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  • 1. Monitoring in septic shock and surviving sepsis guidelines Dr.Ramaning Loni www.picuforum.com
  • 2. SEPSIS • Sepsis is a clinical syndrome that complicates severe infection and is characterized by - the systemic inflammatory response syndrome, - immune dysregulation, - microcirculatory derangements, and - end-organ dysfunction • In this syndrome, tissues remote from the original insult display the cardinal signs of inflammation, including - vasodilatation, - increased microvascular permeability, and - leukocyte accumulation. www.picuforum.com
  • 3. Definitions ●Severe sepsis – Sepsis is considered severe when it is associated with cardiovascular dysfunction, acute respiratory distress syndrome (ARDS), or dysfunction in two or more other organ systems as defined in the section on multiple organ failure . ●Septic shock – Septic shock refers to sepsis with cardiovascular dysfunction (as described in the section on multiple organ failure below) that persists despite the administration of ≥40 mL/kg of isotonic fluid in one hour. ●Refractory septic shock – There are two types of refractory septic shock: fluid-refractory septic shock exists when cardiovascular dysfunction persists despite at least 60 mL/kg of fluid resuscitation; and catecholamine-resistant septic shock exists when shock persists despite therapy with dopamine ≥10 mcg/kg per min and/or direct- acting catecholamines (epinephrine, norepinephrine). Watson RS, Carcillo JA, Linde-Zwirble WT, et al. The epidemiology of severe sepsis in children in the United States. Am J Respir Crit Care Med 2003; 167:695 www.picuforum.com
  • 4. Sepsis Terminology SIRS: Two of four findings • HR ↓↑ ( exclude drugs, pain ) • RR ↑ • Temp ( < 36.0 / > 38.5 ) • TLC ↑ Infection: • Clinical or Lab (culture, serology, PCR, Latex, MP etc ) One of these two is must www.picuforum.com
  • 5. + = Sepsis Sepsis + Organ Dysfunction = Severe Sepsis Severe Sepsis + cardiovascular dysfunction or Persistent shock in fluid resuscitated = Septic shock SIRS Infection www.picuforum.com
  • 6. Epidemiology Disease Burden: Increasing (Improved neonatal survival) “Big four” killers of children: pneumonia, diarrhea, malaria, measles Indian Figures: 12 – 30% ICU admissions Age and sex : Infants at a higher risk , Males > Females Mortality: US 10%, Khilnani et al 12 %, CMC PICU Other predisposing conditions: Trauma, malignancy, CP, CHD, CLD, splenectomy , Nephrotic etc Cost: Very high • Sepsis in children is a major cause of death in industrialized countries with state of the art ICU ,the overall mortality from severe sepsis is much lower than that in adults, estimated at about 2 % to 10%. • The hospital mortality rate for severe sepsis is 2 % in previously healthy child as compared to 8 %in chronically ill child in USA. www.picuforum.com
  • 7. Target points in treatment of shock  Normal heart rate and BP for age  Normal pulses  CRT < 2 sec  Warm extremities  Urine output > 1ml/kg/hour  Decreased serum lactate  Reduced base deficit  Central venous O2 saturation > 70% AHA/PALS 2012 GUIDELINES www.picuforum.com
  • 8. Definition of shock: PALS Shock: “Inadequate tissue perfusion resulting in insufficient delivery of oxygen and metabolic substrates to meet metabolic demands” “ DEMAND > SUPPLY ” Septic Shock: “ Persistent shock + severe sepsis in a fluid replete child” www.picuforum.com
  • 9. Evaluation of “Early Goal Directed Therapy” before admission to ICU (i.e. in Emergency department / Casualty) (N. Engl J Med 2001; 345: 1368-77) www.picuforum.com
  • 10. 46.5% 30.5% 0 10 20 30 40 50 60 Standard Therapy n=133 EGDT n=130 P = 0.009* *Key difference was in sudden CV collapse, not MODS 28-day Mortality Rivers E. N Engl J Med 2001;345:1368-77. Early Goal-Directed Therapy Results www.picuforum.com
  • 11. www.picuforum.com
  • 12. Cardiovascular dysfunction Despite administration of isotonic IV fluid bolus 40 mL/kg in 1 hr: Decrease in BP (hypotension) 5% percentile for age or systolic BP 2 SD below normal for age OR •Need for vasoactive drug to maintain BP in normal range (dopamine 5 mcg/kg/min) or ( dobutamine, epineph, or norepinep 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 sec Core to peripheral temperature gap 3°C •Respiratory system • PaO2/FIO2 ratio 300 in the absence of cyanotic congenital heart disease or preexisting lung disease OR •PaCO2 65 torr or 20 mm Hg above baseline PaCO2 OR •Proven need or 50% FIO2 to maintain saturation ≥92% OR Need for nonelective invasive or noninvasive mechanical ventilation •Central nervous system GCS 11 OR •Acute change in mental status with a decrease in GCS <3 points from abnormal baseline •Hematologic system • Platelet count 80,000/mm3 or a decline of 50% in platelet count from highest valued recorded over 3 days (for chronic heme-onc patients) OR INR 2/ APTT> 60 S Renal system •Serum creatinine level greater than twice the upper limit for age or twofold increase in baseline creatinine Hepatic system •Total serum bilirubin >4 mg/dL (in the absence of hemolysis, hyperbilirubinemia of the newborn, or primary liver disease) OR [ALT twice upper limit of normal for age] www.picuforum.com
  • 13. Age specific vital signs and lab limits Age HR RR TLC SBP 0-1 > 180 < 100 50 > 34 < 65 1wk- 1 mo > 180 < 100 50 > 19.5 / <5.0 < 75 1 -12 mo > 180 < 90 34 > 17.5 / < 5.0 < 100 1 – 5 yrs > 140 NA 22 > 15.5 / < 6.0 < 94 6 – 12 yrs > 130 NA 18 > 13.5 / <4.5 < 105 13 – 18 yrs > 110 NA 14 > 11.0 / < 4.5 < 117 www.picuforum.com
  • 14. SURVIVING SEPSIS BUNDLE CARE GUIDELINES 2012 TO BE COMPLETED WITHIN 3 HOURS: 1) Measure lactate level 2) Obtain blood cultures prior to administration of antibiotics 3) Administer broad spectrum antibiotics 4) Administer 30 mL/kg crystalloid for hypotension or lactate 4mmol/L TO BE COMPLETED WITHIN 6 HOURS: 5) Apply vasopressors (for hypotension that does not respond to initial fluid resuscitation) to maintain a mean arterial pressure (MAP) 65 mm Hg 6) In the event of persistent arterial hypotension despite volume resuscitation (septic shock) or initial lactate 4 mmol/L (36 mg/dL): - Measure central venous pressure (CVP)* - Measure central venous oxygen saturation (ScvO2)* 7) Remeasure lactate if initial lactate was elevated* *Targets for quantitative resuscitation included in the guidelines are CVP of 8 mm Hg, ScvO2 of 70%, and normalization of lactate. www.picuforum.com
  • 15. Stepwise Management of Pediatric Septic Shock Recognize decreased mental status and perfusion Maintain airway & establish access according to PALS guidelines Push 20 cc/kg isotonic saline/colloid boluses upto and over 60 cc/kg Correct hypoglycemia and hypocalcaemia Step I 0 min 5 min 15 min Fluid can be administered as much as 200 ml/kg/ hr www.picuforum.com
  • 16. Stepwise Management of Pediatric Septic Shock Establish central venous access, begin dopamine therapy and establish arterial monitoring Titrate Epinephrine for cold shock, Nor epinephrine for warm shock Step II Fluid Refractory Shock Fluid Refractory Dopamine Resistant Shock 15 min Fluid Responsive Shock Observe in PICU 60 min www.picuforum.com
  • 17. Stepwise Management of Pediatric Septic Shock At risk of Adrenal Insufficiency CNS abnormality – HPA axis Chronic steroid use Purpura fulminans Step III Catecholamine –Resistant Shock No risk of Adrenal Insufficiency Give Hydrocortisone No Hydrocortisone 60 min www.picuforum.com
  • 18. Stepwise Management of Pediatric Septic ShockStep IV Normal Blood Pressure Cold Shock SVC O2 sat < 70% Low Blood Pressure Warm Shock Low Blood Pressure Cold Shock SVC O2 sat < 70% Add Vasodilator or Type III PDE inhibitor with volume loading ( Milrinone ) Titrate volume and Epinephrine Titrate volume and Norepinephrine Persistent Catecholamine Resistant Shock www.picuforum.com
  • 19. Stepwise Management of Pediatric Septic ShockStep V Persistent Catecholamine resistant shock www.picuforum.com
  • 20. Stepwise Management of Pediatric Septic Shock Place Pulmonary artery catheter and direct fluid, ionotrope, vasopressor, vasodilator and hormonal therapies to attain normal MAP – CVP and CI > 3.3 and < 6.0 L/min/m2 Refractory shock Step V Persistent Catecholamine resistant shock Consider ECMO www.picuforum.com
  • 21. Refractory Shock: Causes • Pericardial effusion • Pneumothorax • Hypoadrenalism • Hypothyroidsm • Ongoing blood loss • Intra abdominal catastrophe • Necrotic tissue www.picuforum.com
  • 22. The 10 steps: goal-directed management of pediatric shock in ED Joseph A. Carcillo, Pediatric Emergency Medicine, JULY-2007. www.picuforum.com
  • 23. www.picuforum.com
  • 24. Pathophysiology Inadequate oxygen delivery Anaerobic metabolism (limited cell function). Organ dysfunction. www.picuforum.com
  • 25. Components - tissue oxygen delivery 1. Sufficient O2 content in the blood( Hb concentration and % of Hb that is saturated with oxygen) 2. Adequate blood flow to the tissues (cardiac output and vascular resistance) C.O = S.V x H.R Stroke volume - volume of blood ejected by heartwww.picuforum.com
  • 26. Components - tissue oxygen delivery STROKE VOLUME 3. Appropriate distribution of blood flow to the tissues(size of the blood vessel) Volume of blood in ventricle before contraction Resistance against which the ventricle is ejecting AFTERLOAD CONTRACTILITY PRE-LOAD www.picuforum.com
  • 27. (1) Preload: “ amount of stretch on ventricular muscle before it contracts ” ……. Frank starling relationship (2) After-load : “ Sum of the forces that oppose the ventricular ejection ” (systemic vascular resistance) (3) Contractility www.picuforum.com
  • 28. Shock and Heart Preload Contractility Afterload Distributive ( septic ) ↓ (Vasodilatation) normal / ↓ ( Myocardial Depression ) ↓ / ↑ ↓ / ↑ PVR www.picuforum.com
  • 29. Shock and Heart Preload Contractility Afterload Distributive ( septic ) ↓ (Vasodilatation) normal / ↓ ( Myocardial Depression ) ↓ / ↑ ↓ / ↑ PVR Hypovolemic (Severe dehydration) ↓ Normal Normal Cardiogenic (CCF) ↑ ↓ ↑ www.picuforum.com
  • 30. Resources available at different levels of health care facilities in resource- limited countries and feasibility of monitoring and interventions. P.khilnani et al/septic shock guidelines, Indian J Crit Care Med 2010. Jan-Mar; 14(1): 41- 52. www.picuforum.com
  • 31. Determination of the Quality of Evidence Underlying methodology A (high) RCTs B (moderate) Downgraded RCTs or upgraded observational studies C (low) Well-done observational studies with control RCTs D (very low) Downgraded controlled studies or expert opinion based on other evidence Factors that may decrease the strength of evidence 1. Poor quality of planning and implementation of available RCTs, suggesting high likelihood of bias 2. Inconsistency of results, including problems with subgroup analyses 3. Indirectness of evidence (differing population, intervention, control, outcomes, comparison) 4. Imprecision of results 5. High likelihood of reporting bias Main factors that may increase the strength of evidence 1. Large magnitude of effect (direct evidence, relative risk > 2 with no plausible confounders) 2. Very large magnitude of effect with relative risk > 5 and no threats to validity (by two levels) 3. Dose-response gradient www.picuforum.com
  • 32. Initial Resuscitation and Infection Issues A. Initial Resuscitation 1. We recommend the protocolized, quantitative resuscitation of patients with sepsis- induced tissue hypoperfusion (defined in this document as hypotension persisting after initial fluid challenge or blood lactate concentration ≥ 4 mmol/L). This protocol should be initiated as soon as hypoperfusion is recognized and should not be delayed pending ICU admission. During the first 6 hrs of resuscitation, the goals of initial resuscitation of sepsis-induced hypoperfusion should include all of the following as a part of a treatment protocol (grade 1C): a) CVP 8–12 mm Hg b) MAP ≥ 65 mm Hg c) Urine output ≥ 0.5 mL・kg・hr d) Superior vena cava oxygenation saturation (Scvo2) or mixed venous oxygen saturation (Svo2) 70% or 65%,respectively. 2. We suggest targeting resuscitation to normalize lactate in patients with elevated lactate levels as a marker of tissue hypoperfusion (grade 2C). www.picuforum.com
  • 33. Early Goal-Directed Therapy Collaborative Group of Zhejiang Province: The effect of early goal-directed therapy on treatment of critical patients with severe sepsis/septic shock: A multi-center, prospective, randomized, controlled study [in Chinese]. Zhongguo Wei Zhong Bing Ji Jiu Yi Xue 2010; 6:331–334 • Early goal-directed therapy, was evaluated in a multicenter trial of 314 patients with severe sepsis in eight Chinese canters. • Results ;This trial reported a 17.7% absolute reduction in 28- day mortality (survival rates, 75.2% vs. 57.5%, p = 0.001). www.picuforum.com
  • 34. 6-Hour Bundle Remeasure Lactate If Initial Lactate Was Elevated • Hyperlactatemia is typically present in patients with severe sepsis or septic shock and may be secondary to anaerobic metabolism due to hypoperfusion. • The prognostic value of raised blood lactate levels has been well established in septic shock patients. • Obtaining a lactate level is essential to identifying tissue hypoperfusion in patients who are not yet hypotensive but who are at risk for septic shock. • A number of studies have suggested that elevated lactate levels may result from cellular metabolic failure in sepsis rather than from global hypoperfusion. Elevated lactate levels can also result from decreased clearance by the liver.. 1.Weil MH, Afifi AA. Experimental and clinical studies on lactate and pyruvate as indicators of the severity of acute circulatory failure (shock). Circulation. 1970;41:989-1001. 2. Vincent JL, Dufaye P, Berre J, et al. Serial lactate determinations during circulatory shock. Critical Care Medicine. 1983;11:449-451. www.picuforum.com
  • 35. Serum Lactate level • The global prevalence of severe sepsis patients initially presenting with either hypotension with lactate ≥ 4 mmol//L, hypotension alone, or lactate ≥ 4 mmol/L alone, is reported as 16.6%,49.5%, and 5.4%, respectively. • The mortality rate is high in septic patients with both hypotension and lactate ≥ 4 mmol/L(46.1%), and is also increased in severely septic patients with hypotension alone (36.7%) and lactate ≥ 4 mmol/L alone (30%) . Levy MM, Dellinger RP, Townsend SR, et al; Surviving Sepsis Campaign: The Surviving Sepsis Campaign: Results of an international guideline-based performance improvement program targeting severe sepsis. Crit Care Med 2010; 38:367–374 www.picuforum.com
  • 36. The consensus panel judged use of CVP and Svo 2 targets to be recommended physiologic targets for resuscitation. • Either intermittent or continuous measurements of oxygen saturation were judged to be acceptable. • During the first 6 hrs of resuscitation, if Scvo2 less than 70% or Svo2equivalent of less than 65% persists with what is judged to be adequate intravascular volume repletion in the presence of persisting tissue hypoperfusion, • Then dobutamine infusion (to a maximum of 20 μg/kg/min) or transfusion of packed red blood cells to achieve a hematocrit of greater than or equal to 30% in attempts to achieve the Scvo2 or Svo2 goal are options. • The strong recommendation for achieving a CVP of 8 mm Hg and an Scvo2 of 70% in the first 6 hrs of resuscitation of sepsis-induced tissue hypoperfusion, although deemed desirable, are not yet the standard of care as verified by practice data. The publication of the initial results of the international SSC performance improvement program demonstrated that adherence to CVP and Scvo2 targets for initial resuscitation was low. www.picuforum.com
  • 37. Mixed and central venous O2 saturations SvO2[Mixed venous saturation] • SvO2, (mixed venous oxygen saturation), is obtained from a pulmonary artery catheter and reflects overall SvO2 of blood returning from the upper body, the lower body, and the heart via the coronary sinus. • Placement of a pulmonary artery catheter is associated with increased risks, severe complications and increased health care costs • This risk benefit ratio is still a matter of controversy www.picuforum.com
  • 38. SvO2 and ScvO2 • SvO2 is reflective of the balance between systemic oxygen delivery and consumption and variables which affect these two factors will alter mixed venous oxygen saturation • Situations in which oxygen delivery is increased with fixed oxygen consumption will increase SvO2 • The converse is also true; reduced oxygen delivery with fixed oxygen consumption will result in reduced SvO2. • Healthy individuals at rest have a SvO2 of 65–75%. • Indeed, it has been shown that the SvO2 is well correlated with the ratio of O2 supply to demand www.picuforum.com
  • 39. Central venous O2 saturation • If ScvO 2 is not available, lactate normalization may be a feasible option in the patient with severe sepsis-induced tissue hypoperfusion. • ScvO 2 and lactate normalization may also be used as a combined end point when both are available www.picuforum.com
  • 40. Central venous saturation /ScvO2 • ScvO2 (central venous oxygen saturation) is the oxygen saturation of central venous blood. • This value is obtained by placing a fiberoptic central venous catheter into the SVC (for continuous) or a simple catheter. • It is routinely inserted in critically ill patients for monitoring of CVP and administration of inotropes/vasopressors and TPN. • ScvO2 reflects oxygen saturation of blood returning from the upper body and indicates the balance between oxygen delivery and oxygen consumption in the cranial portion of the body, including the brain. www.picuforum.com
  • 41. ScvO2 www.picuforum.com
  • 42. ScvO2 and SvO2 • Variations in regional blood flow from the upper body, lower body, and heart will affect the absolute values for ScvO2 and SvO2 • Whether the central venous oxygen saturation (ScvO2) reflects changes in SvO2 was investigated as early as in 1969 by Scheinman et al www.picuforum.com
  • 43. Difference between SvO2 and ScvO2 • Central venous blood sampling reflects the venous blood of the upper body but neglects venous blood from the lower body (i.e. intra-abdominal organs). • Venous oxygen saturation differs among several organ systems since they extract different amounts of oxygen. • ScvO2 is usually less than SvO2 by about 2–3% because overall the lower body extracts less oxygen than the upper body, making inferior vena cava oxygen saturation higher www.picuforum.com
  • 44. Venous Oxygen Saturation • Pulmonary artery catheter  SvO2 • Mixed venous oxygen saturation • Global oxygen balance • Central venous catheter  ScvO2 • Central venous oxygen saturation ScvO2 SvO2 SvO2 vs ScvO2 Normal: SvO2 > ScvO2  2~3% (difference decrease as CVP tip in RA) Shock: SvO2 < ScvO2  5~18% (ScvO2 of 50% is considered critical) Anesthesia / Cerebral trauma / Barbiturate coma: SvO2 < ScvO2 (highest difference In IiCP) www.picuforum.com
  • 45. Drop in SvO2 does not necessarily mean that tissue hypoxia is occurring but represents increased metabolic stress. www.picuforum.com
  • 46. Emanuael P.Rivers et al.Early and innovative interventions for severe sepsis and septic shock;taking advantage of a window opportunity;CMAJI,octobe r 2005;173[9].1054-1065. www.picuforum.com
  • 47. Mixed or central venous O2 saturation Emanuael P.Rivers et al.Early and innovative interventions for severe sepsis and septic shock;taking advantage of a window opportunity;CMAJI,october 2005;173[9].1054-1065. www.picuforum.com
  • 48. www.picuforum.com
  • 49. www.picuforum.com
  • 50. Conclusions: This study supports the current ACCM/PALS guidelines. Goal-directed therapy using the endpoint of a ScvO2 ≥ 70% has a significant and additive impact on the outcome of children and adolescents with septic shock. www.picuforum.com
  • 51. • Rivers et al. demonstrated in a recent prospective randomized study in patients with severe sepsis and septic shock that, in addition to maintaining CVP above 8–12 mmHg, MAP above 65 mmHg, and urine output above 0.5 ml/kg per h, the maintenance of a ScvO2 above 70% resulted in an absolute reduction of mortality by 15%. www.picuforum.com
  • 52. Recommandations,SSC guidelines 2012 A. Initial resuscitation : 1. For respiratory distress and hypoxemia, Start O2 with face mask or if needed and available, high flow nasal cannula o2 therapy or NP CPAP. For improved circulation, peripheral iv access can be used for fluid resuscitation and inotropes infusion if central line is not available . if mechanical ventilation is required then cardiovascular instability during intubation is likely after appropriate cardiovascular resuscitation [Grade 2C]. 2. Initial therapeutic end points of septic shock; capillary refill of ≤2 secs, normal blood pressure for age, normal pulses with no differential between peripheral and central pulses, warm extremities, urine output >1 mL·kg-1·hr-1, and normal mental status. Scvo2 saturation ≥70% and cardiac index between 3.3 and 6.0 L/min/m2 should be targeted thereafter (grade 2C). 3. Follow American College of Critical Care Medicine-Pediatric Life Support ( ACCM-PALS guidelines for the management of septic shock (grade 1C). 4. Evaluate for and severe pneumothorax, pericardial tamponade, or endocrine emergencies in patients with refractory shock (grade 1C). www.picuforum.com
  • 53. ABCs: airway and breathing • Airway, breathing and circulation remain the fundamental principles of resuscitation also in patients with septic shock. • Priority is given to the airway, which is immediately assessed and secured, if necessary. High flow oxygen via face mask, nasal cannula or Nasopharyngeal CPAP should be given, even in the absence of respiratory distress or hypoxemia. • Aggressive airway management and ventilation should be considered in any patient not responding to fluid resuscitation and peripherally administered inotropes. • Indeed, early intubation and mechanical ventilation may support cardiac output (CO) by reducing the work of breathing, reduce oxygen consumption by sedation, facilitate procedures for establishing invasive hemodynamic monitoring, provide airway protection. Brierley J, Carcillo JA, Choong K, et al. Clinical practice parameters for hemodynamic support of pediatric and neonatal septic shock: 2007 update from the American College of Critical Care Medicine. Crit Care Med 2009;37:666-88. www.picuforum.com
  • 54. Airway CirculationBreathing Patent / protected Tachypnea / dyspnoea / acidotic CRT, warm / cool extremities BP, HR, pulses, Organ dysfunction (mentation, UO) Keep assessing ‘Airway’ High flow oxygen Keep assessing ‘Work Of Breathing’ Keep assessing ‘circulation’ Ventilate for airway protection and impending respiratory failure Target 1. Preload, 2. Contractility 3. Afterload Start NS 20 cc / kg x 3 times administration immediately www.picuforum.com
  • 55. Preload correction NS 20 cc/kg over 5-10 min up to or more 3 boluses if pulses do not improve : check liver, crepitations for overload • Monitor central venous pressure • Place for CVP : SVC/IVC (cava atrial junction) • Access: Femoral Rt IJV Subclavian • CXR confirmation is must • Confirm oscillation with respiration • Target is 10 mm Hg ( Other signs such as ↑ liver size) www.picuforum.com
  • 56. PICC Line www.picuforum.com
  • 57. Preload correction continues No response (pulse volume not good, no urine output, CRT ↑) Colloid Options: Hetastarch Limited published data Voluven Starch with fewer coagulation problems Haemaccel Acceptable and cheaper has side effects Albumin high cost, no added advantage Plasma Not recommended for volume expansion PCV ↑ O2 carrying capacity Hetastarch / Voluven : 10 -20 ml / kg (longer half life) X twice PCV: 10-15 cc / Kg Volume upto 200ml/kg in first hr may be needed www.picuforum.com
  • 58. B. Screening for Sepsis and Performance Improvement 1. Routine screening of potentially infected seriously ill patients for severe sepsis to allow earlier implementation of therapy (grade 1C). 2. Hospital–based performance improvement efforts in severe sepsis (UG). C. Diagnosis 1. Cultures as clinically appropriate before antimicrobial therapy if no significant delay (> 45 mins) in the start of antimicrobial(s) (grade1C). At least 2 sets of blood cultures (both aerobic and anaerobic bottles) be obtained before antimicrobial therapy with at least 1 drawn percutaneously and 1 drawn through each vascular access device, unless the device was recently (<48 hrs) inserted (grade 1C). 2. Use of the 1,3 beta-D-glucan assay (grade 2B), mannan and anti-mannan antibody assays (2C), if available and invasive candidiasis is in differential diagnosis of cause of infection. 3. Imaging studies performed promptly to confirm a potential source of infection (UG). Surviving sepsis campaign guidelines 2012 www.picuforum.com
  • 59. Surviving sepsis campaign guidelines 2012 D. Antimicrobial Therapy 1. Administration of effective intravenous antimicrobials within the first hour of recognition of septic shock (grade 1B) and severe sepsis without septic shock (grade 1C) as the goal of therapy. 2a. Initial empiric anti-infective therapy of one or more drugs that have activity against all likely pathogens (bacterial and/or fungal or viral) and that penetrate in adequate concentrations into tissues presumed to be the source of sepsis (grade 1B). 2b. Antimicrobial regimen should be reassessed daily for potential deescalation (grade 1B). 3. Use of low procalcitonin levels or similar biomarkers to assist the clinician in the discontinuation of empiric antibiotics in patients who initially appeared septic, but have no subsequent evidence of infection (grade 2C). 4a. Combination empirical therapy for neutropenic patients with severe sepsis (grade 2B) and for patients with difficult-to-treat, multidrug resistant bacterial pathogens such as Acinetobacter and Pseudomonas spp. (grade 2B). For patients with severe infections associated with respiratory failure and septic shock, combination therapy with an extended spectrum beta-lactam and either an aminoglycoside or a fluoroquinolone is for P. aeruginosa bacteremia (grade 2B). A combination of beta-lactam and macrolide for patients with septic shock from bacteremic Streptococcus pneumoniae infections (grade 2B). www.picuforum.com
  • 60. The following are the investigations done in septic shock 1. Rapid blood glucose 2. Arterial or venous blood gas 3. Complete blood count with differential 4. Blood lactate 5. Serum electrolytes 6. Blood urea nitrogen and serum creatinine 7. Ionized blood calcium 8. Serum total bilirubin and alanine aminotransferase 1. Prothrombin and partial thromboplastin times (PT and PTT) International normalized ratio (INR) 2. Fibrinogen and D-dimer 3. Blood culture 4. Urinalysis 5. Urine culture 6. Other cultures as indicated by clinical findings 7. Diagnostic serologic testing as indicated to identify suspected sources of infection 8. Inflammatory biomarkers (eg, C- reactive protein, procalciton) in selected caseswww.picuforum.com
  • 61. continued 4b. Empiric combination therapy should not be administered for more than 3–5 days. De-escalation to the most appropriate single therapy should be performed as soon as the susceptibility profile is known (grade 2B). 5. Duration of therapy typically 7–10 days; longer courses may be appropriate in patients who have a slow clinical response,undrainable foci of infection, bacteremia with S. aureus; some fungal and viral infections or immunologic deficiencies, including neutropenia (grade 2C). 6. Antiviral therapy initiated as early as possible in patients with severe sepsis or septic shock of viral origin (grade 2C). 7. Antimicrobial agents should not be used in patients with severe inflammatory states determined to be of noninfectious cause (UG). www.picuforum.com
  • 62. E. Source Control 1. A specific anatomical diagnosis of infection requiring consideration for emergent source control be sought and diagnosed or excluded as rapidly as possible, and intervention be undertaken for source control within the first 12 hr after the diagnosis is made, if feasible (grade 1C). 2. When infected peripancreatic necrosis is identified as a potential source of infection, definitive intervention is best delayed until adequate demarcation of viable and nonviable tissues has occurred (grade 2B). 3. When source control in a severely septic patient is required, the effective intervention associated with the least physiologic insult should be used (eg, percutaneous rather than surgical drainage of an abscess) (UG). 4. If intravascular access devices are a possible source of severe sepsis or septic shock, they should be removed promptly after other vascular access has been established (UG). www.picuforum.com
  • 63. F. Infection Prevention 1a. Selective oral decontamination and selective digestive decontamination should be introduced and investigated as a method to reduce the incidence of ventilator-associated pneumonia; This infection control measure can then be instituted in health care settings and regions where this methodology is found to be effective (grade 2B). 1b. Oral chlorhexidine gluconate be used as a form of oropharyngeal decontamination to reduce the risk of ventilator-associated pneumonia in ICU patients with severe sepsis (grade 2B). www.picuforum.com
  • 64. Pediatric septic shock SSC 2012 guidelines Antibiotics and Source Control 1. Empiric antibiotics be administered within 1 hr of the identification of severe sepsis. Blood cultures should be obtained before administering antibiotics when possible but this should not delay administration of antibiotics. The empiric drug choice should be changed as epidemic and endemic ecologies dictate (eg H1N1, MRSA, chloroquine resistant malaria, penicillin-resistant pneumococci, recent ICU stay, neutropenia ) (grade 1D). 2. Clindamycin and anti-toxin therapies for toxic shock syndromes with refractory hypotension (grade 2D). 3. Early and aggressive source control (grade 1D). 4. Clostridium difficile colitis should be treated with enteral antibiotics if tolerated. Oral vancomycin is preferred for severe disease (grade 1A). www.picuforum.com
  • 65. How to choose an antibiotic in septic shock Age, community / hospital acquired, underlying condition, site of infection, pattern of resistance in the area/ hospital, indwelling devices, exposure to drugs including antibiotics, safety, cost Likely organisms Decide antibiotic FIRST SHOT should be rapid response and also the BEST SHOT www.picuforum.com
  • 66. G. Fluid Therapy of Severe Sepsis 1. Crystalloids as the initial fluid of choice in the resuscitation of severe sepsis and septic shock (grade 1B). 2. Against the use of hydroxyethyl starches for fluid resuscitation of severe sepsis and septic shock (grade 1B). 3. Albumin in the fluid resuscitation of severe sepsis and septic shock when patients require substantial amounts of crystalloids (grade 2C). 4. Initial fluid challenge in patients with sepsis-induced tissue hypoperfusion with suspicion of hypovolemia to achieve a minimum of 30 mL/kg of crystalloids (a portion of this may be albumin equivalent). More rapid administration and greater amounts of fluid may be needed in some patients (grade 1C). 5. Fluid challenge technique be applied wherein fluid administration is continued as long as there is hemodynamic improvement either based on dynamic (eg, change in pulse pressure, stroke volume variation) or static (eg, arterial pressure, heart rate) variables (UG). www.picuforum.com
  • 67. Dynamic indices of preload assessment • Dynamic tests to assess patients’ responsiveness to fluid replacement have become very popular in recent years in the ICU [marik PE et al 2009] • These tests are based on monitoring changes in stroke volume during mechanical ventilation or after passive leg raising in spontaneously breathing patients. • A systematic review (29 trials, n = 685 critically ill patients) looked at the association between stroke volume variation, pulse pressure variation, and/ or stroke volume variation and the change in stroke volume/ cardiac index after a fluid or positive end-expiratory pressure challenge[marik et al 2009]. • The diagnostic OR of fluid responsiveness was 59.86 (14 trials, 95% CI, 23.88−150.05) and 27.34 (five trials, 95% CI, 3.46−55.53) for the pulse pressure variation and the stroke volume variation, respectively. • Utility of pulse pressure variation and stroke volume variation is limited in the presence of atrial fibrillation, spontaneous breathing, and low pressure support breathing. These techniques generally require sedation. Marik PE, Monnet X, Teboul JL: Hemodynamic parameters to guide fluid therapy. Ann Intensive Care 2011; 1:1 Marik PE, Cavallazzi R, Vasu T, et al: Dynamic changes in arterial waveform derived variables and fluid responsiveness in mechanically ventilated patients: A systematic review of the literature. Crit CareMed 2009; 37:2642–2647 www.picuforum.com
  • 68. Dynamic Marker of fluid responsiveness • Passive Leg raising by 450 – act as one fluid bolus – Fluid responsive – Increases the pulse pressure by 12 % , increases the Aortic blood flow by 10% www.picuforum.com
  • 69. Volume responsiveness Positive response No response www.picuforum.com
  • 70. Pediatric septic shock; initial resuscitation of fluids • In the industrialized world with access to inotropes and mechanical ventilation, initial resuscitation of hypovolemic shock begins with infusion of isotonic crystalloids or albumin with boluses of up to 20 mL/kg crystalloids (or albumin equivalent ) over 5–10 minutes, titrated to reversing hypotension, increasing urine output, and attaining normal capillary refill, peripheral pulses, and level of consciousness without inducing hepatomegaly or rales. If hepatomegaly or rales exist then inotropic support should be implemented, not fluid resuscitation. • In non-hypotensive children with severe hemolytic anemia (severe malaria or sickle cell crises) blood transfusion is considered superior to crystalloid or albumin bolusing (grade 2C). www.picuforum.com
  • 71. Crystalloids vs. Colloids The absence of any clear benefit following the administration of colloid solutions compared to crystalloid solutions, together with the expense associated with colloid solutions, supports a high- grade recommendation for the use of crystalloid solutions in the initial resuscitation of patients with severe sepsis and septic shock. Dellinger et al,SSC guidelines for severe sepsis and septic shock in children,2012 . www.picuforum.com
  • 72. CHRYSTMAS study • The CRYSTMAS study demonstrated no difference in mortality with HES vs. 0.9% normal saline (31% vs. 25.3%, p = 0.37) in the resuscitation of septic shock patients; however the study was underpowered to detect the 6% difference in absolute mortality observed. • Guidet B, Martinet O, Boulain T, et al: Assessment of hemodynamic efficacy and safety of 6% hydroxyethylstarch 130/0.4 vs. 0.9% NaCl fluid replacement in patients with severe sepsis: The CRYSTMAS study. Crit Care 2012; 16:R94 www.picuforum.com
  • 73. The CHEST study, • The CHEST study, conducted in a heterogeneous population of patients admitted to intensive care (HES vs. isotonic saline, n = 7000 critically ill patients), showed no difference in 90-day mortality between resuscitation with 6% HES with a molecular weight of 130 kD/0.40 and isotonic saline (18% vs. 17%, p = 0.26); the need for renal replacement therapy was higher in the HES group (7.0% vs. 5.8%; relative risk [RR], 1.21;95% confidence interval [CI], 1.00−1.45; p = 0.04). • Myburgh JA, Finfer S, Bellomo R, et al; CHEST Investigators; Australian and New Zealand Intensive Care Society Clinical Trials Group: Hydroxyethyl starch or saline for fluid resuscitation in intensive care.N Engl J Med 2012; 367:1901–1911 www.picuforum.com
  • 74. • The SAFE study indicated that albumin administration was safe and equally as effective as 0.9% saline. • A meta-analysis aggregated data from 17 randomized trials (n = 1977) of albumin vs. other fluid solutions in patients with severe sepsis/septic shock ; 279 deaths occurred among 961 albumin-treated patients vs. 343 deaths among .016 patients treated with other fluids, thus favoring albumin (odds ratio [OR], 0.82; 95% CI, 0.67−1.00;= 0%). When albumin-treated patients were compared Finfer S, Bellomo R, Boyce N, et al; SAFE Study Investigators: A comparison of albumin and saline for fluid resuscitation in the intensive care unit. N Engl J Med 2004; 350:2247 2256. Delaney AP, Dan A, McCaffrey J, et al: The role of albumin as a resuscitation fluid for patients with sepsis: A systematic review and metaanalysis.Crit Care Med 2011; 39:386– 391 www.picuforum.com
  • 75. • A meta-analysis of 56 randomized trials found no overall difference in mortality between crystalloids and artificial colloids (modified gelatins, HES, dextran) when used for initial fluid resuscitation. Perel P, Roberts I: Colloids versus crystalloids for fluid resuscitation in critically ill patients. Cochrane Database Syst Rev 2011; 3. www.picuforum.com
  • 76. H. Vasopressors 1. Vasopressor therapy initially to target a mean arterial pressure (MAP) of 65 mm Hg (grade 1C). 2. Nor epinephrine as the first choice vasopressor (grade 1B). 3. Epinephrine (added to and potentially substituted for nor epinephrine) when an additional agent is needed to maintain adequate blood pressure (grade 2B). 4. Vasopressin 0.03 units/minute can be added to nor epinephrine (NE) with intent of either raising MAP or decreasing NE dosage (UG). 5. Low dose vasopressin is not recommended as the single initial vasopressor for treatment of sepsis-induced hypotension and vasopressin doses higher than 0.03-0.04 units/minute should be reserved for salvage therapy (failure to achieve adequate MAP with other vasopressor agents) (UG). www.picuforum.com
  • 77. Vasopressors continued 6. Dopamine as an alternative vasopressor agent to norepinephrine only in highly selected patients (eg, patients with low risk of tachyarrhythmias and absolute or relative bradycardia) (grade 2C). 7. Phenylephrine is not recommended in the treatment of septic shock except in circumstances where (a) norepinephrine isassociated with serious arrhythmias, (b) cardiac output is known to be high and blood pressure persistently low or (c) as salvage therapy when combined inotrope/vasopressor drugs and low dose vasopressin have failed to achieve MAP target (grade 1C). 8. Low-dose dopamine should not be used for renal protection (grade 1A). 9. All patients requiring vasopressors have an arterial catheter placed as soon as practical if resources are available (UG). I. Inotropic Therapy 1. A trial of dobutamine infusion up to 20 micrograms/kg/min be administered or added to vasopressor (if in use) in the presence of (a) myocardial dysfunction as suggested by elevated cardiac filling pressures and low cardiac output, or (b) ongoing signs of hypoperfusion, despite achieving adequate intravascular volume and adequate MAP (grade 1C). 2. Not using a strategy to increase cardiac index to predetermined supranormal levels (grade 1B). www.picuforum.com
  • 78. Pediatric part D. Inotropes/Vasopressors/Vasodilators 1. Begin peripheral inotropic support until central venous access can be attained in children who are not responsive to fluid resuscitation (grade 2C). 2. Patients with low cardiac output and elevated systemic vascular resistance states with normal blood pressure be given vasodilator therapies in addition to inotropes (grade 2C). www.picuforum.com
  • 79. Hemodynamics of Septic Shock Warm Shock: • Warm limbs Low BP (Low SVR) Cold Shock: • Cold limbs Low BP Normal BP (High SVR) MAP proportional to SVR , so normal BP is unreliable Pressors + Inotropes Dilators Inotropes www.picuforum.com
  • 80. Dose Action Indication Dopamine 5-10 >10 Inotropic + pressor Pressor Initial choice Dobutamine 5-20 Inotropic & Mild vasodilator Adjuvant Low BP, Cold shock Adrenaline 0.05 - 0.1 0.1 - 1 Inotropic + dilator Inotropic + pressor Cold Shock first line Noradrenaline 0.05-0.1 (Max 1-2) Pressor Warm shock 2nd line Milrinone 0.3 Drug Low BP Cold shock Vasopressin 0.0005 u/kg/hr Pressor Warm shock 3rd line Pharmacological actions of vasoactive drugs www.picuforum.com
  • 81. www.picuforum.com
  • 82. E. Extracorporeal Membrane Oxygenation (ECMO) Consider ECMO for refractory pediatric septic shock and respiratory failure (grade 2C). F. Corticosteroids Timely hydrocortisone therapy in children with fluid refractory, catecholamine resistant shock and suspected or proven absolute(classic) adrenal insufficiency (grade 1A). G. Protein C and Activated Protein Concentrate No recommendation as no longer available. H. Blood Products and Plasma Therapies 1. Similar hemoglobin targets in children as in adults. During resuscitation of low superior vena cava oxygen saturation shock (< 70%), hemoglobin levels of 10 g/dL are targeted. After stabilization and recovery from shock and hypoxemia then a lower target > 7.0 g/dL can be considered reasonable (grade 1B). 2. Similar platelet transfusion targets in children as in adults (grade 2C). 3. Use plasma therapies in children to correct sepsis-induced thrombotic purpura disorders, including progressive disseminated ntravascular coagulation, secondary thrombotic microangiopathy, and thrombotic thrombocytopenic purpura (grade 2C). www.picuforum.com
  • 83. Role of steroids in pediatric septic shock Hydrocortisone: reserved for Fluid refractory catecholamine resistance and suspected or proven adrenal insufficiency At risk children • Severe septic shock and purpura • Previous exposure to steroids • Pituitary and adrenal abnormality Absolute adrenal insufficiency • Cortisol < 18 microgm /dl Relative adrenal insufficiency • Post ACTH rise cortisol < 9 microgm / dl Stress dose • 50mg /m2/24 hrs Surviving sepsis campaign 2012 CCM www.picuforum.com
  • 84. Pediatric special considerations I. Mechanical Ventilation. Lung-protective strategies during mechanical ventilation (grade 2C J. Sedation/Analgesia/Drug Toxicities 1. We recommend use of sedation with a sedation goal in critically ill mechanically ventilated patients with sepsis (grade 1D). 2. Monitor drug toxicity labs because drug metabolism is reduced during severe sepsis, putting children at greater risk of adverse drug-related events (grade 1C). K. Glycemic Control Control hyperglycemia using a similar target as in adults ≤ 180 mg/dL. Glucose infusion should accompany insulin therapy in newborns and children because some hyperglycemic children make no insulin whereas others are insulin resistant (grade 2C). www.picuforum.com
  • 85. Pediatric considerations of SSC guidelines 2012 L. Diuretics and Renal Replacement Therapy Use diuretics to reverse fluid overload when shock has resolved, and if unsuccessful then continuous venovenous hemofiltration (CVVH) or intermittent dialysis to prevent > 10% total body weight fluid overload (grade 2C). M. Deep Vein Thrombosis (DVT) Prophylaxis No recommendation on the use of DVT prophylaxis in prepubertal children with severe sepsis. N. Stress Ulcer(SU) Prophylaxis No recommendation on the use of SU prophylaxis in prepubertal children with severe sepsis. O. Nutrition Enteral nutrition given to children who can be fed enterally, and parenteral feeding in those who cannot (grade 2C www.picuforum.com
  • 86. Unresolved Issues • Time to achieve various therapeutic endpoints may be variable. There are no evidence-based guidelines for defining expected time frame of response for each of the monitoring parameters. • Arterial blood gases (ABGs) and lactate estimations are available in a few centers; in others this cannot be used. Use of mixed venous oxygen saturations (ScVO2) is still beyond reach of most centers. • Ability to place central lines particularly subclavian or internal jugular vein is still limited. • In children with shock, the noninvasive BP measurements may be unreliable and invasive intra-arterial BP is ideal; it may not be feasible in majority of resource-limited centers. • Echocardiography for determining the cardiac filling is also not practical in many centers. • Precise therapeutic end-points for severely malnourished children are unknown. P.Khilnani et al;Guidelines for treament of septic shock in resource limited environments.Indian J Crit Care Med. 2010 Jan-Mar; 14(1): 41–52. www.picuforum.com
  • 87. Martin.w,Dusner ,et al,Recommandati ons for sepsis management in resource limited setting;intensive care medicine,2012;38: 557-559. www.picuforum.com
  • 88. References • Surviving sepsis campaign guidelines 2012 • P.Khilnani et al;Guidelines for treament of septic shock in resource limited environments.Indian J Crit Care Med. 2010 Jan-Mar; 14(1): 41–52. • Roger’s Textbook of pediatric intensive care, 5th edition,2008. • Paolo Biban et al, Early recognition and management of septic shock in children, Paediatric Reports 2012; volume 4:e13 • Martin.w,Dusner ,et al,Recommandations for sepsis management in resource limited setting;intensive care medicine,2012;38:557-559. • Emanuael P.Rivers et al.Early and innovative interventions for severe sepsis and septic shock;taking advantage of a window opportunity;CMAJI,october 2005;173[9].1054-1065. www.picuforum.com
  • 89. Thank You www.picuforum.com

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