MANAGEMENT OF SEPTIC SHOCK UP DATE

Intended Learning outcomes

Definitions. Hents on the pathophysiology. Understending the priorities in managenet. Understandings the basic pharmacological actions of inotropic and vasopressors. Learning and applying the two main bundles of sepsis management.

systemic inflammatory response syndrome?

1- Abnormal temperature 2-Abnormal leukocyte count 3-Tachycardia OR bradycardia(for children "<1 yr old). 4-Mean respiratory rate>2 SD above normal for age. 5- Any two of them including 1 and 2

Age specific vital signs and laboratory values (SIRS )

Age group

Age group
0-1w >180 >180 >180 >140 >130 >110

Tachycardia Bradycardia Respiratory b/min rate (breaths/mi n) <100 <100 <90 NA NA NA >50 >40 >34 >22 >18 >14

Leukocyte SBP count x1000/cu m >34 >19.5or <5 >17.5or <5 >15.5or <6 >13.5or <4,5 >11or <4,5 <65 <75 <100 <94 <105 <117

1w-1mo 1mo-1yr 2-5yr 6-12yrs

13 -< 18yr

Infection?
A suspected positive findings on clinical exam, chest radiograph consistent with pneumonia, petechial or purpuric rash, or purpura fulminans) proven (by positive culture, tissue stain, or polymerase chain reaction test). infection caused by any pathogen OR a clinical syndrome associated with a high probability of infection, perforated viscus.

Sepsis
SIRS in the presence of or as a result of suspected or proven infection.

Severe sepsis?
sepsis-induced tissue hypoperfusion or organ dysfunction

Organ dysfunction criteria

Cardiovascular Dysfunction:
Decrease in BP (hypotension) <5th percentile for age or OR Need for vasoactive drug to maintain BP in normal range
(dopamine>5 mcg/kg/min or dobutamine, epinephrine, or norepinephrine at any dose)

OR Two of the following Unexplained metabolic acidosis: base deficit>5.0 mEq/L Increased arterial lactate>2 times upper limit of normal Oliguria: urine output <0.5 mL/kg/hr Prolonged capillary refill >5 secs Core to peripheral temperature gap>3C

Organ dysfunction criteria

Respiratory Dysfunction
PaO2/FIO2 <300 in absence of cyanotic heart disease or preexisting lung disease OR PaCO2>65 torr or 20 mm Hg over baseline PaCO2 OR Proven need to >50% FIO2 to maintain saturation>92% OR Need for nonelective invasive or noninvasive mechanical ventilation
acute respiratory distress syndrome must include a PaO2/FIO2 ratio <200 mm Hg, bilateral infiltrates, acute onset, and no evidence of left heart failure . Acute lung injury is defined identically except the PaO2/FIO2 ratio must be <300 mm Hg; c proven need assumes oxygen requirement was tested by decreasing flow with subsequent increase in flow if required

Organ dysfunction criteria

Neurologic
Glasgow Coma Score <11 OR Acute change in mental status with a decrease in Glasgow Coma Score>3 points from abnormal baseline
Hematologic

Platelet count _80,000/mm3 or a decline of 50% in platelet count from highest value recorded over the past 3 days (for chronichematology/oncology patients) OR International normalized ratio>2

Organ dysfunction criteria

Renal
Serum creatinine>2 times upper limit of normal for age or 2-fold increase in baseline creatinine

Hepatic
Total bilirubin>4 mg/dL (not applicable for newborn) OR ALT 2 times upper limit of normal for age

Septic shock
Septic shock Sepsis and cardiovascular organ dysfunction

Rapid cardiopulmonary assessment and clinical examination of a patient in shock

Mental status : Restless, agitated, anxious, progressive lethargy Skin : Temperature, colour, turgor, peticheal rash may be present in meningococcemia or disseminated intravascular coagulation

Cardiovascular :
By far, the most significant physical findings in septic shock results from autonomic responses to stress. In children tachycardia occurs early. The younger the child, cardiac output is more dependent on heart rate rather than on increase in stroke volume. Alteration in blood pressure is a late manifestation of hypovolemia in children. Diastolic blood pressure begins to fall early as vascular tone begins to decrease. Systolic Blood pressure is well maintained initially and only begins to fall once hemodynamic compromise is severe. Decreasing blood pressure signifies decompensted stage of shock. In warm phase of septic shock capillary refill time may be normal, however signs of hyperdynamic circulation, widened pulse pressure, hyperdynamic apex beat are important signs. Capillary refill time of more than 5 seconds is always abnormal.

Respiratory:
Respiratory rate is increased to compensate for metabolic acidosis, secondly if ARDS is developing, progressive worsening of respiratory distress may occur.

Urine output
Oliguria is common leading to anuria.

Rapid assessment of a patient in shock

Mental state Skin and Renal Cardiovascular

Respiratory

Aim of Emergency management

One goal of shock treatment is to maintain perfusion pressure above the critical point below which blood flow cannot be effectively maintained in individual organs.
Management of child with septic shock is best started by aggressive goal directed management in the emergency department. The ultimate goals are to prevent or reverse the defects in cellular substrate delivery and metabolism and to support entire patient until homoeostasis is restored. For all forms of shock, treating the underlying cause is mandatory. Speed is essential. Delays in making the diagnosis and initiating treatment ( fluid resuscitation as well as appropriate antibiotics), as well as suboptimal resuscitation, contribute to the developments of peripheral vascular failure and irreversible defects in oxygen use which can culminate in vital organ dysfunction.

GRADE of evidence
Grades of Recommendation, Assessment, Developmentand Evaluation (GRADE) system to
guide assessment of quality of evidence fromhigh (A) to very low (D) and to determine the strength of recommendations. A strong recommendation (1) indicates that an interventions desirable effects clearly outweigh its undesirable effects (risk, burden, cost) or clearly do not. Weak recommendations (2) indicate that the tradeoff between desirable and undesirable effects is less clear.

Inotropic And Vasoactive Agents

Sepsis induced myocardial depression and Autonomic dysfunction (or paralysis) are the main defects documented with septic shock pathology. Before cardiac output and perfusion pressure are restored with drugs, electrolyte abnormalities (such as ionized hypocalcemia) that might impair cardiac performances should be corrected. Metabolic acidosis secondary to tissue hypoxia should be managed by treating the cause. Sodium bicarbonate should be given only for severe acidosis that fails to respond to adequate resuscitation. If signs of shock persist despite adequate volume replacement and perfusion of vital organs is jeopardized, Inotropic drugs may be used to improve cardiac output. The effects of particular drug in an individual patient are unpredictable and must be closely monitored.

Dopamine :
It has alpha, beta and dopaminergic (delta) actions that are dose dependant. At low doses (<3 mcg/kg/min) it primarily causes weak renal and splanchnic vasodilatation, and at 3mcg to 10mcg/kg/min it exerts a positive myocardial inotropic efect. At higher doses (> 10 mcg/kg/min), it has strong vasoconstricting alpha effect, in addition to positive inotropic effect. So called 'Renal dose' of dopamine (2-5 mcg/kg/min) for renal vasolidation has been over emphasized and is of less practical significance in clinical setting. The primary indication for dopamine is the need to increase myocardial contractility after preload restoration. Usual dose is 5-20 mcg/kg/min titrated to desired effect. Dopamine(in doses>5 mcg/kg/min) should preferably, be given via central line to prevent ischemic necrosis of the skin.

Dobutamine
It is selective beta 1 agonist. It causes an increase in cardiac contractility and reduces peripheral resistance. The reduction in afterload and improved myocardial performance lowers ventricular filling pressures. Usual dose is 5mcg to 20mcg/kg/min. it should not be used alone in septic shock due to risk of further drop in blood pressure. Dopamine or adrenaline can be used to prevent hypotension due to vasoconstrictive effect.

Adrenaline(Epinephrine):
It is an alpha and beta adrenergic agonist. It is used in situations where dominant hemodynamic feature is peripheral vascular failure. At higher doses severe vasoconstriction can lead to lactic acidosis and renal and splanchnic ischemia. The usual dose is 0.1 mcg/kg/min to 1 mcg/kg/min. It should be titrated closely and minimum dose should be used for required

Noradrenaline (Norepinephrine):
An alpha and beta agonist (alpha> beta effect).Cardiac contractility is increased but it also causes massive increase in myocardial oxygen consumption and afterload, so cardiac output may not actually increase. Usual dose is 0.05 -1 mcg/ kg/ min. In severe septic shock with hypotension despite use of adrenaline secondary to intense vasodilatation, noradrenaline may be useful in increasing peripheral vascular resistance to improve blood pressure. Vasopressin In severe warm shock with hypotension resistant to noradrenaline,vasopressin may be tried.

Vasopressin
In severe warm shock with hypotension resistant to noradrenaline, vasopressin may be tried.

Afterload reduction
Caution should be used in using afterload reduction indiscriminately in septic shock without simultaneous inotropic support. Both nitroprusside and nitroglycerin lower systemic vascular resistence in children and are useful afterload reducing agents. These agents act via generation of nitric oxide. Nitroprusside has potent peripheral arterial vasodilating effects. Nitroglycerin is more potent venodilator and pulmonary vasodilator. Close monitoring and volume augmentation are frequently required when vasodilators are used to decrease pulmonary vascular resistance. Amrinone and milrinone are newer inotropic agents with properties of afterload reduction and myocardial diastolic relaxatione(10=12). Milrinone is commonly used for cardiogenic shock which is frequently associated with septic shock..

Initial resuscitation bundle (first 6 hrs) (EGDT)

Begin resuscitation immediately in patients with hypotension or elevated serum lactate 4mmol/L; do not delay pending ICU admission. (1C) Resuscitation goals: (1C) Central venous pressure (CVP) 812 mm Hg* Mean arterial pressure 65 mm Hg Urine output 0.5 mL.kg-1.hr-1 Central venous (superior vena cava) oxygen saturation 70%, or mixed venous 65% If venous O2 saturation target not achieved: (2C) consider further fluid transfuse packed red blood cells if required to hematocrit of 30% and/or dobutamine infusion max 20 g.kg-1.min-1

Fluid therapy
Fluid-resuscitate using crystalloids or colloids (1B) Target a CVP of 8 mm Hg (12 mm Hg if mechanically ventilated) (1C) Use a fluid challenge technique while associated with a hemodynamic improvement (1D) Give fluid challenges of 1000 mL of crystalloids or 300 500 mL of colloids over 30 mins. Morerapid and larger volumes may be required in sepsisinduced tissue hypoperfusion (1D) Rate of fluid administration should be reduced if cardiac filling pressures increase without concurrent hemodynamic improvement (1D)

Diagnosis
Obtain appropriate cultures before starting antibiotics provided this does not significantly delay antimicrobial administration.(1C) Obtain two or more blood cultures (BCs) One or more BCs should be percutaneous One BC from each vascular access device in place >48 hours Culture other sites as clinically indicated Perform imaging studies promptly in order to confirm and sample any source of infection if safe to do so. (1C)

Antibiotic therapy
Begin intravenous antibiotics as early as possible, and always within the first hour of recognizing severe sepsis (1D) and septicshock. (1B) Broad-spectrum: one or more agents active against likely bacterial/ fungal pathogens and with good penetration into presumed source. (1B) Reassess antimicrobial regimen daily to optimize efficacy, prevent resistance, avoid toxicity, & minimize costs. (1C) Consider combination therapy in Pseudomonas infections. (2D) Consider combination empiric therapy in neutropenic patients.(2D) Combination therapy no more than 3-5 days and de-escalation following susceptibilities. (2D) Duration of therapy typically limited to 710 days; longer if response slow, undrainable foci of infection, or immunologic deficiencies. (1D) Stop antimicrobial therapy if cause is found to be non-infectious. (1D)

Vasopressors
Maintain MAP 65 mm Hg (1C), what is The MAP Norepinephrine and dopamine centrally administered are the initial vasopressors of choice (1C) Epinephrine, phenylephrine, or vasopressin should not be administered as the initial vasopressor in septic shock (2C). Use epinephrine as the first alternative agent in septic shock when blood pressure is poorly responsive to norepinephrine or dopamine (2B). Do not use low-dose dopamine for renal protection (1A) In patients requiring vasopressors, insert an arterial catheter as soon as practical (1D)

Inotropic therapy
Use dobutamine in patients with myocardial dysfunction as supported by elevated cardiac filling pressures and low cardiac output (1C) Do not increase cardiac index to predetermined supranormal levels (1B)

Steroid
Consider intravenous hydrocortisone for adult septic shock when hypotension responds poorly to adequate fluid resuscitation and vasopressors (2C) ACTH stimulation test is not recommended to identify the subset of adults with septic shock who should receive hydrocortisone (2B) Hydrocortisone is preferred to dexamethasone (2B) Fludrocortisone (50 g orally once a day) may be included if an alternative to hydrocortisone is being used that lacks significant mineralocorticoid activity. Steroid therapy may be weaned once vasopressors are no longer required (2D)

Steroid
Hydrocortisone dose should be less than 300 mg/day (1A) Do not use corticosteroids to treat sepsis in the absence of shock unless the patients endocrine or corticosteroid history warrants it (1D)

Recombinant human activated protein C

Consider rhAPC in adult patients with sepsis-induced organ dysfunction with clinical. Adult patients with severe sepsis and low risk of death should not receive rhAPC (1A)

Blood product administration

Give red blood cells when hemoglobin decreases to 7.0 g/dL (70 g/L) to target a hemoglobin of 7.09.0 g/dL in adults (1B). A higher hemoglobin level may be required in special circumstances (e.g., myocardial ischaemia, severe hypoxemia, acute hemorrhage, cyanotic heart disease, or lactic acidosis) Do not use erythropoietin to treat sepsis-related anemia. Erythropoietin may be used for other accepted reasons (1B) Do not use fresh frozen plasma to correct laboratory clotting abnormalities unless there is bleeding or planned invasive procedures (2D) Do not use antithrombin therapy (1B) Administer platelets when (2D) Counts are 5000/mm3 regardless of bleeding Counts are 500030,000/mm3 and there is significant bleeding risk Higher platelet counts (50,000/mm3 are required for surgery or invasive procedures

Mechanical ventilation of sepsis-induced ALI/ARDS

Target a tidal volume of 6 mL/kg (predicted) body weight in patients with ALI/ARDS (1B) Target an initial upper limit plateau pressure 30 cm H2O. Consider chest wall compliance when assessing plateau pressure (1C) Allow PaCO2 to increase above normal, if needed, to minimize plateau pressures and tidal volumes (1C) Set PEEP to avoid extensive lung collapse at end-expiration (1C) Consider using the prone position for ARDS patients requiring potentially injurious levels of FIO2 or plateau pressure, provided they are not put at risk from positional changes (2C) Maintain mechanically ventilated patients in a semirecumbent position (head of the bed raised to 45) unless contraindicated (1B), between 30and 45 (2C)

Mechanical ventilation of sepsis-induced ALI/ARDS

Noninvasive ventilation may be considered in the minority of ALI/ARDS patients with mild to moderate hypoxemic respiratory failure. The patients need to be hemodynamically stable, comfortable, easily arousable, able to protect/clear their airway, and expected to recover rapidly (2B) Use a weaning protocol and an SBT regularly to evaluate the potential for discontinuing mechanical ventilation (1A) SBT options include a low level of pressure support with continuous positive airway pressure 5 cm H2O or a T piece Before the SBT, patients should be arousable, be hemodynamically stable without vasopressors, have no new potentially serious conditions, have low ventilatory and end-expiratory pressure requirement, require FIO2 levels that can be safely delivered with a face mask or nasal cannula Do not use a pulmonary artery catheter for the routine monitoring of patients with ALI/ARDS (1A) Use a conservative fluid strategy for patients with established ALI who do not have evidence of tissue hypoperfusion

Glucose control
Use intravenous insulin to control hyperglycemia in patients with severe sepsis following stabilization in the ICU (1B) Aim to keep blood glucose 150 mg/dL (8.3 mmol/L) using a validated protocol for insulin dose adjustment (2C) Provide a glucose calorie source and monitor blood glucose values every 12 hrs (4 hrs when stable) in patients receiving intravenous insulin (1C) Interpret with caution low glucose levels obtained with point of care testing, as these techniques may overestimate arterial blood or plasma glucose values (1B)

Bicarbonate therapy
Do not use bicarbonate therapy for the purpose of improving hemodynamics or reducing vasopressor requirements when treating hypoperfusioninduced lactic acidemia with pH 7.15 (1B)

Deep vein thrombosis prophylaxis

Use either low-dose UFH or LMWH, unless contraindicated (1A) Use a mechanical prophylactic device, such as compression stockings or an intermittent compression device, when heparin is contraindicated (1A) Use a combination of pharmacologic and mechanical therapy for patients who are at very high risk for deep vein thrombosis (2C) In patients at very high risk, LMWH should be used rather than UFH (2C)

Stress ulcer prophylaxis

Provide stress ulcer prophylaxis using H2 blocker (1A) or proton pump inhibitor (1B). Benefits of prevention of upper gastrointestinal bleed must be weighed against the potential for development of ventilator-acquired pneumonia Discuss advance care planning with patients and families. Describe likely outcomes and set realistic expectations (1D)

Steps of initial resuscitation

0 min Recognize mental status, poor perfusion 5 min: Maintain airway ,establish access push 20ml/kg up to 60ml/kg fluid. Observe in picu if +response 15min: Recognize fluid refractory shock, start central line , dopamine (10mic/kg/min), (or NE) establish arterial monitoring. if fluid refractory dopamine (or NE) resistant shock start epinephrine for cold, Vasopressin for warm shock. If Risk of adrenal insufficiency Give hydrocortisone .

Summary of inotropic and vassopressors

Normal BP ,Cold shock, SVC O2 sat <70 add vasodilator, consider volume. Low BP ,Cold shock, SVC O2 sat <70 Titrate volume and Epinephrine Low BP, Warm shock : give Norepinephrine ,fluid, consider Vasopressin Should Only Be Used After Appropriate Volume Resuscitation and normalization of the cardiac filling pressure

Pending researches (not yet evidenced)

Nitric oxide Extracorporeal membrane oxygenation