Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Adaptive immune system wikipedia , lookup
Infection control wikipedia , lookup
Adoptive cell transfer wikipedia , lookup
Hospital-acquired infection wikipedia , lookup
Inflammation wikipedia , lookup
Hygiene hypothesis wikipedia , lookup
Cancer immunotherapy wikipedia , lookup
Immunosuppressive drug wikipedia , lookup
Neonatal infection wikipedia , lookup
Psychoneuroimmunology wikipedia , lookup
Leanna R. Miller, RN, MN, CCRN-CMC, PCCN-CSC, CEN, CNRN, NP Education Specialist LRM Consulting Nashville, TN [email protected] Learning Outcomes Analyze the mediators (cytokines) responsible for cellular and clinical changes during the inflammatory response. Correlate the clinical significance of immunoparalysis to trauma, sepsis and open heart surgery. Evaluate strategies used to manage patients with immunoparalysis. [email protected] recovery from critical illness requires proper immunologic balance between pro- and antiinflammatory forces persistence of a marked compensatory antiinflammatory innate immune response following an insult such as sepsis, surgery, or trauma is termed immunoparalysis [email protected] an acquired immunodeficiency can be quantified through the measurement of: monocyte cell-surface HLA-DR expression analysis of the capacity of whole blood to produce TNFα upon ex vivo stimulation with endotoxin [email protected] during critical illness, there is a systemic anti-inflammatory state intended to avoid the spread of the local proinflammatory response [email protected] resulting immunosuppression increases the risk of nosocomial infections related to an increase in morbidity and mortality in critically ill patients [email protected] Host Defenses exposed to injury & infection defense mechanisms inflammation thrombosis healing [email protected] Stages of Inflammation destruction & removal containment stimulation & amplification of the immune response promotion of healing [email protected] [email protected] [email protected] Innate - Cellular Adaptive - Cellular Phagocytosis Monocytes Neutrophils Dendritic Cells Antibody Production B cells / Plasma cells Antigen Presentation Monocytes Dendritic Cells Cytotoxic Killing CD8 T cells Cytotoxic Killing Natural Killer Cells Neutrophils Cytokine & Chemokine Production CD4 T cells Cytokine & Chemokine Production All of the above [email protected] Innate - Noncellular Elements Cytokines Chemokines Complement Adaptive – Noncellular Elements Immunoglobulins Cytokines Chemokines [email protected] [email protected] Nonspecific Immunity natural killer cells (NK) kill viruses, bacteria, neoplastic cells regulate production of erythrocytes & granulocytes [email protected] Complement activated by: antigen/antibody complex tissue injury tissue ischemia coagulation [email protected] Complement activated by: cell debris kinins endotoxin bacterial cell debris [email protected] Complement opsonization mediator release histamine leukotrienes [email protected] Coagulation activated by: Intrinsic pathway Extrinsic pathway [email protected] [email protected] Coagulation excessive intravascular coagulation leads to: vascular damage tissue ischemia [email protected] Fibrinolysis Hemorrhage leads to: decreased O2 delivery tissue ischemia [email protected] [email protected] [email protected] [email protected] Tumor Necrosis Factor fever endothelial damage anorexia procoagulant activity responsiveness to catecholamine [email protected] Triggers to IIR infection hypoperfusion hypoxemia injury [email protected] Etiology ARDS Sepsis DIC ATN Shock [email protected] Activation of the Immune Response COAGULATION CASCADE Endothelium Tissue Factor Factor VIIIa PAI-1 IL-6 IL-1 TNF- Monocyte Factor Va Suppressed fibrinolysis THROMBIN Neutrophil Fibrin IL-6 Fibrin clot Tissue Factor Inflammatory Response to Infection TAFI Thrombotic Response to Infection [email protected] Fibrinolytic Response to Infection Pathophysiology role of initial insult in promoting INFECTION Immunosuppression downregulation blood stress products response hypercatabolism [email protected] Pathophysiology Transluminal migration SIRS nosocomial pneumonia [email protected] Pathophysiology Flow dependent O2 consumption DO2 > 600 VO2 > 150 [email protected] Pathophysiology tissue ischemia and reperfusion xanthine oxidase O2 free radicals (ROS) tissue injury [email protected] Mortality rates One organ = 1% Two organs = 11% Three organs = 50% Four organs = 75% [email protected] Nurse’s Role in Treatment assessing system failure early identification minimizing complications [email protected] SIRS Criteria (2 or more) Temperature > 38 °C or SIRS??? < 36 °C Heart rate > 90 beats RR > 20 or paCO2 < 32 WBC > 12,000 or < 4,000 or > 10% bands Levy et al. 2001 International Sepsis Definitions Conference [email protected] Definitions SIRS SIRS + Infection = Sepsis Sepsis + Acute Organ Dysfunction or hypoperfusion = Severe Sepsis Severe Sepsis + CV failure = Septic Shock Most common sites of origin Urinary tract GI system Respiratory tract Skin & wounds Predisposing Factors extremes in age granulocytopenia prior antibiotic use severe burn, trauma, surgery functional asplenia Predisposing Factors immunosuppression malnutrition & TPN alcohol & drug abuse prolonged ICU stay Assessing Acute Immune Inflammatory Response Procalcitonin (PCT) 0.12 – 0.26 ng/mL C – reactive protein (CRP) 0 – 5 mg/L IL –6 0 – 28 pg/mL Hermann et al;(2000) Procalcitonin in septic shock. Clin [email protected] Chem Lab Med 38(1):41 - 46 1st Six Hours Resuscitation = Cultures + Antibiotics + Early Goal – Directed Therapy 1st Six Hours Delays in management of the SIR result in higher mortality rates and increased utilization of hospital resources [email protected] Transition from Sepsis to Severe Sepsis occurs most often during the 1st 24 hours of hospitalization increase in mortality of 20 – 46% [email protected] Transition tissue O2 delivery & CV insufficiency accompanies transition usually not detected by VS nor SIRS criteria [email protected] O2 Transport & Utilization O2 delivery is insufficient to meet O2 demands @ cell level results in increased lactate levels [email protected] O2 Transport & Utilization SvO2 < 65% or ScvO2 < 70% result in increased lactate and suggest the presence of global tissue hypoxia – greater extraction by tissues [email protected] [email protected] O2 Transport & Utilization high SvO2, ScvO2 & lactate indicates that despite adequate global systemic O2 delivery, the tissues are unable to extract the O2 [email protected] Sepsis Pathophysiology [email protected] Identification of High Risk Patient single lactate > 4.0 or more at initial presentation failure to clear lactate levels during the 1st 6 hours is associated with increased morbidity and mortality [email protected] Management of IIR Initial Resuscitation Endpoints CVP 8 to 12 mm Hg MAP > 65 mm Hg UO > 0.5 mL/kg/hr SvO2 > 70% [email protected] Management of IIR Early antimicrobial therapy empiric antibiotics within 4 to 8 hours of hospital presentation Surviving Sepsis Campaign recommends antibiotics within 1 hour [email protected] Management of IIR source of infection & local hospital sensitivity & resistance patterns surgical consultation resistant organisms when patients live in nursing homes or are IV drug users [email protected] [email protected] Volume Therapy repletion of intravascular volume rapid, 20 mL/kg boluses of either crystalloid or colloid CVP 8 – 12 mm Hg [email protected] Volume Therapy 4% albumin or NS found no significant difference in mortality between the group [email protected] Vasoactive Agents Norepinephrine 2 – 20 g/min Vasopressin 0.01 – 0.04 units/min – (VASST study) Phenylephrine 40 – 300 g/min Dopamine 5 – 20 g/kg/min [email protected] Vasoactive Agents Adverse consequences splanchnic hypoperfusion excess tachycardia coronary ischemia [email protected] RBC Replacement If ScvO2 remains < 70% after optimization of preload, afterload and arterial O2 saturation increase Hct to 30% optimal erythrocyte transfusion fresh vs. stored blood [email protected] Inotropic Therapy Sepsis may be accompanied by myocardial suppression in 10 – 15% of patients dobutamine titrated at 2.5 g/kg/min every 20 – 30 minutes to ScvO2 of 70% milrinone (long half – life and accumulates in renal failure) [email protected] Decreasing O2 consumption intubation, sedation, analgesia control fever [email protected] Administration of steroids, has theoretical benefits in the setting of severe sepsis by inhibiting the massive inflammatory cascade Steroid Therapy Inflammatory cascade leads to (RAI): inadequate release or response to ACTH peripheral steroid resistance @ receptor level [email protected] Steroid Therapy If on vasopressors, draw random cortisol level; if < 25 mcg/mL give corticosteroids If not on vasopressor, draw baseline random cortisol level, do cort stim test; get levels @ 30 & 60 min – if difference is < 9 give steroids Steroid Therapy low doses of hydrocortisone decreased requirement for vasopressors and lowered mortality Hydrocortisone 50 mg IV every 6 hours Dexamethasone 4 mg IV every 8 hours Fludrocortisone 100 g PFT every day Protective Lung Strategies 6 mL/kg vs. 12 mL/kg 9.9% absolute 28 – day mortality in low TV group [email protected] Tight Glycemic Control 100 – 150 mg/dL 8.0% reduction in mortality [email protected] High – volume Hemofiltration removal of inflammatory cytokines [email protected] CVVH for Treatment low-volume CVVH (20 mL/kg BW), filters changed every 12 hrs high-volume CVVH (100 mL/kg BW), filters changed every 12 hrs [email protected] CVVH ameliorated the initial serum tumor necrosis factor-alpha response and prevented sepsis-induced in vitro endotoxin hyporesponsiveness. down-regulation of major histocompatibility complex II and CD14 expression on monocytes was significantly improved by CVVH. [email protected] improved oxidative burst and phagocytosis capacity in polymorphonuclear leukocytes suggested that leukocyte function was stabilized by CVVH. CVVH significantly reduced bacterial translocation and endotoxemia. [email protected] [email protected] Case Study 66 – year old man victim of violent crime two gunshot sounds to abdomen unconscious & hypotensive on arrival to ED 2 liters LR infusing 40% O2 via face mask [email protected] Case Study HR 130; RR 24; clear breath sounds bilaterally; UO 300 mL; BP 110/76 emergency surgery to large bowel, small bowel & vena cava colostomy performed EBL 2000; 10 units of pRBCs given surgery 6 hours; hypotensive during surgery [email protected] BP RAP / PAOP SVR CI SvO2 120/64/76 6/8 1027 3.5 .74 [email protected] paO2 / SaO2 pH paCO2 / HCO3 85 / .95 7.42 38 /25 SIMV 14; TV 350; PEEP 10; FiO2 .40 [email protected] Na K Cl Glucose Hgb/PCV WBC [email protected] 132 4.8 98 230 12.1 / 35 12,000 Case Study hemodynamically stable day after surgery extubated and placed on 40% venturi mask 3 days later dyspneic & restless with temperature of 103 F [email protected] BP RAP / PAOP SVR CI SvO2 [email protected] 128/68/80 2/7 983 4.1 .72 paO2 / SaO2 pH 80 / .95 7.47 paCO2 / HCO3 32 /24 FiO2 .40 mask [email protected] Hgb/PCV 10.2 / 30 WBC 20,000 Platelets 150,000 CT scan of abdomen [email protected] DO2I = CI ( 1.38 x Hgb x SaO2) 10 4.5 X 1.38 X 8.8 X 0.88 x 10 481 2 mL/min/m (normal = 360 - 600 mL/min/m2) [email protected] VO2I = CI X 1.38 X Hgb X (SaO2 - SvO2) X 10 4.5 x 1.38 x 8.8 x (.88 - .82) x 10 33 mL/min/m2 (Normal 108 - 165 mL/min/m2) [email protected] Case Study day 5 post op BP drops respirations shallow & labored; marked accessory muscle use [email protected] BP HR RAP / PAOP SVR CI SvO2 82/58/70 122 2/5 569 5.3 .88 [email protected] paO2 / SaO2 pH 55 / .88 7.26 paCO2 / HCO3 35 /12 FiO2 .40 mask [email protected] Case Study day 10 post op condition deteriorates dopamine 22 mcg/kg/min responds only to pain PVCs & S3 gallop [email protected] BP HR RAP / PAOP SVR CI SvO2 74/58/70 156 7/22 1600 2.8 .50 [email protected] paO2 / SaO2 pH 45 / .87 7.10 paCO2 / HCO3 50 /10 FiO2 .50 SIMV [email protected] Na K Cl Glucose Creatinine Hgb/PCV WBC [email protected] 150 6.1 98 230 3.5 12.1 / 35 12,000 Amylase AST/ALT BUN Lipase FSP Platelets PT/PTT 300 80/100 40 40 40 80,000 21/97.5 [email protected] [email protected] Pangault C, Le Tulzo Y, Tattevin P, Guilloux V, Bescher N, Drenou B. Down-modulation of granulocyte macrophage-colony stimulating factor receptor on monocytes during human septic shock. Crit Care Med. 2006 Apr;34(4):1193–1201. Le Tulzo Y, Pangault C, Amiot L, et al. Monocyte human leukocyte antigen-DR transcriptional downregulation by cortisol during septic shock. Am J Respir Crit Care Med. 2004 May 15;169(10):1144–1151. Volk T, Schmutzler M, Engelhardt L, et al. Influence of aminosteroid and glucocorticoid treatment on inflammation and immune function during cardiopulmonary bypass. Crit Care Med. 2001 Nov;29(11):2137–2142. Perry SE, Mostafa SM, Wenstone R, Shenkin A, McLaughlin PJ. Is low monocyte HLA-DR expression helpful to predict outcome in severe sepsis? Intensive Care Med. 2003 Aug;29(8):1245–1252 [email protected]