SHOCK Author: Nazanin Meshkat MD, FRCPC, MHSc, Assistant Professor, University of Toronto Date Created: September 2011 Instructions: 1. We recommend taking.

SHOCK Author: Nazanin Meshkat MD, FRCPC, MHSc, Assistant Professor, University of Toronto Date Created: September 2011 Instructions: 1. We recommend taking the learners through this module in two sittings - Part 1 and Part 2 2. Depending on the level of training of the learner, you may use slides 5-25 as a review or skip them completely and proceed to Case 1 in slide 26. 3. In the notes sections we provide supplementary information and evidence that can be used to supplement the teaching session depending on the level of the learners

Objectives: Part 1 To develop an understanding of the definition and pathophysiology of shock To develop an understanding and overview of the different types of shock To develop a systematic approach to the detection and management of shock

Objectives: Part 2 To develop a deeper understanding of sepsis and septic shock To discuss cost effective and high impact interventions to decrease mortality in shock

PART 1 Instructions: Depending on the level of training of the learner, may use slides 5-25 as a review or skip them completely and proceed to Case 1 in slide 26.

Definition of Shock Inadequate perfusion and oxygenation of cells
Notes: Another way to describe Shock is as an imbalance between O2 delivery and demand

Definition of Shock Inadequate perfusion and oxygenation of cells leads to: Cellular dysfunction and damage Organ dysfunction and damage Notes: The inadequate perfusion and oxygenation leads to first cellular dysfunction and then organ dysfunction. -Cellular effects include cell membrane ion pump dysfunction, intracellular edema, leakage of intracellular contents into the extracellular space, and inadequate regulation of intracellular pH. -Systemic effects include alterations in the serum pH, endothelial dysfunction, as well as further stimulation of inflammatory and antiinflammatory cascades that lead to multiorgan dysfunction 6

Why should you care? High mortality - 20-90%
Early on the effects of O2 deprivation on the cell are REVERSIBLE Early intervention reduces mortality Notes: Mortality due to shock is high. It is estimated that 35 to 60% of patients die within one month of the onset of septic shock. The mortality rate may be even higher among patients with cardiogenic shock; it is estimated to be 60 to 90%. Mortality due to hypovolemic shock is more variable. Early intervention can prevent the cascade of detrimental effects of O2 deprivation on the cells and organs

Pathophysiology 4 types of shock Cardiogenic Obstructive Hypovolemic
Distributive Notes: There are different classifications (some classify obstructive shock as a subset of cardiogenic shock)

Pathophysiology: Overview
Tissue perfusion is determined by Mean Arterial Pressure (MAP) MAP = CO x SVR Notes: In any type of SHOCK tissue perfusion is determined by MAP - which is used as a measure of perfusion (MAP as a measure of perfusion is only a surrogate measure, and is not 100% accurate - however sometimes it’s all we have to go by) MAP = cardiac output multiplied by systemic vascular resistance = 2/3 systolic + 1/3 diastolic SVR is governed by the vessel length, blood viscosity, and vessel diameter CO = heart rate (HR) multiplied by Stroke Volume (SV) Heart rate Stroke Volume

Cardiogenic Shock: Pathophysiology
Heart fails to pump blood out MAP = CO x SVR HR Stroke Volume Notes: Cardiogenic shock is a shock state that occurs as a consequence of cardiac pump failure, resulting in decreased cardiac output (CO). Pump failure can occur both as a result of an abnormality of the Heart rate or the Stroke volume

Cardiogenic Shock: Pathophysiology
Normal MAP = CO x SVR Cardiogenic MAP = ↓CO x SVR MAP = ↓CO x ↑ SVR ↓MAP = ↓↓CO x ↑ SVR Notes: -BaroRc sense the decreased cardiac output and leads to increased SVR in an effort to compensate for the diminished CO -The vasoconstrictive mechanisms (I.e. the increase in systemic vascular resistance) compensate for decreased tissue perfusion by redirecting blood from the periphery to the vital organs, thereby maintaining coronary, cerebral, and splanchnic perfusion.

Cardiogenic Shock: Causes
↓MAP = ↓ CO (HR x Stroke Volume) x ↑SVR Decreased Contractility (Myocardial Infarction, myocarditis, cardiomypothy, Post resuscitation syndrome following cardiac arrest) Mechanical Dysfunction – (Papillary muscle rupture post-MI, Severe Aortic Stenosis, rupture of ventricular aneurysms etc) Arrhythmia – (Heart block, ventricular tachycardia, SVT, atrial fibrillation etc.) Cardiotoxicity (B blocker and Calcium Channel Blocker Overdose) Instructions: Ask the learner what are some causes of Cardiogenic Shock. Answer is provided in the slide Notes: Myocardial infarction causes cardiogenic shock when greater than 40 percent of the left ventricular myocardium is involved or when right ventricular infarction leads to decreased preload

Obstructive Shock: Pathophysiology
Heart pumps well, but the output is decreased due to an obstruction (in or out of the heart) MAP = CO x SVR HR x Stroke volume Notes: If the blood outflow from the heart is decreased because there is decreased return to the heart (due to an obstruction) or “obstructed” as the blood leaves the heart the stroke volume diminishes, with the overall effect of decreasing the cardiac output

Obstructive Shock: Pathophysiology
Normal MAP = CO x SVR Obstructive MAP = ↓CO x SVR MAP = ↓CO x ↑ SVR ↓MAP = ↓↓CO x ↑ SVR Notes: -Again the BaroRc sense the decreased cardiac output and lead to increased SVR in an effort to compensate for the diminished CO -The vasoconstrictive mechanisms (I.e. the increase in systemic vascular resistance) compensate for decreased tissue perfusion by redirecting blood from the periphery to the vital organs, thereby maintaining coronary, cerebral, and splanchnic perfusion.

Obstructive Shock: Causes
↓MAP = ↓ CO (HR x Stroke Volume) x ↑SVR Heart is working but there is a block to the outflow Massive pulmonary embolism Aortic dissection Cardiac tamponade Tension pneumothorax Obstruction of venous return to heart Vena cava syndrome - eg. neoplasms, granulomatous disease Sickle cell splenic sequestration Instructions: Ask the learner what are some causes of Obstructive Shock. Answer is provided in the slide

Hypovolemic Shock: Pathophysiology
Heart pumps well, but not enough blood volume to pump MAP = CO x SVR HR x Stroke volume Notes: -Hypovolemic shock is a consequence of decreased preload due to intravascular volume loss. -The decreased preload diminishes stroke volume, resulting in decreased cardiac output (CO).

Hypovolemic Shock: Pathophysiology
Normal MAP = CO x SVR Hypovolemic MAP = ↓CO x SVR MAP = ↓CO x ↑ SVR ↓MAP = ↓↓CO x ↑ SVR Notes: -Again the BaroRc sense the decreased cardiac output and lead to increased SVR in an effort to compensate for the diminished CO -The vasoconstrictive mechanisms (I.e. the increase in systemic vascular resistance) compensate for decreased tissue perfusion by redirecting blood from the periphery to the vital organs, thereby maintaining coronary, cerebral, and splanchnic perfusion.

Hypovolemic Shock: Causes
↓MAP = ↓ CO (HR x Stroke Volume) x ↑SVR Decreased Intravascular volume (Preload) leads to Decreased Stroke Volume Hemorrhagic - trauma, GI bleed, AAA rupture, ectopic pregnancy Hypovolemic - burns, GI losses, dehydration, third spacing (e.g. pancreatitis, bowel obstruction), Adesonian crisis, Diabetic Ketoacidosis Instructions: Ask the learner what are some causes of Hypovolemic Shock. Answer is provided in the slide

Distributive Shock: Pathophysiology
Heart pumps well, but there is peripheral vasodilation due to loss of vessel tone MAP = CO x SVR HR x Stroke volume Notes: Distributive (vasodilatory) shock is a consequence of severely decreased SVR.

Distributive Shock: Pathophysiology
Normal MAP = CO x SVR Distributive MAP = co x ↓ SVR MAP = ↑co x ↓ SVR ↓MAP = ↑co x ↓↓ SVR Notes: The cardiac output (with increases in both heart rate and stroke volume) is typically increased in an effort to compensate for the diminished SVR

Distributive Shock: Causes
↓MAP = ↑CO (HR x SV) x ↓ SVR Loss of Vessel tone Inflammatory cascade Sepsis and Toxic Shock Syndrome Anaphylaxis Post resuscitation syndrome following cardiac arrest Decreased sympathetic nervous system function Neurogenic - C spine or upper thoracic cord injuries Toxins Due to cellular poisons -Carbon monoxide, methemoglobinemia, cyanide Drug overdose (a1 antagonists) Instructions: Ask the learner what are some causes of Distributive Shock. Answer is provided in the slide Notes: In inflammatory cascade the SVR may initially increase to compensate for leaky vessels (third spacing), but eventually to the inflammatory cascade the SVR decreases In anaphylaxis the SVR may initially increase to compensate for leaky vessels (third spacing), but eventually to the inflammatory cascade the SVR decreases Neurogenic shock occurs when injuries to the spine occur above T6 leading to a disruption in the sympathetic chain and therefore decrease vascular tone

To Summarize Type of Shock Insult Physiologic Effect Compensation
Cardiogenic Heart fails to pump blood out ↓CO BaroRc ↑SVR Obstructive Heart pumps well, but the outflow is obstructed Hemorrhagic Heart pumps well, but not enough blood volume to pump Distributive Heart pumps well, but there is peripheral vasodilation ↓SVR ↑CO

Ok…it’s really not THAT simple
MAP = CO x SVR HR x Stroke volume Preload Afterload Contractility

Heart fails to pump blood out ↓CO BaroRc ↑SVR ↑
Type of Shock Insult Physiologic Effect Compensation Heart Rate Contractility Cardiogenic Heart fails to pump blood out ↓CO BaroRc ↑SVR ↑ Obstructive Heart pumps well, but the outflow is obstructed Hemorrhagic Heart pumps well, but not enough blood volume to pump Distributive Heart pumps well, but there is peripheral vasodilation ↓SVR ↑CO No Change - in neurogenic shock Notes: The earlier table was oversimplified. Regardless of the type of SHOCK all components of the equation will compensate for the physiologic change induced by the insult, however some will be more effective than others 24

Additional Compensatory Mechanisms
Renin-Angiotensin-Aldosterone Mechanism AII components lead to vasoconstriction Aldosterone leads to water conservation ADH leads to water retention and thirst Inflammatory cascade 25

Case 1 24 year old male Previously healthy
Lives in a malaria endemic area (PNG) Brought in by friends after a fight - he was kicked in the abdomen He is agitated, and won’t lie flat on the stretcher HR 92, BP 126/72, SaO2 95%, RR 26 Instructions: Ask the learner if the patient in Case 1 is in Shock? If say yes - challenge with “but the blood pressure is normal”. Answer: The patient is in shock because: -his respiratory rate is increased (tachypnea is a compensatory mechanism for early metabolic acidosis) -he is also agitated which means he has altered mental status due to end organ lack of perfusion and dysfuction

Stages of Shock Insult Preshock (Compensation) Shock (Compensation
Timeline and progression will depend on: -Cause -Patient Characteristics -Intervention Insult Preshock (Compensation) Shock (Compensation Overwhelmed) Notes: All forms of shock go through “stages “ of shock. How quickly the patient goes through the stages depends on the cause of shock, patient characteristics, and how quickly we intervene. For example, a healthy adult can be asymptomatic despite a 10% reduction in total effective blood volume. OR if a healthy patient is bleeding slowly from a bleeding ulcer, he will be able to compensate for the blood loss for a long time. If the blood loss is very rapid (e.g. from splenic rupture in Case 1), the patient may progress to death within minutes going through all stages within minutes to hours Preshock — Preshock is also referred to as warm shock or compensated shock. It is characterized by rapid compensation for diminished tissue perfusion by various homeostatic mechanisms. As an example, compensatory mechanisms during preshock may allow an otherwise healthy adult to be asymptomatic despite a 10 percent reduction in total effective blood volume. Tachycardia, peripheral vasoconstriction, and either a modest increase or decrease in systemic blood pressure may be the only clinical signs of shock. Shock — During shock, the compensatory mechanisms become overwhelmed and signs and symptoms of organ dysfunction appear. These include tachycardia, dyspnea, restlessness, diaphoresis, metabolic acidosis, oliguria, and cool clammy skin. End-organ dysfunction — Progressive end-organ dysfunction leads to irreversible organ damage and patient death. End organ dysfunction - typically correspond to a significant physiologic perturbation Examples include a 20 to 25% reduction in effective blood volume in hypovolemic shock, a fall in the cardiac index to less than 2.5 L/min/M2 in cardiogenic shock, or activation of innumerable mediators of the systemic inflammatory response syndrome (SIRS) in distributive shock. During this stage, urine output may decline further (culminating inanuria and acute renal failure), acidemia decreases the cardiac output and alters cellular metabolic processes, and restlessness evolves into agitation, obtundation, and coma. REFERENCES: Up to date - Shock to Adults: Types, presentation, diagnostic approach End organ Damage Death

Case 1: Stages of Shock Stage Pathophysiology Clinical Findings Insult
Splenic Rupture -- Blood Loss Abdominal tenderness and girth Instructions: Take the learner through the different stages of shock for patient in Case 1. 1. Ask the learner what kind of shock is the patient in Case 1 experiencing. I.e. what is the insult. Answer: Hemorrhagic Shock 2. Ask the learner to describe what compensatory mechanisms will be activated (I.e what will happen in the Preshock phase) Answer: is provided in the next slide.

Splenic Rupture -- Blood Loss Abdominal tenderness and girth Preshock Hemostatic compensation MAP =↓CO(↑HR x↓SV) x↑SVR Decreased CO is compensated by increase in HR and SVR MAP is maintained HR will be increased Extremities will be cool due to vasoconstriction Answer: The cardiac output will decrease due to a decrease in stroke volume (decreased preload). Compensation will be an increase in HR and SVR. MAP will be maintained. Instructions: Ask the learner what will happen when these compensatory mechanisms fail. Answer: is provided in the next 2 slides

Splenic Rupture -- Blood Loss Abdominal tenderness and girth Preshock Hemostatic compensation MAP =↓CO(HR x↓SV) x ↑ SVR Decreased CO is compensated by increase in HR and SVR MAP is maintained HR will be increased Extremities will be cool due to vasoconstriction Shock Compensatory mechanisms fail MAP is reduced Tachycardia, dyspnea, restlessness

Splenic Rupture -- Blood Loss Abdominal tenderness and girth Preshock Hemostatic compensation MAP =↓CO(HR x↓SV) x ↑ SVR Decreased CO is compensated by increase in HR and SVR MAP is maintained HR will be increased Extremities will be cool due to vasoconstriction Shock Compensatory mechanisms fail MAP is reduced Tachycardia, dyspnea, restlessness End organ dysfunction Cell death and organ failure Decreased renal function Liver failure Disseminated Intravascular Coagulopathy Death

Is this Shock? Signs and symptoms Laboratory findings
Hemodynamic measures Notes: To determine if we are dealing with shock, there are a few tools at our disposal. The most important are the signs and symptoms. i.e look for cardinal findings. Laboratory and hemodynamic measures can also help us, however these are often not available. Which underscores the importance of being able to identify shock early with our clinical history and physical. Slides describe the signs and symptoms associated with pre-shock and shock

Symptoms and Signs of Shock
Level of consciousness Initially may show few symptoms Continuum starts with Anxiety Agitation Confusion and Delirium Obtundation and Coma In infants Poor tone Unfocused gaze Weak cry Lethargy/Coma (Sunken or bulging fontanelle) Notes: Change in mental status — The continuum of mental status changes frequently encountered in shock begins with agitation, progresses to confusion or delirium, and ends in obtundation or coma.

Pulse Tachycardia HR > What are a few exceptions? Rapid, weak, thready distal pulses Respirations Tachypnea Shallow, irregular, labored Notes: Answer to “What are a few exceptions to tachycardia?” -neurogenic shock -relative tachycardia - e.g. in an athlete HR of 90 is tachycardia -bradycardic causes of shock! -bradycardia in severe shock - an agonal event from any cause of shock Tachypnea occurs due to two reasons -Chemoreceptors sense hypoxia and compensate by causing tachypnea -Also tachypnea is a compensatory mechanism for metabolic acidosis (to blow off CO2)

Blood Pressure May be normal! Definition of hypotension Systolic < 90 mmHg MAP < 65 mmHg 40 mmHg drop systolic BP from from baseline Children Systolic BP < 1 month = < 60 mmHg Systolic BP 1 month - 10 years = < 70 mmHg + (2 x age in years) In children hypotension develops late, late, late A pre-terminal event Notes: In a patient who is hypertensive at baseline, 40 mmHg drop in systolic BP is technically hypotension = relative hypotension

Skin Cold, clammy (Cardiogenic, Obstructive, Hemorrhagic) Warm (Distributive shock) Mottled appearance in children Look for petechia Dry Mucous membranes Low urine output <0.5 ml/kg/hr Notes: -Vasoconstriction causes the cool and clammy skin that is typical of shock. Not all patients with shock have cool and clammy skin, however. Patients with early distributive shock or terminal shock may have flushed, hyperemic skin. The former occurs prior to the onset of compensatory vasoconstriction, while the latter is due to failure of compensatory vasoconstriction. -In most settings of shock (other than early distributive shock) there will be decreased capillary refill -Oliguria — Oliguria may be due to shunting of renal blood flow to other vital organs, intravascular volume depletion, or both. When intravascular volume depletion is a cause, it may be accompanied by orthostatic hypotension, poor skin turgor, absent axillary sweat, or dry mucous membranes.

(Normal in Neurogenic shock) May be increased or decreased
Hypovolemic Shock Distributive Shock Cardiogenic Obstructive HR Increased (Normal in Neurogenic shock) May be increased or decreased JVP Low High BP SKIN Cold Warm (Cold in severe shock) CAP REFILL Slow Notes: This is a summary slide

Empiric Criteria for Shock
4 out of 6 criteria have to be met Ill appearance or altered mental status Heart rate >100 Respiratory rate > 22 (or PaCO2 < 32 mmHg) Urine output < 0.5 ml/kg/hr Arterial hypotension > 20 minutes duration Lactate > 4 Notes: to standardize the diagnosis of shock, 4 of these 6 criteria have to be met to define shock

Lactate Lactate is increased in Shock Predictor of Mortality
Can be used as a guide to resuscitation However it is not necessary, or available in many settings Notes: Lactate is increased due to: -Decreased O2 --> aerobic metabolism switches over to anaerobic --> byproduct = lactate -Decreased hepatic clearance Metabolic acidosis — Metabolic acidosis develops as shock progresses, reflecting decreased clearance of lactate by the liver, kidneys, and skeletal muscle.. Lactate production may increase due to anaerobic metabolism if shock progresses to circulatory failure and tissue hypoxia, which can worsen the acidemia

Management of Shock History Physical exam Labs Other investigations
Treat the Shock - Start treatment as soon as you suspect Pre-shock or Shock Monitor

Historical Features Trauma? Pregnant? Acute abdominal pain?
Vomiting or Diarrhea? Hematochezia or hematemesis? Fever? Focus of infection? Chest pain?

Physical Exam Vitals - HR, BP, Temperature, Respiratory rate, Oxygen Saturation Capillary blood sugar Weight in children

Physical Exam In a patient with normal level of consciousness - Physical exam can be directed to the history

Physical Exam In a patient with abnormal level of consciousness
Primary survey Cardiovascular (murmers, JVP, muffled heart sounds) Respiratory exam (crackles, wheezes), Abdominal exam Rectal and vaginal exam Skin and mucous membranes Neurologic examination

Laboratory Tests CBC, Electrolytes, Creatinine/BUN, glucose
+/- Lactate +/- Capillary blood sugar +/- Cardiac Enzymes Blood Cultures - from two different sites Beta HCG +/- Cross Match

Other investigations ECG Urinalysis CXR +/- Echo +/- FAST

Treatment Start treatment immediately

Early Intervention can arrest or reduce the damage Insult Preshock (Compensation) Shock (Compensation Overwhelmed) Notes: In one pediatric study - death occurred in 16% with no early treatment versus 5% with early treatment. Reference: Carcillo et al. Crit Care Med 2002;30;1365 End organ Damage Death

Treatment ABC’s “5 to 15” Treat underlying cause Airway Breathing
Circulation Put the patient on a monitor if available Treat underlying cause Notes: i.e. ABC’s should be done within 5-15 minutes

Treatment: Airway and Breathing
Give oxygen

Treatment: Airway and Breathing
Consider Intubation Is the cause quickly reversible? Generally no need for intubation 3 reasons to intubate in the setting of shock Inability to oxygenate Inability to maintain airway Work of breathing Notes: Quickly reversible causes - examples = reverse tachyarrhythmia with meds, anaphylaxis than responds quickly to epinephrine Inability to oxygenate - examples = cardiogenic shock leading to pulmonary edema, ARDS Inability to maintain airway - examples = upper airway obstruction due to anaphylaxis or trauma Work of breathing - examples = -in pt with sepsis or cardiogenic shock by eliminating the work of breathing can take a load off the metabolic/hemodynamic stressors, which can lead to improvement of shock -Also if the work of breathing is suggesting that there is impending respiratory fatigue, intubate Choose intubating agent carefully - etomidate, midazolam, fentanyl cause less cardiovascular depression than other agents. -ketamine can be useful as it maintains cardiovascular status (in fact it leads to increased HR and blood pressure) -if have no other agents titrate benzodiazepines -Avoid propofol, thiopental

Treatment: Circulation
Treat the early signs of shock (Cold, clammy? Decreased capillary refill? Tachycardic? Agitated?) DO NOT WAIT for hypotension

Start IV +/- Central line (or Intraosseous) Do Blood Work +/- Blood Cultures

Fluids - 20 ml/kg bolus x 3 Normal saline Ringer’s lactate Notes: -Ongoing fluid resuscitation past the 3 boluses is based on maintaining urine output 1-2 ml/kg/hr -With large volumes of NS (> 4L) can develop a normal anion gap (hyperchloremic) acidosis - may consider switching to Ringer’s Lactate Notes: Crystalloid vs. colloid? -No benefit to colloids = Clinical trials have failed to consistently demonstrate a difference between colloid and crystalloid in the treatment of septic shock (ie. no mortality or clinical outcome difference). Colloids are significantly more expensive than crystalloids. Crystalloid versus colloid trials = -SAFE trial - 4% albumin - no difference in 28 day mortality - Finfer et al NEJM 2004;350:2247 -VISEP trial - pentastarch - no difference in 28 d mortality but a trend toward increased 90 d mortality with pentastarch (stopped early) - Brunkhorst et al NEJM 2008;358:125

Back to Case 1 24 year old male Previously healthy
Lives in a malaria endemic area (PNG) Brought in by friends after a fight - he was kicked in the abdomen He is agitated, and won’t lie flat on the stretcher HR 92, BP 126/72, SaO2 95%, RR 26

Case 1 On examination Extremely agitated Clammy and cold
Heart exam - normal Chest exam - good air entry Abdomen - bruised, tender, distended No other signs of trauma Notes: We have established that the patient is in Hemorrhagic Shock. Instructions: Ask the learner how they would manage the patient Answer: is provided in following slides

Case 1: Management Hemorrhagic (Hypovolemic Shock) ABC’s
Monitors O2 Intubate? IV lines x 2, Fluid boluses, Call for Blood - O type Blood work including cross match Treat Underlying Cause

Case 1: Management Hemorrhagic (Hypovolemic Shock) ABC’s
Monitors O2 Intubate? IV lines x 2, Fluid boluses, Call for Blood - O type Blood work including cross match Treat Underlying Cause Give Blood Call the surgeon stat If the patient does not respond to initial boluses and blood products - take to the Operating Room

Blood Products Use blood products if no improvement to fluids
PRBC 5-10 ml/kg O- in child-bearing years and O+ in everyone else +/- Platelets

Case 2 23 year old woman in Addis Ababa
Has been fatigued and short of breath for a few days She fainted and family brought her in They tell you she has a heart problem

Case 2 HR 132, BP 76/36, SaO2 88%, RR 30, Temp 36.3 Appearance - obtunded Cardiovascular exam - S1, S2, irregular, holosytolic murmer, JVP is 5 cm ASA, no edema Chest - bilateral crackles, accessory muscle use Abdomen - unremarkable Rest of exam is normal Instructions: Ask the learner if this patient is in shock and Why? Answer: Patient meets 4 of the following 6 criteria: Ill appearance or altered mental status HR >100 RR > 22 or PaCO2 < 32 mmHg UO < 0.5 ml/kg/hr Arterial hypotension > 20 mins duration Lactate > 4 Instructions: Ask the learner what type of shock is this? Answer: Cardiogenic Instructions: Ask the learner what the underlying cause could be? -Rheumatic heart disease with mitral valve regurgitation with decompensation likely due to a secondary insult (such as infection or non-compliance with meds) -cardiomyopathy secondary to chronic regurgitation with decompensation likely due to a secondary insult -endocarditis -also consider atrial fibrillation as the cause - however caution as the rapid rate can be a compensatory mechanism

What stage is she at? Insult Preshock (Compensation) Shock (Compensation Overwhelmed) Answer to “What stage is she at?”= Shock/end organ damage as the compensation is overwhelmed Instructions: How do you want to manage it? Answer: provided in next slides End organ Damage Death

Case 2: Management Cardiogenic Shock ABC’s Treat Underlying Cause
Monitors O2 IV and blood work ECG - Atrial Fibrillation, rate 130’s Treat Underlying Cause

Monitors O2 IV and blood work Intubate? ECG - Atrial Fibrillation, rate 130’s Treat Underlying Cause Instructions: Ask the learner if they would intubate Answer is provided in next 3 slides

Case 2: Why would you intubate?
Is the cause quickly reversible? 3 reasons to intubate in the setting of shock Inability to oxygenate Inability to maintain airway Work of breathing UNLIKELY Inability to oxygenate (Pulmonary edema, SaO2 88%) Instructions: Take the learner through these questions from earlier Answers provided in animations -Animation 1 - it is unlikely that this patient’s shock state is quickly reversible -Animation the patient meets two of three reasons to intubate - inability to oxygenate and increase work of breathing Accessory Muscle Use

Case 2: Why Intubate? Strenuous use of accessory respiratory muscles (i.e. work of breathing) can: Increase O2 consumption by % Decrease cerebral blood flow by 50% Notes: The choice of intubation depends on the availability of careful venilatory support. If that option is not available, may be preferable not to intubate Alternative to intubate to provide PEEP would be Bi PAP

Monitors O2 IV and blood work Intubate? ECG - Atrial Fibrillation, rate 130’s Treat Underlying Cause Instructions: How would the learner manage the patient? Answer is provided in the next slide

Case 2: Management Cardiogenic Shock Treat Underlying Cause Lasix
Atrial Fibrillation - Cardioversion? Rate control? Inotropes - Dobutamine +/- Norepinephrine (Vasopressor) Look for precipitating causes - infectious? Notes: -start with diuresing the patient with lasix (decreasing the pulmonary edema, will decrease the work of breathing, and likely lead to improved cardiac output) - in a recent trial low dose lasix may be just as good as high dose lasix (see below for the trial by Felkner et al) in pts with decompensated heart failure -It is often challenging to distinguish what is the primary cause in these patients --> AF causing heart failure or heart failure causing atrial fibrillation -afib may be a chronic condition in these patients, and the high heart rate may be compensatory -one approach is to diurese the patient first - if the heart rate slows down, it suggests that the rapid afib was secondary to the heart failure. If the diuresis does not work, then attempt electrical cardioversion or rate control -if the left atrium is dilated, cardioversion will likely not work (at least in the early stages) -for rate control choose a short acting agents such as esmolol (rarely available) or diltiazem (preferable to verapamil because it is less of a negative inotrope), or long acting agent such as digoxin (which will have a slow onset 6- 12hrs but also has inotropic activity) -amiodarone is an option but rarely available in most settings -don’t forget to anticoagulate this patient with warfarin (and heparin if cardioverting!) - they have a very high risk of stroke -in the next slide we discuss the use of inotropes Felker et al NEJM 2011;364;797 -pts presenting with acute decompensated heart failure eithin 24 hrs (with previous known HF, and previously on diuretics) -pts were randomized to receive furosemide at low or high dose, and by IV or continuous infusion (High dose = doubling the amount of lasix pt was on before presentation) -primary outcome was global assessment of symptoms at 72 hrs -primary safety endpoint was 72 hr change in serum creatinine -308 participants -primary end point did not differ between any group, although the primary outcome was slightly greater in high dose versus low dose groups (P= 0.06) -however, more high dose than low dose pts had an increase in CR level of > 0.3 mg/dL (23% vs 14% p=0.04)

Vasopressors in Cardiogenic Shock
Norepinephrine Dopamine Epinephrine Phenylephrine Notes: This slide discusses the choices of vasorpessors and inotropes available -Dopamine has fallen out of favour as the vasopressor of choice in cardiogenic shock -Dobutamine 2-10 micrograms/kg/minute +/- Norephinephrine micrograms/kg/minute (usual range 8-30 micrograms/minute) -Epi and Dopamine likely not a good idea - can cause increased HR De Backer et al N Engl J Med 2010;362;779 -1679 pts with shock (hypovolemic, cardiogenic, septic shock) were randomized to either dopamine or norepinephrine if still hypotensive after fluids -primary end point was death at 28 days -Dopamine and NE no difference in mortality when used in all-comers with shock -however dopamine increased mortality in cardiogenic shock! -also, significantly more patients on dopamine developed arrythmias (24 vs 12%) Levy B et al. Crit Care Med 2011 Mar; 39:450. -small open randomized trial study (approximately 30 pts in each arm) in pts with cardiogenic shock -norepinephrine/dobutamine versus epinephrine -10/15 in epi group and 11/15 in NE/D group survived -epi was associated with significantly mean higher HR and mean lactate level, and new arrythmias were observed in 2 pts in epi group -small study - therefore hard to draw any conclusions from it

Case 3 36 year old woman Pedestrian hit by a car
She is brought into the hospital 2 hrs after accident Short of breath Has been complaining of chest pain

Case 3 HR 126, SBP 82, SaO2 70%, RR 36, Temp 35 Obtunded, Accessory muscle use Trachea is deviated to Left Heart - distant heart sounds Chest - decreased air entry on the right, broken ribs, subcutaneous emphysema Abdominal exam - normal Apart from bruises and scrapes no other signs of trauma Instructions: Ask the learner Is she in shock? Why? Answer: Meets 4 of 6 criteria: Ill appearance or altered mental status HR >100 RR > 22 or PaCO2 < 32 mmHg UO < 0.5 ml/kg/hr Arterial hypotension >20 mins duration Lactate > 4 Instructions: Ask the learner What type of shock is this? Answer: Obstructive, though hemorrhagic is a definite possibility Instructions: Ask the learner What do you think is the underlying cause? Answer: Tension Pneumothorax

What stage is she at? Insult Preshock (Compensation) Shock (Compensation Overwhelmed) Instructions: Ask the learner What stage of shock is the pt in? Answer: Shock/end organ damage - compensation is overwhelmed Instructions: Ask the learner How do you want to manage this patient? Answer is provided in the next slide End organ Damage Death

Case 3: Management Obstructive Shock ABC’s Treat Underlying Cause
Monitors O2 IV Intubate? BW Treat Underlying Cause Instructions: Ask the learner if they would intubate this patient. Answer is provided in the next slide

Monitors O2 IV Intubate? BW Treat Underlying Cause Needle thoracentesis Chest tube CXR Answer: Don’t intubate this patient! If you do, can worsen the patients condition by worsening the tension pneumothorax

Monitors O2 IV Intubate? BW Treat Underlying Cause Needle thoracentesis Chest tube CXR Notes: Instead intervene with Needle thoracentesis as soon as the tension pneumothorax is identified.

Monitors O2 IV Intubate? BW Treat Underlying Cause Needle thoracentesis Chest tube CXR Intubate if no response

Case 3 You perform a needle thoracentesis - hear a hissing sound
Chest tube is inserted successfully HR 96, BP 100/76, SaO2 96% on O2, RR 26 You resume your clinical duties, and call the surgeon

Case 3 1 hr has gone by You are having lunch
The nurse puts her head through the door to tell you about another patient at triage, and as she is leaving “By the way, that woman with the chest tube, is feeling not so good” and leaves. Instructions: Ask the learner what they would do as they get to the patient’s bedside Answer is provided in the next slide.

Case 3 You are back at the bedside The patient is obtunded again
Pale and Clammy HR 130, BP 86/52, SaO2 96% on O2 Chest tube seems to be working Trachea is midline Heart - Normal Chest - Good air entry Abdomen - decreased bowel sounds, distended Instructions: Ask the learner What’s going on? Answer: Hemorrhagic shock Notes: This case raises two issues - the importance of combined shock (ie different types of shock can coexist) and monitoring/re-evaluating

Combined Shock Different types of shock can coexist
Can you think of other examples? Answer: Patients with septic shock (distributive) can have a hypovolemic component due to decreased oral intake, insensible losses, vomiting, or diarrhea.

Monitoring Vitals - BP, HR, SaO2 Mental Status
Urine Output (> 1-2 ml/kg/hr) When something changes or if you do not observe a response to your treatment - re-examine the patient Notes: These are indirect measures

Can we measure cell hypoxia?
Lactate - we already talked about - a surrogate Venous Oxygen Saturation - more direct measure

Venous Oxygen Saturation
Hg carries O2 A percentage of O2 is extracted by the tissue for cellular respiration Usually the cells extract < 30% of the O2

Venous Oxygen Saturation
Svo2 = Mixed venous oxygen saturation Measured from pulmonary artery by Swan-Ganz catheter. Normal > 65% Scvo2 = Central venous oxygen saturation Measured through central venous cannulation of SVC or R Atrium - i.e. Central Line Normal > 70% Notes: Central venous catheter -can be used to infuse IV fluids quickly, infuse medications, draw blood and hemodynamic monitoring -hemodynamic monitoring = CVP and central venous O2 saturation (ScvO2) Pulmonary artery catheters (or Swan Ganz catheter) can measure the pulmonary occlusion pressure (PAOP) and SvO2 (mixed venous oxyHg saturation) -PAOP has proven to be a poor predictor of fluid responsiveness in sepsis and SvO2 is similar to ScvO2 -also they increase complications without improving outcome - Therefore its use is not recommended = Animation 1-2

PART 2

Case 4 40 year old male RUQ abdominal pain, fever, fatigued for 5-6 days No past medical history

Case 4 HR 110, BP 100/72, SaO2 96%, T 39.2, RR 26 Drowsy Warm skin
Heart - S1, S2, no Murmers Chest - good A/E x 2 Abdomen - decreased bowel sound, tender RUQ Instructions: Ask the learner Is he in shock? Why? Answer: Pt is in early shock - Pt meets 3 of 6 criteria: Ill appearance or altered mental status HR >100 RR > 22 or PaCO2 < 32 mmHg UO < 0.5 ml/kg/hr Arterial hypotension >20 mins duration Lactate > 4 Instructions: What kind of shock is this? Answer: SEPTIC

What stage is he at? Insult Preshock (Compensation) Shock (Compensation Overwhelmed) Instructions: What stage of shock is this Answer: Preshock End organ Damage Death

Stages of Sepsis SIRS SEPSIS SEVERE SEPSIS SEPTIC SHOCK MODS/DEATH
Notes: Septic shock follows several stages as well - These stages parallel the stages of shock In an Adult study - Marshal et al Crit Care Med 1995;23:1638: -48% of patients with SIRS developed part of sepsis continuum -26% sepsis -18% severe sepsis -4% septic shock Early sepsis is characterized by hyperdynamic physiology - decreased SVR, elevated CO, widened pulse pressure, warm and dry extremities SEPTIC SHOCK MODS/DEATH

Definitions of Sepsis Systemic Inflammatory Response Syndrome (SIRS) – 2 or > of: -Temp > 38 or < 36 -RR > 20 -HR > 90/min -WBC >12,000 or <6,000 or more than 10% immature bands Notes: In children - developed by consensus panel -Core T (central probe) > 38.5 or < 36 -Tachycardia > 2 standard deviation above for normal for age OR in children < 1 year of age bradycardia defined as a mean HR < 10th percentile for age -Mean RR > 2 standard devation above normal for age -Leukocyte count elevated or depressed for age > 10% immature neutrophils Other criteria -Serum Glucose >12 and Lactate >4

Definitions of Sepsis Sepsis – SIRS with proven or suspected microbial source Severe Sepsis – sepsis with one or more signs of organ dysfunction or hypoperfusion. Notes: Organ dysfunction = -Hypoperfusion -Metabolic – lactate -Renal – Oliguric -Circulatory – mottled skin, cap refill -Neuro – Altered LOC

Definitions of Sepsis Septic shock = Sepsis + Refractory hypotension
-Unresponsive to initial fluids 20-40cc/kg – Vasopressor dependant MODS – multiple organ dysfunction syndrome -2 or more organs Notes: In terminal stage of septic shock - hypotension, increased systemic vascular resistance and decreased cardiac output

Stages of Sepsis Mortality SIRS 7% SEPSIS 16% SEVERE SEPSIS 20% SEPTIC
Notes: Landmark study by Rangel-Fausto shows stepwise progression with 26% of SIRS developing SEPSIS, 18% of SEPSIS developing SEVERE, and 4% developing SEPTIC SHOCK (JAMA 1995;273;117) -Also showed an increase in mortality with progression SEPTIC SHOCK 70% MODS/DEATH

Pathophysiology Complex pathophysiologic mechanisms

Pathophysiology Inflammatory Cascade:
Humoral, cellular and Neuroendocrine (TNF, IL etc) Endothelial reaction Endothelial permeability = leaking vessels Coagulation and complement systems Microvascular flow impairment

Pathophysiology End result = Global Cellular Hypoxia

Focus of Infection Any focus of infection can cause sepsis
Gastrointestinal GU Oral Skin Notes: -Staphylococcus is the most common infecting organism for children with severe sepsis - 44% in an international multicenter RCT -Strep pneumonia 6% and pseudomonas aeruginosa 13% -Immunization to pneumococcus and H flu have reduced the incidence

Risk Factors for Sepsis
Infants Immunocompromised patients Diabetes Steroids HIV Chemotherapy/malignancy Malnutrition Sickle cell disease Disrupted barriers Foley, burns, central lines, procedures Notes: In Sickle cell disease - encapsulated organisms

Back to Case 4 HR 110, BP 100/72, SaO2 96%, T 39.2, RR 20 Drowsy
Warm skin Heart - S1, S2, no Murmers Chest - good A/E x 2 Abdomen - decreased bowel sound, tender RUQ Instructions: Ask the learner How do you want to manage this patient? Answer: ABC’s - see next slide

Case 4: Management Distributive Shock (SEPSIS) ABC’s
Monitors O2 IV fluids 20 cc/kg x 3 Intubate? BW Treat Underlying Cause Notes: A landmark trial provides guidance on how to resuscitate septic patients. See next slide.

Resuscitation in Sepsis
Early goal directed therapy - Rivers et al NEJM 2001 Used in pt’s who have: an infection, 2 or more SIRS, have a systolic < 90 after 20-30cc/ml or have a lactate > 4. Emergency patients by emergency doctors Resuscitation protocol started early - 6 hrs References: Rivers et al NEJM 2001;345;1368 -Randomized, double blinded, placebo-controlled study showed 16% mortality reduction in pt’s with severe sepsis and septic shock -done in the emergency department by emergency doctors De Oliveira et al. Intensive care med 2008;34:1065 -Validated EGDT in children in an RCT of 102 children -28 day mortality 12 vs 39%

Resuscitation in Sepsis: EGDT
The theory is to normalize… Preload - 1st Afterload - 2nd Contractility - 3rd Notes: …with the ultimate goal to improve O2 delivery

BACK TO OUR EQUATION MAP = CO x SVR (HR x Stroke volume) Afterload
Preload Contractility 103

Preload Dependent on intravascular volume
If depleted intravascular volume (due to increased endothelial permeability) - PRELOAD DECREASES Can use the CVP as measurement of preload Normal = 8-12 mm Hg Notes: -Central venous pressure - in the absence of elevated intra abdominal pressure - correlation between femoral vein pressure and CVP (Subclavian and Internal jugular) is good Bedside doppler US can be used as a noninvasive method to guide vasoactive therapy by calculating cardiac output and systemic vascular resistance from measurements of blood flow over the pulmonary artery or aorta -- Brierly et al Pediatrics 2008; 122:752 Hemodynamic measures -CVP and PAOP = static measures -radial artery pulse pressure, aortic blood flow peak velocity, brachial artery blood flow velocity = dynamic measures -increasing evidence that dynamic measures are more accurate (as long as patient is in sinus and passively ventilated)

Preload How do you correct decreased preload (or intravascular volume)
Give fluids Rivers showed an average of 5 L in first 6 hours What is the end point? Notes: Rivers et al gave 500 ml boluses of crystalloid every 30 minutes End point of fluid resuscitation -normal CVP/BP, pulmonary edema, or no more observed effect Careful with fluid therapy if there is clinical or radiographic evidence of heart failure Monitoring is important b/c patients can develop ARDS and ALI -once that happens a liberal approach to fluid resus can prolong duration of ventilation compared to a more restrictive approach using furosemide -therefore if your circulation is no longer fluid responsive - stop fluid resuscitation A recent trial has challenged the “treat with fluids” dogma - Maitland et al NEJM 2011;364;2483 -This is a pediatric, open, randomized controlled trial -3141 children with a severe febrile illness and impaired perfusion were randomized to receive a 5% albumin bolus, 0.9 saline solution bolus or no bolus at all. -surprisingly the study showed the 48 hr mortality to be 10.6%, 10.5%, 7.3% respectively -however there are a few weaknesses to this study: Pts with gastroenteritis and severe malnutrition were excluded - therefore the study results cannot be extrapolated to these patient populations 57% of patients had malaria, which is a different entity to sepsis. Also 32% had Hemoglobin levels < 5g/dl and 32% showed obvious clinical jaundice. The control group received blood products earlier than the other two groups. Considering that 57% of pts had malaria, and 32% had obvious clinical signs (jaundice) and 32% had severely low Hg levels, earlier blood products could have been what reduced mortality in the control group, rather than the fact that they did not get fluid boluses. The trial was not blinded, which could have potentially led to increased bias during patient selection/randomization, and breaches in study protocol.

Notes: Once you have corrected CVP/Preload, or not more response to fluids, move to afterload correction Afterload Preload Contractility 107

Afterload Afterload determines tissue perfusion
Using the MAP as a surrogate measure - Keep between mm Hg In sepsis afterload is decreased d/t loss of vessel tone Notes: Use this step when -CVP is normalized and still hypotensive -pulmonary edema/ALI/ARDS develops and gas exchange is compromised

Afterload How do you correct decreased afterload?
Use vasopressor agent Norepinephrine Alternative Dopamine or Phenylpehrine Notes: Phenylephrine (pure alpha agonist) is useful if patient is tachycardic or arrhythmias precludes use of other vasopressors If MAP was > 90mmHg - vasodilators were given

Contractility Shown to a be a surrogate for cardiac index
Use the central venous oxygen saturation (ScvO2) as a surrogate measure Shown to a be a surrogate for cardiac index Keep > 70% Notes: Mixed venous O2 saturation has been shown to a be a surrogate for the cardiac index Gattioni et al NEJM 1995;333:1025 Of all the targets this is the one that is studied the best - in Rivers trial Earlier studies of critically ill patients that used similar target of SvO2 > 70% found no mortality benefit - could be that is was not conducted in the first 6 hrs - -Gattioni et al NEJM 1995;333:1025 Systematic review of RCT’s that started therapy within 24 hrs (6 trials) -Jones et al Crit Care Med 2008;36:2734 -Resuscitation targeting physiologic endpoints improved mortality compare to standard resuscitation (39% vs 57%, odds ratio of 0.5, 95% CI ) Systematic review RCTs > 24hrs (3 trials) -no improvement with same measures (64% vs 58%, OR 1.16, 95% CI )

Contractility How to improve ScvO2 > 70%?
Optimize arterial O2 with non-rebreather Ensure a hematocrit > 30 (Transfuse to reach a hematocrit of > 30) Use Inotrope - Dobutamine 2.5ug/kg per minute and titrated (max 20ug/kg) Respiratory Support - Intubation (Don’t forget to sedate and paralyze) Notes: If intubate - PPV mmHg Another trial found that RBC transfusion not as good - Hebert et al NEJM 1999;340:409 -several explanations for conflicting data - EGDT gave blood within 6 hrs, others didn’t -may be an additive effect to the other interventions in EGDT If pt has myocardial dysfunction and ScvO2 remains < 70% after all the interventions above -may add inotropic therapy with dobutamine (do NOT aim for supra-normal levels of cardiac index) -at low doses dobutamine can decrease BP because it can dilate the systemic arteries -not at higher doses because the CO increased to compensate for it

The high risk pt: Systolic < 90 after bolus
EGDT Suspect infection Document source within 2hrs The high risk pt: Systolic < 90 after bolus Or Lactate > 4mmol/l Abx within 1 hr + source control <8mm hg Decrease 02 Consumption CVP Crystalloid > 8 –12 mm hg <65 or >90mmhg Vasoactive agent MAP INTUBATE Notes: This is a summay slide of Rivers protocol > 65 – 95mm hg <70% Scv02 Packed RBC to Hct >30% >70% <70% >70% Goals Achieved Inotropes NO

The high risk pt: systolic < 90 after bolus
EGDT Suspect infection Document source within 2hrs The high risk pt: systolic < 90 after bolus Or Lactate > 4mmol/l INTUBATE EARLY IF IMPENDING RESPIRATORY FAILURE Abx within 1 hr + source control <8mm hg Decrease 02 Consumption CVP Crystalloid > 8 –12 mm hg <65 or >90mmhg Vasopressor MAP INTUBATE Notes: If RR > 30 likely will develop respiratory collapse. Reports as high as 85% require mechanical ventilation during course > 65 – 95mm hg <70% Scv02 Packed RBC to Hct >30% >70% <70% >70% Goals Achieved Inotropes NO

The high risk pt: systolic < 90 after bolus
Suspect infection Document source within 2hrs MODIFIED The high risk pt: systolic < 90 after bolus INTUBATE EARLY IF IMPENDING RESPIRATORY FAILURE Abx within 1 hr And source control < 65 mmHg Decrease 02 Consumption MAP (Urine Output) More fluids >65 mmHg <65 mmHg Vasopressors MAP INTUBATE Notes: In most settings, unable to use obtain CVP or ScVO2 Can use Mean Arterial Pressure or urine output instead - the key is ongoing re-evaluations of the patient’s response to treatment Lactate clearance has been evaluated as a potential substitute for ScvO2 - Jones et al JAMA 2010;303:739 -RCT pts to resus targeting either lactate clearance >10% or an ScvO2 >70% -no difference in hospital mortality, LOS, ventilator free days, incidence of multi-organ failure >65mm hg < 10 % Lactate Clearance Packed RBC to Hct >30% > 10% < 10% > 10% Goals Achieved Inotropes NO

Case 4: Management Distributive Shock (SEPSIS) ABC’s
Monitors O2 IV fluids 20 cc/kg Intubate BW Treat Underlying Cause Acetaminophen Antibiotics - GIVE EARLY Source control - the 4 D’s = Drain, Debride, Device removal, Definitive Control Notes: Definitive control = amputate in gangrene A retrospective cohort study of 2124 patients demonstrated that time to initiation of appropriate antibiotic was strongest predictor of mortality - Kumar et al Crit Care Med 2006;34;1589.

Antibiotics Within 3-6hrs can reduce mortality - 30%
Early Antibiotics Within 3-6hrs can reduce mortality - 30% Within 1 hr for those severely sick Don’t wait for the cultures – treat empirically then change if need. Notes: Choice of antimicrobials will depend on age, cause, comorbidities, Gran stain data, local resistance patterns Remember enteric coverage - GI or GU coverage and Listeria monocytogenes and HSV in infants < 28 days For adults -vanco + 3rd cephalo or pip-tazo or carbapenem -vanco + ceftazidime or imipenem/meropenem or pip tazo or cipro or aminoglycoside if suspect pseudomonas For children > 28 days -vancomycin 15 mg/kg max 1-2 g (to cover for MRSA) -cefotaxime 100mg/kg max 2g or ceftriaxone -aminoglycoside for GU source -clindamycin or metronidazole for GI source -if immunosuppressed and at risk for pseudomonas - switch cephalosporins for Cefepime or ceftazidime For children < 28 days -add ampicillin 50 mg/kg and gentamicin 2.5 mg/ kg to vancomycin and cefotaxime -add acyclovir 20 mg/kg if suspect HSV

Other treatments for severe sepsis:
Glucocorticoids Glycemic Control Activated protein C Notes: There is no real good evidence for the first two - glucocorticoids (discussed in next slide) and glycemic control (evidence provided belwo). APC is expensive and likely has no role in most settings (evidence provided below). Glycemic control -Brunkhorst et al N Engl J Med 2008 Jan 10; 358:125 (VISEP trial) -randomized 537 patients with severe sepsis to intensive insulin therapy (mean blood glucose level, 112 mg/dL) or conventional therapy (mean blood glucose level, 151 mg/dL) -At 28 days, no significant differences were found in mortality between the two groups -The rate of severe hypoglycemia (blood glucose level, <40 mg/dL) was significantly higher in the intensive-therapy group (17% vs. 4%). Activated Protein C is rarely available and is incredibly expensive -if you want to discuss with the learner the role of APC, below is a summary -Protein C is an important player in the body’s response to inflammation, systemic sepsis and the concomitant intravascular coagulopathy. -Activated protein C in severe sepsis AND high risk of death improves outcome -the use of this agent must be balanced by the risk of increased bleeding. -No role in children (increased intracranial hemorrhage) - In 2005 a randomized, placebo-controlled trial of APC in pediatric patients with severe sepsis was discontinued due to significantly higher risk for central nervous system bleeding -The main effect of protein C is to reduce the production of thrombin, by inactivating factors Va and VIII. As we have seen, thrombin is proinflammatory, procoagulant and antifibrinolytic (16). In addition, protein C inhibits the influence of tissue factor on the clotting system, reduces the production of IL-1, IL-6, and TNF-α by monocytes, and has profibrinolytic properties by inactivating PAI-1 (it inactivates the inhibitor of the activator of the agent that converts plasminogen into plasmin) Bernard et al N Engl J Med 2001;344: (PROWESS Trial) -involving 1690 patients showed an absolute reduction in the relative risk of death from all causes at 28 days of 6.1 percent (from 30.8 percent to 24.7 percent, P=0.005) with an increase in serious bleeding (from 2.0 percent among those receiving placebo to 3.5 percent among those receiving activated protein C; P=0.006) -subgroup analysis showed that the benefit is for those with high risk of death Abraham et al N Engl J Med 2005 Sep 29; 353:1332 (ADDRESS trial) a randomized controlled trial looking at severe sepsis in patients at low risk of death (defined as APACHE II score >25 or multiorgan failure) The trial was stopped early as it showed that no improvement in this patient population with increased risk of bleeding (also risk of death was actually higher in patients with APC that had only one organ dysfunction) Systematic Review - Marti-Carvajal et al Cochrane Database Syst Rev 2007;CD004388 -concluded that APC should not be used for any children or for adults who are not severely ill 118

Couple of words about Steroids in sepsis…
New Guidelines for the management of sepsis and septic shock = Surviving Sepsis Campaign Grade 2C – consider steroids for septic shock in patients with BP that responds poorly to fluid resuscitation and vasopressors Critical Care Med 2008 Jan 36:296 Notes: -Dexamethasone does not interfere with ACTH stimulation testing References In Adults: Sprung CL et al - Hydrocortisone therapy for patient with septic shock (CORTICUS) - NEJM 2008 Jan :111 -No significant difference in 28 day mortality (34 vs 32%) -BP improved more quickly with hydrocortisone but there were more episodes of superimposed infections -No difference in cosyntropin responders and non-responders - disputing earlier results in Annan’s study JAMA 2002 References In children -1 RCT in dengue shock showed improved outcomes with hydrocortisone -1 retrospective cohort study showed mortality increased in septic shock -consensus - in those with catecholamie resistant shock who have or are suspected to have adrenal insufficiency should receive glucocorticoids -a total random serum cortisol level < 18ug/dL (496 nmol/L) defines absolute adrenal insufficiency and indicates the need for continued glucocorticoid therapy (preliminary evidence suggests that calculation of free cortisol and free cortisol index is more accurate - derived from total cortisol and cortisol binding globulin

Concluding Remarks Know how to distinguish different types of shock and treat accordingly Look for early signs of shock SHOCK = hypotension

Concluding Remarks Choose cost effective and high impact interventions
Do not need central lines and ScvO2 measurements to make an impact!!

Concluding Remarks ABC’s “5 to 15” Can’t intubate?
Give oxygen Develop algorithms for bag valve mask ventilation Treat fever to decrease respiratory rate Treat early with fluids - need lots of it!!

Concluding Remarks Monitor the patient
Do not need central venous pressure and ScvO2 Use the HR, MAP, mental status, urine output Lactate clearance? …to guide your early directed goal directed therapy

Concluding Remarks Start antibiotics within an hour!
Do not wait for cultures or blood work Notes: Remember that a retrospective cohort study of 2124 patients demonstrated that time to initiation of appropriate antibiotic was strongest predictor of mortality - Kumar et al Crit Care Med 2006;34;1589.

SHOCK Author: Nazanin Meshkat MD, FRCPC, MHSc, Assistant Professor, University of Toronto Date Created: September 2011 Instructions: 1. We recommend taking.

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SHOCK Author: Nazanin Meshkat MD, FRCPC, MHSc, Assistant Professor, University of Toronto Date Created: September 2011 Instructions: 1. We recommend taking.

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Presentation on theme: "SHOCK Author: Nazanin Meshkat MD, FRCPC, MHSc, Assistant Professor, University of Toronto Date Created: September 2011 Instructions: 1. We recommend taking."— Presentation transcript:

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