CARDIOGENIC SHOCK

Etiology:
Arrhythmias Infection Metabolic Obstructive Drug intoxication Congenital heart disease Trauma

CARDIOGENIC SHOCK (cont.)

Differentiation from other types of shock:
History Physical Exam:
Enlarged liver Gallop rhythm Murmur Rales

CXR:
Enlarged heart, pulmonary venous congestion

CARDIOGENIC SHOCK
Etiology:
Arrhythmias Infection Metabolic Obstructive Drug intoxication Congenital heart disease Trauma

CARDIOGENIC SHOCK (cont.)

Management:
Improve cardiac output::
Correct dysrhymias Optimize preload Improve contractility Reduce afterload

Minimize cardiac work:

Maintain normal temperature Sedation Intubation and mechanical ventilation Correct anemia

DISTRIBUTIVE SHOCK
Due to an abnormality in vascular tone leading to peripheral pooling of blood with a relative hypovolemia. Etiology

Anaphylaxis Drug toxicity Neurologic injury Early sepsis Fluid Treat underlying cause

Management

OBSTRUCTIVE SHOCK

Mechanical obstruction to ventricular outflow Etiology: CHD, massive PE, tension pneumothorax, cardiac tamponade Inadequate C.O. in the face of adequate preload and contractility Tamponade: Narrow pulse pressure and/or EMD Treat underlying cause.

DISSOCIATIVE SHOCK

Inability of Hemoglobin molecule to give up the oxygen to tissues Etiology: Carbon Monoxide poisoning, methemoglobinemia,dyshemoglobinemias Tissue perfusion is adequate, but oxygen release to tissue is abnormal Early recognition and treatment of the cause is main therapy

SEPSIS / SIRS MOSF / ARDS

CLINICAL APPROACH, SOME BACKGROUND & the FUTURE

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.

. . .

VOCABULARY II
Drugs: Nitroprusside Nipride [check cyanide or isothiocyanate] Nitroglycerine NTG [check methemoglobin] Adrenaline Epinephrine (USA) Noradrenaline Norepinephrine (USA) Milrinone Primacor Dobutamine Dobutrex

SEPTIC

SHOCK

SIRS/Sepsis/Septic shock

Mediator release: exogenous & endogenous

Maldistribution of blood flow

Cardiac dysfunction

Imbalance of oxygen supply and demand

Alterations in metabolism

INFLAMMATORY EVENTS IN THE SIRS SPECTRUM Primary ProInflammatories: LPS; IL-1; TNF Secondary ProInflammatories: 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

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 (> 2 sec, cold shock) -> common Flash capillary fill (warm shock) -> less common urine output

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 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

SEPTIC SHOCK: COLD SHOCK

Late, uncompensated stage with drop in cardiac output
Clinical signs

Cyanosis, cold and clammy skin, rapid, thready pulses, shallow respirations Decreased mixed venous sats, cardiac output and CVP, increased SVR, thrombocytopenia, oliguria, myocardial dysfunction, capillary leak

Physiologic parameters

Biochemical abnormalities

Metabolic acidosis, hypoxia, coagulopathy, hypoglycemia

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

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 > 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

THRESHOLD HEART RATES AND PERFUSION PRESSURES

GOALS OF 1ST HOUR RESUSCITATION (II)

Airway & breathing: reasons to intubate work of breathing; respiratory acidosis (pCO2 > 60 mmHg, pH < 7.25 with nl BE); hypoxia (pO2/FiO2 < 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).

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 O2 saturation > 70%; 3.3 < CI < 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

PEDIATRIC ALGORITHM

CAN WE CHANGE THE COURSE OF AN INFECTIOUS DISEASE ? OR

IS THE PICU IMPORTANT ?

June 1992 December 1997 (n=331) Demographics: Median age 2 y & 8 m (range 5 w to 17.5 y) M / F - 143:188 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)

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

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

NEONATAL ALGORITHM

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
o
o

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.

o
o

THE NEXT DECADE SAW DOZENS OF FAILED TRIALS AND MILLIARDS OF $$ WASTED

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 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

Hypovolemic Cardiogenic Obstructive Distributive Septic: Early Septic: Late CO SVR MAP Wedge CVP Or Or Or Or Or Or Or or

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.