(Student)Introduction to Sepsis .pptx

INTRODUCTION TO SEPSIS Dr. Abbey Baus DMSc, PA-C, AAHIVS Definitions Bacteremia: viable bacteria growing in the blood stream Sepsis: infection with altered organ function, manifested by derangements such as oliguria, acute kidney injury, coagulopathy, altered mental status, and an elevated lactat...

INTRODUCTION TO SEPSIS Dr. Abbey Baus DMSc, PA-C, AAHIVS Definitions Bacteremia: viable bacteria growing in the blood stream Sepsis: infection with altered organ function, manifested by derangements such as oliguria, acute kidney injury, coagulopathy, altered mental status, and an elevated lactate. Septic shock: sepsis requiring pressors to maintain adequate organ perfusion defined as a mean arterial pressure (MAP) ≥65 mmHg and the presence of a lactate >2. Sepsis Sepsis is the #1 cause of hospital admission and the single biggest cost to US hospitals at $24 billion/year Septic shock is the most common cause of ICU and hospital death and the leading cause of hospital readmissions. Hospital acquired sepsis is most common in patients with cancer, burns, trauma or in the NICU Sepsis Pathogenesis The acute inflammatory process gets started when the body suffers some sort of insult- heat, chemical or infectious. Sepsis Pathogenesis Endotoxin or cell wall products induce pro-inflammatory cytokines These cytokines activate neutrophils and vascular endothelial cells, damaging the endothelium and making blood vessels leaky, causing inflammation Sepsis Pathogenesis The patient develops the systemic effects of inflammationThe bone marrow accelerates production of leukocytes, resulting in increased levels in the bloodstream, possibly bands, which are prematurely released from the marrow. Sepsis Pathogenesis If the patient does not seek medical attention quickly, or the infection is severe, the patient will develop Systemic Inflammatory Response Syndrome (SIRS) Systemic Inflammatory Response Syndrome (SIRS) A response by the body to insults (infection, acute injury or non-infectious disease) The body’s response can cause dysfunction or worsen organ function, leading to multi-system organ failure. As increasing numbers of organs fail, Sepsis Pathogenesis The patient begins to have progressive deterioration of body function at sites far from the infection (Acute Kidney Injury, Altered Mental Status) due to the systemic effects of the illness- this is sepsis. The systemic inflammation activates the coagulation pathways leading to widespread microthrombi, tissue ischemia and depletion of natural Sepsis Pathogenesis If the patient is not treated and the inflammatory process continues to progress, the patient will develop a vasodilatory shock requiring pressor support to ensure adequate perfusion of the brain and kidneys Acute Inflammatory Process Systemic activation of the immune system, if allowed to progress long enough, will cause the patient to develop sepsis and then septic shock, eventually leading to death. If inflammation is not systemic, but is severe or prolonged at the local level, fibrous tissue (scar/ adhesions) may form, limiting flexibility and adhering Normal Vitals for ages 15 and older • Normal respirations: 12-18 per minute •Normal pulse: 60-100 bpm •Normal blood pressure: 100-140/ 50-90 Source: Bates’ Guide to Physical Examination and History Taking Systemic Inflammatory Response Syndrome (SIRS) Criteria Two of the following criteria must be met: • Heart rate > 90 bpm • Tachypnea > 20 breaths/ min or pCO2 < 32mmHg on ABG • Temp > 100.4 (38 C) or < 96.8 (36 C) • WBC greater than 12,000 or less than 4,000, or greater than 10% *Quantifying Sepsis In the 2016 SCCM/ESICM guidelines the qSOFA score replaced SIRS, qSOFA stands for quick Sequential (Sepsis-related) Organ Failure Assessment score and is validated for patients outside the ICU. • 0-1= 3% risk of Patients receive one point each for: • Respirations ≥ death 22 • 2= 18% risk of • Altered death mentation Stages of Shock Pre-Shock Shock End-Stage Shock Stages of Shock: Pre-shock • Pre-shock: Also called warm shock or compensated shock. • A loss of 10% of effective blood volume would cause pre-shock to occur • Characterized by rapid compensation for diminished tissue perfusion by various homeostatic mechanisms Pre-shock Scenario Annalise is a 67-year-old woman who comes to the urgent care with progressively worsening dyspnea over the last week. She is able to talk to the PA who sees her about the time course of her illness, but occasionally forgets an important detail, and her grandson at the bedside reports that this is unusual for her. Pre-shock Scenario On exam, she is noted to have the following vitals: RR: 26, P:120, BP: 144/62 and temp of 101. She appears dyspneic and ill. She has coarse crackles in her right lower lung and tachycardia on exam. Shock A significant reduction of systemic tissue perfusion, from a variety of mechanisms, resulting in decreased tissue oxygen delivery Prolonged oxygen deprivation leads to cellular and systemic derangements. The effects of oxygen deprivation are initially reversible, but rapidly become irreversible. Stages of Shock: Shock During shock, the compensatory mechanisms become overwhelmed, and the signs/symptoms of organ dysfunction are readily apparent. These include tachycardia (compensation of vasodilation), dyspnea, restlessness, diaphoresis, metabolic acidosis, oliguria, and cool clammy skin. A 20-25% reduction in effective blood Shock Scenario Leonard is a 67-year-old man who comes to the ER with progressively worsening dyspnea over the last week. His grandson provides the history. Leonard is restless and confused requiring frequent reassurance from his grandson, who states that he is normally “very sharp”. exam. Shock Scenario On exam, he is noted to have the following vitals: RR: 26, P:120, BP: 100/72 and temp of 101. He appears dyspneic, sweaty and pale. He has coarse crackles in his RLL although is not moving air well and has tachycardia with a End Stage Shock Progressive end-organ dysfunction leads to irreversible organ damage and patient death. During this stage: Urine output may decline further (anuria and acute kidney injury) Acidemia decreases the cardiac output and alters cellular metabolic processes End Stage Shock Pts usually develop leukocytosis with a left shift Overwhelming bacteremia or a severe viral infection may produce leukopenia Thrombocytosis occurs with infection, but progressive sepsis will lead to thrombocytopenia due to platelet consumption Gram negative sepsis frequently produces coagulopathy, 10% of End-Stage Shock Scenario Zelda is a 67-year-old woman who comes to the ER with progressively worsening dyspnea over the last week. She has gasping respirations and is lethargic, moaning and withdrawing when you perform a skin twist. End-Stage Shock Scenario On exam, she is noted to have the following vitals: RR: 24, P:130, BP: 74/32 and temp of 101. He appears dyspneic, sweaty and pale. She has very diminished lung sounds and a non-palpable radial pulse with mottled Determining the Cause of Sepsis Infection severe enough to prompt hospitalization is often from a skin source, UTI or pneumonia. Therefore, every patient hospitalized with suspected infection should have a thorough exam of the skin, a UA with C&S, and a CXR. Additional testing to consider includes blood cultures x 2 q15 min, and possibly stool studies and Cerebral Spinal Fluid exam by a lumbar puncture. Determining the Cause of Sepsis: UA, C&S The urinalysis includes a chemical portion and an exam of the urinary sediments: Specific gravity: generally concentrated in sepsis Ketones: urine ketones are positive if the patient isn’t eating Protein: capillaries may be leaky or patient may have nephropathy Leukocyte estrace: a WBC enzyme Nitrites: produced by some bacteria (E. coli, Klebsiella) when they reduce nitrates which are normally present in the urine. UA, C&S Exam of the urinary sediments: RBCs: presence indicates glomerulonephritis or trauma to the GU tract Epithelial cells: should not be present in a clean (appropriately obtained) specimens, if present in large numbers, the urine is “dirty” and a new sample is needed. WBCs: if found in isolation in high numbers, their presence strongly indicates infection A urinalysis is read immediately, a urine culture takes 48 hours to become negative Determining the Cause: Blood Cx Blood cultures x 2 q15 min, means that two bottles of blood (aerobic, then anaerobic) are drawn from a vein, then another two bottles are drawn from a different vein 15 min later. Sometimes a clinician will order 3 sets if they are highly suspicious of a fastidious bacteremia. If the patient has a line or port, a culture should be drawn from the line. Determining the Cause of Sepsis Blood cannot be gram stained, so the lab looks for bacteria growing in the blood each day. BCx become negative after 5 days, prior to that, the appropriate terminology is NGTD- no growth to date. Stool studies: C diff PCR, GI PCR for bacterial pathogens or stool culture, O&P (if suspicious/world travel) CSF exam: requires an LP, CSF protein, glucose Other Labs in Sepsis • Other labs: • CBC-Complete Blood Count • CMP- Comprehensive Metabolic Panel • Serum lactate: not a diagnostic tool, multiple other disorders cause an elevated lactate, but are a way to allow you to risk stratify patients with sepsis • Procalcitonin: a naturally occurring peptide that elevates in the presence of bacterial infection but is not specific. Also elevated in patients with CA, ESRD, Other Imaging in Sepsis • Although CXR often picks up pneumonia as a common source of infection/sepsis, if it is not present then other sources of infection need to be considered. • Abdominal CT- typically done without IV or oral contrast in the ER, evaluates broadly for many potential causes of infection in the abdomen. • RUQ ultrasound: looks specifically at the biliary tract for cholecystitis, is more Immunosuppressed Patients • Any patient with cancer, especially if it is being actively treated with chemotherapy, radiation, or immunotherapy. • Any patient with advanced HIV, who has a CD4 count less than 200. • Any patient with neutropenia. • Any patients on a systemic steroid (prednisone, cortef). • Any patient who has had an organ transplant or a patient with connective Immune Dysfunction • Relative immunosuppression: patients with a less than robust immune system but are not quite in the immunosuppressed category. This group includes: • Patients without a spleen: includes those who have had surgical removal (asplenia) as well as sickle cell patients who gradually auto-infarct their spleen in childhood (functional asplenia). • Pregnant patients • Immune Dysfunction • Certain co-morbid disease states will predispose patients to particular microorganisms. • Alcoholism: Klebsiella, Strep pneumo • Diabetes: Strep pneumo, slight predisposition to Pseudomonas • Splenic dysfunction/ asplenia: encapsulated organisms, including Strep pneumo, H. flu, Neisseria meningitidis and group B strep (GBS) • Neutropenia: GNR from gut, Summary A patient presenting to the ER with fever and infection on the differential diagnosis needs the following for their first round of testing: • • • • CBC and CMP UA with reflex C&S CXR Blood cultures x 2 • If the diagnosis is not readily apparent with this round of testing, then either the differential diagnosis should be re-thought, or the patient should have: • GI labs and Lumbar Puncture • Abdominal imaging Examples A 45-year-old woman with poorly controlled diabetes presents to the ER with two days of fever that kept her home from work in the glass factory. On exam you see: She denies any URI symptoms, cough, N/V/D or shaking chills. She is vaccinated and boosted x1 against Cellulitis of the left leg; CC0 1.0 What is Important to Consider in This Patient? • A 67-year-old man presents to the ER with confusion and diarrhea x 4 days. He has a history of HTN, and CKD stage IV. His wife reports that he recently went to the State Fair to see his granddaughter compete in the barrel racing 10 days ago and started on antibiotic for a “cold” three weeks ago. He has not been vaccinated against COVID. No new medications and no change in his chronic diseases. • On exam he is oriented to name and year, cannot give a history, appears ill. Vitals: 96.2/ 24/ 110 and 101/65. HEENT, lung and cardiac exams are benign and abd exam is What is Important to Consider in This Patient? • A 24-year-old man presents to the ER with an 18-hour history of fever to 103 and dyspnea. He has a history of IVDA with last use of heroin about 10 hours ago. He reports a “thick” cough for the last 2 weeks with sputum production, pleuritic chest pain and nausea. He is homeless. • On exam, he is A&O x3, is diaphoretic and acutely ill appearing with rigors. 102.8/ 24/ 121 and 144/88. HEENT exam shows a 5mm ahpthous ulcer, lungs have coarse basilar rales and there is a II/IV murmur noted on cardiac exam. Active BS are present, and the abdomen is soft and non- What is Important to Consider in This Patient? Additional Sepsis Manifestations • Most patients develop renal dysfunction and AKI, most frequently secondary to poor perfusion of kidneysfirst pre-renal, then ATN (acute tubular necrosis) as sepsis worsens. • Coagulopathy and thrombocytopenia predispose patients to GI bleeding. • Lab abnormalities frequently include hypoglycemia which can lead to mental Making the Diagnosis • Be sure to elucidate: recent travel or exposures, infectious contacts and allergies/ medication reactions • PE: look for findings to localize the site of infection: lungs, heart, abdomen, neuro, skin. How extensive is the infection? • Studies include CBC, chemistries, blood, urine and sputum culture, wound cultures, CSF exam, as well as diagnostic Sepsis Therapeutics Sepsis Therapeutics • Choose an appropriate empiric antimicrobial • Fluid resuscitation • Oxygenation • Meticulous control of glucose Antimicrobial Therapy Time to initiation of appropriate antimicrobial therapy is the strongest predictor of mortality in sepsis. • Inappropriate antibiotic selection is common (32%). Mortality was markedly increased in these patients compared to those who had received appropriate antibiotics (34% vs 18%). • What strategies can we utilize to make Choosing your Antimicrobial • Need to consider the source of sepsis, if known, to treat the bugs which are most likely • Skin: • DM ulcers: • Burns: Choosing your Antimicrobial • Need to consider the source of sepsis, if known, to treat the bugs which are most likely • Urine: • Lungs: CAP • Lungs: HAP/VAP Choosing your Antimicrobial •Lines •Heart: •Abdomen/ bowel: Choosing your Antimicrobial • Skin: Gram positives (Staphylococcus and Streptococcus) Choosing your Antimicrobial • Ulcerative Infections: Gram positives (Staphylococcus and Streptococcus) but also wounds with poor oxygenation, anaerobic infections (Peptococcus, Peptostreptococcus, Lactobacillus, Propionibacterium, Actinomyces, Clostridium, Bacteroides, Prevotell a, Fusobacterium) and • Other Gram negative bacteria due to poor hygiene(E.coli, Klebsiella pneumoniae, Haemophiles influenz ae, Helicobacter pylori, Pseudomonas aeruginosa, Neisseria gonorrhoeae, Meningococcus, Chlamydia trachomatis) Choosing your Antimicrobial Burns: Gram positives (Staphylococcus and Streptococcus) and Pseudomonas (Gram negative)​ Choosing your Antimicrobial Urine: E-coli, Gram negative aerobic bacilli (from the gut)​ Choosing your Antimicrobial Lungs (CAP): Streptococcus (gram positive), Haemophilus influenzae (gram negative), Moraxella Catarrhalis(gram negative). Choosing your Antimicrobial • Atypical community acquired organisms for pneumonia: (more common in young people)= Legionella(gram negative), Mycoplasma, and Chlamydia ​(gram negative) Choosing your Antimicrobial • Lungs (HAP)/(VAP): Streptococcus is still most common, but also think Gram negatives for inability to keep good hygiene (E.coli, Klebsiella pneumoniae, Haemophiles influenzae, Helicobacter pylori, Pseudomonas aeruginosa, , Choosing your Antimicrobial • Lines: Strep and Staph that live on the skin (gram positive)​ •​ Choosing your Antimicrobial • Heart: If IVDU consider Strep and Staph If instrumentation, consider gram negative source. Choosing your Antimicrobial • Abdomen/bowel: Gram negatives and Gram positive anaerobes in the gut(example;Clostridium) Empiric Antibiotic Therapy Empiric Antibiotic Therapy • Occasionally, we have a patient who does not have a clearly obvious source of infection but does have some symptoms of infection. • If the patient’s clinical picture is stable, and there are possible alternative explanations for their symptoms, it is appropriate to monitor the patient off ABX while awaiting cultures. • If the patient’s clinical picture is Empiric Antibiotic Therapy • Vancomycin with one of the following if Pseudomonas is not a consideration • Cephalosporin, 3rd or 4th generation (eg, ceftriaxone or cefotaxime), or • Beta-lactam/beta-lactamase inhibitor (eg, piperacillin-tazobactam, ticarcillinclavulanate, or ampicillin-sulbactam), or • • If Pseudomonas is a possible pathogen, consider combining vancomycin with two of the following: • Anti-pseudomonal cephalosporin (cefepime), or • Anti-pseudomonal carbapenem (eg, imipenem, meropenem), or • Anti-pseudomonal beta-lactam/betalactamase inhibitor (eg, piperacillintazobactam), or • Fluoroquinolone with good antipseudomonal activity (eg, ciprofloxacin), or IV Fluid Resuscitation in Sepsis/ Septic Shock • Start with 0.9% NS or LR at a dose of 30 mL/kg IV within the first three hours. • May consider blood products if hypotension is severe and anemia is present, but more commonly, pressors are used as the primary means improve blood pressure if IV fluids are insufficient or fail. Pressors • Levophed(Norepinephrine bitartrate): an alpha/beta agonist producing potent vasoconstriction, the first choice in a distributive shock like sepsis. • Dobutamine: reduces afterload and creates an ionotropic effect on cardiac muscle, mainly used for cardiogenic shock Hematologic Treatment of Shock • Packed RBCs: one unit should raise the hematocrit by 3% and the hemoglobin by about 1 gram • Fresh frozen plasma (FFP): contains coagulation factors, usually given as 2-4 units FFP depending on the prolongation of the INR, the effects last only hours • Platelets: one unit of platelets will raise the patient’s platelet count by about 6K. Oxygenation • If patient’s pulse oximetry is low (< 92%) or they complain of dyspnea, they are placed on supplemental oxygen, titrated to SpO2 • ABG is the best test to assess for adequate gas exchange if patients will potentially need intubation. • Arterial blood gases give values for the following: • Partial pressure of O2 in the blood, normal Adequate Gas Exchange Illustration of an endotracheal tube; CC BY-SA 4.0 Patient intubated via oral interface. CC BY-SA 4.0 • Intubation and mechanical ventilation may be needed with hypoxemic or hypercarbic respiratory failure, accompanied by other factors. – RR > 30, mental status decline/ obtundation, Adequate Gas Exchange • Bi-Pap is an alternative to endotracheal intubation for a short time. • Provides noninvasive support to ventilation. • The patient must breathe on their own and must be able to tolerate the mask. BiPAP using a ventilator; CC BY-SA 4.0 Respiratory Status/ Myocardial Function • Once a patient is placed on ventilatory support, serial ABGs are used to monitor the adequacy of ventilation and to determine if the patient can be extubated. • Myocardial function sometimes assessed with bedside echocardiography. If there is concern for myocardial ischemia, serial troponins and a formal echocardiogram Hyperglycemia • It is essential to have meticulous control of glucose during sepsis, and shock treatment overall. • Persistent hyperglycemia will worsen the outcome of any infection or sepsis • Control blood glucose levels with sliding scale insulin but titrate it up