CARDIOGENIC SHOCKCARDIOGENIC SHOCK

Etiology:Etiology:– ArrhythmiasArrhythmias– InfectionInfection– MetabolicMetabolic– ObstructiveObstructive– Drug intoxicationDrug intoxication– Congenital heart diseaseCongenital heart disease– TraumaTrauma

CARDIOGENIC SHOCK (cont.)CARDIOGENIC SHOCK (cont.)

Differentiation from other types of Differentiation from other types of shock:shock:– HistoryHistory– Physical Exam:Physical Exam:

• Enlarged liverEnlarged liver• Gallop rhythmGallop rhythm• MurmurMurmur• RalesRales

– CXR: CXR: • Enlarged heart, pulmonary venous congestionEnlarged heart, pulmonary venous congestion

CARDIOGENIC SHOCKCARDIOGENIC SHOCK

Etiology:Etiology:– ArrhythmiasArrhythmias– InfectionInfection– MetabolicMetabolic– ObstructiveObstructive– Drug intoxicationDrug intoxication– Congenital heart diseaseCongenital heart disease– TraumaTrauma

CARDIOGENIC SHOCK (cont.)CARDIOGENIC SHOCK (cont.)

• Management:Management:– Improve cardiac output::Improve cardiac output::

Correct dysrhymiasCorrect dysrhymias Optimize preloadOptimize preload Improve contractilityImprove contractility Reduce afterloadReduce afterload

– Minimize cardiac work:Minimize cardiac work: Maintain normal temperatureMaintain normal temperature SedationSedation Intubation and mechanical ventilationIntubation and mechanical ventilation Correct anemiaCorrect anemia

DISTRIBUTIVE SHOCKDISTRIBUTIVE SHOCK

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

EtiologyEtiology– AnaphylaxisAnaphylaxis– Drug toxicityDrug toxicity– Neurologic injuryNeurologic injury– Early sepsisEarly sepsis

ManagementManagement– FluidFluid– Treat underlying causeTreat underlying cause

OBSTRUCTIVE SHOCKOBSTRUCTIVE SHOCK

Mechanical obstruction to ventricular Mechanical obstruction to ventricular outflowoutflow

Etiology: CHD, massive PE, tension Etiology: CHD, massive PE, tension pneumothorax, cardiac tamponadepneumothorax, cardiac tamponade

Inadequate C.O. in the face of Inadequate C.O. in the face of adequate preload and contractilityadequate preload and contractility

Tamponade: Narrow pulse pressure Tamponade: Narrow pulse pressure and/or EMDand/or EMD

Treat underlying cause.Treat underlying cause.

DISSOCIATIVE SHOCKDISSOCIATIVE SHOCK

Inability of Hemoglobin molecule to Inability of Hemoglobin molecule to give up the oxygen to tissuesgive up the oxygen to tissues

Etiology: Carbon Monoxide poisoning, Etiology: Carbon Monoxide poisoning, methemoglobinemia,dyshemoglobinemethemoglobinemia,dyshemoglobinemiasmias

Tissue perfusion is adequate, but Tissue perfusion is adequate, but oxygen release to tissue is abnormaloxygen release to tissue is abnormal

Early recognition and treatment of Early recognition and treatment of the cause is main therapythe cause is main therapy

CLINICAL APPROACH, SOME CLINICAL APPROACH, SOME BACKGROUND & the FUTURE BACKGROUND & the FUTURE

SEPSIS / SIRS MOSF / ARDS

VOCABULARY IVOCABULARY I

CO - cardiac output = SV x HR AND also CO - cardiac output = SV x HR AND also

CO = CO = PP / SVR / SVR P (driving pressure) = MAP - CVPP (driving pressure) = MAP - CVP SVR – systemic vascular resistance .SVR – systemic vascular resistance . PVR – pulmonary vascular resistance.PVR – pulmonary vascular resistance. CaOCaO22 – art O – art O22 content [( content [(1.34 x Hb x O1.34 x Hb x O22sat) + (pO2 x 0.003sat) + (pO2 x 0.003)].)].

DODO22 - O - O22 delivery (CO delivery (CO22 x CO). x CO).

VOVO2 2 – O– O22 consumption [CO x CO consumption [CO x CO22 x O x O22 extraction]. extraction].

OO22 extraction – the difference in CO extraction – the difference in CO22 between the between the aorta and the pulmonary artery. aorta and the pulmonary artery.

.

.

. . .

.

VOCABULARY IIVOCABULARY II

Drugs: Nitroprusside – Nipride [check cyanide or

isothiocyanate] Nitroglycerine – NTG [check methemoglobin] Adrenaline – Epinephrine (USA) Noradrenaline – Norepinephrine (USA) Milrinone – Primacor Dobutamine – Dobutrex

SIRS/Sepsis/Septic shockSIRS/Sepsis/Septic shock

Mediator release:Mediator release:

exogenous & endogenousexogenous & endogenous

MaldistributionMaldistribution

of blood flowof blood flow

CardiacCardiac

dysfunctiondysfunction

Imbalance of Imbalance of oxygenoxygen

supply and supply and demanddemand

Alterations inAlterations in

metabolismmetabolism

S E P T I C S H O C KS E P T I C S H O C K

SEPSIS / SIRS MOSF / ARDS

Primary Pro-Inflammatories:LPS;LPS; IL-1; TNF

Proteases Coagulation factorsKininsEicosanoids (PGE2)Nitric Oxide, ROSHeat-Shock proteins

Anti-Inflammatories:

IL-1ra; IL-4; IL-10

INFLAMMATORY EVENTS IN THE SIRS SPECTRUM

Secondary Pro-Inflammatories:IL-6; IL-8

What do we need to diagnose What do we need to diagnose SEPTIC SHOCK ?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 SHOCKDEFINITIONS 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 SHOCKSEPTIC SHOCK: “WARM SHOCK””

Early, compensated, hyperdynamic stateEarly, compensated, hyperdynamic state Clinical signsClinical signs

• Warm extremities with bounding pulses, Warm extremities with bounding pulses, tachycardia, tachypnea, confusiontachycardia, tachypnea, confusion

Physiologic parametersPhysiologic parameters• widened pulse pressure, increased cardiac ouptut widened pulse pressure, increased cardiac ouptut

and mixed venous saturation, decreased systemic and mixed venous saturation, decreased systemic vascular resistancevascular resistance

Biochemical evidence:Biochemical evidence:• Hypocarbia, elevated lactate, hyperglycemiaHypocarbia, elevated lactate, hyperglycemia

SEPTIC SHOCK: “COLD SHOCK”SEPTIC SHOCK: “COLD SHOCK”

Late, uncompensated stage with drop in cardiac outputLate, uncompensated stage with drop in cardiac output Clinical signsClinical signs

Cyanosis, cold and clammy skin, rapid, thready pulses, Cyanosis, cold and clammy skin, rapid, thready pulses, shallow respirationsshallow respirations

Physiologic parametersPhysiologic parameters Decreased mixed venous sats, cardiac output and CVP, Decreased mixed venous sats, cardiac output and CVP,

increased SVR, thrombocytopenia, oliguria, myocardial increased SVR, thrombocytopenia, oliguria, myocardial dysfunction, capillary leakdysfunction, capillary leak

Biochemical abnormalitiesBiochemical abnormalities Metabolic acidosis, hypoxia, coagulopathy, hypoglycemiaMetabolic acidosis, hypoxia, coagulopathy, hypoglycemia

Cold Shock rapidly progresses to MOSF or death, if Cold Shock rapidly progresses to MOSF or death, if

untreateduntreated

MMulti-ulti-OOrgan rgan SSystem ystem FFailure: Coma, ARDS, CHF, ailure: Coma, ARDS, CHF,

Renal Failure, Ileus or GI hemorrhage, DICRenal Failure, Ileus or GI hemorrhage, DIC

More organ systems involved, worse the prognosisMore organ systems involved, worse the prognosis

Therapy: ABCs, fluidTherapy: ABCs, fluid

Appropriate antibiotics, treatment of underlying causeAppropriate antibiotics, treatment of underlying cause

SEPTIC SHOCK (CON’T)SEPTIC SHOCK (CON’T)

GOALS OF 1ST HOUR RESUSCITATION (I)GOALS OF 1ST HOUR RESUSCITATION (I)

Maintain oxygenation, ventilation, circulation and threshold heart Maintain oxygenation, ventilation, circulation and threshold heart

rate (next slide)rate (next slide)

Therapeutic end points:Therapeutic end points:

• Capillary refill; no difference between peripheral & central Capillary refill; no difference between peripheral & central

pulses; warm extremities; urine > 1 mL/kg/h; normal mental pulses; warm extremities; urine > 1 mL/kg/h; normal mental

status & BP for agestatus & BP for age

Monitoring: pulse oximeter; cont ECG; A-line; continuous temp Monitoring: pulse oximeter; cont ECG; A-line; continuous temp

(core & peripheral); bladder catheter; repeated glu & iCa (core & peripheral); bladder catheter; repeated glu & iCa

THRESHOLD HEART RATES AND PERFUSION PRESSURESTHRESHOLD HEART RATES AND PERFUSION PRESSURES

GOALS OF 1ST HOUR RESUSCITATION (II)GOALS OF 1ST HOUR RESUSCITATION (II)

Airway & breathingAirway & breathing: reasons to intubate – : reasons to intubate – work of breathing; work of breathing; respiratory acidosis (pCOrespiratory acidosis (pCO22 > 60 mmHg, pH < 7.25 with nl BE); > 60 mmHg, pH < 7.25 with nl BE);

hypoxia (pOhypoxia (pO22/FiO/FiO22 < 200); loss of airway protection 2nd to < 200); loss of airway protection 2nd to

mental status.mental status. CirculationCirculation: two peripherals, intraosseous, cut-down. If inotropes : two peripherals, intraosseous, cut-down. If inotropes

are to be given are to be given central venous line. central venous line. FluidsFluids: repeated 20 mL/kg boluses. Follow rales, gallop, : repeated 20 mL/kg boluses. Follow rales, gallop,

hepatomegaly, & hepatomegaly, & work of breathing. Sometimes 200 mL/kg work of breathing. Sometimes 200 mL/kg were infused. were infused.

Vasoactive drugsVasoactive drugs: Dopamine is 1: Dopamine is 1stst line. If shock remains line. If shock remains resistent: Adrenaline for ‘cold’ shock (resistent: Adrenaline for ‘cold’ shock ( & & effects) and effects) and Noradrenaline for ‘warm’ shock (Noradrenaline for ‘warm’ shock (-effect).-effect).

GOALS OF 1ST HOUR RESUSCITATION (III)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 STABILISAZTIONGOALS OF STABILISAZTION

GoalsGoals: normal perfusion; perfusion pressure normal for age; : normal perfusion; perfusion pressure normal for age; mixed venous Omixed venous O22 saturation > 70%; 3.3 < CI < 6.0 L/min/m saturation > 70%; 3.3 < CI < 6.0 L/min/m22..

Hemodynamic support Hemodynamic support may be required for days. There may be required for days. There are several variations:are several variations:

low C.O. and high SVR low C.O. and high SVR consider Nipride/NTG consider Nipride/NTG ++ steroids; Milrinone is another option. steroids; Milrinone is another option.

high C.O. and low SVR high C.O. and low SVR Norepinephrine Norepinephrine ++ steroids. steroids. low C.O. and low SVR low C.O. and low SVR Adrenaline Adrenaline ++ steroids. steroids. Shock refractory to cathecolamines Shock refractory to cathecolamines r/o r/o

pneomothorax, tamponade, Addison, hypothyroid, pneomothorax, tamponade, Addison, hypothyroid, ongoing blood loss or an abdominal catastrophy.ongoing blood loss or an abdominal catastrophy.

CONSIDER ECMO CONSIDER ECMO

PEDIATRIC ALGORITHMPEDIATRIC ALGORITHM

CAN WE CHANGE THE COURSE CAN WE CHANGE THE COURSE OF AN INFECTIOUS DISEASE ?OF AN INFECTIOUS DISEASE ?

OROR

IS THE PICU IMPORTANT ?IS THE PICU IMPORTANT ?

June 1992 – December 1997 (June 1992 – December 1997 (nn=331)=331) Demographics:Demographics:• Median age 2 y & 8 m (range 5 w to 17.5 y)Median age 2 y & 8 m (range 5 w to 17.5 y)• M / F - 143:188M / F - 143:188• Septicemia 281; meningitis 50Septicemia 281; meningitis 50• deaths: deaths: In PICU: total 33 [29 (In PICU: total 33 [29 (10%10%) septic, 3 () septic, 3 (6%6%) meningitis]) meningitis] Before arriving PICU: total 29Before arriving PICU: total 29• In 1997 there were In 1997 there were 2/1112/111 deaths ( deaths (predicted 38/111predicted 38/111))• The proportion of complications remained The proportion of complications remained unchangedunchanged

(~5.5% for amputations or skin grafting; ~8% for (~5.5% for amputations or skin grafting; ~8% for neurological abnormalities)neurological abnormalities)

MD – CENTERALIZED CLINICAL MD – CENTERALIZED CLINICAL

MANAGEMENT (I) MANAGEMENT (I)

When dx suspectedWhen dx suspected promptprompt PCN injection by the PCN injection by the family physician (GP)family physician (GP)

Continuous telephone advice by PICU attending prior Continuous telephone advice by PICU attending prior to arrival of mobile team to arrival of mobile team

Mobile Intensive Care Team led by PICU attending & Mobile Intensive Care Team led by PICU attending & nurse transferred all patients to the central unit nurse transferred all patients to the central unit

Elective intubation & ventilation, hemodynamic Elective intubation & ventilation, hemodynamic monitoring, and ongoing resuscitation performed at monitoring, and ongoing resuscitation performed at referring hospitalreferring hospital

Patient stabilized prior to transport Patient stabilized prior to transport

Photocopies of all documentation donePhotocopies of all documentation done Treatment includedTreatment included Aggressive fluid resuscitation (4.5% Albumin)Aggressive fluid resuscitation (4.5% Albumin) Early intubation and ventilationEarly intubation and ventilation Generous use of InotropesGenerous use of Inotropes Correction of coagulopathyCorrection of coagulopathy Correction of metabolic derangements (K, Ca, Mg, Correction of metabolic derangements (K, Ca, Mg,

Phosph, Bicarb & Glu)Phosph, Bicarb & Glu) Early renal replacement therapyEarly renal replacement therapy

MD – CENTERALIZED MD – CENTERALIZED CLINICAL MANAGEMENT (II) CLINICAL MANAGEMENT (II)

NEONATAL ALGORITHMNEONATAL ALGORITHM

DO WE HAVE A SPECIFIC TARGET ?DO WE HAVE A SPECIFIC TARGET ?

TREATMENT OF GRAM-NEGATIVE BACTEREMIA AND TREATMENT OF GRAM-NEGATIVE BACTEREMIA AND SEPTIC SHOCK WITH HA-1A HUMAN MONOCLONAL SEPTIC SHOCK WITH HA-1A HUMAN MONOCLONAL ANTIBODY AGAINST ENDOTOXIN. ZEIGLER EJ ET ALANTIBODY AGAINST ENDOTOXIN. ZEIGLER EJ ET AL

N Engl J Med. 1991 Feb 14;324(7):429-36N Engl J Med. 1991 Feb 14;324(7):429-36 o HA-1AHA-1A is an IgM monoclonal ab that binds to the lipid A is an IgM monoclonal ab that binds to the lipid A

domain of endotoxin.domain of endotoxin.o 543 adult patients with sepsis presumed to be of gram-negative 543 adult patients with sepsis presumed to be of gram-negative

origin (not necessarily shock or bacteremia proven !)origin (not necessarily shock or bacteremia proven !)o Total mortality: placebo 43%; HA-1A 39% (p=0.24).Total mortality: placebo 43%; HA-1A 39% (p=0.24).o Among the 200 Among the 200 who had gram-negative bacteremiawho had gram-negative bacteremia mortality mortality

was 45/92 (49%) in the placebo group and 32/105 (30%) in the was 45/92 (49%) in the placebo group and 32/105 (30%) in the HA-1A group (p=0.014).HA-1A group (p=0.014).

o Follow-up studies Follow-up studies drug increases mortality and was drug increases mortality and was

abandoned. abandoned.

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

WASTEDWASTED

THE SIREN’S SONG THE SIREN’S SONG OF CONFIRMATORY OF CONFIRMATORY SEPSIS TRIALS: SEPSIS TRIALS: SELECTION BIAS and SELECTION BIAS and SAMPLING ERRORSAMPLING ERRORNatanson, Charles MD; Natanson, Charles MD;

Esposito, Claire J. MD; Esposito, Claire J. MD;

Banks, Steven M. PhDBanks, Steven M. PhD

Crit Care Med. 1998 Dec;26(12):1927Crit Care Med. 1998 Dec;26(12):1927

When confronted with the disappointment of failed sepsis trials, it is When confronted with the disappointment of failed sepsis trials, it is alluring to maneuver the data into the conclusion that a given drug alluring to maneuver the data into the conclusion that a given drug was beneficial to certain patients. Unfortunately, was beneficial to certain patients. Unfortunately, the sirens' sweet the sirens' sweet songs of significancesongs of significance (reached via sampling error and selection bias) (reached via sampling error and selection bias) may have set back new drug development for sepsis and left the field may have set back new drug development for sepsis and left the field shipwrecked on the rocksshipwrecked on the rocks. Overall, vast resources have been . Overall, vast resources have been expended on sepsis trials in the last 10 yrs. It is important to realize expended on sepsis trials in the last 10 yrs. It is important to realize that the small nonsignificant treatment effects found in the primary that the small nonsignificant treatment effects found in the primary target populations from large initial sepsis trials have been target populations from large initial sepsis trials have been consistently reproduced in confirmatory trials (PAFra consistently reproduced in confirmatory trials (PAFra [1,2],, interleukin-1 interleukin-1 receptor antagonists receptor antagonists [9,10], anti-TNF-monoclonal antibodies , anti-TNF-monoclonal antibodies [6-8], , and P-55 soluble TNF receptors and P-55 soluble TNF receptors [13,14]) () (Figure 1 and and Figure 2, , Table 1). Faced with such a persistently high mortality rate from ). Faced with such a persistently high mortality rate from sepsis and new agents with such small beneficial effects, we need to sepsis and new agents with such small beneficial effects, we need to increase our efforts to find better therapeutic agents and do the increase our efforts to find better therapeutic agents and do the necessary research to formulate new questions to test these same necessary research to formulate new questions to test these same agents agents

ACTIVATED PROTEIN CACTIVATED PROTEIN C

Rational for using activated protein CRational for using activated protein C

Xigris 12/2003 Xigris 12/2003 NO DATA in CHILDREN !NO DATA in CHILDREN !

Despite that Despite that Eli LillyEli Lilly insists on full price… insists on full price…

HEMODYNAMIC VARIABLES in HEMODYNAMIC VARIABLES in DIFFERENT SHOCK STATESDIFFERENT SHOCK STATES

or or Septic: LateSeptic: Late

Or Or Septic: EarlySeptic: Early

Or Or Or Or Or Or DistributiveDistributive

Or Or ObstructiveObstructive

Or Or CardiogenicCardiogenic

Or Or HypovolemicHypovolemic

CVPCVPWedgeWedgeMAPMAPSVRSVRCOCO

FINAL THOUGHTSFINAL 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.

תודה על ההקשבה !תודה על ההקשבה !

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