Tissue perfusion is adequate, but oxygen release to tissue is abnormal
Early recognition and treatment of the cause is main therapy
CLINICAL APPROACH, SOME BACKGROUND & the FUTURE SEPSIS / SIRS MOSF / ARDS
CO - cardiac output = SV x HR AND also
CO = P / SVR P (driving pressure) = MAP - CVP
SVR – systemic vascular resistance .
PVR – pulmonary vascular resistance.
CaO 2 – art O 2 content [( 1.34 x Hb x O 2 sat) + (pO2 x 0.003 )].
DO 2 - O 2 delivery (CO 2 x CO).
VO 2 – O 2 consumption [CO x CO 2 x O 2 extraction].
O 2 extraction – the difference in CO 2 between the aorta and the pulmonary artery.
. . . . . .
Nitroprusside – Nipride [check cyanide or isothiocyanate]
Nitroglycerine – NTG [check methemoglobin]
Adrenaline – Epinephrine (USA)
Noradrenaline – Norepinephrine (USA)
Milrinone – Primacor
Dobutamine – Dobutrex
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
Septic shock is suspected in children with the inflammatory
triad: fever (or hypothermia), tachycardia & vasodilation (common in benign pediatric infections) + signs of low perfusion
CNS changes ( in mental status, irritability, hypotonia)
Prolonged capillary fill (> 2 sec, ‘cold shock’) -> common
Flash capillary fill (‘warm shock’) -> less common
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
SEPTIC SHOCK: “WARM SHOCK”
Early, compensated, hyperdynamic state
Warm extremities with bounding pulses, tachycardia, tachypnea, confusion
Airway & breathing : reasons to intubate – work of breathing; respiratory acidosis (pCO 2 > 60 mmHg, pH < 7.25 with nl BE); hypoxia (pO 2 /FiO 2 < 200); loss of airway protection 2nd to
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 1 st line. If shock remains resistent: Adrenaline for ‘cold’ shock ( & effects) and Noradrenaline for ‘warm’ shock ( -effect).
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 < 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.
GOALS OF STABILISAZTION
Goals : normal perfusion; perfusion pressure normal for age; mixed venous O 2 saturation > 70%; 3.3 < CI < 6.0 L/min/m 2 .
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.
CAN WE CHANGE THE COURSE OF AN INFECTIOUS DISEASE ? OR IS THE PICU IMPORTANT ?
June 1992 – December 1997 ( n =331)
Median age 2 y & 8 m (range 5 w to 17.5 y)
M / F - 143:188
Septicemia 281; meningitis 50
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)
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
Photocopies of all documentation done
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
MD – CENTERALIZED CLINICAL MANAGEMENT (II)
DO WE HAVE A SPECIFIC TARGET ?
TREATMENT OF GRAM-NEGATIVE BACTEREMIA AND SEPTIC SHOCK WITH HA-1A HUMAN MONOCLONAL ANTIBODY AGAINST ENDOTOXIN. ZEIGLER EJ ET AL N Engl J Med. 1991 Feb 14;324(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% (p=0.24).
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 (p=0.014).
Follow-up studies drug increases mortality and was abandoned.
THE NEXT DECADE SAW DOZENS OF FAILED TRIALS AND MILLIARDS OF $$ WASTED
THE SIREN’S 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 Dec;26(12):1927
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
ACTIVATED PROTEIN C
Rational for using activated protein C
Xigris 12/2003 NO DATA in CHILDREN ! Despite that Eli Lilly insists on full price…
HEMODYNAMIC VARIABLES in DIFFERENT SHOCK STATES or Septic: Late Or Septic: Early Or Or Or Distributive Or Obstructive Or Cardiogenic Or Hypovolemic CVP Wedge MAP SVR CO
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.