Pediatric Shock

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SEPSIS / SIRS MOSF / ARDS

• CLINICAL APPROACH, SOME BACKGROUND the FUTURE

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VOCABULARY I

• CO - cardiac output SV x HR AND also
• CO ?P / SVR ? ?P (driving pressure) MAP
  - CVP
• SVR systemic vascular resistance .
• PVR pulmonary vascular resistance.
• CaO2 art O2 content (1.34 x Hb x O2sat) (pO2
  x 0.003).
• DO2 - O2 delivery (CO2 x CO).
• VO2 O2 consumption CO x CO2 x O2 extraction.
• O2 extraction the difference in CO2 between the
  aorta and the pulmonary artery.

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VOCABULARY II

• Drugs
• Nitroprusside Nipride check cyanide or
  isothiocyanate
• Nitroglycerine NTG check methemoglobin
• Adrenaline Epinephrine (USA)
• Noradrenaline Norepinephrine (USA)
• Milrinone Primacor
• Dobutamine Dobutrex

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S E P T I C S H O C K
SIRS/Sepsis/Septic shock
Mediator release exogenous endogenous
Maldistribution of blood flow
Cardiac dysfunction
Imbalance of oxygen supply and demand
Alterations in metabolism
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INFLAMMATORY EVENTS IN THE SIRS SPECTRUM
Primary Pro- Inflammatories LPS IL-1 TNF
Secondary Pro- Inflammatories IL-6 IL-8
SEPSIS / SIRS MOSF / ARDS
Proteases Coagulation factors Kinins Eicosanoids
(PGE2) Nitric Oxide, ROS Heat-Shock proteins
Anti-Inflammatories IL-1ra IL-4 IL-10
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What do we need to diagnose SEPTIC SHOCK ?

• Septic shock is suspected in children with the
  inflammatory
• triad fever (or hypothermia), tachycardia
  vasodilation (common in benign pediatric
  infections) signs of low perfusion
• such as ?
• CNS changes (? in mental status, irritability,
  hypotonia)
• Prolonged capillary fill (gt 2 sec, cold shock)
  -gt common
• Flash capillary fill (warm shock) -gt less
  common
• ? urine output

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DEFINITIONS OF SHOCK

• Cold or warm shock Decreased perfusion
  including decreased mental status, capillary
  refill 2 secs (cold shock) or flash capillary
  refill (warm shock), diminished (cold shock) or
  bounding (warm shock) peripheral pulses, mottled
  cool extremities (cold shock), or decreased urine
  output 1 mL/kg/hr
• Fluid-refractory/dopamine-resistant shock Shock
  persists despite 60 mL/kg fluid resuscitation in
  first hour and dopamine infusion to 10 g/kg/min
• Catecholamine resistant shock Shock persists
  despite use of catecholamines epinephrine or
  norepinephrine
• Refractory shock Shock persists despite
  goal-directed use of inotropic agents,
  vasopressors, vasodilators, and maintenance of
  metabolic (glucose and calcium) and hormonal
  (thyroid and hydrocortisone) homeostasis
• Crit Care Med 2002 Vol. 30, No. 6

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SEPTIC SHOCK WARM SHOCK

• Early, compensated, hyperdynamic state
• Clinical signs
• Warm extremities with bounding pulses,
  tachycardia, tachypnea, confusion
• Physiologic parameters
• widened pulse pressure, increased cardiac ouptut
  and mixed venous saturation, decreased systemic
  vascular resistance
• Biochemical evidence
• Hypocarbia, elevated lactate, hyperglycemia

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SEPTIC SHOCK COLD SHOCK

• Late, uncompensated stage with drop in cardiac
  output
• Clinical signs
• Cyanosis, cold and clammy skin, rapid, thready
  pulses, shallow respirations
• Physiologic parameters
• Decreased mixed venous sats, cardiac output and
  CVP, increased SVR, thrombocytopenia, oliguria,
  myocardial dysfunction, capillary leak
• Biochemical abnormalities
• Metabolic acidosis, hypoxia, coagulopathy,
  hypoglycemia

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SEPTIC SHOCK (CONT)

• Cold Shock rapidly progresses to MOSF or death,
  if untreated
• Multi-Organ System Failure Coma, ARDS, CHF,
  Renal Failure, Ileus or GI hemorrhage, DIC
• More organ systems involved, worse the prognosis
• Therapy ABCs, fluid
• Appropriate antibiotics, treatment of underlying
  cause

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GOALS OF 1ST HOUR RESUSCITATION (I)

• Maintain oxygenation, ventilation, circulation
  and threshold heart rate (next slide)
• Therapeutic end points
• Capillary refill no difference between
  peripheral central pulses warm extremities
  urine gt 1 mL/kg/h normal mental status BP for
  age
• Monitoring pulse oximeter cont ECG A-line
  continuous temp (core peripheral) bladder
  catheter repeated glu iCa

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THRESHOLD HEART RATES AND PERFUSION PRESSURES
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GOALS OF 1ST HOUR RESUSCITATION (II)

• Airway breathing reasons to intubate ? work
  of breathing respiratory acidosis (pCO2 gt 60
  mmHg, pH lt 7.25 with nl BE) hypoxia (pO2/FiO2 lt
  200) loss of airway protection 2nd to
• ? mental status.
• Circulation two peripherals, intraosseous,
  cut-down. If inotropes are to be given ? central
  venous line.
• Fluids repeated 20 mL/kg boluses. Follow rales,
  gallop, hepatomegaly, ? work of breathing.
  Sometimes 200 mL/kg were infused.
• Vasoactive drugs Dopamine is 1st line. If shock
  remains resistent Adrenaline for cold shock (?
  ? effects) and Noradrenaline for warm shock
  (?-effect).

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GOALS OF 1ST HOUR RESUSCITATION (III)

• Hydrocortisone Tx adrenal insufficiency should
  be suspected (purpura fulminans
  catecholamine-resistance hx of CNS abnormality
  or prior chronic steroid therapy).
• adrenal insufficiency total cortisol lt
  18 mg/dL.
• Dose? 1-2 mg/kg for stress coverage to 50
  mg/kg for shock bolus followed by same dose as a
  24 hour continuous infusion.

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GOALS OF STABILISAZTION

• Goals normal perfusion perfusion pressure
  normal for age mixed venous O2 saturation gt 70
  3.3 lt CI lt 6.0 L/min/m2.
• Hemodynamic support may be required for days.
  There are several variations
• low C.O. and high SVR ? consider Nipride/NTG
  steroids Milrinone is another option.
• high C.O. and low SVR ? Norepinephrine
  steroids.
• low C.O. and low SVR ? Adrenaline steroids.
• Shock refractory to cathecolamines ? r/o
  pneomothorax, tamponade, Addison, hypothyroid,
  ongoing blood loss or an abdominal catastrophy.
• CONSIDER ECMO

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PEDIATRIC ALGORITHM
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CAN WE CHANGE THE COURSE OF AN INFECTIOUS DISEASE
?OR

• IS THE PICU IMPORTANT ?

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• June 1992 December 1997 (n331)
• Demographics
• Median age 2 y 8 m (range 5 w to 17.5 y)
• M / F - 143188
• Septicemia 281 meningitis 50
• deaths
• In PICU total 33 29 (10) septic, 3 (6)
  meningitis
• Before arriving PICU total 29
• In 1997 there were 2/111 deaths (predicted
  38/111)
• The proportion of complications remained
  unchanged (5.5 for amputations or skin
  grafting 8 for neurological abnormalities)

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MD CENTERALIZED CLINICAL
MANAGEMENT (I)

• When dx suspected? prompt PCN injection by the
  family physician (GP)
• Continuous telephone advice by PICU attending
  prior to arrival of mobile team
• Mobile Intensive Care Team led by PICU attending
  nurse transferred all patients to the central
  unit
• Elective intubation ventilation, hemodynamic
  monitoring, and ongoing resuscitation performed
  at referring hospital
• Patient stabilized prior to transport

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MD CENTERALIZED
CLINICAL MANAGEMENT (II)

• Photocopies of all documentation done
• Treatment included
• Aggressive fluid resuscitation (4.5 Albumin)
• Early intubation and ventilation
• Generous use of Inotropes
• Correction of coagulopathy
• Correction of metabolic derangements (K, Ca, Mg,
  Phosph, Bicarb Glu)
• Early renal replacement therapy

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NEONATAL ALGORITHM
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DO WE HAVE A SPECIFIC TARGET ?
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TREATMENT OF GRAM-NEGATIVE BACTEREMIA AND SEPTIC
SHOCK WITH HA-1A HUMAN MONOCLONAL ANTIBODY
AGAINST ENDOTOXIN. ZEIGLER EJ ET ALN Engl J Med.
1991 Feb 14324(7)429-36

• HA-1A is an IgM monoclonal ab that binds to the
  lipid A domain of endotoxin.
• 543 adult patients with sepsis presumed to be of
  gram-negative origin (not necessarily shock or
  bacteremia proven !)
• Total mortality placebo 43 HA-1A 39 (p0.24).
• Among the 200 who had gram-negative bacteremia
  mortality was 45/92 (49) in the placebo group
  and 32/105 (30) in the HA-1A group (p0.014).
• Follow-up studies ?drug increases mortality and
  was abandoned.

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THE NEXT DECADE SAW DOZENS OF FAILED TRIALS AND
MILLIARDS OF WASTED
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THE SIRENS SONG OF CONFIRMATORY SEPSIS TRIALS
SELECTION BIAS and SAMPLING ERROR Natanson,
Charles MD Esposito, Claire J. MD Banks,
Steven M. PhD Crit Care Med. 1998 Dec26(12)1927

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When confronted with the disappointment of failed
sepsis trials, it is alluring to maneuver the
data into the conclusion that a given drug was
beneficial to certain patients. Unfortunately,
the sirens' sweet songs of significance (reached
via sampling error and selection bias) may have
set back new drug development for sepsis and left
the field shipwrecked on the rocks. Overall, vast
resources have been expended on sepsis trials in
the last 10 yrs. It is important to realize that
the small nonsignificant treatment effects found
in the primary target populations from large
initial sepsis trials have been consistently
reproduced in confirmatory trials (PAFra 1,2,
interleukin-1 receptor antagonists 9,10,
anti-TNF-monoclonal antibodies 6-8, and P-55
soluble TNF receptors 13,14) (Figure 1 and
Figure 2, Table 1). Faced with such a
persistently high mortality rate from sepsis and
new agents with such small beneficial effects, we
need to increase our efforts to find better
therapeutic agents and do the necessary research
to formulate new questions to test these same
agents
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ACTIVATED PROTEIN C
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Xigris 12/2003 ? NO DATA in CHILDREN !

• Despite that Eli Lilly insists on full price

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HEMODYNAMIC VARIABLES in DIFFERENT SHOCK STATES
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FINAL THOUGHTS

• Recognize compensated shock quickly- have a high
  index of suspicion, remember tachycardia is first
  sign. Hypotension is late and ominous.
• Gain access quickly- if necessary use an IO line.
• Administer adequate amounts of fluid rapidly.
  Remember ongoing losses.
• Correct electrloytes and glucose problems
  quickly.
• If the patient is not responding the way you
  think he should, broaden your differential, think
  about different types of shock.