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:
1SHOCKAuthor: Nazanin Meshkat MD, FRCPC, MHSc, Assistant Professor, University of TorontoDate Created: September 2011Instructions:1. We recommend taking the learners through this module in two sittings - Part 1 and Part 22. 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
2Objectives: Part 1To develop an understanding of the definition and pathophysiology of shockTo develop an understanding and overview of the different types of shockTo develop a systematic approach to the detection and management of shock
3Objectives: Part 2To develop a deeper understanding of sepsis and septic shockTo discuss cost effective and high impact interventions to decrease mortality in shock
4PART 1Instructions: 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.
5Definition of Shock Inadequate perfusion and oxygenation of cells Notes: Another way to describe Shock is as an imbalance between O2 delivery and demand
6Definition of ShockInadequate perfusion and oxygenation of cells leads to:Cellular dysfunction and damageOrgan dysfunction and damageNotes: 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 theextracellular space, and inadequate regulation of intracellular pH.-Systemic effects include alterations in the serum pH, endothelial dysfunction, as well as further stimulation ofinflammatory and antiinflammatory cascades that lead to multiorgan dysfunction6
7Why should you care? High mortality - 20-90% Early on the effects of O2 deprivation on the cell are REVERSIBLEEarly intervention reduces mortalityNotes: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
8Pathophysiology 4 types of shock Cardiogenic Obstructive Hypovolemic DistributiveNotes: There are different classifications (some classify obstructive shock as a subset of cardiogenic shock)
9Pathophysiology: Overview Tissue perfusion is determined by Mean Arterial Pressure (MAP)MAP = CO x SVRNotes: 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 diastolicSVR is governed by the vessel length, blood viscosity, and vessel diameterCO = heart rate (HR) multiplied by Stroke Volume (SV)Heart rateStroke Volume
10Cardiogenic Shock: Pathophysiology Heart fails to pump blood outMAP = CO x SVRHR Stroke VolumeNotes: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
11Cardiogenic Shock: Pathophysiology NormalMAP = CO x SVRCardiogenicMAP = ↓CO x SVRMAP = ↓CO x ↑ SVR↓MAP = ↓↓CO x ↑ SVRNotes:-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.
12Cardiogenic Shock: Causes ↓MAP = ↓ CO (HR x Stroke Volume) x ↑SVRDecreased 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 slideNotes: 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
13Obstructive Shock: Pathophysiology Heart pumps well, but the output is decreased due to an obstruction (in or out of the heart)MAP = CO x SVRHR x Stroke volumeNotes: 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
14Obstructive Shock: Pathophysiology NormalMAP = CO x SVRObstructiveMAP = ↓CO x SVRMAP = ↓CO x ↑ SVR↓MAP = ↓↓CO x ↑ SVRNotes:-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.
15Obstructive Shock: Causes ↓MAP = ↓ CO (HR x Stroke Volume) x ↑SVRHeart is working but there is a block to the outflowMassive pulmonary embolismAortic dissectionCardiac tamponadeTension pneumothoraxObstruction of venous return to heartVena cava syndrome - eg. neoplasms, granulomatous diseaseSickle cell splenic sequestrationInstructions: Ask the learner what are some causes of Obstructive Shock. Answer is provided in the slide
16Hypovolemic Shock: Pathophysiology Heart pumps well, but not enough blood volume to pumpMAP = CO x SVRHR x Stroke volumeNotes:-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).
17Hypovolemic Shock: Pathophysiology NormalMAP = CO x SVRHypovolemicMAP = ↓CO x SVRMAP = ↓CO x ↑ SVR↓MAP = ↓↓CO x ↑ SVRNotes:-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.
18Hypovolemic Shock: Causes ↓MAP = ↓ CO (HR x Stroke Volume) x ↑SVRDecreased Intravascular volume (Preload) leads to Decreased Stroke VolumeHemorrhagic - trauma, GI bleed, AAA rupture, ectopic pregnancyHypovolemic - burns, GI losses, dehydration, third spacing (e.g. pancreatitis, bowel obstruction), Adesonian crisis, Diabetic KetoacidosisInstructions: Ask the learner what are some causes of Hypovolemic Shock. Answer is provided in the slide
19Distributive Shock: Pathophysiology Heart pumps well, but there is peripheral vasodilation due to loss of vessel toneMAP = CO x SVRHR x Stroke volumeNotes: Distributive (vasodilatory) shock is a consequence of severely decreased SVR.
20Distributive Shock: Pathophysiology NormalMAP = CO x SVRDistributiveMAP = co x ↓ SVRMAP = ↑co x ↓ SVR↓MAP = ↑co x ↓↓ SVRNotes: The cardiac output (with increases in both heart rate and stroke volume) is typically increased in an effort to compensate for the diminished SVR
21Distributive Shock: Causes ↓MAP = ↑CO (HR x SV) x ↓ SVRLoss of Vessel toneInflammatory cascadeSepsis and Toxic Shock SyndromeAnaphylaxisPost resuscitation syndrome following cardiac arrestDecreased sympathetic nervous system functionNeurogenic - C spine or upper thoracic cord injuriesToxinsDue to cellular poisons -Carbon monoxide, methemoglobinemia, cyanideDrug overdose (a1 antagonists)Instructions: Ask the learner what are some causes of Distributive Shock. Answer is provided in the slideNotes:In inflammatory cascade the SVR may initially increase to compensate for leaky vessels (third spacing), but eventually to the inflammatory cascade the SVR decreasesIn anaphylaxis the SVR may initially increase to compensate for leaky vessels (third spacing), but eventually to the inflammatory cascade the SVR decreasesNeurogenic shock occurs when injuries to the spine occur above T6 leading to a disruption in the sympathetic chain and therefore decrease vascular tone
22To Summarize Type of Shock Insult Physiologic Effect Compensation CardiogenicHeart fails to pump blood out↓COBaroRc↑SVRObstructiveHeart pumps well, but the outflow is obstructedHemorrhagicHeart pumps well, but not enough blood volume to pumpDistributiveHeart pumps well, but there is peripheral vasodilation↓SVR↑CO
23Ok…it’s really not THAT simple MAP = CO x SVRHR x Stroke volumePreload Afterload Contractility
24Heart fails to pump blood out ↓CO BaroRc ↑SVR ↑ Type of ShockInsultPhysiologic EffectCompensationHeart RateContractilityCardiogenicHeart fails to pump blood out↓COBaroRc↑SVR↑ObstructiveHeart pumps well, but the outflow is obstructedHemorrhagicHeart pumps well, but not enough blood volume to pumpDistributiveHeart pumps well, but there is peripheral vasodilation↓SVR↑CONo Change - in neurogenic shockNotes: The earlier table was oversimplified. Regardless of the type of SHOCK all components of the equation will compensate forthe physiologic change induced by the insult, however some will be more effective than others24
25Additional Compensatory Mechanisms Renin-Angiotensin-Aldosterone MechanismAII components lead to vasoconstrictionAldosterone leads to water conservationADH leads to water retention and thirstInflammatory cascade25
26Case 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 abdomenHe is agitated, and won’t lie flat on the stretcherHR 92, BP 126/72, SaO2 95%, RR 26Instructions: 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
27Stages of Shock Insult Preshock (Compensation) Shock (Compensation Timeline and progression will depend on:-Cause-Patient Characteristics-InterventionInsultPreshock(Compensation)Shock(CompensationOverwhelmed)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 hoursPreshock — Preshock is also referred to as warm shock or compensated shock. It is characterized by rapidcompensation for diminished tissue perfusion by various homeostatic mechanisms. As an example,compensatory mechanisms during preshock may allow an otherwise healthy adult to be asymptomaticdespite 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 organdysfunction 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 perturbationExamples include a 20 to 25% reduction in effective blood volume in hypovolemic shock, a fall in the cardiacindex to less than 2.5 L/min/M2 in cardiogenic shock, or activation of innumerable mediators of the systemicinflammatory response syndrome (SIRS) in distributive shock.During this stage, urine output may decline further (culminating inanuria and acute renal failure), acidemiadecreases 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 approachEnd organDamageDeath
28Case 1: Stages of Shock Stage Pathophysiology Clinical Findings Insult Splenic Rupture -- Blood LossAbdominal tenderness and girthInstructions: 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 Shock2. 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.
29Case 1: Stages of Shock Stage Pathophysiology Clinical Findings Insult Splenic Rupture -- Blood LossAbdominal tenderness and girthPreshockHemostatic compensationMAP =↓CO(↑HR x↓SV) x↑SVRDecreased CO is compensated by increase in HR and SVRMAP is maintainedHR will be increasedExtremities will be cool due to vasoconstrictionAnswer: 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
30Case 1: Stages of Shock Stage Pathophysiology Clinical Findings Insult Splenic Rupture -- Blood LossAbdominal tenderness and girthPreshockHemostatic compensationMAP =↓CO(HR x↓SV) x ↑ SVRDecreased CO is compensated by increase in HR and SVRMAP is maintainedHR will be increasedExtremities will be cool due to vasoconstrictionShockCompensatory mechanisms failMAP is reducedTachycardia, dyspnea, restlessness
31Case 1: Stages of Shock Stage Pathophysiology Clinical Findings Insult Splenic Rupture -- Blood LossAbdominal tenderness and girthPreshockHemostatic compensationMAP =↓CO(HR x↓SV) x ↑ SVRDecreased CO is compensated by increase in HR and SVRMAP is maintainedHR will be increasedExtremities will be cool due to vasoconstrictionShockCompensatory mechanisms failMAP is reducedTachycardia, dyspnea, restlessnessEnd organ dysfunctionCell death and organ failureDecreased renal functionLiver failureDisseminated Intravascular CoagulopathyDeath
32Is this Shock? Signs and symptoms Laboratory findings Hemodynamic measuresNotes: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. Whichunderscores 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
33Symptoms and Signs of Shock Level of consciousnessInitially may show few symptomsContinuum starts withAnxietyAgitationConfusion and DeliriumObtundation and ComaIn infantsPoor toneUnfocused gazeWeak cryLethargy/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.
34Symptoms and Signs of Shock PulseTachycardia HR > What are a few exceptions?Rapid, weak, thready distal pulsesRespirationsTachypneaShallow, irregular, laboredNotes: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 shockTachypnea 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)
35Symptoms and Signs of Shock Blood PressureMay be normal!Definition of hypotensionSystolic < 90 mmHgMAP < 65 mmHg40 mmHg drop systolic BP from from baselineChildrenSystolic BP < 1 month = < 60 mmHgSystolic BP 1 month - 10 years = < 70 mmHg + (2 x age in years)In children hypotension develops late, late, lateA pre-terminal eventNotes: In a patient who is hypertensive at baseline, 40 mmHg drop in systolic BP is technically hypotension = relative hypotension
36Symptoms and Signs of Shock SkinCold, clammy (Cardiogenic, Obstructive, Hemorrhagic)Warm (Distributive shock)Mottled appearance in childrenLook for petechiaDry Mucous membranesLow urine output <0.5 ml/kg/hrNotes:-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.
37(Normal in Neurogenic shock) May be increased or decreased HypovolemicShockDistributive ShockCardiogenicObstructiveHRIncreased(Normal in Neurogenic shock)May be increased or decreasedJVPLowHighBPSKINColdWarm (Cold in severe shock)CAPREFILLSlowNotes: This is a summary slide
38Empiric Criteria for Shock 4 out of 6 criteria have to be metIll appearance or altered mental statusHeart rate >100Respiratory rate > 22 (or PaCO2 < 32 mmHg)Urine output < 0.5 ml/kg/hrArterial hypotension > 20 minutes durationLactate > 4Notes: to standardize the diagnosis of shock, 4 of these 6 criteria have to be met to define shock
39Lactate Lactate is increased in Shock Predictor of Mortality Can be used as a guide to resuscitationHowever it is not necessary, or available in many settingsNotes:Lactate is increased due to:-Decreased O2 --> aerobic metabolism switches over to anaerobic --> byproduct = lactate-Decreased hepatic clearanceMetabolic 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
40Management of Shock History Physical exam Labs Other investigations Treat the Shock - Start treatment as soon as you suspect Pre-shock or ShockMonitor
41Historical Features Trauma? Pregnant? Acute abdominal pain? Vomiting or Diarrhea?Hematochezia or hematemesis?Fever? Focus of infection?Chest pain?
42Physical ExamVitals - HR, BP, Temperature, Respiratory rate, Oxygen SaturationCapillary blood sugarWeight in children
43Physical ExamIn a patient with normal level of consciousness - Physical exam can be directed to the history
44Physical Exam In a patient with abnormal level of consciousness Primary surveyCardiovascular (murmers, JVP, muffled heart sounds)Respiratory exam (crackles, wheezes),Abdominal examRectal and vaginal examSkin and mucous membranesNeurologic examination
45Laboratory Tests CBC, Electrolytes, Creatinine/BUN, glucose +/- Lactate+/- Capillary blood sugar+/- Cardiac EnzymesBlood Cultures - from two different sitesBeta HCG+/- Cross Match
46Other investigationsECGUrinalysisCXR+/- Echo+/- FAST
48Stages of Shock Insult Preshock (Compensation) Shock (Compensation Early Intervention can arrest orreduce the damageInsultPreshock(Compensation)Shock(CompensationOverwhelmed)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;1365End organDamageDeath
49Treatment ABC’s “5 to 15” Treat underlying cause Airway Breathing CirculationPut the patient on a monitor if availableTreat underlying causeNotes: i.e. ABC’s should be done within 5-15 minutes
51Treatment: Airway and Breathing Consider IntubationIs the cause quickly reversible?Generally no need for intubation3 reasons to intubate in the setting of shockInability to oxygenateInability to maintain airwayWork of breathingNotes:Quickly reversible causes - examples = reverse tachyarrhythmia with meds, anaphylaxis than responds quickly to epinephrineInability to oxygenate - examples = cardiogenic shock leading to pulmonary edema, ARDSInability to maintain airway - examples = upper airway obstruction due to anaphylaxis or traumaWork 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, intubateChoose 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
52Treatment: Circulation Treat the early signs of shock (Cold, clammy? Decreased capillary refill? Tachycardic? Agitated?)DO NOT WAIT for hypotension
53Treatment: Circulation Start IV +/- Central line (or Intraosseous)Do Blood Work +/- Blood Cultures
54Treatment: Circulation Fluids - 20 ml/kg bolus x 3Normal salineRinger’s lactateNotes:-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 LactateNotes: 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 increased90 d mortality with pentastarch (stopped early) - Brunkhorst et al NEJM 2008;358:125
55Back 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 abdomenHe is agitated, and won’t lie flat on the stretcherHR 92, BP 126/72, SaO2 95%, RR 26
56Case 1 On examination Extremely agitated Clammy and cold Heart exam - normalChest exam - good air entryAbdomen - bruised, tender, distendedNo other signs of traumaNotes: We have established that the patient is in Hemorrhagic Shock.Instructions: Ask the learner how they would manage the patientAnswer: is provided in following slides
57Case 1: Management Hemorrhagic (Hypovolemic Shock) ABC’s MonitorsO2Intubate?IV lines x 2, Fluid boluses, Call for Blood - O typeBlood work including cross matchTreat Underlying Cause
58Case 1: Management Hemorrhagic (Hypovolemic Shock) ABC’s MonitorsO2Intubate?IV lines x 2, Fluid boluses, Call for Blood - O typeBlood work including cross matchTreat Underlying CauseGive BloodCall the surgeon statIf the patient does not respond to initial boluses and blood products - take to the Operating Room
59Blood Products Use blood products if no improvement to fluids PRBC 5-10 ml/kgO- in child-bearing years and O+ in everyone else+/- Platelets
60Case 2 23 year old woman in Addis Ababa Has been fatigued and short of breath for a few daysShe fainted and family brought her inThey tell you she has a heart problem
61Case 2HR 132, BP 76/36, SaO2 88%, RR 30, Temp 36.3Appearance - obtundedCardiovascular exam - S1, S2, irregular, holosytolic murmer, JVP is 5 cm ASA, no edemaChest - bilateral crackles, accessory muscle useAbdomen - unremarkableRest of exam is normalInstructions: 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 statusHR >100RR > 22 or PaCO2 < 32 mmHgUO < 0.5 ml/kg/hrArterial hypotension > 20 mins durationLactate > 4Instructions: Ask the learner what type of shock is this?Answer: CardiogenicInstructions: 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
62Stages of Shock Insult Preshock (Compensation) Shock (Compensation What stage is she at?InsultPreshock(Compensation)Shock(CompensationOverwhelmed)Answer to “What stage is she at?”= Shock/end organ damage as the compensation is overwhelmedInstructions: How do you want to manage it?Answer: provided in next slidesEnd organDamageDeath
63Case 2: Management Cardiogenic Shock ABC’s Treat Underlying Cause MonitorsO2IV and blood workECG - Atrial Fibrillation, rate 130’sTreat Underlying Cause
64Case 2: Management Cardiogenic Shock ABC’s Treat Underlying Cause MonitorsO2IV and blood workIntubate?ECG - Atrial Fibrillation, rate 130’sTreat Underlying CauseInstructions: Ask the learner if they would intubateAnswer is provided in next 3 slides
65Case 2: Why would you intubate? Is the cause quickly reversible?3 reasons to intubate in the setting of shockInability to oxygenateInability to maintain airwayWork of breathingUNLIKELYInability to oxygenate(Pulmonary edema,SaO2 88%)Instructions: Take the learner through these questions from earlierAnswers 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 breathingAccessoryMuscle Use
66Case 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 intubateAlternative to intubate to provide PEEP would be Bi PAP
67Case 2: Management Cardiogenic Shock ABC’s Treat Underlying Cause MonitorsO2IV and blood workIntubate?ECG - Atrial Fibrillation, rate 130’sTreat Underlying CauseInstructions: How would the learner manage the patient?Answer is provided in the next slide
68Case 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 inotropesFelker 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)
69Vasopressors in Cardiogenic Shock NorepinephrineDopamineEpinephrinePhenylephrineNotes: 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 HRDe 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
70Case 3 36 year old woman Pedestrian hit by a car She is brought into the hospital 2 hrs after accidentShort of breathHas been complaining of chest pain
71Case 3HR 126, SBP 82, SaO2 70%, RR 36, Temp 35Obtunded, Accessory muscle useTrachea is deviated to LeftHeart - distant heart soundsChest - decreased air entry on the right, broken ribs, subcutaneous emphysemaAbdominal exam - normalApart from bruises and scrapes no other signs of traumaInstructions: Ask the learner Is she in shock? Why?Answer: Meets 4 of 6 criteria:Ill appearance or altered mental statusHR >100RR > 22 or PaCO2 < 32 mmHgUO < 0.5 ml/kg/hrArterial hypotension >20 mins durationLactate > 4Instructions: Ask the learner What type of shock is this?Answer: Obstructive, though hemorrhagic is a definite possibilityInstructions: Ask the learner What do you think is the underlying cause?Answer: Tension Pneumothorax
72Stages of Shock Insult Preshock (Compensation) Shock (Compensation What stage is she at?InsultPreshock(Compensation)Shock(CompensationOverwhelmed)Instructions: Ask the learner What stage of shock is the pt in?Answer: Shock/end organ damage - compensation is overwhelmedInstructions: Ask the learner How do you want to manage this patient?Answer is provided in the next slideEnd organDamageDeath
73Case 3: Management Obstructive Shock ABC’s Treat Underlying Cause MonitorsO2IVIntubate?BWTreat Underlying CauseInstructions: Ask the learner if they would intubate this patient.Answer is provided in the next slide
74Case 3: Management Obstructive Shock ABC’s Treat Underlying Cause MonitorsO2IVIntubate?BWTreat Underlying CauseNeedle thoracentesisChest tubeCXRAnswer: Don’t intubate this patient! If you do, can worsen the patients condition by worsening the tension pneumothorax
75Case 3: Management Obstructive Shock ABC’s Treat Underlying Cause MonitorsO2IVIntubate?BWTreat Underlying CauseNeedle thoracentesisChest tubeCXRNotes: Instead intervene with Needle thoracentesis as soon as the tension pneumothorax is identified.
76Case 3: Management Obstructive Shock ABC’s Treat Underlying Cause MonitorsO2IVIntubate?BWTreat Underlying CauseNeedle thoracentesisChest tubeCXRIntubate if no response
77Case 3 You perform a needle thoracentesis - hear a hissing sound Chest tube is inserted successfullyHR 96, BP 100/76, SaO2 96% on O2, RR 26You resume your clinical duties, and call the surgeon
78Case 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 bedsideAnswer is provided in the next slide.
79Case 3 You are back at the bedside The patient is obtunded again Pale and ClammyHR 130, BP 86/52, SaO2 96% on O2Chest tube seems to be workingTrachea is midlineHeart - NormalChest - Good air entryAbdomen - decreased bowel sounds, distendedInstructions: Ask the learner What’s going on?Answer: Hemorrhagic shockNotes: This case raises two issues - the importance of combined shock (ie different types of shock can coexist) and monitoring/re-evaluating
80Combined 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 decreasedoral intake, insensible losses, vomiting, or diarrhea.
81Monitoring 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 patientNotes: These are indirect measures
82Can we measure cell hypoxia? Lactate - we already talked about - a surrogateVenous Oxygen Saturation - more direct measure
83Venous Oxygen Saturation Hg carries O2A percentage of O2 is extracted by the tissue for cellular respirationUsually the cells extract < 30% of the O2
84Venous Oxygen Saturation Svo2 = Mixed venous oxygen saturationMeasured from pulmonary artery by Swan-Ganz catheter.Normal > 65%Scvo2 = Central venous oxygen saturationMeasured through central venous cannulation of SVC or R Atrium - i.e. Central LineNormal > 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
86Case 440 year old maleRUQ abdominal pain, fever, fatigued for 5-6 daysNo past medical history
87Case 4 HR 110, BP 100/72, SaO2 96%, T 39.2, RR 26 Drowsy Warm skin Heart - S1, S2, no MurmersChest - good A/E x 2Abdomen - decreased bowel sound, tender RUQInstructions: 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 statusHR >100RR > 22 or PaCO2 < 32 mmHgUO < 0.5 ml/kg/hrArterial hypotension >20 mins durationLactate > 4Instructions: What kind of shock is this?Answer: SEPTIC
88Stages of Shock Insult Preshock (Compensation) Shock (Compensation What stage is he at?InsultPreshock(Compensation)Shock(CompensationOverwhelmed)Instructions: What stage of shock is thisAnswer: PreshockEnd organDamageDeath
89Stages of Sepsis SIRS SEPSIS SEVERE SEPSIS SEPTIC SHOCK MODS/DEATH Notes: Septic shock follows several stages as well - These stages parallel the stages of shockIn 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 shockEarly sepsis is characterized by hyperdynamic physiology - decreased SVR, elevated CO, widened pulse pressure, warm and dry extremitiesSEPTICSHOCKMODS/DEATH
90Definitions of SepsisSystemic 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 bandsNotes:In children - developed by consensus panel-Core T (central probe) > 38.5 or < 36-Tachycardia > 2 standard deviation above for normal for age ORin 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 neutrophilsOther criteria -Serum Glucose >12 and Lactate >4
91Definitions of SepsisSepsis – SIRS with proven or suspected microbial sourceSevere 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
92Definitions of Sepsis Septic shock = Sepsis + Refractory hypotension -Unresponsive to initial fluids 20-40cc/kg – Vasopressor dependantMODS – multiple organ dysfunction syndrome-2 or more organsNotes: In terminal stage of septic shock - hypotension, increased systemic vascular resistance and decreased cardiac output
93Stages 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 progressionSEPTICSHOCK70%MODS/DEATH
95Pathophysiology Inflammatory Cascade: Humoral, cellular and Neuroendocrine (TNF, IL etc)Endothelial reactionEndothelial permeability = leaking vesselsCoagulation and complement systemsMicrovascular flow impairment
96PathophysiologyEnd result = Global Cellular Hypoxia
97Focus of Infection Any focus of infection can cause sepsis GastrointestinalGUOralSkinNotes:-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
98Risk Factors for Sepsis InfantsImmunocompromised patientsDiabetesSteroidsHIVChemotherapy/malignancyMalnutritionSickle cell diseaseDisrupted barriersFoley, burns, central lines, proceduresNotes: In Sickle cell disease - encapsulated organisms
99Back to Case 4 HR 110, BP 100/72, SaO2 96%, T 39.2, RR 20 Drowsy Warm skinHeart - S1, S2, no MurmersChest - good A/E x 2Abdomen - decreased bowel sound, tender RUQInstructions: Ask the learner How do you want to manage this patient?Answer: ABC’s - see next slide
100Case 4: Management Distributive Shock (SEPSIS) ABC’s MonitorsO2IV fluids 20 cc/kg x 3Intubate?BWTreat Underlying CauseNotes: A landmark trial provides guidance on how to resuscitate septic patients. See next slide.
101Resuscitation in Sepsis Early goal directed therapy - Rivers et al NEJM 2001Used 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 doctorsResuscitation protocol started early - 6 hrsReferences: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 doctorsDe 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%
102Resuscitation in Sepsis: EGDT The theory is to normalize…Preload - 1stAfterload - 2ndContractility - 3rdNotes: …with the ultimate goal to improve O2 delivery
103BACK TO OUR EQUATION MAP = CO x SVR (HR x Stroke volume) Afterload PreloadContractility103
104BACK TO OUR EQUATION MAP = CO x SVR (HR x Stroke volume) Afterload PreloadContractility104
105Preload Dependent on intravascular volume If depleted intravascular volume (due to increased endothelial permeability) - PRELOAD DECREASESCan use the CVP as measurement of preloadNormal = 8-12 mm HgNotes:-Central venous pressure - in the absence of elevated intra abdominal pressure - correlationbetween femoral vein pressure and CVP (Subclavian and Internal jugular) is goodBedside doppler US can be used as a noninvasive method to guide vasoactive therapy bycalculating cardiac output and systemic vascular resistance from measurements of bloodflow over the pulmonary artery or aorta -- Brierly et al Pediatrics 2008; 122:752Hemodynamic 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)
106Preload How do you correct decreased preload (or intravascular volume) Give fluidsRivers showed an average of 5 L in first 6 hoursWhat is the end point?Notes:Rivers et al gave 500 ml boluses of crystalloid every 30 minutesEnd point of fluid resuscitation -normal CVP/BP, pulmonary edema, or no more observed effectCareful with fluid therapy if there is clinical or radiographic evidence of heart failureMonitoring 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 resuscitationA 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 populations57% 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.
107BACK TO OUR EQUATION MAP = CO x SVR (HR x Stroke volume) Afterload Notes: Once you have corrected CVP/Preload, or not more response to fluids, move to afterload correctionAfterloadPreloadContractility107
108Afterload Afterload determines tissue perfusion Using the MAP as a surrogate measure - Keep between mm HgIn sepsis afterload is decreased d/t loss of vessel toneNotes: Use this step when-CVP is normalized and still hypotensive-pulmonary edema/ALI/ARDS develops and gas exchange is compromised
109Afterload How do you correct decreased afterload? Use vasopressor agentNorepinephrineAlternative Dopamine or PhenylpehrineNotes:Phenylephrine (pure alpha agonist) is useful if patient is tachycardic or arrhythmias precludes use of other vasopressorsIf MAP was > 90mmHg - vasodilators were given
110BACK TO OUR EQUATION MAP = CO x SVR (HR x Stroke volume) Afterload PreloadContractility110
111Contractility Shown to a be a surrogate for cardiac index Use the central venous oxygen saturation (ScvO2) as a surrogate measureShown to a be a surrogate for cardiac indexKeep > 70%Notes:Mixed venous O2 saturation has been shown to a be a surrogate for the cardiac indexGattioni et al NEJM 1995;333:1025Of all the targets this is the one that is studied the best - in Rivers trialEarlier 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;333:1025Systematic 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 )
112Contractility How to improve ScvO2 > 70%? Optimize arterial O2 with non-rebreatherEnsure 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 mmHgAnother 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 EGDTIf 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
113The high risk pt: Systolic < 90 after bolus EGDTSuspect infectionDocument source within 2hrsThe high risk pt: Systolic < 90 after bolusOrLactate > 4mmol/lAbx within 1 hr+ source control<8mm hgDecrease 02ConsumptionCVPCrystalloid> 8 –12 mm hg<65 or >90mmhgVasoactiveagentMAPINTUBATENotes: This is a summay slide of Rivers protocol> 65 – 95mm hg<70%Scv02Packed RBCto Hct >30%>70%<70%>70%Goals AchievedInotropesNO
114The high risk pt: systolic < 90 after bolus EGDTSuspect infectionDocument source within 2hrsThe high risk pt: systolic < 90 after bolusOrLactate > 4mmol/lINTUBATE EARLYIF IMPENDINGRESPIRATORYFAILUREAbx within 1 hr+ source control<8mm hgDecrease 02ConsumptionCVPCrystalloid> 8 –12 mm hg<65 or >90mmhgVasopressorMAPINTUBATENotes: If RR > 30 likely will develop respiratory collapse. Reports as high as 85% require mechanical ventilation during course> 65 – 95mm hg<70%Scv02Packed RBCto Hct >30%>70%<70%>70%Goals AchievedInotropesNO
115The high risk pt: systolic < 90 after bolus Suspect infectionDocument source within 2hrsMODIFIEDThe high risk pt: systolic < 90 after bolusINTUBATE EARLYIF IMPENDINGRESPIRATORYFAILUREAbx within 1 hrAnd source control< 65 mmHgDecrease 02ConsumptionMAP (UrineOutput)More fluids>65 mmHg<65 mmHgVasopressorsMAPINTUBATENotes:In most settings, unable to use obtain CVP or ScVO2Can use Mean Arterial Pressure or urine output instead - the key is ongoing re-evaluations of the patient’s response to treatmentLactate 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 %LactateClearancePacked RBCto Hct >30%> 10%< 10%> 10%Goals AchievedInotropesNO
116Case 4: Management Distributive Shock (SEPSIS) ABC’s MonitorsO2IV fluids 20 cc/kgIntubateBWTreat Underlying CauseAcetaminophenAntibiotics - GIVE EARLYSource control - the 4 D’s = Drain, Debride, Device removal, Definitive ControlNotes:Definitive control = amputate in gangreneA 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.
117Antibiotics Within 3-6hrs can reduce mortality - 30% Early AntibioticsWithin 3-6hrs can reduce mortality - 30%Within 1 hr for those severely sickDon’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 patternsRemember enteric coverage - GI or GU coverage and Listeria monocytogenes and HSV in infants < 28 daysFor adults-vanco + 3rd cephalo or pip-tazo or carbapenem-vanco + ceftazidime or imipenem/meropenem or pip tazo or cipro or aminoglycoside if suspect pseudomonasFor 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 ceftazidimeFor 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
118Other treatments for severe sepsis: GlucocorticoidsGlycemic ControlActivated protein CNotes: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 deathAbraham 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 ill118
119Couple of words about Steroids in sepsis… New Guidelines for the management of sepsis and septic shock = Surviving Sepsis CampaignGrade 2C – consider steroids for septic shock in patients with BP that responds poorly to fluid resuscitation and vasopressorsCritical Care Med 2008 Jan 36:296Notes:-Dexamethasone does not interfere with ACTH stimulation testingReferences 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 2002References 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
120Concluding RemarksKnow how to distinguish different types of shock and treat accordinglyLook for early signs of shockSHOCK = hypotension
121Concluding Remarks Choose cost effective and high impact interventions Do not need central lines and ScvO2 measurements to make an impact!!
122Concluding Remarks ABC’s “5 to 15” Can’t intubate? Give oxygenDevelop algorithms for bag valve mask ventilationTreat fever to decrease respiratory rateTreat early with fluids - need lots of it!!
123Concluding Remarks Monitor the patient Do not need central venous pressure and ScvO2Use the HR, MAP, mental status, urine outputLactate clearance?…to guide your early directed goal directed therapy
124Concluding Remarks Start antibiotics within an hour! Do not wait for cultures or blood workNotes: 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.