cold extremities: Epinephrine 0.05-0.3 mcg/kg/minPICU Sensitization and Observership Program AIIMS Patna
Within first hour:
First dose of broad-spectrum
antibiotic

5/25/20
25
Physiology of Circulation
Cardiac
Output
Preload
Myocardial
Contractility
Afterload
Stroke
Volume
Heart
Rate
SVR Blood
Pressure/
Perfusion
pressure
O2 content (CaO2) = (Hb x 1.34 x SaO2) + (0.003 x PaO2)
Tissue Oxygen Delivery
DO2 = C O X CaO2
Oxygen Extraction
ScvO2
Choice of Inotropes
Drug Dose α1 ß1 ß2 DA V1 V2 cAMP
Norepineph
(mcg/kg/min)
0.01 - 3 ++++ ++ - - - - -
Epinephrine
(mcg/kg/min)
0.01 – 0.05 + +++ ++ - - - -
> 0.05 ++++ ++ ++ - - - -
Dopamine
(mcg/kg/min)
1 - 5 - + - ++++ - - -
5 - 10 + ++ - +++ - - -
10 - 20 +++ ++ - + - - -
Vasopressin
(units/min)
0.03 – 0.04 - - - - ++++ +++ -
Dobutamine
(mcg/kg/min)
2 - 20 + ++++ ++ - - - -
Milrinone
(mcg/kg/min)
0.125 – 0.75 - - - - - - ++++

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26
Choice of Inotropes
Norepineph
(mcg/kg/min)
0.01 - 3 ++++ ++ - - - - -
Epinephrine
(mcg/kg/min)
0.01 – 0.05 + +++ ++ - - - -
> 0.05 ++++ ++ ++ - - - -
Dopamine
(mcg/kg/min)
1 - 5 - + - ++++ - - -
5 - 10 + ++ - +++ - - -
10 - 20 +++ ++ - + - - -
Vasopressin
(units/min)
0.03 – 0.04 - - - - ++++ +++ -
Dobutamine
(mcg/kg/min)
2 - 20 + ++++ ++ - - - -
Milrinone
(mcg/kg/min)
0.125 – 0.75 - - - - - - ++++
• Norepinephrine
• It increases SVR (α1)
• Tachycardia as dose escalates
and variable impact on cardiac
contractility
• First line agent in adults with
fluid-refractory shock /Warm
Septic shock
• Less arrhythmogenic than
dopamine and dobutamine
Choice of Inotropes
Norepineph
(mcg/kg/min)
0.01 - 3 ++++ ++ - - - - -
Epinephrine
(mcg/kg/min)
0.01 – 0.05 + +++ ++ - - - -
> 0.05 ++++ ++ ++ - - - -
Dopamine
(mcg/kg/min)
1 - 5 - + - ++++ - - -
5 - 10 + ++ - +++ - - -
10 - 20 +++ ++ - + - - -
Vasopressin
(units/min)
0.03 – 0.04 - - - - ++++ +++ -
Dobutamine
(mcg/kg/min)
2 - 20 + ++++ ++ - - - -
Milrinone
(mcg/kg/min)
0.125 – 0.75 - - - - - - ++++
• Epinephrine
• First-line choice for cold
hypodynamic shock due to β1-
adrenergic effects
• β2-adrenergic effects on
vasculature
• Stimulates gluconeogenesis and
glycogenolysis, and inhibits the
action of insulinà
Hyperglycemia and high lactate
independent of changes in organ
perfusion.
• High-dose α1 effect (as
vasopressor in warm shock)

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27
Choice of Inotropes
Norepineph
(mcg/kg/min)
0.01 - 3 ++++ ++ - - - - -
Epinephrine
(mcg/kg/min)
0.01 – 0.05 + +++ ++ - - - -
> 0.05 ++++ ++ ++ - - - -
Dopamine
(mcg/kg/min)
1 - 5 - + - ++++ - - -
5 - 10 + ++ - +++ - - -
10 - 20 +++ ++ - + - - -
Vasopressin
(units/min)
0.03 – 0.04 - - - - ++++ +++ -
Dobutamine
(mcg/kg/min)
2 - 20 + ++++ ++ - - - -
Milrinone
(mcg/kg/min)
0.125 – 0.75 - - - - - - ++++
• Dopamine: low doses
(DA) minimal effect on
hemodynamics
• As the dose escalates,
b1 effect (increase in HR
and cardiac
contractility
• > 15 μg/kg/min α1
effect (vasopressor
property)
Choice of Inotropes
Norepineph
(mcg/kg/min)
0.01 - 3 ++++ ++ - - - - -
Epinephrine
(mcg/kg/min)
0.01 – 0.05 + +++ ++ - - - -
> 0.05 ++++ ++ ++ - - - -
Dopamine
(mcg/kg/min)
1 - 5 - + - ++++ - - -
5 - 10 + ++ - +++ - - -
10 - 20 +++ ++ - + - - -
Vasopressin
(units/min)
0.03 – 0.04 - - - - ++++ +++ -
Dobutamine
(mcg/kg/min)
2 - 20 + ++++ ++ - - - -
Milrinone
(mcg/kg/min)
0.125 – 0.75 - - - - - - ++++
• Dobutamine: increases
HR and cardiac
contractility (β1), with a
variable response on
MAP, depending upon
the degree of systemic
vasodilation (β2)
• Reasonable adjunct to
norepinephrine in
setting of low output
heart failure.

5/25/20
28
Choice of Inotropes
Norepineph
(mcg/kg/min)
0.01 - 3 ++++ ++ - - - - -
Epinephrine
(mcg/kg/min)
0.01 – 0.05 + +++ ++ - - - -
> 0.05 ++++ ++ ++ - - - -
Dopamine
(mcg/kg/min)
1 - 5 - + - ++++ - - -
5 - 10 + ++ - +++ - - -
10 - 20 +++ ++ - + - - -
Vasopressin
(units/min)
0.03 – 0.04 - - - - ++++ +++ -
Dobutamine
(mcg/kg/min)
2 - 20 + ++++ ++ - - - -
Milrinone
(mcg/kg/min)
0.125 – 0.75 - - - - - - ++++
• Vasopressin: At low doses (<
0.04 units/min), increases SVR
(V1) without effects on HR and
cardiac contractility.
• Mild fluid retention (V2)
• May restore catecholamine
receptor responsiveness
Choice of Inotropes
Norepineph
(mcg/kg/min)
0.01 - 3 ++++ ++ - - - - -
Epinephrine
(mcg/kg/min)
0.01 – 0.05 + +++ ++ - - - -
> 0.05 ++++ ++ ++ - - - -
Dopamine
(mcg/kg/min)
1 - 5 - + - ++++ - - -
5 - 10 + ++ - +++ - - -
10 - 20 +++ ++ - + - - -
Vasopressin
(units/min)
0.03 – 0.04 - - - - ++++ +++ -
Dobutamine
(mcg/kg/min)
2 - 20 + ++++ ++ - - - -
Milrinone
(mcg/kg/min)
0.125 – 0.75 - - - - - - ++++
• Milrinone: increases HR and
cardiac contractility, with a
decrease in both systemic and
pulm vascular resistance (cAMP)
• An initial bolus is avoided
• Useful in catecholamine
desensitization in sepsis
• Caution in renal impairment as it
is excreted via the kidney (83%
unchanged)

5/25/20
29
Other agents
Levosimendan
• Increases Ca++/actin/tropomyosin complex binding sensitivity and
also has some type III PDEI and adenosine triphosphate–sensitive K+
channel activity.
HR, Peripheral pulses, CRT, Skin color & Temp, BP, GCS /AVPU
Improved GCS/AVPU, normal HR and
temp, CRT <2 sec, adequate systolic and
diastolic BP
Ongoing Care, treat infection, organ
support
5
Min
15
Min
1
HrPICU care, Central venous access, Invasive BP monitoring, Consider mechanical ventilation
Continue and titrate epinephrine/norepinephrine, and bolus fluid therapy as needed
Catecholamine Resistant Shock
Continue and titrate vasoactive drugs and add newer agent.
Stress-dose hydrocortisone for absolute adrenal insufficiency, Evaluate cortisol if at risk for relative adrenal insufficiency

5/25/20
30
Improved GCS/AVPU, normal HR and
temp, CRT <2 sec, adequate systolic and
diastolic BP
Ongoing Care, treat infection, organ
support
5
Min
15
Min
1
HrPICU care, Central venous access, Invasive BP monitoring, Consider mechanical ventilation
Continue and titrate vasoactive drugs and add newer agent.
Important Formulae useful in management of septic shock
Cardiac Output (CO) Heart Rate (HR) × Stroke Volume (SV)
Cardiac Index (CI) Cardiac Output (CO) / Body Surface Area (BSA) = (HR X SV) / BSA
(L/min/m2). Target CI for management of septic shock is between 3.3
and 6.0 L/min/m2
Shock index HR / systolic blood pressure
1.2 for 4-6 years; 1 for 6-12 years; and 0.9 for > 12 years.
For normal healthy adults: 0.5 to 0.7
Target Perfusion Pressure
(MAP – CVP)
55 + (age x 1.5).
Here CVP is considered 0 but in setting of higher CVP or intra-abdominal
pressure (IAP), appropriate correction of targeted perfusion pressure
should be done by adding actual value of CVP or IAP to this formula.
HR, Peripheral pulses, CRT, Skin color & Temperature, Blood pressure, GCS /AVPU
ScvO2 ≥70%, cardiac output/index and perfusion pressure (MAP-CVP) = (55 + age x 1.5)
ScvO2 ≥70%,
cardiac index 3.3 to 6.0 L/min/m2
Signs of shock resolved
Assess for therapeutic end points
Normal HR & pulses, CRT < 2 sec, warm
extremities, Normal BP, GCS / AVPU Urine
output > 1 ml/kg/hr, Improving lactate and
metabolic acidosis
Monitor in ICU, Support organ function,
Treat infection source
ScvO2 ≥70%
warm extremities
despite norepinephrine
Additional fluid boluses
Titrate norepinephrine
Add additional vasopressor (vasopressin /
terlipressin) and inotropic therapy
If ScVO2 <70% consider low dose
epinephrine
Support organ function
ScvO2 < 70%
Cold extremities
despite epinephrine
Transfuse if Hgb < 10 g/dL
Low BP: Titrate epinephrine, add
norepinephrine if diastolic BP low
Adequate BP: Add milrinone / dobutamine/
levosimendan and/or vasodilator therapy
Persistent catecholamine resistant Shock
Rule out tension pneumothorax, pericardial effusion, intra-abdominal pressure >12 mmHg
Invasive and non-invasive (USG) measurements to guide fluid and inotropic support
Refractory Shock: ECMO
B
E
Y
O
N
D
1
Hour
P
I
C
U

5/25/20
31
Therapeutic End-points of Shock Resolution
• Normal HR or declining from very high towards normal
• Normal peripheral pulses and capillary refill time < 2 sec and warm
extremities
• Normal mental status/ responsiveness
• Normal blood pressure
• Urine output > 1 ml/kg/hr
• Improving serum lactate and metabolic acidosis
• ScvO2 ≥ 70% and cardiac index 3.3 to 6.0 L/min/m2
Continuation of care in PICU
• Shock is resolved and therapeutic end points are achieved, organ support to
continue in PICU
• Infection control
• Mechanical ventilation,
• Renal replacement therapy,
• Intracranial pressure management
• Blood transfusion,
• Nutritional supplementation,
• Hypo or hyperglycaemia, dys-electrolytemia, venous thromboembolism, DIC etc.
• Speciality consultations
• Discussion with family on Goals of care and prognosis

5/25/20
32
Antimicrobial therapy and source control
• Cultures with at least two sets of blood cultures (aerobic and
anaerobic) before starting antimicrobial therapy if doing so results in
no substantial delay in the start of antimicrobials.
• Empiric broad-spectrum IV antimicrobials as soon as possible but
within one hour after recognition of sepsis and septic shock.
• Narrow down and de-escalation
• Serum procalcitonin levels can be used to guide
• Specific anatomic diagnosis of infection and emergent source control
• Empiric antibiotic treatment reduces mortality in severe sepsis and septic shock from the first hour:
results from a guideline-based performance improvement program. Crit Care Med (2014)
• Time from admission to initiation of surgery for source control is a critical determinant of survival in
patients with gastrointestinal perforation with associated septic shock. Crit Care (2014)PICU Sensitization and Observership Program AIIMS Patna
Mechanical Ventilation
• Early intubation and positive pressure ventilation.
• Sepsis induced ARDS: lung protective strategy
• Low tidal volume 6 mL/kg predicted body weight,
• Max plateau pressure limit of 30 cm H2O,
• Higher PEEP, guided by PEEP- FiO2 tables,
• Recruitment maneuvers and
• To try prone position
• 30 to 45 degrees of head end elevation to limit aspiration risk and to
prevent the development of VAP.
• Spontaneous breathing trials and weaning protocol
• Specific sedation and analgesia scales minimize sedation
Acute respiratory distress syndrome: the Berlin Definition. JAMA (2012)
Shehabi Y, Bellomo R, Reade MC et al Am J Respir Crit Care Med (2012)PICU Sensitization and Observership Program AIIMS Patna

5/25/20
33
Blood products
• Targeted Hb in resuscitation phase
• EGDT protocol: 10 gm/dl,
• Surviving sepsis guideline 2017: 7.0 g/dL if there is no myocardial ischemia, severe
hypoxemia, or acute haemorrhage
• FFP for bleeding or an invasive procedure is planned in presence of coagulopathy
• Should not be given just to correct clotting abnormalities in the absence of bleeding
• Platelet transfusion:
• Plt count < 10,000/mm3 in the absence of apparent bleeding
• Plt count < 20,000/mm3 with a significant risk of bleeding
• Target platelet counts 50,000/mm3 for active bleeding, surgery, or invasive procedures
• No evidence to suggest use of IV IG, blood purification techniques, antithrombin,
thrombomodulin or heparin in patients with sepsis or septic shock
• Recommendations for the transfusion of plasma and platelets. Blood Transfus. (2009)
• An evaluation of the feasibility, cost and value of IVIG for sepsis, severe sepsis and septic shock: Health Technol Assess (2012)
• IVIG for treating sepsis, severe sepsis and septic shock. Cochrane Database Syst Rev 9:CD001090 (2013)
Lower versus higher hemoglobin threshold for transfusion in septic shock. N Engl J Med (2014)
Glucose control
• A regular monitoring protocol to maintain blood sugar around 150 mg/dL.
• Hypoglycemia (< 60 mg/ dL beyond neonatal period)
• Corrected immediately with IV dextrose (25% dextrose 2-4 ml/kg or 10%
dextrose 5-10 ml/kg).
• Hyperglycaemia (two consecutive blood glucose levels are > 180 mg/dL)
• Insulin infusion (0.05-0.1 unit /kg/hr)
• Monitor every 1 to 2 hours until glucose values and insulin infusion rates
are stable, then every 4 hours
• Glucose levels obtained with POC testing of capillary blood should be
interpreted with caution
• Finfer S, Blair D, Bellomo R et al (2009) N Engl J Med
• Song F, Zhong LJ, Han L et al Intensive insulin therapy for septic patients: a
meta-analysis of randomized controlled trials. Biomed Res Int. 2014:698265PICU Sensitization and Observership Program AIIMS Patna

5/25/20
34
Renal Replacement Therapy
• Continuous or intermittent renal replacement therapy (RRT) for
patients with sepsis and acute kidney injury with definitive indications
for dialysis
• Not merely for increase in creatinine or oliguria
• Continuous therapies are preferred for management of fluid balance
in hemodynamically unstable septic patients
John S, Griesbach D, Baumgartel M, et al. (2001) Effects of continuous haemofiltration vs intermittent
haemodialysis on systemic haemodynamics and splanchnic regional perfusion in septic shock patients: a
prospective, randomized clinical trial. Nephrol Dial Transplant
Bicarbonate Therapy
• Sodium bicarbonate should not be used to improve hemodynamics or
to reduce vasopressor requirements in patients with hypoperfusion-
induced lactic acidemia with pH ≥ 7.15
Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016. Crit Care Med.2017

5/25/20
35
Venous Thromboembolism Prophylaxis
• Low-molecular-weight heparin (preferred) or unfractionated heparin
(UFH) should be used as prophylaxis against VTE in the absence of
contraindications
• Pharmacologic VTE prophylaxis should be combined with mechanical
prophylaxis, whenever possible.
• If pharmacologic VTE is contraindicated, only mechanical VTE
prophylaxis should be used.
Cochrane Database Syst Rev 9:CD007557 (2012)
Cochrane Database Syst Rev 4:CD005258 (2008)
Gastrointestinal Support
• Stress ulcer prophylaxis
• Proton pump inhibitors or histamine-2 receptor antagonists for patients who
have risk factors for GI bleeding
• Ileus and abdominal distention with respiratory compromise.
• Check for hypokalemia and corrected under cardiac monitoring
Society of Critical Care Medicine and American Society for Parenteral and Enteral Nutrition. JPEN J Parenter Enteral
Nutr. 2017

5/25/20
36
Nutrition
• Enteral nutritional support ASAP with close monitoring of caloric intake
serum albumin, electrolytes and liver function
• If intolerance: Continue IV glucose and advance enteral feeds as tolerated
• Prokinetic agents, trophic/hypocaloric feeding and post-pyloric feeding
tubes
• Parenteral nutrition alone or in combination with enteral feedings is NOT
recommended in first 7 days.
• No role of routinely monitoring gastric residual volumes in nonsurgical
critically ill patients without feeding intolerance
• Immunonutrition: omega-3 fatty acids, arginine, IV selenium, glutamine or
carnitine have been studied but none of them are recommended in
critically ill patients at the moment pending further studies.
Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016. Crit Care Med.2017
Society of Critical Care Medicine and American Society for Parenteral and Enteral Nutrition. JPEN J Parenter Enteral
Nutr. 2017 PICU Sensitization and Observership Program AIIMS Patna

5/25/20
37
Improved GCS/AVPU, normal HR
and temp, CRT <2 sec, adequate
systolic and diastolic BP
Ongoing Care, treat infection,
organ support
PICU care, Central venous access, Invasive BP monitoring, Consider mechanical ventilation
5 Min
15
Min
1
Hour
HR, Peripheral pulses, CRT, Skin color & Temperature, Blood pressure, GCS /AVPU
ScvO2 ≥70%, cardiac output/index and perfusion pressure (MAP-CVP) = (55 + age x 1.5)
ScvO2 ≥70%,
cardiac index 3.3 to 6.0 L/min/m2
Signs of shock resolved
Assess for therapeutic end points
Normal HR & pulses, CRT < 2 sec, warm
extremities, Normal BP, GCS / AVPU Urine
output > 1 ml/kg/hr, Improving lactate and
metabolic acidosis
Monitor in ICU, Support organ function,
Treat infection source
ScvO2 ≥70%
warm extremities
despite norepinephrine
Titrate norepinephrine
Add additional vasopressor (vasopressin /
terlipressin) and inotropic therapy
If ScVO2 <70% consider low dose
epinephrine
ScvO2 < 70%
Cold extremities
despite epinephrine
Transfuse if Hgb < 10 g/dL
Low BP: Titrate epinephrine, add
norepinephrine if diastolic BP low
Adequate BP: Add milrinone / dobutamine/
levosimendan and/or vasodilator therapy
Persistent catecholamine resistant Shock
Rule out tension pneumothorax, pericardial effusion, intra-abdominal pressure >12 mmHg
Invasive and non-invasive (USG) measurements to guide fluid and inotropic support
Refractory Shock: ECMO
B
E
Y
O
N
D
1
Hour
P
I
C
U

5/25/20
38
State of the art PICU at AIIMS Patna
AIIMS Patna PICU Protocol book for standard and safe treatmentPICU Sensitization and Observership Program AIIMS Patna

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